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

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.

• Authors: Yun Suk Lee, Hee Kim, Young-Ho Kim, Eun Joo Roh, Hogyu Han, Kye Jung Shin
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 24 Pg. 7555-61 (Dec 15 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 23140885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Thiazoles

Topics

• Alzheimer Disease (drug therapy)
• Dose-Response Relationship, Drug
• Humans
• Molecular Structure
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (antagonists & inhibitors)
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, pharmacology)