The synthesis of new derivatives of pyrimido [5,4-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazine is described. These derivatives have a wide range of medicinal applications. Their inhibitory activity against the enzyme 15-lipoxygenase was also investigated.

A series of new 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their cyclized products 'pyrimidinylthio pyrimidotriazolothiadiazines' were designed, synthesized, and evaluated as potential inhibitors of 15-lipo-oxygenase (15-LO). Their syntheses started by initial condensation of 2:1 equivalents of pyrimidine with triazole and subsequent nucleophilic displacement of the chlorine atoms with secondary amines and finally cyclocondensation in the presence of NaNH2. The compounds 4d and 4f showed the best IC50 of 15-LO inhibition (IC50 = 9 and 12 μm, respectively). Compounds 4a-g were docked into 15-LO. We suggest that the hydrogen bonds in quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play major role in lipo-oxygenase inhibition by this set of synthesized analogs and hydrophobic nature of this protein's binding site should be considered in ongoing investigations.

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An efficient and convenient synthesis of new thiazino [2,3-b]quinoxaline derivatives has been developed by employing a one-pot cyclo-condensation of several α-haloketones and 3-aminoquinoxaline-2-thiol in acetic acid. A similar reaction with 4-bromo-3-methyl-4,5-dihydro-1H-5-pyrazolone gave a new heterocyclic system, 3-methyl-1,4-dihydropyrazolo[4′,3′:5,6][1,4] thiazino [2,3-b]quinoxaline.

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