TW200422293A - Novel aminoindazole derivatives as medicaments and pharmaceutical compositions including them - Google Patents

Abstract

The present invention relates to novel derivatives of general formula (I), in which R3 is a (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, aryl or heteroaryl fused to a (1-10C) cycloalkyl, heterocycle, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, COOR1, SO2R1, C(=NH)R1 or C(=NH)NR1 radical; R5, R6 and R7 are, independently of one another, chosen from the following radicals: halogen, CN, NO2, NH2, OH, OR8, 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.

Description

2004222 93 A7 B7 V. Description of the invention (1) The present invention relates to derivatives of formula (I)

Printed by the Shellfish Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

, NH

Or use of a pharmaceutically acceptable salt thereof as a kinase inhibitor. The main purpose of the present invention is the use of the formula amide amino derivative and its pharmaceutically acceptable salt for the preparation of a pharmaceutical composition for preventing and treating diseases caused by abnormal kinase activity. For example, they involve Neurodegenerative diseases, Alzheimer's disease, Bayeuson's disease, frontal and parietal dementia, degeneration of the cortical base, Pick's disease, stroke, cranial and spinal trauma, side neuropathy, Obesity, metabolic diseases, type H diabetes, essential hypertension, arteriosclerotic cardiovascular disease, polycystic ovary syndrome, χ 15 syndrome, immunodeficiency and cancer, and the novel amine indazole derivative and its medicine Pharmaceutically acceptable salts of the pharmaceutical composition, and the neolysamine 1 salivary derivative and a pharmaceutically acceptable salt thereof. Patent application WO 02/074388 describes (a) type amino indazole derivative 'and its potassium channel activator 20 G, -3- 2004222 93 A7 _____ B7 V. Description of the invention (2)

z is NXO, s or 〇, E is N or CX1, 5 γ is halogen., X2 or 0X2, X〇, XI and X2 are halide, alkyl or substituted alkyl, A, B and D are hydrogen , Halogen, substituted or unsubstituted alkyl, C (0) pR13, C (〇) NR13R14, S02NR13, R14, S (0) pR15, 〇R15, or NR13R14, lOP is an integer from 0 to 2, R13 and R14 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroalkane , Substituted or future generation heteroaryl-heteroalkyl, or substituted or unsubstituted aryl_heteroalkyl, 15 R15 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkane Group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroaryl-heteroalkyl, or substituted or unsubstituted Substituted aryl-heteroalkyl. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs This invention is related to the formula VII derivative, its racemate, enantiomer or 20 diastereomer and its mixture, its tautomer and its pharmaceutically acceptable Salt, wherein: R3 is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, and (ii〇C) ring Alkyl-fused aryl or heteroaryl, heterocyclic, heterocyclic alkyl, cycloalkyl, adamantine, polycyclic alkyl, alkenyl, fast-4- This paper applies to Chinese National Standards (CNS) A4 specification (210 X 297 mm) 2004222 93 A7 B7 V. Description of the invention (3) base, C0NR1R2, CSNR1R2, C00R1, S02R1, C (= NH) R1 or C (= NH) NR1 group; these groups Optionally substituted with one or more substituents selected from the group consisting of halogen, CN, N02, NH2, 0H, 0R1, COOH, C (0) 0R1, -0-C (0) R1, NR1R2, 5 NHC (0 ) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1, -0-SO2RI, -SO2-O-RI, aryl, Heteroaryl, heterocyclic, methyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethyloxy (1-6C) alkyl; R5, R6 and R7 printed by the Industrial Property Cooperative of the Intellectual Property Bureau of the Ministry of Economy are each independently selected from the group consisting of: halogen, CN, 10 N02, NH2, OH, COOH, C (0) 0R8, -0-C (0) R8, NR8R9, NHC (0) R8, C (Q) NR8R9, NHC (S > R8 ,, --C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0-S02R8, -SCVO-R8, trifluoromethyl, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl ( 1-6C) alkyl, 15 heteroaryl, heteroaryl (1-6C) alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, adamantyl or polycyclic alkyl; these groups are visible Need to be substituted with one or more substituents selected from: halogen, CN, N02, NH2, 0H, ORIO, COOH, C (O) OR10, -OC (O) R10, NR10R11, NHC (O) R10, C (O) NR10Rll, NHC (S) R10, 20 C (S) NR10R11, SR10, S (O) R10, SO2R10, NHSO2R10, SO2NR10Rll, -0-SO2R10, -so2-o-rio, aryl, heteroaryl , Fluorenyl, trifluoromethyl, trifluoromethoxy, or (1-6C) alkyl; RJ, R2, R8, R9, R10, and R11 are separate; J is independently hydrogen, (1-6C) alkyl , Aryl, alkenyl, alkyne Heteroaryl, which itself can be applied to a Chinese standard (CNS) A4 specification (210x297 mm) via this paper size as required. 2004222 93 A7 ----- B7 5. Description of the invention (4) or more selected from the following Substituted by substituents: halogen, alkyl, (1-6C) alkyloxy, CN, no2, NH2, OH, COOH, COO alkyl, CONH2, formamyl, trifluorofluorenyl, trifluorofluorenyloxy; R1 and R2 or R8 and R9 or Ri〇 and R11 may form a 5-membered or 6-membered ring, 5 of which may or may not contain heteroatoms, such as: 0, s or N; and when R3 is a 6-membered nitrogen-containing heterocyclic ring In the case of aryl or thiazolyl or imidazolyl or azazolyl, then at least one of R5 and R6 is an aryl group, which may be optionally substituted with one or more substituents selected from the group consisting of halogen, CN, N02, NH2, OH ORIO, COOH, C (O) OR10, -0-C (0) R10, 10 NR10R11, NHC (0) R1〇, C (O) NR10Rll, NHC (S) R10, C (S) NR1GR11, s | jL0, S (O) R10, SO2R10, NHSO2R10, SO2NR10Rll, -〇 ^ 〇2ri〇, -SO2-O-R10, aryl, _aryl, formamyl, trifluoromethyl i, trifluoroamyloxy or (i-6C) alkyl. More specifically, the present invention relates to derivatives of formula (I), the racemates, 15 enantiomers or diastereomers and mixtures thereof, tautomers and pharmaceutically acceptable salts thereof, of which: The R3 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, and (1- 10C) Cycloalkyl fused aryl or heteroaryl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl 20, CONR1R2, CSNR1R2, COOR1, S02R1 , C (= NH) R1 or C (= NH) NR1 groups; these groups may be optionally substituted with one or more substituents selected from the group of halogen, CN, N02, NH2, OH, OR1, COOH , C (0) 0R1, -0-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, -6- This paper standard applies to Chinese national standards (CNS) A4 specification (210 X297 mm) 2004222 93 A7 V. Description of the invention (5) NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1, -0-S02R1, -S02-0-Rl, Fang Radical, heteroaryl, heterocyclic, formamyl, trifluorofluorenyl, trifluoromethylsulfanyl, tris Fluorofluorenyl or (1-6C) alkyl; R5 and R6 are each independently selected from the group consisting of halogen, CN, N02, 5 NH2, OH, C00H, C (0) 0R8, -0-C ( 0) R8, NR8R9, NHC (0) R8, C (0) NR8R9, NHC (S) R8, C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0-S02R8,- S02-0-R8, trifluorofluorenyl, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl10 (1-6C) alkyl, heterocyclic, cycloalkyl, dialkyl, alkynyl, adamantyl, polycycloalkyl; these groups may be substituted with one or more substituents selected from the following: Halogen, CN, No2, NH2, OH, OR10, COOH, C (O) OR10, -〇-C (O) R10, NR10R11, NHC (O) R10, C (O) NR10Rll, NHC (S) R10 , C (S) NR10R11, SR10, 15 S (O) R10, SO2R10, NHSO2R10, SO2NR10Rll, -0_SO2R10, -S〇2-〇-R1〇, aryl, heteroaryl, fluorenyl, trifluoromethyl Base, trifluorofluorenyloxy or (1_6C) alkyl; printed by R7 for halogen, methyl, cyclopropyl, cn, 0H, fluorenyloxy, trifluoromethyl, vinyl B , Trifluoromethoxy, no2, NH2 or NMe2, 2〇α, R2, R8, R9, R10 and R11 are each independently hydrogen, (1-6Q alkyl, aryl, alkenyl, alkynyl or Heteroaryl, itself may be substituted with one or more substituents selected from the group consisting of dentin, (1-6C) alkyl, (1-6C) oxy, CN, N02, NH2, OH, COOH , COO alkyl, CONH2, ethyl alcohol, trifluorofluorenyl or trifluoromethoxy; -7- This paper size applies to China National Standards (CNs) A4 (210x297 public love) 2004222 93 B7 V. Description of the invention (6) R1 and R2 or R8 and R9 or R10 and R11 may form a 5- or 6-membered ring, which may or may not contain heteroatoms, such as: 〇, S or N; and when R3 is 6-membered nitrogen When heteroaryl or thiazolyl, imidazolyl or oxazolyl, at least one of R5 and R6 is an aryl group, which may be substituted with 5 or more substituents selected from halogen, CN, N02, NH2 , OH, ORIO, COOH, C (0) 〇R1〇, -〇-C (0) R1〇, NR10R11, NHC (0) R1〇, C (0) NR10R11, NHC (S) R10, C (S) NR10R1 SR10, S (O) R10, SO2R10, NHS02R1〇, SO2NR10RU, -O-SO2R10, -so2-o-rio, Group, a heteroaryl group, Yue 10 acyl, trifluoromethyl, trifluoromethoxy 'and (1-6C) alkyl. According to the present invention, the guanidinium derivative is preferably a racemic poplar, a spectral enantiomer or a diastereomer and a mixture thereof, a tautomer and a true pharmaceutically acceptable salt thereof, wherein: Ministry of Economic Affairs The Intellectual Property Bureau Shellfish Consumer Cooperative printed R3 as (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl 15 (1-6C) alkyl, and ( M0C) cycloalkyl fused aryl or heteroaryl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, S02R1 or C (= NH) NR1 groups; these groups may optionally be substituted with one or more substituents selected from the group consisting of: halogen, CN, N02, NH2, OH, OR1, 20 COOH, C (0) 0R1,- 0-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) iU, -0 -S02Rl, -S02-0-R1, aryl, heteroaryl, fluorenyl, oxo, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C) alkane Basic; -8- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 2004222 93 V. Invention (7) R5 is aryl; 6 and R7 are independently halogen, fluorenyl, cyclopropyl, OH, fluorenyloxy, difluorofluorenyl, vinyl, ethynyl, trifluorofluorenyl ,, NH2 or NMe2, R1 and R2 are each independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl or heterosquaryl, and may be substituted by one or more substituents selected from the following: Halogen, (1-6C) alkyl, (1-6C) alkoxy, CN, N02, NH2, oh, COOH, COO alkyl, CONH2, formamyl, oxo, trifluorofluorenyl or trifluoro Phenoxy; 10 15 Printed by Shelley Consumer Cooperatives, Bureau of Intellectual Property, Ministry of Economic Affairs 20 R1 and R2 may form a 5- or 6-membered ring, which may or may not contain heteroatoms, such as: 〇, S or N〇 This invention Preferably, the related formula VII derivative is a racemate, an enantiomer or a diastereomer and a mixture thereof, a tautomer and a pharmaceutically acceptable salt thereof, wherein: R3 is (1-6C) Aryl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, aryl or heteroaryl fused with (moc) cycloalkyl, heterocyclic ring, heterocyclic ring Alkyl, cycloalkyl, adamantyl, poly Alkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, S02R1 or C (= NH) NR1 groups; these groups may be optionally substituted with one or more substituents selected from the group consisting of: halogen, CN, N 〇2, NH2, OH, OR1, COOH, C (0) 0R1, -0-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1 NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1, -0-S02Rl, -S02-0-

