Journal article
4-Phenoxypiperidine pyridazin-3-one histamine H-3 receptor inverse agonists demonstrating potent and robust wake promoting activity
Bioorganic & medicinal chemistry letters, v 22(4), pp 1504-1509
15 Feb 2012
PMID: 22290075
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.
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Details
- Title
- 4-Phenoxypiperidine pyridazin-3-one histamine H-3 receptor inverse agonists demonstrating potent and robust wake promoting activity
- Creators
- Robert L. Hudkins - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAAllison L. Zulli - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAReddeppa Reddy Dandu - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAMing Tao - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAKurt A. Josef - Cephalon Inc, Discovery Res, W Chester, PA 19380 USALisa D. Aimone - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAR. Curtis Haltiwanger - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAZeqi Huang - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAJacquelyn A. Lyons - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAJoanne R. Mathiasen - Cephalon Inc, Discovery Res, W Chester, PA 19380 USARita Raddatz - Cephalon Inc, Discovery Res, W Chester, PA 19380 USAJohn A. Gruner - Cephalon Inc, Discovery Res, W Chester, PA 19380 USA
- Publication Details
- Bioorganic & medicinal chemistry letters, v 22(4), pp 1504-1509
- Publisher
- Elsevier
- Number of pages
- 6
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000300404900003
- Scopus ID
- 2-s2.0-84856679176
- Other Identifier
- 991021900194304721
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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