1,5-benzodiazepines. Part XIII. Substituted 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines and 4H-imidazo[1,2-a][1,5]benzodiazepin-5-amines as analgesic, anti-inflammatory and/or antipyretic agents with low acute toxicity.
The reaction of proper N,N-dialkyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines (1) with N-chlorosuccinimide afforded their 4-chloroderivatives 3 which in turn were treated with cyclic amines to give the corresponding 4,5-diaminoderivatives 4. The N,N-dialkyl-4H-imidazo[1,2-a][1,5]benzodiazepin-5-amines (5) were prepared starting from suitable 4-(dialkylamino)-1,3-dihydro-2H-1,5-benzodiazepin-2-ones (8), through multistep synthetic routes. At the 200 mg kg(-1) os dose, some compounds 3 and 4 showed notable analgesic or anti-inflammatory activity but no antipyretic properties, whereas the 5-(dibutylamino) derivatives 5b and 5f proved to be significantly endowed with all these activities. Almost all the compounds 3, 4 and 5 did not show acute toxicity in mice up to 800 mg kg(-1) os dose.
Grossi
Giancarlo
G
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genoa, Italy.
Di Braccio
Mario
M
Roma
Giorgio
G
Ballabeni
Vigilio
V
Tognolini
Massimiliano
M
Calcina
Francesco
F
Barocelli
Elisabetta
E
D000700:Analgesics / Q000009:adverse effects* / Q000737:chemistry* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects* / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000737:chemistry* / Q000494:pharmacology; D001569:Benzodiazepines / Q000009:adverse effects* / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D005334:Fever / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D001569:Benzodiazepines