寻找新的M1受体激动剂先导化合物。在M1受体三维结构未知的情况下,利用距离比较法(DISCO)将10个结构特征具有代表性的M1受体激动剂的分子构象进行叠合,建立了可能的药效团模型,初步验证了该模型的可靠性。利用该模型对ACD-SC数据库进行虚拟筛选,购买了22个与药效团叠合较好、与已知M1受体激动剂结构类型不同的化合物,并对其进行活性测定。结果发现了一个具有M1受体激动活性的化合物,其EC50为4.90μmol/L,最大响应倍数为10.0,值得进行更深入研究。 Look for new M1 receptor agonist lead compounds. Under the condition that the three-dimensional structure of M1 receptor is unknown, the molecular conformations of 10 structurally representative M1 receptor agonists are overlapped by the distance comparison method (DISCO), and a possible pharmacophore model is established, and preliminary verification The reliability of the model. Using this model, we screened the ACD-SC database and purchased 22 compounds which have good overlapping with the pharmacophore and different structures from the known M1 receptor agonists. The activity of the compounds was determined. As a result, it was found that a compound having M1 receptor agonistic activity with an EC50 of 4.90 μmol / L and a maximum response multiple of 10.0 deserved further study.