具有改善药代动力学性质的β3肾上腺素能受体的3-吡啶氧基丙醇胺激动剂。
3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties.
作者信息
Weber A E, Ok H O, Alvaro R F, Candelore M R, Cascieri M A, Chiu S H, Deng L, Forrest M J, Hom G J, Hutchins J E, Kao J, MacIntyre D E, Mathvink R J, McLoughlin D, Miller R R, Newbold R C, Olah T V, Parmee E R, Perkins L, Stearns R A, Strader C D, Szumiloski J, Tang Y S, Tota L, Fisher M H
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
出版信息
Bioorg Med Chem Lett. 1998 Aug 18;8(16):2111-6. doi: 10.1016/s0960-894x(98)00381-3.
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.
吡啶氧基丙醇胺类药物L - 749,372（8，β3的半数有效浓度EC50 = 3.6 nM）和L - 750,355（29，β3的半数有效浓度EC50 = 13 nM）是人类受体的选择性部分激动剂，激活率分别为33%和49%。两者均能刺激恒河猴的脂肪分解（半数有效剂量ED50分别为2和0.8 mg/kg），对心率的影响极小。与酚类类似物相比，L - 749,372在犬类中的口服生物利用度为41%，L - 750,355为47%，均有所提高。
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