US EPA

2837294 

Journal Article 

Synthesis of new 1-(4-methane(amino)sulfonylphenyl)-5-(4-substituted-aminomethylphenyl)-3-trifluoromethyl-1H-pyrazoles: a search for novel nitric oxide donor anti-inflammatory agents 

Abdellatif, KR; Moawad, A; Knaus, EE 

2014 

Yes 

Bioorganic & Medicinal Chemistry Letters
ISSN: 0960-894X
EISSN: 1464-3405 

Elsevier 

24 

21 

5015-5021 

English 

25304893 

10.1016/j.bmcl.2014.09.024 

WOS:000343309800019 

https://linkinghub.elsevier.com/retrieve/pii/S0960894X14009494
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A group of 1-(4-methane(amino)sulfonylphenyl)-5-(4-substituted-aminomethylphenyl)-3-trifluoromethyl-1H-pyrazoles (12a-f) was synthesized and evaluated as anti-inflammatory agents. While all the compounds (20mg/kg) showed significant anti-inflammatory activity after 3h of inflammation induction (69-89%) as compared to celecoxib (80%), 1-(4-methanesulfonylphenyl)-5-(4-methylaminomethylphenyl)-3-trifluoromethyl-1H-pyrazole (12 a) was found to be the most effective one (89%). The synthesis of model hybrid nitric oxide donor N-diazen-1-ium-1,2-diolate derivatives of 1-(4-methanesulfonylphenyl)-5-(4-substituted-aminomethylphenyl)-3-trifluoromethyl-1H-pyrazoles (10a-f) requires further investigation since the reaction of N-(4-(1-(4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzyl)ethanamine (12 b) or 1-(4-(1-(4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzyl)piperazine (12c) with nitric oxide furnished N-nitroso derivatives (13 and 14), respectively, rather than the desired N-diazen-1-ium-1,2-diolate derivatives (10b and 10 c). 

Pyrazoles; Cyclooxygenase; Diazen-1-ium-1,2-diolate nitric oxide donors; Anti-inflammatory activity