Lipinski’s rule of five, famous extensions and famous exceptions

Chemia Naissensis Volume 3, No.1 (2020) (стр. 171-181) 

АУТОР(И) / AUTHOR(S): Violeta Ivanović, Miroslav Rančić, Biljana Arsić, Aleksandra Pavlović

Е-АДРЕСА / E-MAIL: violeta.ivanovic@pmf.edu.rs

Download Full Pdf   

DOI: 10.46793/ChemN3.1.171I

САЖЕТАК / ABSTRACT:

Mathematical models show qualitative and quantitative dependencies between the structure, physico- chemical properties and activities of the investigated compounds. There are different rules for the prediction of good bioavailability, and one of the most well-known is the Lipinski rule. The rule is related to the molecular properties important for a drug’s pharmacokinetics in the human body: absorption, distribution, metabolism, and excretion (ADME). In addition to the Lipinski rule, there are reported different combinations of criteria that are important predictors of permeability. An additional rule was proposed by Veber. He compared the oral bioavailability of the compound and the permeability of the compound with the molecular flexibility.

КЉУЧНЕ РЕЧИ / KEYWORDS:

absorption, acceptors, biological activity, donors, exceptions

ЛИТЕРАТУРА / REFERENCES:

  • Apostolov S., & Vastag D. (2017). Proučavanje lipofilnosti potencijalno biološki aktivnih derivata cijanoacetamida. Journal of Engineering & Processing Management, 9 (1), 01-09.
  • Congreve, M., Carr, R., Murray, C., & Jhoti, H. (2003). A “rule of three” for fragment-based lead discovery? Drug Discovery Today, 8, 876-877.
  • Lipinski, C. A., Lombardo F., Dominy B. W., & Feeney P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23, 3-25.
  • Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46, 3–26.
  • Petit, J., Meurice, N., Kaiser, C., & Maggiora, G. (2012). Softening the Rule of Five—where to draw the line? Bioorganic and Medicinal Chemistry, 20,5343–5351.
  • Pollastri, M. (2010). Overview on the Rule of Five. Department of Chemical Biology, Northeastern University, Boston, Massachusetts, 49:9.12.1-9.12.8.