New pyridazino[4,5-b]indole derivatives with inodilator and antiaggregatory activities.
Some 4-(3,5-dimethylpyrazol) 5H-pyridazino [4,5-b]indoles (7), 1,2,4-triazolo [4,3-b]pyridazino [4,5-b]indoles (9) and 1,2,4-tetrazolo [4,5-b]pyridazino [4,5-b] indoles (11) substituted in position 1 by amino groups have been synthesized and tested as inotropic agents and inhibitors of platelet aggregation. 6-Imidazolyl-11H-1,2,4-triazolo [4,3-b]pyridazino [4,5-b]indole (9) shows an activity superior to that of amrinone, with a notable selectivity towards phosphodiesterase (PDE) IV and PDEV, vasodilator activity and a good effect on blood platelet aggregation.
Monge
A
A
Departamento de Química Orgánica y Farmacéutica, Universidad de Navarra, Pamplona, Spain.
Aldana
I
I
Losa
M J
MJ
Font
M
M
Cenarruzabeitia
E
E
Castiella
E
E
Frechilla
D
D
Santiago
E
E
Martínez de Irujo
J J
JJ
Alberdi
E
E
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D002316:Cardiotonic Agents; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; D014665:Vasodilator Agents; D013930:Thromboxane-A Synthase