发明名称 Substituted pyrrolotriazines as protein kinase inhibitors
摘要 The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) pyrrolotriazines inhibit protein kinase activity thereby making them useful as anticancer agents.;
申请公布号 US8791257(B2) 申请公布日期 2014.07.29
申请号 US201113638210 申请日期 2011.03.30
申请人 Bristol-Myers Squibb Company 发明人 Markwalder Jay A.;Fink Brian E.;Gavai Ashvinikumar V.;He Liqi;Kim Soong-Hoon;Seitz Steven P.
分类号 C07D487/04;A61K31/53;A61P19/02;C07D401/04;C07D401/14;C07D403/04;C07D403/14;C07D407/04;C07D407/14;C07D409/04;C07D409/14;C07D417/04;C07D417/14 主分类号 C07D487/04
代理机构 代理人 Liu Hong
主权项 1. A compound of formula (I):or a pharmaceutically acceptable salt thereof, wherein R1 is selected from H, NRaRa, C1-6alkyl substituted with 0-5 R1a, C2-6alkenyl substituted with 0-5 R1a, C2-6alkynyl substituted with 0-5 R1a, —(CHR)r-carbocyclyl substituted with 0-5 R1a, —(CHR)r— heterocyclyl substituted with 0-5 R1a; R1a, at each occurrence, is independently selected from C1-6alkyl substituted with 0-5 Re, C2-6alkenyl substituted with 0-5 Re, C2-6alkynyl substituted with 0-5 Re, C1-6haloalkyl, F, Cl, Br, NO2, CN, ═O, —(CHR)rOH, —(CHR)rSH, (CHR)rORb, —(CHR)rS(O)pRb, —(CHR)rC(O)Rd, —(CHR)rNRaRa, —(CHR)rC(O)NRaRa, —(CHR)rC(O)NRaNRaRa, —(CHR)rNRaC(O)Rd, —(CHR)rNRaC(O)ORb, —(CHR)rNRaC(O)(CRR)rOC(O)NRaRa, —(CHR)rNRaC(O)(CRR)rNRaRa, —(CHR)rNRaC(O)(CRR)rNRaC(O)ORd, —(CHR)rOC(O)NRaRa, —(CHR)rC(O)ORd, —(CHR)rS(O)pNRaRa, —(CHR)rNRaS(O)pRb, —(CHR)r-carbocyclyl substituted with 0-5 Re and —(CHR)r-heterocyclyl substituted with 0-5 Re; R2 is selected from H and C1-6alkyl substituted with 0-3 R2a; R2a is selected from F, Cl, and Br; alternatively, R1 and R2 are taken together with the nitrogen atom to which they are attached to form a heterocyclyl substituted with 0-5 R1a; R3 is selected from aryl substituted with 0-5 R3a and heteroaryl substituted with 0-5 R3a; R3a, at each occurrence, is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, F, Cl, Br, NO2, CN, —OH, —SH, —ORb, —S(O)pRb, C(O)Rd, —NRaRa, —C(O)NRaRa, —NRaC(O)Rd, —NRaC(O)ORb, —OC(O)NRaRa, —C(O)ORd, —S(O)pNRaRa, —NRaS(O)pRb; R4 is selected from H, C1-6alkyl, and C3-6cycloalkyl; Ra, at each occurrence, is independently selected from H, NH2, C1-6alkyl substituted with 0-3 Re, C2-6alkenyl substituted with 0-3 Re, C2-6alkynyl substituted with 0-3 Re, C1-6haloalkyl, —(CH2)rOH, (CH2)rcarbocyclyl substituted with 0-3 Re, and (CH2)r-heterocyclyl substituted with 0-3 Re, or Ra and Ra together with the nitrogen atom to which they are attached form a heterocyclyl substituted with 0-3 Re; Rb, at each occurrence, is independently selected from C1-6alkyl substituted with 0-3 Re, C1-6haloalkyl, C2-6alkenyl substituted with 0-3 Re, C2-6alkynyl substituted with 0-3 Re, —(CH2)rcarbocyclyl substituted with 0-3 Re, and —(CH2)rheterocyclyl substituted with 0-3 Re; Rd, at each occurrence, is independently selected from H, C1-6alkyl substituted with 0-3 Re, C1-6haloalkyl, C2-6alkenyl substituted with 0-3 Re, C2-6alkynyl substituted with 0-3 Re, —(CH2)r— carbocyclyl substituted with 0-3 Re, and —(CH2)r-heterocyclyl substituted with 0-3 Re; Re, at each occurrence, is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)rC3-6cycloalkyl, F, Cl, Br, CN, NO2, CO2H, ═O, —C(O)NRfRf, (CF2)rCF3, —(CH2)rOC1-5alkyl, —(CH2)rOH, SH, —(CH2)rSC1-5alkyl, —(CH2)rNRfRf, —(CH2)rphenyl, and (CH2)rheterocyclyl; Rf, at each occurrence, is independently selected from H, C1-5alkyl, C3-6cycloalkyl, and phenyl; R, at each occurrence, is independently selected from H, —(CH2)rOH, C1-6alkyl, C1-6haloalkyl, and —(CH2)r-aryl; p, at each occurrence, is independently selected from 0, 1, and 2; and r, at each occurrence, is independently selected from 0, 1, 2, 3, and 4.
地址 Princeton NJ US