학술논문

Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores – A cautionary disclosure.
Document Type
Article
Source
Bioorganic & Medicinal Chemistry Letters. Feb2019, Vol. 29 Issue 4, p560-562. 3p.
Subject
*CYCLOPROPYLAMINES
*FLUORINATION
*ADENOSINE diphosphate ribose
*PHARMACEUTICAL chemistry
*IN vivo studies
Language
ISSN
0960-894X
Abstract
Graphical abstract 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. [ABSTRACT FROM AUTHOR]