发明名称 Mediators of hedgehog signaling pathways, compositions and uses related thereto
摘要 The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.
申请公布号 US9173869(B2) 申请公布日期 2015.11.03
申请号 US201012769112 申请日期 2010.04.28
申请人 CURIS, INC. 发明人 Guicherit Oivin M.;Rubin Lee
分类号 A61K31/381;A61K31/517;C07D239/91 主分类号 A61K31/381
代理机构 Millen, White, Zelano & Branigan, P.C. 代理人 Millen, White, Zelano & Branigan, P.C.
主权项 1. A compound of the formula (II): wherein, as valence and stability permit, R1 and R2, independently for each occurrence, are H, lower alkyl, substituted or unsubstituted —(CH2)naryl or substituted or unsubstituted —(CH2)nheteroaryl, wherein the optional substitutions are by halogen, cyano, unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, aryl, hydroxyl, unbranched alkyl-O—, silyloxy, amino, nitro, thiol, imino, amido, carboxyl, silyl, thioether, alkylsulfonyl, arylsulfonyl, sulfoxido, selenoether or ester, provided that, when R1 is substituted or unsubstituted —(CH2)naryl, n is 0; L adjacent to X is —(CH2)n′—where n′ is an integer of 1-10, -alkenyl-, -alkynyl-, —(CH2)nalkenyl-, —(CH2)nalkynyl-, —(CH2)nO(CH2)p—, —(CH2)nNR2(CH2)p—, —(CH2)nS(CH2)p—, —(CH2)nalkenyl(CH2)p—, —(CH2)nalkynyl(CH2)p—, —O(CH2)n—, —NR2(CH2)n—, or —S(CH2)n—; L, adjacent to R1 is absent, L adjacent to R2 is —(CH2)n—, -alkenyl-, -alkynyl-, —(CH2)nalkenyl-, —(CH2)nalkynyl-, —(CH2)nO(CH2)p—, —(CH2)nNR2(CH2)p—, —(CH2)nS(CH2)p—, —(CH2)nalkenyl(CH2)p—, —(CH2)nalkynyl(CH2)p—,—O(CH2)n—, —NR2(CH2)n—, or —S(CH2)n—; X—Y—Z together is —N(R12)—C(═O)—N(R8)—or —N(R 12)—C(═O)—, where R12 is lower alkyl; R8 is H, lower alkyl, substituted or unsubstituted —(CH2)naryl, or substituted or unsubstituted —(CH2)nheteroaryl; W is a substituted or unsubstituted benzene ring fused to the pyrimidone ring; p is, independently for each occurrence, an integer from 0 to 10; and n, independently for each occurrence, is an integer from 0 to 10; or a pharmaceutically acceptable salt thereof.
地址 Cambridge MA US