Ri, aryl, heteroaryl, fluorenyl, oxo, trifluorofluorenyl, trifluorofluorene-9- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 2004222 93 Β7 V. Description of the invention (8) sulfanyl, trifluorofluorenyl or (1-6C) alkyl; R5 is aryl; R6 is halogen, methyl, cyclopropyl, CN, OH, fluorenyl, Trifluorofluorenyl, vinyl, ethynyl, trifluoromethoxy, No2, NH2 or NMe2; 5 R7 is halogen; R1 and R2 are independently hydrogen, (1-6C) alkyl, aryl, dilute Group, alkynyl or heteroaryl group, which may itself be substituted with one or more substituents selected from the group consisting of halogen, (1-6C) alkyl, (1-6C) alkoxy, CN, N02, NH2 , OH, COOH, COO alkyl, CONH2, fluorenyl, oxo 10, trifluoromethyl, or trifluorofluorenyl; R1 and R2 may form a ^ or 6-membered ring, which may include heteroatoms as required, For example: 〇, S or N 〇 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs above and below. In the above definition, (1-6C) alkyl contains 1 to 6 carbon atoms in the linear or i-chain; olefins are based on straight bonds. Or 2 to 6 branches 15 carbon atoms with 1 to 3 common or non-conjugated double bonds; alkynes are based on straight or branched bonds containing 2 to 6 carbon atoms and 1 to 3 conjugated or non-conjugated reference bonds; aryl groups are optional From: phenyl, naphthyl or indenyl; heteroaryl contains 3 to 10 ring members, which may optionally contain one or more heteroatoms selected from: oxygen, sulfur and nitrogen, specifically thiazolyl, Thienyl, pyrrolyl, pyridyl, 20 ° sulfonyl, imosalyl, "f" phenyl, hydrazone, tetra "phenyl, uf difluorenyl, thiadiazolyl, isodiadiazole , Isothiazolyl, isothiazolyl, isomorphazolyl, tris. Sitting on the base. Biazolyl or indolyl; halogen group is chlorine, iodine, fluorine or bromine; polycyclic alkyl is selected from the group consisting of adamantyl, quinuclidinyl, norbornyl, and original ice-10- This paper size Applicable to Chinese specifications (210 χ 297 mm) 2004222 93 V. Description of the invention (0 burned base, borneol dilute base, original borneol base; Heteroaryl group slightly compatible with (Moc) ring courtyard base is selected from: Indanyl, isochromanyl, chromanyl, i, 2,3,4-tetrahydroisohaloyl or 1,2,3,4-tetrahydrolinyl; heterocyclyl contains i to 2 options Since ... heteroatoms in oxygen, sulfur, and nitrogen, specifically, hexahydroquinone, 5-morpholinyl, transionate, odorol, "biqenyl, isofluorene, thiazole , Different. Seated bite "No. saliva, hexahydro ^, ah, denyl, 2-hexahydro roar, 3. hexahydro σ ratio bite, hexanitrogen, 2 ice Luo 阙 or 3- "Than slightly 阙. The compound of formula (I) has one or more asymmetric carbons, so it can be in the form of 10 isomers, racemates, isomers and diastereomers; the latter Also as a mixture thereof, g becomes part of the present invention. In the following compounds, the following compounds can be mentioned: UL · N · (Bicyclic [2.2.im-5- 稀 · 2-ylmethyl) _6_ 气 _7_ 气 _5phenyl_ih "15 azole_ 3-Amine 6-Ga-7-Fluoro-N- (3,3--methylbutyl) -5-phenyl-1H- "bow Preparation of 6-Ga-7-Fluoro-N- (3-phenylpropyl) -5 · phenyl-1 H-indazol-3-amine 6-Ga-7-say-N- (cyclopropylmethyl ) -5-phenyl-1fluorene-fluorene-3-amine 6-gas-7-fluoro (cyclopentylfluorenyl) -5-phenyl-1fluorene-indazole jamine 20 6-gas | fluorine- N- [3_ (methylthio) propyl] -5-phenylazolamine 6-gas-7-fluoro-N- (phenethyl) -5-phenyl-1H-indazole-3-amine 6 -Ga-7-deca-N- (cyclohexylmethyl) _5-phenylene. Sitting-3-amine 6-Ga-7-fluoro-N-propyl-5-phenyl-lH-i. Sitting- 3-amine 6-gas-7-fluoro small- (2,2,3,3,4,4,4-heptafluorobutyl) -5-benzyl-111_, azole_3-amine-11- this paper Standards apply to China National Standard (CNS) A4 specifications (210x297 mm) 2004222 93 B7 V. Description of the invention (10) Hydrate 6-gas-7-fluoro-N- (4,4,4-trifluorobutyl)- 5-phenyl-1H-indazole-3-amine 6-gas-7-fluoro-N-[(4-methoxyphenyl) fluorenyl] -5-phenyl-1H-indazole-3-amine 6-Ga-7-Fluoro (benzylmethyl) -5-phenyl-1H-indazole-3 -Amine 5 6-Ga-7-Fluoro "N-[(4-cyanophenyl) fluorenyl] _5-phenyl-1H-indazole-3-amine N-[(4-Gaphenyl) methyl ] -6-Ga-7-fluoro-5-phenyl-1H-indazol-3-amine 6-Ga-7-fluoro-N-[(3-methoxyoxyphenyl) methyl] -5-benzene 1H-indazole-3-amine 6-gas-7-fluoro-N-[[4_ (trifluorofluorenyloxy) phenyl] fluorenyl] -5-phenyl-1H-indazole · 3-amine 10 N- [4-[[[6-Ga-7-fluoro-5-phenyl-1H-indazol-3-yl] amino] methyl] phenyl] ethanamine read 6 · Ga-7- Fluoro-N · [(3,5-Difluorophenyl) fluorenyl] _5_phenyl-1H-ind $ 3-amine 6-gas-7-fluoro-5-phenyl-N-[[4- (tri Fluoromethyl) phenyl] fluorenyl] -_- indazol-3-amine 15 6-gas-7-fluoro-N · [(4-fluorophenyl) fluorenyl] -5-phenyl-1fluorenyl-indole Azole-3-amine 6-gas-7-fluoro-N- [3- (4-methylphenoxy) phenylmethyl] -5-phenyl-1fluorene-indazole- • 3 fluoramine intellectual property (2,2,3,3,4,4,4-heptafluorobutyl) -6-gas_7-fluoro-5-phenyl-111-indazole-3-amine 6 -Ga-7-fluoro-5-phenyl-N-[[3,5-bis (trifluorofluorenyl) phenyl] methyl] -1Η-ind20azole-3-amine 6-gas-7-fluoro -5-phenyl-N-[[3- (trifluorofluorenyl) phenyl] fluorenyl] -1 fluorene-indazole-3-amine 6-gas-7-fluoro-N-[(6-fluorenyloxy Yl-2-naphthyl) fluorenyl] -5- -1A-indazol-3-amine 6-Ga-7-fluoro-N-[(pentafluorophenyl) methyl] -5-phenyl-l-A-11-11 Paper size applies to China National Standard (CNS) A4 specification (210x297 mm) 2004222 93 A7 V. Description of invention (η) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs-7-Fluoro-N-[[4- ( Fluorenylthio) phenyl] methyl] iphenyl · 1Η ^ σaspartate N-[(4-Ga_3 · fluorobenzyl) fluorenyl] -6-Ga-7-fluoro-5-phenyl -1Η · indazole-3-amine 6-Ga-7-fluoro-5-phenyl-N- (3,3,3-trifluoropropyl) -1 hafnium, oxazamine 6-Ga-7-fluoro -5-phenyl-N- (3-thienylfluorenyl) -1fluorene-indazol-3-amine 5 NR- (bicyclo [2 · 2 · 1] hept-5-en-2-ylfluorenyl)- 6-Ga-7-fluoro · 5-phenyl-1Η-indazole-3-amine N- (1, Γ-biphenyl-4-ylfluorenyl) winter gas-7-fluoro-5-phenyl · 1Η -Indazol-3-amine 6mN-[[4- (dimethylamino) phenyl] methyl] phenyl_ιη-ιικι-3-amine 10 Ν- (2,2'-linked Thien-5-ylfluorenyl) winter gas-7-fluoro: phenyl-11 !, azole_3-amine 6-gas-7-fluoro-5-phenyl-1nJ _ [[1- (phenylfluorenyl) -1 crush_imidazole, 2-yl] methyl] "fluorene-indazol-3-amine 6-gas-7-fluoro-N-[[1-methyl-1H-imidazol-2-yl] methyl] -5-benzyl-1 GAHN-[(1-methyl-1H-decadol) methyl] jphenyl-1Hn 3-amine 6-gas-7-deca-qin [(5-fluorenyl-2-furanyl) fluorene Yl] _5_phenyl-1H, azole-3-amine 6-gas_7_fluoro-5-phenyllo-2-ylmethyl) -1Η- «bow 丨 sia-3-amine 6-gas-7 -Fluoro-5-phenyl-N-[(1H-imido-2_yl) methyl] -1H-®gumbu-3 -amine 6-gas "7-fluoro-5-phenyl · N- [(ΙΗ-Miso-4-yl) methyl] pyroxy-3-amine 6-air-7-fluoro-5-phenyl-NχΐΗ-11 than jun-3-ylmethyl) -1Η- ° 5azo-3-amine 6-gas-7-fluoro-N-[[2-methyl-1fluorenyl-imidino] fluorenyl] -5-phenyl-lim 3-amine 6-gas-7 · fluoro -N _ [(3,5-Difluorenyl-1-phenyl-1Η- ° than fluorenyl) fluorenyl] -5-ben 15 20 13- 4 Order

4 II This paper size is in accordance with China National Standard (CNS) A4 specification (210x297 public love) 2004222 93 A7 B7 V. Description of the invention (12) 1H-indazole-3-amine 6-gas-7-fluoro-5- Phenylhydrazone- [| > phenyl-111-imidazol-4-yl] methyl] -1H-indazol-3-amine 6-gas-7-fluoro-N-[[5- (4-chlorobenzene ) -2-furanyl] fluorenyl] -5-benzyl-1H-ind5azol-3-amine6-gas-7-fluoro-5_phenyl-N-[(1-fluorenyl-1H -Pyrrole-2-yl) fluorenyl] -1fluorene-indazole- 3-amine 4- [5-[[[6- ] Amine] methyl] -2-sigmadol] -benzenesulfonamide 10 6-Ga-7-Ga-5-phenyl-N_ (3-fluorenylfluorenyl) -1Η-σbow 丨17 guan-3-amine 6-gas-7-fluoro-5-phenyl;-[] > phenyl-1'-imidazol-4-yl] methyl] -1'-indazole-: fluorene: 3-amine .- ·. 2-[[[6- 气 -7- 气 -5- 东 基 -1Η-ββ | Jun-3 -yl] amino] methyl] -5- (fluorenylthio) -1Η- Imidazole-4-carboxylic acid ethyl ester 15 6-Ga-7-fluoro-5-phenyl-N-[[5- [4- (trifluoromethyl) phenyl] -2-furanyl] methyl]- 1Η-Indazole-3-amine Printed by 6-Ga-7-Fluoro-5-phenyl-N- [2- (l-Hexahydropyridyl) ethyl] -1Η_indazole-3-amine 6-air-7-fluoro-N- [2- (4-morpholinyl) Ethyl] -5-phenyl-1fluorene-indazol-3-amine N- (6-gas-7-fluoro-5-phenyl-1fluorene-indazol-3-yl) -N ·-(3,5 -Digas phenyl) urea 20 Ν- (6-Ga-7-Fluoro "-5-phenyl-1σ-σbow | ° Sit-3-yl) -N ·-(2-propenyl) vein N -(6-Ga-7-fluoro-5-phenyl-1 ''-indazol-3-yl) -N′phenylmethyl) urea N- (6-Ga-7-fluoro-5-phenyl-1′- Indazol-3-yl) -N ·-(4-phenoxyphenyl) urea N- (6-Ga-7-fluoro-5-phenyl-1H-indazol-3-yl) -N ·- (4-Methoxyphenyl) fluorenyl] Urea-14- This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 public «) 2004222 93 A7 V. Description of the invention (13) N- (6- GA-7-fluoro-5-phenyl-1H-indazol-3-yl) -N44- (trifluoromethyl) phenyl] urea N- (6-gas-7-fluoro-5-phenyl-1H -Indazol-3-yl) -N ·-(4-methoxyphenyl) urea N- (6-Ga-7-fluoro-5-phenyl-1fluorene · indazol-3-yl) -N ' -Cyclohexyl urea 5 Ν- (6-Ga-7-fluoro-5-benzyl-1H-indazol-3-yl) -N · -propylurea N- (6-Ga-7-fluoro >>-5 -Phenyl11-sit-3-ylphenylphenyl) N- (6-qi-7-fluoro-5-phenyl-1H-indazol-3-yl) -NH4-fluorophenyl) urea N- [ 6 · Ga-7-fluoro-5-phenyl-1H_indazol-3-yl] -N,-(tricyclic [3 · 3 · 1 · 13,7] dec) -1-yl vein 10 Ν- ( 6 · qi-7-qi-5-benzene Group sigma-3-yl) -N *-(4-fluorenylphenyl) vein N- (6-air-7-fluoro-5-phenyldan-1l-indazol-3-yl) urea 丨 N- (6-Gas-7-methyl-5-phenyl-1H-indazol-3-yl) urea N- (6-Gas-7-cyano-5-phenyl-1H-indazol-3-yl ) Urea N- (6-Ga-7-cyclopropyl-5-phenyl-1H-indazol-3-yl) urea 15 N- (6-Ga-7-hydroxy-5-phenyl-1H-ind N- (6-oxo-7-fluorenyl-5-phenyl-1H-indazol-3-yl) urea N- (6- GA-7-trifluoromethyl-5-phenyl-1H-indazol-3-yl) urea N- (6-Ga-7-trifluoromethoxy-5-phenyl-1H-indazole-3 -Yl) gland N- (6-Ga-7-nitro-5-phenyl-1 H-indazol-3-yl) urea 20 N- (6-Ga-7-amino-5-phenyl- 1H-indazol-3-yl) urea N- (6-Ga-7-diamidinoamino-5-phenyl-1H-indazol-3-yl) urea N- (6-Ga-7-acetylene Methyl-5-phenyl-1H-indazol-3-yl) urea N- [6-gas-7-fluoro-5-phenyl-1H-indazol-3-yl] -4-methyl-benzylsulfonate Ammonium N- [6-Ga-7-Fluoro-5-phenyl-1H-indazol-3-yl] sulfenamidin-15- This paper is dimensioned to the Chinese National Standard (CNS) A4 (210x297 mm) 2004222 93 Α7 ---------__ B7 V. Description of the invention (14) N- [6-Ga-7-fluoro-5-benzyl-1H-indazol-3-yl] propanesulfonium Ν- [6-GaHibenzyl_1H_0indolazole__yl] _2,2-trifluoroethanesulfonamide N- [6-Ga-7-fluorobenzyl_1H-indazole_3_yl] _2 _Thiophenesulfonamide N- [6-Ga-7-fluorobenzyl_1H-indazole_3 • yl] benzenesulfonamide. 5 N_ [6m.5 · benzyl heart 』丨 心 3_ 基] Bing (trimethylol) benzene_continamidine N- [6-Ga-7-fluorobenzyl-1H_indazol-3_yl] _5_ (3_isoxazolyl) fluorenylthiophene_sulfonamide -[6-Ga · 7ϋphenyl-1H-, azole-3-yl] -4-fluorobenzenesulfonamide [6 · Ga · 7 · Fluoro_5-phenyl-1] 9 ^ 丨 丨 azole_ 3_yl] _4methoxymethoxysulfonamide 10 N- [6-Ga-7-fluoro-5-benzyl-1H-indazol-3-yl] benzenesulfonamide N · [6 · Ga · 7-Fluoro-5-bi 1-1fluorene-indazol-3-yl] small methyl-1fluorene-amidazole-4-sulfofluorene

DrH amines ... Ν · [6-Ga · 7-fluoro-5-benzyl_1H-indazoledimethylethyl) benzimidamine 15 Ν · [4 · [((6- 气 · ^ Fluoro-5-phenyl_1H, azole 3yl) amino] phenyl] phenyl > Ethylamine Printed by N_ [6 · Gafluoro · 5-phenyl-1H 』Arbazole_3_yl] Icemethyl benzylsulfonamide 6-gas-7-fluoro-N- (pentafluorophenyl) -5_phenyl_1Η_indazolamine 6-gas-7 · Fluoro-N- (3,4-difluorophenyl) -5-phenyl-1fluorene-indazole-3-amine 20fluorofluoro-5_phenyl-N- (2,3,5,6-tetrakis Fluorophenyl) _1H-indazole! Amine 6-Ga-7-fluoro-5-phenyl-N- (2S4,6-trifluorophenyl) -iH-indazole each amine 6-oxy-N- (4-fluorobenzyl) _5_benzene -1H-indazole-3-amine 6-Ga-7-fluoro-N- [3- (trifluorofluorenyl) phenyl] • 5-phenyl-111-indazole-3-amine 6-Ga-7 -Fluoro-N- [4- (trifluorofluorenyl) phenyl] _5 · benzyl-1H-indazole · 3-amine-16- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 2004222 93 A7 B7 V. Description of the invention (15) Buqi-7-fluoro_team [3-fluoro-5- (trifluoromethyl) phenyl] -5-phenyl-1H-indazole-3-amine 6 -Ga-7-fluoro-N · (4-stone phenyl) -5-benzyl-fluorenyl-pyridine-3-amine 6-gas-7-fluoro-N- (3-nitrophenyl) _5_benzyl-1fluorene-indazole-3-amine 6-gas-7-fluoro-N- (3-methoxyphenyl) -5_phenyl-1fluorene-indazole-3-amine 5 6-gas- 7-H_N- (4-Methoxyphenyl) -5-benzyl-1H-sigmato-3-amine 6-gas-7-fluoro-N, 5-diphenylbenza-3-amine 6 · Ga-7-fluoro specific phenyl group) -5-benzyl-1Η-σ bow 丨 嗤 -3-amine 6-Ga-7-fluoro-N- (2-pyridyl) -5-phenyl-1Η -Indazol-3-amine N-butyl each gas-7-fluoro-5-phenyl-1H-indazol-3-amine 10 N_ (6-chloroaspartyfluorophenyl-1H-indazol-3-yl ) _N, _phenylurea N_ (6-chloro_7_fluorofluorenyl-1H-indazolyl) -3_methoxybenzylsulfonium Its isomers, mixtures thereof, its racemates, enantiomers, diastereomers or tautomers, and its pharmaceutically acceptable, and more specifically, the following compounds: 15 Six Hydropyridine-1-fluorenic acid (6,7-difluoro-5-phenyl-1H-indazol-3-yl) fluorenamine "than pyridin-1-carboxylic acid (6,7-difluoro-5- Phenyl-1H-indazol-3-yl) fluorenamine 1- (6,7-difluoro-5-benzyl-1H-indazol-3-yl) -3- [3- (4-methylhexa Hydropyridine small group) propyl] urea N- (6,7-difluoro-5_phenyl-1H-indazol-3-yl) -N, -benzene Tylurea 20 is a tautomer and a pharmaceutically acceptable salt thereof. The present invention also relates to a derivative comprising formula VII, a racemate, an enantiomer or a diastereomer, and a mixture thereof, which is a tautomer And its pharmaceutically acceptable salt as the active ingredient of the pharmaceutical composition, wherein: R3 is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl-17- this paper Standards suitable for financial countries (CNS) A4s (Germany) 2004222 93 A7 B7 V. Description of the invention (16) (1-6C) alkyl group, aryl group fused with (1_10C) cycloalkyl Or heteroaryl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, C00R1, S02R1, C (= NH) R1 or C (= = NH) NR1 group; these groups may optionally be substituted with one or more substituents selected from the group consisting of CN, N02, NH2, OH, OR1, COOH, C (0) 0R1, -0-C ( 0) Rl, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1, -0-S02Rl,- S02-0-

