4-(1-芳基-3-氧代-5-苯基戊氨基)苯磺酰胺的合成与抗糖尿病活性初步研究  

Synthesis and investigation on antidiabetic activity of 4-(1-aryl-3-oxo-5-phenylpentylamino) benzenesulfonamide

作　　者：杨大成[1] 晏菊芳 许荩[1] 叶飞 周祖文[1] 张蔚瑜 范莉[1] 陈欣 

机构地区：[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

出　　处：《药学学报》2010年第1期66-71,共6页Acta Pharmaceutica Sinica

基　　金：重庆市自然科学基金资助项目(2005BB5095);西南师范大学博士科研基金资助项目(SWNU.B2005010)

摘　　要：采用分段投料法,通过Mannich反应直接合成了12个含有磺胺的β-氨基酮化合物,收率23%～97%。所制备的新化合物采用FTIR、ESI-MS、1HNMR、13CNMR和HR-MS等方法进行结构确证。初步抗糖尿病活性筛选结果显示,所合成的含有磺胺的β-氨基酮化合物具有不同程度的抗糖尿病活性,其中目标分子1e具有较好的α-葡萄糖苷酶抑制活性,1l表现出较好的过氧化物酶体增殖物激活受体反应元件(PPRE)激动活性。在此基础上,讨论了所得化合物的构效关系。Searching for new antidiabetic lead compound, 4-（1-aryl-3-oxo-5-phenylpentylamino） benzene- sulfonamides were designed and synthesized directly by three component one-pot condensation of 4-phenyl- 2-butanone and sulfanilamide with some aromatic aldehydes at an yield of 23%-97%. The chemical structures of the twelve new Mannich bases were confirmed by 1H NMR, 13C NMR, FTIR, ESI-MS and HR-MS. The screening results of antidiabetic activity indicated that most of these title compounds possess α-glucosidase inhibitory activity, among which compound 1e is the strongest one. And compound 1l possesses good peroxisome proliferator-activated receptor response element （PPRE） agonist activity. The structure-activity relationship of these new β-amino ketones containing benzenesulfonamide unit was also discussed preliminarily.

关 键 词：糖尿病 Α-葡萄糖苷酶 过氧化物酶体增殖物激活受体 β-氨基酮 MANNICH反应 磺胺 

分 类 号：R916.1[医药卫生—药学]