Convenient Synthesis and Biological Activity of 4-minomethylene 1-phenylpyrazolidine-3,5-diones

Abstract

Reaction of (<em>Z</em>)-4-((dimethylamino)methylene)-1-phenylpyrazolidine-3,5-dione (<strong>1</strong>) with different nucleophiles is described. Treatment of enaminone <strong>1 </strong>with phenylhydrazine led to 3-oxo-<em>N’</em>,2-diphenyl-2,3-dihydro-1<em>H</em>-pyrazole-4-carbohydrazide <strong>7</strong>. New enaminone derivatives <strong>2–6 </strong>and <strong>12–14 </strong>were conveniently obtained in high yields via nucleophilic substitution of the dimethylamino group in enaminone <strong>1 </strong>when reacted with <em>o</em>-aminophenol, <em>o</em>-aminothiophenol, ethanolamine, cysteamine hydrochloride, piperidine, morpholine, 2-aminopyridine and glycine. Reaction of enaminone <strong>1 </strong>with diaza-nucleophiles, such as hydrazine hydrate, ethylenediamine and <em>o</em>-phenylenediamine, afforded the corresponding <em>bis</em>-enaminones <strong>9–11</strong>. Anti-inflammatory and antimicrobial activities of some new products were evaluated. Compounds <strong>1, 2, 4, 7, 12a</strong>, and <strong>12b </strong>showed high anti- inflammatory activity compared with indomethacin as the reference, while the highest antimicrobial effect was observed in the case of compound <strong>3</strong>.