rule of five

https://doi.org/10.1351/goldbook.11507

The rule of five states that molecules that violate two or more of the following rules are likely to have permeability problems; (1) CLOGP calculated octan-1-ol-water log P greater than 5.0; (2) molecular weight greater than 500; (3) more than five hydrogen bond donors; and (4) the sum of oxygen and nitrogen atoms is greater than 10.

Notes:
  1. Natural products, peptides and other substrates for biological transporters are exceptions.
  2. The original authors also noted that one can calculate the octan-1-ol-water log P with the program MLOGP for which the cut-off is \(\pu{4.15}\). Users often use log P’s calculated with other programs or measured values.
Source:
PAC, 2016, 88, 239. (Glossary of terms used in computational drug design, part II (IUPAC Recommendations 2015)) on page 255 [Terms] [Paper]
Citation: 'rule of five' in IUPAC Compendium of Chemical Terminology, 5th ed. International Union of Pure and Applied Chemistry; 2025. Online version 5.0.0, 2025. https://doi.org/10.1351/goldbook.11507 RIS BibTex EndNote
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