作　　者： (赵松峰）; (张晓）; (师秀琴）; (王存良）; (杨志衡）; (张晓坚）;

机构地区： 郑州大学第一附属医院,河南郑州450052

出　　处： 《化学试剂》 2017年第9期999-1002,1006,共5页

摘　　要： HIV-1蛋白酶为成熟病毒颗粒的正常组装提供必需的结构蛋白和功能蛋白,因此,HIV-1蛋白酶抑制剂可有效阻止病毒的进一步感染。然而,耐药性一直是抗HIV药物面临的一个关键科学问题,设计一类具有新型骨架特征的HIV-1蛋白酶抑制剂不失为一种好的解决方案。以Darunavir为先导化合物,运用骨架跃迁和拼合等药物设计策略,设计合成了3个结构新颖的化合物,均未见文献报道,目标化合物经~1HNMR、^(13)CNMR和MS确证。 HIV-1 protease plays an essential role in the viral life cycle.It generates mature infectious virus particles through cleavage of the viral Gag and Gag Pol precursor proteins.So HIV-1 protease inhibitors can prevent the virus from further infection effectively.However,the ability of HIV to rapidly mutate and replicate has given rise to the development of drug resistance which is always a key scientific problem,alternatively,novel structures of HIV-1 protease inhibitors could be a good solution for drug resistance.Three new compounds were synthesized using compound Darunavir as the main compound based on the drug design principle of scaffold-hopping and combination. All the compounds are unreported in literatures,and the structures were confirmed by 1^HNMR,13^CNMR and MS.

关 键 词： 蛋白酶 合成 抑制剂 骨架跃迁