Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
Medicinal Chemistry of Adenosine Receptor Antagonists
share announcement

Medicinal Chemistry of Adenosine Receptor Antagonists

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 8155

Special Issue Editors

Dr. Catia Lambertucci

E-Mail Website
Guest Editor
Università degli Studi di Camerino, Camerino, Italy
Interests: medicinal chemistry; organic synthesis; synthesis of receptor ligands; adenosine receptor agonists; adenosine receptor antagonists; P2 purinergic receptor ligands
Dr. Rosaria Volpini

E-Mail Website
Co-Guest Editor
Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università degli Studi di Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Interests: medicinal chemistry; organic synthesis; synthesis of receptor ligands; adenosine receptor agonists; adenosine receptor antagonists; P2 purinergic receptor ligands

Special Issue Information

Dear Colleagues,

This is an invitation to submit your research results in the field of medicinal chemistry of the adenosinergic system.

Adenosine (Ado) is an extracellular signalling molecule which, by activating specific receptors, is involved in a variety of physiological and pathological processes, including central and peripheral nervous system functions, modulation of cardiovascular and respiratory activity, regulation of immune systems in humans and other species. Ado receptors (ARs) are G protein-coupled receptors classified as A1, A2A, A2B, and A3 subtypes, which are expressed throughout the body with different tissue/organ distribution and signalling. The role of ARs in different pathologies confirms this receptor system as a potential therapeutic target in a variety of pathological conditions, such as neurological disorders, cardiovascular diseases, cancer, inflammatory and autoimmune diseases.

A big effort has been made in the design of molecules able to modulate the activity of ARs, although few of them, mainly agonists, have entered clinical practice. Among the AR antagonists, only the xanthine derivative istradefylline was first approved in Japan and recently also by the FDA for use as an adjunctive treatment to levodopa/carbidopa in the treatment of Parkinson’s disease.

This Special Issue aims to provide readers with recent advances in the medicinal chemistry of AR antagonists. The topics proposed include molecules endowed with AR antagonist properties and designed as pharmacological tools and diagnostic probes, their synthesis, biological evaluation and pharmacokinetic properties. Molecular modelling studies are also welcome.

Authors are invited to submit original articles or reviews in this area of investigation.

Researchers interested in this issue are encouraged to suggest topics that will be evaluated.

Dr. Catia Lambertucci
Guest Editor
Dr. Rosaria Volpini
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

19 pages, 21570 KiB  
Article
Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives with High Affinity for Both the Adenosine A1 and A2A Receptors, and Efficacy in Animal Models of Depression
by Flavia Varano, Daniela Catarzi, Erica Vigiani, Diego Dal Ben, Michela Buccioni, Gabriella Marucci, Lorenzo Di Cesare Mannelli, Elena Lucarini, Carla Ghelardini, Rosaria Volpini and Vittoria Colotta
Pharmaceuticals 2021, 14(7), 657; https://doi.org/10.3390/ph14070657 - 9 Jul 2021
Cited by 4 | Viewed by 2210
Abstract
New compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8– [...] Read more.
New compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8–10, 13, 18, 19) were characterized by nanomolar and subnanomolar binding affinities for the hA1 and the hA2A AR, respectively. Results of molecular docking studies supported the in vitro results. The 2-(2-fluorobenzyl)-5-(furan-2yl)-thiazolo[5,4-d]pyrimidin-7-amine derivative 18 (hA1 Ki = 1.9 nM; hA2A Ki = 0.06 nM) was evaluated for its antidepressant-like activity in in vivo studies, the forced swimming test (FST), the tail suspension test (TST), and the sucrose preference test (SPT) in mice, showing an effect comparable to that of the reference amitriptyline. Full article
(This article belongs to the Special Issue Medicinal Chemistry of Adenosine Receptor Antagonists)
►▼ Show Figures

Graphical abstract

10 pages, 2242 KiB  
Communication
Synthesis of Novel Fluorinated Xanthine Derivatives with High Adenosine A2B Receptor Binding Affinity
by Marcel Lindemann, Sladjana Dukic-Stefanovic, Sonja Hinz, Winnie Deuther-Conrad, Rodrigo Teodoro, Cathleen Juhl, Jörg Steinbach, Peter Brust, Christa E. Müller and Barbara Wenzel
Pharmaceuticals 2021, 14(5), 485; https://doi.org/10.3390/ph14050485 - 19 May 2021
Cited by 1 | Viewed by 3040
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Medicinal Chemistry of Adenosine Receptor Antagonists)
►▼ Show Figures

Figure 1

14 pages, 1602 KiB  
Article
Design and Synthesis of 2,6-Disubstituted-4′-Selenoadenosine-5′-N,N-Dimethyluronamide Derivatives as Human A3 Adenosine Receptor Antagonists
by Hongseok Choi, Kenneth A. Jacobson, Jinha Yu and Lak Shin Jeong
Pharmaceuticals 2021, 14(4), 363; https://doi.org/10.3390/ph14040363 - 14 Apr 2021
Cited by 3 | Viewed by 2195
Abstract
A new series of 4′-selenoadenosine-5′-N,N-dimethyluronamide derivatives as highly potent and selective human A3 adenosine receptor (hA3AR) antagonists, is described. The highly selective A3AR agonists, 4′-selenoadenosine-5′-N-methyluronamides were successfully converted into selective antagonists by adding a [...] Read more.
A new series of 4′-selenoadenosine-5′-N,N-dimethyluronamide derivatives as highly potent and selective human A3 adenosine receptor (hA3AR) antagonists, is described. The highly selective A3AR agonists, 4′-selenoadenosine-5′-N-methyluronamides were successfully converted into selective antagonists by adding a second N-methyl group to the 5′-uronamide position. All the synthesized compounds showed medium to high binding affinity at the hA3AR. Among the synthesized compounds, 2-H-N6-3-iodobenzylamine derivative 9f exhibited the highest binding affinity at hA3AR. (Ki = 22.7 nM). The 2-H analogues generally showed better binding affinity than the 2-Cl analogues. The cAMP functional assay with 2-Cl-N6-3-iodobenzylamine derivative 9l demonstrated hA3AR antagonist activity. A molecular modelling study suggests an important role of the hydrogen of 5′-uronamide as an essential hydrogen bonding donor for hA3AR activation. Full article
(This article belongs to the Special Issue Medicinal Chemistry of Adenosine Receptor Antagonists)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop