Kaminski J J, Perkins D G, Frantz J D, Solomon D M, Elliott A J, Chiu P J, Long J F
Pharmaceutical Research Division, Schering-Plough Corporation, Bloomfield, New Jersey 07003.
J Med Chem. 1987 Nov;30(11):2047-51. doi: 10.1021/jm00394a019.
Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.
对一系列从构效关系研究中选出的化合物（这些研究旨在寻找3-(氰基甲基)-2-甲基-8-(苄氧基)咪唑并[1,2-a]吡啶（Sch 28080，1）的替代物）所得到的结构、抗溃疡活性和毒理学筛选数据之间的相互关系进行研究，确定了3-(氰基甲基)-2,7-二甲基-8-(苄氧基)咪唑并[1,2-a]吡啶（5）、3-氨基-2-甲基-8-(2-苯乙基)咪唑并[1,2-a]吡啶（6）和3-氨基-2-甲基-8-(苄氧基)咪唑并[1,2-a]吡嗪（7）。这些类似物在动物模型中表现出抗分泌和细胞保护活性的组合，同时消除了原型化合物1的不良反应。其中之一，3-氨基-2-甲基-8-(苄氧基)咪唑并[1,2-a]吡嗪，Sch 32651（7），其特性符合所有标准。
