Journal article
Synthesis and structure-activity relationship of 5-pyridazin-3-one phenoxypiperidines as potent, selective histamine H-3 receptor inverse agonists
Bioorganic & medicinal chemistry letters, v 22(2), pp 1073-1077
15 Jan 2012
PMID: 22197136
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Optimization of the R-2 and R-6 positions of (5-{4-[3-(R)-2-methylpyrrolin-1-yl-propoxylphenyl)-2H-pyridazin-3-one) 2a with constrained phenoxypiperidines led to the identification of 5-[4-(cyclobutyl-piperidin-4-yloxy)-phenyl]-6-methyl-2H-pyridazin-3-one 8b as a potent, selective histamine H-3 receptor antagonist with favorable pharmacokinetic properties. Compound 8b had an excellent safety genotoxocity profile for a CNS-active compound in the Ames and micronucleus tests, also displayed potent H3R antagonist activity in the brain in the rat dipsogenia model and robust wake activity in the rat EEG/EMG model. (C) 2011 Elsevier Ltd. All rights reserved.
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Details
- Title
- Synthesis and structure-activity relationship of 5-pyridazin-3-one phenoxypiperidines as potent, selective histamine H-3 receptor inverse agonists
- Creators
- Ming Tao - Cephalon Inc, Discovery Res, W Chester, PA 19380 USALisa D. Aimone - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAJohn A. Gruner - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAJoanne R. Mathiasen - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAZeqi Huang - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAJacquelyn Lyons - Cephalon Inc, Discovery Res, W Chester, PA 19380 USARita Raddatz - Cephalon Inc, Discovery Res, W Chester, PA 19380 USARobert L. Hudkins - Cephalon Inc, Discovery Res, W Chester, PA 19380 USA
- Publication Details
- Bioorganic & medicinal chemistry letters, v 22(2), pp 1073-1077
- Publisher
- Elsevier
- Number of pages
- 5
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000299653500061
- Scopus ID
- 2-s2.0-84855706109
- Other Identifier
- 991021900192104721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Chemistry, Medicinal
- Chemistry, Organic