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US 12,753,190 B2Granted
Spirotricycle RIPK1 inhibitors and methods of uses thereof
AssigneeMerck Sharp & Dohme Corp.
InventorsAbdelghani Abe Achab, Jenny Lorena Rico Duque, Xavier Fradera, Joey L. Methot, Phieng Siliphaivanh, Brandon A Vara, Hongjun Zhang
Life of this patent
Estimating the term…
Abstract
Described herein are compounds of Formula I; and pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, m, n, and p are as defined herein. The compounds of Formula I, and pharmaceutically acceptable salts thereof, act as RIPK1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for RIPK1-related diseases.
Claims23
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- A is aryl, heteroaryl, heterocycloalkyl or C3-C6cycloalkyl;
- each occurrence of R1 is independently —OH, C1-C6alkylOH, —CN, C1-C6alkylCN, C1-C6alkyl, haloC1-C6alkyl, halogen, —NH2, —N(C1-C6alkyl)2, —NH(C1-C6alkyl) or C1-C6alkoxy;
- R2 is hydrogen, —OH, C1-C6alkylOH, —CN, C1-C6alkylCN, C1-C6alkyl, haloC1-C6alkyl, halogen, —NH2, —N(C1-C6alkyl)2, —NH(C1-C6alkyl) or C1-C6alkoxy;
- X is-CN, aryl, C1-C6alkylaryl, —COaryl, —CONHaryl, —SO2aryl, C3-C10cycloalkyl, C1-C6alkylC3-C10cycloalkyl, —COC3-C10cycloalkyl, —CONHC3-C10cycloalkyl, —SO2C3-C10cycloalkyl, heteroaryl, C1-C6alkylheteroaryl, —COheteroaryl, —CONHheteroaryl, —SO2heteroaryl, heterocycloalkyl, C1-C6alkylheterocycloalkyl, —COheterocycloalkyl, —CONHheterocycloalkyl, SO2heterocycloalkyl, —COOC1-C6alkyl or —COOC3-C6cycloalkyl, wherein the aryl, C1-C6alkylaryl, —COaryl, —CONHaryl, —SO2aryl, C3-C10cycloalkyl, C1-C6alkylC3-C10cycloalkyl, —COC3-C10cycloalkyl, —CONHC3-C10cycloalkyl, —SO2C3-C10cycloalkyl, heteroaryl, C1-C6alkylheteroaryl, —COheteroaryl, —CONHheteroaryl, —SO2heteroaryl, heterocycloalkyl, C1-C6alkylheterocycloalkyl, —COheterocycloalkyl, —CONHheterocycloalkyl, —COOC3-C6cycloalkyl or —SO2heterocycloalkyl is unsubstituted or substituted with one to four substituents selected from the group consisting of —CN, —OH, halogen, C1-C6alkylCN, C1-C6alkylOH, C1-C6alkyl, C1-C6alkynyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, —COOC1-C6alkyl, —COC1-C6alkyl, —SC1-C6alkyl, oxo, C3-C6cycloalkyl, aryl, heteroaryl, heterocycloalkyl, —CONH(C1-C6alkyl), —CONH2, —CON(C1-C6alkyl)2, —NH(C1-C6alkyl), —NH2, and —N(C1-C6alkyl)2, wherein the heteroaryl, heterocycloalkyl, C3-C6cycloalkyl, aryl, C1-C6alkynyl, C1-C6alkoxy, is unsubstituted or substituted with one to two substituents independently selected from the group consisting of halogen, —CN, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, —OH and heterocycloalkyl;
- m is 0, 1, 2 or 3;
- n is 1, 2 or 3;
- and
- p is 1, 2 or 3.
6 more elements
A compound of Formula IV:
- or a pharmaceutically acceptable salt thereof, wherein:
- A is aryl;
- R1 is halogen;
- X is —COaryl, —SO2aryl, heteroaryl, C1-C6alkylheteroaryl, —COheteroaryl, heterocycloalkyl, or —COOC1-C6alkyl, wherein the —COaryl, heteroaryl, or —COheteroaryl is unsubstituted or substituted with one to four substituents independently selected from the group consisting of —CN, —OH, halogen, C1-C6alkylOH, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, —COC1-C6alkyl, —SC1-C6alkyl, oxo, C3-C6cycloalkyl, aryl, heteroaryl, heterocycloalkyl, —CONH(C1-C6alkyl), —CONH2, —CON(C1-C6alkyl)2, and —N(C1-C6alkyl)2, wherein the heteroaryl or aryl is unsubstituted or substituted with one to two substituents independently selected from the group consisting of halogen, C1-C6haloalkyl and C1-C6alkyl;
- and
- m is 0, 1, 2 or 3.
3 more elements
A compound of Formula V:
- or a pharmaceutically acceptable salt thereof, wherein:
- each occurrence of R1 is independently —OH, C1-C6alkylOH, —CN, C1-C6alkylCN, C1-C6alkyl, haloC1-C6alkyl, halogen or C1-C6alkoxy;
- X is —COaryl, —SO2aryl, heteroaryl, C1-C6alkylheteroaryl, —COheteroaryl, heterocycloalkyl, or —COOC1-C6alkyl, wherein the —COaryl, heteroaryl, or —COheteroaryl is unsubstituted or substituted with one to four substituents independently selected from the group consisting of CN, OH, halogen, C1-C6alkylOH, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, —COC1-C6alkyl, —SC1-C6alkyl, oxo, C3-C6cycloalkyl, aryl, heteroaryl, heterocycloalkyl, —CONH(C1-C6alkyl), —CONH2, —CON(C1-C6alkyl)2, and —N(C1-C6alkyl)2, wherein the heteroaryl, or aryl, is unsubstituted or substituted with one to two substituents independently selected from the group consisting of halogen, C1-C6haloalkyl and C1-C6alkyl;
- and
- m is 0, 1, 2 or 3.
2 more elements
Dependencies are inferred from the claim text.