Glucal-conjugated sterols as novel vascular leakage blocker: Structure–activity relationship focusing on the C17-side chain

•Synthesis of novel sterol analogs with the constrained side chains was reported.•New compounds showed anti-apoptotic activities and tight junction protective activities in the in vitro and in vivo models.•The structure–activity relationship of these compounds was discussed.

A series of glucal-conjugated sterols as novel vascular leakage blocker were identified through design, synthesis and biologically evaluation. In addition, the structure-activity relationship (SAR) of the glucal-conjugated sterols focusing on the C17-side chain was also established. The sterol analogs linked with the rigid C17-side chain side chains exhibited potent cell survival activities. In particular, analog 21l, which possesses a cyclopentyl oxime moiety, was shown to have excellent pharmacological effects on retinal vascular leakage in a diabetic mouse model.

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