Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators.
On treatment of N-substituted isatoic anhydrides with 2-methylmercaptoimidazolines, 10-substituted imidazo[2,1-b]quinazolin-5(10H)-ones are obtained. Several members of this class exhibited pronounced broncholytic activity. The structure-activity relationships (based on results obtained in the guinea pig histamine aerosol test) of these nonsympathomimetic bronchodilators are discussed. In addition, the detailed pharmacological evaluation of two analogs found to be five to ten times more active than theophyline as bronchodilators without having central nervous system or cardiovascular side effects is described.
D000818:Animals; D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D001993:Bronchodilator Agents; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D011799:Quinazolines; D006632:Histamine; D010047:Ovalbumin; D013806:Theophylline; D007545:Isoproterenol