Design, synthesis and antidiabetic activity of some new 4-amino (or 6-oxo)-2-methyl/benzylthio (or substituted amino) pyrimidine derivatives

Abstract

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-6-oxo-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 2-phenylethylamine) 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, 1HNMR, 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.