1,8-Naphthyridines VII. New substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides and their isosteric analogues, exhibiting notable anti-inflammatory and/or analgesic activities, but no acute gastrolesivity

The [1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamide derivatives 5-amino (2) or 5-alkoxy (3) substituted and the 5-amino[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide derivatives (4), designed to obtain new effective analgesic and/or anti-inflammatory agents were synthesized. Ten compounds 2 and 4 showed an interesting analgesic activity: the most potent ones are 2j (36% inhibition, P < 0.05) and 4b (77% inhibition, P < 0.01) at 6.25 and 25 mg kg−1 doses, respectively. Compounds 2i–l and 4c showed notable anti-inflammatory properties: the most potent ones are 2i (68% inhibition, P < 0.01) and 2l (42% inhibition, P < 0.05) at 12.5 and 6.25 mg kg−1 doses, respectively. The replacement in compounds 2 of the N-substituted 5-amino substituents with similar alkoxy groups usually afforded less active compounds 3.

Graphical abstract A number of new substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]-naphthyridine-6-carboxamides 2 and some of their isosteric analogues 3 and 4 were synthesized. Many compounds 2 showed a notable analgesic and/or potent anti-inflammatory activities. Lower but interesting activities were exhibited by compounds 4, whereas the 5-alkoxy substituted compounds 3 were clearly less active.Figure optionsDownload full-size imageDownload as PowerPoint slide