选择性毒蕈碱型乙酰胆碱受体亚型1（M1 mAChR）拮抗剂的合成与构效关系
Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists.
作者信息
Lewis L Michelle, Sheffler Douglas, Williams Richard, Bridges Thomas M, Kennedy J Phillip, Brogan J T, Mulder Matthew J, Williams Lyndsey, Nalywajko Natalia T, Niswender Colleen M, Weaver Charles D, Conn P Jeffrey, Lindsley Craig W
机构信息
Vanderbilt Program in Drug Discovery, Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2008 Feb 1;18(3):885-90. doi: 10.1016/j.bmcl.2007.12.051. Epub 2008 Jan 4.
Abstract
This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a novel series of selective M1 mAChR antagonists for the potential treatment of Parkinson's disease, dystonia and other movement disorders. Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5.
摘要
本信函描述了通过迭代类似物库方法开发的一系列新型选择性M1毒蕈碱乙酰胆碱受体拮抗剂的合成及其构效关系，这些拮抗剂可用于潜在治疗帕金森病、肌张力障碍和其他运动障碍。该系列化合物的M1拮抗剂IC50值在441 nM至19 μM范围内，相对于rM2 - rM5具有8至>340倍的功能选择性。
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