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
Sansebastiano, L.; Mosti, L.; Menozzi, G.; Schenone, P.; Muratore, O.; Petta, A.; Debbia, E.; Schito, A.P.; Schito, G.C.
Farmaco 48(3): 335-355
1993
ISSN/ISBN: 0014-827X PMID: 8391820 Document Number: 420650
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 (NH-2, CH-3, C-6H-5) 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 virust 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 compouned being 3 h, which achieved a 80.9% inhibition of HSV-1 infectivity at 12 mu-g/ml. Moreover, esters 3 f, 8 l and acid 9 o were active against some fungal strains.