H-pyrazole Derivatives Research Articles

2 H-Azirines as dipolarophiles

2 H-Azirine-3-carboxylates unsubstituted at C-2 act as dipolarophiles in the reaction with diazomethane giving new 4,5-dihydro-3 H-pyrazole derivatives. The synthesis of a pyrimidine was also achieved via 1,3-dipolar cycloaddition of methyl 2-bromo-3-phenyl-2 H-azirine-2-carboxylate with an azomethine ylide.

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.

Synthesis and antimycobacterial activity of 5-aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1 H-pyrazole derivatives

5-Aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1 H-pyrazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. The compounds showed an interesting activity against a strain of Mycobacterium tuberculosis and a human strain of M. tuberculosis H4.

Study of reactions between 1,2-diaza-1,3-butadienes and N, N′-diaryl- or N, N′-dialkylthioureas

1,2-Diaza-1,3-butadienes react with N, N′-diarylthioureas to give 2-(arylimino)-2,3-dihydrothiazole derivatives, whereas with N, N′-dialkylthioureas to afford 5,5-disubstituted 3-alkyl-2-(alkylimino)-thiazolidin-4-one derivatives. Under basic conditions, these last products surprisingly give rise to 2-thioxo-1,3,7-triazaspiro[4.4]non-8-en-4-one and 5-oxo-4-(4-substituted 5-oxo-2-thioxoimidazolidin-4-yl)-2,5-dihydro-1 H-pyrazole derivatives. In acidic medium, 5,5-disubstituted 3-alkyl-2-(alkylimino)-thiazolidin-4-ones are converted into 2-(alkylimino)-1-thia-3,7-diazaspiro[4.4]non-8-en-4-ones. X-Ray crystal structures of two products were determined.

Synthesis, structure and inhibitory effects on cyclooxygenase, lipoxygenase, thromboxane synthetase and platelet aggregation of 3-amino-4,5-dihydro-1 H-pyrazole derivatives

3-Amino-4,5-dihydro-1 H-pyrazoles ( 1–4, 7) and related compounds ( 5, 6) and some pyrazoles ( 8b–13b) were prepared. The structures were mainly determined by 13C NMR spectroscopy. The inhibitory activities on cyclooxygenase, 15-lipoxygenase, thromboxane synthetase and platelet aggregation were assayed. Some compounds are potent inhibitors of 15-lipoxygenase; 4,5-dihydro-3-(1-pyrrolyl)-1-(3-trifluoromethylphenyl)-1 H-pyrazole 7aw was the most potent. 7aw also had a potent inhibitory effect on cyclooxygenase and thromboxane synthetase.