新型γ-分泌酶抑制剂的设计与合成  

Design and Synthesis of New γ-Secretase Inhibitors

作　　者：鄢浩[1] 李娟[1] 鄢嘉[2] 姜凤超[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,武汉430030 [2]华中科技大学同济医学院药学院,武汉430030

出　　处：《华中科技大学学报（医学版）》2009年第6期784-788,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的通过在数据库中虚拟筛选,以期发现新的γ-分泌酶抑制剂。方法在MDL数据库中以γ-分泌酶抑制剂药效团模型为条件进行搜寻、设计并合成了一系列化合物。结果所设计的目标化合物均经类药性分析,具有类药性;合成的化合物结构均经IR、1H-NMR及13C-NMR等验证。结论设计并合成的新的γ-分泌酶抑制剂经药效团模型预测,具有更高的预测活性。其中最佳化合物的预测活性值为0.025 nmol/L,可作为先导化合物进一步研究。Objective By virtual screening in MDL,to search for a novel γ-secretase inhibitor.Methods A series of compounds were designed,synthesized,and evaluated based on pharmacophore model of γ-secretase inhibitors by virtual screening in MDL.Results The drug-likeness analytic data synthesized indicated that target compounds had drug-likeness.Each synthesized compound was checked by IR spectroscopy,1H and 13C-NMR spectroscopy.Conclusion The designed compounds had better activity by model prediction.And the optimal compound showed a significant estimated activity value of 0.025 nmol/L and can be used as a lead for further drug development.

关 键 词：药效团模型 Γ-分泌酶抑制剂 虚拟筛选 药物合成 

分 类 号：R916.1[医药卫生—药学]