340021-17-2Relevant articles and documents
Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A1Receptor in Living Cells
Comeo, Eleonora,Trinh, Phuc,Nguyen, Anh T.,Nowell, Cameron J.,Kindon, Nicholas D.,Soave, Mark,Stoddart, Leigh A.,White, Jonathan M.,Hill, Stephen J.,Kellam, Barrie,Halls, Michelle L.,May, Lauren T.,Scammells, Peter J.
, p. 6670 - 6695 (2021/04/12)
The adenosine A1 receptor (A1AR) is a G-protein-coupled receptor (GPCR) that provides important therapeutic opportunities for a number of conditions including congestive heart failure, tachycardia, and neuropathic pain. The development of A1AR-selective fluorescent ligands will enhance our understanding of the subcellular mechanisms underlying A1AR pharmacology facilitating the development of more efficacious and selective therapies. Herein, we report the design, synthesis, and application of a novel series of A1AR-selective fluorescent probes based on 8-functionalized bicyclo[2.2.2]octylxanthine and 3-functionalized 8-(adamant-1-yl) xanthine scaffolds. These fluorescent conjugates allowed quantification of kinetic and equilibrium ligand binding parameters using NanoBRET and visualization of specific receptor distribution patterns in living cells by confocal imaging and total internal reflection fluorescence (TIRF) microscopy. As such, the novel A1AR-selective fluorescent antagonists described herein can be applied in conjunction with a series of fluorescence-based techniques to foster understanding of A1AR molecular pharmacology and signaling in living cells.
Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists
Kiesman, William F.,Zhao, Jin,Conlon, Patrick R.,Dowling, James E.,Petter, Russell C.,Lutterodt, Frank,Jin, Xiaowei,Smits, Glenn,Fure, Mary,Jayaraj, Andrew,Kim, John,Sullivan, Gail,Linden, Joel
, p. 7119 - 7131 (2008/04/18)
In the search for a selective adenosine A1 receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4-substituted 8-cyclohexyl and 8-bicyclo-[2.2.2] octylxanthines were inve
Adenosine receptor antagonists and methods of making and using the same
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Page/Page column 60, (2008/06/13)
The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A1receptor. Adenosine A1antagonists can be usefull in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula I: wherein: R3is an optionally substituted bicyclic, tricylic, or pentacyclic group selected from: ?and wherein R1, R2, R6, X1, X2, and Z are as described in the specification.