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 spectroscopic studies of lansoprazole, pantoprazole and ilaprazole. It was found that 15N-NMR chemical shifts of the doubly bonded benzimidazole nitrogen of proton pump inhibitors showed correlation with pKa2, protein binding and logP while 15N-NMR chemical shifts of the pyridine nitrogen correlate with protein binding and tmax. Sum of 15N-NMR chemical shifts and sum of 13C -NMR chemical shifts, both, exhibit correlation with half-life, logP and tmax. The sum of 13C chemical shifts of the pyridine moiety exhibit correlation with pKa1 while the sum of 13C chemical shifts of the benzimidazole moiety exhibit correlation with half-life. NMR chemical shifts may, hence, be useful as molecular descriptors in development of Quantitative Structure/Spectral Data Property Relationship models.
Key words: 15N-NMR, 13C-NMR, omeprazole, ilaprazole, molecular descriptors
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