4-Amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive agents: Synthesis, SARs, and preliminary studies on the mechanism of action.
A series of 4-amino-5-vinyl-3(2H)-pyridazinones and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Several of the novel compounds showed ED(50) values in the range 6-20mg/kg/sc and demonstrated to be able to completely protect all the treated animals from the effect of the noxious stimulus at 30 mg/kg/sc. SAR studies confirmed the essential role played by an amino or substituted amino function at position 4 and by a vinyl group at position 5 of the diazine system.
Vergelli
Claudia
C
Dipartimento di Scienze Farmaceutiche, via Ugo Schiff 6, Sesto Fiorentino, 50019 Firenze, Italy.
Giovannoni
Maria Paola
MP
Pieretti
Stefano
S
Di Giannuario
Amalia
A
Dal Piaz
Vittorio
V
Biagini
Pierfrancesco
P
Biancalani
Claudio
C
Graziano
Alessia
A
Cesari
Nicoletta
N
D000586:Amination; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009619:Nociceptors / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011725:Pyridines