Library privileged scaffold

A list of privileged scaffolds - several of which are natural-product derived - for target-family-biased combinatorial libraries was recently presented by Muller [94], These scaffolds were proven to produce biologically active compounds for more than one member of a given target family. A rough-and-ready in-silico evaluation... 

Figure 13.13 SOM showing the distribution of known serine protease inhibitors (left), and a virtual combinatorial library that was constructed around a serine protease-privileged scaffold [94], Red areas indicate high compound density. Note that each map forms a torus.

Figure 13 Four examples of biologically active compounds discovered from libraries based on the tetrahydro-P-carboline natural product privileged scaffold...

Libraries Based on a Privileged Scaffold-Discovery of Fexaramine... 

Fig. 15.4-5 Examples of CPCR active the library against several CPCRs led to the compounds based on the 2-aryl-indoles discovery of NPYs, NKi, chemokine privileged scaffold identified from a focused CCR3/CCR5, serotonin 5-HT2a/5-HT6. and combinatorial library at Merck. Screening of SST4 receptor antagonists [91].

Compound library designed around selected, often privileged scaffolds tailored toward targeting specific protein families (GPCRs, kinases, etc.). 

Welsch, ME, Snyder, S.A., and Stockwell, B.R. (2010) Privileged scaffolds for library design and drug discovery. Curr. Opin. Chem. Biol., 14, 347 -361. 

In this chapter, we present an overview of domino reactions that have been used to construct various types of compound libraries targeting either natural product (NP) structures and privileged scaffolds or diverse ring systems. 

The utility of the privileged structure concept is illustrated by compound library synthesis based on the indole scaffold and the biologically active compounds resulting from that. The indole scaffold is found in natural products, like for example, the neurotransmitter serotonin (5-hydoxytriptamine, 5-HT) and in well-know drugs, like for example, the... 

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. ... 

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