Polar surface area

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Polar surface area (in red) of paracetamol

The polar surface area (PSA) of a molecule is defined as the surface sum over all polar atoms, primarily oxygen and nitrogen, also including their attached hydrogens.

PSA is a commonly used medicinal chemistry metric for the optimisation of a drug's ability to permeate cells. Molecules with a polar surface area of greater than 140 angstroms squared tend to be poor at permeating cell membranes. [1] For molecules to penetrate the blood–brain barrier (and thus act on receptors in the central nervous system), a PSA less than 90 angstroms squared is usually needed.[2]

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  1. ^ Pajouhesh H, Lenz GR (Oct 2005). "Medicinal Chemical Properties of Successful Central Nervous System Drugs.". NeuroRx. 2 (4): 541–553. doi:10.1602/neurorx.2.4.541. 
  2. ^ Hitchcock SA, Pennington LD (May 2006). "Structure - Brain Exposure Relationships". J Med. Chem. 49 (26): 7559–7583. doi:10.1021/jm060642i. 
  • Pajouhesh H, Lenz GR. Medicinal Chemical Properties of Successful Central Nervous System Drugs. NeuroRx. 2005 Oct; 2(4): 541–553. doi: 10.1602/neurorx.2.4.541
  • Clark, D.E., Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J.Pharm.Sci. 1999, 88, 807-814. (doi:10.1021/js9804011)
  • Palm, K., Stenberg, P., Luthman, K., Artursson, P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 1997, 14, 568–571. (doi:10.1023/A:1012188625088)
  • Ertl, P., Rohde, B., Selzer, P. Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties. J. Med. Chem. 2000, 43, 3714–3717. (doi:10.1021/jm000942e)
  • Ertl, P. Polar Surface Area, in Molecular Drug Properties, R. Mannhold (ed), Wiley-VCH, pp. 111–126, 2007
  • Shityakov, S., Neuhaus, W., Dandekar, T., Förster, C. Analysing molecular polar surface descriptors to predict blood-brain barrier permeation. Int. J. Comput. Biol. Drug Des. 2013, 6(1-2), 146-156. (doi: 10.1504/IJCBDD.2013.052195)

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