{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:12:33Z","timestamp":1788999153548,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Rouen Normandy","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"University of Rouen Normandy","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"INSA Rouen Normandy","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"INSA Rouen Normandy","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"Centre National de la Recherche Scientifique (CNRS)","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"Centre National de la Recherche Scientifique (CNRS)","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"European Regional Development Fund (ERDF)","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"European Regional Development Fund (ERDF)","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"Labex SynOrg","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"Labex SynOrg","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"Carnot Institute I2C","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"Carnot Institute I2C","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"graduate school for research Xl-Chem","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"graduate school for research Xl-Chem","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]},{"name":"R\u00e9gion Normandie","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]},{"name":"R\u00e9gion Normandie","award":["ANR-18-EURE-0020 XL CHEM"],"award-info":[{"award-number":["ANR-18-EURE-0020 XL CHEM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The DYRK (Dual-specificity tyrosine phosphorylation-regulated kinase) family of protein kinases is involved in the pathogenesis of several neurodegenerative diseases. Among them, the DYRK1A protein kinase is thought to be implicated in Alzheimer\u2019s disease (AD) and Down syndrome, and as such, has emerged as an appealing therapeutic target. DYRKs are a subset of the CMGC (CDK, MAPKK, GSK3 and CLK) group of kinases. Within this group of kinases, the CDC2-like kinases (CLKs), such as CLK1, are closely related to DYRKs and have also sparked great interest as potential therapeutic targets for AD. Based on inhibitors previously described in the literature (namely TG003 and INDY), we report in this work a new class of dihydroquinolines exhibiting inhibitory activities in the nanomolar range on hDYRK1A and hCLK1. Moreover, there is overwhelming evidence that oxidative stress plays an important role in AD. Pleasingly, the most potent dual kinase inhibitor 1p exhibited antioxidant and radical scavenging properties. Finally, drug-likeness and molecular docking studies of this new class of DYRK1A\/CLK1 inhibitors are also discussed in this article.<\/jats:p>","DOI":"10.3390\/molecules28010036","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T05:42:53Z","timestamp":1671601373000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Straightforward Access to a New Class of Dual DYRK1A\/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-8080","authenticated-orcid":false,"given":"Mihaela-Liliana","family":"\u0162\u00een\u0163a\u015f","sequence":"first","affiliation":[{"name":"INSA Rouen Normandie, Univ. Rouen Normandie, CNRS UMR 6014 COBRA, FR 3038, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-1471","authenticated-orcid":false,"given":"Ludovic","family":"Peauger","sequence":"additional","affiliation":[{"name":"VFP Therapies, 15 rue Fran\u00e7ois Couperin, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Alix","sequence":"additional","affiliation":[{"name":"VFP Therapies, 15 rue Fran\u00e7ois Couperin, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-6844","authenticated-orcid":false,"given":"Cyril","family":"Papamica\u00ebl","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ. Rouen Normandie, CNRS UMR 6014 COBRA, FR 3038, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3025-6659","authenticated-orcid":false,"given":"Thierry","family":"Besson","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ. Rouen Normandie, CNRS UMR 6014 COBRA, FR 3038, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-8120","authenticated-orcid":false,"given":"Jana","family":"Sopkov\u00e1-de Oliveira Santos","sequence":"additional","affiliation":[{"name":"UNICAEN, CERMN (Centre d\u2019Etudes et de Recherche sur le M\u00e9dicament de Normandie), Normandie Univ., Bd Becquerel, F-14032 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Gembus","sequence":"additional","affiliation":[{"name":"VFP Therapies, 15 rue Fran\u00e7ois Couperin, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-1965","authenticated-orcid":false,"given":"Vincent","family":"Levacher","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ. Rouen Normandie, CNRS UMR 6014 COBRA, FR 3038, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2022). Alzheimer\u2019s association report, 2022 Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 18, 700\u2013789.","DOI":"10.1002\/alz.12638"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-neuro-061010-113613","article-title":"Amyloid precursor protein processing and Alzheimer\u2019s disease","volume":"34","author":"Wong","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharm. 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