Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity
| Autor: | Robert W. Allcock, Satoshi Takita, Tetsuya Kishi, Tomohiko Eiraku, Zhong Jiang, Tokutaro Yasue, David R. Adams, Koji Ochiai, Yasushi Kohno, Kazunori Fukuchi, Kazuhiko Iwase, Akihiko Kojima |
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| Rok vydání: | 2011 |
| Předmět: |
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Molecular medicine.drug_class Stereochemistry Pyridines Bronchoconstriction Clinical Biochemistry Phosphodiesterase 3 Anti-Inflammatory Agents Pharmaceutical Science Phosphodiesterase 3 Inhibitors Biochemistry Anti-inflammatory chemistry.chemical_compound Structure-Activity Relationship In vivo Drug Discovery Pyridine medicine Structure–activity relationship Humans Molecular Biology Trifluoromethyl Bicyclic molecule Chemistry Organic Chemistry Phosphodiesterase Bridged Bicyclo Compounds Heterocyclic Bronchodilator Agents Drug Design Molecular Medicine Phosphodiesterase 4 Inhibitors |
| Zdroj: | Bioorganicmedicinal chemistry. 20(5) |
| ISSN: | 1464-3391 |
| Popis: | (-)-6-(7-Methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydro-3-(2H)-pyridazinone (KCA-1490) is a dual PDE3/4 inhibitor that exhibits potent combined bronchodilatory and anti-inflammatory activity. A survey of potential bicyclic heteroaromatic replacement subunits for the pyrazolo[1,5-a]pyridine core of KCA-1490 has identified the 4-methoxy-2-(trifluoromethyl)benzo[d]thiazol-7-yl and 8-methoxy-2-(trifluoromethyl)quinolin-5-yl analogues as dual PDE3/4-inhibitory compounds that potently suppress histamine-induced bronchoconstriction and exhibit anti-inflammatory activity in vivo. |
| Databáze: | OpenAIRE |
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