抗病毒药物研究：酞丁安类似物的合成

ITUDIES ON ANTIVIRAL AGENTS: SYNTHESIS OF TAI DING-AN ANALOGS

酞丁安是我国在临床使用的抗病毒化疗药物之一，为了优化其活性，增加其水（脂）溶性，对酞丁安结构中氨基侧链部分及母体进行结构修饰与改造，共合成十个酞丁安类似物，其抗病毒作用表明化合物ＩＩＩｃ，ＶＩＩａ．与ＶＩＩｂ，显示抗疱疹病毒活性，其中化合物ＩＩＩｃ活性最强，其体外抗病毒活性较酞丁安强１０倍，其余化合物均无活性。

Tai-Ding-An(3-phthalimido-2-oxo-n-butyraldehyde bisthiosemicarbazine, TDA)is a synthetic antiviral drug developed by our institute. Because of its Iow water/lipid solubility.Tai～Ding-An is limited to topical treatment of herpes viruses infected skin diseases and of condylomataacuminata ( ginital warts ),one of sexual transmited diseases(STD), caused by human papillomavirus(HPV).Ten TDA derivatives IIIb～e,Va,Vb,VIIa～e have been synthesized in order to search forcompounds with higher antiviral activity and better solubility than the parent compound as well as toexplore structure and activity relationship.Among the ten analogs,three compounds(IIIc, VIIa andVIIb)were found to be effective against herpes simplex virus. The most potent inhibitor was 3-phthalimido-2-oxo-n-butyraldehyde bis- N4- phenylthiosemicarbazone(IIIc,PTDA ) which wasapproximately 10 times more active against HSV-2 as compared with TDA. Compound IIIc was alsofound to be effctive on the topical treatment of herpetic epithelial keratitis in rabbits.