Bridged ring compounds as hepatitis C virus (HCV) inhibitors and pharmaceutical applications thereof

1. A compound of Formula (I):

or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug thereof,

wherein each of A and A′ is independently a bond, alkyl, alkenyl, cycloalkyl, heterocycloalkyl, —(CR 8 R 8a ) n —O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, or —(CR 8 R 8a ) n —N(R 5 )—C(═O)—O—(CR 8 R 8a ) p —, or each of A and A′ is independently

wherein each X 1 is independently O, S, NR 6 , or CR 7 R 7a ;

each X 2 is independently NR 6 , O or S;

each Y 1 and Y 2 is independently CR 7 ;

Z is —(CH 2 ) a —, —CH═CH—, —N═CH—, —(CH 2 ) a —N(R 5 )—(CH 2 ) b —, or —(CH 2 ) a —O—(CH 2 ) b —, wherein

each a and b is independently 0, 1, 2 or 3;

each c is independently 1 or 2;

each d is independently 1 or 2;

each n is independently 0, 1, 2 or 3;

each p is independently 0, 1, 2 or 3;

each r is independently 0, 1 or 2;

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

each of X and X′ is independently N;

each of Y and Y′ is independently —C(═O)—(CR 9 R 9a ) n —N(R 11 )—C(═O)—O—R 13 where n is selected from 1, 2, or 3;

R 1 and R 2 , together with X—CH they are attached to, form a 3-8 membered heterocycle, C 5-12 fused heterobicycle or C 5-12 spiro heterobicycle and R 3 and R 4 , together with X′—CH they are attached to, form a 3-8 membered heterocycle, C 5-12 fused heterobicycle or C 5-12 spiro heterobicycle;

each R 5 is independently H, deuterium, hydroxy, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, alkoxy, alkyl-OC(═O)—, alkyl-C(═O)—, carbamoyl, alkyl-OS(═O) r —, alkyl-S(═O) r O—, alkyl-S(═O) r — or aminosulfonyl;

each R 5a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, R 7a R 7 N—, —C(═O)NR 7 R 7a , —OC(═O)NR 7 R 7a , —OC(═O)OR 7 , —N(R 7 )C(═O)NR 7 R 7a , —N(R 7 )C(═O)OR 7a , —N(R 7 )C(═O)—R 7a , R 7 R 7a N—S(═O) 2 —, R 7 S(═O) 2 —, R 7 S(═O) 2 N(R 7a )—, R 7a R 7 N-alkyl, R 7 S(═O)-alkyl, R 7 R 7a N—C(═O)-alkyl, R 7a R 7 N-alkoxy, R 7 S(═O)-alkoxy, R 7 R 7a N—C(═O)-alkoxy, aryl, heteroaryl, alkoxy, alkylamino, alkyl, haloalkyl, alkenyl, alkynyl, heterocyclyl, cycloalkyl, mercapto, nitro, aralkyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino or aryloxy;

each R 6 is independently H, deuterium, R 7 R 7a NC(═O)—, R 7 OC(═O)—, R 7 C(═O)—, R 7 R 7a NS(═O)—, R 7 OS(═O)—, R 7 S(═O)—, R 7 R 7a NS(═O) 2 —, R 7 OS(═O) 2 —, R 7 S(═O) 2 —, aliphatic, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl;

each R 6a is independently H, deuterium, hydroxy, amino, F, Cl, Br, I, cyano, oxo (═O), R 7a R 7 N—, —C(═O)NR 7 R 7a , —OC(═O)NR 7 R 7a , —OC(═O)OR 7 , —N(R 7 )C(═O)NR 7 R 7a , —N(R 7 )C(═O)OR 7a , —N(R 7 )C(═O)—R 7a , R 7 R 7a N—S(═O) 2 —, R 7 S(═O) 2 —, R 7 S(═O) 2 N(R 7a )—, R 7a R 7 N-alkyl, R 7 S(═O)-alkyl, R 7 R 7a N—C(═O)-alkyl, R 7a R 7 N-alkoxy, R 7 S(═O)-alkoxy, R 7 R 7a N—C(═O)-alkoxy, aryl, heteroaryl, alkoxy, alkylamino, alkyl, haloalkyl, alkenyl, alkynyl, heterocyclyl, cycloalkyl, mercapto, nitro, aralkyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino, or aryloxy;

