Identification of 2-amino-5-(thioaryl)thiazoles as inhibitors of nerve growth factor receptor TrkA

Soong-Hoon Kim; John S Tokarski; Kenneth J Leavitt; Brian E Fink; Mark E Salvati; Robert Moquin; Mary T Obermeier; George L Trainor; Gregory G Vite; Linda K Stadnick; Jonathan S Lippy; Dan You; Matthew V Lorenzi; Ping Chen

doi:10.1016/j.bmcl.2007.11.076

Identification of 2-amino-5-(thioaryl)thiazoles as inhibitors of nerve growth factor receptor TrkA

Bioorg Med Chem Lett. 2008 Jan 15;18(2):634-9. doi: 10.1016/j.bmcl.2007.11.076. Epub 2007 Nov 28.

Authors

Soong-Hoon Kim¹, John S Tokarski, Kenneth J Leavitt, Brian E Fink, Mark E Salvati, Robert Moquin, Mary T Obermeier, George L Trainor, Gregory G Vite, Linda K Stadnick, Jonathan S Lippy, Dan You, Matthew V Lorenzi, Ping Chen

Affiliation

¹ Department of Oncology Chemistry, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. [email protected]

PMID: 18055203
DOI: 10.1016/j.bmcl.2007.11.076

Abstract

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.

MeSH terms

Phosphorylation
Receptor, trkA / antagonists & inhibitors*
Receptor, trkA / metabolism
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Thiazoles
Receptor, trkA