scholarly journals Synthesis of Novel Fluorinated Xanthine Derivatives with High Adenosine A2B Receptor Binding Affinity

2021 ◽  
Vol 14 (5) ◽  
pp. 485
Author(s):  
Marcel Lindemann ◽  
Sladjana Dukic-Stefanovic ◽  
Sonja Hinz ◽  
Winnie Deuther-Conrad ◽  
Rodrigo Teodoro ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Receptor Subtypes ◽  
Binding Assays ◽  
Adenosine A2b Receptor ◽  
Xanthine Derivative ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
A2b Receptor ◽  
Novel Target ◽  
Adenosine A2b

The G protein-coupled adenosine A2B receptor is suggested to be involved in various pathological processes accompanied by increased levels of adenosine as found in inflammation, hypoxia, and cancer. Therefore, the adenosine A2B receptor is currently in focus as a novel target for cancer therapy as well as for noninvasive molecular imaging via positron emission tomography (PET). Aiming at the development of a radiotracer labeled with the PET radionuclide fluorine-18 for imaging the adenosine A2B receptor in brain tumors, one of the most potent and selective antagonists, the xanthine derivative PSB-603, was selected as a lead compound. As initial biodistribution studies in mice revealed a negligible brain uptake of [3H]PSB-603 (SUV3min: 0.2), structural modifications were performed to optimize the physicochemical properties regarding blood–brain barrier penetration. Two novel fluorinated derivatives bearing a 2-fluoropyridine (5) moiety and a 4-fluoro-piperidine (6) moiety were synthesized, and their affinity towards the four adenosine receptor subtypes was determined in competition binding assays. Both compounds showed high affinity towards the adenosine A2B receptor (Ki (5) = 9.97 ± 0.86 nM; Ki (6) = 12.3 ± 3.6 nM) with moderate selectivity versus the other adenosine receptor subtypes.

scholarly journals Development of a Radiofluorinated Adenosine A2B Receptor Antagonist as Potential Ligand for PET Imaging

2020 ◽  
Vol 21 (9) ◽  
pp. 3197
Author(s):  
Marcel Lindemann ◽  
Rareş-Petru Moldovan ◽  
Sonja Hinz ◽  
Winnie Deuther-Conrad ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Nucleophilic Aromatic Substitution ◽  
Receptor Subtypes ◽  
Cancer Therapies ◽  
Aromatic Substitution ◽  
Adenosine A2b Receptor ◽  
Positron Emission ◽  
A2b Receptor ◽  
Potential Ligand ◽  
Adenosine A2b

The adenosine A2B receptor has been proposed as a novel therapeutic target in cancer, as its expression is drastically elevated in several tumors and cancer cells. Noninvasive molecular imaging via positron emission tomography (PET) would allow the in vivo quantification of this receptor in pathological processes and most likely enable the identification and clinical monitoring of respective cancer therapies. On the basis of a bicyclic pyridopyrimidine-2,4-dione core structure, the new adenosine A2B receptor ligand 9 was synthesized, containing a 2-fluoropyridine moiety suitable for labeling with the short-lived PET radionuclide fluorine-18. Compound 9 showed a high binding affinity for the human A2B receptor (Ki(A2B) = 2.51 nM), along with high selectivities versus the A1, A2A, and A3 receptor subtypes. Therefore, it was radiofluorinated via nucleophilic aromatic substitution of the corresponding nitro precursor using [18F]F-/K2.2.2./K2CO3 in DMSO at 120 °C. Metabolic studies of [18F]9 in mice revealed about 60% of radiotracer intact in plasma at 30 minutes p.i. A preliminary PET study in healthy mice showed an overall biodistribution of [18F]9, corresponding to the known ubiquitous but low expression of the A2B receptor. Consequently, [18F]9 represents a novel PET radiotracer with high affinity and selectivity toward the adenosine A2B receptor and a suitable in vivo profile. Subsequent studies are envisaged to investigate the applicability of [18F]9 to detect alterations in the receptor density in certain cancer-related disease models.

Potent antagonists for the human adenosine A2B receptor. Derivatives of the triazolotriazine adenosine receptor antagonist ZM241385 with high affinity

1999 ◽  
Vol 48 (3) ◽  
pp. 95-103 ◽  
Author(s):  
Maarten de Zwart ◽  
Roel C. Vollinga ◽  
Margot W. Beukers ◽  
Danielle F. Sleegers ◽  
Jacobien K. von Frijtag Drabbe K�nzel ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Adenosine A2b Receptor ◽  
Adenosine Receptor Antagonist ◽  
High Affinity ◽  
A2b Receptor ◽  
Derivatives Of ◽  
Adenosine A2b

scholarly journals MP06-16 THE FUNCTIONAL ROLE OF ADENOSINE A2B RECEPTOR SUBTYPES IN THE BLADDER OF MALE RATS WITH BLADDER OUTLET OBSTRUCTION

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Masahiro Kurobe* ◽  
Ei-ichiro Takaoka ◽  
Takahisa Suzuki ◽  
Shinsuke Mizoguchi ◽  
Tetsuichi Saito ◽  
...  
Keyword(s):  
Bladder Outlet Obstruction ◽  
Functional Role ◽  
Outlet Obstruction ◽  
Male Rats ◽  
Receptor Subtypes ◽  
Adenosine A2b Receptor ◽  
A2b Receptor ◽  
Adenosine A2b

scholarly journals Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity

Blood ◽  
2015 ◽  
Vol 125 (10) ◽  
pp. 1643-1652 ◽  
Author(s):  
Kaiqi Sun ◽  
Yujin Zhang ◽  
Mikhail V. Bogdanov ◽  
Hongyu Wu ◽  
Anren Song ◽  
...  
Keyword(s):  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Adenosine A2b Receptor ◽  
Sickle Erythrocyte ◽  
Key Points ◽  
A2b Receptor ◽  
Specific Antagonist ◽  
Adenosine A2b ◽  
Adenosine Signaling

Key Points Adenosine signaling via ADORA2B induces SphK1 activity in sickle and normal erythrocytes via PKA-mediated ERK1/2 activation. Lowering adenosine by PEG-ADA or interfering ADORA2B activation by specific antagonist decreases SphK1 activity in normal and sickle RBCs.

Novel Adenosine A2B Receptor Signalling in Cardiac Fibroblasts: Uncovering Context-Specific Biased Agonism

2018 ◽  
Vol 27 ◽  
pp. S115-S116
Author(s):  
E. Vecchio ◽  
J. Baltos ◽  
C. Qin ◽  
R. Ritchie ◽  
A. Christopoulos ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Adenosine A2b Receptor ◽  
Biased Agonism ◽  
Receptor Signalling ◽  
A2b Receptor ◽  
Context Specific ◽  
Adenosine A2b
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