新型苯胺类苯并咪唑衍生物的合成及其生物活性  

Design and synthesis of the novel aniline-type derivatives of benzimidazole and their biological activities

作　　者：杨日芳[1] 恽榴红[1] 丁振凯[1] 柳用绍[1] 马秀英[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药物化学杂志》2003年第1期1-7,共7页Chinese Journal of Medicinal Chemistry

摘　　要：目的设计合成新型苯胺类苯并咪唑衍生物 ,并评价其对大白鼠胃液分泌和胃酸分泌的作用。方法以没食子酸、胡椒醛和香草醛为原料 ,经多步反应合成目标化合物 ,并通过大白鼠灌胃给药、幽门结扎、测定胃液量和胃酸量 ,来确定所合成化合物对其胃液和胃酸分泌率的影响。结果共合成 8个新化合物、5个前体及 1个对照药物 (NC 130 0 ) ,经元素分析 ,IR ,1H NMR和MS确证其结构 ;其中 2个化合物对胃酸分泌抑制作用与NC 130 0相当 ,所有化合物均对胃液分泌无显著影响。在中间体制备中提出了经取代的邻硝基苯甲醛一步催化氢化制备取代的邻氨基苯甲醇的方法及其选择性N ,N 二甲基化法。结论以没食子酸为原料所合成的NC 130 0类似物的胃酸分泌抑制作用与NC 130 0相当 ,是强的质子泵抑制剂。Aim To design and synthesize the novel aniline-type derivatives of benzimidazole,and to assay their activities of inhibiting secretion of gastric juice and gastric acids.Methods Target compounds were synthesized from gallic acid,piperonal and vanillin and the activities of inhibiting secretion of gastric juice and gastric acids in pylorus ligature rats were evaluated.Results A new procedure for preparation of o-aminobenzenemethanols from o-nitrobenzaldehydes has been proposed,and an efficient procedure for selective N,N-dimethylation of o-aminobenzene-methanols has also been proposed.Eight target compounds and five of their precursors and NC-1300 were synthesized and assayed,wherein two target compounds are as potent as NC-1300 in inhibition of secretion of gastric acids in pylorus ligature rats.All the compounds are inactive in inhibition of secretion of gastric juice in rats.Conclusion Preliminary pharmacological tests show that the two novel aniline-type derivatives of benzimidazole synthesized from gallic acid exert appreciable activity of inhibition of secretion of gastric acids in rats.

关 键 词：药物化学 制备 化学合成 苯并眯哩衍生物 质子泵抑制剂 分泌抑制 胃酸 

分 类 号：R914[医药卫生—药物化学]