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.
Roma
Giorgio
G
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova, Italy. roma@unige.it
Grossi
Giancarlo
G
Di Braccio
Mario
M
Piras
Daniela
D
Ballabeni
Vigilio
V
Tognolini
Massimiliano
M
Bertoni
Simona
S
Barocelli
Elisabetta
E
D000208:Acute Disease; D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003613:Danazol / Q000737:chemistry*; D005260:Female; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013272:Stomach Diseases / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000577:Amides; D000588:Amines; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D009287:Naphthyridines; D003613:Danazol