Patent DE-102005020104-A1 (DE)
Title: 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
Inventor: PRIEN OLAF
IPC: A61P9/00
Filed: 2005-04-25
Abstract: 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 : heteroaryl; A, B 1>H, halo, OH, NR 3>R 4>, CN, NO 2, 1-4C-alkyl, 1-6C-alkoxy, 3-6C-heterocycloalkyl (optionally substituted by halo, OH, 3-6C heterocycloalkyl, NR 3>R 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 3>R 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 3>R 4>, NR 3>SO 2-M, SO 2-NR 3>R 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 3>R 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 3>R 4>; M : 1-6C-alkyl substituted by NR 3>R 4> or 3-6C-heterocycloalkyl; R 1>1-4C-alkyl (optionally substituted with halo, 3C-cycloalkyl, allyl or propargyl); X : -NH- or -NR5; R 2>H or optionally 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 the group of-S-1-6C alkyl, -COR 6>, -NR 3>R 4>, -NR 3>(CO)-L or -NR 3>COOR 7> substituted 1-6C alkyl, 1-6C alkoxy, 1-6C alkenyl, 1-6C alkynyl, 3-6C cycloalkyl, 3-6C heterocycloalkyl or (hetero)aryl, NR 3>R 4>, -NR 3>(CO)-L, -NR 3>(CS)NR 3>R 4>, 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; R 2>R 5>3-6C 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 3>R 4> or -COR 6> or (hetero)aryl, which is optionally with halo, 1-6C alkoxy or COR 6>; either R 3>, R 4>1-6C alkyl, 1-6C-alkoxy, -CO-1-6C alkyl (all optionally substituted with halo, OH, 3-6C heterocycloalkyl, 1-6C hydroxyalkoxy or NR 3>R 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 3>R 4> or -CO-NR 3>R 4>, or H; or R 3>R 4>3-6C 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 3>R 4>; R 5>1-6C 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 3>R 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 3>R 4>, -CO-NR 3>R 4>; R 6>OH, 1-6C alkyl, 1-6C alkoxy or NR 3>R 4>; R 7>-(CH 2) n-aryl or -(CH 2) n-heteroaryl; and n : 1-6. An independent claim is included for a thiazolidinone compound of formula (II) as intermediate in the preparation of (I). [Image] [Image] ACTIVITY : Cytostatic; Antiinflammatory; Immunosuppressive; Neuroprotective; Endocrine-Gen.; Cardiovascular-Gen.; Antimicrobial; Nephrotropic; Virucide; Antipsoriatic; Dermatological; Antiarteriosclerotic; Vasotropic; Anticonvulsant; Nootropic; Muscular-Gen.; Antiparkinsonian; Anti-HIV; Vulnerary; 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.