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 (1ceg), designed to obtain new effective analgesic and/or antiinflammatory 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 (2bed). Besides, a new class of analogues of compounds 1 and 2, bearing a Mannich base moiety at the 9-position (12aed), 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 1ceg exhibited very interesting anti-inflammatory properties in rats, whereas compounds 2bed and 15 proved to be endowed with prevalent analgesic activity frequently associated with sedative effects in mice. On the contrary, the Mannich bases 12aed resulted inactive. The most effective (80% inhibition of oedema) and potent (threshold dose 1.6 mg kg1 with 31% inhibition of oedema) anti-inflammatory compound 1d did not show gastrolesive effects following 100 mg kg1 oral administration in rats.