摘要
目的 :建立具有尿道选择性α1 肾上腺素受体拮抗剂的药效团模型。方法 :选择对受体亚型和尿道组织均有高亲和力的化合物 ,经计算机建模、分子动力学优化、系统搜索得到一系列低能构象 ,通过Apex 3D软件计算并构建药效团初步模型 ,再参照已有的构效关系数据进行筛选、判别。结果 :得到 3个符合要求的药效团 ,它们均含有一个碱性中心和芳环中心 ,还存在一个氢位点 (HST)。结论 :该模型有助于我们设计、合成活性高且副作用低的新型抗前列腺增生药物。
Purpose: To establish the biophore of prostate selective α 1 adrenoceptor antagonist. Method: Five compounds were selected with high affinity on α 1A AR and prostate. The structures of each compound were built and further optimized by dynamic methods. Then the systematic searching method was used to seek out a series lower energy conformations. The Apex 3D software identified biophore and the biophores were chosen by the structure activity relationship of α 1 adrenoceptor antagonist. Result: Three biophores conform our demand. Each biophore contains a basic nitrogen atom, an aromatic ring center and a H site. Conclusion:This will help us design and synthesis of structurally new prostate selective α 1 AR antagonists with higher acitvity and lower side effect.
出处
《计算机与应用化学》
CAS
CSCD
2000年第5期453-456,共4页
Computers and Applied Chemistry
基金
北京医科大学天然药物与仿生药物国家重点实验室基金
