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

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.