4-Amino-3(2H)-pyridazinones bearing arylpiperazinylalkyl groups and related compounds: synthesis and antinociceptive activity.
A series of 4-amino-3(2H)-pyridazinones substituted at position 2 with arylpiperazinylalkyl groups and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Preliminary SARs studies were performed. Several of the novel compounds dosed at 100 mg/kg s.c. significantly reduced the number of writhes induced by the noxious stimulus. Compound 12e showed 100% inhibition of writhes and was able to protect all the treated animals from the effect of the chemical stimulus. Subsequent dose-response studies revealed 12e to be almost 40-fold more potent than the structurally related Emorfazone.
Piaz
Vittorio Dal
VD
Dipartimento di Scienze Farmaceutiche, Università di Firenze, via G. Capponi 9, 50121 Firenze, Italy. vittorio.dalpiaz@unifi.it
Vergelli
Claudia
C
Giovannoni
Maria Paola
MP
Scheideler
Mark A
MA
Petrone
Giuseppe
G
Zaratin
Paola
P
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000700:Analgesics; D010879:Piperazines; D011724:Pyridazines