Discovery of potent imidazole and cyanophenyl containing farnesyltransferase inhibitors with improved oral bioavailability.
A pyridyl moiety was introduced into a previously developed series of farnesyltransferase inhibitors containing imidazole and cyanophenyl (such as 4), resulting in potent inhibitors with improved pharmacokinetics.
Tong
Yunsong
Y
R47B, AP10, Global Pharmaceutical R&D, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6101, USA. yunsong.tong@abbott.com
Lin
Nan-Horng
NH
Wang
Le
L
Hasvold
Lisa
L
Wang
Weibo
W
Leonard
Nicholas
N
Li
Tongmei
T
Li
Qun
Q
Cohen
Jerry
J
Gu
Wen-Zhen
WZ
Zhang
Haiying
H
Stoll
Vincent
V
Bauch
Joy
J
Marsh
Kennan
K
Rosenberg
Saul H
SH
Sham
Hing L
HL
D000284:Administration, Oral; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D018360:Crystallography, X-Ray; D004285:Dogs; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051231:Farnesyltranstransferase; D000882:Haplorhini; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase