title: Synthesis of N,N'-disubstituted 3-aminobenzo[c] and [d]azepin-2-ones as potent and specific farnesyl transferase inhibitors.
abstract: A structure-activity study was performed by synthesis on N,N'-disubstitution of 3-aminobenzo[c] and [d]azepin-2-one 2 and 3 to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities.
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: 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: Eric
authors.initials: E
authors.lastname: Raimbaud
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*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018938:Caco-2 Cells / Q000187:drug effects / Q000201:enzymology; D002461:Cell Line, Transformed / Q000637:transplantation; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D011905:Genes, ras; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase