作用于5-HT_(1A/2A)受体的苯并咪唑类抗精神分裂症分子的设计、合成与药理活性研究  

Design,Synthesis and Pharmacological Activity of Benzimidazole Antischizophrenic Molecules Acting on 5-HT_(1A/2A) Receptors

作　　者：张晓晰 李江月 王培生 吴林韬[2] Zhang Xiao-xi;Li Jiang-yue;Wang Pei-sheng;Wu Lin-tao(Department of Psychiatry Changzhi Medical College,Changzhi Shanxi 046000;Department of Chemistry Changzhi University,Changzhi Shanxi 046011)

机构地区：[1]长治医学院精神卫生系,山西长治046000 [2]长治学院化学系,山西长治046011

出　　处：《长治学院学报》2021年第2期38-42,共5页Journal of Changzhi University

基　　金：山西省高等学校科技创新项目(2019L0668);山西省大学生创新实验项目(2018409)。

摘　　要：为寻找新型靶向5-HT_(1A/2A)受体的抗精神分裂症小分子,通过计算机药物辅助手段,合成其衍生物,通过体外亲和力实验、受体功能实验等药理实验评价其对5-HT_(1A/2A)受体抑制能力。结果表明:化合物8对5-HT_(1A)受体、5-HT_(2A)的体外亲和力ki值分别为7.01 nM、10.23 nM;化合物9对5-HT_(1A)受体、5-HT_(2A)的体外亲和力ki值分别为10.85 nM、13.24 nM,与阳性药卡利拉嗪活性相当。所以苯并咪唑类化合物具有良好的5-HT_(1A/2A)受体抑制能力,具有较高的研究价值。To search for novel anti-schizophrenic small molecules targeting 5-HT_(1A/2A) receptors,its derivatives were synthesized by computer-aided drug design method,and its inhibitory ability to 5-HT_(1A/2A) receptor was evaluated by in vitro affinity test,receptor function test and other pharmacological experiments.Results show the in vitro affinity Ki values of compound 8 for 5-HT_(1A) receptor and 5-HT_(2A) were 7.01 nM and 10.23 nM,respectively.The in vitro affinity Ki values of compound 9 for 5-HT_(1A) receptor and 5-HT_(2A) were 10.85nM and 13.24 nM,respectively,which was similar to the activity of the positive drug Calirazine.The conclusion is that Benzimidazole compounds have good 5-HT_(1A/2A) receptor inhibition ability and have high research value.

关 键 词：抗精神分裂症 作用机制 5-HT_(1A/2A)受体 苯并咪唑类化合物 

分 类 号：R914.5[医药卫生—药物化学]