REVIEW ON IMIDAZOPYRIDINE DERIVATIVES AS POTENT REVERSIBLE INHIBITORS OF THE GASTRIC H+, K+-ATPASE

The gastric H+, K+-ATPase is the preferred target for acid suppression. PPIs are acid-activated prodrug that requires acid protection. Once acid-activated, PPIs bind to cysteine of the ATPase, resulting in covalent, long-lasting inhibition. The currently available PPIs require around 3–5 days to achieve maximum acid inhibition at existent therapeutic doses, primarily due to their chemical structures and irreversible inhibition of H+,K+-ATPase. Therefore, many novel strategies to address the unmet needs of PPI therapy have been investigated, and acid pump antagonists (APAs) could play a promising role, as they provide faster onset and longer duration of action than irreversible PPIs by virtue of their ability to reversibly bind to the proton pump. They are active in absence of acid secretion and bind to specific sites in the membrane domain of the H+/K+-ATPase. The imidazopyridine based compound was the prototype of this class. Comparison was made between to the classic PPIs and P-CABs. SAR of imidazo [1,2-a]pyridines related to SCH 28080 is described. Various modifications were done on imidazopyridine nucleus, to search for lead molecule is also described. Some of the potent compounds are SCH28080, Soraprazan, Revaprazan, Linaprazan, Vonoprazan, Tak- 438-1, AZD 0865, BY841.