Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives.
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.
Yamaguchi
M
M
Fuji-gotemba Research Laboratories, Chugai Pharmaceutical Company, Ltd., Shizuoka, Japan.
Maruyama
N
N
Koga
T
T
Kamei
K
K
Akima
M
M
Kuroki
T
T
Hamana
M
M
Ohi
N
N
D000284:Administration, Oral; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D011724:Pyridazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D001993:Bronchodilator Agents; D011724:Pyridazines; D006632:Histamine; D013930:Thromboxane-A Synthase