Synthesis of N,N'-disubstituted 3-aminobenzo[c] and [d]azepin-2-ones as potent and specific farnesyl transferase inhibitors.
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.
Le Diguarher
Thierry
T
Department of Medicinal Chemistry, Institut de Recherches Servier, 125 chemin de Ronde, 78290 Croissy sur Seine, France.
Ortuno
Jean-Claude
JC
Shanks
David
D
Guilbaud
Nicolas
N
Pierré
Alain
A
Raimbaud
Eric
E
Fauchère
Jean-Luc
JL
Hickman
John A
JA
Tucker
Gordon C
GC
Casara
Patrick J
PJ
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
D000970:Antineoplastic Agents; D001381:Azepines; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase