1,8-Naphthyridines VIII. Novel 5-aminoimidazo[1,2-a] [1,8]naphthyridine-6-carboxamide and 5-amino[1,2,4]triazolo[4,3-a] [1,8]naphthyridine-6-carboxamide derivatives showing potent analgesic or anti-inflammatory activity, respectively, and completely devoid of acute gastrolesivity.
On the basis of the very interesting pharmacological properties shown by the 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamide derivatives 1, previously described by us, we have now prepared the 5-aminoimidazo[1,2-a][1,8]naphthyridine-6-carboxamide derivatives 2a-o (a new structural class) whose tricyclic system is isosteric to that of compounds 1. Both compounds 2 and some new properly substituted compounds 1 (1f-k) now synthesized were tested in vivo for their analgesic and anti-inflammatory activities: on the whole, compounds 2 showed notable analgesic properties, whereas many compounds 1 exhibited a very potent anti-inflammatory activity, coupled to scarce analgesic activity. All the effective compounds proved to be completely devoid of acute gastrolesivity (gastric damage) in rats (at the 200 mg kg(-1) oral dose).
Roma
Giorgio
G
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova, Italy. roma@unige.it
Di Braccio
Mario
M
Grossi
Giancarlo
G
Piras
Daniela
D
Ballabeni
Vigilio
V
Tognolini
Massimiliano
M
Bertoni
Simona
S
Barocelli
Elisabetta
E
D000700:Analgesics / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009287:Naphthyridines / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013270:Stomach / Q000187:drug effects* / Q000473:pathology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D009287:Naphthyridines