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    • 13. 发明申请
    • PYRROLOPYRIMIDINE DERIVATIVES HAVING HSP90 INHIBITORY ACTIVITY
    • 具有HSP90抑制活性的吡咯烷酮衍生物
    • WO2009030871A1
    • 2009-03-12
    • PCT/GB2007/003353
    • 2007-09-07
    • VERNALIS R & D LTDBROUGH, PaulDRYSDALE, MartinDAVIS, Nicholas
    • BROUGH, PaulDRYSDALE, MartinDAVIS, Nicholas
    • C07D487/04A61K31/519A61P35/00
    • C07D487/04
    • Compounds of formula (I) are inhibitors of HSP90, and are useful inter alia in the treatment of cancers, wherein R is cyano or methoxy; R 1 and R 2 are independently selected from hydrogen, optionally substituted C 1 -C 3 alkyl, and optionally substituted C 3 -C 6 cycloalkyl; or R 1 and R 2 taken together with the nitrogen to which they are attached form a 3- to 7-membered ring optionally substituted by chloro, bromo, cyano, C 1 -C 3 alkyl in which one or more hydrogens are optionally replaced by fluorine, or hydroxy(C 1 -C 3 alkyl)- in which one or more hydrogens in the alkyl part are optionally replaced by fluorine; R3 and R4 are independently selected from hydrogen, C 1 -C 3 alkyl in which one or more hydrogens are optionally replaced by fluorine, and cyclopropyl; or R 2 and R 3 taken together with the carbon to which they are attached form a 3- to 6-membered ring cycloalkyl ring; n is 1, 2 or 3; and Z is (i) -NR 5 R 6 wherein R 5 and R 6 are independently selected from hydrogen, C 1 -C 3 alkyl, and C 3 -C 6 cycloalkyl; or R 5 and R 6 taken together with the nitrogen to which they are attached form a 3- to 7-membered ring optionally substituted by chloro, bromo, cyano, C 1 -C 3 alkyl in which one or more hydrogens are optionally replaced by fluorine, or hydroxy(C 1 -C 3 alkyl)- in which one or more hydrogens in the alkyl part are optionally replaced by fluorine; or (ii) C 1 -C 3 alkoxy in which one or more hydrogens in the alkyl part are optionally replaced by fluorine.
    • 式(I)的化合物是HSP90的抑制剂,尤其用于治疗癌症,其中R是氰基或甲氧基; R 1和R 2独立地选自氢,任选取代的C 1 -C 3烷基和任选取代的C 3 -C 6环烷基; 或R 1和R 2与它们所连接的氮一起形成任选被氯,溴,氰基,C 1 -C 3烷基取代的3-至7-元环,其中一个或多个氢任选被氟取代,或羟基 (C 1 -C 3烷基) - 其中烷基部分中的一个或多个氢任选被氟取代; R3和R4独立地选自氢,其中一个或多个氢任选被氟取代的C 1 -C 3烷基和环丙基; 或者R 2和R 3与它们所连接的碳一起形成3至6元环环烷基环; n为1,2或3; 并且Z是(i)-NR5R6,其中R5和R6独立地选自氢,C1-C3烷基和C3-C6环烷基; 或R 5和R 6与它们所连接的氮原子一起形成任选被氯,溴,氰基,C 1 -C 3烷基取代的3-至7-元环,其中一个或多个氢任选被氟取代,或羟基 (C 1 -C 3烷基) - 其中烷基部分中的一个或多个氢任选被氟取代; 或(ii)其中烷基部分中的一个或多个氢任选被氟取代的C 1 -C 3烷氧基。