title: Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase.
abstract: The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell-active inhibitor.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Ciccarone
authors.forename: S C
authors.initials: SC
authors.lastname: MacTough
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: C J
authors.initials: CJ
authors.lastname: Dinsmore
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Neill
authors.forename: D
authors.initials: D
authors.lastname: Shah
authors.forename: J C
authors.initials: JC
authors.lastname: Culberson
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* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013438:Sulfhydryl Compounds; C029899:imidazole; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase