Lead optimization, integrated

If small or medium libraries for lead optimization are demanded and all synthetic products are to be screened individually, most often parallel synthesis is the method of choice. Parallel syntheses can be conducted in solution, on solid phase, with polymer-assisted solution phase syntheses or with a combination of several of these methods. Preferably, parallel syntheses are automated, either employing integrated synthesis robots or by automation of single steps such as washing, isolation, or identification. The latter concept often allows a more flexible and less expensive automation of parallel synthesis. 

These presented examples of quantitative descriptions of protein-ligand interactions remain to be a very promising area to address affinity and the selectivity challenge in the future. Those approaches are collectively seen as interesting for a more integrated lead optimization on a simultaneous consideration of numerous balanced descriptors and models for optimization. 

Kariv, I., Rourick, R.A., Kassel, D.B., and Chung, T.D.Y. Improvement of hit-to-lead optimization by integration of in vitro HTS experimental models for early determination of pharmacokinetic properties. Comb. Chem. High Throughput Screen. 2002, 5, 459-472. 

Bryant, M. S. Veals, J. Ng, K. et ah HPLC-APl/MS/MS a powerful tool for integrating drug metabolism into the drug discovery process. Drug Discov Today 1997, 2, 532-537. Korfmacher, W. A. Lead optimization strategies as part of a drug metabolism environment. Curr Opin Drug Discov Dev 2003, 6, 481-485. 

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