AMINOINDAZOLE DERIVATIVES AS PROTEIN-KINASE INHIBITORS

• Main Authors: LESUISSE, DOMINIQUE, ROONEY, THOMAS, DUTRUC-ROSSET, GILLES, HALLEY, FRANCK
• Format: Patent
• Language: English; French; German
• Published: 26.02.2014
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; 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

3-Acylamino-1H-indazole derivatives (I) are new. Indazole derivatives of formula (I) (including racemates, enantiomers, diastereomers and their mixtures) and their tautomers and salts are new. R = O, S or NH; R3 = alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryl or heteroaryl fused with 1-10C cycloalkyl, heterocyclyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl or alkynyl (all optionally substituted by one or more of halo, CN, NO2, NH2, OH, OR8, COOH, COOR8, OCOR8, NR8R9, NHCOR8, CONR8R9, SR8, SOR8, SO2R8, NHSO2R8, SO2NR8R9, CSNR8R9, NHCSR8, OSO2R8, SO2-OR8, aryl, heteroaryl, CHO, CF3, SCF3 or OCF3); R4 - R7 = H, halo, CN, NO2, NH2, OH, OR8, COOH, COOR8, OCOR8, NR8R9, NHCOR8, CONR8R9, NHCSR8, CSNR8R9, SR8, SOR8, SO2R8, NHSO2R8, SO2NR8R9, OSO2R8, SO2-OR8, CF3 or OCF3; or alkyl, alkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycyl, cycloalkyl, alkenyl, alkynyl, adamantyl or polycycloalkyl (all optionally substituted by one or more of halo, CN, NO2, NH2, OH, OR10, COOH, COOR10, OCOR10, NR10R11, NHCOR10, CONR10R11, NHCSR10, CSNR10R11, SR10, SOR10, SO2R10, NHSO2R10, SO2NR10R11, OSO2R10, SO2-OR10, aryl, heteroaryl, CHO, CF3 or OCF3); and R8 - R11 = H; or alkyl, aryl, alkenyl, alkynyl or heteroaryl (all optionally substituted by one or more of halo, alkyl, alkoxy, CN, NO2, NH2, OH, COOH, alkoxycarbonyl (no C-number given), CONH2, CHO, CF3 or OCF3). alkyl moieties have 1-6C unless specified otherwise. Independent claims are included for: (1) the preparation of (I); (2) the following specific new intermediates: 3-amino-6-chloro-1-tert. butoxycarbonyl-indazole, N-(6-chloro-1-tert. butoxycarbonyl-indazol-3-yl)-3-butenamide, 3-amino-6-chloro-1-((2-trimethylsilyl-ethoxy)-methyl)-indazole, N-((6-chloro-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-propanamide, N-((6-chloro-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide, N-((6-(3-pyridyl)-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide, N-(6-(3-pyridyl)-indazol-3-yl)-butanamide, N-((6-phenyl-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide, N-((6-(furan-3-yl)-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide, N-((6-(4-benzyloxy-phenyl)-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide, N-((6-(3,5-difluorophenyl)-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide and N-((6-(3-thienyl)-1-((2-trimethylsilyl-ethoxy)-methyl)-indazol-3-yl))-butanamide.