Monday, 6 April 2009

Physicochemical properties

Fragments typically have to be screened at high concentration because they normally only bind weakly to their targets and the physicochemical property most relevant to FBDD is aqueous solubility. Both charge state and lipophilicity influence solubility in aqueous media.


Avdeef, Physicochemical profiling (solubility, permeability, and charge state). Curr. Top. Med. Chem. 2001, 1, 277-351 Link

Hydrogen bonding

Kenny, Hydrogen bonding, electrostatic potential, and molecular design. J. Chem. Inf. Model. 2009, 49, 1234-1244 DOI

Laurence & Berthelot, Observations on the strength of hydrogen bonding. Perspect. Drug Discov. Des. 2000, 18, 39-60 DOI

Kenny, Prediction of hydrogen bond basicity from computed molecular electrostatic properties: implications for comparative molecular field analysis. J. Chem. Soc., Perkin Trans. 2, 1994, 199-202 DOI

Abraham et al, Hydrogen bonding. Part 9. Solute proton donor and proton acceptor scales for use in drug design. J. Chem. Soc., Perkin Trans. 2, 1989, 1355-1375 DOI

Partition coefficients

Toulmin et al, Toward Prediction of Alkane/Water Partition Coefficients. J. Med. Chem. 2008, 51, 3720-3730 DOI

Leahy et al, Model solvent systems for QSAR. Part 2. Fragment values (f-values) for the critical quartet. J. Chem. Soc., Perkin Trans. 2, 1992, 723-731 DOI


Colclough et al, High throughput solubility determination with application to selection of compounds for fragment screening. Bioorg. Med. Chem. 2008, 16, 6611-6616 DOI

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