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Molecular Libraries in Liquid Phase Via Ugi-Mcr

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Abstraet--Standard chemistry prescribes the conversion of one or two compounds into their products. In contrast, Eintopf (one-pot) multicomponent reactions (MCRs) involve at least three different compounds. One-pot MCRs are a useful tool in combinatorial chemistry: From a mixture of educts a large number of products can be simultaneously formed in liquid phase, called a soluble molecular library. The member compounds of such libraries are investigated simultaneously for desired properties, e.g. antibiotic activity. The main constraint is, that the underlying chemistry must not produce unknown side reactions and must lead to a broad spectrum of stable products with high yields. Isocyanide multicomponent chemistry allows the generation of soluble libraries of very different sizes, which are easy to screen for biological or pharmaceutical efficacy using the algorithms presented. Products can easily be enumerated and the kinetics of the isocyanide chemistry is simple to investigate. Combinatorial chemistry is capable of generating and optimizing leads faster and with fewer resources than by conventional means. Combinatorial chemistry based on isocyanide chemistry is by far the most important and most impressive technique in use today to reducing time and costs associated with lead generation and optimization during the drug discovery process. The simplicity of the reaction conditions involved means that the generation and screening of libraries can be automated.

Affiliations: 1: Institute für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstr. 4, D-85747 7 Garching, Germany; 2: Department of Chemistry CYN-2, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.


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