Synthesis of certain nitropyridine derivatives bearing 2-thiazolyl hydrazines with expected monoamine oxidase inhibitory activity

Two series of nitropyridine derivs. bearing 2-​thiazolyl hydrazines were synthesized and evaluated for their monoamine oxidase (MAO) inhibitory activity by in vitro tests to assay their effect on rat liver mitochondria by a kynuramine fluorimetric assay.  The two key intermediates, 6-​methyl-​5-​nitropyridine-​2-​carboxaldehyde thiosemicarbazone (I) and 1-​(6-​methyl-​5-​nitropicolinoyl)​thiosemicarbazide (II)​, were prepd. by conventional methods.  The target compds., N-​(6-​methyl-​5-​nitropyridin-​2-​ylmethylidene)​-​N'-​(4-​substituted thiazol-​2-​yl)​hydrazines III (R = Me, Ph, 4-​BrC₆H₄, 4-​ClC₆H₄, 4-​MeOC₆H₄, 4-​O₂NC₆H₄, X = CH:NNH) and 6-​methyl-​5-​nitropyridine-​2-​carboxylic acid N'-​(4-​substituted thiazol-​2-​yl)​hydrazides III (R = Me, Ph, 4-​BrC₆H₄, 4-​ClC₆H₄, 4-​MeOC₆H₄, X = CONHNH)​, were prepd. by condensation of I or II with the appropriate α-​halogeno-​ketone, chloroacetone or phenacyl bromides.  All the assayed compd. posses in vitro monoamine oxidase inhibitory activity at a concn. of 0.33 - 1.66 x 10⁵ M.