新型5-HT_(2A)选择性配体——N-取代哌啶-4-苯硫醚和砜类衍生物的合成及其生物活性  

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF NEW 5-HT_(2A) SELECTIVE LIGANDS N -SUBSTITUTED-PIPERIDINYL- 4-PHENYLTHIOETHER AND SULFONE DERIVATIVES

作　　者：王浩[1] 闻韧[1] 黄磊[1] RobertB.Innis 谈平中[2] 

机构地区：[1]复旦大学药学院,上海200032 [2]耶鲁大学医学院

出　　处：《药学学报》2001年第4期274-277,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目! (2 9872 0 2 9)

摘　　要：目的　为寻找新型的 5 HT2A受体选择性配体 ,设计合成了一系列二芳烷基哌啶类化合物的含硫衍生物。方法　以 2 ,3 二甲氧基硫酚为原料 ,经烃化、氧化和水解等反应合成 3个N 取代哌啶 4 苯硫醚和砜类化合物 ,所有目标化合物结构均经元素分析、1HNMR谱、质谱和红外光谱确证 ,并测定其对 5 HT2A,5 HT2C,5 HT6和 5 HT7受体及其他一些中枢神经递质受体的体外亲和力。结果　 3个目标化合物 ( 2a - 2c)及 5个中间体均为新化合物。体外受体竞争结合试验结果表明 2a - 2c均有较高的 5 HT2A受体选择性。结论　此类化合物对 5 HT2A受体的选择性较高 。AIM A series of 4-piperidinylthioether and sulfone derivatives of 4-[1-hydroxy-1-(2,3-dimethoxyphenyl) methyl]- N -2-(4-fluorophenylethyl) piperidine (MDL 100907) were synthesized in order to find new 5-HT 2A selective ligands. METHODS Title compounds 2a-2c were synthesized from 2,3-dimethoxythiophenol and tested for their affinities to 5-HT 2A , 5-HT 2C , 5-HT 6 and 5-HT 7 receptors and some other nervous transmitter receptors in vitro . RESULTS Compounds 2a-2c are new compounds. The results of the binding assay demonstrated that they have relatively high selectivity for 5-HT 2A receptor in vitro . CONCLUSION Some sulfur containing analogues of MDL 100907 showed selective affinity to 5-HT 2A receptor and are worth further study.

关 键 词：5-HT2A受体 选择性配体 4-(2 3-二甲氧苯硫基)-N-4-氟苯乙基哌淀 砜类衍生物 

分 类 号：TQ463.54[化学工程—制药化工]