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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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dc.contributor.author | Rodil, Andrea | |
dc.contributor.author | Bosisio, Stefano | |
dc.contributor.author | Salah Ayoup, Mohammed | |
dc.contributor.author | Quinn, Laura | |
dc.contributor.author | Cordes, David B. | |
dc.contributor.author | Slawin, Alexandra M. Z. | |
dc.contributor.author | Murphy, Cormac | |
dc.contributor.author | Michel, Julien | |
dc.contributor.author | O'Hagan, David | |
dc.date.accessioned | 2018-02-27T11:30:08Z | |
dc.date.available | 2018-02-27T11:30:08Z | |
dc.date.issued | 2018-03-21 | |
dc.identifier | 252372855 | |
dc.identifier | 41506857-0c41-43de-a17b-d37a25f062c7 | |
dc.identifier | 85044082693 | |
dc.identifier | 000431100800020 | |
dc.identifier.citation | Rodil , A , Bosisio , S , Salah Ayoup , M , Quinn , L , Cordes , D B , Slawin , A M Z , Murphy , C , Michel , J & O'Hagan , D 2018 , ' Metabolism and hydrophilicity of the polarised ‘Janus face’ all- cis tetrafluorocyclohexyl ring, a candidate motif for drug discovery ' , Chemical Science , vol. 9 , no. 11 , pp. 3023-3028 . https://doi.org/10.1039/C8SC00299A | en |
dc.identifier.issn | 2041-6520 | |
dc.identifier.other | ORCID: /0000-0002-5366-9168/work/42023871 | |
dc.identifier.other | ORCID: /0000-0002-9527-6418/work/56861738 | |
dc.identifier.other | ORCID: /0000-0002-0510-5552/work/68281259 | |
dc.identifier.uri | https://hdl.handle.net/10023/12800 | |
dc.description | This work was supported by the Initial Training Network, FLUOR21, funded by the FP7 Marie Curie Actions of the European Commission (FP7-PEOPLE-2013-ITN-607787). JM is supported by a University Research Fellowship from the Royal Society. The research leading to these results has received funding from the European Research Council under the EU 7th Framework Programme (FP7/2007-2013)/ERC No 336289. | en |
dc.description.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) indicate 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. | |
dc.format.extent | 582323 | |
dc.language.iso | eng | |
dc.relation.ispartof | Chemical Science | en |
dc.subject | QD Chemistry | en |
dc.subject | NDAS | en |
dc.subject.lcc | QD | en |
dc.title | Metabolism and hydrophilicity of the polarised ‘Janus face’ all-cis tetrafluorocyclohexyl ring, a candidate motif for drug discovery | en |
dc.type | Journal article | en |
dc.contributor.sponsor | European Commission | en |
dc.contributor.institution | University of St Andrews. School of Chemistry | en |
dc.contributor.institution | University of St Andrews. EaSTCHEM | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1039/C8SC00299A | |
dc.description.status | Peer reviewed | en |
dc.identifier.url | http://www.rsc.org/suppdata/c8/sc/c8sc00299a/c8sc00299a1.pdf | en |
dc.identifier.grantnumber | 607787 | en |
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