Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071

  • Bioorg Med Chem Lett. 2011 Nov 1;21(21):6451-5. doi: 10.1016/j.bmcl.2011.08.084.
Evan P Lebois  1 ,  Gregory J Digby ,  Douglas J Sheffler ,  Bruce J Melancon ,  James C Tarr ,  Hyekyung P Cho ,  Nicole R Miller ,  Ryan Morrison ,  Thomas M Bridges ,  Zixiu Xiang ,  J Scott Daniels ,  Michael R Wood ,  P Jeffrey Conn ,  Craig W Lindsley
Affiliations
  • 1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 21930376 DOI: 10.1016/j.bmcl.2011.08.084
Abstract

Herein we report the discovery and SAR of a novel series of M(1) agonists based on the MLPCN probe, ML071. From this, VU0364572 emerged as a potent, orally bioavailable and CNS penetrant M(1) agonist with high selectivity, clean ancillary pharmacology and enantiospecific activity.

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