通式 G(q)mAChR M(1)、M(3)、M(5) 正变构调节剂 (PAM) 先导化合物的化学 lead 优化。第一部分：第一个高选择性 M(5) PAM 的开发。
Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) 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 Jan 15;20(2):558-62. doi: 10.1016/j.bmcl.2009.11.089. Epub 2009 Nov 22.
Abstract
This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS.
摘要
这封信件描述了一项针对 VU0238429 的化学先导优化活动，VU0238429 是通过对 VU0119498（一种 pan G(q) mAChR M(1)、M(3)、M(5) 正变别构调节剂（PAM））的类似物工作发现的首个 M(5) 优先 PAM。一种迭代文库合成方法提供了首个选择性 M(5) PAM（在 30μM 时对 M(1)-M(4) 无活性），这是一种重要的工具化合物，可用于研究 M(5) 在中枢神经系统中的作用。
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