%0 Journal Article %T Exploring the Synthesis of New 1-(4-Substitutedphenylamino) imidazo[1,5-a]indol-3-one Derivatives as Cyclized Analogs of Leucettines %+ ManRos Therapeutics %+ Institut des Sciences Chimiques de Rennes (ISCR) %A Burgy, Guillaume %A Limanton, Emmanuelle %A Carreaux, François %A Durieu, Emilie %A Meijer, Laurent %A Bazureau, Jean-Pierre %Z This research was supported by grants from the ‘Fonds Unique Interministériel” (FUI) PHARMASEA project (LM), the “Association France-Alzheimer (Finistère)” (LM) and “Fondation Jérôme Lejeune” (LM). Guillaume BURGY is recipient of a “CIFRE” PhD fellowship. %< avec comité de lecture %@ 2231-3354 %J Journal of Applied Pharmaceutical Science %I MediPoeia %V 4 %N 6 %P 25 - 32 %8 2014-06 %D 2014 %R 10.7324/JAPS.2014.40604 %K imidazo[1 %K 5-a]indol-3-one %K thiourea %K isothiorurea %K intramolecular %K sulphur/ nitrogen displacement %K protein kinase %K DYRKs %K CLKs %K Leucettines %Z Chemical Sciences %Z Life Sciences [q-bio]/Pharmaceutical sciencesJournal articles %X New 1-arylaminoimidazo[1,5-a]indol-3-ones were synthesized as cyclized derivatives of leucettine L41, a low molecular weight inhibitor of the DYRKs/CLKs protein kinases with potential applications in Alzheimer's disease and Down syndrome. In this first approach, access to the desired 1-aminoimidazo[1,5-a]indol-3-ones involved 5 steps and was explored with a series of various primary amines and polar secondary amines in order to introduce molecular diversity on N-1 position. The 5 step synthesis of the 1-arylaminoimidazo[1,5-a]indol-3-ones was achieved and the limiting step of this process was the final cyclization via a sulphur/nitrogen displacement from methylsulfanyl thiourea intermediates. Good results were obtained for isothioureas derived from primary amines. The 1-arylaminoimidazo[1,5-a]indol-3-ones were evaluated on a panel of five protein kinases (DYRK1A, CK1, CDK5/p25, GSK3α/β and CLK1). %G English %2 https://univ-rennes.hal.science/hal-01116022/document %2 https://univ-rennes.hal.science/hal-01116022/file/1261_pdf.pdf %L hal-01116022 %U https://univ-rennes.hal.science/hal-01116022 %~ UNIV-RENNES1 %~ CNRS %~ INSA-RENNES %~ ENSC-RENNES %~ ISCR %~ SCR_ICMV %~ STATS-UR1 %~ UR1-SPM %~ INC-CNRS %~ UR1-UFR-SPM %~ UR1-HAL %~ ISCR-CORINT %~ UR1-SDLM %~ UR1-SDLMJONCH %~ TEST-UNIV-RENNES %~ TEST-UR-CSS %~ UNIV-RENNES %~ INSA-GROUPE %~ ISCR-CORINT1 %~ UR1-MMS %~ TEST2-HALCNRS