B-Raf kinase inhibitors: Hit enrichment through scaffold hopping |
| |
Authors: | Ariamala Gopalsamy Mengxiao Shi Yongbo Hu Frederick Lee Larry Feldberg Eileen Frommer Steven Kim Karen Collins Donald Wojciechowicz Robert Mallon |
| |
Institution: | 1. Chemical 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: | In continuation of our efforts toward hit identification and optimization for a B-Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moieties in order to generate novel B-raf kinase inhibitors with desirable potency and properties. This strategy led to the identification of additional lead compound 11b which had good enzyme and cell potency, while maintaining selectivity over a number of kinases. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|