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- W2057232072 abstract "A variety of small-molecule combinatorial libraries have been prepared on solid support using a binary encoding strategy employing non-sequenceable encoding molecules. Library members are attached to the support using photolabile linkers which permit their release for assay free in solution. The encoding molecules are attached using a carbene insertion reaction and are released via oxidation. A wide variety of synthetic reactions have been utilized for library synthesis including, for example, cyclocondensations, reductive aminations, and heteroaromatic halide displacements, as well as acylations and sulfonylations. Initial screening of two such libraries identified lead structures for the inhibition of carbonic anhydrase. Subsequently, based upon these leads a smaller focused combinatorial library was constructed and used to analyze the structure-activity relationships (SARs) governing enzyme inhibition and isozyme selectivity. The combination of random screening with a broad diversity of compounds, followed by focused libraries for detailed SARs and selectivity, demonstrates the power of binary encoded small-molecule combinatorial libraries for drug discovery." @default.
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- W2057232072 date "1995-04-01" @default.
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- W2057232072 title "Binary encoded small-molecule libraries in drug discovery and optimization" @default.
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