Synthesis and biological activity of 3-substituted imidazo[1,2-a]pyridines as antiulcer agents.
Synthesis and biological activity of 3-substituted imidazo[1,2-a]pyridines as antiulcer agents.
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DOI：
10.1021/jm00129a028
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发表时间：
1989-09
影响因子：
7.3
通讯作者：
J. Starrett;T. A. Montzka;A. R. Crosswell;R. L. Cavanagh
中科院分区：
文献类型：
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作者：
J. Starrett;T. A. Montzka;A. R. Crosswell;R. L. Cavanagh
合成了3位取代的咪唑并[1，2-a]吡啶类新化合物，作为潜在的抗分泌性和细胞保护性抗溃疡药物。合成路线从氨基吡啶5a，b和氯酮6a，b环合得到咪唑并[1，2-a]吡啶7-9。伯胺12a-c与丁氧氨基环丁二酮13或甲氧氨基噻二唑1-氧化物(15)反应，分别得到14a、b和16a-c。噻二唑1-氧化物16a-c在两步反应中转化为噻二唑19a-c，其中包括挤压16a-c中的亚砜，得到二亚胺17a-c，然后用硫代双邻苯二甲酰亚胺(18)处理。在胃瘘大鼠模型中，没有一种化合物表现出显著的抗分泌活性，但在乙醇和盐酸模型中，有几种化合物表现出良好的细胞保护作用。8-(Benzyloxy)-3-[1-[[2-[(4-amino-1，2，5-thiadiazol-3-yl)amino]ethyl]thio]ethyl]-2-methylimidazo[1，2-a]pyridine(19c)具有与SCH-28080(4)相当的细胞保护活性。
New imidazo[1,2-a]pyridines substituted at the 3-position have been synthesized as potential antisecretory and cytoprotective antiulcer agents. The synthetic routes began with cyclization of aminopyridines 5a,b and chloro ketones 6a,b to give imidazo[1,2-a]pyridines 7-9. The side chain at the 3-position was elaborated to give primary amines 12a-c, which were treated with either butoxyaminocyclobutenedione 13 or methoxyaminothiadiazole 1-oxide (15) to give 14a,b and 16a-c, respectively. Thiadiazole 1-oxides 16a-c were converted to thiadiazoles 19a-c in a two-step process which involved extrusion of the sulfoxide in 16a-c to afford diimidamides 17a-c, which were subsequently treated with thiobisphthalimide (18). None of the compounds displayed significant antisecretory activity in the gastric fistula rat model, but several demonstrated good cytoprotective properties in both the EtOH and HCl models. 8-(Benzyloxy)-3-[1-[[2-[(4-amino-1,2,5-thiadiazol-3- yl)amino]ethyl]thio]ethyl]-2-methylimidazo[1,2-a]pyridine (19c) showed comparable cytoprotective activity to SCH-28080 (4).