NON-ACIDIC ANTIINFLAMMATORY COMPOUNDS - ACTIVITY OF N-(4,6-DIMETHYL-2-PYRIDINYL) BENZAMIDES AND DERIVATIVES

The inhibition of the carragenin-induced rat-paw edema by previously synthesized N-(4,6-dimethyl)-2-pyridinyl) benzamides was evaluated. Among the 29 tested compounds, secondary benzamides 1, 12 and tertiary benzamide 60 exhibited a significant anti-inflammatory activity. It prompted us to envision a pharmacomodulation in this series by structural modifications on the homocycle, the amide function and the heterocycle. Although benzamide 38, acetamide 50 and benzylamine 56 elicited marked inhibitory activity, none was more active than N-(4,6-dimethyl-2-pyridinyl) benzamide 1. The mechanism of the anti-inflammatory action of 1 was investigated. The results showed that this molecule reduced eicosanoid biosynthesis but was unable to reduce cyclooxygenase or lipoxygenase activities. Although it did not directly block phospholipase activity, however, an inhibitory process at this level is likely. © 1990.