Abstract
A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated as dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high β2-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R,R)-11c, exhibited agonist (EC50=1.05nM, pEC50=9.0) and potent PDE4B2 inhibitory activities (IC50=0.092μM).
Keywords:
Bronchodilator; Chronic obstructive pulmonary disease (COPD); PDE4 inhibitor; β(2)-Adrenoceptor agonist.
Copyright © 2013. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic beta-2 Receptor Agonists / chemical synthesis
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Adrenergic beta-2 Receptor Agonists / chemistry
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Adrenergic beta-2 Receptor Agonists / pharmacology*
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Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
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Dose-Response Relationship, Drug
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Drug Design*
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Ethanolamines / chemical synthesis
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Ethanolamines / chemistry
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Ethanolamines / pharmacology*
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Formoterol Fumarate
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Humans
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Molecular Structure
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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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Phthalazines / chemical synthesis
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Phthalazines / chemistry
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Phthalazines / pharmacology*
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Receptors, Adrenergic, beta-2 / metabolism
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Adrenergic beta-2 Receptor Agonists
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Ethanolamines
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Phosphodiesterase 4 Inhibitors
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Phthalazines
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Receptors, Adrenergic, beta-2
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Recombinant Proteins
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Formoterol Fumarate