Synthesis and Pharmacological Evaluation of M4 Muscarinic Receptor Positive Allosteric Modulators Derived from VU10004
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- 作者：Tracey Huynh ; Celine Valant ; Ian T. Crosby ; Patrick M. Sexton ; Arthur Christopoulos ; Ben Capuano
- 刊名：ACS Chemical Neuroscience
- 出版年：2015
- 出版时间：June 17, 2015
- 年：2015
- 卷：6
- 期：6
- 页码：838-844
- 全文大小：345K
- ISSN：1948-7193
文摘
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 VU10004. These compounds investigate the pharmacological effects of target thieno[2,3-b]pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (KB), cooperativity (伪尾), and direct agonist properties (蟿B).