Combinatorial chemistry history

Molecular diversity has a relatively brief history, which began in the late eighties and somewhat parallels the development of combinatorial chemistry [1]. Unlike molecular similarity [2-4], which is a pairwise measure, molecular diversity is a measure of the similarity distribution over a population of molecules. Alternatively, molecular diversity can be assessed in terms of the dissimilarity distribution over a population of molecules since the dissimilarity of two molecules i and j is the complement of their similarity, that is D i,j) = 1 — S i,j). 

Combinatorial chemistry has an unusual patent history. No single company or individual has control of any one strategic patent and there is no single strategic patent that defines the field. Many companies have patents that enable them to pursue unique chemistries, and this provides investors with many choices. On the other side, exclusivity is reduced. 

AIDS, hepatitis, blood disorders, multiple sclerosis and others. At present, another 300 potential therapeutics are in various human clinical trials, although it is impossible to estimate how many of those will actually reach the marketplace. Combinatorial chemistry promises to revolutionize the rate of new-drug development by accelerating initial lead generation. Already, in its approximately 8-year corporate history, combinatorial chemistry has produced about 350 leads in various stages of preclinical development. 

In closing, we suggest that interested readers should consult the following three recent review papers that demonstrate how, even today, almost 20 years into the combinatorial chemistry era, chemists and biologists are still learning chemical history from Nature —the review by Kaiser et al. on biology-inspired compound libraries,88 and the two reviews on natural products in the modern age by Ganesan89 and Butler.90... 

Beeren SR, Sanders JKM (2010) History and principles of dynamic combinatorial chemistry. In Reek JNH, Otto S (eds) Dynamic combinatorial chemistry. Wiley-VCH, Weinheim... 

Application of this procedure at each step of a multistep synthesis either before or after addition of a ligand monomer, but prior to pooling the resin, allows the chemical reaction history of each bead to be labeled. Approximately 10% ( 30 pmol) of the reactive sites of a bead are tagged, with the rest being available for ligand synthesis. It is essential that any encoding scheme be compatible with the specific combinatorial chemistry of the ligand synthesis. 

Combinatorial chemistry and combmatonal technologies fall into a new interdisciplinary field joining combmatonal informatics with automated synthesis of chemical "libranes" followed by automated screening, with the mam output m medicinal chemistry and drug discovery This nascent technology has produced more new compounds in just a few years than the pharmaceutical industry did m its entire previous history... 

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