强效且口服生物可利用的基于杂环的β3肾上腺素能受体激动剂的发现，肥胖症治疗的潜在疗法。
Discovery of potent and orally bioavailable heterocycle-based beta3-adrenergic receptor agonists, potential therapeutics for the treatment of obesity.
作者信息
Lafontaine Jennifer A, Day Robert F, Dibrino Joe, Hadcock John R, Hargrove Diane M, Linhares Michael, Martin Kelly A, Maurer Tristan S, Nardone Nancy A, Tess David A, Dasilva-Jardine Paul
机构信息
Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA.
出版信息
Bioorg Med Chem Lett. 2007 Sep 15;17(18):5245-50. doi: 10.1016/j.bmcl.2007.06.072. Epub 2007 Jun 30.
A novel series of heterocycle-based analogs were prepared and evaluated for their in vitro and in vivo biological activity as human beta(3)-adrenergic receptor (AR) agonists. Several analogs demonstrated potent agonist activity at the beta(3)-AR, functional selectivity against beta(1)- and beta(2)-ARs, and favorable pharmacokinetic profiles in vivo. Compound 17 increased oxygen consumption in rats, a measure of energy expenditure, with an ED(20%) of 2mg/kg.
制备了一系列新型的基于杂环的类似物，并对其作为人β(3)-肾上腺素能受体（AR）激动剂的体外和体内生物活性进行了评估。几种类似物在β(3)-AR上表现出强效激动剂活性，对β(1)-和β(2)-AR具有功能选择性，并且在体内具有良好的药代动力学特征。化合物17增加了大鼠的耗氧量，这是能量消耗的一种衡量指标，其20%有效剂量（ED(20%)）为2mg/kg。
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