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

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.

SUBMITTER: Thomas R

PROVIDER: S-EPMC4346301 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Thomas Rhiannon R Lee Joslynn J Chevalier Vincent V Sadler Sara S Selesniemi Kaisa K Hatfield Stephen S Sitkovsky Michail M Ondrechen Mary Jo MJ Jones Graham B GB

Bioorganic & medicinal chemistry 20130928 23

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. ...[more]

PMID: 24126093

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