An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent

Diabetes mellitus is the global health issue and become an alarming threat in the modern era where human lifestyle gets compromised with modernization. According to the latest statistical report 2020, USA has 9.47% (31 million among 32.72 cr), China has 8.3% (116.4 million among 139.27 cr) and India has 5.6% (77 million among 135.26 cr) of the diabetic people, indicating that diabetes is more prevailing in developed countries as compared to the developing countries. The number of diabetic patients is rising day by day at a tremendous rate and soon it may affect each and every person in a family. So, there is an urgent need to develop novel entities that can meet the scarcity of present antidiabetic agents. In the last few decades, the sodium-glucose co-transporter 2 (SGLT2) has emerged as a prominent target for the treatment of Type 2 diabetes mellitus due to its novel mechanism of action & no involvement in insulin signaling pathway. Most of the inhibitors that target SGLT2 contain three basic moieties: glucose, two benzene rings (one is connected with glucose and the other with methylene), and the methylene bridge which are similar to dapagliflozin. Several SGLT2 inhibitors and their derivatives such as remogliflozin etabonate (phase-II), sotagliflozin (phase-III) and bexagliflozin (phase-III) are under different phases of clinical trial studies and some have been patented. The present review is focused on SGLT2 inhibitors, structure activity relationships (SARs) of dapagliflozin and its several analogues for their binding affinity with SGLT2. We have also presented and summarized the efforts made by various researchers in terms of the synthesis of various dapagliflozin derivatives till date.