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)).
|Journal||Bioorganic & Medicinal Chemistry Letters|
|Number of pages||4|
|Publication status||Published - 15 Mar 2010|
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- Allosteric Regulation, Cholinergic Agents/chemistry, Drug Design, Receptors, Muscarinic/drug effects, Structure-Activity Relationship