DESIGN, SYNTHESIS AND ANTIDIABETIC ACTIVITY OF SOME NEW 4-AMINO (OR 6-OXO)-2-METHYL/BENZYLTHIO (OR SUBSTITUTED AMINO) PYRIMIDINE DERIVATIVES

A new series of 4-amino-5-cyano-2-methyl/benzylthio (or substituted amino) 6-substituted phenyl pyrimidines 5a-l, and 2-methyl/benzylthio (or substituted amino)-5-cyano-1,6-dihydro-6oxo-4-(substitutedphenyl) pyrimidines 6a-l was prepared. The reaction of S-methyl (or benzyl) isothiourea salts 1a,b with benzylidenemalononitriles 2a-c afforded compounds 5a-f. Reaction of compounds 5a-c (R= methylthio) with the appropriate amines 4a,b (cyclohexylamine or 2phenylethylamine) afforded 4-amino-2-substituted amino-5-cyano-6- (substituted phenyl) pyrimidines 5g-l. On the other hand, reaction of S-methyl (or benzyl) isothiourea salts 1a,b with ethyl α-cyanocinnamates 3a-c afforded compounds 6a-f. Reaction of compounds 6a-c (R= methylthio) with the appropriate amines 4a,b afforded 2-substituted amino-5-cyano-4-oxo-6(substituted phenyl) pyrimidines 6g-l. The purity of the new compounds was checked by TLC and elucidation of their structures was confirmed by IR, 1H-NMR, and mass spectrometry along with elemental microanalyses. All the target compounds were evaluated for their in-vivo antidiabetic effects in rates in comparison with metformin as a reference drug.