Pyrrolo[2, 3-d] pyrimidine derivatives as corticotropin releasing factor antagonists
申请人:Glaxo Group Limited
公开号:US07462622B2
公开(公告)日:2008-12-09
The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof
wherein
R is aryl or heteroaryl and each of the above groups R may be substituted by 1 to 4 groups selected from:
halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, —COR4, nitro, —NR3R4 cyano, or a group R5;
R1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, halogen, NR3R4 or cyano;
R2 corresponds to a group CHR6R7;
R3 is hydrogen, C1-C6 alkyl;
R4 independently from R3, has the same meanings;
R5 is C3-C7 cycloalkyl, which may contain one or more double bonds; aryl; or a 5-6 membered heterocycle;
wherein each of the above groups R5 may be substituted by one or more groups selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, C1-C6 dialkylamino, nitro or cyano;
R6 is hydrogen, C2-C6 alkenyl or C1-C6 alkyl, wherein each of the above groups R6 may be substituted by one or more groups selected from: C1-C6 alkoxy and hydroxy;
R7 independently from R6, has the same meanings;
X is carbon or nitrogen;
to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).
本发明提供了式(I)的化合物,包括立体异构体、前药和其药学上可接受的盐或溶剂,其中R是芳基或杂芳基,并且上述每个R基团都可以被1至4个选择自卤素、C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷氧基、-COR4、硝基、-NR3R4氰基或R5基团的基团所取代;R1是氢、C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷基、卤代C1-C6烷氧基、卤素、NR3R4或氰基;R2对应于CHR6R7基团;R3是氢、C1-C6烷基;R4独立于R3,具有相同的含义;R5是C3-C7环烷基,可以含有一个或多个双键;芳基;或5-6成员杂环;其中上述每个R5基团都可以被一个或多个选择自卤素、C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷氧基、C1-C6二烷基氨基、硝基或氰基的基团所取代;R6是氢、C2-C6烯基或C1-C6烷基,其中上述每个R6基团都可以被一个或多个选择自C1-C6烷氧基和羟基的基团所取代;R7独立于R6,具有相同的含义;X是碳或氮;本发明还涉及制备它们的方法,含有它们的制药组合物以及它们在治疗由促肾上腺皮质激素释放因子(CRF)介导的疾病中的应用。