Human beta3 adrenergic receptor agonists containing cyclic ureidobenzenesulfonamides

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 an...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1999-03, Vol.9 (5), p.749-754
Main Authors: Parmee, E R, Naylor, E M, Perkins, L, Colandrea, V J, Ok, H O, Candelore, M R, Cascieri, M A, Deng, L, Feeney, W P, Forrest, M J, Hom, G J, MacIntyre, D E, Miller, R R, Stearns, R A, Strader, C D, Tota, L, Wyvratt, M J, Fisher, M H, Weber, A E
Format: Article
Language:English
Subjects:
Administration, Oral
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists - chemical synthesis
Adrenergic beta-Agonists - pharmacokinetics
Adrenergic beta-Agonists - pharmacology
Animals
Dogs
Heart Rate - drug effects
Humans
Macaca mulatta
Receptors, Adrenergic, beta - drug effects
Receptors, Adrenergic, beta - metabolism
Receptors, Adrenergic, beta-3
Structure-Activity Relationship
Sulfonamides - chemical synthesis
Sulfonamides - pharmacokinetics
Sulfonamides - pharmacology
Urea - analogs & derivatives
Urea - chemical synthesis
Urea - pharmacokinetics
Urea - pharmacology
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Summary: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.
ISSN:0960-894X