Lipinski's Rule of Five
In 1997 Christopher A. Lipinski published a seminal paper identifying a series of features commonly found in orally active drugs. These features are referred to as Lipinski's rule of five and can be used as a rule of thumb to indicate whether a molecule is likely to be orally bioavailable (bioactive) (See also ADME). The "rule of five" is so called because most of the features start with the number five.
In general, an orally active drug has:
- not more than 5 hydrogen bond donors (OH and NH groups)
- not more than 10 hydrogen bond acceptors (notably N and O)
- a molecular weight under 500
- a LogP under 5
Lipinski's work has since been extended to include properties such as the number of rings and rotatable bonds.
References
- CA Lipinski, Adv. Drug Del. Rev. 1997, 23, 3