中文摘要：

目的探索通过前药途径改善MG132稳定性和成药性的方法。方法基于前药设计原理，设计并合成5种MG132前药，通过体外模拟实验，即分别在pH7．4的PBS、pH1．0的盐酸溶液和兔血浆中，考察5种前药的稳定性及在兔血浆中MG132的释放情况。结果与结论体外模拟实验发现，前药1可作为注射类前药深入研究；前药2和3适合于作为酶靶向类前药深入研究；作为意外得到的前药4’在中性溶液中稳定，在酸性溶液和血浆中均很不稳定，故不能作为口服类前药；前药5在中性条件下和血浆中都比较稳定，但不释放MG132，可能是生成了稳定的新代谢产物。

英文摘要：

Proteasome inhibitor is one kind of important antitumor drugs. MG132 , a peptide aldehyde proteasome inhibitor, has become an indispensable tool-drug in the study of the proteasome behavior in cells and tissues. However, the poor chemical stability and metabolism stability limit its clinical application due to the presence of aldehyde group in the structure. In order to improve its druggability, we designed and synthesized five prodrugs of MG132 based on the prodrug principle and examined properties of them as prodrugs. The results demonstrated that 1 ） prodrug 1 may be a promising prodrug on injection delivery; 2） prodrug 2 and 3 are worth to further study as target prodrugs ;3 ） prodrug 4＇ is relatively stable in pH 7.4 PBS but is unstable either in pH 1.0 HCl solution or in rabbit plasma, which demonstrate that it can not be used as an oral prodrug; 4） prodrug 5 is stable in PBS and pH 1.0 HCl solution,but no MG132 was released.