Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 22, Issue 22, Pages 6923-6928Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.09.011
Keywords
Muscarinic acetylcholine receptor 1; M-1 antagonist; VU0433670; VU0431263; Fluorination
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Funding
- NIMH NIH HHS [R01 MH073676] Funding Source: Medline
- NINDS NIH HHS [R01 NS031373] Funding Source: Medline
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Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M-1 acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M-1 antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement experiments demonstrated the competitive, orthosteric binding of these compounds; human selectivity data are presented. (C) 2012 Elsevier Ltd. All rights reserved.
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