NOVEL ANTI-RESPIRATORY SYNCYTIAL(RS) VIRAL COMPOUNDS - BENZODITHIIN DERIVATIVES

Benzodithiin derivatives are highly potent and specific inhibitors of respiratory syncytial virus (RSV) replication in vitro. The most poten t and selective congener of a benzodithiin derivative is 1,4-dihydro-2 ,3-benzodithiin(RD3 0028). According to the modified 3-(4,5-dimethylth iazole-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay developed i n our laboratories, this compound has a 50% effective concentration of 4.5 mu M and a 50% cytotoxic concentration of 271.0 mu M, which is su perior 60 that of ribavirin. This compound also inhibits RSV strain su bgroups A and B and clinical isolates. RD3-0028, however, does not inh ibit the replication of influenza A virus, measles virus, herpes simpl ex virus types 1 and 2, or human cytomegalovirus. Two other benzodithi in derivatives [1,4-dihydro-6-methyl-2,3-benzodithiin (RD3-0270) and 1 ,8-dihydro-5-methyl-2,3-benzodithiin (RD3-0284)] also inhibit RSV repl ication at a selectivity index greater than a factor of 20. These resu lts suggest that the benzodithiin skeleton is an important structure f or inhibitory activity against RSV replication. (C) 1998 Academic Pres s.