Fragment libraries focused sets

In the technique of post hoc design, a set of descriptors are built up by examination of a set of compounds active at a particular receptor family or sub-class. Normally, the set of drugs would be from a commercial database such as MDDR or the Merck Index, etc. and the descriptors would usually be substructural fragment or key based. One example would be the GPCR-PA+ sub-class referred to above, where BCUT descriptors have been used to aid the design of a focused library of aroimd 2000 compoimds based on 8 scaffolds. Libraries have also been constructed based on peptidomimetic principles as well as on the concepts of privileged structures. ... 

Thus, both fragment-based and whole-molecule-based approaches require approximations. The fragment approach assumes that a diverse set of substituents will yield diverse libraries. The whole-molecule approach is very slow and also assumes that similarity can be adequately characterized by very crude computations. This chapter focuses on the fragment-based approach, calculating properties on the substituents only, the site of attachment being replaced by a dummy atom. 

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