探究 M4 毒蕈碱型乙酰胆碱受体正变构调节剂的结构要求。
Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor.
机构信息
Medicinal Chemistry and ‡Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University , 381-399 Royal Parade, Parkville VIC 3052, Australia.
出版信息
J Med Chem. 2013 Oct 24;56(20):8196-200. doi: 10.1021/jm401032k. Epub 2013 Oct 11.
The M4 mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M4 PAMs derived from VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (KB), cooperativity (αβ), and direct agonist properties (τB).
M4 mAChR 参与多种中枢神经系统疾病，并且具有变构结合位点，可利用调节乙酰胆碱亲和力和/或效力的配体进行选择性受体靶向。我们报告了源自 VU0152100 和 VU10005 的假定 M4 PAMs 的聚焦文库的合成。这些化合物研究了先前鉴定的甲氧基和氟取代基的药理作用，提供了亲和力（KB）、协同作用（αβ）和直接激动剂性质（τB）的有用估计值。
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