title: Diaryl ether inhibitors of farnesyl-protein transferase.
abstract: Imidazolemethyl diaryl ethers are potent inhibitors of farnesyl-protein transferase. The SNAr displacement reaction used to prepare these diaryl ethers was amenable to rapid parallel synthesis of FPTase inhibitors. The use of a broad range of commercially available phenols quickly identified compounds which proved active in cells.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486. USA. sue_mactough@merck.com
authors.forename: S C
authors.initials: SC
authors.lastname: Mactough
authors.forename: S J
authors.initials: SJ
authors.lastname: Desolms
authors.forename: A W
authors.initials: AW
authors.lastname: Shaw
authors.forename: M T
authors.initials: MT
authors.lastname: Abrams
authors.forename: T M
authors.initials: TM
authors.lastname: Ciccarone
authors.forename: J P
authors.initials: JP
authors.lastname: Davide
authors.forename: K A
authors.initials: KA
authors.lastname: Hamilton
authors.forename: J H
authors.initials: JH
authors.lastname: Hutchinson
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: R G
authors.initials: RG
authors.lastname: Robinson
authors.forename: S L
authors.initials: SL
authors.lastname: Graham
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D019151:Peptide Library; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D019151:Peptide Library; D010647:Phenyl Ethers; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase