Discovery of a Series of 2-Phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as Novel Molecular Switches that Modulate Modes of Kv7.2 (KCNQ2) Channel Pharmacology: Identification of (
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- 作者：Yiu-Yin Cheung ; Haibo Yu ; Kaiping Xu ; Beiyan Zou ; Meng Wu ; Owen B. McManus ; Min Li ; Craig W. Lindsley ; Corey R. Hopkins
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：August 9, 2012
- 年：2012
- 卷：55
- 期：15
- 页码：6975-6979
- 全文大小：260K
- 年卷期：v.55,no.15(August 9, 2012)
- ISSN：1520-4804
文摘
A potent and selective inhibitor of KCNQ2, (S)-5 (ML252, IC50 = 69 nM), was discovered after a high-throughput screen of the MLPCN library was performed. SAR studies revealed a small structural change (ethyl group to hydrogen) caused a functional shift from antagonist to agonist activity (37, EC50 = 170 nM), suggesting an interaction at a critical site for controlling gating of KCNQ2 channels.