Lipinski's rule of five

The Rule of Five (English for " 5- rule" ) is a rule of thumb for the oral bioavailability of a chemical compound. It was erected in 1997 by the chemist Christopher Lipinski. Lipinski noted that many common drugs are relatively small and lipophilic molecules. The "Rule of Five" is used for example in pharmaceutical research, to assess whether a newly developed drug can be used as an oral drug.

Definition

A chemical compound has good oral bioavailability, if it meets the following conditions:

  • Not more than five donors of hydrogen bonds (eg, OH or NH groups )
  • Not more than ten acceptors of hydrogen bonds (eg, oxygen or nitrogen atoms )
  • A molecular mass of not more than 500 g / mol
  • A partition coefficient (log P) between octanol and water ( octanol - water partition coefficient) of a maximum of 5

The name " Rule of Five " comes from the fact that all numerical values ​​equal to or an even multiple of five are.

Extensions

For better assessment of drug likeness the original rules were extended to 1999 by Ghose et al. published:

  • The partition coefficient ( log P) is in a range between -0.4 and 5.6
  • The molecular refraction is between 40 and 130
  • The molar mass is 160-480
  • The total number of atoms is between 20 and 70
Active ingredient Digital Object Identifier
514826
de