{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:25:18Z","timestamp":1760059518902,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016190","name":"Trond Mohn Foundation","doi-asserted-by":"publisher","award":["TMS2019TMT07"],"award-info":[{"award-number":["TMS2019TMT07"]}],"id":[{"id":"10.13039\/100016190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>6-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines have promising properties as colony-stimulating factor 1 receptor (CSF1R) inhibitors. Inspired by these antagonists, two series of 1,2,3-triazole analogues (28 compounds) were synthesized and evaluated as CSF1R inhibitors. Enzymatic IC50 profiling showed that 27 of the 28 derivatives had lower IC50 than the reference drug PLX-3397. Three derivatives displayed CSF1R Ba\/F3 cellular IC50 well below 1 \u00b5M. Profiling of the most promising triazole analogue (compound 27a) toward a panel of kinases reveals a high selectivity for CSF1R with respect to its family kinases, but 27a also inhibits ABL, SRC, and YES kinases. Molecular docking of 27a toward two CSF1R X-ray structures identified two different ligand-inverted binding poses, which triggers interest for further investigations.<\/jats:p>","DOI":"10.3390\/molecules30122641","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T09:36:00Z","timestamp":1750239360000},"page":"2641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating Triazole-Substituted Pyrrolopyrimidines as CSF1R Inhibitors"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-0965","authenticated-orcid":false,"given":"Srinivasulu","family":"Cherukupalli","sequence":"first","affiliation":[{"name":"Department of Chemistry, Norwegian University of Science and Technology (NTNU), H\u00f8gskoleringen 5, NO-7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-438X","authenticated-orcid":false,"given":"Jan","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH (LDC), Otto-Hahn-Strasse 15, 44227 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Degenhart","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH (LDC), Otto-Hahn-Strasse 15, 44227 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-264X","authenticated-orcid":false,"given":"Peter","family":"Habenberger","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH (LDC), Otto-Hahn-Strasse 15, 44227 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-3763","authenticated-orcid":false,"given":"Anke","family":"Unger","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH (LDC), Otto-Hahn-Strasse 15, 44227 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7859-7810","authenticated-orcid":false,"given":"B\u00e5rd Helge","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Norwegian University of Science and Technology (NTNU), H\u00f8gskoleringen 5, NO-7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirik","family":"Sundby","sequence":"additional","affiliation":[{"name":"Department of Material Science, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.1154370","article-title":"Discovery of a cytokine and its receptor by functional screening of the extracellular proteome","volume":"320","author":"Lin","year":"2008","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cersosimo, F., Lonardi, S., Ulivieri, C., Martini, P., Morrione, A., Vermi, W., Giordano, A., and Giurisato, E. 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