CORRELATION BETWEEN PHARMACOKINETIC PROPERTIES AND 15N-NMR AND 13C-NMR CHEMICAL SHIFTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS

Abstract

In the current study, angiotensin converting enzyme inhibitor molecules (enalapril, perindopril, ramipril and benazepril) were studied using 15N-nuclear magnetic resonance techniques like insensitive nuclei enhanced by polarization technique and heteronuclear multiple bond correlation. the chemical shift data and different pharmacokinetic and physicochemical properties of the molecules like pKa, half-life, time taken to reach maximum concentration in vivo, were compared and found to exhibit a good linear relationship. Further, a similar comparative study of the same parameters was performed using 13c chemical shifts of the molecules. Molecular docking studies were also performed to understand the structure of the enzyme bound to the ligand. this is perhaps the first report of 15N-nuclear magnetic resonance studies of the molecules as well as studies correlating the relationships between 15N chemical shifts, pharmacokinetics and physicochemical properties in molecules which could be used for the prediction of properties for which experimental data is currently not available.