Abstract
(-)-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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Bronchoconstriction / drug effects
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Bronchodilator Agents / chemical synthesis
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Bronchodilator Agents / chemistry
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Bronchodilator Agents / pharmacology
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Drug Design
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Humans
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Models, Molecular
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Phosphodiesterase 3 Inhibitors / chemical synthesis
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Phosphodiesterase 3 Inhibitors / chemistry*
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Phosphodiesterase 3 Inhibitors / pharmacology*
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Phosphodiesterase 4 Inhibitors / chemical synthesis
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Phosphodiesterase 4 Inhibitors / chemistry*
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Phosphodiesterase 4 Inhibitors / pharmacology*
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Pyridines / chemical synthesis
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Pyridines / chemistry
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Pyridines / pharmacology
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Bridged Bicyclo Compounds, Heterocyclic
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Bronchodilator Agents
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Phosphodiesterase 3 Inhibitors
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Phosphodiesterase 4 Inhibitors
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Pyridines