5,6-二芳基-2,3-二氢-1-吡咯里嗪酮类化合物抗炎作用的三维构效关系研究

3D-QSAR OF ANTIINFLAMMATORY ACTIVITIES OF-5,6-DIARYL-2,3-DIHYDRO-1-PYRROLIZINONE DERIVATIVES

目的 研究 5 ,6 二芳基 2 ,3 二氢 1 吡咯里嗪酮类化合物抗炎作用的三维构效关系 ,为进一步设计新结构类型化合物提供理论依据。方法和结果 用计算机辅助药物设计专家系统 (Apex 3D)软件模拟并构建药效基团模型和三维构效关系 (3D QSAR)方程。结论 化合物的抗炎活性与分子总疏水性、空间体积和吡里酮环 1位基团和两个次级作用部位的性质有关 ;增加吡里酮环 1位基团π电子密度 ,降低分子总疏水性 ,及减弱 6位苯环对位取代 。

AIM To study the SARs of 5,6 diaryl 2,3 dihydro 1 pyrrolizinone derivatives to provide information for the design of new structural compounds. METHODS AND RESULTS Three dimensional quantitative structure activity relationship (3D QSAR) model was constructed by Apex 3D. CONCLUSION The antiinflammatory activities of 5,6 diaryl pyrrolizinones were related to the global hydrophobicity and volume, the properties of the group at 1 position of pyrrolizinone ring and the two secondary sites; improved the π electronic density of the group at 1 position of pyrrolizinone ring and lowered the global hydrophobicity and the volume of p substituent of the phenyl ring at 6 position of pyrrolizinone contributed to the antiinflammatory activities of the title compounds.