Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: A new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6

摘要

A series of hydroxamate based HDAC inhibitors containing a phenylisoxazole as the CAP group has been synthesized using nitrile oxide cycloaddition chemistry. An HDAC6 selective inhibitor having a potency of -2 picomolar was identified. Some of the compounds were examined for their ability to block pancreatic cancer cell growth and found to be about 10-fold more potent than SAHA. This research provides valuable, new molecular probes for use in exploring HDAC biology.