Synthesis of N-Pyridinyl(methyl)-1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamides and analogues and their anti-inflammatory activity in mice and rats

The topical anti‐inflammatory activity of a series of N‐pyridinyl(methyl)1,2‐dihydro‐4‐hydroxy‐2‐oxoquinoline‐3‐carboxamides, analogues of roquinimex, has been evaluated by measuring their inhibitory effect in the phorbol myristate acetate (PMA)‐induced mouse ear swelling test, used as a screening t...

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Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2001-03, Vol.53 (3), p.417-423
Main Authors: Collin, X., Robert, J. M., Duflos, M., Wielgosz, G., Baut, G. Le, Robin-Dubigeon, C., Grimaud, N., Lang, F., Petit, J. Y.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Carrageenan
Ear, External - pathology
Edema - chemically induced
Edema - prevention & control
Foot - pathology
Male
Medical sciences
Mice
Pharmacology. Drug treatments
Pyridines - chemical synthesis
Pyridines - pharmacology
Quinolones - chemical synthesis
Quinolones - pharmacology
Rats
Rats, Wistar
Tetradecanoylphorbol Acetate
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Summary:The topical anti‐inflammatory activity of a series of N‐pyridinyl(methyl)1,2‐dihydro‐4‐hydroxy‐2‐oxoquinoline‐3‐carboxamides, analogues of roquinimex, has been evaluated by measuring their inhibitory effect in the phorbol myristate acetate (PMA)‐induced mouse ear swelling test, used as a screening test. All the eight carboxamides tested (9–16) exhibited significant inhibitory activity at 0.4 and 0.2 mm kg−1. The most potent compound, the 6‐bromo derivative 12, induced a 73% inhibition at 0.2 mm kg−1. Pharmacomodulation was carried out by heterocycle opening and molecular simplification leading to pentafluorobenzoylacetamide 17, pentafluorocinnamamides 18 and 19, and pentafluorobenzaldimines 20 and 21. All the five compounds exerted a reduction in swelling (49–63% at 0.2 mm kg−1) comparable with ibuprofen (56%). Anti‐inflammatory activity of the most efficient compounds was evaluated by carrageenan‐induced rat paw oedema inhibition. The pentafluorobenzaldimine 20 showed the highest activity with an inhibition percentage of 85% at 0.2 mm kg−1.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357011775505