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4,5-Dihydropyridazin-3-one derivatives as histamine H-3 receptor inverse agonists
Journal article   Open access   Peer reviewed

4,5-Dihydropyridazin-3-one derivatives as histamine H-3 receptor inverse agonists

Robert L. Hudkins, Lisa D. Aimone, Reddeppa Reddy Dandu, Derek Dunn, John A. Gruner, Zeqi Huang, Kurt A. Josef, Jacquelyn A. Lyons, Joanne R. Mathiasen, Ming Tao, …
Bioorganic & medicinal chemistry letters, v 22(1), pp 194-198
01 Jan 2012
PMID: 22142542
url
https://doi.org/10.7270/q25q4wjvView
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Abstract

Chemistry Chemistry, Medicinal Chemistry, Organic Life Sciences & Biomedicine Pharmacology & Pharmacy Physical Sciences Science & Technology
H3R structure-activity relationships for a new class of 4,5-dihydropyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modification of the 4,5-dihydropyridazinone moiety to block in vivo metabolism identified 4,4-dimethyl-6-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4,5-dihydro-2H-pyridazin-3-one 22 as a lead candidate demonstrating potent in vivo functional H3R antagonism in the rat dipsogenia model and robust wake promoting activity in the rat EEG/EMG model. (C) 2011 Elsevier Ltd. All rights reserved.

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Web of Science research areas
Chemistry, Medicinal
Chemistry, Organic
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