Hit to lead optimization of pyrazolo[1,5-a]pyrimidines as B-Raf kinase inhibitors |
| |
| Authors: | Ariamala Gopalsamy Greg Ciszewski Mengxiao Shi Dan Berger Yongbo Hu Frederick Lee Larry Feldberg Eileen Frommer Steven Kim Karen Collins Donald Wojciechowicz Robert Mallon |
| |
| Institution: | 1. Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA;2. Discovery Oncology, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA |
| |
| Abstract: | Our continued effort towards optimization of the pyrazolo1,5-a]pyrimidine scaffold as B-Raf kinase inhibitors is described. Structure guided design was utilized to introduce kinase hinge region interacting groups in the 2-position of the scaffold. This strategy led to the identification of lead compound 9 with enhanced enzyme and cellular potency, while maintaining good selectivity over a number of kinases. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
