Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors
作者:Zhuang Miao、Yu-meng Sun、Lan-ying Zhao、Yue-shan Li、Yi-fei Wang、Jin-shan Nan、Ze-en Qiao、Lin-li Li、Sheng-yong Yang
DOI:10.1016/j.bmcl.2020.126966
日期:2020.3
Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50 values of 0.004 μM and 0.001 μM against ROCK Ⅰ and
在本文中,我们报告了一系列噻吩[2,3-d]嘧啶-4(3H)-一衍生物作为一类新的ROCK抑制剂的发现。这些化合物的结构活性关系研究导致最有效的化合物,3-(3-甲氧基苄基)-6-(1H-吡咯并[2,3-b]吡啶-4-基)噻吩并[2,3]的鉴定-d] pyrimidin-4(3H)-one(8k),对ROCKⅠ和ROCKⅡ的IC50值分别为0.004μM和0.001μM。在体外,8k显着降低了ROCK下游信号蛋白的磷酸化水平,并诱导细胞形态和迁移的改变。总体而言,这项研究为靶向ROCKs的药物发现提供了有希望的先导化合物。