Discovery of highly potent and selective type I B-Raf kinase inhibitors

Xiaolun Wang; Dan M Berger; Edward J Salaski; Nancy Torres; Yongbo Hu; Jeremy I Levin; Dennis Powell; Donald Wojciechowicz; Karen Collins; Eileen Frommer

doi:10.1016/j.bmcl.2009.10.030

Discovery of highly potent and selective type I B-Raf kinase inhibitors

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6571-4. doi: 10.1016/j.bmcl.2009.10.030. Epub 2009 Oct 13.

Authors

Xiaolun Wang¹, Dan M Berger, Edward J Salaski, Nancy Torres, Yongbo Hu, Jeremy I Levin, Dennis Powell, Donald Wojciechowicz, Karen Collins, Eileen Frommer

Affiliation

¹ Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. xxw104@gmail.com

PMID: 19854649
DOI: 10.1016/j.bmcl.2009.10.030

Abstract

A series of pyrazolo[1,5-alpha]pyrimidine analogs has been prepared and found to be potent and selective B-Raf inhibitors. Molecular modeling suggests they bind to the active conformation of the enzyme.

MeSH terms

Drug Discovery*
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
Proto-Oncogene Proteins B-raf / metabolism
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship
Substrate Specificity

Substances

Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
pyrazolo(1,5-a)pyrimidine
Proto-Oncogene Proteins B-raf