Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives

Chem Pharm Bull (Tokyo). 1995 Feb;43(2):236-40. doi: 10.1248/cpb.43.236.

Abstract

Synthesis and pharmacological evaluation of novel thienopyridazinones and related compounds are described. A thiophene ring was found to be able to replace the benzene ring of a phthalazinone without loss of biological activities. This observation supports our hypothesis that the benzene ring plays an important role in both thromboxane A2 (TXA2) synthetase-inhibitory and bronchodilatory activities. Further, it was shown that the carbonyl moiety of a phthalazinone is not necessary for these activities.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology
  • Bronchoconstriction / drug effects*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / chemical synthesis
  • Bronchodilator Agents / pharmacology*
  • Guinea Pigs
  • Histamine / toxicity
  • In Vitro Techniques
  • Male
  • Mass Spectrometry
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Pyridazines / chemistry
  • Pyridazines / metabolism
  • Pyridazines / pharmacology*
  • Rabbits
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship
  • Thromboxane-A Synthase / antagonists & inhibitors*
  • Trachea / drug effects

Substances

  • Bronchodilator Agents
  • Pyridazines
  • Histamine
  • Thromboxane-A Synthase