CAJ | 학술논문

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.
심조신적M1수체격동제선도화합물.재M1수체삼유결구미지적정황하,이용거리비교법(DISCO)장10개결구특정구유대표성적M1수체격동제적분자구상진행첩합,건립료가능적약효단모형,초보험증료해모형적가고성.이용해모형대ACD-SC수거고진행허의사선,구매료22개여약효단첩합교호、여이지M1수체격동제결구류형불동적화합물,병대기진행활성측정.결과발현료일개구유M1수체격동활성적화합물,기EC50위4.90μmol/L,최대향응배수위10.0,치득진행경심입연구.
To discover new lead compounds for M1 agonists.Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisous (DISCO) method without the previous knowledge of the three-dimeusional structure of M1 receptor.Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds (ACD-SC) to identify possible new hits.Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity.One of them shows M1 receptor agonist activity with ECs0 of 4.90 μmol/L and maximum respouse.Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.