Journal article
Discovery of (1R, 6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]3,4-diaza-bicyclo[4.1.0] hept-4-en-2-one (R, S-4a): Histamine H3 receptor inverse agonist demonstrating potent cognitive enhancing and wake promoting activity
Bioorganic & medicinal chemistry letters, v 24(5), pp 1303-1306
01 Mar 2014
PMID: 24513042
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A series of fused cyclopropyl-4,5-dihydropyridazin-3-one (3,4-diaza-bicyclo[4.1.0] hept-4-en-2-one) phenoxypiperidine analogs was designed and synthesized, leading to the identification of (1R, 6S)-5[ 4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-3,4-diaza-bicyclo[4.1.0] hept-4-en-2-one (R, S-4a) as a secondgeneration pyridazin-3-one H3R antagonist. Compound R, S-4a was a potent H3R functional antagonist in vivo in the rat dipsogenia model, demonstrated potent wake activity in the rat EEG/EMG model, and enhanced short-term memory in the rat social recognition memory model at doses as low as 0.03-0.3 mg/kg po. (C) 2014 Elsevier Ltd. All rights reserved.
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Details
- Title
- Discovery of (1R, 6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]3,4-diaza-bicyclo[4.1.0] hept-4-en-2-one (R, S-4a): Histamine H3 receptor inverse agonist demonstrating potent cognitive enhancing and wake promoting activity
- Creators
- Robert L. Hudkins - Teva PharmaceuticalsKurt A. Josef - Teva PharmaceuticalsNadine C. Becknell - Teva PharmaceuticalsLisa D. Aimone - Teva PharmaceuticalsJacquelyn A. Lyons - Teva PharmaceuticalsJoanne R. Mathiasen - Teva PharmaceuticalsJohn A. Gruner - Teva PharmaceuticalsRita Raddatz - Teva Pharmaceuticals
- Publication Details
- Bioorganic & medicinal chemistry letters, v 24(5), pp 1303-1306
- Publisher
- Elsevier
- Number of pages
- 4
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000331705200011
- Scopus ID
- 2-s2.0-84894519100
- Other Identifier
- 991021900191904721
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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