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"Multi-component Reactions : Emerging Chemistry in Drug Discovery" 'From Xylocain to Crixivan'

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Abstract:



With the recent emergence of combinatorial chemistry and high-speed parallel synthesis for drug discovery applications, the multi-component reaction (MCR) has seen a resurgence of interest. Easily automated one-pot reactions, such as the Ugi and Passerini reactions, are powerful tools for producing diverse arrays of compounds, often in one step and high yield. Despite this synthetic potential, the Ugi reaction is limited by producing products that are flexible and peptide-like, often being classified as ‘non drug-like’. This review details developments of new, highly atom-economic MCR derived chemical methods, which enable the fast and efficient production of chemical libraries comprised of a variety of biologically relevant templates. Representative examples will also be given demonstrating the successful impact of MCR combinatorial methods at different stages of the lead discovery, lead optimization and pre-clinical process development arenas. This will include applications spanning biological tools, natural products and natural product-like diversity, traditional small molecule and ‘biotech’therapeutics respectively. In particular, this review will focus on applications of isocyanide based MCR (IMCR) reactions.

Keywords: Crixivan; Drug Discovery; Emerging Chemistry; Multi-component Reactions; Xylocain; biotech

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867033368600

Publication date: January 1, 2003

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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