Drug-like space

Today s drug targets are less druggable than in the past [23] the low-hanging fruit in the center of drug-like space has already been picked... 

A recent report presented the so-called MultiLevel Chemical Compatibility (MLCC) to determine the similarity of any structure to known drug-compatible compounds from representative databases (124) although by definition incomplete, as all the drug-like space is far from being determined, this and similar tools can... 

Improvement of coverage of the chemical space within a drug-like space and away from the industrial chemicals space that is currently dominating the toxicity databases. 

If this is true then why does so much of medicinal chemistry, and hence drug discovery, still suffer from a lack of awareness of these facts After all they can save enormous amounts of time and money that are spent on taking forward compounds that fall outside of drug-like space until they predictably failed. 

Table 1.1 Drug-like space guidance on physchem properties.

If one begins to venture outside of drug-like space (e.g., PPIs), then the numbers would be expected to be significantly higher than 10 °. One can then begin to understand why an SAR by your favorite chemical vendor approach to... 

Available "drug-like" space Typical screening collection... 

In this context, it is important to mention that various attempts have been made in recent years to stmnount this barrier, particularly using statistical analysis to define descriptors for small-molecule, drug-like space. The most familiar approach is Lipimki s Rule of Five that predicts oral absorption on the basis of values containing 5 for log P, molecular weight and H-bond donors and acceptors [15]. Other approaches consider the importance of parameters such as the number of rotatable bonds and polar surface area (PSA) [16]. 

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