Abstract: 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 III_b～e,V_a,V_b,VII_a～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(III_c,VII_a and VII_b)were found to be effective against herpes simplex virus.The most potent inhibitor was 3-phthalimido-2-oxo-n-butyraldehyde bis- N⁴- phenylthiosemicarbazone(III_c,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.