Biological space combinatorial libraries

Figure 1 Representation of some of the interfaces between biology and chemistry space (a) the continuum of chemistry space continuum with representative regions of specific biological activity highlighted (b) large combinatorial libraries seek to cover as much space as possible across several biological families but with one core scaffold (c) smaller focused libraries, shown as the small blue cubes, are designed with relevant biological targets in mind and(d) libraries that do not overlap with relevant biological space are undesirable...

The success of both target-based and phenotype-based methods relies heavily on the qualities of the chemical libraries used. Although combinatorial technologies allow the synthesis of a large number of molecules with immense structural diversity, it is impossible to saturate the chemical space, which has been estimated to contain more than 10 molecules (8). Because biological space interacts with only a fraction of chemical space, synthetic attempts to increase randomly the molecular... 

Fig. 15.1-3 Schematic visualization of the various concepts to address chemical and biological space (shaded areas) in drug discovery. Medicinal chemistry focused on compound series (red dots) that had shown activity in pharmacological assays and compound optimization was driven by a tight feedback from biological experiments, leading to a focused nonarrayed addressing of chemical space. The combinatorial promise was to systemically explore the chemical space with diverse arrays of compounds (blue dots) to find the suitable starting points. Analysis of combinatorial chemistry libraries showed their limited...

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