4-[3-(4-溴苯基)-3-氧代-1-芳基丙氨基]苯磺酰胺的合成与抗糖尿病活性的初步研究  

Synthesis and Preliminary Evaluation of Antidiabetic Activity of 4-[3-(4-Bromophenyl)-3-oxo-1-arylpropylamino]benzenesulfonamide

作　　者：杨大成[1] 晏菊芳 宋小礼[1] 张蔚瑜 唐雪梅[1] 陈欣 范莉[1] 

机构地区：[1]西南大学化学化工学院,重庆400715 [2]成都地奥制药集团有限公司药物筛选中心,成都610041

出　　处：《化学学报》2010年第6期515-522,共8页Acta Chimica Sinica

基　　金：重庆市自然科学基金(No.2005BB5095);西南师范大学博士科研基金(No.SWNU.B2005010)资助项目

摘　　要：实现了4-氨基苯磺酰胺、对溴苯乙酮和芳香醛之间的Mannich反应,直接合成了14个未见报道的β-氨基酮化合物,制备方法简便,反应条件温和,产物收率44%～92%.通过1HNMR,13CNMR,MS和HRMS表征并确证了目标分子的化学结构.生物活性试验显示,所得化合物具有一定的α-葡萄糖苷酶抑制活性和PPRE激动活性,由此发现某些含有磺胺结构的β-氨基酮具有抗糖尿病活性.In order to find a novel antidiabetic lead compound, fourteen new β-amino ketone derivatives containing a sulfanilamide moiety were designed and synthesized directly through Mannich reaction of sulfanilamide, 4-bromoacetophenone and some aromatic aldehydes catalyzed by concentrated hydogen chloride in a solution of ethanol in 27～30 ℃ with convenient operation, mild reaction condition and middle to high yields （44%～92%）. The chemical structures of these title compounds were confirmed by ^1H NMR, ^13C NMR, MS and HRMS techniques. Biological activity tests showed that these compounds possessed very weak α-glucosidase inhibitory activity but could activate PPAR response element moderately, thus it was found that some β-amino ketone derivatives containing a sulfanilamide moiety had antidiabetic activity.

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 磺胺 β-氨基酮 MANNICH反应 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]