200557-55-7Relevant academic research and scientific papers
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.
Novel adenosine A3 receptor modulators
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Page/Page column 17, (2008/06/13)
A class of novel antagonists for the adenosine A3 receptor are disclosed. These compounds are useful as therapeutic agents for a number of diseases and medical conditions that are mediated by the A3 receptor. The compounds of this in
New pyrrolo[2,1-f]purine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives as potent and selective human A3 adenosine receptor antagonists
Baraldi, Pier Giovanni,Preti, Delia,Tabrizi, Mojgan Aghazadeh,Fruttarolo, Francesca,Romagnoli, Romeo,Zaid, Naser Abdel,Moorman, Allan R.,Merighi, Stefania,Varani, Katia,Borea, Pier Andrea
, p. 4697 - 4701 (2007/10/03)
Compounds presenting an additional fused ring on the xanthine nucleus have been reported to exhibit antagonistic activity with various levels of affinity and selectivity toward the four adenosine receptors subtypes A1, A2A, A2B
A1 adenosine receptor antagonists as ligands for positron emission tomography (PET) and single-photon emission tomography (SPET).
Holschbach,Fein,Krummeich,Lewis,Wutz,Schwabe,Unterlugauer,Olsson
, p. 555 - 563 (2007/10/03)
The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A1 adenosine receptor (A1AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-11, fluorine-18, or radioiodine will not alter affinity for the A1AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [3H]CPX to the A1AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the Ki of antagonism was > or = 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A1AR.
