title: 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.
authors.affiliation: Bioorganic and Medicinal Chemistry Laboratories, Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Thomas
authors.forename: Joslynn
authors.initials: J
authors.lastname: Lee
authors.forename: Vincent
authors.initials: V
authors.lastname: Chevalier
authors.forename: Sara
authors.initials: S
authors.lastname: Sadler
authors.forename: Kaisa
authors.initials: K
authors.lastname: Selesniemi
authors.forename: Stephen
authors.initials: S
authors.lastname: Hatfield
authors.forename: Michail
authors.initials: M
authors.lastname: Sitkovsky
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Ondrechen
authors.forename: Graham B
authors.initials: GB
authors.lastname: Jones
mesh_terms: D002460:Cell Line; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D000860:Hypoxia / Q000628:therapy; D007167:Immunotherapy; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000378:metabolism*; D019820:Xanthine / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D019820:Xanthine; D011092:Polyethylene Glycols
keywords: A(2A); Adenosine receptor; Hypoxia; KW-6002; Synthesis; Xanthine