Rl, aryl, heteroaryl, heterocyclic, methylfluorenyl, trifluorofluorenyl, trifluorofluorenyl 10 sulfanyl, trifluoromethoxy or (1-6C) alkyl; consumption by shellfish of Intellectual Property Bureau, Ministry of Economic Affairs The cooperative prints R5, R6 and R7 points. _ Is a group selected from the following: fan, ™, No. 02, NH2, OH, COOH, C (0) 0R8, -0_C (0) R8, NR8R9, NHC (0) k8, C (0) NR8R9, NHC (S) R8, C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, 15 S02NR8R9, -0-S02R8, -S02-0-R8 , Trifluoromethyl, trifluorofluorenyloxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl ( 1-6C) alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, adamantyl or polycyclic alkyl; these groups may optionally be substituted with one or more substituents selected from the group consisting of halogen, CN, N02, NH2, OH, 20 ORIO, COOH, C (O) OR10, -OC (O) R10, NR10R11, NHC (O) R10, C (O) NR10Rll, NHC (S) R10, C (S) NR10R11, SR10, S (O) R10, SO2R10, NHS02R1〇, SO2NR10Rll, -〇-S〇2R10, -SO2-O-R10, aryl, heteroaryl, formamyl, trifluoromethyl, trifluorofluorenyloxy Or (1-6C) alkane -18- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 2004222 93 A7 ______ B7 V. Description of the invention (17) R1, R2, R8, R9, R10 and R11 are independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl, and heteroaryl, which may be substituted by one or more substituents selected from halogen, (16C) alkyl, alkyloxy, CN, N02, NH2, OH, COOH, C00 alkyl, 5 conH2, fluorenyl, trifluoromethyl, tridecylmethoxy; R1 and R2 or R8 and R9 or R10 and R11 can form 5- or 6 items Ring, which may or may not contain heteroatoms, such as: 0, S or N; and when R3 is a 6-membered nitrogen-containing heteroaryl or thiazolyl or imidazolyl or oxazolyl, then at least R5 and R6 One is an aryl group, which may be optionally substituted with 10 or more substituents selected from the group consisting of halogen, CN, NO2, NH2, OH, ORIO, COh, c (O) OR10, -OC (O) R10, NR10RH, NHC (〇) R1〇, c (O) NR10Rll; NHC (S) R10, C (S) NR10R11, $ R10, s (〇) R10, S02R1 (i, NHSO2R10, SO2NR10RU, -〇 -SO2R10, -SorO-R10, aryl, heteroaryl, 15fluorenyl Yue trifluoromethyl group, trifluoromethoxy group, Yue or (1-6C) alkyl. Printed by the Shelley Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. More specifically, the present invention relates to compounds containing formula VII derivatives, their racemates, enantiomers or diastereomers and their mixtures, which are mutually variable. And its pharmaceutically acceptable salts as active ingredients in the pharmaceutical composition, wherein: 20 R3 is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, aryl or heteroaryl fused with (1-10C) cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl , Alkynyl, CONR1R2 ,, CSNR1R2, COOR1, SO2RI, C (= NH) R1 or C (= NH) NR1 groups; these groups can be selected by one or more as required -19- This paper is applicable to China Standard (CNS) A4 specification (210 X 297 mm) 2004222 93 B7 V. Description of the invention (18) Substituted from the following substituents: halogen, CN, N02, NH2, 0H, 0R1, COOH, C (0) 0R1, -0-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1,- O-5 SO2RI, -SO2-O-RI, aryl, heteroaryl, heterocyclic, formamidine , Tridenylmethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C) alkyl; printed by Shelley Consumer Cooperatives, Bureau of Intellectual Property, Ministry of Economic Affairs, R5 and R6 are each independently selected from the following bases Group: halogen, CN, No2, NH2, OH, COOH, C (0) OR8, -0-C (0) R8, NR8R9, NHC (0) R8, C (0) NR8R9, NHC (S) R8 , C (S) NR8R9, 10 SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0_ S02R8, -SCVO-RS, trifluoromethane, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, adamantane Group, polycycloalkyl group; these groups may be optionally substituted with one or more 15-generation groups selected from the group consisting of: halogen, CN, NO2, NH2, OH, OR10, C00H, C (O) OR10,-. -C (O) R10, NR10R11, NHC (O) R10, C (O) NR10Rll, NHC (S) R10, C (S) NR10R11, SR10, S (O) R10, S02R1〇, NHSO2R10, SO2NR10Rll, -O -SO2R10, -SCVO-RIO, aryl, heteroaryl, formamyl, trifluorofluorenyl 20, trifluoromethoxy or (1-6C) alkyl; R7 is halogen, methyl, cyclopropyl , CN, OH, Oxy, trifluoromethyl, vinyl, ethynyl, trifluoromethoxy, N02, NH2 or NMe2, IU, R2, R8, R9, R10 and R11 are each independently hydrogen, (1-6C) alkyl, The aryl, alkenyl, alkynyl or heteroaryl group can be passed through a -20 as required. This paper size applies the Chinese National Standard (CNS) A4 specification (210x297 mm) 2004222 93 --- B7 V. Description of the invention ( l9) or more than one substituent selected from the group consisting of: halogen, (1-6C) alkyl, (1-6C) alkoxy, CN, NO2, NH2, OH, COOH, C00 alkyl, CONH2, formamidine Group, trifluoromethyl or trifluoromethoxy; R1 and R24R8 and R9 or R10 and R11 may form a 5- or 6-membered ring, 5 of which may or may not contain heteroatoms, such as: 0, s or N; And when R3 is a 6-membered nitrogen-containing heteroaryl or thiazolyl, imidazolyl, or oxazolyl, then at least one of R5 and R6 is an aryl group, which may be substituted with one or more substituents selected from the following as necessary : Halogen, CN, N02, NH2, OH-〇R1〇χ COOH 'C (O) OR10' -OC (O) R10 '10 NR10R11, NHC (0) R1〇, C (O) NR10Rll, NHC (S) R10, C (S) NR10R11, _10, S (〇) R4〇, SO2RO NHSO2R10, SO2NR10RU, -〇〇〇2R1〇, _s〇2_o-R10, reference group, heteroaryl, formyl, trifluoromethane, trifluoromethoxy, and (l-6C) k group. The present invention preferably relates to a medicine comprising a derivative of formula VII, a racemate, an enantiomer 15 or a diastereomer thereof, and a mixture thereof, a tautomer thereof and a pharmaceutically acceptable salt thereof as an active ingredient. The composition, where the R3 printed by the Shelley Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1- 6C) Alkyl, aryl or heteroaryl fused with (iiOC) cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkyne 20 Group, CONR1R2, CSNR1R2, COOR1, S02R1 or C (= NH) NR1 group; these groups can be optionally substituted with one or more substituents selected from the group consisting of: halogen, CN, N02, NH2, OH, OR1 COOH, C (0) 0R1, -0-C (0) Rl, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, -21- This paper size applies China National Standard (CNS) A4 Specification (210 X 297 mm) 2004222 93 B7 V. Description of Invention (2) S02NR1R2, C (S) NR1R2, NHC (S) R1, -0-S02IU, -S〇2- 〇-

