Discovery, Synthesis and Evaluation of Novel Cholesterol Absorption Inhibitors


Corresponding authors: Hai Qian,; Wenlong Huang,


Chemical-based common feature pharmacophore modelling of Niemann Pick C1 Like 1 inhibitors was performed to provide some insights on the important pharmacophore features essential for Niemann Pick C1 Like 1 inhibition using Discovery Studio V2.5. After in-house database screening, a new series of substituted oxazolidinones, selected from the top ranked hits, have been synthesized and evaluated as novel cholesterol absorption inhibitors. All compounds demonstrated effect of different degrees in lowering the total cholesterol in serum, especially compounds 1a, 2a and 2d, the potency of which was comparable to that of ezetimibe. It was also found that 1a, 1d and 2d could raise high-density lipoprotein cholesterol levels markedly. Interestingly, compounds 2a–2f appeared to have the moderate potential to lower triglyceride levels, which were superior to that of normal cholesterol absorption inhibitors including ezetimibe.