Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule

Research output: Contribution to journalJournal articleResearchpeer-review

  • Bruce J Melancon
  • Michael S Poslusney
  • Gentry, Patrick Ryan
  • James C Tarr
  • Douglas J Sheffler
  • Margrith E Mattmann
  • Thomas M Bridges
  • Thomas J Utley
  • J Scott Daniels
  • Colleen M Niswender
  • P Jeffrey Conn
  • Craig W Lindsley
  • Michael R Wood

This Letter describes the continued optimization of an MLPCN probe molecule (ML137) with a focused effort on the replacement/modification of the isatin moiety present in this highly selective M(1) PAM. A diverse range of structures were validated as viable replacements for the isatin, many of which engendered sizeable improvements in their ability to enhance the potency and efficacy of acetylcholine when compared to ML137. Muscarinic receptor subtype selectivity for the M(1) receptor was also maintained.

Original languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Issue number2
Pages (from-to)412-6
Number of pages5
Publication statusPublished - 15 Jan 2013
Externally publishedYes

Bibliographical note

Copyright © 2012 Elsevier Ltd. All rights reserved.

    Research areas

  • Inhibitory Concentration 50, Isatin/analogs & derivatives, Molecular Probes/chemistry, Molecular Structure, Monoamine Oxidase Inhibitors/pharmacology, Receptor, Muscarinic M1/drug effects

ID: 213625756