Substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones.
The synthesis of a series of substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones is described. Several members of the series exhibit enhanced antiallergic and bronchodilator activity and reduced side effects as compared to theophylline. Structure-activity relationships and metabolic considerations are discussed for the series. Analogues substituted with a 4-(4-chlorobenzyl) moiety, such as 33 and 40, shown an optimal balance of antiallergic and bronchodilator activity and are of particular interest. Compound 33 is significantly more potent than theophylline against both metacholine- and antigen-induced bronchospasms, does not affect spontaneous motor activity, and shows minimal cardiovascular effects in the rat.
D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced; D001993:Bronchodilator Agents / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011688:Purinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D001993:Bronchodilator Agents; D007093:Imidazoles; D011688:Purinones