Pyridazines. Part XXIX: synthesis and platelet aggregation inhibition activity of 5-substituted-6-phenyl-3(2H)-pyridazinones. Novel aspects of their biological actions

Bioorg Med Chem. 2002 Sep;10(9):2873-82. doi: 10.1016/s0968-0896(02)00146-3.

Abstract

A series of 6-phenyl-3(2H)-pyridazinones with a diverse range of substituents in the 5-position have been prepared and evaluated in the search for new antiplatelet agents. A significant dependence of the substituent on the inhibitory effect has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at position 5 of the 6-phenyl-3(2H)-pyridazinone system influences both variations in the antiplatelet activity and the mechanism of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Calcium / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cytosol / chemistry
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Phosphodiesterase Inhibitors / chemical synthesis
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphorylation
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Structure-Activity Relationship

Substances

  • Phosphodiesterase Inhibitors
  • Platelet Aggregation Inhibitors
  • Pyridazines
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Calcium