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Positron emission tomography is a noninvasive imaging technique for diagnosing disease states, but requires radiotracers with high affinity and selectivity towards CB\n                    <jats:sub>2<\/jats:sub>\n                    R. Currently, there is no suitable candidate routinely used in the clinics. The naphthyridinone scaffold, a promising core structure, has been modified in the past years. The modification of naphthyridinone carboxamides with carboranes as hydrophobic surrogates for purely organic moieties can lead to beneficial CB\n                    <jats:sub>2<\/jats:sub>\n                    R ligands with high affinity, selectivity, and metabolic stability. Herein, synthesis and characterization of eight\n                    <jats:italic>ortho<\/jats:italic>\n                    \u2010,\n                    <jats:italic>meta<\/jats:italic>\n                    \u2010,\n                    <jats:italic>para<\/jats:italic>\n                    \u2010, and\n                    <jats:italic>nido<\/jats:italic>\n                    \u2010carborane\u2010based naphthyridinone ligands are reported, along with their in\u2009vitro binding affinity towards human CB\n                    <jats:sub>1<\/jats:sub>\n                    R and CB\n                    <jats:sub>2<\/jats:sub>\n                    R. Additionally, the results of in silico investigations are presented. The\n                    <jats:italic>meta<\/jats:italic>\n                    \u2010 and\n                    <jats:italic>para<\/jats:italic>\n                    \u2010carborane derivatives show high affinity in the low nanomolar range and good selectivity towards CB\n                    <jats:sub>2<\/jats:sub>\n                    R. Only a minor influence of bromo\u2010 versus iodo\u2010substitution of the compounds is observed experimentally, while in silico data suggest a stronger influence of the halogen atom, resulting in a different order of the respective carborane isomers regarding their CB\n                    <jats:sub>2<\/jats:sub>\n                    R affinity. Although these compounds do not outperform the known organic derivatives, these promising carborane\u2010based naphthyridinones extend the portfolio of potentially useful CB\n                    <jats:sub>2<\/jats:sub>\n                    R ligands.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500251","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T22:00:03Z","timestamp":1747778403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Carborane\u2010Based Halogenated Naphthyridinone\u2010Analogues as Cannabinoid Receptor Type 2 (CB\n                    <sub>2<\/sub>\n                    R) Ligands"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9166-2269","authenticated-orcid":false,"given":"Lea","family":"Ueberham","sequence":"first","affiliation":[{"name":"Institute of Bioanalytical Chemistry Centre for Biotechnology and Biomedicine (BBZ) Faculty of Chemistry and Mineralogy Universit\u00e4t Leipzig  Deutscher Platz 5 04103 Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3062","authenticated-orcid":false,"given":"Winnie","family":"Deuther\u2010Conrad","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurooncological Radiopharmacy, Institute of Radiopharmaceutical Cancer Research Helmholtz\u2010Zentrum Dresden\u2010Rossendorf (HZDR) Research Site Leipzig  Permoserstra\u00dfe 15 04318 Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1335-0897","authenticated-orcid":false,"given":"Peter","family":"L\u00f6nnecke","sequence":"additional","affiliation":[{"name":"Institute of Bioanalytical Chemistry Centre for Biotechnology and Biomedicine (BBZ) Faculty of Chemistry and Mineralogy Universit\u00e4t Leipzig  Deutscher Platz 5 04103 Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-1638","authenticated-orcid":false,"given":"Aleksandr","family":"Kazimir","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery Faculty of Medicine Universit\u00e4t Leipzig  Br\u00fcderstra\u00dfe 34 04103 Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-0603","authenticated-orcid":false,"given":"Evamarie","family":"Hey\u2010Hawkins","sequence":"additional","affiliation":[{"name":"Institute of Bioanalytical Chemistry Centre for Biotechnology and Biomedicine (BBZ) Faculty of Chemistry and Mineralogy Universit\u00e4t Leipzig  Deutscher Platz 5 04103 Leipzig Germany"},{"name":"Faculty of Chemistry and Chemical Engineering, Department of Chemistry Babe\u0219\u2010Bolyai University  Str. 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