Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space

Manuela Therese Jorg, Jeremy Shonberg, Frankie S Mak, Neil D Miller, Elizabeth Yuriev, Peter John Scammells, Benvenuto Capuano

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

Growing evidence has suggested a role in targeting the adenosine A(2A) receptor for the treatment of Parkinson s disease. The literature compounds KW 6002 (2) and ZM 241385 (5) were used as a starting point from which a series of novel ligands targeting the adenosine A(2A) receptor were synthesized and tested in a recombinant human adenosine A(2A) receptor functional assay. In order to further explore these molecules, we investigated the biological effects of assorted linkers attached to different positions on selected adenosine A(2A) receptor antagonists, and assessed their potential binding modes using molecular docking studies. The results suggest that linking from the phenolic oxygen of selected adenosine A(2A) receptor antagonists is relatively well tolerated due to the extension towards extracellular space, and leads to the potential of attaching further functionality from this position.
Original languageEnglish
Pages (from-to)3427 - 3433
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number11
DOIs
Publication statusPublished - 2013

Cite this

@article{a1cc282c8d384cfbb79f61bd651d36aa,
title = "Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space",
abstract = "Growing evidence has suggested a role in targeting the adenosine A(2A) receptor for the treatment of Parkinson s disease. The literature compounds KW 6002 (2) and ZM 241385 (5) were used as a starting point from which a series of novel ligands targeting the adenosine A(2A) receptor were synthesized and tested in a recombinant human adenosine A(2A) receptor functional assay. In order to further explore these molecules, we investigated the biological effects of assorted linkers attached to different positions on selected adenosine A(2A) receptor antagonists, and assessed their potential binding modes using molecular docking studies. The results suggest that linking from the phenolic oxygen of selected adenosine A(2A) receptor antagonists is relatively well tolerated due to the extension towards extracellular space, and leads to the potential of attaching further functionality from this position.",
author = "Jorg, {Manuela Therese} and Jeremy Shonberg and Mak, {Frankie S} and Miller, {Neil D} and Elizabeth Yuriev and Scammells, {Peter John} and Benvenuto Capuano",
year = "2013",
doi = "10.1016/j.bmcl.2013.03.070",
language = "English",
volume = "23",
pages = "3427 -- 3433",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Pergamon",
number = "11",

}

TY - JOUR

T1 - Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space

AU - Jorg, Manuela Therese

AU - Shonberg, Jeremy

AU - Mak, Frankie S

AU - Miller, Neil D

AU - Yuriev, Elizabeth

AU - Scammells, Peter John

AU - Capuano, Benvenuto

PY - 2013

Y1 - 2013

N2 - Growing evidence has suggested a role in targeting the adenosine A(2A) receptor for the treatment of Parkinson s disease. The literature compounds KW 6002 (2) and ZM 241385 (5) were used as a starting point from which a series of novel ligands targeting the adenosine A(2A) receptor were synthesized and tested in a recombinant human adenosine A(2A) receptor functional assay. In order to further explore these molecules, we investigated the biological effects of assorted linkers attached to different positions on selected adenosine A(2A) receptor antagonists, and assessed their potential binding modes using molecular docking studies. The results suggest that linking from the phenolic oxygen of selected adenosine A(2A) receptor antagonists is relatively well tolerated due to the extension towards extracellular space, and leads to the potential of attaching further functionality from this position.

AB - Growing evidence has suggested a role in targeting the adenosine A(2A) receptor for the treatment of Parkinson s disease. The literature compounds KW 6002 (2) and ZM 241385 (5) were used as a starting point from which a series of novel ligands targeting the adenosine A(2A) receptor were synthesized and tested in a recombinant human adenosine A(2A) receptor functional assay. In order to further explore these molecules, we investigated the biological effects of assorted linkers attached to different positions on selected adenosine A(2A) receptor antagonists, and assessed their potential binding modes using molecular docking studies. The results suggest that linking from the phenolic oxygen of selected adenosine A(2A) receptor antagonists is relatively well tolerated due to the extension towards extracellular space, and leads to the potential of attaching further functionality from this position.

UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science/article/pii/S0960894X13003983#

U2 - 10.1016/j.bmcl.2013.03.070

DO - 10.1016/j.bmcl.2013.03.070

M3 - Article

VL - 23

SP - 3427

EP - 3433

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 11

ER -