Drug development combinatorial chemistry

To speed the process of drug discovery, combinatorial chemistry> has been developed to prepare what are called combinatorial libraries, in which anywhere from a few dozen to several hundred thousand substances are prepared simultaneously. Among the early successes of combinatorial chemistry is the development of a benzodiazepine library, a class of aromatic compounds much used as antianxiety agents. 

The identification of compounds with a desired property is a central pursuit in science. In the field of drug discovery combinatorial chemistry has played an increasingly important role for identification and optimization of drug leads which target therapeutically important biomolecules. For the successful implementation of combinatorial methods, new and innovative synthesis methods have been developed. Additionally, novel conceptual approaches to the design of compounds have been pursued to more efficiently generate libraries of small molecules. 

Burke, T.J., Loniello, K.R., Beebe, J.A. and Ervin, K.M. (2003) Development and application of fluorescence polarization assays in drug discovery. Combinatorial Chemistry High Throughput Screening, 6, 183-194. 

Today, it is obvious that in drug discovery combinatorial chemistry cannot displace natural product research. However, natural product chemistry can take advantage of combinatorial strategies. In our opinion, the discovery and development of innovative therapeutic agents will substantially benefit from the... 

Combinatorial chemistry for drug discovery is now extensively used. Hue et al. have developed combinatorial chemistry based on dynamic equilibration, in which a set of four amines and three aldehydes (attached to aromatic carboxylates, sulfonates, or sulfonamides) are mixed to yield 12 imines reversibly and these reaction mixtures were reduced.When this reaction was carried out in the presence of CA, the chemical yield derived from an aromatic sulfonamide derivative was almost doubled, implying that CA worked as a template to choose the best ligand. 

Howard, M.L., HiU, XX, GaUuppi, G.R., et al. (2010) Plasma protein binding in drug discovery and development. Combinatorial Chemistry and High Throughput Screening, 13,170-187. 

The major impetus for the development of solid phase synthesis centers around applications in combinatorial chemistry. The notion that new drug leads and catalysts can be discovered in a high tiuoughput fashion has been demonstrated many times over as is evidenced from the number of publications that have arisen (see references at the end of this chapter). A number of )proaches to combinatorial chemistry exist. These include the split-mix method, serial techniques and parallel methods to generate libraries of compounds. The advances in combinatorial chemistry are also accompani by sophisticated methods in deconvolution and identification of compounds from libraries. In a number of cases, innovative hardware and software has been developed tor these purposes. 

Combinatorial chemistry, a new chapter of organic synthesis, is now developing rapidly. This new approach to synthesizing large designed or random chemical libraries through application of solid phase synthetic methods, promises to revolutionize the process of drug discovery in the pharmaceutical industry.24... 

Since drug development has turned into a systematic and rational task of optimizing molecules and their interactions with proteins, cells, and organisms, combinatorial chemistry has become a significant part of this endeavor. Combinatorial methods are mainly employed in the initial (preclinical) stages of drug development. 

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