New thiazolidinone compounds are polo-like kinase inhibitors, useful for the preparation of medicament to treat e.g. cancer, autoimmune disease, cardiovascular disease stenosis and infection disease

摘要

Thiazolidinone compounds (I) and their solvates, hydrates, stereoiosomers, diasteromers, enantiomeres or salts are new. Thiazolidinone compounds of formula (I) and their solvates, hydrates, stereoiosomers, diasteromers, enantiomeres or salts are new. Q : aryl; A, B 1H, halo, OH, NR 3R 4, CN, NO 2, 1-4C-alkyl, 1-6C-alkoxy, 3-6C-heterocycloalkyl (optionally substituted by halo, OH, 3-6C heterocycloalkyl, NR 3R 4 or CO(NR 3)-M), (where the heterocycloalkyl contains one or more N, O, S, where -(CO)-, SO 2 or double bonds in the ring is optionally interrupted, where the ring is optionally substituted with 1-6C-alkyl, 3-6C-cycloalkyl, 1-6C-hydroxyalkyl or NR 3R 4), NR 3(CO)-L, -NR 3(CO)-NR 3-L, COR 6, -O-(CH2) pR 6, CO(NR 3)-M, NR 3(CS)NR 3R 4, NR 3SO 2-M, SO 2-NR 3R 4, SO 2(NR 3)-M or O-(CH 2) p-aryl; p : 0-4; L : 1-6C-alkyl, 3-6C-heterocycloalkyl (optionally substituted with NR 3R 4), 1-6C-hydroxyalkoxy, 1-6C-dialkoxy or 3-6C-heterocycloalkyl, where the heterocycloalkyl contains one or more N, O, S, where -(CO)-, SO 2 or double bonds in the ring is optionally interrupted, where the ring is optionally substituted with 1-6C-alkyl, 3-6C-cycloalkyl, 1-6C-hydroxyalkyl or NR 3R 4; M : 1-6C-alkyl (substituted with NR 3R 4 or 3-6C-heterocycloalkyl); R 11-4C-alkyl (optionally substituted with halo, 3C-cycloalkyl, allyl or propargyl); either R 2H or 1-6C alkyl, 1-6C alkoxy, 1-6C alkenyl, 1-6C alkynyl, 3-6C cycloalkyl, 3-6C heterocycloalkyl, aryl or heteroaryl (all optionally substituted with halo, OH, CN, 1-6C alkyl, 1-6C alkoxy, 1-6C hydroxyalkyl, 3-6C cycloalkyl, 3-6C heterocycloalkyl, 1-6C alkynyl, aryloxy, (hetero)aryl or with a group of -S-1-6C alkyl, -COR 6, -NR 3R 4, -NR 3(CO)-L or -NR 3COOR 7), where the heterocycloalkyl is optionally interrupted by one or more N, O or S atoms and/or optionally one or more -(CO)- or -SO 2- group in the ring are interrupted and/or optionally one or more double bonds in the ring, and the (hetero)aryl, 3-6C cycloalkyl or 3-6C heterocycloalkyl ring in each case optionally substituted with one or more CN, halo, OH, 1-6C alkyl, 1-6C hydroxyalkyl, halo substituted 1-6C alkoxy, 3-6C cycloalkyl, 3-6C heterocycloalkyl, benzyl or (hetero)aryl; or R 2R 53-6C heterocycloalkyl ring interrupted by at least one nitrogen and optionally interrupted by one or more O or S, or -(CO)- or -SO 2- group in the ring and one or more double bonds in the ring are interrupted or the ring is optionally substituted by one or more CN, halo, OH, 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, 1-6C alkoxyalkyl or NR 3R 4 or -COR 6 or (hetero)aryl, which is optionally with halo, 1-6C alkoxy, COR 6 or (hetero)aryl; either R 3, R 41-6C alkyl, 1-6C-alkoxy, -CO-1-6C alkyl (all optionally substituted with halo, OH, 3-6C heterocycloalkyl, 1-6C hydroxyalkoxy or NR 3R 4) or aryl and the heterocycloalkyl is optionally substituted by one or more N, O or S or -(CO)- or -SO 2- group in the ring and one or more double bonds in the ring are interrupted or 3-6C heterocycloalkyl ring is optionally substituted by one or more CN, halo, OH, 1-6C alkyl, 1-6C hydroxyalkyl, 1-6C alkoxy, 3-6C cycloalkyl, -NR 3R 4 or -CO-NR 3R 4, or H; or R 3R 43-6C heterocycloalkyl ring interrupted by at least one nitrogen and optionally interrupted by one or more O or S, or -(CO)- or -SO 2- group in the ring and one or more double bonds in the ring are interrupted or the ring is optionally substituted by one or more 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, 1-6C alkoxyalkyl, CN, OH or NR 3R 4; R 51-6C alkyl, 1-6C alkenyl, 1-6C alkynyl (all optionally substituted with halo, OH, CN, 1-6C alkoxy, 3-6C cycloalkyl, 3-6C heterocycloalkyl or NR 3R 4), where heterocycloalkyl is optionally interrupted by one or more N, O or S atoms or -(CO)- or -SO 2- group in the ring and one or more double bonds in the ring are interrupted or the 3-6C heterocycloalkyl ring is optionally substituted by CN, halo, 1-6C alkyl, 1-6C hydroxyalkyl, 1-6C alkoxy, 3-6C cycloalkyl, NR 3R 4, -CO-NR 3R 4; R 6OH, 1-6C alkyl, 1-6C alkoxy or NR 3R 4; R 7-(CH 2) n-aryl or -(CH 2) n-heteroaryl; and n : 1-6. [Image] ACTIVITY : Cytostatic; Immunosuppressive; Endocrine-Gen.; Cardiovascular-Gen.; Antimicrobial; Neuroprotective; Virucide; Antipsoriatic; Dermatological; Antiarteriosclerotic; Vasotropic; Antiparasitic; Nephrotropic; Anticonvulsant; Nootropic; Muscular-Gen.; Antiparkinsonian; Anti-HIV; Antiinflammatory; Hepatotropic. MECHANISM OF ACTION : Polo-like kinase (PLK 1, PLK 2, PLK 3 or PLK 4) inhibitor. The polo-like kinase inhibiting activity of (I) was tested using biological assays. The results showed the (I) exhibited a median inhibitory concentration (IC 5 0) value of 230 nM.