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

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

doi:10.1016/j.bmcl.2016.11.048

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

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

Department of Clinical Medicine

3 Citations (Scopus)

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 (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 language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	27
Issue number	2
Pages (from-to)	319-322
Number of pages	4
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2016.11.048
Publication status	Published - 15 Jan 2017

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Stéen, E. J. L., Nyberg, N., Lehel, S., Andersen, V. L., Di Pilato, P., Knudsen, G. M., Kristensen, J. L., & Herth, M. M. (2017). 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. Bioorganic & Medicinal Chemistry Letters, 27(2), 319-322. https://doi.org/10.1016/j.bmcl.2016.11.048

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. / Stéen, E Johanna L; Nyberg, Nils; Lehel, Szabolcs et al.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 27, No. 2, 15.01.2017, p. 319-322.

Research output: Contribution to journal › Journal article › Research › peer-review

Stéen, EJL, Nyberg, N, Lehel, S, Andersen, VL, Di Pilato, P, Knudsen, GM , Kristensen, JL & Herth, MM 2017, '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', Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 2, pp. 319-322. https://doi.org/10.1016/j.bmcl.2016.11.048

Stéen EJL, Nyberg N, Lehel S, Andersen VL, Di Pilato P, Knudsen GM et al. 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. Bioorganic & Medicinal Chemistry Letters. 2017 Jan 15;27(2):319-322. doi: 10.1016/j.bmcl.2016.11.048

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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 (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.",

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AU - Stéen, E Johanna L

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AU - Lehel, Szabolcs

AU - Andersen, Valdemar L

AU - Di Pilato, Pantaleo

AU - Knudsen, Gitte M

AU - Kristensen, Jesper L

AU - Herth, Matthias M

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AB - 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.

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