1,8-Naphthyridines IV. 9-substituted N,N-dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4]triazolo[4,3-a][1, 8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities.
The title compounds (8) were synthesized through the cyclocondensation of the corresponding N-substituted 4-amino-2-chloro-1,8-naphthyridine-3-carboxamides (4) with the proper hydrazides, in order to evaluate their anti-inflammatory and anti-aggressive properties. Several compounds 8 exhibited high anti-inflammatory activity (carrageenin-induced paw edema assay in the rat) along with appreciable anti-aggressive properties (isolation-induced aggressiveness test in mice). With respect to anti-inflammatory activity, the most active compounds (8n and 8c) produced a 61% edema inhibition at the 25 mg/kg dose, and 50 or 35% inhibition, respectively, at the 12.5 mg/kg dose. The structure-activity relationships are discussed.
Roma
G
G
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, 16132, Genoa, Italy. roma@unige.it
Di Braccio
M
M
Grossi
G
G
Mattioli
F
F
Ghia
M
M
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009287:Naphthyridines