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Issue 11, 2018
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Metabolism and hydrophilicity of the polarised ‘Janus face’ all-cis tetrafluorocyclohexyl ring, a candidate motif for drug discovery

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Abstract

The metabolism and polarity of the all-cis tetra-fluorocyclohexane motif is explored in the context of its potential as a motif for inclusion in drug discovery programmes. Biotransformations of phenyl all-cis tetra-, tri- and di- fluoro cyclohexanes with the human metabolism model organism Cunninghamella elegans illustrates various hydroxylated products, but limited to benzylic hydroxylation for the phenyl all-cis tetrafluorocyclohexyl ring system. Evaluation of the lipophilicities (log P) indicates a significant and progressive increase in polarity with increasing fluorination on the cyclohexane ring system. Molecular dynamics simulations indicate that water associates much more closely with the hydrogen face of these Janus face cyclohexyl rings than the fluorine face owing to enhanced hydrogen bonding interactions with the polarised hydrogens and water.

Graphical abstract: Metabolism and hydrophilicity of the polarised ‘Janus face’ all-cis tetrafluorocyclohexyl ring, a candidate motif for drug discovery

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Article information


Submitted
18 Jan 2018
Accepted
17 Feb 2018
First published
19 Feb 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2018,9, 3023-3028
Article type
Edge Article

Metabolism and hydrophilicity of the polarised ‘Janus face’ all-cis tetrafluorocyclohexyl ring, a candidate motif for drug discovery

A. Rodil, S. Bosisio, M. S. Ayoup, L. Quinn, D. B. Cordes, A. M. Z. Slawin, C. D. Murphy, J. Michel and D. O'Hagan, Chem. Sci., 2018, 9, 3023
DOI: 10.1039/C8SC00299A

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