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ID: ALA1133209
Journal: Bioorg Med Chem Lett
Title: Synthesis and SAR of benzyl and phenoxymethylene oxadiazole benzenesulfonamides as selective beta3 adrenergic receptor agonist antiobesity agents.
Authors: Biftu T, Feng DD, Liang GB, Kuo H, Qian X, Naylor EM, Colandrea VJ, Candelore MR, Cascieri MA, Colwell LF, Forrest MJ, Hom GJ, MacIntyre DE, Stearns RA, Strader CD, Wyvratt MJ, Fisher MH, Weber AE.
Abstract: Benzyl and phenoxymethylene substituted oxadiazoles are potent and orally bioavailable beta3 adrenergic receptor (AR) agonists. The 4-trifluormethoxy substituted 5-benzyl oxadiazole 5f has an EC50 of 8 nM in the beta3 AR agonist assay with 100-fold selectivity over beta1 and beta2 AR binding inhibition activity. Its oral bioavailability in dogs is 30 +/- 4%, with a half-life of 3.8 +/- 0.4 h. In the anesthetized rhesus, 5f evoked a dose-dependent glycerolemia (ED50Gly = 0.15 mg/kg). Under these conditions a heart rate increase of 15% was observed at a dose level of 10 mg/kg.
CiteXplore: 10888325