R1, square group, hetero square group, methyl group, oxo group, trifluoromethyl group, trifluoromethylsulfanyl group, trifluoromethoxy group or (1-6C) alkyl group; R5 is aryl group; 5 R6 and R7 · are independently halogen, methyl, cyclopropyl, cn, 0H, methoxy, trifluoromethyl, vinyl, ethynyl, trifluoromethoxy, No2, NH2 or NMe2, R1 and R2 are independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl, or heteroaryl, and may be substituted with one or more substituents selected from the group consisting of: halogen, ( 1-6C) alkyl, (1-6C) alkoxy, CN, NO2, NH2, OH, COOH, COO, alkynyl, CONH2, fluorenyl, trifluorofluorenyl or trifluoromethoxy; R1 and R2 A 5- or 6-membered ring may be formed, which may include heteroatoms as required, such as: 0, S, or N. The present invention is also preferably related to an aminoindazole derivative of formula (I), the racemate, the Enantiomers or diastereomers and their mixtures, their tautomers and their pharmaceutically acceptable salts for pharmaceutical use, of which R3 is printed by Shelley Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs (1_6C) Alkyl, aryl, aryl (1 -6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, aryl or heteroaryl that is slightly compatible with (1-10C) cycloalkyl, hetero20 ring, heterocycloalkyl, cycloalkyl , Adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, S02R1, C (= NH) R1, or C (= NH) NR1 groups; these groups may optionally pass one or more Substituents selected from the following: CN, NO2, NH2, OH, 〇R1, COOH, C (0) 0R1, -0-C (0) R1, NR1R2 'NHC (〇) R1, • 22- this paper Standards apply to China National Standard (CNS) A4 specifications (210x297 mm) 2004222 93 A7 B7 V. Description of invention (21) C (0) NR1R2, SRI, S (0) R1, S02R1 'NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) IU, -0-S02IU, -S02-0-R1, aryl, heteroaryl, heterocyclomethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy Or (1-6C) alkyl; 5 R5, R6 and R7 are groups independently selected from the following: halogen, CN, N02, NH2, OH, COOH, C (0) OR8, -0-C (0 ) R8, NR8R9, NHC (0) R8, C (0) NR8R9, NHC ⑻ R8, C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0-S02R8, -S02-0 -R8, trifluoro Radical, trifluorofluorenyl 10 radical, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) alkyl, heteroaryl, heteroarylfluorene 1 [1- 6 (:) alkyl, heterocyclic, cycloalkenyl, alkenyl, alkynyl, adamantyl, or polycyclic alkyl; these groups may be; ^ 霈 to be substituted with one or more substituents selected from : Halogen, cn, no2, nh2, oh, OR10, COOH, C (O) OR10, -〇-C (O) R10, NR10R11, 15 NHC (O) R10 C (O) NR10Rll, NHC (S) R10, Printed by C.S.NR10R11, SR10, S (O) R10, SO2R10, NHSO2R10, SO2NR10Rll, -〇-S〇2R1〇, -SCVO-RIO, aryl, heteroaryl , Formamyl, trifluorofluorenyl, trifluoromethoxy or (1-6C) alkyl; αα, R2, R8, R9, R10 and R11 are independently hydrogen, (1-6Q alkyl, 20 aryl, aryl , Alkenyl, alkynyl, or heteroaryl, which may be substituted by one or more substituents selected from halogen, (1-6C) alkyl, (1-6C) alkyloxy, CN, N02, NH2 , OH, COOH, COO alkyl, CONH2, alkynyl 'trifluoromethyl or trifluoromethoxy; R1 and R2 or R8 and R9 or R10 and R11 may Become a 5- or divination ring, its -23- SS mound standard (° ^) A4 size (two ^; 297 public love) when the paper ruler 2004222 93 A7 B7 V. Description of the invention (22) ^ ~ may include Or does not contain heteroatoms, such as: 0, s, or N; and when R3 is a 6-membered nitrogen-containing heteroaryl or sigma, sialyl, or purino, then at least one of R5 and R6 is aromatic Group, which may be optionally substituted with one or more substituents selected from the group consisting of halogen, CN, NO 2, NO 2, 5 OH, ORIO, COOH, C (0) OR10, -0-C (0) R1. , NR10R11, NHC (0) R1〇, C (O) NR10Rll, NHC (S) R10, C (S) NR10R11, SR10, S (O) R10, SO2R10, NHS02R1〇, SO2NR10Rll, -O-SO2R10, -so2 -o-rio, aryl, heteroaryl, formamyl, trifluoromethyl, trifluoromethoxy or (KQ alkyl). 10 More specifically, the present invention relates to an aminoindazole derivative of formula (I), a racemate, an enantiomer, or a di-isomer and a mixture thereof, a tautomer and a medicament thereof. Acceptable salts for pharmaceutical use, where ... R3 is (1-6C) alkyl, square, square (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, Aryl or heteroaryl fused with (1-10C) cycloalkyl, hetero 15 soil, hetero soil xanthyl, soil alkyl, adamantine, polycyclic alkyl, dilute radical, fast radical, CONR1R2, CSNR1R2, COOR1, S02R1, C (= NH) R1 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs or C (-NH) NR1 groups, these groups may be subject to · or more substituents selected from the following Substitution: Halogen, CN, N02, NH2, OH, OR1, COOH, C (0) 0R1, -0-C (0) Rl-NR1R2, 20 NHC (0) R1, C (0) NR1R2, SRI, S ( 0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1, -〇- SO2RI, -SO2-O-RI, aryl, heteroaryl, heterocyclic ring, formamyl, three gas Fluorenyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C) alkyl; R5 and R6 are each independently selected from the following groups ： Halogen, CN, N02, -24- This paper size is applicable to Chinese National Standard (CNS) A4 (210 X297 mm) 2004222 93 Α7 Β7 V. Description of the invention (23) NH2, OH, COOH, C (0) 0R8 , -0-C (0) R8, NR8R9, NHC (0) R8, C (0) NR8R9, NHC (S) R8, C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0-S02R8, -S02-0-R8, trifluoromethyl, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) alkane Group, heteroaryl, heteroaryl (1-6C) alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, adamantyl, polycycloalkyl; these groups may be subjected to one or more Substituents selected from the group consisting of halogen, CN, N02, NH2, OH, OR10, C00H, C (O) OR10, -0-C (0) R10, NR10R11, NHC (O) R10, 10 C (O ) NR10Rll, NHC (S) R10, C (S) NR10R11, SR10, S (O) R10, S02Ri0, NHSO2R10, SO2NR10Rll, -0-SO2R10, -so2-o-rio, aryl, heteroaryl, formamidine Base, trifluoromethyl ;; V .; ·: · base, trifluoromethoxy or (1-6C) alkyl; printed by R7 for halogen, methyl, cyclopropyl, etc., by the Consumers' Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs CN, 0H, methoxy, trifluorofluorenyl 15, vinyl, ethynyl, trifluoromethoxy, N02, NH2 or NMe2, IU, R2, R8, R9, R10 and R11 are each independently nitrogen, (1 -6C) alkyl, aryl, dilute, fast or heteroaryl, which may itself be substituted with one or more substituents selected from halogen, (1-6C) alkyl, (1-6C) ) Alkoxy, CN, N02, NH2, OH, COOH, C00 alkyl, 20 CONH2, fluorenyl, trifluorofluorenyl or trifluoromethoxy; R1 and R2 or R8 and R9 or R10 and R11 can form 5- or 6-membered ring, which may or may not contain heteroatoms, such as · 0, S, or N; and when R3 is a 6-membered nitrogen-containing heteroaryl or fluorenyl group, odorant group, or 4 In the β-base group, at least one of R5 and R6 is an aryl group, and it can be adjusted by a -25 if necessary. This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 2004222 93 A7 B7 V. Invention Note (24) or more substituents selected from halogen, CN, NO2, NH2, OH, OR10, COOH, C (O) OR10, -OC (O) R10, NR10R11, NHC (Q) R10, C (O) NR10Rll, NHC (S) R10, C (S) NR10R11, SR10, S (O) R10 SO2R10, NHSO2R10, 5 S〇2NR10R11, -〇-S02R1〇, -SCVO-RIO, aryl, heteroaryl, fluorenyl, trifluoromethyl, trifluoromethoxy, and (1-6C) alkyl . The present invention is preferably related to the aminoindazole derivative of formula (I), its racemate, enantiomer or diastereomer and its mixture, its tautomer and its pharmaceutically acceptable salt For medical purposes, 10 R3 is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, and | ϊ- ΐ〇〇 cycloalkyl fused aryl or heteroaryl, hetero · '. · * ring, heterocycloalkyl, far alkyl, adamantyl, polycycloalkane, alkenyl, alkyne V; ί Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Industrial Consumer Cooperatives, CONR1R2, CSNR1R2, COOR1, S02R1, or C (= NH) NR1 groups; these groups may be substituted with one or more substituents selected from 15 as required : Halogen, CN, N02, NH2, OH, OR1, COOH 'C (0) 0R1, -〇_C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) IU, -0-S02IU, -S02-0-R1, aryl, heteroaryl, formamyl, oxo, trifluoromethyl R5 is aryl; R5 is aryl; R6 and R7 are independently Lithium halogen, fluorenyl, cyclopropyl, CN, OH, fluorenyl, trifluorofluorenyl, vinyl, ethynyl, trifluorofluorenyl, N02, NH2 or NMe2, -26- ^ Paper size applies to China National Plant Year (CNS) A4 size (210x297 mm 1

Printed by Shelley Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 2004222 93 A7 _ B7___ V. Description of the invention (25) R1 and R2 are independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl or heterocyclic Aryl, which may be substituted by one or more substituents selected from halogen, (1-6C) alkyl, (1-6C) alkoxy, CN, N02, NH2, OH, COOH, COO Alkyl, CONH2, formamyl, oxo-5, trifluoromethyl or trifluoromethoxy; and R2 can form a 5- or 6-shell, which may contain heteroatoms as required, such as: 0, S or N. Derivatives of formula VII can be prepared from the corresponding 3-amino derivative (V), and the nitrogen at the 1-position can be optionally protected by the group Pr. Pr is trimethylsilylethoxylmethyl, tolylsulfonyl, mesylsulfonyl or benzyl or as indicated in TW Greene, Protective Groups in Organic Synthesis, J. Wiley-Interscience Publication (1999), Known groups for protecting NH groups in aromatic rings. 15 Formula (11) 3-amino-1H-, azole can be prepared from 2-fluorophenylcyanide and hydrazine hydrate or hydrochloride according to RF · Kaltenbach, Bioorg · Med.Chem. Lett "(15), 2259-62 (1999), refluxing in ethanol or n-butanol for 2 to 18 hours: -27-

2004222 93 A7 V. Description of Invention (26

(NI) νη2νη2, η2ο reflux alcohol (ethanol, butanol)

