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

Abstract

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 B4 (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 microM.