Design and evaluation of xanthine based adenosine receptor antagonists: Potential hypoxia targeted immunotherapies

Rhiannon Thomas; Joslynn Lee; Vincent Chevalier; Sara Sadler; Kaisa Selesniemi; Stephen Hatfield; Michail Sitkovsky; Mary Jo Ondrechen; Graham B. Jones

doi:10.1016/j.bmc.2013.09.043

Design and evaluation of xanthine based adenosine receptor antagonists: Potential hypoxia targeted immunotherapies

Rhiannon Thomas, Joslynn Lee, Vincent Chevalier, Sara Sadler, Kaisa Selesniemi, Stephen Hatfield, Michail Sitkovsky, Mary Jo Ondrechen, Graham B. Jones

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

12 Scopus citations

Abstract

Molecular modeling techniques were applied to the design, synthesis and optimization of a new series of xanthine based adenosine A_2A receptor antagonists. The optimized lead compound was converted to a PEG derivative and a functional in vitro bioassay used to confirm efficacy. Additionally, the PEGylated version showed enhanced aqueous solubility and was inert to photoisomerization, a known limitation of existing antagonists of this class.

Original language	English (US)
Pages (from-to)	7453-7464
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	23
DOIs	https://doi.org/10.1016/j.bmc.2013.09.043
State	Published - Dec 1 2013
Externally published	Yes

Keywords

A
Adenosine receptor
Hypoxia
KW-6002
Synthesis
Xanthine

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AU - Thomas, Rhiannon

AU - Lee, Joslynn

AU - Chevalier, Vincent

AU - Sadler, Sara

AU - Selesniemi, Kaisa

AU - Hatfield, Stephen

AU - Sitkovsky, Michail

AU - Ondrechen, Mary Jo

AU - Jones, Graham B.

PY - 2013/12/1

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AB - Molecular modeling techniques were applied to the design, synthesis and optimization of a new series of xanthine based adenosine A2A receptor antagonists. The optimized lead compound was converted to a PEG derivative and a functional in vitro bioassay used to confirm efficacy. Additionally, the PEGylated version showed enhanced aqueous solubility and was inert to photoisomerization, a known limitation of existing antagonists of this class.

KW - A

KW - Adenosine receptor

KW - Hypoxia

KW - KW-6002

KW - Synthesis

KW - Xanthine

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JO - Bioorganic and Medicinal Chemistry

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ER -

Design and evaluation of xanthine based adenosine receptor antagonists: Potential hypoxia targeted immunotherapies

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