N_1_5_二芳基_3_戊酮_1_基_4__省略_基苯甲酸的合成与_葡糖苷酶抑制.pdfVIP

· · 48 药学学报 Acta Pharmaceutica Sinica 2009, 44(1): 48~55 N -(1,5-二芳基-3-戊酮-1-基)-4-氨基苯甲酸的合成与 α-葡糖苷酶 抑制活性初步研究 1 2 1 1 1 1* 许 荩 , 晏菊芳 , 范 莉 , 宋小礼 , 唐雪梅 , 杨大成 (1. 西南大学化学化工学院, 重庆 400715; 2. 成都地奥制药集团药物筛选中心, 四川 成都 610041) 摘要: 由Mannich 反应直接合成了 16 个β-氨基酮化合物, 制备方法简单、反应条件温和、产品易纯化, 收率 1 13 达到45%～90% 。所制备的化合物通过IR 、ESI-MS 、H NMR 、 C NMR 和HR-MS 等方法进行了结构表征。α- 葡糖苷酶抑制活性检测表明, 所合成的化合物对该酶的抑制活性顺序为: 2c 最强, 2b、2h、1a、1f 有一定的抑制活 性。在此基础上, 对合成化合物的构-效关系进行了讨论。 关键词: 糖尿病; α-葡糖苷酶; β-氨基酮化合物; Mannich 反应 中图分类号: R916.1 文献标识码: A 文章编号: 0513-4870(2009)01-0048-08 Synthesis and α-glucosidase inhibitory activity of N-(1,5-diaryl-3- pentone-1-yl)-4-aminobenzoic acid 1 2 1 1 1 1* XU Jin , YAN Ju-fang , FAN Li , SONG Xiao-li , TANG Xue-mei , YANG Da-cheng (1. School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China; 2. Chengdu Di Ao Pharmaceutical Group, Chengdu 610041, China) Abstract: In order to find highly active antidiabetic lead compound, sixteen 4-aminobenzoic acid derivatives were designed and synthesized directly through Mannich reaction in the solution of ethanol at 15−35 ℃with facile method, mild reaction condition and high yield (45%−90%). Fifteen of them are new compounds. Their structures were confirmed by 1H NMR, 13C NMR, IR, ESI-MS and HR-MS. α-Glucosidase inhibitory activity of these compounds indicated that most of these compounds possess the activity with the order: 2c