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ID: ALA4330125

Journal: Bioorg Med Chem Lett

Title: Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores - A cautionary disclosure.

Authors: Acton B, Small HF, Smith KM, McGonagle A, Stowell AIJ, James DI, Hamilton NM, Hamilton N, Hitchin JR, Hutton CP, Waddell ID, Ogilvie DJ, Jordan AM.

Abstract: 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.

CiteXplore: 30616904

DOI: 10.1016/j.bmcl.2018.12.066