Identification of 2-amino-5-(thioaryl)thiazoles as inhibitors of nerve growth factor receptor TrkA.
2-Amino-5-(thioaryl)thiazoles are potent inhibitors of TrkA (e.g., 20h, TrkA IC(50)=0.6 nM) that show anti-proliferative effect in cellular assays. A proposed inhibitor binding mode to TrkA active site is consistent with key SAR observations.
Kim
Soong-Hoon
SH
Department of Oncology Chemistry, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. soonghoon.kim@bms.com
Tokarski
John S
JS
Leavitt
Kenneth J
KJ
Fink
Brian E
BE
Salvati
Mark E
ME
Moquin
Robert
R
Obermeier
Mary T
MT
Trainor
George L
GL
Vite
Gregory G
GG
Stadnick
Linda K
LK
Lippy
Jonathan S
JS
You
Dan
D
Lorenzi
Matthew V
MV
Chen
Ping
P
D010766:Phosphorylation; D020917:Receptor, trkA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D013844:Thiazoles; D020917:Receptor, trkA