Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors

1 . A compound of formula I or a pharmaceutically acceptable salt thereof:

Wherein,

ring A is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —;

each of R G is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted;

ring B is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring, a 3-10 membered carbocyclic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

T is absent, O, NR 1 or CR 1 R 2 ;

each of R 1 and R 2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or

R I and R 2 together with the carbon atom to which they are both attached form CO or C═NR 5 ;

p is 0, 1, 2, 3 or 4;

each of R 3 and R 4 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or

R 3 and R 4 together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or a 5-12 membered heteroaromatic ring or C═NR 5 , and each of the ring systems is independently optionally substituted or unsubstituted;

each of R 5 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy;

q is 0, 1, 2, 3 or 4;

W is absent, O, S or —C(R W ) 2 -; and each of R W is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkylene-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

when ring C is absent, Y 5 is CR 5a R 5b , NR 5a or O, and Y 6 is CR 6a R 6b , NR 6a or O;

when ring C is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring;

i) Y 5 is CR 5a or N, and Y 6 is CR 6a or N, when the “ ” in the term “Y 5 Y 6 ” represents a single bond; or

ii) Y 5 is C, and Y 6 is C, when the “ ” in the term “Y 5 Y 6 ” represents a double bond;

each of R 5a and R 5b is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

each of R 6a and R 6b is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

each of R a is independently selected from hydrogen, deuterium, halogen, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-6 alkoxy, —C 1-6 alkyl, —C 3-8 cycloalkyl, —C 1-6 alkylene—NR a1 R a2 , —C 1-6 alkylene-O—C 1-6 alkyl, —C 1-6 alkylene-(3-10 membered heterocyclic), —C 1-6 alkylene-(5-10 membered heteroaryl), —C 1-6 alkylene—CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—C 1-6 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-10 carbocyclic, −5-10 membered heteroaryl, −3-10 membered heterocyclic, —CO—C 1-6 alkyl, —CO—C 1-6 alkylene—NR a1 R a2 , —CO—NR a1 -(3-10 membered heterocyclic), —CO—NR a1 -(3-10 membered heterocyclic), —CO-(3-10 membered heterocyclic), —O—C 1-6 alkylene—CO—OR a1 , —O—C 1-6 alkylene—CO—NR a1 R a2 , —O—C 1-6 alkylene—NR a1 R a2 , —O—C 3-10 carbocyclic, —O-(3-10 membered heterocyclic), —NR a1 —CO—C 1-6 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-10 membered heteroaryl), —NR a1 —CO—C 3-8 cycloalkyl,—NR a1 —C 1-6 alkylene—NR a1 R a2 , —NR a1 —C 1-6 alkylene-(3-10 membered heterocyclic), —NR a1 —C 1-6 alkylene-(5-10 membered heteroaryl), —NR a1 —SO 2 C 1-6 alkyl, —S—C 1-6 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-6 alkyl, —SO 2 —C 1-6 alkyl, —PO(C 1-6 alkyl) 2 , —PO(C 1-6 alkoxy) 2 ,−3-10 membered heterocyclic or −5-10 membered heteroaryl; each of which is independently optionally substituted; and n iso, 1, 2, 3, 4, 5 or 6; or

two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted; or

R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted;

each of R a1 and R a2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

2 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein ring A is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

3 . The compound or pharmaceutically acceptable salt thereof of claim 1 or claim 2 , wherein ring A is a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

4 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 3 , wherein ring A is a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

5 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 4 , wherein ring A is

represents a single bond or a double bond;

X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ;

each of R X1 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy;

X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO;

each of R X2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X1 and R X2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3 ;

each of R X3 is independently selected from hydrogen, deuterium, halogen, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X2 and R X3 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted ;

X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ;

each of R X4 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or a 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X3 and R X4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ;

each of R X5 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X4 and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 6 is O, S, CO or NR X6 , or C(R X6 ) 2 ;

each of R X6 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X5 and R X6 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted.

6 . The compound or pharmaceutically acceptable salt thereof of claim 5 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

7 . The compound or pharmaceutically acceptable salt thereof of claim 5 or claim 6 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

8 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 7 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

9 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 8 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

10 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 9 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

11 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 10 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

12 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 11 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

13 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 12 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 ,CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-4 alkyl, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl or 3-6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

14 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 13 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

15 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 14 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene—C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

16 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 15 , wherein R X1 and R X2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

17 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 16 , wherein R X1 and R X2 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

18 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 17 , wherein R X1 and R X2 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted.

19 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 18 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

20 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 19 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl,—O—C 1-6 alkylene-C 1-6 alkyl, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

21 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 20 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-3 alkyl, —C 1-3 alkoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene-C 1-3 alkyl, —O—C 5-6 aryl or —O—C 1-3 alkylene-C 5-6 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

22 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 21 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene-C 1-3 alkyl, —O—C 5-6 aryl or —O—C 1-3 alkylene-C 5-6 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

23 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 22 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene—C 1-3 alkyl, —O—C 5-6 aryl or —O—C 1-3 alkylene-C 5-6 aryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

24 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 23 , wherein R X2 and R X3 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

25 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 24 , wherein R X2 and R X3 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

26 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 25 , wherein R X2 and R X3 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, an 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted.

27 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 26 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

28 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 27 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

29 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 28 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl, —C 1-3 alkoxy, —NHCO-(5-10 membered heterocyclyl) or 5-10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

30 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 29 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

31 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 30 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

32 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 31 , wherein R X3 and R X4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

33 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 32 , wherein R X3 and R X4 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

34 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 33 , wherein R X3 and R X4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

35 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 34 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

36 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 35 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or -C 1-3 alkoxy.

37 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 36 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

38 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 37 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

39 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 38 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

40 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 39 , wherein R X4 and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

41 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 40 , wherein R X4 and R X5 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

42 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 41 , wherein R X4 and R X5 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

43 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 42 , wherein X 6 is O, S, CO or NR X6 , or C(R X6 ) 2 ; each of R X6 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

44 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 43 , wherein X 6 is O, S, CO or NR X6, or C(R X6 ) 2 ; each of R X6 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

45 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 44 , wherein X 6 is O, S, CO or NR X6, or C(R X6 ) 2 ; each of R X6 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

46 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 45 , wherein X 6 is O, S, CO or NR X6 , or C(R X6 ) 2 ; each of R X6 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

47 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 46 , wherein X 6 is O, S, CO or NR X6 , or C(R X6 ) 2 ; each of R X6 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

48 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 47 , wherein R X5 and R X6 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

49 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 48 , wherein R X5 and R X6 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

50 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 49 , wherein R X5 and R X6 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

51 . The compound or pharmaceutically acceptable salt thereof of any one of claims 5 - 50 , wherein ring A is selected from

52 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 51 ,

wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —; each of R G is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted.

53 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 52 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —; each of R G is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted or unsubstituted.

54 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 53 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —; each of R G is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted or unsubstituted.

55 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 54 , wherein ring B is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring, a 3-10 membered carbocyclic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2,3, 4, 5 or 6 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2, 3, 4, 5 or 6heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

56 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 55 , wherein ring B is a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered carbocyclic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2,3, 4, 5 or 6 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

57 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 56 , wherein ring B is a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, a 7 membered carbocyclic ring, a 8 membered carbocyclic ring, a 9 membered carbocyclic ring, a 10 membered carbocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, a 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2, 3 or 4 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2, 3 or 4 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

58 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 57 ,

wherein ring B is

Y 1 is N or CR Y1 ,

R Y1 is selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —N—(C 1-6 alkyl) 2 , —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy;

Y 2 is N or CR Y2 ;

R Y2 is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —N—(C 1-6 alkyl) 2 , alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R Y1 and R Y2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

when the “ ” in the term “Y 3 Y 4 ” represents a single bond, Y 3 is NR Y3 or C(R Y3 ) 2 , and Y 4 is CO, C(R Y4 ) 2 or NR Y4 ;

when the “ ” in the term “Y 3 Y 4 ” represents a double bond, Y 3 is N or CR Y3 , and Y 4 is N or CR Y4 ;

R Y3 and R Y4 are independently selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH —CO—C 3-8 heterocyclic ring, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl, —C 1-6 alkyl substituted with —OH, or —C 1-6 alkoxy; or

R Y3 and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted.

59 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 58 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

60 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 59 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

61 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 60 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

62 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 61 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

63 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 62 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

64 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 63 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

65 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 64 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

66 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 65 , wherein Y 2 is N or CR Y2 ; Rye is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

67 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 66 , wherein R Y1 and R Y2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

68 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 67 , wherein R Y1 and R Y2 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

69 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 68 , wherein R Y1 and R Y2 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

70 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 69 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl, —C 1-6 alkyl substituted with —OH or —C 1-6 alkoxy.

71 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 70 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl, —C 1-3 alkyl substituted with —OH or —C 1-3 alkoxy.

72 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 71 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl, —C 1-3 alkyl substituted with —OH or —C 1-3 alkoxy.

73 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 72 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, ethyl substituted with —OH, methoxy, ethoxy, propoxy or isopropoxy.

74 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 73 , wherein R Y3 and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

75 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 74 , wherein R Y3 and R Y4 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

76 . The compound or pharmaceutically acceptable salt there of any one of claims 1 - 75 , wherein R Y3 and R Y4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

77 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 75 , wherein ring B is selected from

78 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 77 , wherein each of R 1 and R 2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

79 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 78 , wherein each of R 1 and R 2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

80 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 79 , wherein each of R 1 and R 2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

81 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 80 , wherein each of R 1 and R 2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

82 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 81 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form CO or C═NR 5.

83 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 82 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form CO.

84 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 83 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form C═NR 5.

85 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 84 , wherein each of R 3 and R 4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

86 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 85 , wherein each of R 3 and R 4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

87 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 86 , wherein each of R 3 and R 4 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

88 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 87 , wherein each of R 3 and R 4 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

89 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 88 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form 3-12 membered heterocyclic ring or 5-12 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

90 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 89 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form 3-10 membered heterocyclic ring or 5-10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

91 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 90 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form 3 membered heterocyclic ring, 4 membered heterocyclic ring, 5 membered heterocyclic ring, 6 membered heterocyclic ring, 7 membered heterocyclic ring, 8 membered heterocyclic ring, 9 membered heterocyclic ring, 10 membered heterocyclic ring, 5 membered heteroaromatic ring, 6 membered heteroaromatic ring, 7 membered heteroaromatic ring, 8 membered heteroaromatic ring, 9 membered heteroaromatic ring, 10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

92 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 91 , wherein each of R 5 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy.

93 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 92 , wherein each of R 5 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy.

94 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 93 , wherein each of R 5 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy

95 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 94 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkylene-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

96 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 95 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-3 alkyl, —CO—OC 1-3 alkyl, —C 1-3 alkylene-O—C 1-3 alkoxy, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

97 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 96 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkylene-O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

98 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 97 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkylene-O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

99 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 98 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkylene-O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

100 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 99 , wherein ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

101 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 100 , wherein ring C is absent, a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

102 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 101 , wherein ring C is absent, a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

103 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 102 , wherein ring C is selected from

104 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 103 , wherein each of R 5a and R 5b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

105 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 104 , wherein each of R 5a and R 5b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

106 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 105 , wherein each of R 5a and R 5b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

107 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 106 , wherein each of R 5a and R 5b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

108 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 107 , wherein each of RY 6 , and R 6b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

109 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 108 , wherein each of R 6a and R 6b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

110 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 109 , wherein each of R 6a and R 6b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

111 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 110 , wherein each of Rha and R 6b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

112 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 111 , wherein each of R a is independently hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-3 alkoxy,—C 1-4 alkyl, —C 3-6 cycloalkyl, —C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—C 1-3 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −5-8 membered heteroaryl, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR-(3-8 membered heterocyclic), —CO—NR-(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene—CO—OR a1 , —O—C 1-3 alkylene—CO—NR a1 R a2 , —O—C 1-3 alkylene—NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —S—C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 —C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6.

113 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 112 , wherein each of R a is independently hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, methoxy, ethoxy, propoxy, isopropoxy methyl, ethyl, propyl, isopropyl, butyl, isobutyl, —C 3-6 cycloalkyl,-C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene—CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—NR a1 R a2 , —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −5-8 membered heteroaryl, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR-(3-8 membered heterocyclic), —CO—NR-(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene—CO—OR a1 , —O—C 1-3 alkylene—CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, -NL1—CO—NR a1 R a2 , -NL1—CO-(5-8 membered heteroaryl), -NLI—CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —S—C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, −50 2 —C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6.

114 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 113 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

115 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 114 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

116 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 115 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 3 membered carbocyclic ring, a 4 membered carbocyclic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, wherein each of the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

117 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 116 , R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

118 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 117 , R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, -C 1-3 alkyl or —C 1-3 alkoxy.

119 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 118 , R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

120 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 116 , R a and R w with the atom to which they are both attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 5 membered heteroaryl ring, a 6 membered heteroaryl ring, a 5 membered heterocyclic ring or a 6 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

121 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 120 , wherein each of R a1 and R a2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted -C 1-6 alkyl.

122 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 121 , wherein each of R a1 and R a2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

123 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 122 , wherein each of R a1 and R a2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

124 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 123 , wherein each of R a1 and R a2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

125 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 124 , wherein the compound is of Formula II:

X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ;

each of R X1 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy;

X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO;

each of R X2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF S , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X1 and R X2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 3 is N, S, NR X3 , C(R X3 ) 2 or CR X3 ;

each of R X3 is independently selected from hydrogen, deuterium, halogen, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X2 and R X3 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted ;

X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ;

each of R X4 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl,-C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X3 and R X4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ;

each of R X5 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X4 and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

represents a single bond or a double bond;

G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —;

each of R G is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted;

Y 1 is N or CR Y1 ,

R Y1 is selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy;

Y 2 is N or CR Y2 ;

R Y2 is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R Y1 and R Y2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

when the “ ” in the term “Y 3 Y 4 ” represents a single bond, Y 3 is NR Y3 or C(R Y3 ) 2 , and Y 4 is CO, C(R Y4 ) 2 or NR Y4 ;

when the “ ” in the term “Y 3 Y 4 ” represents a double bond, Y 3 is N or CR Y3 , and Y 4 is N or CR Y4 ;

R Y3 and R Y4 are independently selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH , —C 1-6 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R Y3 and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

T is absent, O, NR 1 or CR 1 R 2 ;

each of R 1 and R 2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or

R 1 and R 2 together with the carbon atom to which they are both attached form CO or C═NR 5 ;

p is 0, 1, 2 or 3;

each of R 3 and R 4 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or

R 3 and R 4 together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or a 5-12 membered heteroaromatic ring or C═NR 5 , and each of the ring systems is independently optionally substituted or unsubstituted;

each of R 5 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy;

q is 0, 1, 2, 3 or 4;

W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

when ring C is absent, Y 5 is CR 5a R 5b , NR 5a or O, and Y 6 is CR 6a R 6b , NR 6a or O;

when ring C is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring;

i) Y 5 is CR 5a or N, and Y 6 is CR 6a or N, when the “ ” in the term “Y 5 Y 6 ” represents a single bond; or

ii) Y 5 is C, and Y 6 is C, when the “ ” in the term “Y 5 Y 6 ” represents a double bond;

each of R 5a and R 5b is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

each of R 6a and R 6b is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

each of R a is independently hydrogen, deuterium, halogen, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-6 alkoxy, —C 1-6 alkyl, —C 3-8 cycloalkyl,-C 1-6 alkylene—NR a1 R a2 , —C 1-6 alkylene-O—C 1-6 alkyl, —C 1-6 alkylene-(3-10 membered heterocyclic), —C 1-6 alkylene-(5-10 membered heteroaryl), —C 1-6 alkylene—CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—NR a1 R a2 , —C 1 , 6 alkylene—NR a1 —CO—C 1-6 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-10 carbocyclic, −5-10 membered heteroaryl, −3-10 membered heterocyclic, —CO—C 1-6 alkyl, —CO—C 1-6 alkylene—NR a1 R a2 , —CO—NR a1 -(3-10 membered heterocyclic), —CO—NR a1 -(3-10 membered heterocyclic), —CO-(3-10 membered heterocyclic), —O—C 1-6 alkylene—CO—OR a1 , —O—C 1-6 alkylene—CO—NR a1 R a2 , —O—C 1-6 alkylene—NR a1 R a2 , —O—C 3-10 carbocyclic, —O-(3-10 membered heterocyclic), —NR a1 —CO—C 1-6 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-10 membered heteroaryl), —NR a1 —CO—C 3-8 cycloalkyl,—NR a1 —C 1-6 alkylene—NR a1 R a2 , —NR a1 —C 1-6 alkylene-(3-10 membered heterocyclic), —NR a1 —C 1-6 alkylene-(5-10 membered heteroaryl), —NR a1 —SO 2 C 1-6 alkyl, —S—C 1-6 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-6 alkyl, —PO(C 1-6 alkyl) 2 , —PO(C 1-6 alkoxy) 2 , −3-10 membered heterocyclic or −5-10 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6; or

two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted;

each of R a1 and R a2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

126 . The compound or pharmaceutically acceptable salt thereof of claim 125 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

127 . The compound or pharmaceutically acceptable salt thereof of claim 122 or claim 126 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

128 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 127 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

129 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 128 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

130 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 129 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

131 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 130 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SFS, —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

132 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 131 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

133 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 132 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene—C 3-6 cycloalkyl or 3-6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

134 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 133 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

135 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 134 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

136 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 135 , wherein R X1 and R X2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

137 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 137 , wherein R X1 and R X2 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

138 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 137 , wherein R X1 and R X2 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted.

139 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 138 , wherein X 3 is N, S, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl,—O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

140 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 139 , wherein X 3 is N, S, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

141 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 140 , wherein X 3 is N, S, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-3 alkyl, —C 1-3 alkoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene-C 1-3 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

142 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 141 , wherein X 3 is N, S, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene—C 1-3 alkoxy, −0—C 5-8 aryl or —O—C 1-3 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

143 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 142 , wherein X 3 is N, S, NR X3 , C(R X3 ) 2 or CR X3 ; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene-C 1-3 alkoxy, —O—C 5-8 aryl or —O—C 1-3 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

144 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 143 , wherein R X2 and R X3 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

145 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 144 , wherein R X2 and R X3 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

146 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 145 , wherein R X2 and R X3 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted.

147 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 146 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

148 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 147 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

149 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 148 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl, —C 1-3 alkoxy, —NHCO-(5-10 membered heterocyclyl) or 5-10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

150 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 149 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

151 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 150 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

152 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 151 , wherein R X3 and R X4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

153 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 152 , wherein R X3 and R X4 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

154 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 153 , wherein R X3 and R X4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

155 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 154 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

156 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 155 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

157 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 156 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

158 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 157 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

159 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 158 , wherein X 5 is N, S, NR X5 , C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

160 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 159 , wherein R X4 and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

161 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 160 , wherein R X4 and R X5 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

162 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 161 , wherein R X4 and R X5 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

163 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 162 , wherein ring A is selected from

164 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 163 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —,

—NR G —SO 2 —, —C(R G ) 2 — or —SO 2 —NR G —; each of R G is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted.

165 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 164 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —; each of R G is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted or unsubstituted.

166 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 165 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —; each of R G is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted or unsubstituted.

167 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 166 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C s-m aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

168 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 167 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

169 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 168 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

170 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 169 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

171 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 170 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

172 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 171 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

173 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 172 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

174 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 173 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

175 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 174 , R Y1 and R Y2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

176 . The compound or pharmaceutically acceptable salt thereof of any one of claims 122 - 172 , R Y1 and R Y2 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

177 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 176 , R Y1 and R Y2 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

178 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 177 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

179 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 178 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

180 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 179 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

181 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 180 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

182 . The compound or pharmaceutically acceptable salt thereof of any one claims 125 - 181 , wherein R Y3 and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

183 . The compound or pharmaceutically acceptable salt thereof of any one claims 125 - 182 , wherein R Y3 and R Y4 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

184 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 183 , wherein R Y3 and R Y4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

185 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 184 , wherein ring B is selected from

186 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 185 , wherein each of R 1 and R 2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

187 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 186 , wherein each of R 1 and R 2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

188 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 187 , wherein each of R 1 and R 2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

189 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 188 , wherein each of R 1 and R 2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

190 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 189 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form CO or C═NR 5 .

191 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 190 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form CO.

192 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 191 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form C═NR 5 .

193 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 192 , wherein each of R 3 and R 4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

194 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 193 , wherein each of R 3 and R 4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

195 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 194 , wherein each of R 3 and R 4 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

196 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 195 , wherein each of R 3 and R 4 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

197 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 196 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or a 5-12 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

198 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 197 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form a 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

199 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 198 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

200 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 199 , wherein each of R 5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy.

201 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 200 , wherein each of R 5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy.

202 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 201 , wherein each of R 5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy

203 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 202 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkyl-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

204 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 203 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-3 alkyl, —CO—OC 1-3 alkyl, —C 1-3 alkyl—O—C 1-3 alkoxy, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

205 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 204 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

206 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 205 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

207 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 206 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

208 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 207 , wherein ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

209 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 208 , wherein ring C is absent, a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

210 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 209 , wherein ring C is absent, a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, a 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

211 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 210 , wherein ring C is selected from

212 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 211 , wherein each of R 5a and R 5b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

213 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 212 , wherein each of R 5a and R 5b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

214 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 213 , wherein each of R 5a and R 5b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

215 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 214 , wherein each of R sa and R 5b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

216 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 215 , wherein each of R 6a and R 6b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

217 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 216 , wherein each of R 6a and R 6b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

218 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 217 , wherein each of R 6a and R 6b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

219 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 218 , wherein each of R 6a and R 6b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

220 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 219 , wherein each of R a is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-3 alkoxy, —C 1-3 alkyl, —C 3-6 cycloalkyl, —C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene—CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene-NR a1 —CO—C 1-3 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −5-10 membered heteroaryl, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene-NR a1 R a2 , —CO—NR a1 -(3-8 membered heterocyclic), —CO—NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene-CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, −0-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl, —NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1 - 3 alkyl, —S—C 1-3 alkyl, —SO 2 NR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6.

221 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 220 , wherein each of R a is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, methoxy, ethoxy, propoxy, isopropoxy methyl, ethyl, propyl, isopropyl, —C 3-6 cycloalkyl, —C 1-3 alkylene-NR a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene-CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—NR a1 —C—NR a1 R a2 , —CO—NR a1 R a2 , —C 3-8 carbocyclic, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene-NR a1 R a2 , —CO—NR a1 -(3-8 membered heterocyclic), —CO-NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene-CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, −O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, -NIU-00-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —S—C 1-3 alkyl, —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6.

222 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 221 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

223 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 222 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

224 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 223 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 3 membered carbocyclic ring, a 4 membered carbocyclic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, wherein each of the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

225 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 224 , wherein each of R a1 and R a2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted -C 1-6 alkyl.

226 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 225 , wherein each of R a1 and R a2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

227 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 226 , wherein each of R a1 and R a2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ;

—CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl;

—C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

228 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 227 , wherein each of R a1 and R a2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ;

—CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

229 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 228 , wherein the compound is of Formula II-a:

Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y1 , R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in claims 125 - 228 .

230 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 229 , wherein the compound is of Formula II-b

Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y1 , R Ya , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in claims 125 - 228 .

231 . The compound or pharmaceutically acceptable salt thereof of any one of claims 125 - 230 , wherein the compound is of Formula II-c

Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y1 , R Y2 , R Ya , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in claims 125 - 228 .

232 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 124 , wherein the compound is of Formula III:

X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ;

each of R X1 is selected from hydrogen, deuterium, halogen, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxyl;

X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO;

each of R X2 is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X1 and R X2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3 ;

each of R X3 is independently selected from hydrogen, deuterium, halogen, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl,-C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl or —O—C 1-6 alkylene-C 1-6 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X2 and R X3 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted ;

X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ;

each of R X4 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X3 and R X4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

X 5 is N, NR X5 C(R X5 ) 2 or CR X5 ;

each of R X5 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or

R X4 and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

represents a single bond or a double bond;

G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —,

—C(R G ) 2 — or —SO 2 —NR G —,

each of R G is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted;

Y 1 is N or CR Y1 ,

R Y1 is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy;

Y 2 is N or CR Y2 ,

R Y2 is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy;

when the “ ” in the term “Y 3 Y 4 ” represents a single bond, Y 3 is NR Y3 , and Y 4 is CO;

when the “ ” in the term “Y 3 Y 4 ” represents a double bond, Y 3 is N or CR Y3 , and Y 4 is N or CR Y4 ;

R Y3 and R Y4 are independently selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH ,-C 1-6 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxyl;

T is absent, O, NR 1 or CRIR 2 ;

each of R 1 and R 2 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or

R 1 and R 2 together with the carbon atom to which they are both attached form CO or C═NR 5 ;

p is 0, 1, 2 or 3;

each of R 3 and R 4 is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or

R 3 and R 4 together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or 5-12 membered heteroaromatic ring or C═NR 5 , and each of the ring systems is independently optionally substituted or unsubstituted;

each of R 5 is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy;

q is 0, 1, 2, 3 or 4;

W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkyl-O—C 16 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted;

when ring C is absent, Y 5 is CR 5a R 5b , NR 5a or O, and Y 6 is CR 6a R 6b , NR 6a or O;

when ring C is 5-12 membered aromatic ring, 5-12 membered heteroaromatic ring or 5-12 membered heterocyclic ring;

i) Y 5 is CR 5a or N, and Y 6 is CR 6a or N, when the “ ” in the term “Y 5 Y 6 ” represents a single bond; or

ii) Y 5 is C, and Y 6 is C, when the “ ” in the term “Y 5 Y 6 ” represents a double bond;

each of R 5a and R 5b is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

each of R 6. and R 6b is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl;

each of R a is independently hydrogen, deuterium, halogen, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-6 alkoxy, —C 1-6 alkyl, —C 3-8 cycloalkyl,-C 1-6 alkylene—NR a1 R a2 , —C 1-6 alkylene-O—C 1-6 alkyl, —C 1-6 alkylene—CO—OR a1 , —C 1-6 alkylene-(3-10 membered heterocyclic), —C 1-6 alkylene-(5-10 membered heteroaryl), —C 1-6 alkylene—CO—NR a1 R a2 , —C 1-6 alkylene - NR a1 —CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—C 1-6 alkyl, —CO—NR a1 R a2 , —COO—C 1-6 alkyl, —CO—CO—NR a1 R. 2 , —C 3-10 carbocyclic, −5-10 membered heteroaryl, −3-10 membered heterocyclic, —CO—C 1-6 alkyl, —CO—C 1-6 alkylene—NR a1 R a2 , —CO—NR a1 -(3-10 membered heterocyclic), —CO—NR a1 -(3-10 membered heterocyclic), —CO-(3-10 membered heterocyclic), —O—C 1-6 alkylene—CO—OR a1 , —O—C 1-6 alkylene—CO—NR a1 R.2,—O—C 1-6 alkylene—NR a1 R a2 , —O—C 3-10 carbocyclic, —O-(3-10 membered heterocyclic), —NR a1 —CO—C 1-6 alkyl, —NR a1 —CO—NR a1 R. 2 , —NR—CO-(5-10 membered heteroaryl), —NR a1 —CO—C 3-8 cycloalkyl,—NR a1 —C 1-6 alkylene—NR a1 R a2 , —NR a1 —C 1-6 alkylene-(3-10 membered heterocyclic), —NR a1 —C 1-6 alkylene-(5-10 membered heteroaryl), —NR a1 —SO 2 C 1-6 alkyl, —S—C 1-6 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-6 alkyl, —SO 2 C 1-6 alkyl, —PO(C 1-6 alkyl) 2 , —PO(C 1-6 alkoxy) 2 , −3-10 membered heterocyclic or −5-10 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6; or

two adjacent R a can be joined together to form a 6-membered aryl ring, 5-membered heteroaryl ring, 6-membered heteroaryl ring, −3-6 membered heterocyclic or -3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted; or

R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, 3-10 membered heteroaromatic ring or 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted;

each of R a1 and R a e is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

233 . The compound or pharmaceutically acceptable salt thereof of claim 232 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

234 . The compound or pharmaceutically acceptable salt thereof of claim 232 or claim 233 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

235 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 234 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

236 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 235 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

237 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 236 , wherein X 1 is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

238 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 237 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

239 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 238 wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

240 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 239 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-4 alkyl, —C 1-3 alkoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl or 3-6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

241 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 240 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

242 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 241 , wherein X 2 is N, S, NR X2 , C(R X2 ) 2 , CR X2 or CO; each of R X2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

243 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 242 , wherein R X1 and R X2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

244 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 243 , wherein R X1 and R X2 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

245 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 244 , wherein R X1 and R X2 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted.

246 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 245 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl or —O—C 1-6 alkylene-C 1-6 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

247 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 246 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl or —O—C 1-6 alkylene-C 1-6 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

248 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 247 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-3 alkyl,—C 1-3 alkoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene—C 1-3 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

249 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 248 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene-C 1-3 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

250 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 249 , wherein X 3 is N, S, O, NR X3 , C(R X3 ) 2 or CR X3; each of R X3 is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene —C 1-3 alkyl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

251 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 250 , wherein R X2 and R X3 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

252 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 251 , wherein R X2 and R X3 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

253 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 252 , wherein R X2 and R X3 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted.

254 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 253 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

255 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 254 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

256 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 255 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl,—C 1-3 alkoxy, —NHCO-(5-10 membered heterocyclyl) or 5-10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

257 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 256 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

258 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 257 , wherein X 4 is N, S, NR X4 , C(R X4 ) 2 or CR X4 ; each of R X4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

259 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 258 , wherein R X3 and R X4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

260 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 259 , wherein R X3 and R X4 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

261 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 260 , wherein R X3 and R X4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

262 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 261 , wherein X 5 is N, S, NR X5 C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

263 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 262 , wherein X 5 is N, S, NR X5 C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

264 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 263 , wherein X 5 is N, S, NR X5 C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

265 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 264 , wherein X 5 is N, S, NR X5 C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

266 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 265 , wherein X 5 is N, S, NR X5 C(R X5 ) 2 or CR X5 ; each of R X5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

267 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 266 , wherein R X4 and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

268 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 267 , wherein R X4 and R X5 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

269 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 268 , wherein R X4 and R X5 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

270 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 269 , wherein ring A is selected from

271 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 270 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —,

—C(R G ) 2 — or —SO 2 —NR G —;

each of R G is independent selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted.

272 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 271 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —,

—C(R G ) 2 — or —SO 2 —NR G —;

each of R G is independent selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted or unsubstituted.

273 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 272 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —,

—C(R G ) 2 — or −502—NR G —;

each of R G is independent selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted or unsubstituted.

274 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 273 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, -C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, -C 1-6 alkyl or —C 1-6 alkoxy.

275 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 274 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

276 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 275 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

277 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 276 , wherein Y 1 is N or CR Y1 ; R Y1 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

278 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 277 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

279 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 278 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

280 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 279 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

281 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 280 , wherein Y 2 is N or CR Y2 ; R Y2 is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

282 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 281 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH , —C 1-6 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

283 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 282 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH ,-C 1-6 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

284 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 283 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH ,—C 1-3 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

285 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 284 , wherein R Y3 and R Y4 are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH ,—C 1-3 alkylene—OH, —CONH 2 or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

286 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 285 , wherein ring B is selected from

287 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 286 , wherein each of R 1 and R 2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

288 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 287 , wherein each of R 1 and R 2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

289 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 288 wherein each of R 1 and R 2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

290 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 289 , wherein each of R 1 and R 2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

291 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 290 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form CO or C═NR 5.

292 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 291 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form CO.

293 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 292 , wherein R 1 and R 2 together with the carbon atom to which they are both attached form C═NR 5 .

294 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 293 , wherein each of R 3 and R 4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

295 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 294 , wherein each of R 3 and R 4 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted

296 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 295 wherein each of R 3 and R 4 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

297 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 296 , wherein each of R 3 and R 4 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

298 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 297 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form 3-12 membered heterocyclic ring or 5-12 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

299 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 298 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form 3-10 membered heterocyclic ring or 5-10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

300 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 299 , wherein R 3 and R 4 together with the carbon atom to which they are both attached form 3 membered heterocyclic ring, 4 membered heterocyclic ring, 5 membered heterocyclic ring, 6 membered heterocyclic ring, 7 membered heterocyclic ring, 8 membered heterocyclic ring, 9 membered heterocyclic ring, 10 membered heterocyclic ring, 5 membered heteroaromatic ring, 6 membered heteroaromatic ring, 7 membered heteroaromatic ring, 8 membered heteroaromatic ring, 9 membered heteroaromatic ring, 10 membered heteroaromatic ring or C═NR 5 , and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

301 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 300 , wherein each of R 5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy.

302 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 301 , wherein each of R 5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy.

303 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 302 , wherein each of R 5 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

304 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 303 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkyl-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

305 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 304 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-3 alkyl, —CO—OC 1-3 alkyl, —C 1-3 alkyl—O—C 1-3 alkoxy, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl

306 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 305 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

307 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 306 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

308 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 307 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

309 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 308 , wherein ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

310 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 309 , wherein ring C is absent, a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

311 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 310 , wherein ring C is absent, a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted.

312 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 311 , wherein ring C is selected from

313 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 312 , wherein each of R 5a and R 5b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

314 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 313 , wherein each of R 5a and R 5b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

315 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 314 , wherein each of R 5a and R 5b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

316 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 315 , wherein each of R Ya and R 5b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ;

—CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

317 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 316 , wherein each of R 6a and R 6b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl.

318 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 317 , wherein each of R 6a and R 6b is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

319 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 318 , wherein each of R 6a and R 6b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

320 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 319 , wherein each of R 6a and R 6b is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

321 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 320 , wherein each of R a is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-3 alkoxy,—C 1-4 alkyl, —C 3-6 cycloalkyl, —C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene—CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—C 1-3 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR a1 -(3-8 membered heterocyclic), —CO—NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene-CO—NR a1 R a2 , - 0 - C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6.

322 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 321 , wherein each of R a is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R. 2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, methoxy, ethoxy, propoxy, isopropoxy methyl, ethyl, propyl, isopropyl, butyl, isobutyl, —C 3-6 cycloalkyl,-C 1-3 alkylene - NR a1 R a2 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), - 3 alkylene - CO - NR a1 R a2 , - 3 alkylene - NR a1 - CO - NR a1 R a2 , —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR.1-(3-8 membered heterocyclic), —CO—NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene—CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6.

323 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 322 , wherein each of R a1 and R a e is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted

324 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 323 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

325 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 324 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

326 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 325 , wherein two adjacent R a can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 3 membered carbocyclic ring, a 4 membered carbocyclic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, wherein each of the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

327 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 326 , R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy.

328 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 327 , R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

329 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 328 , R a and R w with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

330 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 329 , R a and R w with the atom to which they are both attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 5 membered heteroaryl ring, a 6 membered heteroaryl ring, a 5 membered heterocyclic ring or a 6 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy.

331 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 330 , wherein each of R a1 and R a2 is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl.

332 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 331 , wherein each of R a1 and R a2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy.

333 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 332 , wherein each of R a1 and R a2 is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy.

334 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 333 , wherein the compound is of Formula III-a:

Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in claims 232 - 333 .

335 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 334 , wherein the compound is of Formula III-b:

Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in claims 232 - 334 .

336 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 335 , wherein the compound is of Formula III-c:

Wherein X 1 , X 2 , X 3 , X 4 , X 5 , G, R Y3 , T, R 3 , R 4 , W, Y 5 , Y 6 , R a , p, q and n are as defined in claims 232 - 335 .

337 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 336 , wherein the compound is of Formula III-d:

Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in claims 232 - 336 .

338 . The compound or pharmaceutically acceptable salt thereof of any one of claims 232 - 337 , wherein the compound is of Formula III-e:

Wherein X 1 , X 2 , X 3 , X 4 , X 5 , G, R Ya , T, R 3 , R 4 , W, Y 5 , Y 6 , R a , p, q and n are as defined in claims 232 - 337 .

339 . The compound or pharmaceutically acceptable salt thereof of any one of claims 1 - 338 , wherein the compound is selected from

1

ethyl (S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5--2-

carboxylate

2

(S)-1′-(5-(2,3-dichlorophenyl)-6-methylpyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-

6,4′-piperidin]-5-amine

3

(S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5-

methylpyrazine-2-carboxylic acid

4

(S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5-

methylplyrazine-2-carboxamide

5

ethyl (S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((2-amino-3-chloropyridin-

4-yl)thio)-5-methylpyrazine-2-carboxylate

6

(S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-methylpyrazin-2-yl)-1,3-dihydrospiro[indene-2

4′-piperidin]-1-amine

7

(S)-1′-(6-amino-5-((2,3-dichlorophenyl)thio)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

8

(S)-1′-(4-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrimidin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

9

(S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

10

(S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-(methylamino)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

11

(S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-(dimethylamino)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

12

(S)-1′-(6-amino-5-(thiazol-4-ylthio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-

piperidin]-5-amine

13

(S)-1′-(6-amino-5-(thiazol-2-ylthio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-

piperidin]-5-amine

14

(S)-1′-(6-amino-5-(quinolin-3-ylthio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-

piperidin]-5-amine

15

(S)-5-amino-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidine]-3-carbonitrile

16

(S)-1′-(5-((2-ammo-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-N-methyl-1,3-dihydrospiro[indene-

2,4′-piperidin]-1-amine

17

(S)-1′-(5-((3,5-dichloropyridin-4-yl)thio)pyrazin-2-yl)-5,6,7-trifluoro-1,3-dihydrospiro[indene-

2,4′-piperidin]-1-amine

18

(S)-1-amino-1′-(2-((2-cyanopyridin-3-yl)thio)pyrimidin-5-yl)-1,3-dihydrospiro[indene-2,4′-

piperidine]-4-carbonitrile

19

(S)-1′-(5-((3-chloro-2-methoxypyridin-4-yl)thio)pyrazin-2-yl)-6-(methylthio)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

20

(S)-1-(5-((5-(4-amino-2-(tert-butyl)-4,6-dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-1′-

yl)pyrazin-2-yl)thio)-2-chlorophenyl)ethan-1-one

21

(S)-1′-(5-((3-chloro-2-(isopropylamino)pyridin-4-yl)thio)pyrazin-2-yl)-6-(methylsulfonyl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

22

(S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-7,7-d2-5-amine

23

(S)-(3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5-

methylpyrazin-2-yl)methanol

24

(S)-(3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((2-amino-3-chloropyridin-4-

yl)thio)-5-methylpyrazin-2-yl)methanol

25

(S)-1′-(3-bromo-5-(2,3-dichlorophenyl)-6-methylpyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

26

(S)-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(2,3-

dichlorophenyl)-5-methylpyrazine-2-carbonitrile

27

(S)-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(2,3-

dichlorophenyl)-5-methylpyrazine-2-carboxamide

28

(S)-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(2,3-

dichlorophenyl)-5-methylpyrazin-2-ol

29

(S)-1′-(6-amino-3-bromo-5-((2,3-dichlorophenyl)thio)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

30

(S)-5-amino-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-((2,3-

dichlorophenyl)thio)pyrazine-2-carbonitrile

31

(S)-5-amino-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-((2,3-

dichlorophenyl)thio)pyrazine-2-carboxamide

32

(S)-1′-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

33

(S)-1′-(6-((2-amino-3-chloropyridin-4-yl)thio)pyridin-3-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

34

(S)-1′-(4-((2-amino-3-chloropyridin-4-yl)thio)phenyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-

6,4′-piperidin]-5-amine

35

(S)-1′-(4-((2-amino-3-chloropyridin-4-yl)thio)isoquinolin-1-yl)-1,3-dihydrospiro[indene-2,4′-

piperidin]-1-amine

36

(S)-6-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-3-(2,3-

dichlorophenyl)-5-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

37

(S)-6-(1-amino-6-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(2,3-dichlorophenyl)-

5-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

38

(S)-6-(1-amino-5,6,7-trifluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-methyl-3-(5-

methylthiophen-2-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

39

(S)-2-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-5-(2,3-

dichlorophenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

40

(S)-6-amino-2-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-((2-amino-3-

chloropyridin-4-yl)thio)-3-methylpyrimidin-4(3H)-one

41

(S)-1′-(6-amino-5-((4-chlorothiazol-2-yl)thio)pyrazin-2-yl)-4,6-

dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine

42

(S)-1-amino-1′-(5-((4-amino-5-bromopyrimidin-2-yl)thio)-1-methyl-6-oxo-1,6-dihydropyridin-2-

yl)-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile

43

(S)-6-(1-amino-6-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-((3-chloro-2-

methoxypyridin-4-yl)thio)-1-methylpyridin-2(1H)-one

44

(S)-1-amino-1′-(4-(6-bromonaphthalen-2-yl)thiazol-2-yl)-1,3-dihydrospiro[indene-2,4′-

piperidine]-6-carbonitrile

45

(S)-1′-(6-amino-5-(2-chloro-3-methylphenyl)pyrazin-2-yl)-6-bromo-1,3-dihydrospiro[indene-2,4′-

piperidin]-1-amine

46

(S)-1′-(5-(3-amino-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)-1,3-dihydrospiro[indene-2,4′-

piperidine]-1,6-diamine

47

(S)-1′-(6-amino-5-(2-chloro-3-methylphenyl)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′-

piperidine]-1,6-diamine

48

(S)-1′-(6-(5-chlorothiophen-2-yl)pyridazin-3-yl)-5-methyl-1,3-dihydrospiro[indene-2,4′-

piperidin]-1-amine

49

(S)-1′-(6′-chloro-[3,3′-bipyridazin]-6-yl)-5-methyl-1,3-dihydrospiro[indene-2,4′-piperidin]-1-

amine

50

(S)-1′-(3-(3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

51

(R)-1′-(5-(2,3-dichloro-5-methoxyphenyl)pyridin-2-yl)-2,3-dihydrospiro[indene-1,4′-piperidin]-

2-amine

52

(S)-6′-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1′-methyl-2′-oxo-1′,2′-

dihydro-[3,3′-bipyridine]-2-carbonitrile

53

(S)-6′-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1′-methyl-2′-oxo-1′,2′-

dihydro-[3,3′-bipyridine]-2-carboxamide

54

(S)-1′-(4-(3-methoxyphenyl)cyclohexyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-

5-amine

55

(S)-1-amino-1′-(6-((3-amino-2-chlorophenyl)thio)-1,2,4-triazin-3-yl)-1,3-dihydrospiro[indene-

2,4′-piperidine]-6-carbonitrile

56

1-(5-((5-((1S)-1-amino-6-(methylsulfmyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyrazin-

2-yl)thio)-2-chlorophenyl)ethan-1-one

57

(S)-1′-(5-(pyrimidin-2-ylthio)pyrazin-2-yl)-6-(trifluoromethyl)-1,3-dihydrospiro[indene-2,4′-

piperidin]-1-amine

58

(S)-6-bromo-5-fluoro-1′-(5-(quinolin-4-ylthio)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′-

piperidin]-1-amine

59

(S)-6-(4-amino-4,6-dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-1′-yl)-3-(3-

(trifluoromethyl)pyridin-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

60

(S)-2-(1-amino-6-chloro-5-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(3,5-

dichloropyridin-4-yl)-3-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

61

(S)-1′-(7-(5-chloropyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-1,3-

dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-3-amine

62

(S)-1′-(7-(3-chloropyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-1H,3H-spiro[phenalene-2,4′-

piperidin]-1-amine

63

(R)-1′-(3-(2-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3,4-dihydro-1H-

spiro[naphthalene-2,4′-piperidin]-3-amine

64

(S)-6-amino-2-(1-amino-7-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-methyl-5-

phenylpyrimidin-4(3H)-one

65

(S)-1-amino-1′-(4-amino-6-oxo-5-(pyridazin-3-ylthio)-1,6-dihydropyrimidin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidine]-7-carbonitrile

66

(S)-1-amino-1′-(1-methyl-6-oxo-5-(pyrazin-2-yl)-1,6-dihydropyrimidin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidine]-7-carbonitrile

67

(S)-2-(1-amino-6-chloro-5-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-((4-

isopropylphenyl)thio)pyrimidin-4(3H)-one

68

(S)-4-amino-6-(1-amino-6-bromo-5-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(2-

chloro-3-methylphenyl)-1-methylpyridin-2(1H)-one

69

(S)-6-(4-acetyl-1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-4-amino-3-(4-

(trifluoromethyl)phenyl)pyridin-2(1H)-one

70

(S)-6′-(1-amino-4-hydroxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-2′-oxo-1′,2′-dihydro-

[3,3′-bipyridine]-2-carbonitrile

71

(S)-1′-(3-bromo-5-(1H-indol-6-yl)-6-methylpyrazin-2-yl)-4,6-

dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine

72

(S)-3-(4-amino-4,6-dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-1′-yl)-5-methyl-6-(2-

oxoindolin-7-yl)pyrazine-2-carbonitrile

73

(S)-1′-(5-amino-6-((2-amino-3-chloropyridin-4-yl)thio)-1,2,4-triazin-3-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

74

(S)-1′-(5-amino-6-((2-amino-3-chloropyridin-4-yl)thio)pyridin-3-yl)-6-chloro-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

75

(S)-1′-(4-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

76

(S)-1′-(5-((2,3-dichlorophenyl)thio)thiazol-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-

piperidin]-7-amine

77

(R)-1′-(4-((3-chloropyridin-4-yl)thio)thiazol-2-yl)spiro[indoline-2,4′-piperidin]-3-amine

78

(R)-1′-(2-(7-chloro-1H-indol-1-yl)thiazol-4-yl)-2,3-dihydrospiro[indene-1,4′-piperidin]-2-amine

79

(R)-1′-(2-((2-(trifluoromethyl)phenyl)thio)thiazol-5-yl)-3H-spiro[benzofuran-2,4′-piperidin]-3-

amine

80

(S)-(5-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyrazin-2-yl)(2,3-

dichlorophenyl)methanone

81

(S)-2-(1-amino-6-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(indolin-1-yl)-3-methyl-

3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

82

(S)-1′-(5-((1,2,3,4-tetrahydroquinolin-8-yl)thio)pyrazin-2-yl)-1,3-

dihydrospiro[cyclopenta[b]naphthalene-2,4′-piperidin]-1-amine

83

(S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-1,3-

dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-1-amine

84

1′-(5-((3-amino-2-chlorophenyl)thio)-6-methylpyrazin-2-yl)-1-methyl-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

85

(R)-1′-(7-((2-amino-3-chloropyridin-4-yl)thio)-1H-indol-4-yl)-3H-spiro[benzofuran-2,4′-

piperidin]-3-amine

86

(S)-1′-(7-((2-amino-3-chloropyridin-4-yl)thio)isoquinolin-3-yl)-5,6-dibromo-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

87

(S)-4-((5-(5-acetyl-1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-aminopyrazin-2-

yl)thio)-3-chloro-1-methylpyridin-2(1H)-one

88

(S)-5-(1-amino-6-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-2-((2,3-dichlorophenyl)thio)-

6-(hydroxymethyl)pyridin-3-ol

89

(S)-6-bromo-1′-(5-(2,3-dichlorophenyl)-6-methylimidazo[1,5-a]pyrazin-8-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

90

(S)-1′-(7-((2-amino-3-chloropyridin-4-yl)thio)-[1,2,5]thiadiazolo[3,4-c]pyridin-4-yl)-6-bromo-1,3-

dihydrospiroindene-2,4′-piperidin]-1-amine

91

(S)-1′-(8-((2-amino-3-chloropyridin-4-yl)thio)pyrido[4,3-d]pyrimidin-5-yl)-6-bromo-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

92

(S)-3-(5-(1-amino-6-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyridin-2-yl)-4,5-

dichlorophenol

93

(S)-1-amino-1′-(5-(5-methylthiophen-2-yl)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-

6-ol

94

(S)-1′-(5-(1H-indol-7-yl)pyrazin-2-yl)-5-ethyl-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine

95

(S)-1′-(5-(cyclohex-1-en-1-yl)pyrazin-2-yl)-5-isopropyl-1,3-dihydrospiro[indene-2,4′-piperidin]-

1-amine

96

(S)-N-(1-amino-1′-(5-(2-(trifluoromethyl)phenyl)pyrimidin-2-yl)-1,3-dihydrospiro[indene-2,4′-

piperidin]-6-yl)methanesulfonamide

97

(S)-1′-(5-((4-(trifluoromethyl)pyrimidin-5-yl)thio)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[c]pyridine-6,4′-piperidin]-7-amine

98

(S)-1′-(5-((2-chloropyridin-3-yl)thio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[c]pyridine-6,4′-

piperidin]-5-amine

99

(S)-4-((5-(5-amino-5,7-dihydrospiro[cyclopenta[d]pyrimidine-6,4′-piperidin]-1′-yl)pyrazin-2-

yl)thio)-3-chlorobenzoic acid

100

(S)-1′-(5-((3-(trifluoromethyl)pyrazin-2-yl)thio)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-7-amine

101

(S)-1′-(5-((3-chloropyridazin-4-yl)thio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[d]pyrimidine-

6,4′-piperidin]-7-amine

102

(S)-4-((5-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyrazine-6,4′-piperidin]-1′-yl)pyrazin-2-

yl)thio)-3-chlorobenzamide

103

(S)-(1-amino-1′-(5-((3-chloro-2-(methylamino)pyridin-4-yl)thio)pyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-6-yl)dimethylphosphine oxide

104

(S)-1-amino-1′-(6-amino-5-((3-chloro-2-(dimethylamino)pyridin-4-yl)thio)pyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidine]-5-carboxylic acid

105

ethyl (S)-1-amino-1′-(5-((3-chloro-2-(methylamino)pyridin-4-yl)thio)pyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidine]-5-carboxylate

106

(S)-1′-(5-((3-(morpholinomethyl)phenyl)thio)pyrazin-2-yl)-6-(trifluoromethyl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

107

(S)-6-bromo-5-fluoro-1′-(5-((3-(pentafluoro-16-sulfanyl)phenyl)thio)pyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

108

(S)-N-(3-((5-(1-amino-6-(methylthio)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyrazin-2-

yl)thio)phenyl)cyclopropanecarboxamide

109

(S)-6-(6-amino-1-bromo-4H,6H-spiro[cyclopenta[c]thiophene-5,4′-piperidin]-1′-yl)-3-(m-tolyl)-

1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

110

(S)-2-(1-amino-5,6,7-trifluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(3-ethylphenyl)-3-

methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

111

(R)-1′-(3-(3-(tert-butyl)phenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3,4-dihydro-1H-

spiro[naphthalene-2,4′-piperidin]-3-amine

112

(S)-2-(3-amino-1,3-dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-1′-yl)-5-

(3-isopropylphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

113

(S)-1-amino-1′-(3-(3-chloro-2-morpholinopyridin-4-yl)-4-oxo-4,5-dihydro-1H-

pyrrolo[3,2-c]pyridin-6-yl)-5-fluoro-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile

114

(S)-1′-(7-(3-chloro-2-(cyclobutylamino)pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-1,3-

dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-3-amine

115

(S)-1′-(3-(3-chloro-2-(cyclopropylamino)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-N6-

methyl-1,3-dihydrospiro[indene-2,4′-piperidine]-1,6-diamine

116

(S)-5-amino-1′-(3-(3-chloro-2-(pyrrolidin-1-yl)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-2-

fluoro-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidine]-3-carboxamide

117

1-(4-(6-((S)-4-amino-2-chloro-4,6-dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-3-chloropyridin-2-yl)pyrrolidin-3-ol

118

(S)-1′-(3-(3-chloro-2-((cyclopropylmethyl)amino)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-

N6,N6-dimethyl-1,3-dihydrospiro[indene-2,4′-piperidine]-1,6-diamine

119

(S)-1′-(3-(2-amino-6-chloropyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-2-(tert-butyl)-4,6-

dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-4-amine

120

(S)-2-chloro-1′-(3-(1,3-dihydroisobenzofuran-5-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6-

dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-6-amine

121

(S)-3-chloro-1′-(3-((2-chlorophenyl)thio)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

122

(S)-1′-(3-(3-chloro-2-(ethylamino)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6-

dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-4-amine

123

(R)-1′-(7-(methyl(pyridin-4-yl)amino)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-3H-

spiro[furo[2,3-b]pyridine-2,4′-piperidin]-3-amine

124

(R)-1′-(3-((3-chloropyridin-4-yl)amino)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-6,7-

dihydrospiro[cyclopenta[b]pyridine-5,4′-piperidin]-6-amine

125

(S)-2-methoxy-1′-(3-(1-phenylvinyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6-

dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine

126

(R)-1-(3-benzyl-1H-pyrazolo[3,4-b]pyrazin-6-yl)-1′,3′-dihydrospiro[piperidine-4,2′-

pyrrolo[2,3-b]pyridin]-3′-amine

127

(S)-(6-(6-amino-4,6-dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)(phenyl)methanone

128

(4S)-1′-(3-(1-phenylethyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6-

dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine

129

1-(6-((S)-5-amino-2-methoxy-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-1-phenylethan-1-ol

130

(S)-1′-(3-((2,3-dichloropyridin-4-yl)oxy)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

131

(S)-6-bromo-1′-(3-(5-(3,4-difluorophenyl)-3,4-dihydroquinolin-1(2H)-yl)-1H-

pyrazolo[3,4-b]pyrazin-6-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine

132

(S)-6-amino-2-(1-amino-6-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(4-

cyclopropoxyphenyl)-3-methylpyrimidin-4(3H)-one

133

(S)-N-(1-amino-1′-(4-amino-5-((4-(methylthio)phenyl)thio)-6-oxo-1,6-dihydropyrimidin-2-yl)-

1,3-dihydrospiro[indene-2,4′-piperidin]-6-yl)acetamide

134

(S)-2-(1-amino-6-(methylamino)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(4-

(benzyloxy)phenyl)-3-methylpyrimidin-4(3H)-one

135

(S)-2-(7-acetyl-1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(benzo[d][1,3]dioxol-

4-ylthio)pyrimidin-4(3H)-one

136

4-amino-6-((1S)-1-amino-7-(1-hydroxyethyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-

(4-(difluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one

137

(S)-1-amino-1′-(4-amino-6-oxo-5-(4-phenoxyphenyl)-1,6-dihydropyridin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidine]-4-carbonitrile

138

(S)-6-(1-amino-4-hydroxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(4-

cyclohexylphenyl)-1-methylpyridin-2(1H)-one

139

(S)-3-([1,1′-biphenyl]-4-yl)-6-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-

yl)pyridin-2(1H)-one

140

(S)-6-amino-2-(1-amino-6-(2-oxopiperidin-1-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-

methyl-5-(4-(trifluoromethoxy)phenyl)pyrimidin-4(3H)-one

141

(S)-1-(1-amino-1′-(4-amino-5-((4-cyanophenyl)thio)-1-methyl-6-oxo-1,6-dihydropyrimidin-2-

yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-6-yl)urea

142

(S)-4-amino-6-(1-amino-6-chloro-5-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1-

methyl-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-2(1H)-one

143

(S)-6-(1-amino-6-(trifluoromethyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(4-(2-

methoxyethoxy)phenyl)-1-methylpyridin-2(1H)-one

144

(S)-6-amino-2-(1-amino-6-(piperidine-1-carbonyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-

3-methyl-5-(quinolin-8-ylthio)pyrimidin-4(3H)-one

145

(S)-6-amino-2-(1-amino-6-morpholino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-methyl-

5-((4-nitrophenyl)thio)pyrimidin-4(3H)-one

146

(S)-6-amino-2-(5-amino-3-nitro-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-3-

methyl-5-(quinolin-8-ylthio)pyrimidin-4(3H)-one

147

(S)-6-(5-amino-3-(4-methylpiperazin-1-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-

piperidin]-1′-yl)-1-methyl-3-(naphthalen-1-ylthio)pyridin-2(1H)-one

148

(S)-2-(1-amino-6-(1H-pyrrol-1-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-((2,2-

difluorobenzo[d][1,3]dioxol-4-yl)thio)pyrimidin-4(3H)-one

149

(S)-7-(5-(1-amino-6-(1H-imidazol-1-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-

(hydroxymethyl)-3-methylpyrazin-2-yl)isoindolin-1-one

150

(S)-3-(1-amino-6-(ethylamino)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(1H-indol-5-yl)-

5-methylpyrazine-2-carboxamide

151

(S)-N-(1-amino-1′-(3-bromo-5-(1H-indol-6-yl)-6-methylpyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-6-yl)cyclopropanecarboxamide

152

(S)-4-(6-amino-5-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-

methylpyrazin-2-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

153

(S)-3-(1-amino-5-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-methyl-6-(2-

oxoindolin-7-yl)pyrazine-2-carbonitrile

154

(S)-N-(5-(1-amino-7-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((2-

hydroxyethyl)amino)-3-methylpyrazin-2-yl)benzenesulfonamide

155

(S)-1′-(6-methyl-3-(1H-pyrazol-5-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

156

(S)-2-(3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(8-

chlorochroman-7-yl)-5-methylpyrazin-2-yl)propan-2-ol

157

(S)-6-chloro-1′-(5-(7-chloro-2,3-dihydrobenzofuran-6-yl)pyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

158

(S)-4-bromo-1′-(5-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)pyrazin-2-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

