Assessment on Prominent Synthetic Approaches for the Cholesterol Absorption Inhibitor Ezetimibe and Their Process Impurities: A Review

Hyperlipidemia, a major global health concern and a primary cause of high mortality, is exacerbated by elevated cholesterol and triglyceride profiles. Thus, it is possible to optimally control lipid levels and prevention of the progression of hyperlipidemia and associated diseases through drug treatments, emerging therapies, and lifestyle modifications. Among antihyperlipidemia therapeutic drugs, the cholesterol absorption inhibitor (CAI) ezetimibe is an important lipid‐lowering agent that actively reduces dietary and biliary cholesterol absorption. Accordingly, the present review summarizes the prominent synthetic approaches of ezetimibe and their synthetic analogues, as well as their process impurities. In addition, the inclusive study highlights the expansions of API impurities and their optimization for scale‐up techniques for ezetimibe drug. Further, this study also collectively abridges the research and developments of ezetimibe analogues such as glucuronide fluorescent derivatives, sulfonyl‐glucuronides, amide‐, and sulfonamide derivatives for enriched antihyperlipidemia drug developments. Therefore, this review précises the important synthetic developments of ezetimibe and its derivatives that could be assisted as a template for the further expansion of antihyperlipidemia and azetidinone based drug leads.