SYNTHESIS, ANTIVIRAL (HSV-1) AND ANTIMYCOTIC ACTIVITIES OF ETHYL OR METHYL 2,4-DISUBSTITUTED 5-PYRIMIDINECARBOXYLATES, 2,4-DISUBSTITUTED 5-PYRIMIDINECARBOXYLIC ACIDS AND 2,4-DISUBSTITUTED PYRIMIDINES

The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-meth ylthio-5-pyrimidinecarboxylates 3 a-i and 8 o mainly by reaction of et hyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with 2-methylis othiourea is described. Also some ethyl 2-substituted (NH2, CH3, C6H5) 4-trifluoromethyl-5-pyrimidinecarboxylates were prepared. Some of the above esters were hydrolyzed to the relative carboxylic acids, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines . Esters 3 a-i and 8 o were tested for their toxicity on Vero cultured cells and for their inhibitory activity against herpes simplex virus type 1 (HSV-1) infectivity in a short-term plaque assay. At non toxic concentrations, each ester was found to be active, the most interestin g compound being 3 h, which achieved a 80.9% inhibition of HSV-1 infec tivity at 12 mug/ml. Moreover, esters 3 f, 8 l and acid 9 o were activ e against some fungal strains.