发明名称 TGF BETA R ANTAGONISTS
摘要 The invention relates generally to compounds that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.
申请公布号 US2016176871(A1) 申请公布日期 2016.06.23
申请号 US201514977709 申请日期 2015.12.22
申请人 Bristol-Myers Squibb Company 发明人 Fink Brian E.;Zhao Yufen;Borzilleri Robert M.;Zhang Liping;Kim Kyoung S.;Kamau Muthoni G.;Tebben Andrew J.
分类号 C07D471/04;A61K31/506;A61K31/4709;A61K31/501;A61K31/4985;A61K31/5377;A61K31/496;A61K31/541;A61K31/437;C07D487/04 主分类号 C07D471/04
代理机构 代理人
主权项 1. The compound of the formulawherein: R isor a heterocylic or heterobicyclic group substituted with 0-4 R2; X1, X2, X3 and X4 are independently —CR4 or —N—, wherein at least one is —N—; R1 is hydrogen, (C1-C6)alkyl, (C3-C8)cycloalkyl, —CONHR9, —COOR9, —COR9 or —SO2R9, any of which except the hydrogen is substituted with 0-3 Rx; Rx is hydrogen, halogen, —OH, halo(C1-C3)alkyl, hydroxy(C1-C3)alkyl, -amino(C1-C3)alkyl, or —CN; R2 is independently one or more hydrogen, —CD3, OCD3, halogen, —CF3, —CHF2, —CN, (C1-C6)alkyl, (C1-C6)alkoxy or —SO2 (C1-C6)alkyl; R3 is independently one or more hydrogen, CD3, OCD3, halogen, —CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkoxy, (C3-C8)cycloalkyl, hydroxy(C1-C3)alkyl, (C1-C6)alkylamino-, (C1-C6)alkylamino(C1-C6)alkyl, 5-6 membered heteroaryl, heterocyclyl, O-heterocyclyl, —NR5R6, —CONR5R6, —COOR4, —COR4, —SO2R4, —CHCF2COOCH2OH or —CHCF2CONH2, any of which except the hydrogen is substituted with 0-4 Ry; Ry is hydrogen, halogen, —OH, (C1-C3)alkyl, halo(C1-C3)alkyl, hydroxy(C1-C3)alkyl, -amino(C1-C3)alkyl, —NHCOOH, or —CN; R4 is hydrogen or (C1-C6)alkyl; R5 and R6 are independently hydrogen, —C(O)alkyl or (C1-C6)alkyl; or R5 and R6 can be taken together with the nitrogen atom to which they are attached to form a 5-7 membered heterocyclo ring; R7 is independently one or more hydrogen, halogen, halo(C1-C6)alkyl or —CN; R8 is hydrogen, (C1-C6)alkyl, (C3-C8)cycloalkyl, —CONHR9, —COOR9, —COR9 or —SO2R9; R9 is hydrogen, (C1-C6)alkyl, (C3-C8)cycloalkyl, heterocyclylalkyl-, heterocyclyl(C1-C3)alkylamino(C1-C3)alkyl- or (C1-C3)alkylamino(C1-C3)alkyl; m is 0, 1, 2, 3, or 4; n is 0, 1, 2 or 3; and/or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
地址 Princeton NJ US