Il Farmaco 1993-03-01

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.

L Sansebastiano, L Mosti, G Menozzi, P Schenone, O Muratore, A Petta, E Debbia, A P Schito, G C Schito

Index: Il Farmaco 48 , 335, (1993)

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Abstract

The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-methylthio-5-pyrimidinecarboxylates 3 a-i and 8 o mainly by reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with 2-methylisothiourea 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 interesting compound being 3 h, which achieved a 80.9% inhibition of HSV-1 infectivity at 12 micrograms/ml. Moreover, esters 3 f, 8 l and acid 9 o were active against some fungal strains.