Synthesis and pharmacological study of 5-aryl-6-methyl-4,5-dihydro-pyridazin-3(2H)ones and related 5-aryl-6-methyl-pyridazin-3(2H)ones.
New 5-aryl-6-methyl-4,5-dihydropyridazin-3(2H)ones (III) and related 5-aryl-6-methyl-pyridazin-3(2H)ones (IV) were synthesized in order to evaluate their pharmacological profile in comparison with that of the known class of antihypertensive and platelet aggregation inhibitors 5-methyl-6-aryl-4,5-dihydropyridazin 3(2H)ones (I). Though none of the tested derivatives was found to possess the antihypertensive potency of the reference compounds, some of them displayed significant antithrombotic and antiulcer properties. In particular, 5(p. acetylaminophenyl)-6-methyl-pyridazin-3-one (IV c) was found highly effective (ED50 = 1.2 mg/kg) in inhibiting indomethacin-induced ulcers.
Pinna
G A
GA
Istituto di Chimica Farmaceutica, Facoltà di Farmacia, Università di Sassari, Italy.
Curzu
M M
MM
Barlocco
D
D
Cignarella
G
G
Cavalletti
E
E
Germini
M
M
Berger
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D005343:Fibrinolytic Agents / Q000138:chemical synthesis*; D007928:Lethal Dose 50; D051379:Mice; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D011724:Pyridazines