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