Impact on farnesyltransferase inhibition of 4-chlorophenyl moiety replacement in the Zarnestra series.
Based on the structure of R115777 (tipifarnib, Zarnestra), a series of farnesyltransferase inhibitors have been synthesized by modification of the 2-quinolinone motif and transposition of the 4-chlorophenyl ring to the imidazole or its replacement by 5-membered rings. This has yielded a novel series of potent farnesyltransferase inhibitors.
Angibaud
Patrick
P
Medicinal Chemistry Department, Johnson & Johnson Pharmaceutical Research and Development (J&JPRD), Campus de Maigremont BP615, Val de Reuil, France. pangibau@prdfr.jnj.com
Mevellec
Laurence
L
Meyer
Christophe
C
Bourdrez
Xavier
X
Lezouret
Patricia
P
Pilatte
Isabelle
I
Poncelet
Virginie
V
Roux
Bruno
B
Merillon
Sophie
S
End
David W
DW
Van Dun
Jacky
J
Wouters
Walter
W
Venet
Marc
M
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D015363:Quinolones; D051231:Farnesyltranstransferase; C402769:tipifarnib