发明名称 TRICYCLIC PYRIDO-CARBOXAMIDE DERIVATIVES AS ROCK INHIBITORS
摘要 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.;
申请公布号 US2016152627(A1) 申请公布日期 2016.06.02
申请号 US201414900228 申请日期 2014.07.01
申请人 BRISTOL-MYERS SQUIBB COMPANY 发明人 Quan Mimi L.;Hu Zilun;Wang Cailan
分类号 C07D491/052;C07D471/04 主分类号 C07D491/052
代理机构 代理人
主权项 1. A compound according to formula (Ia): or a stereoisomer, tautomer, pharmaceutically acceptable salt thereof, wherein B is independently selected from —CR3R4O—, —OCR3R4—, and —NRa—; L is independently selected from —(CR6R7)q—, NR5(CR6R7)q—, and —O(CR6R7)q—; provided when B is —NRa—, L is —(CR6R7)q—; R1 and R2 are independently selected from H, F, Cl, Br, CN, NRaRa, —OC1-4 alkyl substituted with 0-3 Re, C1-4 alkyl substituted with 0-3 Re, and —(CH2)rORb; R3 and R4 are independently selected from H and C1-4 alkyl; R5 is independently selected from H and C1-4 alkyl; R6 and R7 are independently selected from H, C1-4alkyl substituted with 0-4 Re, —(CH2)rORb, —(CH2)rS(O)pRc, —(CH2)rC(═O)Rb, —(CH2)rNRaRa, —(CH2)rC(═O)(CH2)rNRaRa, —(CH2)rNRaC(═O)Rb, —(CH2)rNRaC(═O)ORb, —(CH2)rOC(═O)NRaRa, —(CH2)rNRaC(═O)NRaRa, —(CH2)rC(═O)ORb, —(CH2)rS(O)pNRaRa, —(CH2)rNRaS(O)pNRaRa, —(CH2)rNRaS(O)pRc, (CH2)r—C3-6 carbocyclyl substituted with 0-3 Re, and —(CH2)r-heterocyclyl substituted with 0-3 Re; R8 is selected from aryl, bicyclic carbocyclyl, and heteroaryl, each substituted with 0-5 R9; R9 is independently selected from F, Cl, Br, C1-4alkyl substituted with 0-5 Re, C2-4alkenyl substituted with 0-5 Re, C2-4alkynyl substituted with 0-5 Re, nitro, —(CHRd)rS(O)pRc, —(CHRd)rS(O)pNRaRa, —(CHRd)rNRaS(O)pRc, —(CHRd)rORb, —(CHRd)r CN, —(CHRd)rNRaRa, —(CHRd)rNRaC(═O)Rb, —(CHRd)rNRaC(═O)NRaRa, —(CHRd)rC(═O)ORb, —(CHRd)rC(═O)Rb, —(CHRd)rOC(═O)Rb, —(CHRd)rC(═O)NRaRa, —(CHRd)r-cycloalkyl, —(CHRd)r-heterocyclyl, —(CHRd)r-aryl, and —(CHRd)r-heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is substituted with 0-4 Re; alternatively, two adjacent R9 groups are combined to form a carbocyclic or heterocyclic ring comprising carbon atoms and 1-3 hetero atoms selected from N, O, and S(O)p, wherein the carbocyclic and heterocyclic rings are substituted with 0-4 Re; Ra, at each occurrence, is independently selected from H, C1-6 alkyl substituted with 0-5 Re, —(CH2)r—C3-10carbocyclyl substituted with 0-5 Re, and —(CH2)r-heterocyclyl substituted with 0-5 Re; or Ra and Ra together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 Re; Rb, at each occurrence, is independently selected from H, C1-6 alkyl substituted with 0-5 Re, C2-6 alkenyl substituted with 0-5 Re, C2-6 alkynyl substituted with 0-5 Re, —(CH2)r—C3-10carbocyclyl substituted with 0-5 Re, and —(CH2)r-heterocyclyl substituted with 0-5 Re; Re, at each occurrence, is independently selected from C1-6 alkyl substituted with 0-5 Re, C2-6alkenyl substituted with 0-5 Re, C2-6alkynyl substituted with 0-5 Re, C3-6carbocyclyl, and heterocyclyl; Rd, at each occurrence, is independently selected from H and C1-4alkyl substituted with 0-5 Re; Re, at each occurrence, is independently selected from C1-6 alkyl (optionally substituted with F, Cl, Br, and OH), C2-6 alkenyl, C2-6 alkynyl, —(CH2)r—C3-10 carbocyclyl substituted with Rf, —(CH2)r-heterocyclyl substituted with Rf, F, Cl, Br, CN, NO2, ═O, CO2H, CO2C1-6 alkyl, —(CH2)rOC1-5 alkyl, —(CH2)rOH, —(CH2)rNRfRf, —(CH2)rNRfRfC(═O) C1-4alkyl, —C(═O)NRfRf, —C(═O)Rf, S(O)pNRfRf, NRfRfS(O)p C1-4alkyl, and S(O)pC1-4alkyl; Rf, at each occurrence, is independently selected from H, F, Cl, Br, CN, C1-5alkyl, and C3-6 cycloalkyl; or Rf and Rf together with the nitrogen atom to which they are both attached form a heterocyclic ring; p, at each occurrence, is independently selected from zero, 1, and 2; q, at each occurrence, is independently selected from zero, 1, 2, and 3; r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.
地址 Princeton NJ US