title: Antitumor 8-chlorobenzocycloheptapyridines: a new class of selective, nonpeptidic, nonsulfhydryl inhibitors of ras farnesylation.
abstract: Ras farnesylation by farnesyl protein transferase (FPT) is an intracellular event that facilitates the membrane association of the ras protein and is involved in the signal transduction process. FPT inhibition could be a novel, noncytotoxic method of treating ras dependent tumor growth. We report here three structural classes of 8-chlorobenzocycloheptapyridines as novel, nonpeptidic, nonsulfhydryl FPT inhibitors having antitumor activity in mice when dosed orally. We discuss structural and conformational aspects of these compounds in relation to biological activities as well as a comparison to the conformation of a bound tetrapeptide FPT inhibitor.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Mallams
authors.forename: F G
authors.initials: FG
authors.lastname: Njoroge
authors.forename: R J
authors.initials: RJ
authors.lastname: Doll
authors.forename: M E
authors.initials: ME
authors.lastname: Snow
authors.forename: J J
authors.initials: JJ
authors.lastname: Kaminski
authors.forename: R R
authors.initials: RR
authors.lastname: Rossman
authors.forename: B
authors.initials: B
authors.lastname: Vibulbhan
authors.forename: W R
authors.initials: WR
authors.lastname: Bishop
authors.forename: P
authors.initials: P
authors.lastname: Kirschmeier
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: M S
authors.initials: MS
authors.lastname: Bryant
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.forename: D
authors.initials: D
authors.lastname: Carr
authors.forename: L
authors.initials: L
authors.lastname: James
authors.forename: I
authors.initials: I
authors.lastname: King
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Nardo
authors.forename: J
authors.initials: J
authors.lastname: Petrin
authors.forename: S W
authors.initials: SW
authors.lastname: Remiszewski
authors.forename: A G
authors.initials: AG
authors.lastname: Taveras
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: J
authors.initials: J
authors.lastname: Catino
authors.forename: A K
authors.initials: AK
authors.lastname: Ganguly
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001552:Benzazepines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001552:Benzazepines; D010880:Piperidines; D011725:Pyridines; C097312:SCH 44342