title: Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives.
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.
authors.affiliation: Fuji-gotemba Research Laboratories, Chugai Pharmaceutical Company, Ltd., Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Maruyama
authors.forename: T
authors.initials: T
authors.lastname: Koga
authors.forename: K
authors.initials: K
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Akima
authors.forename: T
authors.initials: T
authors.lastname: Kuroki
authors.forename: M
authors.initials: M
authors.lastname: Hamana
authors.forename: N
authors.initials: N
authors.lastname: Ohi
mesh_terms: 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
chemical_list: D001993:Bronchodilator Agents; D011724:Pyridazines; D006632:Histamine; D013930:Thromboxane-A Synthase