2. Academic Validation
  3. Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012

Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012

  • Bioorg Med Chem Lett. 2012 Jan 15;22(2):1044-8. doi: 10.1016/j.bmcl.2011.11.110.
Bruce J Melancon 1,  Alexander P Lamers,  Thomas M Bridges,  Gary A Sulikowski,  Thomas J Utley,  Douglas J Sheffler,  Meredith J Noetzel,  Ryan D Morrison,  J Scott Daniels,  Colleen M Niswender,  Carrie K Jones,  P Jeffrey Conn,  Craig W Lindsley,  Michael R Wood
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 22197142 DOI: 10.1016/j.bmcl.2011.11.110
Abstract

This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M(1)-selective antagonist, compound 13l (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented.

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