Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease

Yun Suk Lee, Hee Kim, Young Ho Kim, Eun Joo Roh, Hogyu Han, Kye Jung Shin

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

A series of thiazole derivatives were designed, and prepared to develop RAGE antagonist for the treatment of Alzheimer's disease (AD). SAR studies were performed to optimize inhibitory activity on Aβ-RAGE binding. SAR studies showed that introducing an amino group at part A was essential for inhibitory activity on Aβ-RAGE binding. Compounds selected from Aβ-RAGE binding screening displayed inhibitory activity on Aβ transport across BBB. They also showed inhibitory activity against Aβ-induced NF-κB activation. These results indicated that our derivatives had a potential as therapeutic agent for the treatment of AD.

Original languageEnglish
Pages (from-to)7555-7561
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number24
DOIs
Publication statusPublished - 2012 Dec 15

Bibliographical note

Funding Information:
This work was financially supported by Research Fund 2011 of The Catholic University of Korea, and National Research Foundation grant of Korea government (MEST) as a part of Global Drug Candidate Development Program for Neurodegenerative Disease ( 2011-0018334 ).

Keywords

  • Alzheimer's disease
  • NF-κB
  • RAGE antagonist
  • β-Amyloid

ASJC Scopus subject areas

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

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