Synthesis and antiviral activity of phthiobuzone analogues.

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 (IC(50)=8.56 and 2.85 microg/ml, respectively) and herpes simplex virus 2 (IC(50)=1.75 and 4.11 microg/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 (IC(50)=2.85 and 4.11 microg/ml, respectively).