LIPOXYGENASE INHIBITORS .6. SYNTHESIS OF NEW TETRAHYDROPYRAZINE AND OTHER HETEROCYCLIC-COMPOUNDS BY REACTION OF HYDRAZONOYL CHLORIDES

Cyclization reactions of alpha-ketoarylhydrazonoyl chlorides with vari ous dinucleophiles lead to new 1,4-benzothiazine, quinoxaline, tetrahy dropyrazine, thiazole, and thiadiazoline derivatives of methyl butanoa te or methyl 5-oxopentanoate. The inhibition of 5-lipoxygenase (LO) wa s determined by monitoring the leukotriene B-4 (LTB4) formation of hum an polymorphonuclear leukocytes (PMNL). The IC50 values for the most a ctive compounds with an arylhydrazone structure were found to lie betw een 0.7 and 7.5 mu M.