Aminoindazole derivatives as medicaments and pharmaceutical compositions including them

A method of treating a disease selected from the group consisting of Alzheimer's, fronto-parietal dementia, Pick's disease, Parkinson's disease, type II diabetes and corticobasal degeneration, in which phosphorylation of the tau protein is observed, comprising administering to a subject in need thereof, an effective amount of a compound of formula (I):

• wherein
• R3 is a (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, aryl or heteroaryl fused to a (3-10C) cycloalkyl, heterocycle, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, SO2R1, C(═NH)R1 or C(═NH)NHR1 radical;
• these radicals optionally being substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR1, COOH, C(O)OR1, —O—C(O)R1, NR1R2, NHC(O)R1, C(O)NR1R2, SR1, S(O)R1, SO2R1, NHSO2R1, SO2NR1R2, C(S)NR1R2, NHC(S)R1, —O—SO2R1, —SO2—O—R1, aryl, heteroaryl, heterocycle, formyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C)alkyl;
• R5 is an aryl optionally substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, —O—C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, —O—SO2R10, —SO2—O—R10, aryl, heteroaryl, formyl, trifluoromethyl, trifluoromethoxy or (1-6C)alkyl;
• R6 is a halogen, methyl, cyclopropyl, CN, OH, methoxy, trifluoromethyl, ethylenyl, acetylenyl, trifluoromethoxy, NO2, NH2 or NMe2 radical;
• R1, R2, R10 and R11 are, independently of one another, a hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, themselves optionally being substituted by 1 or more substituents chosen from halogen, (1-6C)alkyl, (1-6C)alkoxy, CN, NO2, NH2, OH, COOH, COOalkyl, CONH2, formyl, oxo, trifluoromethyl or trifluoromethoxy;
• or
• R1 and R2 can form a 5- or 6-membered ring which may have an additional heteroatom, such as O, S or N;
• or a racemate, enantiomer, diastereoisomer, tautomer or mixture thereof, or pharmaceutically acceptable salt thereof.

A method of treating a disease selected from the group consisting of Alzheimer's, fronto-parietal dementia, Pick's disease, Parkinson's disease, type II diabetes and corticobasal degeneration, in which phosphorylation of the tau protein is observed, comprising administering to a subject in need thereof, an effective amount of a compound of formula (I):

• wherein
• R3 is a (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, aryl or heteroaryl fused to a (3-10C) cycloalkyl, heterocycle, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, SO2R1, C(═NH)R1 or C(═NH)NHR1 radical;
• these radicals optionally being substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR1, COOH, C(O)OR1, —O—C(O)R1, NR1R2, NHC(O)R1, C(O)NR1R2, SR1, S(O)R1, SO2R1, NHSO2R1, SO2NR1R2, C(S)NR1R2, NHC(S)R1, —O—SO2R1, —SO2—O—R1, aryl, heteroaryl, heterocycle, formyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C)alkyl;
• R5 is a phenyl optionally substituted by 1 or more substituents selected from halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, —O—C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, —O—SO2R10, —SO2—O—R10, aryl, heteroaryl, formyl, trifluoromethyl, trifluoromethoxy or (1-6C)alkyl;
• R6 is a halogen, methyl, cyclopropyl, CN, OH, methoxy, trifluoromethyl, ethylenyl, acetylenyl, trifluoromethoxy, NO2, NH2 or NMe2 radical;
• R1, R2, R10 and R11 are, independently of one another, a hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, themselves optionally being substituted by 1 or more substituents chosen from halogen, (1-6C)alkyl, (1-6C)alkoxy, CN, NO2, NH2, OH, COOH, COOalkyl, CONH2, formyl, oxo, trifluoromethyl or trifluoromethoxy;
• or
• R1 and R2 can form a 5- or 6-membered ring which may have an additional heteroatom, such as O, S or N;
• or a racemate, enantiomer, diastereoisomer or a mixture thereof, or a tautomer or a pharmaceutically acceptable salt thereof.

A method of treating a disease selected from the group consisting of Alzheimer's, fronto-parietal dementia, Pick's disease, Parkinson's disease, and corticobasal degeneration;

• comprising administering to a subject in need thereof, an effective amount of a compound of formula (I):
• wherein
• R3 is selected from the group consisting of a (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, aryl or heteroaryl fused to a (3-10C) cycloalkyl, heterocycle, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, SO2R1, C(═NH)R1 or C(═NH)NR1 radical;
• these radicals optionally being substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR1, COOH, C(O)OR1, —O—C(O)R1, NR1R2, NHC(O)R1, C(O)NR1R2, SR1, S(O)R1, SO2R1, NHSO2R1, SO2NR1R2, C(S)NR1R2, NHC(S)R1, —O—SO2R1, —SO2—O—R1, aryl, heteroaryl, heterocycle, formyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C)alkyl;
• R5 and R6 are, independently of one another, chosen from the following radicals:
• halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, —O—C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, —O—SO2R8, —SO2—O—R8, trifluoromethyl, trifluoromethoxy, (1-6C)alkyl, (1-6C)alkoxy, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, heterocycle, cycloalkyl, alkenyl, alkynyl, adamantyl or polycycloalkyl;
• these radicals optionally being substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, —O—C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, —O—SO2R10, —SO2—O—R10, aryl, heteroaryl, formyl, trifluoromethyl, trifluoromethoxy or (1-6C)alkyl;
• R1, R2, R8, R9, R10 and R11 are, independently of one another, a hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl, or a heteroaryl, themselves optionally being substituted by 1 or more substituents selected from the group consisting of halogen, (1-6C)alkyl, (1-6C)alkoxy, CN, NO2, NH2, OH, COOH, COOalkyl, CONH2, formyl, trifluoromethyl, and trifluoromethoxy;
• or
• R1 and R2 or R8 and R9 or R10 and R11 can form a 5- or 6-membered ring which may or may not have an additional heteroatom, such as O, S or N;
• and, when R3 is a 6-membered nitrogenous heteroaryl or a thiazolyl or an imidazolyl or an oxazolyl, then at least one of the R5 and R6 groups is an aryl which is optionally substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, —O—C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, —O—SO2R10, —SO2—O—R10, aryl, heteroaryl, formyl, trifluoromethyl, trifluoromethoxy or (1-6C)alkyl;
• its' racemates, enantiomers or diastereoisomers and their mixtures, its tautomers and or its pharmaceutically acceptable salts.

A method of treating type II diabetes;

• comprising administering to a subject in need thereof, an effective amount of a compound of formula (I)
• wherein
• R3 is a (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, aryl or heteroaryl fused to a (3-10C) cycloalkyl, heterocycle, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, SO2R1, C(═NH)R1 or C(═NH)NHR1 radical;
• these radicals optionally being substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR1, COOH, C(O)OR1, —O—C(O)R1, NR1R2, NHC(O)R1, C(O)NR1R2, SR1, S(O)R1, SO2R1, NHSO2R1, SO2NR1R2, C(S)NR1R2, NHC(S)R1, —O—SO2R1, —SO2—O—R1, aryl, heteroaryl, heterocycle, formyl, trifluoromethyl, trifluoro-methylsulfanyl, trifluoromethoxy or (1-6C)alkyl;
• R5 is an aryl optionally substituted by 1 or more substituents chosen from halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, —O—C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, —O—SO2R10, —SO2—O—R10, aryl, heteroaryl, formyl, trifluoromethyl, trifluoromethoxy or (1-6C)alkyl;
• R6 is a halogen, methyl, cyclopropyl, CN, OH, methoxy, trifluoromethyl, ethylenyl, acetylenyl, trifluoromethoxy, NO2, NH2 or NMe2 radical;
• R1, R2, R10 and R11 are, independently of one another, a hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, themselves optionally being substituted by 1 or more substituents chosen from halogen, (1-6C)alkyl, (1-6C)alkoxy, —CN, —NO2, —NH2, —OH, —COOH, —COOalkyl, —CONH2, formyl, oxo, trifluoromethyl or trifluoromethoxy;
• or
• R1 and R2 can form a 5- or 6-membered ring which may have an additional heteroatom, such as O, S or N;
• or a racemate, enantiomer, diastereoisomer, tautomer, or mixture thereof, or pharmaceutically acceptable salt thereof.