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Isatin replacements applied to the highly selective,muscarinic M1 PAM ML137: Continued optimization of an MLPCN probe molecule |
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| Authors: | Bruce J Melancon 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 |
| Institution: | 1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA;3. Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA;4. Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN 37232, USA |
| 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 M1 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 M1 receptor was also maintained. |
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