Aryl tetrahydropyridine inhibitors of farnesyltransferase: bioavailable analogues with improved cellular potency.
Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered bioavailable aryl tetrahydropyridines that are potent in cell culture. The design, synthesis, SAR and biological properties of these compounds will be discussed.
Gwaltney
Stephen L
SL
Pharmaceutical Discovery, R47B, Building AP-10, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. stephen.gwaltney@syrrx.com
O'Connor
Stephen J
SJ
Nelson
Lissa T J
LT
Sullivan
Gerard M
GM
Imade
Hovis
H
Wang
Weibo
W
Hasvold
Lisa
L
Li
Qun
Q
Cohen
Jerome
J
Gu
Wen-Zhen
WZ
Tahir
Stephen K
SK
Bauch
Joy
J
Marsh
Kennan
K
Ng
Shi-Chung
SC
Frost
David J
DJ
Zhang
Haiying
H
Muchmore
Steve
S
Jakob
Clarissa G
CG
Stoll
Vincent
V
Hutchins
Charles
C
Rosenberg
Saul H
SH
Sham
Hing L
HL
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000478:Alkylation; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D006207:Half-Life; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011725:Pyridines; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase