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How medicinal chemists learned about log P

Abstract

Although log P is now recognized to be a key factor that determines the bioactivity of a molecule, the focus of medicinal chemists on hydrophobicity and log P started with the quantitative structure–activity relationships (QSAR) publications of Hansch and Fujita. Their original publication represents a dramatic change of focus to incorporate consideration of log P after a decade of work unsuccessfully attempting to use the Hammett equation to explain the structure-activity relationships of plant growth regulators. QSAR allows one to explore the quantitative relationship between log P and biological activity even when other factors also influence potency. In particular, Hansch’s publications of thousands of QSAR equations demonstrate that a relationship of biological activity with log P is indeed a general phenomenon. Hansch’s group also provided data and tools that enable others to explore the relationship between log P and the biological activity of compounds of interest.

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Correspondence to Yvonne Connolly Martin.

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Martin, Y.C. How medicinal chemists learned about log P. J Comput Aided Mol Des 32, 809–819 (2018). https://doi.org/10.1007/s10822-018-0127-9

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Keywords

  • QSAR
  • Hydrophobicity
  • Log P
  • Quantitative structure–activity relationships
  • Hansch
  • Fujita
  • Overton
  • Meyer
  • Collander