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

doi:10.1016/j.bmcl.2012.10.022

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 journal › Article › peer-review

45 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 language	English
Pages (from-to)	7555-7561
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2012.10.022
Publication status	Published - 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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10.1016/j.bmcl.2012.10.022

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title = "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.",

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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 ).",

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AU - Roh, Eun Joo

AU - Han, Hogyu

AU - Shin, Kye Jung

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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