Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 3, aryl substituted pyrrolidines
Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 3, aryl substituted pyrrolidines
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DOI：
10.1016/j.bmcl.2010.04.069
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发表时间：
2010-06-15
影响因子：
2.7
通讯作者：
Young, Erick R. R.
中科院分区：
文献类型：
--
作者：
Bosanac, Todd;Hickey, Eugene R.;Young, Erick R. R.
本文描述了一系列衍生自2的β-芳基取代吡咯烷2 H-异喹啉-1-酮Rho激酶（ROCK）抑制剂的发现和构效关系。SAR研究表明，β-位上的芳基基团对效力最佳。我们的努力集中在提高这种异喹诺酮类抑制剂的ROCK效力，这导致鉴定出吡咯烷32，其证明主动脉环（AR）效力比2提高10倍。(C)2010爱思唯尔有限公司保留所有权利。NH
The discovery and SAR of a series of beta-aryl substituted pyrrolidine 2H-isoquinolin-1-one inhibitors of Rho-kinase (ROCK) derived from 2 is herein described. SAR studies have shown that aryl groups in the beta-position are optimal for potency. Our efforts focused on improving the ROCK potency of this isoquinolone class of inhibitors which led to the identification of pyrrolidine 32 which demonstrated a 10-fold improvement in aortic ring (AR) potency over 2. (C) 2010 Elsevier Ltd. All rights reserved. NH