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Human beta3-adrenergic receptor agonists containing 1,2,3-triazole-substituted benzenesulfonamides
Journal article   Peer reviewed

Human beta3-adrenergic receptor agonists containing 1,2,3-triazole-substituted benzenesulfonamides

L L Brockunier, E R Parmee, H O Ok, M R Candelore, M A Cascieri, L F Colwell, Jr, L Deng, W P Feeney, M J Forrest, G J Hom, …
Bioorganic & medicinal chemistry letters, Vol.10(18), pp.2111-2114
09/18/2000
PMID: 10999482

Abstract

Cricetinae Lipolysis - drug effects Administration, Oral Tachycardia - chemically induced Humans Infusions, Parenteral Biological Availability Macaca mulatta Structure-Activity Relationship Receptors, Adrenergic, beta-3 - metabolism Sulfonamides - pharmacokinetics Dose-Response Relationship, Drug Sulfonamides - chemical synthesis Triazoles - metabolism Animals Isoproterenol - pharmacology Dogs Sulfonamides - metabolism Protein Binding Triazoles - chemical synthesis Triazoles - pharmacokinetics Cyclic AMP - metabolism Adrenergic beta-3 Receptor Agonists CHO Cells
Compounds containing a 1,2,3-triazole-substituted benzenesulfonamide were prepared and found to be potent and selective human beta3-adrenergic receptor agonists. The most interesting compound, trifluoromethylbenzyl analogue 12e (beta3 EC50 = 3.1 nM with >1500-fold selectivity over binding to both beta1- and beta2 receptors), stimulates lipolysis in the rhesus monkey (ED50 = 0.36 mg/kg) and is 25% orally bioavailable in the dog.

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