title: Synthesis and structure-activity relationship of N-(2-arylethyl) isoquinoline derivatives as human scavenger receptor CD36 antagonists.
abstract: By using human scavenger receptor CD36 as the target, twenty-five N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their antagonistic activities for CD36-oxidatively low density lipoprotein (oxLDL) binding. The primary analysis of structure-activity relationship (SAR) indicated a methoxyl at the 7-position and a hydroxyl at the 6- or 8-position could afford good activities. Among these analogs, compounds 7e and 7t showed the potential CD36 antagonistic activities with IC(50) values of 0.2 and 0.8 μg/mL, respectively. Furthermore, both of them could effectively inhibit oxLDL uptake in insect Sf9 cells overexpressing human CD36, and thus have been selected for further investigation. We consider N-(2-arylethyl) isoquinoline analogs to be a family of novel CD36 antagonists.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Xu
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Si
authors.forename: Yang-Biao
authors.initials: YB
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Shan
authors.forename: Bin
authors.initials: B
authors.lastname: Hong
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008856:Microscopy, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D018955:CD36 Antigens; D007546:Isoquinolines; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C039109:isoquinoline