title: Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I.
abstract: A series of aryloxy substituted piperazinones with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to have potent inhibitory activity in vitro and are promising agents for the inhibition of Ki-Ras signaling.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Bergman
authors.forename: M T
authors.initials: MT
authors.lastname: Abrams
authors.forename: J P
authors.initials: JP
authors.lastname: Davide
authors.forename: I B
authors.initials: IB
authors.lastname: Greenberg
authors.forename: R G
authors.initials: RG
authors.lastname: Robinson
authors.forename: C A
authors.initials: CA
authors.lastname: Buser
authors.forename: H E
authors.initials: HE
authors.lastname: Huber
authors.forename: K S
authors.initials: KS
authors.lastname: Koblan
authors.forename: N E
authors.initials: NE
authors.lastname: Kohl
authors.forename: R B
authors.initials: RB
authors.lastname: Lobell
authors.forename: S L
authors.initials: SL
authors.lastname: Graham
authors.forename: G D
authors.initials: GD
authors.lastname: Hartman
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: C J
authors.initials: CJ
authors.lastname: Dinsmore
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D011905:Genes, ras / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010879:Piperazines; D011108:Polymers; C017027:arylox; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase