Development of a simple proton nuclear magnetic resonance-based procedure to estimate the approximate distribution coefficient at physiological pH (log D_7.4): Evaluation and comparison to existing practices

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• 作者：E. Johanna L. Sté ; en^a ; ¹ ; Nils Nyberg^a ; ¹ ; Szabolcs Lehel^b ; Valdemar L. Andersen^b ; Pantaleo Di Pilato^c ; Gitte M. Knudsen^d ; Jesper L. Kristensen^a ; Matthias M. Herth^a ; ^b ; ^d ; ^{matthias.herth@sund.ku.dk}
• 关键词：Lipophilicity ; Distribution coefficient ; Log  ; D7.4 ; NMR
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：27
• 期：2
• 页码：319-322
• 全文大小：773 K
• 卷排序：27

文摘

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 D7.4) 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 log D7.4 can be accurately measured using 1H NMR for compounds within the log D7.4 interval between 0.7 and 3.3. The method was also compared to a previously described HPLC method.