Lipoxygenase inhibitors .6. Synthesis of new tetrahydropyrazine and other heterocyclic compounds by reaction of hydrazonoyl chlorides

Cyclization reactions of alpha-ketoarylhydrazonoyl chlorides with various dinucleophiles lead to new 1,4-benzothiazine, quinoxaline, tetrahydropyrazine, thiazole, and thiadiazoline derivatives of methyl butanoate or methyl 5-oxopentanoate. The inhibition of 5-lipoxygenase (LO) was determined by monitoring the leukotriene B-4 (LTB4) formation of human polymorphonuclear leukocytes (PMNL). The IC50 values for the most active compounds with an arylhydrazone structure were found to lie between 0.7 and 7.5 mu M.