Sulfonimide and Amide Derivatives as Novel PPARα Antagonists: Synthesis, Antiproliferative Activity, and Docking Studies.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
14 May 2020
14 May 2020
Historique:
received:
30
12
2019
accepted:
03
03
2020
entrez:
22
5
2020
pubmed:
22
5
2020
medline:
22
5
2020
Statut:
epublish
Résumé
An agonist-antagonist switching strategy was performed to discover novel PPARα antagonists. Phenyldiazenyl derivatives of fibrates were developed, bearing sulfonimide or amide functional groups. A second series of compounds was synthesized, replacing the phenyldiazenyl moiety with amide or urea portions. Final compounds were screened by transactivation assay, showing good PPARα antagonism and selectivity at submicromolar concentrations. When tested in cancer cell models expressing PPARα, selected derivatives induced marked effects on cell viability. Notably,
Identifiants
pubmed: 32435362
doi: 10.1021/acsmedchemlett.9b00666
pmc: PMC7236056
doi:
Types de publication
Journal Article
Langues
eng
Pagination
624-632Informations de copyright
Copyright © 2020 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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