新型支气管扩张剂——一些10-取代的2,3-二氢咪唑并[2,1-b]喹唑啉-5(10H)-酮的合成与生物学评价

Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators.

作者信息

Hardtmann G E, Koletar G, Pfister O R, Gogerty J H, Iorio L C

出版信息

J Med Chem. 1975 May;18(5):447-53. doi: 10.1021/jm00239a001.

Abstract

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.

摘要

用2-甲基巯基咪唑啉处理N-取代的异吲哚酮酸酐时，可得到10-取代的咪唑并[2,1-b]喹唑啉-5(10H)-酮。该类化合物中的几个成员表现出显著的支气管舒张活性。讨论了这些非拟交感神经支气管扩张剂的构效关系（基于豚鼠组胺气雾剂试验的结果）。此外，还描述了对两种类似物的详细药理学评价，这两种类似物作为支气管扩张剂的活性比茶碱高五到十倍，且无中枢神经系统或心血管副作用。