取代的6,7-二氢咪唑并[1,2-a]嘌呤-9(4H)-酮。

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

作者信息

Temple D L, Yevich J P, Catt J D, Owens D, Hanning C, Covington R R, Seidehamel R J, Dungan K W

出版信息

J Med Chem. 1980 Nov;23(11):1188-98. doi: 10.1021/jm00185a008.

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. 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.

摘要

描述了一系列取代的6,7-二氢咪唑并[1,2-a]嘌呤-9(4H)-酮的合成。与茶碱相比，该系列中的几个成员表现出增强的抗过敏和支气管扩张活性以及减少的副作用。讨论了该系列的构效关系和代谢方面的考虑因素。用4-(4-氯苄基)部分取代的类似物，如33和40，显示出抗过敏和支气管扩张活性的最佳平衡，特别令人感兴趣。化合物33在对抗乙酰甲胆碱和抗原诱导的支气管痉挛方面比茶碱显著更有效，不影响自发运动活性，并且在大鼠中显示出最小的心血管效应。