Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Eur J Med Chem. 2011 Apr;46(4):1066-73. doi: 10.1016/j.ejmech.2011.01.022. Epub 2011 Jan 21.
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.
以人源清道夫受体 CD36 为靶标，设计、合成了 25 个 N-(2-芳基乙基)异喹啉衍生物，并对其拮抗 CD36-氧化型低密度脂蛋白（oxLDL）结合的活性进行了评价。初步的构效关系（SAR）分析表明，7 位的甲氧基和 6 位或 8 位的羟基可以提供较好的活性。在这些类似物中，化合物 7e 和 7t 表现出潜在的 CD36 拮抗活性，IC50 值分别为 0.2 和 0.8 μg/mL。此外，它们都能有效抑制过表达人源 CD36 的昆虫 Sf9 细胞摄取 oxLDL，因此被选为进一步研究的对象。我们认为 N-(2-芳基乙基)异喹啉类似物是一类新型的 CD36 拮抗剂。
