A novel class of cardiotonic agents: synthesis and biological evaluation of pyridazino[4,5-b]indoles with cyclic AMP phosphodiesterases inhibiting properties

J Pharm Sci. 1993 May;82(5):526-30. doi: 10.1002/jps.2600820519.

Abstract

Some fused pyridazino[4,5-b]indoles (7) were synthesized. These new compounds present a planar topography and some resemblance to carbazeram, imadozan, and other pyridazino agents with cardiotonic activity. These compounds also possess a complementary effect as inhibitors of platelet aggregation. 6-(3,5-Dimethylpyrazolyl)-1,2,4-triazolo[4,3-b]pyridazino[4, 5-b]indole (7a) has a good profile as an inodilatador with antiaggregate activity due to the inhibition of phosphodiesterase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Animals
  • Aorta, Thoracic / drug effects
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / pharmacology
  • Dogs
  • Female
  • Guinea Pigs
  • Heart / drug effects
  • Humans
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Male
  • Myocardium / enzymology
  • Phosphodiesterase Inhibitors / pharmacology
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Cardiotonic Agents
  • Indoles
  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Platelet Aggregation Inhibitors
  • Pyridazines
  • 3',5'-Cyclic-AMP Phosphodiesterases