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.
Aluru Rammohan, G. Zyryanov· Journal of Heterocyclic Chem...· 0 citations
We herein report the anticancer activity and molecular docking studies of a series of amide derivatives of two nonsteroidal anti-inflammatory drugs (mefenamic acid and ibuprofen). The hypothesis of drug repurposing has been successfully employed to explore the promising anticancer activity of analogs of known anti-inflammatory agents. The compounds have been tested for their inhibitory potential against cervical cancer cell lines by MTT assay using 5-fluorouracil as the reference standard. Among the compounds screened, 3aa [2-(2,3-dimethylamino)phenyl)(1H-indol-1-yl)methanone] and 3ad [2-(2,3-dimethylphenylamino)phenyl)(9H-carbazol-9-yl)methanone] displayed good potency of less than 25 µg/mL half-maximal inhibitory concentration (IC50). The docking analysis has confirmed that molecule 3aa effectively binds to the active site of the target protein CDK2, with a docking score of −9.21 Kcal/mol and a binding energy of −46.44 Kcal/mol, involving a hydrogen bond with Ile 10. The molecule 3ad also exhibited a good glide score of −6.78 Kcal/mol with the binding energy of −45.90 Kcal/mol. As many of the tested compounds displayed promising potency against cervical cancer cell lines, our investigation revealed the importance of drug repurposing in the development of lead molecules in medicinal chemistry.
Nivedya Prasad SreeNilayam, J. Abhithaj, S. Remeshan et al.· Biophysica· 0 citations