Abstract
The protein-protein interaction of p53 and mdm2 is an important anticancer target. The interface, however, is very hydrophobic and naturally results in very hydrophobic antagonists. We used the Orru three component reaction (O-3CR) along with a rapid and efficient, recently discovered amidation reaction to dramatically improve the water solubility of our recently discovered low molecular weight p53/mdm2 antagonists. Arrays of amides were synthesized with improved hydrophilicity and retainment and/or improvement of p53/mdm2 inhibitory activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Combinatorial Chemistry Techniques / economics
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Combinatorial Chemistry Techniques / methods*
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Humans
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Hydrophobic and Hydrophilic Interactions
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Imidazolines / chemical synthesis*
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Imidazolines / chemistry
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Models, Molecular
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Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
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Solubility
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Tumor Suppressor Protein p53 / antagonists & inhibitors*
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Water / chemistry*
Substances
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Amides
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Imidazolines
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Tumor Suppressor Protein p53
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Water
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2