159

(S)-1-amino-1′-(6-cyano-5-(1H-indazol-7-yl)pyrazin-2-yl)-5-fluoro-1,3-dihydrospiro[indene-2,4′-

piperidine]-6-carboxamide

160

(S)-1′-(5-(1H-indol-3-yl)-6-iodopyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-

piperidin]-5-amine

161

(R)-6-(5-(7′-amino-7′,8′-dihydro-5′H-spiro[piperidine-4,6′-quinolin]-1-yl)-3-vinylpyrazin-2-

yl)isoindolin-1-one

162

(R)-1-(4-(5-(6-amino-6,7-dihydrospiro[cyclopenta[b]pyridine-5,4′-piperidin]-1′-yl)-3-

ethylpyrazin-2-yl)-3,3-difluoroindolin-1-yl)ethan-1-one

163

(S)-1′-(5-(3-methyl-1H-indazol-6-yl)-6-phenylpyrazin-2-yl)-5,7-

dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine

164

(S)-1′-(5-(1H-benzo[d][1,2,3]triazol-6-yl)-6-cyclopropylpyrazin-2-yl)-6-((tetrahydro-2H-pyran-

4-yl)oxy)-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine

165

(S)-1-amino-1′-(3-((1-methyl-1H-imidazol-2-yl)thio)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-1,3-

dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile

166

(S)-1′-(3-(1H-benzo[d]imidazol-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-6-bromo-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

167

(S)-1-(6-(1-amino-5-chloro-6-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-3,4-dihydro-1,5-naphthyridin-2(1H)-one

168

(1-(6-((S)-1-amino-6-(methylthio)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-1,2,3,4-tetrahydro-1,5-naphthyridin-4-yl)methanol

169

1-(6-((1S)-1-amino-6-(methylsulfinyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-5-fluoro-1,2,3,4-tetrahydroquinoline-6-carbonitrile

170

(S)-6-chloro-1′-(3-(2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-

5-methyl-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine

171

(S)-5-(6-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H-pyrazolo[3,4-

b]pyrazin-3-yl)-N-(2-methoxyethyl)-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carboxamide

172

(S)-1-amino-5-fluoro-1′-(3-(6-(piperazin-1-yl)-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H-

pyrazolo[3,4-b]pyrazin-6-yl)-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile

173

(S)-2-(1-(6-(1-amino-6-(methylthio)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-1,2,3,4-tetrahydroquinolin-5-yl)thiazole-4-carboxylic acid

174

(S)-1′-(6-(aminomethyl)-5-(2,3-dichloropyridin-4-yl)pyrazin-2-yl)-6-(1H-imidazol-1-yl)-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

175

(1S)-1-amino-1′-(5-(2,3-dichloropyridin-4-yl)-3-(2-(hydroxymethyl)pyrrolidine-1-carbonyl)-6-

methylpyrazin-2-yl)-N,N-dimethyl-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carboxamide

176

(S)-1′-(8-(2-amino-3-chloropyridin-4-yl)-7-methylimidazo[1,2-c]pyrimidin-5-yl)-5-fluoro-1,3-

dihydrospiro[indene-2,4′-piperidin]-1-amine

177

(S)-1′-(5-(1-methyl-1H-indol-2-yl)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-3,3-d2-

1-amine

178

(S)-1-(6-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-1H-

pyrazolo[3,4-b]pyrazin-3-yl)-1,2,3,4-tetrahydro-6H-pyrido[1,2-a]pyrimidin-6-one

179

(S)-1′-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7-

dihydrospiro[cyclopenta[c]pyridine-6,4′-piperidin]-5-amine

180

(3-((S)-1-amino-6-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((R)-1-

methylisoindolin-2-yl)pyrazin-2-yl)methanol

181

(S)-1′-(3-(6,7-dihydropyrazolo[1,5-a]pyrimidin-4(5H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7-

dihydrospiro[cyclopenta[c]pyridine-6,4′-piperidin]-5,5-d2-7-amine

182

(S)-4-(difluoromethyl)-1′-(5-methyl-6-((R)-2-methyl-3,4-dihydro-1,5-naphthyridin-1(2H)-

yl)pyridin-3-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine

183

(S)-1′-(8-(2-chloro-3-(isopropyl(methyl)amino)phenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)-

2,3,6,8-tetrahydrospiro[indeno[5,6-b][1,4]dioxine-7,4′-piperidin]-6-amine

184

(S)-1-(5-amino-1′-(8-((5-chloro-1-methylindolin-6-yl)thio)imidazo[1,5-a]pyridin-5-yl)-2,3,5,7-

tetrahydro-1H-spiro[cyclopenta[b]pyrrolo[3,2-e]pyridine-6,4′-piperidin]-1-yl)ethan-1-one

340 . A pharmaceutical composition comprising at least one compound or a pharmaceutically acceptable salt thereof as defined in any one of claims 1 - 339 and at least one pharmaceutically acceptable excipient.

341 . The pharmaceutical composition of claim 340 , wherein, the compound in a weight ratio to the said excipient within the range from about 0.0001 to about 10.

342 . A combination pharmaceutical product comprising the compound or a pharmaceutically acceptable salt thereof of any of claims 1 - 339 , together with one or more other therapeutically active agents.

343 . Use of the compound or a pharmaceutically acceptable salt thereof of any one of claim 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 342 for the preparation of a medicament.

344 . The use of claim 343 , wherein the medicament is used for the treatment or prevention of cancer, cancer metastasis, cardiovascular disease, an immunological disorder or an ocular disorder.

345 . Use, in the manufacture of a medicament for use as an inhibitor of SHP2, of at least one compound or a pharmaceutically acceptable salt thereof any one of claims 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 342 .

346 . Use of the compound or a pharmaceutically acceptable salt thereof of any one of claims 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 342 for the preparation of a medicament in the treatment of diseases or conditions mediated by the activity of SHP2.

347 . The use of claim 346 , wherein the diseases or conditions mediated by the activity of SHP2 is cancer.

348 . The use of claim 346 , wherein the diseases or conditions mediated by the activity of SHP2 is selected from Noonan syndrome, leopard syndrome, juvenile myelomonocytic leukemias, liver cancer, neuroblastoma, melanoma, squamous-cell carcinoma of the head and neck, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, gastric carcinoma, neuroblastoma, anaplastic large-cell lymphoma and glioblastoma.

349 . A method for preventing or treating a disease, lessening a disease symptoms, delaying the progression or onset of a disease, comprising administering to the patient in need thereof a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof of any one of claims 1 - 339 , the pharmaceutical composition of claims 340 or 341 , or the combination pharmaceutical product of claim 342 , wherein the disease is cancer, cancer metastasis, cardiovascular disease, an immunological disorder or an ocular disorder.

350 . A method for inhibiting the activity of SHP2 level, comprising administering to the patient in need thereof a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof of any one of claims 1 - 339 , or the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 342 .

351 . A method for preventing or treating a disease, lessening a disease symptoms, delaying the progression or onset of a disease, comprising administering to the patient in need thereof a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof of any one of claims 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 342 , wherein the disease is mediated by the activity of SHP2.

352 . The method of claim 351 , wherein the disease mediated by the activity of SHP2 is cancer.

353 . The method of claim 351 , wherein the disease mediated by the activity of SHP2 is selected from Noonan syndrome, leopard syndrome, juvenile myelomonocytic leukemias, liver cancer, neuroblastoma, melanoma, squamous-cell carcinoma of the head and neck, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, gastric carcinoma, neuroblastoma, anaplastic large-cell lymphoma and glioblastoma.

354 . The compound or the pharmaceutically acceptable salt thereof of any one of claims 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 342 for use in preventing or treating a disease, lessening a disease symptom, delaying the progression or onset of a disease, wherein the disease is cancer, cancer metastasis, cardiovascular disease, an immunological disorder or an ocular disorder.

355 . The compound or the pharmaceutically acceptable slat thereof any one of claims 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 339 , for use in inhibiting the activity of SHP2.

356 . The compound or the pharmaceutically acceptable salt thereof of any one of claims 1 - 339 , the pharmaceutical composition of claim 340 or 341 , or the combination pharmaceutical product of claim 339 for use in preventing or treating a disease, lessening a disease symptom, delaying the progression or onset of a disease, wherein the disease is mediated by the activity of SHP2.

357 . The compound or the pharmaceutically acceptable salt thereof, the pharmaceutical composition, or the combination pharmaceutical product of claim 356 , wherein the disease mediated by the activity of SHP2 is cancer.

358 . The compound or the pharmaceutically acceptable salt thereof, the pharmaceutical composition, or the combination pharmaceutical product of claim 356 , wherein the disease mediated by the activity of SHP2 is selected from Noonan syndrome, leopard syndrome, juvenile myelomonocytic leukemias, liver cancer, neuroblastoma, melanoma, squamous-cell carcinoma of the head and neck, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, gastric carcinoma, neuroblastoma, anaplastic large-cell lymphoma and glioblastoma.