Discovery of a series of 2-phenyl- N -(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K v7.2 (KCNQ2) channel pharmacology: Identification of (S)-2-phenyl- N -(2-(pyrrolidin-1-yl) phenyl)butanamide (ML252) as a potent, brain penetrant K v7.2 channel inhibitor

Yiu Yin Cheung, Haibo Yu, Kaiping Xu, Beiyan Zou, Meng Wu, Owen B. McManus, Min Li, Craig W. Lindsley, Corey R. Hopkins

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

A potent and selective inhibitor of KCNQ2, (S)-5 (ML252, IC 50 = 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, EC 50 = 170 nM), suggesting an interaction at a critical site for controlling gating of KCNQ2 channels.

Original languageEnglish (US)
Pages (from-to)6975-6979
Number of pages5
JournalJournal of Medicinal Chemistry
Volume55
Issue number15
DOIs
Publication statusPublished - Aug 9 2012

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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