title: [Design, synthesis, and PPARalpha/gamma agonistic activity of novel tetrahydroisoquinoline derivatives].
abstract: A series of tetrahydroisoquinoline derivatives were prepared and their peroxisome proliferator-activated receptor (PPAR) alpha/gamma 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 PPARgamma than that of the comparison, six compounds exhibited higher agonistic activities of PPARalpha than that of the comparison, and compound 8a was discovered as a highly potent PPARalpha/gamma 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.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Yu
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Huan
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Zhu-Fang
authors.initials: ZF
authors.lastname: Shen
authors.forename: Zhan-Zhu
authors.initials: ZZ
authors.lastname: Liu
mesh_terms: D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection
chemical_list: D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D044005:Tetrahydroisoquinolines