Abstract
A series of novel, potent and selective human β(2) adrenoceptor agonists incorporating a urea moiety on the terminal right-hand side phenyl ring of (R)-salmeterol is presented. Urea 9j had long duration of action in vitro on guinea pig trachea, and also in vivo similar to that of salmeterol. It had lower oral absorption and bioavailability than salmeterol in both rat and dog. It had a turnover ratio similar to salmeterol, with no evidence for formation of any aniline metabolites in human liver microsomes and hepatocytes. However no crystalline salts suitable for inhaled delivery were identified.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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 / pharmacokinetics
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Adrenergic beta-2 Receptor Agonists / pharmacology
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Albuterol / analogs & derivatives
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Albuterol / chemistry
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Albuterol / pharmacokinetics
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Albuterol / pharmacology
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Animals
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Asthenia / drug therapy*
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Bronchodilator Agents / pharmacology*
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CHO Cells
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Cricetinae
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Cricetulus
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Dogs
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Dose-Response Relationship, Drug
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Female
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Guinea Pigs
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Humans
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Male
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Rats
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Salmeterol Xinafoate
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Stereoisomerism
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Urea / analogs & derivatives*
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Urea / pharmacology*
Substances
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Adrenergic beta-2 Receptor Agonists
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Bronchodilator Agents
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Salmeterol Xinafoate
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Urea
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Albuterol