Benzimidazole derivatives with atypical antiinflammatory activity

A number of substituted 2-[(2,2,2-trifluoroethyl)sulfonyl]-1H-benzimidazoles (4) have demonstrated antiinflammatory activity that appears to have a mechanism distinct from typical cyclooxygenase inhibiting nonsteroidal antiinflammatory drugs. Several of these compounds inhibit adjuvant-induced arthr...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1987-04, Vol.30 (4), p.726-729
Main Authors: Lazer, Edward S, Matteo, Martha R, Possanza, Genus J
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Arthritis - drug therapy
Arthritis, Experimental - drug therapy
Benzimidazoles - therapeutic use
Carrageenan - toxicity
Chemistry
Cyclooxygenase Inhibitors
Edema - drug therapy
Exact sciences and technology
Exocytosis - drug effects
Heterocyclic compounds
Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings
Humans
Lysosomes - drug effects
Male
Neutrophils - drug effects
Neutrophils - metabolism
Organic chemistry
Preparations and properties
Rats
Rats, Inbred Lew
Structure-Activity Relationship
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Summary:A number of substituted 2-[(2,2,2-trifluoroethyl)sulfonyl]-1H-benzimidazoles (4) have demonstrated antiinflammatory activity that appears to have a mechanism distinct from typical cyclooxygenase inhibiting nonsteroidal antiinflammatory drugs. Several of these compounds inhibit adjuvant-induced arthritis in rats at 25 mg/kg while showing no activity in the carrageenan paw edema model at up to 100 mg/kg. Two compounds, 4a and 4b, showed no significant inhibition of cyclooxygenase in vitro at concentrations as high as 5 X 10(-5) M. All compounds 4 active in adjuvant-induced arthritis were also found to inhibit release of lysosomal enzymes from neutrophils, raising the possibility that their antiinflammatory effect is at least partially mediated by an effect on neutrophil function.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00387a026