View : 156 Download: 0

Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide

Title
Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide
Authors
Van Hieu TranPark, HyunjunPark, JaekyungKwon, Young-DoKang, ShinwooJung, Jae HoChang, Keun-ALee, Byung ChulLee, Sang-YoonKang, SoosungKim, Hee-Kwon
Ewha Authors
강수성
Issue Date
2019
Journal Title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN
0968-0896JCR Link

1464-3391JCR Link
Citation
BIOORGANIC & MEDICINAL CHEMISTRY vol. 27, no. 18, pp. 4069 - 4080
Keywords
Translocator proteinPositron emission tomography probeStructure activity relationshipsNeuroinflammation
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Translocator protein (TSPO) expression is closely related with neuroinflammation and neuronal damage which might cause several central nervous system diseases. Herein, a series of TSPO ligands (11a-c and 13a-d) with a 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide structure were prepared and evaluated via an in vitro binding assay. Most of the novel ligands exhibited a nano-molar affinity for TSPO, which was better than that of DPA-714. Particularly, 11a exhibited a subnano-molar TSPO binding affinity with suitable lipophilicity for in vivo brain studies. After radiolabeling with fluorine-18, [F-18] 11a Filla was used for a dynamic positron emission tomography (PET) study in a rat LPS-induced neuroinflammation model; the inflammatory lesion was clearly visualized with a superior target-to-background ratio compared to [F-18]DPA-714. An immunohistochemical examination of the dissected brains confirmed that the uptake location of [F-18] 11a in the PET study was consistent with a positively activated microglia region. This study proved that [F-18] 11a could be employed as a potential PET tracer for detecting neuroinflammation and could give possibility for diagnosis of other diseases, such as cancers related with TSPO expression.
DOI
10.1016/j.bmc.2019.07.036
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE