ACD/LogP - Rule of 5

Both ACD/LogP DB and ACD/LogP Batch can check whether your compound meets the "Rule of 5" requirements and report this information after logP calculation is complete.

"The Rule of 5" got its name from the cutoff values for each of the four parameters that define the "drug-likeness" of the potential drug candidates: all of these values are close to five or a multiple of five.

The quote from: Christopher A. Lipinski, Franco Lombardo, Beryl W. Dominy, Paul J. Feeney "Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings", Adv. Drug Delivery Rev., 1997, 23(1-3), 3-25:

"In the USAN set we found that the sum of Ns and Os in the molecular formula was greater than 10 in 12% of the compounds. Eleven percent of compounds had a MWT of over 500. Ten percent of compounds had a CLogP larger than 5 (or an MLogP larger than 4.15) and in 8% of compounds the sum of OHs and NHs in the chemical structure was larger than 5. The "rule of 5" states that: poor absorption or permeation is more likely when:

1. There are more than 5 H-bond donors (expressed as the sum of OHs and NHs).
2. The MWT is over 500.
3. The LogP is over 5 (or MLogP is over 4.15).
4. There are more than 10 H-bond acceptors (expressed as the sum of Ns and Os).

Compound classes that are substrates for biological transporters are exceptions to the rule."

If two parameters are out of range, a "poor absorption or permeability is possible" alert is a very visible educational tool for the chemist and serves as a tracking tool for the research organization.

"Rule of 5": How do these common compounds measure up?

See also: The Design of Drug-Like Properties by C. Lipinski.