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

Abstract

Abstract 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.