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Benzamides I, phenylalkanamides II and cinnamamides III are structurally related to the antiinflammatory N-(4,6-dimethylpyridin-2-yl)benzamide I. These were synthesized and the transformation of the 2-aminopyridine nucleus of benzamides I into a 2-imino-1,2-dihydropyridine structure (compounds IV) was also carried out. Of the 49 new derivatives, the 3-fluorobenzamide 9 was the most potent in the oral treatment of carrageenen-induced peripheral edema; IC50 = 12.2 mg·kg−1. It was 3 times as active as benzamide 1, but the latter nevertheless had a better therapeutic index (LD50/IC50) of 52 against 23. Benzamide 1, a non-acidic antiinflammatory compound devoid of any blocking activity on cyclooxygenase, markedly reduces the production of reactive oxygen species in rat peritoneal macrophages. This compound probably acts at the membrane, perhaps by interference with transmembrane events.

The 1-O-stearoyl-2-O-[3H] arachidonyl-sn-glycero-3-phosphocholine, introduced in the culture medium, was taken up by the peritoneal macrophages activated by the ionophore A 23187. After intracellular phospholipase A2 activity, the [3H] arachidonic acid was found in cells and in extracellular fluids. It also reached the eicosanoid synthesis. When it was introduced in the culture medium with the tritiated phospholipid, the 1, 2 di-O-hexadecyl-rac-glycero-3-phosphocholine, which has a non hydrolysable alkylated structure in the 2 position of the glycerol, inhibited the intracellular phospholipase A2, then contributed to lower the eicosanoid synthesis.