Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores – a cautionary disclosure.

Ben Acton; Helen Small; Kate Smith; Alison Mcgonagle; Alexandra Stowell; Dominic James; Niall Hamilton; Nicola Hamilton; James Hitchin; Colin Hutton; Ian Waddell; Donald Ogilvie; Allan Jordan

doi:83288294

Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores – a cautionary disclosure.

Ben Acton
, Helen Small
, Kate Smith
, Alison Mcgonagle
, Alexandra Stowell
, Dominic James
, Niall Hamilton
, Nicola Hamilton
, James Hitchin
, Colin Hutton
, Ian Waddell
, Donald Ogilvie
, Allan Jordan

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	560-562
Number of pages	2
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	4
Early online date	2 Jan 2019
DOIs	https://doi.org/83288294
Publication status	Published - 15 Feb 2019

Keywords

Ataxia
Animal welfare
Toxicophore

Research Highlights, Institutes and Platforms

Manchester Cancer Research Centre

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83288294Licence: CC BY

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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. ",

keywords = "Ataxia, Animal welfare, Toxicophore",

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T1 - Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores – a cautionary disclosure.

AU - Acton, Ben

AU - Small, Helen

AU - Smith, Kate

AU - Mcgonagle, Alison

AU - Stowell, Alexandra

AU - James, Dominic

AU - Hamilton, Niall

AU - Hamilton, Nicola

AU - Hitchin, James

AU - Hutton, Colin

AU - Waddell, Ian

AU - Ogilvie, Donald

AU - Jordan, Allan

PY - 2019/2/15

Y1 - 2019/2/15

N2 - 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.

AB - 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.

KW - Ataxia

KW - Animal welfare

KW - Toxicophore

UR - https://www.scopus.com/pages/publications/85059476959

U2 - 83288294

DO - 83288294

M3 - Article

SN - 0960-894X

VL - 29

SP - 560

EP - 562

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores – a cautionary disclosure.

Abstract

Keywords

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