TLR inhibitors

1. A compound of general formula (I):

wherein,

ring B is a substituted or unsubstituted monocycle containing 5-6 atoms, the monocycle being selected from an aryl, or heteroaryl,

wherein the or heteroaryl has 1 heteroatom that is nitrogen;

G represents a bond;

one of W, U, E and J represents CR-T and the rest of W, U, E and J are independently absent or independently represent CR 2 ;

T represents:

wherein,

Z is selected from —N—C(O)— or —(O)C—N;

X represents (—CH 2 —) n , wherein n=1 to 24, thereby forming an alkylene chain, the alkylene chain is optionally substituted with a halogen, C 1 -C 20 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogenated C 1 -C 10 alkyl, hydroxy C 1 -C 10 alkyl, or C 1 -C 10 alkoxy;

A is one of pyridinyl, pyrrolidinyl, A1, A2, A3, or A4,

which A is unsubstituted or substituted with one or more R groups,

R1 is one or more of, independently of each other, H, C 1 -C 20 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogen, halogenated C 1 -C 10 alkyl, hydroxy C 1 -C 10 alkyl, C 1 -C 10 alkoxy, —CN, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms that are independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms that are independently selected from nitrogen, oxygen, or sulfur;

R2 is one or more of, independently on each other, H, C 1 -C 20 alkyl, halogenated C 1 -C 20 alkyl, —OR, —SR, —CN, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms that are independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms that are independently selected from nitrogen, oxygen, or sulfur; and

each R is independently H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, halogenated C 1 -C 20 alkyl, halogen, —OH, —OR, —NO 2 , —CN, —COOH, —CHO, —SO 3 H, —SO 2 R, —SOR, —NH 2 , —NHR, —NR 2 , —CHal 3 , —NHCO(C 1 -C 10 )alkyl, —CONHR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, a 3-8 membered saturated or partially unsaturated cycloalkyl, C 3−10 aryl, a 3-7 membered heterocyclic ring having 1-4 heteroatoms that are independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl having 1-4 heteroatoms that are independently selected from nitrogen, oxygen, or sulfur,

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

2. The compound of claim 1 , wherein the compound has general formula (II):

wherein,

Y and L are independently CR1 or N, where at least one of Y and L is CR1; or optionally one of Y and L is absent,

one of W, U, E and J represents —CH(T)- and the rest of W, U, E and J are independently absent or independently represent CR 2 ;

X represents (—CH 2 —) n , wherein n=1 to 12, thereby forming an alkylene chain, the alkylene chain is optionally substituted with a halogen, C 1 -C 20 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogenated C 1 -C 10 alkyl, hydroxy C 1 -C 10 alkyl, or C 1 -C 10 alkoxy;

R1 is one or more of, independently of each other, H, C 1 -C 12 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, F, Cl, halogenated C 1 -C 4 alkyl, hydroxy C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or —CN;

R2 is one or more of, independently of each other, H, C 1 -C 20 alkyl, halogenated C 1 -C 20 alkyl, —OR, —SR, or —CN; and

each R is independently H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogenated C 1 -C 20 alkyl, halogen, —OH, —OR, —NO 2 , —CN, —COOH, —CHO, —SO 3 H, —SO 2 R, —SOR, —NH 2 , —NHR, —NR 2 , —CHal 3 , —NHCO(C 1 -C 10 )alkyl, —CONHR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, a 3-8 membered saturated or partially unsaturated cycloalkyl, C 3 -10 aryl, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

3. The compound of claim 1 , wherein the compound has general formula (III):

wherein,

Y and L are independently CR1 or N, where at least one of Y and L is CR1, and

optionally, one of Y and L can be absent;

one of W, U, E and J represents —CH(T)- and the rest of W, U, E and J are independently absent or independently represent CR 2 ;

T represents T1 or T2:

wherein,

X represents —(CH 2 —) n , wherein n=1 to 6, thereby forming an alkylene chain; the chain is optionally substituted with a halogen, C 1 -C 20 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogenated C 1 -C 10 alkyl, hydroxy C 1 -C 10 alkyl, or C 1 -C 10 alkoxy;

R1 is one or more of, independently of each other, H, C 1 -C 12 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, F, Cl, halogenated C 1 -C 4 alkyl, hydroxy C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or —CN;

R2 is one or more of, independently of each other, H, C 1 -C 20 alkyl, halogenated C 1 -C 20 alkyl, —OR, —SR, or —CN; and

each R is independently H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogenated C 1 -C 20 alkyl, halogen, —OH, —OR, —NO 2 , —CN, —COOH, —CHO, —SO 3 H, —SO 2 R, —SOR, —NH 2 , —NHR, —NR 2 , —CHal 3 , —NHCO(C 1 -C 10 )alkyl, —CONHR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, a 3-8 membered saturated or partially unsaturated cycloalkyl, C 3 -10 aryl, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

4. The compound of claim 3 , wherein in the formula (III), T represents T1:

wherein X is —(CH 2 ) n — and n is 1 to 5,

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

5. The compound of claim 1 , wherein in the formula (III), T represents:

wherein rings in T4, T5, T8, and/or T9, are unsubstituted or substituted with one or more R groups,

wherein each R is independently H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, halogenated C 1 -C 20 alkyl, halogen, —OH, —OR, —NO 2 , —CN, —COOH, —CHO, —SO 3 H, —SO 2 R, —SOR, —NH 2 , —NHR, —NR 2 , —CHal 3 , —NHCO(C 1 -C 10 )alkyl, —CONHR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, a 3-8 membered saturated or partially unsaturated cycloalkyl, C 3 -10 aryl, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

6. The compound of claim 1 , wherein:

one of W, U, E and J represents —CH(T)- and the rest of W, U, E and J are independently absent or independently represent CR 2 ;

X represents (—CH 2 —) n , wherein n=1 to 6, thereby forming an alkylene chain, the alkylene chain is optionally substituted with a halogen, C 1 -C 6 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyl, C 2 -C 8 alkynyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, or C 1 -C 6 alkoxy;

A represents a structure selected from:

which is unsubstituted or substituted with one or more R groups independently selected from C 1 -C 6 alkyl, —F, —CHF 2 , —CF 3 , —OMe, —OEt, hydroxy C 1 -C 4 alkyl, C 1 -C 6 alkoxy, —OH, or —CN;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

7. The compound of claim 1 wherein:

R1 and R2 are independently selected from halogen, —CN, C 1 -C 10 alkoxy, —CHal 3 , —C(O)OR wherein R is H, C 1 -C 10 alkyl, NR 2 wherein R is independently H, C 1 -C 10 alkyl or together form 3-8 membered saturated or unsaturated carbocyclic or heterocyclic ring which contains at least one heteroatom selected from N, S and O, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

8. The compound of claim 4 , wherein in the formula (III), T represents T1:

wherein X is —(CH 2 ) n — and n is 1 to 5,

R1 is one or two substituents, and each R 1 independently represents CF 3 , F, or —CN,

R2 represents H,

A is substituted with C 1 -C 10 alkoxy,

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

9. The compound of claim 3 , wherein in the formula (III), T represents T1:

X represents (—CH 2 —) n , wherein n=1 to 6, thereby forming an alkylene chain, wherein the alkylene chain is optionally substituted with a halogen, C 1 -C 6 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyl, C 2 -C 8 alkynyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, or C 1 -C 6 alkoxy;

A represents:

wherein the number of R groups is varied from 1 to 3 and each R is independently selected from a halogen, hydroxy, C 1 -C 6 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyl, C 2 -C 8 alkynyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, or C 1 -C 6 alkoxy-,

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

10. The compound of claim 9 , wherein A represents:

wherein R represents F, Cl, OH, CN, OMe, OEt, OPr, O-iPr, NH 2 , NO 2 , COOH, COOMe, or COOEt,

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

11. The compound of claim 3 , wherein the compound has a structure of formula (IV):

wherein,

Y and L are independently CH or N, wherein at least one of Y or L is CH; or optionally one of Y and L is absent,

G1 is CH 2 or absent,

each R is independently selected from H, halogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 1 -C 6 alkoxy, or —CN;

X represents (—CH 2 —) n , wherein n=1 to 6, thereby forming an alkylene chain that is optionally substituted with a halogen, C 1 -C 6 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyl, C 8 alkynyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, or C 1 -C 6 alkoxy;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salt thereof.

12. The compound of claim 3 , wherein the compound has formula (V):

wherein,

Y is CH or N; or optionally Y is absent,

each R is independently selected from H, halogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 1 -C 6 alkoxy, or —CN;

X represents (—CH 2 —) n , wherein n=1 to 6, thereby forming an alkylene chain that is optionally substituted with a halogen, C 1 -C 6 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyl, C 8 alkynyl, halogenated C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, or C 1 -C 6 alkoxy;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof,

salts thereof.

13. A pharmaceutical composition comprising one or more compounds according to claim 1 or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

14. The compound of claim 1 , wherein the compound is Compound 27:

15. The compound of claim 1 , wherein:

B is phenyl or pyridinyl;

G is a bond;

U is CR 2 ;

W is CR-T or CR 2 ;

E is CR-T or CR 2 ;

J is CR-T or CR 2 , wherein only one of W, E, or J is CR-T;

Z is an amide;

X is a substituted or unsubstituted C 1 -C 24 alkyl chain; and

A is one of pyridinyl, pyrrolidinyl, A1, A2, A3, or A4, which A is unsubstituted or substituted with one or more R groups;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

16. The compound of claim 1 , wherein:

B is pyridinyl;

G is a bond;

U is CH 2 ;

W is CH 2 ;

E is CH-T;

J is CH 2 ;

Z is an amide;

X is a substituted or unsubstituted C 1 -C 24 alkyl chain; and

A is one of pyridinyl, pyrrolidinyl, A1, A2, A3, or A4, which A is unsubstituted or substituted with one or more R groups;

or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof.

17. The compound of claim 1 , wherein the compound is selected from one of the following structures: