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Bioorg Med Chem Lett. 2011 May 1;21(9):2711-4. doi: 10.1016/j.bmcl.2010.11.119. Epub 2010 Dec 3.

Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.

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  • 1Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Abstract

This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID:
21183344
[PubMed - indexed for MEDLINE]
PMCID:
PMC3179182
Free PMC Article
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