title: Parallel liquid synthesis of N,N'-Disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitors.
abstract: A rapid structure-activity study was performed by parallel liquid synthesis on N,N'-disubstitution of 3-amino azepin-2-one to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities. The activities of the selected compounds were validated in vivo, and compounds 41a and 44a presented significant antitumour activity.
authors.affiliation: Department of Medicinal Chemistry, Institut de Recherches Servier, 125 chemin de Ronde, 78290 Croissy sur Seine, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Diguarher
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Ortuno
authors.forename: Gilbert
authors.initials: G
authors.lastname: Dorey
authors.forename: David
authors.initials: D
authors.lastname: Shanks
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guilbaud
authors.forename: Alain
authors.initials: A
authors.lastname: Pierré
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Fauchère
authors.forename: John A
authors.initials: JA
authors.lastname: Hickman
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Tucker
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Casara
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000588:Amines / Q000138:chemical synthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D007093:Imidazoles / Q000138:chemical synthesis; D007769:Lactams / Q000138:chemical synthesis; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D001381:Azepines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007769:Lactams; C029899:imidazole; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase