Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369433 | Bioorganic & Medicinal Chemistry Letters | 2016 | 5 Pages |
Abstract
A number of new nucleoside derivatives are disclosed as inhibitors of DOT1L activity. SARs established that DOT1L inhibition could be achieved through incorporation of polar groups and small heterocycles at the 5-position (5, 6, 12) or by the application of alternative nitrogenous bases (18). Based on these results, CN-SAH (19) was identified as a potent and selective inhibitor of DOT1L activity where the polar 5-nitrile group was shown by crystallography to bind in the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group can be used as a non-traditional replacement for heavy halogen atoms.
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Related Topics
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Organic Chemistry
Authors
Sophie S. Spurr, Elliott D. Bayle, Wenyu Yu, Fengling Li, Wolfram Tempel, Masoud Vedadi, Matthieu Schapira, Paul V. Fish,