具有良好理化性质和药代动力学性质的强效和选择性吡唑并[1,5-a]嘧啶类 B-Raf(V600E)激酶抑制剂。
Potent and selective pyrazolo[1,5-a]pyrimidine based inhibitors of B-Raf(V600E) kinase with favorable physicochemical and pharmacokinetic properties.
机构信息
Array BioPharma, Inc., 3200 Walnut Street, Boulder, CO 80301, USA.
出版信息
Bioorg Med Chem Lett. 2012 Jan 15;22(2):1165-8. doi: 10.1016/j.bmcl.2011.11.092. Epub 2011 Nov 30.
PMID:22196124
Abstract
Herein we describe a novel series of ATP competitive B-Raf inhibitors based on the pyrazolo[1,5-a]pyrimidine scaffold. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective and orally available agent with improved physicochemical and pharmacokinetic properties.
摘要
在此，我们描述了一系列基于吡唑并[1,5-a]嘧啶骨架的新型 ATP 竞争型 B-Raf 抑制剂。这些抑制剂具有优异的细胞活性和显著的 B-Raf 选择性。通过优化，我们确定了化合物 17，这是一种具有高活性、选择性和口服生物利用度的候选药物，具有改善的理化性质和药代动力学特性。
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