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3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties
Journal article   Peer reviewed

3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties

A E Weber, H O Ok, R F Alvaro, M R Candelore, M A Cascieri, S H Chiu, L Deng, M J Forrest, G J Hom, J E Hutchins, …
Bioorganic & medicinal chemistry letters, Vol.8(16), pp.2111-2116
08/18/1998
PMID: 9873496

Abstract

Lipolysis - drug effects Humans Biological Availability Macaca mulatta Structure-Activity Relationship Propanolamines - pharmacokinetics Adrenergic beta-Agonists - chemistry Molecular Structure Adrenergic beta-Agonists - chemical synthesis Receptors, Adrenergic, beta - drug effects Propanolamines - chemical synthesis Binding, Competitive Pyridines Sulfonamides - chemistry Receptors, Adrenergic, beta-3 Adrenergic beta-Agonists - pharmacokinetics Receptors, Adrenergic, beta - physiology Sulfonamides - pharmacology Sulfonamides - pharmacokinetics Sulfonamides - chemical synthesis Animals Propanolamines - chemistry Dogs Kinetics Propanolamines - pharmacology
Pyridyloxypropanolamines L-749,372 (8, beta 3 EC50 = 3.6 nM) and L-750,355 (29, beta 3 EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimulate lipolysis in rhesus monkeys (ED50 = 2 and 0.8 mg/kg, respectively), with minimal effects on heart rate. Oral bioavailability in dogs, 41% for L-749,372 and 47% for L-750,355, is improved relative to phenol analogs.

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