each R 7 and R 7a is independently H, deuterium, F, Cl, aliphatic, heteroalkyl, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl, with the proviso that where R 7 and R 7a are bonded to the same nitrogen atom, R 7 and R 7a , together with the nitrogen atom they are attached to, optionally form a substituted or unsubstituted 3-8 membered ring, or a substituted or unsubstituted spiro or fused bicyclic ring;

each R 8 and R 8a is independently H, deuterium, hydroxy, cyano, nitro, F, Cl, Br, I, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, alkoxy, alkyl-OC(═O)—, alkyl-C(═O)—, carbamoyl, alkyl-OS(═O) c —, alkyl-S(═O) c O—, alkyl-S(═O) c —, or aminosulfonyl;

each R 9 , R 9a , and R 11 is independently H, deuterium, alkyl, cycloalkyl, aryl, or cycloalkylalkyl;

each R 13 and R 13a is independently H, deuterium, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl;

wherein each of —(CR 8 R 8a ) n —O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —S(═O) t —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—O—(CR 8 R 8a ) p —, NR 6 , CR 7 R 7a , CR 7 , —(CH 2 ) a —, —CH═CH—, —N═CH—, —(CH 2 ) a —N(R 5 )—(CH 2 ) b —, —(CH 2 ) a —O—(CH 2 ) b —, R 13a R 13 N—, —C(═O)R 13 , —C(═S)R 13 , —C(═O)—O—R 13 , —C(═O)NR 13 R 13a , —OC(═O)NR 13 R 13a , —OC(═O)OR 13 , —N(R 13 )C(═O)NR 13 R 13a , —N(R 13 )C(═O)OR 13a , —N(R 13 )C(═O)—R 13a , R 13 R 13a N—S(═O) 2 —, R 13 S(═O) 2 —, R 13 S(═O) 2 N(R 13a )—, R 13 OS(═O) 2 —, R 7a R 7 N—, —C(═O)NR 7 R 7a , —OC(═O)NR 7 R 7a , —OC(═)OR 7 , —N(R 7 )C(═O)NR 7 R 7a , —N(R 7 )C(═O)OR 7a , —N(R 7 )C(═O)—R 7a , R 7 R 7a N—S(═O) 2 —, R 7 S(═O) 2 —, R 7 S(═O) 2 N(R 7a )—, alkyl-OC(═O)—, alkyl-C(═O)—, alkyl-OS(═O) c —, alkyl-S(═O) c O—, alkyl-S(═O) c —, R 7 R 7a NC(═O)—, R 7 OC(═O)—, R 7 C(═O)—, R 7 R 7a NS(═O)—, R 7 OS(═O)—, R 7 S(═O)—, R 7 R 7a NS(═O) 2 —, R 7 OS(═O) 2 —, R 7a R 7 N-alkyl, R 7 S(═O)-alkyl, R 7 R 7a N—C(═O)-alkyl, R 7a R 7 N-alkoxy, R 7 S(═O)-alkoxy, R 7 R 7a N—C(═O)-alkylamino, alkyl, heteroalkyl, carbocyclyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, C 5-12 fused bicycle, C 5-12 fused heterobicycle, C 5-12 spiro bicycle, C 5-12 spiro heterobicycle, alkoxy, aliphatic, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, haloalkyl, alkenyl, alkynyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino and aryloxy is optionally substituted with one or more substituents, wherein the substituent is deuterium, hydroxy, amino, halo, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyl, alkenyl, alkynyl, heterocyclyl, mercapto, nitro, aryloxy, heteroaryloxy, oxo (═O), carboxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C(═O)—, alkyl-C(═O)—, alkyl-S(═O)—, alkyl-S(═O) 2 —, hydroxy-substituted alkyl-S(═O)—, hydroxy-substituted alkyl-S(═O) 2 —, or carboxy-substituted alkoxy.

