pan Gq mAChR M1、M3、M5 正变构调节剂 (PAM) 先导的化学 Lead 优化。第二部分：开发一种强效且高度选择性的 M1 PAM。
Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM.
机构信息
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2010 Mar 15;20(6):1972-5. doi: 10.1016/j.bmcl.2010.01.109. Epub 2010 Feb 1.
Abstract
This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) with the goal of developing a selective M(1) PAM. An iterative library synthesis approach delivered a potent (M(1) EC(50)=830 nM) and highly selective M(1) PAM (>30 microM vs M(2)-M(5)).
摘要
这封信件描述了一项针对 VU0119498 的化学先导优化活动，VU0119498 是一种全 G(q) mAChR M(1)、M(3)、M(5) 正变构调节剂 (PAM)，旨在开发一种选择性 M(1) PAM。一种迭代文库合成方法提供了一种强效的（M(1) EC(50)=830 nM）和高度选择性的 M(1) PAM（>30 microM 对比 M(2)-M(5)）。
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