Medicinal chemistry building block

Johnson, D.E., Blower, P.E., Jr, Myatt, G.J., Wolfgang, G.H. Chem-tox informatics data mining using a medicinal chemistry building block approach. Curr. Opin. Drug Disc. Dev. 

TetrahydroisoquinoHnes and tetrahydro-(3-carbohnes, which represent exceedingly medicinally relevant building blocks, are mostly prepared according to the well-known Pictet-Spengler reaction [398]. A number of solid-phase applications of this reaction have been published in the recent literature, and thus it deserves a supplementary paragraph to those on the more general N-acyhminium and iminium ion chemistry (see above). 

The synthesis of nitriles from halides is valuable in medicinal chemistry because nitriles are flexible building blocks readily converted into carboxylic acids, amides, amines, or a variety of heterocycles, e. g. thiazoles, oxazolidones, triazoles, and tetrazoles. The importance of the tetrazole group in medicinal chemistry is easily understood if we consider that it is the most commonly used bioisostere of the carboxyl group. 

The discovery of this lead compound as a potent PDF inhibitor was a result of an integrated combinatorial and medicinal chemistry approach based on the proposed generic PDF inhibitor structure. This focused chemical library was designed by Chen et al. [79], and was prepared using solid-phase parallel synthesis in which 22 amines and 24 amino acids were used as building blocks, as outlined in Scheme 23. 

This chapter has provided an introduction to the ideas underlying the quantum theory of atoms in molecules, the theory that gives theoretical expression to chemical concepts and enables one to employ these concepts in a quantitative manner for prediction and for understanding of chemical problems. The theory is particularly well-suited to problems in medicinal chemistry where the important role of building block molecules enables one to make maximum use of the transferability of atoms and groups defined as open quantum systems. 

As a result, practical solutions for building block and library designs usually incorporate some aspect of biological targeting and expertise in medicinal chemistry. 

These seven groups of compounds, and the diversity of compounds within each group, are the molecular building blocks that enable structure and function. A brief overview of the relevant biochemistry for each class is pertinent to an appreciation of their role in medicinal chemistry and drug design. 

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