Designs and syntheses of oxathiin carboxanilide analogues and their antiviral activities

Syntheses of new analogues of oxathiin carboxanilide (UC84) and their antiv iral activities were described. The heterocyclic carboxylic acids including oxathiins (4), thiazines (9) and dithiins (13) in which the methyl was rep laced either by lipophilic trifluoromethyl- or bulky phenyl-group were synt hesized starting from beta-keto esters (5). Reaction of 4, 9 and 13 with th ionyl chloride followed by treatment of the substituted aniline 22 gave the corresponding carboxanilides (24a similar to 24f). The carboxanilides were subjected to Laweson's reagent the corresponding thiocarboxanilides (24g s imilar to 24k). The antiviral activities of the synthesized compounds again st human immunodeficiency virus type 1 (HIV-1), poliovirus type 1 (PV-1), c oxsackie B virus type 3 (CoxB-3), vesicular stomatitis virus (VSV) and herp es simplex virus type 1 (HSV-1) were presented. The antiviral activity agai nst HIV-1 of dithiin carboxanilide (24e) was similar with that of UC84 (24a ). The corresponding thiocarboxanilides (24g similar to 24k) showed higher inhibitory activity against HIV-1 than the carboxanilides (24a, 24b, 24d, 2 4e). The compounds in which ether the lipophilic trifluoromethyl substituen ts (24d, 24f, 24i, 24k) or bulky phenyl substituent is present in the heter ocyclic compounds showed lower inhibitory activity than that of the methyl substituents is present in the compounds against the HIV-1. But the trifluo romethylated dithiin (24f) showed higher inhibitory activity against PV-1 a nd CoxB-3 virus than commercial antiviral agents, ribavirin (RV).