New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics.
Some fused 5H-pyridazino[4,5-b]indoles (7-10), substituted in positions 1 and 4 by hydrazine and/or amino groups, have been synthesized. These new compounds present a planar topography, a dipole with an adjacent acidic proton, and a basic hydrogen-acceptor site opposite the dipole. These compounds have some resemblance to carbazeram and other pyridazino agents with cardiotonic activity. Some of the new compounds here described possess inotropic activity (Table I and II), with a complementary effect as inhibitors of platelet aggregation (Table III and IV). 1-Hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino[4,5-b ]indole hydrochloride (7a.HCl) is the first compound described in the literature with activities as inhibitor of PDE-IV and as selective inhibitor of TXA2 synthetase (Table V).
Monge
A
A
Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, Pamplona, Spain.
Aldana
I
I
Alvarez
T
T
Font
M
M
Santiago
E
E
Latre
J A
JA
Bermejillo
M J
MJ
Lopez-Unzu
M J
MJ
Fernandez-Alvarez
E
E
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002316:Cardiotonic Agents; D007211:Indoles; D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; C071273:1-hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino(4,5-b)indole; D013928:Thromboxane A2; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D013930:Thromboxane-A Synthase; D015232:Dinoprostone