HU QI-YING,KSANDER GARY,MEREDITH ERIK,MONOVICH LAUREN G,PAPILLON JULIEN,SCHUMACHER CHRISTOPH
申请号：
NZ60107711
公开号：
NZ601077A
申请日:
2011.01.13
申请国别(地区):
NZ
年份:
2014
代理人:
摘要：
Disclosed are 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile derivatives as represented formula (I), wherein n is 1 or 3； R is hydrogen or -C(O)N(Ra)(Rb) wherein Ra and Rb are independently alkyl, alkyl-aryl, each of Ra and Rb is optionally substituted by one or two alkoxy substituents； R1, R2, and R3, are selected independently hydrogen, halogen, cyano and aryl, said aryl is optionally substituted one or two substituents selected from halogen, with the proviso that no more than one of R1, R2, and R3 is hydrogen； and R4 and R5 are hydrogen； or a pharmaceutically acceptable salt thereof. In particular the use of a compound of formula (I) as defined above for the preparation of a pharmaceutical composition for the treatment of Cushing&rsquo；s syndrome, Cushing&rsquo；s disease or hypercortisolemia in a subject is also disclosed. Important compounds of formula (I) include 4&rsquo；-fluoro-6-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl} biphenyl-3-carbonitrile, 3-bromo-4-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)benzonitrile, 5-(2-chloro-4-cyanophenyl)-N-(4-methoxybenzyl)-N-methyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxamide, 5-(4-cyano-2-methoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid (4-fluorobenzyl)methylamide, 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile, 5-(3-fluoro-4-methoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2 -c]imidazole, 5-(2-chloro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid 4-fluorobenzyl ester, 5-(2-bromo-4-fluorophenyl)-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine, 2-bromo-4-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)benzonitrile, 3-pyridin-3-yl-4-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl} benzonitrile, and 3-chloro-4-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)benzonitrile. The preferred compound of formula (I) which is disclosed is 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile.
