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Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists
Journal article   Open access   Peer reviewed

Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists

Allison L. Zulli, Lisa D. Aimone, Joanne R. Mathiasen, John A. Gruner, Rita Raddatz, Edward R. Bacon and Robert L. Hudkins
Bioorganic & medicinal chemistry letters, v 22(8), pp 2807-2810
15 Apr 2012
PMID: 22450133
url
https://doi.org/10.7270/q26m37vxView
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Abstract

Chemistry Chemistry, Medicinal Chemistry, Organic Life Sciences & Biomedicine Pharmacology & Pharmacy Physical Sciences Science & Technology
Optimization of a series of aminomethyl ketone diamine H3R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H3R and demonstrated in vivo H3R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.

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Web of Science research areas
Chemistry, Medicinal
Chemistry, Organic
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