Synthetic Compound Libraries

Amlodipine 20 Calcium-channel (blocker) Analog of nifedipine Synthetic compound libraries derived from the Hantzch reaction Overcame short duration- Angina and hypertension Peripheral vasculature... 

Woiwode, T.R ef a/. Synthetic compound libraries displayed on the surface of encoded bactenophage. Chem. Biol. 10, 847-858 (2003). 

This chapter presents methods and protocols suitable for the identification and characterization of inhibitors of the prokaryotic and/or eukaryotic translational apparatus as a whole or targeting specific, underexploited targets of the bacterial protein synthetic machinery such as translation initiation and amino-acylation. Some of the methods described have been used successfully for the high-throughput screening of libraries of natural or synthetic compounds and make use of model universal mRNAs that can be translated with similar efficiency by cellfree extracts of bacterial, yeast, and HeLa cells. Other methods presented here are suitable for secondary screening tests aimed at identifying a ... 

Parallel processing of synthetic operations has been one of the cornerstones of medicinal and high-throughput synthesis for years. In the parallel synthesis of compound libraries, compounds are synthesized using ordered arrays of spatially separated reaction vessels adhering to the traditional one vessel/one compound philosophy. The defined location of the compound in the array provides the structure of the compound. A commonly used format for parallel synthesis is the 96-well microtiter plate, and today combinatorial libraries comprising hundreds to thousands of compounds can be synthesized by parallel synthesis, often in an automated fashion. 

We still need much better medicines to cure cancer, heart disease, stroke, and Alzheimer s disease. We need better drugs to deal with obesity, diabetes, arthritis, and schizophrenia. The treatments of diabetes, arthritis, and mental defects such as schizophrenia or manic depression are not yet cures, just ways to keep the symptoms under control. Cures are needed. Insights from genetics may help guide us toward elegant and rational cures, but we will also make use of screens to identify natural products and libraries of randomly generated synthetic compounds (combinatorial chemistry). A semi-empirical approach may be the best hope over the next two decades to yield drugs to alleviate these diseases. 

Fig. 18.5 A typical compound library. Compounds are clustered in descriptor space (for example, around synthetically accessible scaffolds). For clusters with overlapping neighborhoods, efficiency may be increased by testing representative compounds from each cluster analogs of hits...

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