College of Pharmacy & Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
Bioorg Med Chem. 2010 Feb 15;18(4):1665-75. doi: 10.1016/j.bmc.2009.12.067. Epub 2010 Jan 4.
A novel series of 5-HT(2A) ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)butan-2-yl)-arylsulfonamide compounds were obtained. The binding of these compounds to the 5-HT(2A), 5-HT(2C), and 5-HT(7) receptors was evaluated. Most of the compounds showed IC(50) values of less than 100 nM and exhibited high selectivity for the 5-HT(2A) receptor. Among the synthesized compounds, 16a and 16d showed good affinity at 5-HT(2A) (IC(50)=0.7 nM and 0.5 nM) and good selectivity over 5-HT(2C) (50-100 times) and 5-HT(7) (1500-3000 times).
合成了一系列新型 5-HT(2A) 配体，它们含有（苯哌嗪基-丙基）芳基磺酰胺骨架。得到了 37 种 N-（环烷基甲基）-4-甲氧基-N-（3-（4-芳基哌嗪-1-基）丙基）-芳基磺酰胺和 N-（4-（4-芳基哌嗪-1-基）丁-2-基）-芳基磺酰胺化合物。评估了这些化合物与 5-HT(2A)、5-HT(2C) 和 5-HT(7) 受体的结合情况。大多数化合物的 IC(50) 值均小于 100 nM，对 5-HT(2A) 受体具有高选择性。在合成的化合物中，16a 和 16d 在 5-HT(2A) 受体上表现出良好的亲和力（IC(50)=0.7 nM 和 0.5 nM），对 5-HT(2C)（50-100 倍）和 5-HT(7)（1500-3000 倍）具有良好的选择性。
