Abstract
Human beta3 adrenergic receptor agonists containing 5-membered ring ureas were shown to be potent partial agonists with excellent selectivity over beta1 and beta2 binding. L-760,087 (4a) and L-764,646 (5a) (beta3 EC50 = 18 and 14 nM, respectively) stimulate lipolysis in rhesus monkeys (ED50 = 0.2 and 0.1 mg/kg, respectively) with minimal effects on heart rate. Oral absorption in dogs is improved over other urea analogs.
MeSH terms
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Administration, Oral
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Adrenergic beta-1 Receptor Agonists
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Adrenergic beta-2 Receptor Agonists
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Adrenergic beta-Agonists / chemical synthesis*
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Adrenergic beta-Agonists / pharmacokinetics
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Adrenergic beta-Agonists / pharmacology
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Animals
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Dogs
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Heart Rate / drug effects
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Humans
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Macaca mulatta
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Receptors, Adrenergic, beta / drug effects
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Receptors, Adrenergic, beta / metabolism*
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Receptors, Adrenergic, beta-3
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / pharmacokinetics
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Sulfonamides / pharmacology
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Urea / analogs & derivatives
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Urea / chemical synthesis
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Urea / pharmacokinetics
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Urea / pharmacology
Substances
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Adrenergic beta-1 Receptor Agonists
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Adrenergic beta-2 Receptor Agonists
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Adrenergic beta-Agonists
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L 755507
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L 757793
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L 760087
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L 764646
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Receptors, Adrenergic, beta
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Receptors, Adrenergic, beta-3
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Sulfonamides
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Urea