2. Academic Validation
  3. Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012

Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012

  • Bioorg Med Chem Lett. 2012 Aug 1;22(15):5035-40. doi: 10.1016/j.bmcl.2012.06.018.
Bruce J Melancon 1,  Thomas J Utley,  Christian Sevel,  Margrith E Mattmann,  Yiu-Yin Cheung,  Thomas M Bridges,  Ryan D Morrison,  Douglas J Sheffler,  Colleen M Niswender,  J Scott Daniels,  P Jeffrey Conn,  Craig W Lindsley,  Michael R Wood
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. [email protected]
PMID: 22749871 DOI: 10.1016/j.bmcl.2012.06.018
Abstract

This Paper describes the continued optimization of an MLPCN probe molecule M(1) antagonist (ML012) through an iterative parallel synthesis approach. After several rounds of modifications of the parent compound, we arrived at a new azetidine scaffold that displayed improved potency while maintaining a desirable level of selectivity over other muscarinic receptor subtypes. Data for representative molecules 7w (VU0452865) and 12a (VU0455691) are presented.

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