title: New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics.
abstract: 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).
authors.affiliation: Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Monge
authors.forename: I
authors.initials: I
authors.lastname: Aldana
authors.forename: T
authors.initials: T
authors.lastname: Alvarez
authors.forename: M
authors.initials: M
authors.lastname: Font
authors.forename: E
authors.initials: E
authors.lastname: Santiago
authors.forename: J A
authors.initials: JA
authors.lastname: Latre
authors.forename: M J
authors.initials: MJ
authors.lastname: Bermejillo
authors.forename: M J
authors.initials: MJ
authors.lastname: Lopez-Unzu
authors.forename: E
authors.initials: E
authors.lastname: Fernandez-Alvarez
mesh_terms: 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
chemical_list: 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