[Studies on antiviral agents: synthesis of tai-ding-an analogs]

Tai-Ding-An (3-phthalimido-2-oxo-n-butyraldehyde bisthiosemicarbazone, TDA) is a synthetic antiviral drug developed by our institute. Because of its low water/lipid solubility. Tai-Ding-An is limited to topical treatment of herpes viruses infected skin diseases and of condylomata acuminata (ginital warts), one of sexual transmitted diseases (STD), caused by human papilloma virus (HPV). Ten TDA derivatives IIIb-e, Va, Vb, VIIa-e have been synthesized in order to search for compounds with higher antiviral activity and better solubility than the parent compound as well as to explore structure and activity relationship. Among the ten analogs, three compounds (IIIc, VIIa and VIIb) 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 was approximately 10 times more active against HSV-2 as compared with TDA. Compound IIIc was also found to be effective on the topical treatment of herpetic epithelial keratitis in rabbits.