H+/K+-ATPase inhibitors: a patent review

Abstract

Introduction: H(+)/K(+)-ATPase is a P-type ATP-driven cation transporter which exchanges ions (protons, chloride ions, and potassium ions) across the cell membrane. Modulators of H(+)/K(+)-ATPase affect H(+)/K(+) exchange.

Areas covered: This article describes various H(+)/K(+)-ATPase inhibitors of biological importance in clinical studies and drug development for gastric acid-related diseases and gastrointestinal disorders.

Expert opinion: H(+)/K(+)-ATPase modulators have attracted much interest for their clinical implication in gastric acid-related diseases. Future studies of gastric H(+)/K(+)-ATPase inhibitors may focus on the correlation of pharmacogenetics and pharmacogenomics with the gastric acid secretion and development of more effective H(+)/K(+)-ATPase inhibitors to increase their residence time such as tenatoprazole and novel chemical-mediated absorption chemicals. The K(+)-competitive acid pump antagonists (APAs) are invented and independent of an acidic environment with better inhibition of the pump rapidly control acid secretion with a larger extent. The most innovative and promising compounds of APAs is AZD-0865, which is a modification of SCH28080. H(+)/K(+)-ATPase inhibitors can be tried to treat other diseases, especially viral infection after numerous clinical trials, and respiratory disease.