Substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones

Abstract

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. Analogs substituted with a 4-(4-chlorobenzyl) moiety, i.e., 33 [4-[(4-chlorophenyl)methyl]-6,7-dihydro-3H-imidazo[1,2-a]purin-9(4H)-one], show 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.