title: Organoruthenium antagonists of human A₃ adenosine receptors.
abstract: Human A₃ adenosine receptor (A₃AR) is a membrane-bound G protein-coupled receptor implicated in a number of severe pathological conditions, including cancer, in which it acts as a potential therapeutic target. To derive structure-activity relationships on pyrazolo-triazolo-pyrimidine (PTP)-based A₃AR antagonists, we developed a new class of organometallic inhibitors through replacement of the triazolo moiety with an organoruthenium fragment. The objective was to introduce by design structural diversity into the PTP scaffold in order to tune their binding efficacy toward the target receptor. These novel organoruthenium antagonists displayed good aquatic stability and moderate binding affinity toward the hA₃ receptor in the low micromolar range. The assembly of these complexes through a template-driven approach with selective ligand replacement at the metal center to control their steric and receptor-binding properties is discussed.
authors.affiliation: Department of Pharmacy, National University of Singapore, 3 Science Drive 2, Singapore 117543, Singapore.
authors.forename: Priyankar
authors.initials: P
authors.lastname: Paira
authors.forename: Mun Juinn
authors.initials: MJ
authors.lastname: Chow
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Venkatesan
authors.forename: Vamsi Krishna
authors.initials: VK
authors.lastname: Kosaraju
authors.forename: Siew Lee
authors.initials: SL
authors.lastname: Cheong
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Ang
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
mesh_terms: D058918:Adenosine A3 Receptor Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D043684:Receptor, Adenosine A3 / Q000737:chemistry / Q000378:metabolism*; D017975:Ruthenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D011743:Pyrimidines; D043684:Receptor, Adenosine A3; D017975:Ruthenium Compounds