Design and synthesis of some substituted 1H-pyrazolyl-oxazolidines or 1H-pyrazolyl-thiazolidines as anti-inflammatory-antimicrobial agents.

Four series of 1 H-pyrazole derivatives have been synthesized. The first series was synthesized starting with the reaction of 3-(5-bromo-2-thienyl)-1-phenyl-1 H-pyrazole-4-carboxaldehyde 1 with L-serine, L-cysteine, or L-penicillamine, followed by N-protection using (Boc)(2)O to provide compounds 2. The latter compounds could be N-deprotected by 4N HCl/dioxane to afford the second series 3 or reacted with NH(4)OH in the presence of DCC/HOBt to give the corresponding amides 4 followed by N-deprotection giving rise to compounds 5. The newly synthesized compounds were evaluated for their anti-inflammatory-antimicrobial activities. In addition, the ulcerogenic and acute toxicity profiles were determined. Compound 5b (2RS, 4R)-2-[3-(5-bromo-2-thienyl)-1-phenyl-1H-pyrazol-4-yl]-5-methylthiazolidine-4-carboxamide, proved to be the most active anti-inflammatory-antimicrobial agent in the present study with a good safety margin and no ulcerogenic effect.