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US 8,802,721 B2Granted
Thiophene compounds for inflammation and immune-related uses
AssigneeSynta Pharmaceuticals Corp.
InventorsLijun Sun, Shoujun Chen, Jun Jiang, Zhi-Qiang Xia, Yu Xie, Chih-Yi Yu
Life of this patent
Estimating the term…
Abstract
The invention relates to compounds of structural formulas (I) and (XVI): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein X1, X2, Z, L, L2, R1, R2, R3, R21, n, q, and t are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.
Claims45
A compound represented by structural formula (VII):
- or a pharmaceutically acceptable salt, solvate, or clathrate thereof, wherein:
- L is a linker selected from the group consisting of —NR—C(O)—, —C(O)—NR—, —NR—C(S)—, —C(S)—NR—, —NR—C(NR8)—, or —C(NR8)—NR—;
- X1 is CH, CR2, or N;
- X6 is CH or N;
- each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, cyano, nitro, or lower haloalkoxy;
- R, for each occurrence is independently selected from —H, an alkyl, —C(O)R5, or —C(O)OR5;
- R1, for each occurrence is, independently, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, —F, a haloalkyl, a haloalkoxy, —OR5, SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S(O)pR5, —OS(O)pR5, S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5) (R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4) (R5)2;
- R2, for each occurrence is, independently, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, a halo, a haloalkyl, a haloalkoxy, —OR5, —SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S(O)pR5, —OS(O)pR5, —S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5)(R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4)(R5)2;
- R4, for each occurrence is, independently, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, —F, a haloalkyl, a haloalkoxy, —OR5, —SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S (O)pR5, —OS(O)pR5, —S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5)(R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4)(R5)2;
- X3 is =O, =S, or ═NR8;
- X4 is ═O or ═S;
- X5 is —O— or —S—;
- R5, for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- R6 and R7, for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- or R6 and R7 taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;
- R8, for each occurrence, is independently —H, a halo, an alkyl, —OR5, —NR6R7, —C(O)R5, —C(O)OR5, or —C(O)NR6R7;
- n is zero or an integer from 1 to 2;
- p, for each occurrence, is independently 1 or 2;
- and
- t is zero or an integer from 1 to 4.
17 more elements
A compound represented by structural formula (IX):
- or a pharmaceutically acceptable salt, solvate, or clathrate thereof, wherein:
- L is a linker selected from the group consisting of —NR—C(O)—, —C(O)—NR—, —NR—C(S)—, —C(S)—NR—, —NR—C(NR8)—, or —C(NR8)—NR—;
- X1 is CH, CR2, or N;
- each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, cyano, nitro, or lower haloalkoxy;
- R, for each occurrence is independently selected from —H, an alkyl, —C(O)R5, or —C(O)OR5;
- R1, and R2 and R3, for each occurrence are, independently, is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, a halo, a haloalkyl, a haloalkoxy, —OR5, —SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S(O)pR5, —OS (O)pR5, —S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5)(R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4)(R5)2;
- X3 is =O, =S, or ═NRg;
- X4 is ═O or ═S;
- X5 is —O— or —S—;
- R5, for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- R6 and R7, for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- or R6 and R7 taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;
- R8, for each occurrence, is independently —H, a halo, an alkyl, —OR5, —NR6R7, —C(O)R5, —C(O)OR5, or —C(O)NR6R7;
- n is zero or an integer from 1 to 2;
- p, for each occurrence, is independently 1 or 2;
- m is zero or an integer from 1 to 3;
- and
- t is zero or an integer from 1 to 4.
15 more elements
A compound represented by structural formula (XIII):
- or a pharmaceutically acceptable salt, solvate, or clathrate thereof, wherein:
- L is a linker selected from the group consisting of —NR—C(O)—, —C(O)—NR—, —NR—C(S)—, —C(S)—NR—, —NR—C(NR8)—, or —C(NR8)—NR—;
- X2 is CH, CR3, or N;
- X7 is CH or N;
- each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, cyano, nitro, or lower haloalkoxy;
- R, for each occurrence is independently selected from —H, an alkyl, —C(O)R5, or —C(O)OR5;
- R1 and R3, for each occurrence are, independently, is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, a halo, a haloalkyl, a haloalkoxy, —OR5, —SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S(O)pR5, —OS(O)pR5, —S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5)(R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4)(R5)2;
- X3 is =O, =S, or ═NR8;
- X4 is ═O or ═S;
- X5 is —O— or —S—;
- R5, for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- R6 and R7, for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- or R6 and R7 taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;
- R8, for each occurrence, is independently —H, a halo, an alkyl, —OR5, —NR6R7, —C(O)R5, —C(O)OR5, or —C(O)NR6R7;
- R11 and R12 are each, independently, a halo, a lower alkyl, a lower haloalkyl, a lower alkoxy, a lower haloalkoxy, a 5-membered heteroaryl which is optionally substituted with one to three lower alkyl groups, —C(O)OR13, —C(O)NR14R15, or cyano;
- R13, R14, and R15, for each occurrence, are independently, H, a lower alkyl, or a lower alkyl substituted with an alkoxy group;
- n is zero or an integer from 1 to 2;
- p, for each occurrence, is independently 1 or 2;
- and
- q is zero or an integer from 1 to 3.
17 more elements
A compound selected from the group consisting of:
- 5-(2-Chloro-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(2-Chloro-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 3-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid methyl ester;
- 4-Methyl-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid methyl ester;
- 3-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid propyl ester;
- 3-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid 2-methoxy-ethyl ester;
- 4-Chloro-3-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid methyl ester;
- 4-Chloro-3-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid ethyl ester;
- 4-Chloro-3-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid propyl ester;
- 4-Chloro-3-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid 2-methoxy-ethyl ester;
- 5-(5-Furan-2-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(5-Furan-3-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(5-Chloro-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(5-Bromo-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(2-Ethyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(2-Methyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(5-Carbamoyl-2-methyl-phenyl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 5-(5-Carbamoyl-2-methyl-phenyl)-thiophene-2-carboxylic acid (2,6-difluoro-phenyl)-amide;
- 4-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-3-methyl-benzoic acid methyl ester;
- 4-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-3-methyl-benzoic acid ethyl ester;
- 4-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-3-methyl-benzoic acid propyl ester;
- 4-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-3-methyl-benzoic acid 2-methoxy-ethyl ester;
- 3-Chloro-4-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid methyl ester;
- 3-Chloro-4-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid ethyl ester;
- 4-Chloro-3-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid propyl ester;
- 3-Chloro-4-[5-(2,6-difluoro-phenylcarbamoyl)-thiophen-2-yl]-benzoic acid 2-methoxy-ethyl ester;
- 5-(5-Furan-2-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(5-Furan-3-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(5-Chloro-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(5-Bromo-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(2-Ethyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(2-Methyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(5-Carbamoyl-2-methyl-phenyl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 5-(5-Cyano-2-methyl-phenyl)-thiophene-2-carboxylic acid (3-fluoro-pyridin-4-yl)-amide;
- 3-[5-(3,5-Difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid methyl ester;
- 3-[5-(3,5-Difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid ethyl ester;
- 3-[5-(3,5-Difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid propyl ester;
- 3-[5-(3,5-Difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid 2-methoxy-ethyl ester;
- 4-Chloro-3-[5-(3,5-difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid methyl ester;
- 4-Chloro-3-[5-(3,5-difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid ethyl ester;
- 4-Chloro-3-[5-(3,5-difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid propyl ester;
- 4-Chloro-3-[5-(3,5-difluoro-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid 2-methoxy-ethyl ester;
- 5-(5-Furan-2-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(5-Furan-3-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(5-Chloro-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(5-Bromo-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(2-Ethyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(2-Methyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(5-Carbamoyl-2-methyl-phenyl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 5-(5-Cyano-2-methyl-phenyl)-thiophene-2-carboxylic acid (3,5-difluoro-pyridin-4-yl)-amide;
- 4-Methyl-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid methyl ester;
- 4-Methyl-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid ethyl ester;
- 4-Methyl-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid propyl ester;
- 4-Methyl-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid 2-methoxy-ethyl ester;
- 4-Chloro-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid methyl ester;
- 4-Chloro-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid ethyl ester;
- 4-Chloro-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid propyl ester;
- 4-Chloro-3-[5-(3-methyl-pyridin-4-ylcarbamoyl)-thiophen-2-yl]-benzoic acid 2-methoxy-ethyl ester;
- 5-(5-Furan-2-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(5-Furan-3-yl-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(5-Chloro-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(5-Bromo-2-methoxy-pyridin-3-yl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(2-Ethyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(2-Methyl-5-trifluoromethyl-phenyl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(5-Carbamoyl-2-methyl-phenyl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 5-(5-Cyano-2-methyl-phenyl)-thiophene-2-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
- 3-[5-(2,6-Difluoro-phenylcarbamoyl)-thiophen-2-yl]-4-methyl-benzoic acid ethyl ester;
- [5-(2-Chloro-5-trifluoromethyl-phenyl)-thiophen-2-ylmethyl]-(2,6-difluoro-phenyl)-amine;
- 3-Fluoro-N-[5-(5-isoxazol-5-yl-2-methyl-phenyl)-thiophen-2-yl]-isonicotinamide;
- N-[5-(5-Isoxazol-5-yl-2-methyl-phenyl)-thiophen-2-yl]-3-methyl-isonicotinamide;
- 3,5-Difluoro-N-[5-(5-isoxazol-5-yl-2-methyl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Fluoro-N-[5-(5-isothiazol-5-yl-2-methyl-phenyl)-thiophen-2-yl]-isonicotinamide;
- N-[5-(5-Isothiazol-5-yl-2-methyl-phenyl)-thiophen-2-yl]-3-methyl-isonicotinamide;
- 3,5-Difluoro-N-[5-(5-isothiazol-5-yl-2-methyl-phenyl)-thiophen-2-yl]-isonicotinamide;
- N-[5-(2-Chloro-5-isoxazol-5-yl-phenyl)-thiophen-2-yl]-3-fluoro-isonicotinamide;
- N-[5-(2-Chloro-5-isoxazol-5-yl-phenyl)-thiophen-2-yl]-3-methyl-isonicotinamide;
- N-[5-(2-Chloro-5-isoxazol-5-yl-phenyl)-thiophen-2-yl]-3,5-difluoro-isonicotinamide;
- 3-Fluoro-N-[5-(2-methyl-5-oxazol-5-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Methyl-N-[5-(2-methyl-5-oxazol-5-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3,5-Difluoro-N-[5-(2-methyl-5-oxazol-5-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Fluoro-N-[5-(2-methyl-5-thiazol-5-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Methyl-N-[5-(2-methyl-5-thiazol-5-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3,5-Difluoro-N-[5-(2-methyl-5-thiazol-5-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- N-[5-(2-Chloro-5-oxazol-5-yl-phenyl)-thiophen-2-yl]-3-fluoro-isonicotinamide;
- N-[5-(2-Chloro-5-oxazol-5-yl-phenyl)-thiophen-2-yl]-3-methyl-isonicotinamide;
- N-[5-(2-Chloro-5-oxazol-5-yl-phenyl)-thiophen-2-yl]-3,5-difluoro-isonicotinamide;
- 3-Fluoro-N-[5-(2-methyl-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Methyl-N-[5-(2-methyl-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3,5-Difluoro-N-[5-(2-methyl-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Fluoro-N-[5-(2-methyl-5-thiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Methyl-N-[5-(2-methyl-5-thiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3,5-Difluoro-N-[5-(2-methyl-5-thiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- N-[5-(2-Chloro-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-3-fluoro-isonicotinamide;
- N-[5-(2-Chloro-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-3-methyl-isonicotinamide;
- N-[5-(2-Chloro-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-3,5-difluoro-isonicotinamide;
- 3-Fluoro-N-[5-(2-methyl-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Methyl-N-[5-(2-methyl-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3,5-Difluoro-N-[5-(2-methyl-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Fluoro-N-[5-(2-methyl-5-[1,3,4]thiadiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3-Methyl-N-[5-(2-methyl-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- 3,5-Difluoro-N-[5-(2-methyl-5-[1,3,4]thiadiazol-2-yl-phenyl)-thiophen-2-yl]-isonicotinamide;
- N-[5-(2-Chloro-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-3-fluoro-isonicotinamide;
- N-[5-(2-Chloro-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-3-methyl-isonicotinamide;
- N-[5-(2-Chloro-5-[1,3,4]oxadiazol-2-yl-phenyl)-thiophen-2-yl]-3,5-difluoro-isonicotinamide
- 2,6-Difluoro-N-[5-(3-trifluoromethyl-phenyl)-thiophen-2-yl]-benzamide;
- 3-[5-(2,6-Difluoro-benzoylamino)-thiophen-2-yl]-4-methyl-benzoic acid methyl ester;
- 2,6-Difluoro-N-[5-(2-methyl-5-oxazol-2-yl-phenyl)-thiophen-2-yl]-benzamide;
- and
- pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof.
