1,8-Naphthyridines IX. Potent anti-inflammatory and/or analgesic activity of a new group of substituted 5 amino[1,2,4]triazolo[4,3-a] [1,8]naphthyridine-6 carboxamides, of some their Mannich base derivatives and of one novel substituted 5-amino-10-oxo-10Hpyrimido[1,2-a [1,8]naphthyridine-6-carboxamide derivative

A new group of 5-(alkylamino)-9-isopropyl[1,2,4]triazolo[4,3-a][1,8]naphthyridine derivatives bearing a CONHR group at the 6-position (1c–g), designed to obtain new effective analgesic and/or anti-inflammatory agents, were synthesized and tested along with three new 9-alkyl-5-(4-alkyl-1-piperazinyl)-N,N-diethyl [1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides (2b–d). Besides, a new class of analogues of compounds 1 and 2, bearing a Mannich base moiety at the 9-position (12a–d), as well as the novel N,N-diethyl-5-(isobutylamino)-8-methyl-10-oxo-10H-pyrimido[1,2-a][1,8]naphthyridine-6-carboxamide (15) were prepared and tested. Compounds 1c–g exhibited very interesting anti-inflammatory properties in rats, whereas compounds 2b–d and 15 proved to be endowed with prevalent analgesic activity frequently associated with sedative effects in mice. On the contrary, the Mannich bases 12a–d resulted inactive. The most effective (80% inhibition of oedema) and potent (threshold dose 1.6 mg kg−1 with 31% inhibition of oedema) anti-inflammatory compound 1d did not show gastrolesive effects following 100 mg kg−1 oral administration in rats.