title: Imidazole-containing diarylether and diarylsulfone inhibitors of farnesyl-protein transferase.
abstract: The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Optimization of cysteine-substituted diarylethers led to highly potent imidazole-containing diarylethers and diarylsulfones. Polar diaryl linkers dramatically improved potency and gave highly cell active compounds.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Dinsmore
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Neill
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Rands
authors.forename: J C
authors.initials: JC
authors.lastname: Culberson
authors.forename: R B
authors.initials: RB
authors.lastname: Lobell
authors.forename: K S
authors.initials: KS
authors.lastname: Koblan
authors.forename: N E
authors.initials: NE
authors.lastname: Kohl
authors.forename: J B
authors.initials: JB
authors.lastname: Gibbs
authors.forename: A I
authors.initials: AI
authors.lastname: Oliff
authors.forename: S L
authors.initials: SL
authors.lastname: Graham
authors.forename: G D
authors.initials: GD
authors.lastname: Hartman
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004987:Ethers / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013450:Sulfones / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D004987:Ethers; D007093:Imidazoles; D013450:Sulfones; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase