New 3-acylamino-1H-indazole derivatives, are tau-protein phosphorylation inhibitors useful e.g. for treating neurodegenerative diseases, metabolic diseases, hypertension or cancer

摘要

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.