Organoruthenium Antagonists of Human A3 Adenosine Receptors |
| |
Authors: | Dr Priyankar Paira Mun Juinn Chow Gopalakrishnan Venkatesan Vamsi Krishna Kosaraju Dr Siew Lee Cheong Karl‐Norbert Klotz Dr Wee Han Ang AssocProf Giorgia Pastorin |
| |
Institution: | 1. Department of Pharmacy, National University of Singapore, 3 Science Drive 2, Singapore 117543 (Singapore), Fax: (+65)?6779 1554;2. Department of Chemistry, National University of Singapore, 3 Science Drive 2, Singapore 117543 (Singapore), Fax: (+65)?6779‐1691;3. NUS Graduate School for Integrative Sciences and Engineering, Center for Life Sciences (CeLS), 28 Medical Drive, 05‐01, Singapore 117456 (Singapore);4. Institut für Pharmakologie und Toxikologie, Universit?t Würzburg, 97078 Würzburg (Germany) |
| |
Abstract: | Human A3 adenosine receptor (hA3AR) 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. |
| |
Keywords: | adenosine ligand design nitrogen heterocycles ruthenium templated assembly |
|
|