公开(公告)号：US09127003B2

公开(公告)日：2015-09-08

申请号：US14416937

申请日：2012-07-26

申请人： Stephen John Atkinson ,  Michael David Barker ,  Matthew Campbell ,  Hawa Diallo ,  Clement Douault ,  Neil Stuart Garton ,  John Liddle ,  Robert John Sheppard ,  Ann Louise Walker ,  Christopher Wellaway ,  David Matthew Wilson

发明人： Stephen John Atkinson ,  Michael David Barker ,  Matthew Campbell ,  Hawa Diallo ,  Clement Douault ,  Neil Stuart Garton ,  John Liddle ,  Robert John Sheppard ,  Ann Louise Walker ,  Christopher Wellaway ,  David Matthew Wilson

IPC分类号： C07D471/04 ,  A61K31/407 ,  A61K31/4184

CPC分类号： A61K31/4545 ,  A61K31/407 ,  A61K31/4184 ,  C07D471/04

摘要： Compounds of formula (I): wherein; R1 is hydrogen or C1-6alkyl; R2 is hydrogen, C1-6alkyl, perhalomethylC0-5alkyl-O—, or C1-6alkoxy; R3 is hydrogen, C1-6alkyl, or C1-6alkoxyC1-6alkyl; R4 is hydrogen, C1-6alkyl, perhalomethylC1-6alkyl; or unsubstituted C3-6cycloalkylC1-6 alkyl; A is C—R5 or N; B is C—R6 or N; D is C—R7 or N; with the proviso that at least one of A, B, and D, is N; R5 is hydrogen or C1-6alkyl; R6 is hydrogen or C1-6alkyl; R7 is hydrogen, C1-6alkyl, C1-6alkoxy, or hydroxy; R8 is hydrogen or C1-6alkyl, with the proviso that one of R4 and R8 is hydrogen; R9 is hydrogen or hydroxy; R10 is hydrogen or C1-6alkyl; and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.

摘要翻译： 式（I）的化合物：其中; R1是氢或C1-6烷基; R 2是氢，C 1-6烷基，全卤代甲基C 0-5烷基-O-或C 1-6烷氧基; R3是氢，C1-6烷基或C1-6烷氧基C1-6烷基; R 4是氢，C 1-6烷基，全卤代甲基C 1-6烷基; 或未取代的C 3-6环烷基C 1-6烷基; A为C-R5或N; B为C-R6或N; D为C-R7或N; 条件是A，B和D中的至少一个为N; R5是氢或C1-6烷基; R6是氢或C1-6烷基; R7是氢，C1-6烷基，C1-6烷氧基或羟基; R8是氢或C1-6烷基，条件是R4和R8中的一个是氢; R9是氢或羟基; R 10是氢或C 1-6烷基; 其盐是PAD4抑制剂，并且可用于治疗各种疾病，例如类风湿性关节炎，血管炎，系统性红斑狼疮，溃疡性结肠炎，癌症，囊性纤维化，哮喘，皮肤红斑狼疮和牛皮癣。