{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:56:53Z","timestamp":1779245813378,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["Neuroallianz D11B"],"award-info":[{"award-number":["Neuroallianz D11B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2013brain 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 \u00b1 0.86 nM; Ki (6) = 12.3 \u00b1 3.6 nM) with moderate selectivity versus the other adenosine receptor subtypes.<\/jats:p>","DOI":"10.3390\/ph14050485","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T21:49:21Z","timestamp":1621460961000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis of Novel Fluorinated Xanthine Derivatives with High Adenosine A2B Receptor Binding Affinity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5883-8004","authenticated-orcid":false,"given":"Marcel","family":"Lindemann","sequence":"first","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sladjana","family":"Dukic-Stefanovic","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"},{"name":"ROTOP Pharmaka GmbH, 01328 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Hinz","sequence":"additional","affiliation":[{"name":"Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical &amp; Medicinal Chemistry, University of Bonn, 53121 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3062","authenticated-orcid":false,"given":"Winnie","family":"Deuther-Conrad","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-0567","authenticated-orcid":false,"given":"Rodrigo","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathleen","family":"Juhl","sequence":"additional","affiliation":[{"name":"ROTOP Pharmaka GmbH, 01328 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Steinbach","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-7058","authenticated-orcid":false,"given":"Peter","family":"Brust","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0013-6624","authenticated-orcid":false,"given":"Christa E.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Pharma Center Bonn, Pharmaceutical Institute, Pharmaceutical &amp; Medicinal Chemistry, University of Bonn, 53121 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7390-3575","authenticated-orcid":false,"given":"Barbara","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"ref_1","first-page":"381","article-title":"Adenosine A2B receptors","volume":"49","author":"Feoktistov","year":"1997","journal-title":"Pharmacol. 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