A series of novel derivatives of dipyrimido[4,5-b:4′,5′-e][1,4]thiazepine were synthesized by the treatment of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine with 2-substituted-5-amino-6-methyl-pyrimidine-4-thiol in the presence of trimethylamine in acetonitrile as solvent and subsequently with various appropriate amines in boiling ethanol. The regioselectivity of heterocyclizaion was confirmed by GIAO calculations. The theoretical result revealed that the attachment of -SH moiety to the CH2 group is more plausible. Also, the theoretical inhibitory activity of the newly synthesized compounds against soybean 15-lipoxygenase was studied. The docking results showed that the theoretical inhibitory activity (ki) of compounds (10a), (10b), (10e), (10j) was lower than 4-MMPB as the standard inhibitor of 15-SLO. Among them, compound (10e) was a potent theoretical inhibitor with (Ki = 1.13 nM) and binding energy -12.21 kcal mol-1. We propose that the orientation of the four synthesized compounds towards the Fe-OH and the hydrogen bond interaction between a sulfur atom of thiazepine ring and His 518 of 15-lipoxygenase seems to play an essential role in lipoxygenase inhibition.

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