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.
Dipartimento di Scienze Farmaceutiche, Università di Firenze, via G. Capponi 9, 50121 Firenze, Italy. vittorio.dalpiaz@unifi.it
Vittorio Dal
VD
Piaz
Claudia
C
Vergelli
Maria Paola
MP
Giovannoni
Mark A
MA
Scheideler
Giuseppe
G
Petrone
Paola
P
Zaratin
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