Fluorination of metabolic hotspots in a molecule is a common medicinal chemistry strategy to improve in vivo half-life and exposure and, generally, this strategy offers significant benefits. Here, we report the application of this strategy to a series of poly-ADP ribose glycohydrolase (PARG) inhibitors, resulting in unexpected in vivo toxicity which was attributed to this single-atom modification.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376317PMC
http://dx.doi.org/10.1016/j.bmcl.2018.12.066DOI Listing

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