Development of a simple proton nuclear magnetic resonance-based procedure to estimate the approximate distribution coefficient at physiological pH (logD7.4): Evaluation and comparison to existing practices

Research output: Contribution to journalJournal articleResearchpeer-review

E Johanna L Stéen, Nils Nyberg, Szabolcs Lehel, Valdemar L Andersen, Pantaleo Di Pilato, Gitte M Knudsen, Jesper L Kristensen, Matthias M Herth

In drug discovery, lipophilicity is a key parameter for drug optimization. Lipophilicity determinations can be both work and time consuming, especially for non-UV active compounds. Herein, an improved and simple 1H NMR-based method is described to estimate the lipophilicity at physiological pH (logD7.4) in 1-octanol and D2O buffer. The method can be applied to both UV and non-UV active compounds. In addition, neither calibration curves nor internal/external standards are needed. We have demonstrated that logD7.4 can be accurately measured using 1H NMR for compounds within the logD7.4 interval between 0.7 and 3.3. The method was also compared to a previously described HPLC method.

Original languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Issue number2
Pages (from-to)319-322
Number of pages4
Publication statusPublished - 15 Jan 2017

ID: 169641117