CORRELATION BETWEEN PHARMACOKINETIC PROPERTIES AND ~(15)N-NMR AND ~(13)C-NMR CHEMICAL SHIFTS OF ANGIOTENSIN CONVERTING ENZYMEINHIBITORS

摘要

In the current study, angiotensin converting enzyme inhibitor molecules (enalapril, perindopril, ramipril and benazepril) were studied using ~(15)N-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 ~(13)C 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 ~(15)N-nuclear magnetic resonance studies of the molecules as well as studies correlating the relationships between ~(15)N chemical shifts, pharmacokinetics and physicochemical properties in molecules which could be used for theprediction of properties for which experimental data is currently not available.