Abstract
The search for new lead structures and the optimization of their activity profile by systematic modification belong to the time- and cost-demanding steps in drug research. The optimization of a small organic molecule can serve as an example. Even if the number of different groups per position is limited to relatively few, in the case of the multisubstituted tetrahydroisoquinoline carboxylic acid amide 11.1 (Fig. 11.1) several million structures are possible. The combinatorial explosion of all imaginable substitution possibilities can no longer be realized with classical chemical techniques. The diversity increases even more when the different stereoisomers are considered. Their number is already considerably larger than the number of all of the compounds referenced in Chemical Abstracts (33 million) or in Beilstein (10 million compounds).
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Klebe, G. (2013). Combinatorics: Chemistry with Big Numbers. In: Klebe, G. (eds) Drug Design. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17907-5_11
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