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dc.contributor.author
Mäder, Patrick
dc.contributor.author
Bartholomäus, Ruben
dc.contributor.author
Nicolussi, Simon
dc.contributor.author
Baumann, Alice
dc.contributor.author
Weis, Melanie
dc.contributor.author
Chicca, Andrea
dc.contributor.author
Rau, Mark
dc.contributor.author
Simão, Ana C.
dc.contributor.author
Gertsch, Jürg
dc.contributor.author
Altmann, Karl-Heinz
dc.date.accessioned
2021-01-25T19:57:00Z
dc.date.available
2020-06-05T13:32:14Z
dc.date.available
2020-06-10T14:53:35Z
dc.date.available
2021-01-25T19:57:00Z
dc.date.issued
2021-01-08
dc.identifier.issn
1860-7179
dc.identifier.issn
1860-7187
dc.identifier.other
10.1002/cmdc.202000153
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/418581
dc.description.abstract
WOBE437 ((2E,4E)‐N‐(3,4‐dimethoxyphenethyl)dodeca‐2,4‐dienamide, 1) is a natural product‐derived, highly potent inhibitor of endocannabinoid reuptake. In this study, we synthesized almost 80 analogues of 1 with different types of modifications in the dodecadienoyl domain as well as the dimethoxyphenylethyl head group, and we investigated their effects on anandamide uptake into U937 cells. Intriguingly, none of these analogues was a more potent inhibitor of anandamide uptake than WOBE437 (1). At the same time, a number of WOBE437 variants exhibited potencies in the sub‐100 nM range, with high selectivity over inhibition of the endocannabinoid‐degrading enzyme fatty acid amide hydrolase; two compounds were virtually equipotent with 1. Interestingly, profound activity differences were observed between analogues in which either of the two methoxy substituents in the head group had been replaced by the same bulkier alkoxy group. Some of the compounds described here could be interesting departure points for the development of potent endocannabinoid uptake inhibitors with more drug‐like properties.
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.subject
anandamide transport inhibitor
en_US
dc.subject
endocannabinoid membrane transport
en_US
dc.subject
endocannabinoid system
en_US
dc.subject
structure-activity relationship
en_US
dc.subject
WOBE437
en_US
dc.title
Synthesis and Biological Evaluation of Endocannabinoid Uptake Inhibitors Derived from WOBE437
en_US
dc.type
Journal Article
dc.date.published
2020-05-05
ethz.journal.title
ChemMedChem
ethz.journal.volume
16
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
ChemMedChem
ethz.pages.start
145
en_US
ethz.pages.end
154
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Weinheim
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03647 - Altmann, Karl-Heinz / Altmann, Karl-Heinz
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03647 - Altmann, Karl-Heinz / Altmann, Karl-Heinz
ethz.date.deposited
2020-06-05T13:32:21Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2021-01-25T19:57:12Z
ethz.rosetta.lastUpdated
2021-02-15T23:33:16Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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