A series of novel 1,3,4-thiadiazine derivatives were synthesized via chemical optimization on phthiobuzone. Their anti-herpes simplex virus (HSV) activities in vitro were also tested. Several compounds exhibited more highly potent anti-HSV activity and much higher selectivity index (SI) values than those of phthiobuzone. The most potent anti-HSV compound was 4f, which showed marked inhibition against HSV-1 (IC(50)=77.04 µg/ml) and HSV-2 (IC(50)=30.00 µg/ml). Meanwhile it had low cytotoxicity (CC(50)=1000.00 µg/ml), resulting in high (SI(HSV-1)=12.98, SI(HSV-2)=33.33, respectively). Furthermore, a computational study for prediction of absorption, distribution, metabolism, excretion (ADME) properties of compound 4f was performed by determination of topological polar surface area, absorption and Lipinski parameters.
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