Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule

Research output: Contribution to journalJournal articleResearchpeer-review

Michael S Poslusney, Bruce J Melancon, Patrick R Gentry, Douglas J Sheffler, 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 further optimization of an MLPCN probe molecule (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M1 PAMs, are presented. These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype.

Original languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Volume23
Issue number6
Pages (from-to)1860-4
Number of pages5
ISSN0960-894X
DOIs
Publication statusPublished - 15 Mar 2013
Externally publishedYes

Bibliographical note

Copyright © 2013 Elsevier Ltd. All rights reserved.

    Research areas

  • Allosteric Regulation, Animals, Humans, Isatin/analogs & derivatives, Protein Binding, Pyrrolidines/chemical synthesis, Rats, Receptor, Muscarinic M1/antagonists & inhibitors, Spiro Compounds/chemistry, Structure-Activity Relationship

ID: 213625595