一类新型的四氢异喹啉类PPARα/γ受体激动剂的设计、合成与活性研究  

Design,synthesis,and PPARα/γ agonistic activity of novel tetrahydroisoquinoline derivatives

作　　者：于然[1] 周艳丽[1] 环奕[1] 刘泉[1] 申竹芳[1] 刘站柱[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2011年第3期311-316,共6页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项综合性新药研究开发技术大平台资助项目(2009ZX09301-003-12-1)

摘　　要：为得到更高效的PPAR(过氧化物酶体增殖激活受体)α/γ受体激动剂,设计合成了新型的四氢异喹啉类化合物,通过1H NMR、HR-MS对化合物结构进行了确证,并测定了化合物的体外PPARα/γ受体激动活性。其中化合物8a具有PPARα/γ双受体激动活性,其PPARα/γ受体激动活性与阳性对照品WY14643、罗格列酮相比活性更强。A series of tetrahydroisoquinoline derivatives were prepared and their peroxisome proliferator-activated receptor（PPAR） α/γ agonistic activities were evaluated to obtain more potent PPAR agonist.All of them were new compounds,and their structures were confirmed by 1H NMR and HR-MS.Three compounds exhibited higher agonistic activities of PPARγ than that of the comparison,six compounds exhibited higher agonistic activities of PPARα than that of the comparison,and compound 8a was discovered as a highly potent PPARα/γ agonist that is much more active than that of WY14643 and rosiglitazone.The development of potent PPAR agonists may offer a new choice for the treatment of diabetes.

关 键 词：四氢异喹啉 PPAR激动剂 抗糖尿病 合成 

分 类 号：R916[医药卫生—药学]