Info

Targeted libraries:

Targeted libraries:

Fingerprints 192 (192)

Substructure descriptors 189 (192)

3-D -autocorrelation 180 (192)

Random library 192 (192)

32 16.9

7.7.4 Summary

The examples demonstrate opportunities of computer-assisted optimization in library design. The quality of combinatorial libraries can be improved by computing similarities of vir-

tual compounds or by estimation of activities [7,109]. However, high diversity and high hit rates are usually not attainable in one library, and must be addressed in different design steps.

The examples also show that the benefit of a theoretical investigation depends on the methods used -the choice of descriptors is especially crucial. Different descriptors must be applied for different design tasks, and all scientists who use computer-assisted library design methods should know the characteristics of basic descriptor sets.

On the other hand, differences in mapping and clustering algorithms have only a minor influence on the result, and may be applied as "black boxes". The results of diversity assessment and similarity computation can provide valuable information about combinatorial libraries at an early stage (even before synthesis).This information helps the chemist to select certain building blocks or libraries.

Last, but not least, the importance of a close co-operation between the computational and the medicinal chemist is to be highlighted. Only the combination of theoretical investigations and experience of medicinal chemists allows goal-directed design of optimized combinatorial libraries.

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8 Organic reactions on solid phase -A survey of the literature from 1970 to 1998

Anne Scannell-Lansky and Christian Zechel

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