A series of phthiobuzone analogs, prepared from potassium phthalimide or phthalandione, have been evaluated for their antiviral activities. Among the candidates, compounds 5j and 5k, which contain the substituted 4-halogenated phenyl ring at N -4′,4″ position, show more potent antiviral activity than phthiobuzone against herpes simplex virus 1 (IC₅₀=8.56 and 2.85 μg/ml, respectively) and herpes simplex virus 2 (IC₅₀=1.75 and 4.11 μg/ml, respectively). Compounds 9c and 9d with a propylene linker between the phthalimide and bisthiosemicarbazone moieties display similar antiviral potency against herpes simplex virus 1 (IC₅₀=2.85 and 4.11 μg/ml, respectively).