106 more elements
A compound represented by structural formula (XVI):
- or a pharmaceutically acceptable salt, solvate, or clathrate thereof, wherein:
- L2 is a linker selected from the group consisting of —NR—C(O)—, —C(O)—NR—, —NR—C(S)—, —C(S)—NR—, —CH2NR—, —NRCH2—, —C(O)—, —C(S)—, —NR—C(NR8)—, or —C(NR8)—NR—;
- X1 is CH, CR2, or N;
- each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, cyano, nitro, or lower haloalkoxy;
- R, for each occurrence is independently selected from —H, an alkyl, —C(O)R5, or —C(O)OR5;
- R2, for each occurrence is, independently, is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, a halo, a haloalkyl, a haloalkoxy, —OR5, —SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S(O)pR5, —OS(O)pR5, —S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5)(R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4)(R5)2;
- R21 is H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl, nitro, cyano, a halo, a haloalkyl, a haloalkoxy, —OR5, —SR5, —NR6R7, —C(X3)R5, —C(X3)OR5, —OC(X3)R5, —NR5C(X3)OR5, —C(X3)NR6R7, —NR5C(X3)R5, —NR5C(X3)NR6R7, —OC(X3)NR6R7, —C(X3)SR5, —SC(X3)R5, —S(O)pR5, —OS(O)pR5, —S(O)pOR5, —NR5S(O)pR5, —S(O)pNR6R7, —P(X4)(R5)2, —P(X4)(X5R5)(R5), —P(X4)(X5R5)2, —X5P(X4)(X5R5)2, —X5P(X4)(R5)(X5R5), or —X5P(X4)(R5)2;
- X3 is =O, =S, or ═NRg;
- X4 is ═O or ═S;
- X5 is —O— or —S—;
- R5, for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- R6 and R7, for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- or R6 and R7 taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;
- R8, for each occurrence, is independently —H, a halo, an alkyl, —OR5, —NR6R7, —C(O)R5, —C(O)OR5, or —C(O)NR6R7;
- n is zero or an integer from 1 to 2;
- p, for each occurrence, is independently 1 or 2;
- and
- t is zero or an integer from 1 to 4.
15 more elements
A compound represented by structural formula (XX):
- or a pharmaceutically acceptable salt, solvate, or clathrate thereof, wherein:
- L3 is a linker selected from the group consisting of —NR—C(O)—, —C(O)—NR—, —NR—C(S)—, —C(S)—NR—, —CH2NR—, —NRCH2—, —C(S)—, —NR—C(NR8)—, or —C(NR8)—NR—;
- each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, cyano, nitro, or lower haloalkoxy;
- R, for each occurrence is independently selected from —H, an alkyl, —C(O)R5, or —C(O)OR5;
- R5, for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;
- R8, for each occurrence, is independently —H, a halo, an alkyl, —OR5, —NR6R7, —C(O)R5, —C(O)OR5, or —C(O)NR6R7;
- R25 is an optionally substituted alkyl or an optionally substituted cycloalkyl;
- R23 and R24 are each, independently, a substituent;
- and
- n is zero or an integer from 1 to 2.
7 more elements
Dependencies are inferred from the claim text.