Parallel liquid synthesis of N,N'-Disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitors.
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.
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
Dorey
Gilbert
G
Shanks
David
D
Guilbaud
Nicolas
N
Pierré
Alain
A
Fauchère
Jean Luc
JL
Hickman
John A
JA
Tucker
Gordon C
GC
Casara
Patrick J
PJ
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
D000588:Amines; D000970:Antineoplastic Agents; D001381:Azepines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007769:Lactams; C029899:imidazole; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase