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本文通过分析已有CLR/RAMP1胞外区与其拮抗剂分子共结晶结构以及已有小分子拮抗剂Telcagepant的构效关系,借助计算机辅助药物设计方法,以Telcagepant为模板进行形状筛选以得到结构新颖化合物,结合对接优化设计得到具有异黄酮结构母核的全新结构的化合物作为CLR/RAMP1拮抗剂。完成了化合物合成及细胞水平活性评价,为之后继续进行结构优化改造奠定基础。
In this paper, through the analysis of the existing crystal structure of CLR / RAMP1 extracellular domain and its antagonist molecules and the structure-activity relationship of the existing small molecule antagonist Telcagepant, computer-aided drug design method and Telcagepant template for shape screening to obtain novel structural compounds , Combined with docking optimization design to obtain a new structure of the isoflavone structural mother nucleus compound as a CLR / RAMP1 antagonist. The compound synthesis and cell-level activity evaluation were completed, which laid the foundation for further structural optimization and transformation.