2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2010 Mar 15;20(6):1972-5. doi: 10.1016/j.bmcl.2010.01.109.
Thomas M Bridges 1,  J Phillip Kennedy,  Meredith J Noetzel,  Micah L Breininger,  Patrick R Gentry,  P Jeffrey Conn,  Craig W Lindsley
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 20156687 DOI: 10.1016/j.bmcl.2010.01.109
Abstract

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)).

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