Replacing alkyl sulfonamide with aromatic sulfonamide in sulfonamide-type RXR agonists favors switch towards antagonist activity

Ken ichi Morishita, Nobumasa Yakushiji, Fuminori Ohsawa, Kayo Takamatsu, Nobuyasu Matsuura, Makoto Makishima, Masatoshi Kawahata, Kentaro Yamaguchi, Akihiro Tai, Kenji Sasaki, Hiroki Kakuta

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Retinoid X receptor (RXR) ligands are attractive candidates for clinical application because of their activity against tamoxifen-resistant breast cancer, taxol-resistant lung cancer, metabolic syndrome, and allergy. Though several RXR ligands, especially RXR antagonists, have been reported, the rational molecular design of such compounds is not well advanced. 4-[N-Methanesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthy l)amino]nicotinic acid (5a) is a moderately RXRα-preferential agonist, and we examined the feasibility of replacing the methyl group on the sulfonamide with a longer alkyl chain or an aromatic ring as an approach to produce new RXR antagonists. Several of the resulting benzenesulfonanilide-type compounds showed RXR antagonist activity. This design strategy should be a useful approach for addressing the lack of structure diversity of RXR antagonists.

Original languageEnglish
Pages (from-to)1001-1003
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number3
DOIs
Publication statusPublished - Feb 1 2009

Keywords

  • Antagonists
  • Molecular design
  • RXR
  • Retinoid X receptor
  • Sulfonamide

ASJC Scopus subject areas

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

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