15N-NMR spectroscopic studies and investigation of spectral data property relationships of proton pump inhibitors

In this study, the relationships between 15N-NMR and 13C-NMR chemical shifts of omeprazole, lansoprazole, ilaprazole,pantoprazole, and rabeprazole and their physicochemical and pharmacokinetic properties, namely, pKa, half-life,tmax, logP, and protein binding were investigated. This study also presents the first report of 15N-NMR spectroscopicstudies of lansoprazole, pantoprazole, and ilaprazole. It was found that 15N-NMR chemical shifts of the doubly bondedbenzimidazole nitrogen of proton pump inhibitors showed correlation with pKa2, protein binding and logP, while 15NNMR chemical shifts of the pyridine nitrogen correlate with protein binding and tmax. Sum of 15N-NMR chemical shiftsand sum of 13C-NMR chemical shifts, both, exhibit correlation with half-life, logP, and tmax. The sum of 13C chemicalshifts of the pyridine moiety exhibits correlation with pKa1, while the sum of 13C chemical shifts of the benzimidazolemoiety exhibits correlation with half-life. NMR chemical shifts may, hence, be useful as molecular descriptors in thedevelopment of Quantitative Structure/Spectral Data Property Relationship models.