New imidazolone derivatives are dual-specificity tyrosine-phosphorylation regulated kinase 1A inhibitors useful for treating neurodegenerative diseases, preferably Alzheimer disease and other taupathy, Pick diseases or trisomy 21

摘要

Imidazolone derivatives (I), useful as medicament, are new. Imidazolone derivatives of formula (I), useful as medicament, are new. R 1H, 1-5C alkyl (optionally substituted), aryl or 5 or 6 heterocyclic group (where the aryl and heterocyclic groups comprise optionally one or more substituents occupying any positions); Ar 1aryl group (comprising optionally one or more substituents and two adjacent substituents forming 5 or 6 membered ring (optionally substituted)) or aromatic heterocycle with optionally one or more substituents and/or condensed with 5 or 6 membered aromatic cycle or heteroatoms of N, S or O; R : R 2-S-, R 3-HN-, R 4COHN or Ar 2; R 2linear, branched or cyclic 1-5C alkyl, vinyl or 1-5C vinyl-alkyl, nitrile or 1-5C nitrile-alkyl, aryl or benzyl (all optionally substituted, on one or more carbon atoms, by one or more groups occupying any positions and two adjacent substituents forming 5 or 6-membered ring (optionally substituted)); R 3R 2or H; R 43-5C alkyl; and Ar 2optionally substituted aryl or two adjacent substituents forming 5 or 6-membered ring (optionally substituted). [Image] ACTIVITY : Neuroprotective; Nootropic; Cerebroprotective. MECHANISM OF ACTION : Dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) 1A inhibitor. The ability of (I) to inhibit dual-specificity tyrosine-phosphorylation regulated kinase was tested. The result showed that (I) exhibited an IC 50value of less than 5 ~mM, preferably less than 1 ~mM.