一类新型N型钙通道阻滞剂的比较定量构效关系研究

使用结构和量子化学参数对一系列N取代N-甲基二肽衍生物的N型钙通道阻滞活性进行了定量构效关系研究, 并使用SOMFA方法建立了三维定量构效关系模型. 结果表明分子的范德华体积和最低未占据轨道能量是影响化合物生物活性的主要因素. N原子上取代基的溶剂可及面积也对化合物的钙通道阻滞活性有重要影响. 三维定量构效关系模型进一步支持了以上结果. 这些研究结果可为设计更高活性的N型钙通道阻滞剂提供有价值的参考信息.

Comparative QSAR Study on a Novel Class of N-type Calcium Channel Blocks

The quantitative structure-activity relationship study has been made on a series of N-methyl- N-substituted dipeptide derivative acting as N-type calcium channel blocks, using some structural and quan- tum chemical parameters. The self-organizing molecular field analysis method was also used to build a 3D quantitative structure-activity relationship model. It has been found that the van der Walls volume of mole- cule and the energy of the lowest unoccupied molecular orbital are the main independent factors contributing to the biological activity of the compounds. The solvent accessible area of the N-substituted groups is also important variable in terms of the N-type calcium channel blocker activity. The 3D quantitative struc- ture-activity relationship model can prove the results demonstrated above. These research results can provide valuable information for designing potent N-type calcium channel blocks with high affinity.