Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM

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Thomas M Bridges, J Phillip Kennedy, Meredith J Noetzel, Micah L Breininger, Patrick R Gentry, P Jeffrey Conn, Craig W Lindsley

This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) with the goal of developing a selective M(1) PAM. An iterative library synthesis approach delivered a potent (M(1) EC(50)=830 nM) and highly selective M(1) PAM (>30 microM vs M(2)-M(5)).

Original languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Volume20
Issue number6
Pages (from-to)1972-5
Number of pages4
ISSN0960-894X
DOIs
Publication statusPublished - 15 Mar 2010
Externally publishedYes

Bibliographical note

Copyright 2010 Elsevier Ltd. All rights reserved.

    Research areas

  • Allosteric Regulation, Cholinergic Agents/chemistry, Drug Design, Receptors, Muscarinic/drug effects, Structure-Activity Relationship

ID: 213626845