Development of a simple proton nuclear magnetic resonance-based procedure to estimate the approximate distribution coefficient at physiological pH (log D7.4): Evaluation and comparison to existing practices

Abstract 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 (log  D 7.4 ) in 1-octanol and D 2 O 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 log  D 7.4 can be accurately measured using 1H NMR for compounds within the log  D 7.4 interval between 0.7 and 3.3. The method was also compared to a previously described HPLC method.