Abstract
We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both β(2)-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC(50)=0.278 μM, which was more potent than phthalazinone, IC(50)=0.520 μM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50)=9.3).
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic beta-2 Receptor Agonists* / chemistry
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Adrenergic beta-2 Receptor Agonists* / pharmacology
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Animals
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Asthma / drug therapy*
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Drug Design*
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Guinea Pigs
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Inhibitory Concentration 50
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Molecular Structure
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Phosphodiesterase 4 Inhibitors / chemistry*
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Phosphodiesterase 4 Inhibitors / pharmacology
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Phosphodiesterase 4 Inhibitors / therapeutic use*
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Pulmonary Disease, Chronic Obstructive / drug therapy*
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Trachea / drug effects*
Substances
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Adrenergic beta-2 Receptor Agonists
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Phosphodiesterase 4 Inhibitors