Avoiding known threats

One approach to define a space of drug-like molecules is to do so by elimination. There are molecular features that in industry experience are known to cause toxicity, lack of 

In order to be bioavailable, a drag molecule must be transported through biological membranes. Therefore, molecular properties that correlate with poor membrane permeabihty (in the absence of active transport) can be used to filter out undesirable molecules. 

The Rule-of-Five (Ro5) is one of the best known and widely accepted drag-likeness filters. The Ro5 was derived from an analysis of 2,245 drag candidates from World Drag Index (WDl) with assigned United States Adopted Name (USAN) or International Proprietary Name (INN) that are believed to have reached Phase n trials. It states that a compound violating any two of the following rales is likely to be poorly absorbed  

number of hydrogen bond donors (OH or NH groups) equal or less than 5  

number of hydrogen bond acceptors less than 10  

---