发明名称 IMIDAZOTRIAZINECARBONITRILES USEFUL AS KINASE INHIBITORS
摘要 The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) imidazotriazines inhibit protein kinase activity thereby making them useful as anticancer agents.;
申请公布号 US2015210697(A1) 申请公布日期 2015.07.30
申请号 US201314414152 申请日期 2013.07.12
申请人 Bristol-Myers Squibb Company 发明人 Purandare Ashok Vinayak;Fink Brian E.;Johnson Walter Lewis;Hart Amy C.;He Liqi;Huynh Tram N.;Inghrim Jennifer;Mastalerz Harold;Sang Xiaopeng;Tarby Christine M.;Wan Honghe;Vaccaro Wayne;Zhang Guifen;Zhao Yufen;Zimmermann Kurt;Zhang Yong;Chen Libing;Chen Bin;Tokarski John S.;Gavai Ashvinikumar V.
分类号 C07D487/04;C07F7/18;C07D487/10;C07D487/08;C07D471/10 主分类号 C07D487/04
代理机构 代理人
主权项 1. A compound according to Formula (I):or a pharmaceutically acceptable salt thereof, wherein R1 is selected from the group consisting of H, F, Cl, Br, CN, and C1-6alkyl; R2 is selected from the group consisting of aryl substituted with 1-5 R6 and heteroaryl substituted with 1-5 R6; R3 is selected from the group consisting of hydrogen and C1-6alkyl substituted with 1-5 Re; optionally R2 and R3 together with the nitrogen atom to which they are attached form a heterocyclic ring substituted with 1-5 R6; R4 is selected from the group consisting of H, C1-6alkyl substituted with 1-5 Re, —(CH2)rORb, —(CH2)rS(O)pRc, —(CH2)rC(═O)Rd, —(CH2)rNRaRa, —(CH2)rC(═O)NRaRa, —(CH2)rNRaC(═O)Rd, —(CH2)rNRaC(═O)ORb, —(CH2)rOC(═O)NRaRa, —(CH2)rNRaC(═O)NRaRa, —(CH2)rC(═O)ORb, —(CH2)rS(O)2NRaRa, —(CH2)rNRaS(O)2NRaRa, —(CH2)rNRaS(O)2Rc, —(CH2)r—C3-10carbocyclyl substituted with 1-5 Re, —(CH2)r-heterocyclyl substituted with 1-5 Re; R5 is selected from the group consisting of H and C1-6alkyl substituted with 1-5 Re; R6, at each occurrence, is independently selected from the group consisting of H, F, Cl, Br, CN, —(CRgRg)rNR7R7, NO2, —ORb, —C(═O)NR7R7, —C(═O)Rb, —NRaC(═O)ORb, —NRaC(═O)(CRgRg)rNRaRa, C1-6 alkyl substituted with 1-5 Re, C2-4 alkenyl substituted with 1-5 Re, —(CRgRg)rC3-6carbocyclyl substituted with 1-5 R8, and —(CRgRg)rheterocyclyl substituted with 1-5 R8; or two adjacent R6 groups are taken together with the ring atoms to which they are attached to form a fused heterocyclyl or carbocyclyl, each substituted with 1-5 R8; R7, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl substituted with 1-5 Re, —(CH2)r—C3-10carbocyclyl substituted with 1-5 R8, and —(CH2)r-heterocyclyl substituted with 1-5 R8; or R7 and R7 together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 1-5 R8; R8, at each occurrence, is independently selected from the group consisting of H, F, Cl, Br, C1-6 alkyl substituted with 1-5 Re, C2-6 alkenyl substituted with 1-5 Re, C2-6 alkynyl substituted with 1-5 Re, ═O, —(CRgRg)rORb, —(CRgRg)rS(O)pRc, —(CRgRg)rC(═O)(CRgRg)rRd, —(CRgRg)rNRaRa, —(CRgRg)rC(═O)NRaRa, —(CRgRg)rC(═O)NRaS(O)pRc, —(CRgRg)rNRa(CRgRg)rC(═O)Rd, —(CRgRg)rNRaC(═O)ORb, —(CRgRg)rOC(═O)(CRgRg)rRd, —(CRgRg)rOC(═O)(CRgRg)rC(═O)ORd, —(CRgRg)rOC(═O)(CRgRg)rC(═O)NRaRa, —(CRgRg)rOC(═O)(CRgRg)rNRaC(═O) Rb, —(CRgRg)rOC(═O)(CRgRg)rNRaRa, —(CRgRg)rNRa(CRgRg)rC(═O)NRaRa, —(CRgRg)rC(═O)(CH2)rORb, —(CRgRg)rC(═O)(CRgRg)rOC(═O)Rb—(CRgRg)rS(O)pNRaRa, —(CRgRg)rNRaS(O)pNRaRa, —(CRgRg)rNRaS(O)pRc, —OPO3H, —(CRgRg)rNRaC(═O)O(CRgRg)rO(CRgRg)rO(CRgRg)rO(CRgRg)rO(CRgRg)rO(C RgRg)rOC1-4alkyl, —(CRgRg)r—C3-10 carbocyclyl substituted with 1-5 Re and —(CRgRg)rheterocyclyl substituted with 1-5 Re; Ra, at each occurrence, is independently selected from the group consisting of H, CN, C1-6 alkyl substituted with 1-5 Re, C2-6 alkenyl substituted with 1-5 Re, C2-6 alkynyl substituted with 1-5 Re, —(CH2)r—C3-10carbocyclyl substituted with 1-5 Re, and —(CH2)r-heterocyclyl substituted with 1-5 Re; or Ra and Ra together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 1-5 Re; Rb, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl substituted with 1-5 Re, C2-6 alkenyl substituted with 1-5 Re, C2-6 alkynyl substituted with 1-5 Re, —(CH2)r—C3-10carbocyclyl substituted with 1-5 Re, and —(CH2)rheterocyclyl substituted with 1-5 Re; Rc, at each occurrence, is independently selected from the group consisting of C1-6 alkyl substituted with 1-5 Re, C2-6alkenyl substituted with 1-5 Re, C2-6alkynyl substituted with 1-5 Re, C3-6carbocyclyl, and heterocyclyl; Rd, at each occurrence, is independently selected from the group consisting of H, OH, C1-6 alkyl substituted with 1-5 Re, C2-6alkenyl substituted with 1-5 Re, C2-6alkynyl substituted with 1-5 Re, —(CH2)r—C3-10carbocyclyl substituted with 1-5 Re, and —(CH2)r-heterocyclyl substituted with 1-5 Re; Re, at each occurrence, is independently selected from the group consisting of H, N3, C1-6alkyl substituted with 1-5 Rf, C2-6alkenyl, C2-6alkynyl, —(CH2)r—C3-6 cycloalkyl, —(CH2)r-heterocyclyl, F, Cl, Br, —(CH2)rCN, NO2, ═O, —OPO3H, —OSi(C1-4alkyl)3, —(CH2)rOC1-5 alkyl, —(CH2)rO(CH2)rOC1-5 alkyl, —(CH2)rOH, —(CH2)rS(O)2C1-5alkyl, —(CH2)rS(O)2Rf, —(CH2)rNHS(O)2C1-5alkyl, —S(O)2NH2, SH, —(CH2)rNRfRf, —(CH2)rNHC(═O)ORf, —(CH2)rNHC(═O)Rf, —(CH2)rNHC(═NH)NRfRf, —(CH2)rC(═O)(CH2)rRf, and —(CH2)rC(═O)ORf; Rf, at each occurrence, is independently selected from the group consisting of H, —(CH2)rOH, —(CH2)rOC1-5alkyl, C1-5alkyl (optionally substituted with F, Cl, OH, NH2), C3-6 cycloalkyl optionally substituted with NH2, —(CH2)rS(O)pC1-4alkyl, —NHC(═O)C1-4alkyl, —C(═O)NH2, —C(═O)OC1-4alkyl, —C(═O)C1-4alkyl, —(CH2)rphenyl, —(CH2)rheterocyclyl optionally substituted with alkyl and CN, or Rf and Rf together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C1-4alkyl; Rg, at each occurrence, is independently selected from the group consisting of H, F, OH, and C1-5alkyl; p, at each occurrence, is independently selected from the group consisting of zero, 1, and 2; and r, at each occurrence, is independently selected from the group consisting of zero, 1, 2, 3, 4, and 5.
地址 Princeton NJ US
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