Rule of Five
The Rule of Five ( Engl. For "5-rule") is a rule of thumb for the oral bioavailability of a chemical compound . It was set up in 1997 by the chemist Christopher Lipinski . Lipinski found 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 substance has good oral bioavailability if it meets the following conditions:
- Not more than five donors of hydrogen bonds (e.g. OH or NH groups )
- No more than ten acceptors of hydrogen bonds (e.g. oxygen or nitrogen atoms )
- A molecular mass of no more than 500 Daltons
- A distribution coefficient ( log P ) between octanol and water ( octanol-water distribution coefficient ) of maximum 5
The name “Rule of Five” comes from the fact that all numerical values are equal or an even multiple of five.
Extensions
For a better assessment of druglikeness , the original rules were extended and 1999 by Ghose et al. published:
- The distribution coefficient (log P) lies in a range between -0.4 and +5.6
- The molecular refraction for "molar refractivity" is between 40 and 130
- The molar mass is between 160 and 480
- The total number of atoms is between 20 and 70
Individual evidence
- ↑ CA Lipinski, F. Lombardo, BW Dominy, PJ Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings , Adv. Drug Del. Rev., 2001, 46 , 3-26 ( doi : 10.1016 / S0169-409X (00) 00129-0 ).
- ↑ Arup K. Ghose, Vellarkad N. Viswanadhan John J. Wendoloski: In J. Combin. Chem. 1999, 55-68, A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery ( doi : 10.1021 / cc9800071 ).