In the discovery setting the Lipinski Alert Index, also known as 'the rule of 5' predicts that poor absorption or permeation is more likely when:

 

• there are more than 5 H-bond donors
• there are more than 10 H-bond acceptors
• the molecular weight is over 500
• the Moriguchi's logP is over 4.15

 

This computational alert is a filter that identifies compounds lying in a region of property space where the probability of useful oral activity is very low. A compound that fails the alert will likely be poorly bioavailable because of poor absorption or permeation [C.A.Lipinski, F.Lombardo, B.W.Dominy, P.J. Feeney, Advanced Drug Delivery Reviews 1997, 23, 3-25; C.A.Lipinski, F.Lombardo, B.W.Dominy, P.J. Feeney, Advanced Drug Delivery Reviews 2001, 46, 3-26].

The alert index is a dummy variable taking value 1 when two or more properties are out of range.

The 'H-bond donors' property is determined by adding all of the hydrogens bonded to Os and Ns. The 'H-bond acceptors' property is determined by adding all of the Os and Ns in the molecule. The Moriguchi MlogP is calculated according to the rules implemented in DRAGON, which parlty differ from those proposed in the Lipinski's papers.