New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics

J Med Chem. 1991 Oct;34(10):3023-9. doi: 10.1021/jm00114a010.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • Animals
  • Cardiotonic Agents / chemical synthesis
  • Cardiotonic Agents / pharmacology*
  • Dinoprostone / metabolism
  • Female
  • Guinea Pigs
  • Humans
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Platelet Aggregation Inhibitors / pharmacology*
  • Pyridazines / chemical synthesis
  • Pyridazines / pharmacology*
  • Thromboxane A2 / metabolism
  • Thromboxane-A Synthase / antagonists & inhibitors

Substances

  • Cardiotonic Agents
  • Indoles
  • Platelet Aggregation Inhibitors
  • Pyridazines
  • 1-hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino(4,5-b)indole
  • Thromboxane A2
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Thromboxane-A Synthase
  • Dinoprostone