Literature DB >> 23237839

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

Bruce J Melancon1, Michael S Poslusney, Patrick R Gentry, 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.   

Abstract

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.
Copyright © 2012 Elsevier Ltd. All rights reserved.

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Year:  2012        PMID： 23237839      PMCID： PMC3534865          DOI： 10.1016/j.bmcl.2012.11.092

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


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