噻吩并吡啶类化合物的设计、合成及 CHK1 抑制剂的构效关系研究。
Design, synthesis and SAR of thienopyridines as potent CHK1 inhibitors.
机构信息
Department of Chemistry, Merck Research Laboratories, Cambridge, MA 02141, USA.
出版信息
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7216-21. doi: 10.1016/j.bmcl.2010.10.105. Epub 2010 Oct 26.
PMID:21074424
Abstract
A novel series of CHK1 inhibitors based on thienopyridine template has been designed and synthesized. These inhibitors maintain critical hydrogen bonding with the hinge and conserved water in the ATP binding site. Several compounds show single digit nanomolar CHK1 activities. Compound 70 shows excellent enzymatic activity of 1 nM.
摘要
我们设计并合成了一系列基于噻吩吡啶模板的新型 CHK1 抑制剂。这些抑制剂与 hinge 区和 ATP 结合位点的保守水分子保持关键氢键相互作用。部分化合物对 CHK1 的抑制活性达到纳摩尔级别，其中化合物 70 的酶活最好，IC50 为 1 nM。
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