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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

49 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

Access to Document

10.1016/j.bmcl.2012.10.022

Cite this

@article{2660fdefb0514b5eb596d05ad5845066,

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.",

keywords = "Alzheimer's disease, NF-κB, RAGE antagonist, β-Amyloid",

author = "Lee, \{Yun Suk\} and Hee Kim and Kim, \{Young Ho\} and Roh, \{Eun Joo\} and Hogyu Han and Shin, \{Kye Jung\}",

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 ).",

year = "2012",

month = dec,

day = "15",

doi = "10.1016/j.bmcl.2012.10.022",

language = "English",

volume = "22",

pages = "7555--7561",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "24",

}

TY - JOUR

T1 - Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease

AU - Lee, Yun Suk

AU - Kim, Hee

AU - Kim, Young Ho

AU - Roh, Eun Joo

AU - Han, Hogyu

AU - Shin, Kye Jung

N1 - 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 ).

PY - 2012/12/15

Y1 - 2012/12/15

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.

AB - 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.

KW - Alzheimer's disease

KW - NF-κB

KW - RAGE antagonist

KW - β-Amyloid

UR - https://www.scopus.com/pages/publications/84870238175

U2 - 10.1016/j.bmcl.2012.10.022

DO - 10.1016/j.bmcl.2012.10.022

M3 - Article

C2 - 23140885

AN - SCOPUS:84870238175

SN - 0960-894X

VL - 22

SP - 7555

EP - 7561

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 24

ER -

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

Access to Document

Other files and links

Fingerprint

Cite this