Perez M, Fourrier C, Sigogneau I, Pauwels P J, Palmier C, John G W, Valentin J P, Halazy S
Medicinal Chemistry Division, Centre de Recherche Pierre Fabre, Castres, France.
J Med Chem. 1995 Sep 1;38(18):3602-7. doi: 10.1021/jm00018a020.
A series of new arylpiperazide derivatives of serotonin has been prepared and evaluated as 5-HT1D receptor agonists. Binding experiments at cloned human 5-HT1D alpha, 5-HT1D beta, and 5-HT1A receptors show that all the compounds are very potent and selective ligands for 5-HT1D receptor subtypes. Functional activity studies (contraction of the New Zealand white rabbit saphenous vein) demonstrate that most of the derivatives behave as full agonists. Among them, the aryl sulfonamide derivative 5q (pD2 = 8.33 compare to 5.75 for sumatriptan) was also identified as a very potent agonist in inhibiting the forskolin-mediated cyclase coupled to 5-HT1D beta receptors (EC50 = 0.52nM).
已制备了一系列新型的血清素芳基哌嗪衍生物，并将其作为5-HT1D受体激动剂进行了评估。在克隆的人5-HT1Dα、5-HT1Dβ和5-HT1A受体上进行的结合实验表明，所有化合物都是5-HT1D受体亚型非常有效的选择性配体。功能活性研究（新西兰白兔隐静脉收缩实验）表明，大多数衍生物表现为完全激动剂。其中，芳基磺酰胺衍生物5q（pD2 = 8.33，舒马曲坦为5.75）在抑制与5-HT1Dβ受体偶联的福斯高林介导的环化酶方面也被鉴定为非常有效的激动剂（EC50 = 0.52nM）。
