Inflamation of the liver can be caused by viral infections. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are two of the dreadful viruses and have infected billion people worldwide. Therefore huge reaserch effort is being made to discover new, more efficacious, antiviral compounds.

     The [4,5-d] isomer of thiazolopyrimidines can be considered as 7-thio analogues of guanine and adenine. Thiazolo- [4,5-d]pyrimidines  were reported to possess a broad range of biological activity. A number of the new derivatives of thiazolo[4,5-d]pyrimidin-2-tione-7one have been synthesized and biologically screened in vitro against both hepatitis viruses HBV and HCV. The synthesis of the active compounds is depicted  in Scheme 1. The necessary N-(haloaryl-methyleneamino)-2-cyano-acetamides 1 were prepared by reacting 2-cyanoacetohydrazide with appropriate substituted aromatic aldehyde. Thiazoloderivatives 2 were synthesized by the condensation of 1 with sulfur and phenyl isothiocyanate under the reaction conditions described by Gewald. The title derivatives 3a-d were prepared by heating 1 with aldehyde in the presence of a basic catalyst.

      Anti-HCV activity was assessed by the primary HCV RNA replicon assay using Huh 7 cell line. Four compounds 3a-d showed  antiviral activity , they inhibited HCV replication in 48-68%. In further testing 3a and 3b exhibited 50% effective contrentration EC₅₀=0,41  µM.

     Compound 3b , specifically tested for inhibition of replication hepatitis B virus in cultured  hepatoblastoma 2.2.15 cells exhibited a good toxity/activity profile against HBV by inhibition of the synthesis of extracellular virion release EC₅₀=1,4 µM, EC₉₀=3,6 µM, CC₅₀=148 µM, SI=41 and intracellular HBV replication intermediates EC₅₀=3,5 µM, EC₉₀=15 µM, CC₅₀=148 µM, SI=10, SI= selectivity index was calculated as CC₅₀ (toxity) and EC₉₀ (activity) ratio. The study of the hepatitis caused by B and C viruses has been hindered by the lack of a small animal model. In 1995, an HBV transgenic mouse model was created to evaluate the antiviral activity of new compounds. As a result of in vitro screens compound 3b is actually tested in vivo in the chimeric mouse model suffering from a transgene-induced liver disease.    In conclusion, the new thiazolo[4,5-d]pyrimidines exhibit in vitro activity against both hepatitis viruses despite the fact that the two viruses have different genomes.

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1. New 4,8-dihydroxy-1-oxo-6-phenyl-1,2-dihydro-2,7-naphthyridine-3-carboxylate derivatives with potential anticancer activity
2. Synthesis and in vitro anticancer evaluation of the new thiazolo[4,5-d]pyrimidines.