title: Trihalobenzocycloheptapyridine analogues of Sch 66336 as potent inhibitors of farnesyl protein transferase.
abstract: SCH 66336 is a trihalo tricyclic compound that is currently undergoing Phase II clinical trials for the treatment of solid tumors. Modifications of SCH 66336 by incorporating such groups as amides, acids, esters, ureas and lactams off the first or the distal piperidine (from the tricycle) provided potent FPT inhibitors some of which exhibited good cellular activity. A number of these compounds incorporate properties that might improve pharmacokinetic stability of these inhibitors by virtue of their increased solubility or by their change in log P.
authors.affiliation: Schering-Plough Research Institute, Department of Chemistry and Tumor Biology, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. george.njoroge@spcorp.com
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge
authors.forename: Bancha
authors.initials: B
authors.lastname: Vibulbhan
authors.forename: Patrick
authors.initials: P
authors.lastname: Pinto
authors.forename: Corey L
authors.initials: CL
authors.lastname: Strickland
authors.forename: W Robert
authors.initials: WR
authors.lastname: Bishop
authors.forename: Paul
authors.initials: P
authors.lastname: Kirschmeir
authors.forename: V
authors.initials: V
authors.lastname: Girijavallabhan
authors.forename: Ashit K
authors.initials: AK
authors.lastname: Ganguly
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D019556:COS Cells; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D014316:Tritium; D003986:Dibenzocycloheptenes
chemical_list: D019883:Alkyl and Aryl Transferases; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010880:Piperidines; D011725:Pyridines; D014316:Tritium; C121493:trihalobenzocycloheptapyridine; C064911:p21(ras) farnesyl-protein transferase; C115354:lonafarnib; D003986:Dibenzocycloheptenes