Regioselective synthesis of 2- and 4-diarylpyridine ethers and their inhibitory activities against phosphodiesterase 4B

Xinyun Zhao; Huihui Chen; Suting Xing; Wei Yuan; L. Wu; Xi Chen; Chang Guo Zhan

doi:10.1016/j.molstruc.2019.06.086

Regioselective synthesis of 2- and 4-diarylpyridine ethers and their inhibitory activities against phosphodiesterase 4B

Xinyun Zhao, Huihui Chen, Suting Xing, Wei Yuan, L. Wu, Xi Chen, Chang Guo Zhan

Pharmaceutical Sciences

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

2 Scopus citations

Abstract

Two diaryl ether regioisomers of pyridine were prepared through the CuI/TMEDA/Cs₂CO₃-catalyzed reaction of 2,4-dibromopyridine with phenol derivatives under nitrogen atmosphere. The polar solvent DMSO gave 4-isomer as the major product whereas less polar toluene resulted in 2-isomer as a major product. Structures of regioisomers were confirmed by single crystal X-ray diffraction analysis. 4-regioisomer shows higher biological activity against phosphodiesterase 4B (PDE4B) than that of 2-isomer. Molecular docking simulations revealed that the PDE4B-inhibitory activity difference between the two regioisomers was mainly attributed to the atomic charge difference on the –O– linker.

Original language	English
Pages (from-to)	455-461
Number of pages	7
Journal	Journal of Molecular Structure
Volume	1196
DOIs	https://doi.org/10.1016/j.molstruc.2019.06.086
State	Published - Nov 15 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

2,4-Dibromopyridine
Diaryl ethers
PDE4B inhibitory activity
Regioselectivity
X-ray crystal structure

ASJC Scopus subject areas

Analytical Chemistry
Spectroscopy
Organic Chemistry
Inorganic Chemistry

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10.1016/j.molstruc.2019.06.086

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title = "Regioselective synthesis of 2- and 4-diarylpyridine ethers and their inhibitory activities against phosphodiesterase 4B",

abstract = "Two diaryl ether regioisomers of pyridine were prepared through the CuI/TMEDA/Cs2CO3-catalyzed reaction of 2,4-dibromopyridine with phenol derivatives under nitrogen atmosphere. The polar solvent DMSO gave 4-isomer as the major product whereas less polar toluene resulted in 2-isomer as a major product. Structures of regioisomers were confirmed by single crystal X-ray diffraction analysis. 4-regioisomer shows higher biological activity against phosphodiesterase 4B (PDE4B) than that of 2-isomer. Molecular docking simulations revealed that the PDE4B-inhibitory activity difference between the two regioisomers was mainly attributed to the atomic charge difference on the –O– linker.",

keywords = "2,4-Dibromopyridine, Diaryl ethers, PDE4B inhibitory activity, Regioselectivity, X-ray crystal structure",

author = "Xinyun Zhao and Huihui Chen and Suting Xing and Wei Yuan and L. Wu and Xi Chen and Zhan, {Chang Guo}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2019",

month = nov,

day = "15",

doi = "10.1016/j.molstruc.2019.06.086",

language = "English",

volume = "1196",

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TY - JOUR

T1 - Regioselective synthesis of 2- and 4-diarylpyridine ethers and their inhibitory activities against phosphodiesterase 4B

AU - Zhao, Xinyun

AU - Chen, Huihui

AU - Xing, Suting

AU - Yuan, Wei

AU - Wu, L.

AU - Chen, Xi

AU - Zhan, Chang Guo

PY - 2019/11/15

Y1 - 2019/11/15

N2 - Two diaryl ether regioisomers of pyridine were prepared through the CuI/TMEDA/Cs2CO3-catalyzed reaction of 2,4-dibromopyridine with phenol derivatives under nitrogen atmosphere. The polar solvent DMSO gave 4-isomer as the major product whereas less polar toluene resulted in 2-isomer as a major product. Structures of regioisomers were confirmed by single crystal X-ray diffraction analysis. 4-regioisomer shows higher biological activity against phosphodiesterase 4B (PDE4B) than that of 2-isomer. Molecular docking simulations revealed that the PDE4B-inhibitory activity difference between the two regioisomers was mainly attributed to the atomic charge difference on the –O– linker.

AB - Two diaryl ether regioisomers of pyridine were prepared through the CuI/TMEDA/Cs2CO3-catalyzed reaction of 2,4-dibromopyridine with phenol derivatives under nitrogen atmosphere. The polar solvent DMSO gave 4-isomer as the major product whereas less polar toluene resulted in 2-isomer as a major product. Structures of regioisomers were confirmed by single crystal X-ray diffraction analysis. 4-regioisomer shows higher biological activity against phosphodiesterase 4B (PDE4B) than that of 2-isomer. Molecular docking simulations revealed that the PDE4B-inhibitory activity difference between the two regioisomers was mainly attributed to the atomic charge difference on the –O– linker.

KW - 2,4-Dibromopyridine

KW - Diaryl ethers

KW - PDE4B inhibitory activity

KW - Regioselectivity

KW - X-ray crystal structure

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U2 - 10.1016/j.molstruc.2019.06.086

DO - 10.1016/j.molstruc.2019.06.086

M3 - Article

AN - SCOPUS:85068261056

SN - 0022-2860

VL - 1196

SP - 455

EP - 461

JO - Journal of Molecular Structure

JF - Journal of Molecular Structure

ER -

Regioselective synthesis of 2- and 4-diarylpyridine ethers and their inhibitory activities against phosphodiesterase 4B

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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