Synthesis and structure–activity relationship of N-(2-arylethyl) isoquinoline derivatives as human scavenger receptor CD36 antagonists

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. N-(2-Arylethyl) isoquinoline analogs are supposed to be a family of novel CD36 antagonists for CD36-oxLDL binding. [Display omitted] ► N-(2-Arylethyl) isoquinoline analogs are a family of novel CD36 antagonists for CD36-oxLDL binding. ► A methoxyl at the 7-position and a hydroxyl at the 6- or 8-position of the ring D afford good antagonistic activities. ► Compounds 7e and 7t show the potent CD36 antagonistic activities on both the molecular and cellular levels.