ub.xmlui.mirage2.page-structure.muninLogoub.xmlui.mirage2.page-structure.openResearchArchiveLogo
    • EnglishEnglish
    • norsknorsk
  • Velg spraakEnglish 
    • EnglishEnglish
    • norsknorsk
  • Administration/UB
View Item 
  •   Home
  • Det helsevitenskapelige fakultet
  • Institutt for medisinsk biologi
  • Artikler, rapporter og annet (medisinsk biologi)
  • View Item
  •   Home
  • Det helsevitenskapelige fakultet
  • Institutt for medisinsk biologi
  • Artikler, rapporter og annet (medisinsk biologi)
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors

Permanent link
https://hdl.handle.net/10037/17682
DOI
https://doi.org/10.1002/ardp.201900101
Thumbnail
View/Open
article.pdf (2.375Mb)
Published version (PDF)
Date
2019-08-15
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Lien, Vegard Torp; Pettersen, Solveig; Haugen, Mads Haugland; Olberg, Dag Erlend; Mælandsmo, Gunhild Mari; Klaveness, Jo
Abstract
Based 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.
Publisher
Wiley
Citation
Lien VT, Pettersen S, Haugen MH, Olberg DE, Mælandsmo GM, Klaveness J. Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors. Archiv der Pharmazie. 2019;352(9)
Metadata
Show full item record
Collections
  • Artikler, rapporter og annet (medisinsk biologi) [1105]
Copyright 2019 The Author(s)

Browse

Browse all of MuninCommunities & CollectionsAuthor listTitlesBy Issue DateBrowse this CollectionAuthor listTitlesBy Issue Date
Login

Statistics

View Usage Statistics
UiT

Munin is powered by DSpace

UiT The Arctic University of Norway
The University Library
uit.no/ub - munin@ub.uit.no

Accessibility statement (Norwegian only)