Tautomerism in drug discovery

Abstract

The influence of tautomerism on the precise structure of drugs and thus of their potential to interact with biological systems is discussed from thermodynamic and kinetic aspects. The types of tautomerism encountered in the structure of drugs in current use are surveyed together with the effect of pH, solvent polarity, and temperature.

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Notes

  1. 1.

    The indistinct line between slowly inter-converting tautomers and structural isomers is generally considered to fall somewhere in between CH/CH tautomerism (ΔG ≈ 25–35 kcal mol−1) and cis/trans isomers (ΔG ≥ 60 kcal mol−1 since the average energy for cleavage of a π bond is 63 kcal mol−1).

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Correspondence to Alan R. Katritzky.

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Katritzky, A.R., Hall, C.D., El-Gendy, B.ED.M. et al. Tautomerism in drug discovery. J Comput Aided Mol Des 24, 475–484 (2010). https://doi.org/10.1007/s10822-010-9359-z

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Keywords

  • Tautomerism
  • Heterocycles
  • Energetics
  • Biological processes
  • Drugs