2. Academic Validation
  3. Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM

Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM

  • Bioorg Med Chem Lett. 2010 Jan 15;20(2):558-62. doi: 10.1016/j.bmcl.2009.11.089.
Thomas M Bridges 1,  J Phillip Kennedy,  Hyekyung P Cho,  Micah L Breininger,  Patrick R Gentry,  Corey R Hopkins,  P Jeffrey Conn,  Craig W Lindsley
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 20004578 DOI: 10.1016/j.bmcl.2009.11.089
Abstract

This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS.

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