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US 11,447,487 B2Granted
Spiroheptanyl hydantoins as rock inhibitors
AssigneeBristol-Myers Squibb Company
InventorsBenjamin P. Vokits, Scott A. Shaw
Life of this patent
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Abstract
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.
Claims5
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- Ring A is 6-membered heteroaryl comprising carbon and 1-2 nitrogen atoms;
- R1 is selected from H, C1-7 alkyl, C2-7 alkenyl, and C2-7 alkynyl, wherein said alkyl, alkenyl, and alkynyl are substituted with 1-4 R7;
- R2 is H;
- R3 is H;
- R6, at each occurrence, is independently selected from H, halogen, C1-6 alkyl, and C1-4 alkoxy;
- R7, at each occurrence, is independently selected from H, ═O, NO2, halogen, C1-7 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, CN, OH, CHF2, CF3, —(CH2)n—CO2H, —(CH2)n—CO2(C1-4 alkyl), —NHCOH, —NHCO(C1-4 alkyl), —NHCOCF3, —NHCO2(C1-4 alkyl), —NHCO2(CH2)2O(C1-4 alkyl), —NHCO2(CH2)3O(C1-4 alkyl), —NHCO2(CH2)2OH, —NHCO2(CH2)2NH2, —NHCO2(CH2)2N(C1-4 alkyl)2, —NHCO2CH2CO2H, —CH2NHCO2(C1-4 alkyl), —NHSO2(C1-4 alkyl), —S(O)p(C1-4 alkyl), —SO2NH2, —SO2NH(C1-4 alkyl), —SO2N(C1-4 alkyl)2, —SO2NH(CH2)2OH, and —SO2NH(CH2)2O(C1-4 alkyl), wherein said alkyl, alkenyl, alkynyl, and alkoxy are substituted with 0-4 R9;
- R9, at each occurrence, is independently selected from halogen, OH, ═O, CN, NO2, C1-4 alkyl, C1-4 alkoxy, CO(C1-4 alkyl), CO2H, CO2(C1-4 alkyl), —(CHR10)nNRaRa, S(O)p(C1-4 alkyl), —(CHR10)nCONRaRa, —(CHR10)nNRaCO(C1-4 alkyl), —(CHR10)nOCONRa(CH2)nCO2Ra, S(O)pC1-4 alkyl, and S(O)pNRaRa;
- R10, at each occurrence, is independently selected from H and C1-4 alkyl;
- R11 is H;
- R12 and R13 are independently H;
- Ra, at each occurrence, is independently selected from H, C1-4 alkyl, —(CH2)nOH, CO(C1-4 alkyl), COCF3, CO2(C1-4 alkyl), —CONH2, —CONH—C1-4 alkylene—CO2(C1-4 alkyl), C1-4 alkylene—CO2(C1-4 alkyl), Rc, CO2Rc, and CONHRc;
- alternatively, Ra and Ra are taken together with the nitrogen atom to which they are attached to form a 4- to 10-membered heterocycle, wherein said alkyl, alkylene, and heterocycle are substituted with 0-4 Rb;
- Rb, at each occurrence, is independently selected from ═O, OH, halogen, C1-4 alkyl, C1-4 alkoxy, OCF3, OC(O)C1-4 alkyl, NH2, NO2, N(C1-4 alkyl)2, CO(C1-4 alkyl), CO(C1-4 haloalkyl), CO2H, CO2(C1-4 alkyl), CONH2, —CONH(C1-4 alkyl), —CON(C1-4 alkyl)2, —CONH—C1-4 alkylene—O(C1-4 alkyl), —CONH—C1-4 alkylene—NH(C1-4 alkyl), —CONH—C1-4 alkylene—N(C1-4 alkyl)2, —C1-4 alkylene—O—P(O)(OH)2, —NHCO2(C1-4 alkyl), —Rc, CORc, CO2Rc, and CONHRc, wherein said alkyl and alkoxy are substituted with Rd;
- Rc, at each occurrence, is independently selected from —(CH2)n—C3-6 cycloalkyl, —(CH2)n-phenyl, and —(CH2)n-5- to 6-membered heterocycle containing carbon atoms and 1-4 heteroatoms selected from the group consisting of:
- N, NH, N(C1-4 alkyl), O, and S(O)p, wherein each ring moiety is substituted with 0-2 Rd;
- Rd, at each occurrence, is independently selected from ═O, halogen, —OH, C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, C1-4 alkoxy, and —NHCO(C1-4 alkyl);
- n, at each occurrence, is independently selected from 0, 1, 2, 3, and 4;
- and
- p, at each occurrence, is independently selected from 0, 1, and 2.
17 more elements
Dependencies are inferred from the claim text.