1,8-naphthyridines II. 2,4-disubstituted N,N-dialkyl-1,8-naphthyridine-3-carboxamides with anti-inflammatory and/or antiaggressive activities.
The preparation of the novel N,N-dialkyl-2,4-dichloro-1,8-naphthyridine-3-carboxamides 1c, e and N,N-dialkyl-2-(alkylamino or cycloalkylamino)-4-chloro-1,8-naphthyridine-3- carboxamides 2b, d-g, j-p is described. These compounds and the previously obtained analogs 1a, b, d, f and 2a, c, h, i have been tested for their anti-inflammatory and antiaggressive activities, as well as for their gross behavioral effects and acute toxicity. Nine of the twenty-two tested compounds exhibited a statistically significant anti-inflammatory activity in the carrageenin-induced edema assay in the rat (1e, f and 2h, o were the most active compounds). On the other hand, an interesting antiaggressive activity was displayed by ten compounds in the isolation-induced aggressiveness test in mice (compounds 2d, i, k showed the highest activity). Structure-activity relationships are briefly discussed.
Di Braccio
M
M
Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Roma
G
G
Ghia
M
M
Mattioli
F
F
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D009287:Naphthyridines; D002351:Carrageenan