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dc.date.accessioned2020-05-16T18:36:28Z
dc.date.available2020-05-16T18:36:28Z
dc.date.created2019-09-03T09:19:31Z
dc.date.issued2019
dc.identifier.citationLien, Vegard Torp Pettersen, Solveig Haugen, Mads Haugland Olberg, Dag Erlend Mælandsmo, Gunhild Mari Klaveness, Jo . Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors. Archiv der Pharmazie. 2019, 352(9)
dc.identifier.urihttp://hdl.handle.net/10852/75797
dc.description.abstractBased on the cabozantinib scaffold, novel c‐Met inhibitors were rationalized from the limited knowledge of structure‐activity relationships for the quinoline 6‐position. Emphasis was given to modifications capable of engaging in additional polar interactions with the c‐Met active site. In addition, ortho‐fluorinations of the terminal benzene ring were explored. Fifteen new molecules were synthesized and evaluated in a c‐Met enzymatic binding assay. A wide range of substituents were tolerated in the quinoline 6‐position, while the ortho‐fluorinations performed were shown to give considerable reductions in the c‐Met binding affinity. The antiproliferative effects of the compounds were evaluated in the NCI60 cancer cell line panel. Most notably, compounds 15b and 18b were able to inhibit cell proliferation more efficiently than cabozantinib in leukemia, CNS, and breast cancer cell lines. The in vitro data agreed well with the in silico docking results, where additional hydrogen bonding was identified in the enzymatic pocket for the para‐amino substituted 15b and 18b.en_US
dc.languageEN
dc.publisherWiley - VCH Verlag GmbH
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleDesign, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitorsen_US
dc.typeJournal articleen_US
dc.creator.authorLien, Vegard Torp
dc.creator.authorPettersen, Solveig
dc.creator.authorHaugen, Mads Haugland
dc.creator.authorOlberg, Dag Erlend
dc.creator.authorMælandsmo, Gunhild Mari
dc.creator.authorKlaveness, Jo
cristin.unitcode185,15,23,20
cristin.unitnameSeksjon for farmasøytisk kjemi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1720828
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Archiv der Pharmazie&rft.volume=352&rft.spage=&rft.date=2019
dc.identifier.jtitleArchiv der Pharmazie
dc.identifier.volume352
dc.identifier.issue9
dc.identifier.doihttps://doi.org/10.1002/ardp.201900101
dc.identifier.urnURN:NBN:no-78853
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn0365-6233
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/75797/2/artikkel55215.pdf
dc.type.versionPublishedVersion
cristin.articleid1900101


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