Separation of α-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRα-selective antagonists

Kazunori Motoshima, Tomomi Noguchi-Yachide, Kazuyuki Sugita, Yuichi Hashimoto, Minoru Ishikawa

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Liver X receptor (LXR) α/β dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXRβ. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXRα. Combination of an LXRα-selective antagonist with an LXRα/β dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXRα/β dual-antagonistic activity and α-glucosidase-inhibitory activity, led to the LXRα-selective antagonist 23f. Specific α-glucosidase inhibitors were also obtained.

Original languageEnglish
Pages (from-to)5001-5014
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number14
DOIs
Publication statusPublished - 2009 Jul 15
Externally publishedYes

Keywords

  • LXR antagonist
  • Thalidomide analog
  • α-Glucosidase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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