Thiazolidnones for use as inhibitors of Polo-like kinase (Plk)

• Main Authors: HESS-STUMPP, HOLGER, SIEMEISTER, GERHARD, KOSEMUND, DIRK, EBERSPAECHER, UWE, EIS, KNUT, WORTMANN, LARS, PRIEN, OLAF, ARNAIZ, DAMIAN O, SCHULZE, VOLKER
• Format: Patent
• Language: English
• Published: 26.11.2008
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Thiazolidinone compounds (I) and their salts, solvates, hydrates, stereoisomers, diastereomers and enantiomers are new. Thiazolidinone compounds of formula (I) and their salts, solvates, hydrates, stereoisomers, diastereomers, and enantiomers are new. Q : (hetero)aryl; A, B 1>1-6C alkyl or 1-6-C alkoxy (both optionally substituted by halo, -OH, 2-9C heterocycloalkyl, -NR 3>R 4> or -CO(NR 3>)-M) (where the heterocycloalkyl contains N, O or S and optionally: interrupted by -(CO)-, -SO 2- or double bond in the ring; and the ring is optionally substituted by -CN, halo, halo substituted 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, -COR 2> or -NR 3>R 4>), H, halo, -OH, -NH 2, -NO 2, NR 3>R 4>, -NR 3>(CO)-L, -NR 3>(CO)-NR 3>-L, -COR 2>, -CO(NR 3>)-M, -NR 3>(CS)NR 3>R 4>, -NR 3>SO 2-L, -SO 2-NR 3>R 4> or -SO 2(NR 3>)-M; L : 1-6C alkyl or heteroaryl (both optionally substituted by -OH, 1-6C hydroxyalkoxy, 1-6C alkoxyalkoxy, 2-6C heterocycloalkyl or -NR 3>R 4>, where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bond in the ring; and the ring is optionally substituted by -CN, halo, halo substituted 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, -COR 2> or -NR 3>R 4>); M : 1-6C alkyl (optionally substituted by -NR 3>R 4> or 2-6C heterocycloalkyl), where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bond in the ring; and the ring is optionally substituted by -CN, halo, halo substituted 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, -COR 2> or -NR 3>R 4>; either W 1>heteroaryl or 2-9C heterocycloalkyl, where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bonds in the ring; and X, Y 1>1-6C alkyl, aryl (both optionally substituted by halo, -OH, 1-6C alkoxy, 1-6C alkylthio or aryl), -COOR 5>, -CONR 3>R 4> or H; or W 1>+X+Y 1>3-6C cycloalkyl ring or 2-6C heterocycloalkyl ring, where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bonds in the ring; and the ring is optionally substituted by 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl or -NR 3>R 1>; R 1>1-4C alkyl, 3C-cycloalkyl, allyl or propargyl (all optionally substituted by -CN or halo); R 2>-OH, 1-6C alkyl, 1-6C alkoxy or -NR 3>R 4>; either R 3>, R 4>1-6C alkyl, 1-6C alkoxy, CO-(1-6C)-alkyl, aryl (all optionally substituted by halo, -OH, 2-6C heterocycloalkyl, 1-6C hydroxyalkoxy or -NR 3>R 4>) or H, where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bond in the ring; and 2-6C heterocycloalkyl ring substituted by -CN, halo, 1-6C alkyl, 1-6C hydroxyalkyl, 1-6C alkoxy, 3-6C cycloalkyl, -NR 3>R 4> or -CO-NR 3>R 4>; or R 3>R 4>2-6C heterocycloalkyl ring, where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bonds in the ring; and the ring optionally substituted by halo, 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, 1-6C alkoxyalkyl, -CN, -OH or -NR 3>R 4>; and R 5>1-6C alkyl (optionally substituted by halo, -OH, 2-6C heterocycloalkyl, 1-6C hydroxyalkoxy or -NR 3>R 4>), where the heterocycloalkyl contains N, O or S and optionally interrupted by -(CO)-, -SO 2- or double bonds in the ring; and the ring optionally substituted by 1-6C alkyl, 3-6C cycloalkyl, 1-6C hydroxyalkyl, 1-6C alkoxyalkyl, -CN, -OH or -NR 3>R 4>. An independent claim is also included for an intermediate substituted heterocyclic compound of formula (II). R x>1-3C alkyl. [Image] [Image] ACTIVITY : Cytostatic; Immunosuppressive; Endocrine-Gen.; Cardiovascular-Gen.; Antimicrobial; Neuroprotective. MECHANISM OF ACTION : Polo-like kinase inhibitor.