title: Discovery of C-imidazole azaheptapyridine FPT inhibitors.
abstract: The discovery of C-linked imidazole azaheptapyridine bridgehead FPT inhibitors is described. This novel class of compounds are sub nM FPT enzyme inhibitors with potent cellular inhibitory activities. This series also has reduced hERG activity versus previous N-linked imidazole series. X-ray of compound 10a bound to FTase revealed strong interaction between bridgehead imidazole 3N with catalytic zinc atom.
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. hugh.zhu@spcorp.com
authors.forename: Hugh Y
authors.initials: HY
authors.lastname: Zhu
authors.forename: Alan B
authors.initials: AB
authors.lastname: Cooper
authors.forename: Jagdish
authors.initials: J
authors.lastname: Desai
authors.forename: George
authors.initials: G
authors.lastname: Njoroge
authors.forename: Paul
authors.initials: P
authors.lastname: Kirschmeier
authors.forename: W Robert
authors.initials: WR
authors.lastname: Bishop
authors.forename: Corey
authors.initials: C
authors.lastname: Strickland
authors.forename: Alan
authors.initials: A
authors.lastname: Hruza
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Doll
authors.forename: Viyyoor M
authors.initials: VM
authors.lastname: Girijavallabhan
mesh_terms: D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D011725:Pyridines; D051231:Farnesyltranstransferase