2. The compound according to claim 1 , wherein

each R 5a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, R 7a R 7 N—, —C(═O)NR 7 R 7a , —OC(═O)NR 7 R 7a , —OC(═O)OR 7 , —N(R 7 )C(═O)NR 7 R 7a , —N(R 7 )C(═O)OR 7a , —N(R 7 )C(═O)—R 7a , R 7 R 7a N—S(═O) 2 —, S(═O) 2 —, R 7 S(═O) 2 N(R 7a )—, R 7a R 7 N—C 1-6 alkyl, R 7 S(═O)—C 1-6 alkyl, R 7 R 7a N—C(═O)—C 1-6 alkyl, R 7a R 7 N—C 1-6 alkoxy, R 7 S(═O)—C 1-6 alkoxy, R 7 R 7a N—C(═O)—C 1-6 alkoxy, C 6-10 aryl, C 1-9 heteroaryl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-10 heterocyclyl, C 3-8 cycloalkyl, mercapto, nitro, C 6-10 aralkyl, C 6-10 arylamino, C 1-9 heteroarylamino, C 6-10 aryl-C 1-6 -alkylamino, C 1-9 heteroaryl-C 1-6 -alkylamino, C 1-9 heteroaryloxy, C 1-9 heteroaryl-C 1-6 -alkyl, C 6-10 aryl-C 1-6 -alkoxy, C 1-9 heteroaryl-C 1-6 -alkoxy, C 2-10 heterocyclyloxy, C 2-10 heterocyclyl-C 1-6 -alkoxy, C 2-10 heterocyclylamino, C 2-10 heterocyclyl-C 1-6 -alkylamino or C 6-10 aryloxy;

each R 6 is independently H, deuterium, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 alkoxy-C 1-6 -alkyl, C 1-6 alkylamino-C 1-6 -alkyl, C 1-6 alkylthio-C 1-6 -alkyl, C 6-10 aryl-C 1-6 -alkyl, C 1-6 heteroaryl, C 6-10 aryl, C 3-6 heterocyclyl or C 3-8 carbocyclyl; and

each R 7 and R 7a is independently H, deuterium, F, Cl, C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 haloalkyl, hydroxy, amino, C 1-6 alkoxy, C 6-10 aryl, C 2-9 heterocyclyl, C 3-9 cycloalkyl, C 6-10 aryloxy, C 2-9 heterocyclyloxy, C 6-10 arylamino, C 2-9 heterocyclylamino, C 3-9 cycloalkylamino, C 1-9 heteroaryl or C 3-9 carbocyclyl, with the proviso that where R 7 and R 7a are bonded to the same nitrogen atom, R 7 and R 7a , together with the nitrogen atom they are attached to, optionally form a substituted or unsubstituted 3-8 membered ring, or a substituted or unsubstituted spiro or fused bicyclic ring.

3. The compound according to claim 1 , wherein each R 5a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, C 1-4 alkyl, —CF 3 , —OCF 3 , mercapto, nitro, or C 1-4 alkylamino.

4. The compound according to claim 1 , wherein each of A and A′ is independently a bond, C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 2-10 heterocycloalkyl, —(CR 8 R 8a ) n —O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—O—(CR 8 R 8a ) p —, or each of A and A′ is independently

wherein each R 5 is independently H, deuterium, hydroxy, C 1-6 alkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 6-10 aryl-C 1-6 -alkyl, C 1-6 alkoxy, C 1-6 alkyl-OC(═O)—, C 1-6 alkyl-C(═O)—, carbamoyl, C 1-6 alkyl-OS(═O) n —, C 1-6 alkyl-S(═O) n O—, C 1-6 alkyl-S(═O) n —, or aminosulfonyl;

each R 6a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, R 7a R 7 N—, —C(═O)NR 7 R 7a , —OC(═O)NR 7 R 7a , —OC(═O)OR 7 , —N(R 7 )C(═O)NR 7 R 7a , —N(R 7 )C(═O)OR 7a , —N(R 7 )C(═O)—R 7a , R 7 R 7a N—S(═O) 2 —, R 7 S(═O) 2 —, R 7 S(═O) 2 N(R 7a )—, R 7a R 7 N—C 1-6 alkyl, R 7 S(═O)—C 1-6 alkyl, R 7 R 7a N—C(═O)—C 1-6 alkyl, R 7a R 7 N—C 1-6 alkoxy, R 7 S(═O)—C 1-6 alkoxy, R 7 R 7a N—C(═O)—C 1-6 alkoxy, C 6-10 aryl, C 1-9 heteroaryl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-10 heterocyclyl, C 3-8 cycloalkyl, mercapto, nitro, C 6-10 aryl-C 1-6 -alkyl, C 6-10 arylamino, C 1-6 heteroarylamino, or C 6-10 aryloxy;

each R 7 and R 7a is independently H, deuterium, F, Cl, C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 haloaliphatic, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkoxy-C 1-6 -alkyl, C 1-6 alkylamino-C 1-6 -alkyl, C 1-6 alkylthio-C 1-6 -alkyl, C 6-10 aryl-C 1-6 -alkyl, C 1-6 heterocyclyl-C 1-6 -alkyl, C 3-8 cycloalkyl-C 1-6 -alkyl, C 6-10 aryloxy-C 1-6 -alkyl, C 2-10 heterocyclyloxy-C 1-6 -alkyl, C 3-8 cycloalkyloxy-C 1-6 -alkyl, C 6-10 arylamino-C 1-6 -alkyl, C 2-10 heterocyclylamino-C 1-6 -alkyl, C 3-8 cycloalkylamino-C 1-6 -alkyl, C 6-10 aryl, C 1-9 heteroaryl, C 2-10 heterocyclyl, or C 3-8 carbocyclyl; with the proviso that where R 7 and R 7a are bonded to the same nitrogen atom, R 7 and R 7a , together with the nitrogen atom they are attached to, optionally form a substituted or unsubstituted 3-8 membered ring, a substituted or unsubstituted C 5-12 spiro or fused bicyclic ring; and

each R 8 and R 8a is independently H, deuterium, hydroxy, cyano, nitro, F, Cl, Br, I, C 1-6 alkyl, C 1-6 heteroalkyl, C 3-10 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 6-10 aryl-C 1-6 -alkyl, C 1-6 alkoxy, C 1-6 alkyl-OC(═O)—, C 1-6 alkyl-C(═O)—, carbamoyl, C 1-6 alkyl-OS(═O) n —, C 1-6 alkyl-S(═O) n O—, C 1-6 alkyl-S(═O) n —, or aminosulfonyl.

5. The compound according to claim 1 , wherein each of A and A′ is independently a bond, —CH 2 —, —(CH 2 ) 2 —, —CH═CH—, —CH═CH—CH 2 —, —C(═O)—O—, —C(═O)—N(R 5 )—, —N(R 5 )—C(═O)O—, —N(R 5 )C(═O)N(R 5 )—, —(R 5 )N—S(═O) 2 —, —(R 5 )N—S(═O)—, or each of A and A′ is independently

wherein X 1 is O or S;

each R 6 is independently H, deuterium, C 1-4 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 alkoxy-C 1-4 -alkyl, C 1-6 alkylamino-C 1-4 -alkyl, C 1-6 alkylthio-C 1-4 -alkyl, C 6-10 aryl-C 1-4 -alkyl, C 1-9 heteroaryl, C 6-10 aryl, C 3-9 heterocyclyl or C 3-8 carbocyclyl;

each R 6a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, R 7a R 7 N—, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, mercapto or nitro; and

each R 7 and R 7a is independently H, deuterium, F, Cl, C 1-6 alkyl, C 1-6 heteroalkyl, C 1-6 haloalkyl, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkoxy-C 1-6 -alkyl, C 1-6 alkylamino-C 1-6 -alkyl, or C 1-6 alkylthio-C 1-6 -alkyl.

6. The compound according to claim 1 , wherein the R 1 , R 2 and X—CH together form one of the following monovalent groups:

wherein each R 15 is independently H, deuterium, F, Cl, Br, I, cyano, hydroxy, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, C 1-3 alkylthio, C 6-10 arylamino, C 6-10 aryloxy, C 1-9 heteroaryl, C 1-9 heteroaryloxy, C 1-9 heteroaryl-C 1-3 -alkyl, or C 2-10 heterocyclyl;

each R 6 is independently H, deuterium, C 1-4 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 alkoxy-C 1-4 -alkyl, C 1-6 alkylamino-C 1-4 -alkyl, C 1-6 alkylthio-C 1-4 -alkyl, C 6-10 aryl-C 1-4 -alkyl, C 1-9 heteroaryl, C 6-10 aryl, C 3-9 heterocyclyl or C 3-8 carbocyclyl; and

each n 1 and n 2 is independently 1, 2, 3 or 4.

7. The compound according to claim 1 , wherein the R 3 , R 4 and X′—CH together form one of the following monovalent groups:

wherein each R 15 is independently H, deuterium, F, Cl, Br, I, cyano, hydroxy, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, C 1-3 alkylthio, C 6-10 arylamino, C 6-10 aryloxy, C 1-9 heteroaryl, C 1-9 heteroaryloxy, C 1-9 heteroaryl-C 1-3 -alkyl, or C 2-10 heterocyclyl;

each R 6 is independently H, deuterium, C 1-4 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 alkoxy-C 14 -alkyl, C 1-6 alkylamino-C 1-4 -alkyl, C 1-6 alkylthio-C 1-4 -alkyl, C 6-10 aryl-C 1-4 -alkyl, C 1-9 heteroaryl, C 6-10 aryl, C 2-10 heterocyclyl or C 3-8 carbocyclyl; and

each n 1 and n 2 is independently 1, 2, 3 or 4.

8. The compound according to claim 1 having Formula (IV):

wherein X 3 is C(═O) or CH 2 ;

each of Y 4 and Y 4 ′ is independently a bond, O, S, —CH═CH—, —S(═O) n —, —CH 2 O—, —CH 2 S—, —CH 2 S(═O) n —, —CHR 5a — or —CH 2 N(R 6 )—;

each R 5a is independently H, deuterium, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, C 1-6 alkylacyl, C 1-6 alkylacyloxy, C 1-6 alkoxyacyl, C 1-6 alkylsulfonyl, C 1-6 alkoxysulfonyl, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyloxy, C 1-6 alkylsulfinyloxy, C 1-6 alkoxy, C 1-6 alkyl, C 6-10 aryl, —CF 3 , —OCF 3 , mercapto, nitro, C 1-6 alkylamino, C 3-10 cycloalkyl or C 6-10 aryloxy;

f is 0, 1, 2, or 3; and

each R 7 and R 7a is independently H, deuterium, C 1-4 alkyl, C 1-4 heteroalkyl, C 1-6 alkoxyalkyl, C 1-6 alkylaminoalkyl, C 6-10 aryl, C 2-10 heterocyclyl, C 3-8 cycloalkyl, C 1-6 heteroaryl; with the proviso that where R 7 and R 7a are bonded to the same nitrogen atom, R 7 and R 7a , together with the nitrogen atom they are attached to, optionally form a substituted or unsubstituted 3-8 membered ring, a substituted or unsubstituted spiro or fused bicyclic ring.

9. The compound according to claim 1 , wherein each of R 9 , R 9a , and R H is independently H, deuterium, C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, or C 3-8 cycloalkyl-C 1-6 -alkyl; and

R 13 is H, deuterium, C 1-6 alkyl, C 1-6 heteroalkyl, C 3-10 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, or C 6-10 aryl-C 1-6 -alkyl.

10. The compound according to claim 9 , wherein each of R 9 , R 9a , and R 11 is independently H, deuterium, methyl, ethyl, isopropyl, cyclohexyl, isobutyl or phenyl; and

R 13 is H, deuterium, methyl, ethyl, propyl, phenyl, or cyclohexyl.

11. The compound according to claim 1 having Formula (VIII):

wherein each of R 14 and R 14a is independently H, deuterium, methyl, ethyl, isopropyl, isobutyl, tert-butyl, phenyl, cyclopentyl, cyclopropyl, or cyclohexyl; wherein each of methyl, ethyl, isopropyl, isobutyl, tert-butyl, phenyl, cyclopentyl, cyclopropyl and cyclohexyl is optionally substituted with one or more substituents, wherein the substituent is deuterium, F, Cl, Br, hydroxy or cyano;

each Q 1 and Q 2 is independently CH 2 ;

each Y 1 and Y 2 is independently CR 7 ;

each of Y 4 and Y 4 ′ is independently a bond, O, S, —(CH 2 ) n —, —CH═CH—, —S(═O) r —, —CH 2 O—, —CH 2 S—, —CH 2 S(═O) r —, —CF 2 —, —CHR 5a — or —CH 2 N(R 6 )—;

each X 3 is independently C(═O) or CH 2 ; e is 1;

f is 0, 1, 2, 3 or 4; and

each of A and A′ is independently a bond, C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 2-10 heterocycloalkyl, —(CR 8 R 8a ) n —O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —C(═O)—O—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—S(═O) r —N(R 5 )—(CR 8 R 8a ) p —, —(CR 8 R 8a ) n —N(R 5 )—C(═O)—O—(CR 8 R 8a ) p —, or each of A and A′ is independently

12. A compound having Formula (XI):

wherein each R 5a is independently H, deuterium, methyl, ethyl, F, Cl, Br or I;

each of R 14 and R 14a is independently H, deuterium, methyl, ethyl, phenyl, cyclohexyl, 1-methyl propyl, isopropyl or tert-butyl;

each of R 16 and R 16a is independently hydroxy, methoxy, ethoxy, phenoxy, or tert-butoxy;

wherein each of methyl, ethyl, phenyl, cyclohexyl, 1-methyl propyl, isopropyl, methoxy, ethoxy, tert-butoxy and tert-butyl is optionally substituted with one or more substituents, wherein the substituent is deuterium, F, Cl, Br, hydroxy or cyano;

each of A and A′ is independently

wherein R 1 , R 2 and N—CH together form one of the following divalent groups:

and

wherein R 3 , R 4 and N—CH together form one of the following divalent groups:

13. The compound according to claim 12 having Formula (XII):

wherein R 5a is H or methyl;

each of Q 1 and Q 2 is independently CH 2 ;

each of Y 1 and Y 2 is independently CH 2 ;

each of R 14 and R 14a is independently H, deuterium, methyl, ethyl, isobutyl, cyclohexyl, phenyl or isopropyl;

each of R 15 and R 15a is independently H, deuterium, F, Cl, Br, methyl, ethyl, isopropyl or tert-butyl;

each of R 17 and R 17a is independently methyl, phenyl or ethyl;

each X 3 is independently C(═O) or CH 2 ;

e is 1 or 2 with the proviso that where X 3 is C(═O), e is 1;

wherein each of methyl, ethyl, phenyl, cyclohexyl, isopropyl and tert-butyl is optionally substituted with one or more substituents, wherein the substituent is deuterium, F, Cl, Br, hydroxy or cyano; and

each of A and A′ is independently

14. A compound of claim 1 having one of the following structures:

or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising the compound according to claim 1 ; and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof.