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 journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7453-7464
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number23
DOIs
StatePublished - Dec 1 2013

Keywords

  • A
  • Adenosine receptor
  • Hypoxia
  • KW-6002
  • Synthesis
  • Xanthine

Fingerprint Dive into the research topics of 'Design and evaluation of xanthine based adenosine receptor antagonists: Potential hypoxia targeted immunotherapies'. Together they form a unique fingerprint.

  • Cite this

    Thomas, R., Lee, J., Chevalier, V., Sadler, S., Selesniemi, K., Hatfield, S., Sitkovsky, M., Ondrechen, M. J., & Jones, G. B. (2013). Design and evaluation of xanthine based adenosine receptor antagonists: Potential hypoxia targeted immunotherapies. Bioorganic and Medicinal Chemistry, 21(23), 7453-7464. https://doi.org/10.1016/j.bmc.2013.09.043