一种新型抗癌放射性药物前体的设计与合成

Design and synthesis of a new ^(122)Ⅰ labeled prodrug

设计并合成一种用于治疗肿瘤的放射性^(125)I标记的药物前体:2-(2,-磷酸化羟苯基)-6-碘-4-(3氢)-喹唑啉酮,并经荧光光谱、FTIR、MS和NMR确证了目标化合物的结构。在碘标记当中,使用双(三丁基)锡来活化标记困难的有机分子,方法操作简单,定位准确,结果证明有用。

In this paper we try to synthesis a new water-soluble radiolabeled prodrug 2-（2,-phosphoryloxyphpheny）-6-^125I-4-（3H）-quinazolinne, which is converted to a water-insoluble radiolabeled drug by the action of alkaline phosphatase for antibody-directed enzyme prodrug therapy （ADEPT）. when The prodrug react with special enzyme on the surface of tumour, the prodrug changes to therapeutic drug and then pervades into tumour tissue and the radioactive ^125I will use it radiancy to kill the tumor cell. we choose to use radiolabeled 2-（2,-Phosphoryloxyphenyl） -6-idio-4-（3H）-quinazolinone which is derivative of quinazolinone as the prodrug substrates. This compound, known as the ELF （enzyme-labeled-fluorescence） phosphatase substrate, produces a precipitate that fluoresces at about 500-600nm（bright yellow- green）. The radiolabeled precipitate will be trapped within the tumor mass and should lead to protracted irradiation of tumor cells. We have demonstrated the compound can hydrolyed to water-insoluble 2-（2,- hydroxyphenyl）-6-idio-4-（3H）-quinazolinone when incubated with alkaline phosphatase. We use tributylstannyl to active organic compound in the process of labelling and proved to be good.