N NH. R5 and R6 in the compounds printed by the Shellfish Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs are independently selected from the group consisting of: halogen, 0 > 1, > 102, Qing, 011, (: 0011, (: (0) 0118, -0-C (0) R8, NR8R9, NHC (0) R8, C (0) NR8R9, NHC (S) R8, 10 C (S) NR8R9, SR8, S (0) R8, S02R8 , NHSO2R8, S02NR8R9, -0, S02R8, -S02-0-R8, trifluoromethyl, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6 alkyl, heteroaryl, heteroaryl (1-6C) alkyl, cycloalkyl, alkenyl, alkynyl, or adamantyl; these groups may be selected from one or more as required Substituted by the following substituents: dentin, CN, N02, NH2, OH, OR10, COOH, C (O) OR10, -0-C (O) R10, NR10R11, NHC (O) R10, C (O) NR10Rll , NHC (S) R10, C (S) NR10R11, SR10, S (O) R10, SO2R10, NHSO2R10, SO2NR10Rll, -O-SO2R10, -so2-o-rio, aryl, heteroaryl, formyl, In the case of trifluorofluorene 20 group, trifluoromethoxy group or (1-6C) alkyl group, the preparation method involves chemical reactions involving the corresponding halogenated derivatives: Suzuki (A. Suzuki, Pure Appl · Che m ·, 63, 419-22 (1991), Stille (J. Stille, Angew · Chem ·, Int. Ed ·, 25, 508-24 (1986)), Heck (RF Heck, Org · React ·, 27, 345-90 (1982)), Sonogashira (K. Sonogashira, -28-) This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 2004222 93 A7 B7 V. Description of the invention (27)

Synthesis, 777 (1977)), Buckwald (S.L. Buckwald, Ace. Chem. Re., 31, 805 (1998)). Therefore, it is necessary to protect the reactive functional group. Therefore, the OH, SH, COOH, and NH2 functional groups must be protected before the coupling reaction. Protective group 5 was introduced in any way known to those skilled in the related art, and specifically described in TW · Greene's "Protective groups in Organic Synthesis, J. Wiley-interscience Publication (1999)". 1-position The nitrogen is best protected with a third butoxycarbonyl group or a silicon derivative. It is best to use a third butyl difluorenylsilyl group or 10 triisopropylsilyl group which can be removed using a fluoride anion or acetic acid, more specifically Trisylsilylethoxyfluorenyl is selected, which can be removed by using tetrabutyl sulfide, in a refluxing solvent (such as tetrahydrofuran or dioxane) (J. t Whitten, J. Org · Chem., 51, 1891 (1986); Beta · Lipshutz, Tetrahedron Lett "4095 (1986)) or using 2N hydrochloric acid in methanol or ethanol and remove under reflux. The 15.1-position protected derivative with trimethylsilylethoxymethyl is prepared from the starting compound and trimethylsilylethoxymethyl gas in the presence of sodium hydride in a solvent (eg dimethyl Methylformamide), reacted at room temperature (jp Whitten, J. Org. Chem "51, 1891 (1986); printed by the Consumer Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs

Edwards, Tetrahedron, 42,3723 (1986)). In the same way, the 1-N-nitrogen functional group of indazole can be protected with, for example, a silyl derivative, benzyl, amidinate or sulfenylsulfenyl. For example, if palladium is required for coupling with a 6-position via a derivative, the nitrogen at the 1-position must be protected (X = C1, βΓ, or 1) as shown in Figure 1 below: -29- Paper size applies to China National Standard (CNS) A4 (210x297 mm) 2004222 93 A7 _ B7 V. Description of the invention (28

5 The reaction to remove the protecting group is performed in a manner known to those skilled in the art, which is described in T.W. Greene, Protective Groups in Organic Synthesis, J. Wiley-Interscience Publication (1999). For example, if the protective group at the 1-position is tris (silyl) ethoxymethyl, it can be reacted with tetrabutylammonium fluoride to remove the protective group 10 as shown in the following reaction scheme: 15

SiMe3 HNrR3

Bu4NF, THF, reflux

Printed by Shelley Consumer Cooperatives, Bureau of Intellectual Property, Ministry of Economic Affairs 20 When one of the R5 or R6 groups involved in the use of palladium chemistry has a reactive functional group, such as: hydroxyl, amine, thiol, or acid or When a heteroatom is usually included, it is also necessary to protect the latter before using the coupling reaction. Therefore, for example, the phenol functional group will be introduced in a protected form (for example, 0-phenylfluorenyl) from a gasified derivative, and the nitrogen at the 1-position will be protected in the form previously described: -30- Zhang ms / fl γ due to national standard (cns) a4 regulation; ^ (21Gχ297 public love) 2004222 93 A7

The benzyl group is subsequently removed by, for example, trimethylsilyl iodide, refluxing in acetonitrile. It can also be protected by trimethylsilyl ethoxymethyl, which can be removed by using tetrabutylammonium fluoride in a refluxing solvent (such as tetrahydrofuran or dihydrogen 10 15) (J · P · Whitten, J · Org · Chem "51, 1891 (1986); Beta Lipshutz, Tetrahedron Lett" 4095 (1986)) or using 2N hydrochloric acid in methanol or ethanol, remove under reflux :. •. · · ·

When R5 and R6 are independently an aryl group and a halogen, the aryl functional group is introduced to the bromination position through a coupling reaction with Yuki, and the nitrogen at the 1_ and 3_ positions is appropriately protected. Preferably, PΓ represents a tris-silylethoxyfluorenyl group, and Pr represents a n-butylcarbonyl group, which forms n-butylfluorenamine with nitrogen. When the amidine protective group was removed, it was refluxed in DMF for 1 week in the presence of ethanolamine. This cracking reaction can also be carried out in ethanol using stannous gasification (R J Printed by Shelley Consumer Cooperative, Intellectual Property Bureau, Ministry of Economic Affairs 20

R7 Pr J. Chem · Soc · Perkin I, 1992, 181M819) or using sodium alkoxide in methanol (Y. Furukawa, Chem · Pharm. Bull "1968, 16, 1076) or using any other burned alkoxide, Performed in the corresponding alcohol.

Removal of protective groups

This paper size applies to the Chinese National Standard (CNS) A4 specification (210x297 mm) 2004222 93 A7 B7 V. Description of the invention (30) When R5 and R6 are independently aryl and dentin, the aryl functional group is The coupling reaction is introduced to the bromination site, and the nitrogen at the 3-position is properly protected. Preferably, Pr represents trimethylsilylethoxymethyl, and Pr represents n-butyl condensate, which forms n-butylamidamine with nitrogen. Electron substitution reaction with, for example: tetragas 5 boric acid pin (NOiBF4). A 5-position coupling reaction (Suzuki, Heck or Sonogashira coupling method) is performed using a palladium chemical reaction. The 7-position is functionalized according to the required substituents, such as: reduction, dentification, introduction, or chemical reaction coupling (Suzuki, Heck, or Sonogashira coupling) introduction of aryl, heteroaryl, alkyl, alkenyl , An alkynyl group or an alkyne functional group. When the protecting group of amidine was removed, it was refluxed in DMF for 1 week in the presence of ethanolamine. This cleavage reaction can also be carried out in ethanol (RJ GRiffin, J. Chem · Soc · Perkiii I, 1992, 1811-1819) or Chem · Pharm · Bull · in methanol using sodium methoxide, 1968, 16, 1076) or using any other alkanol 15 salt, in the corresponding alcohol. After the 3-position removal of the protective group, an NH2 functional group is generated which can react with the desired group to introduce the desired substituent to the fluorene position. This reaction is described below: Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

-32- The paper size is applicable to Chinese W 蓼 橾 ping (UMS) A4 specification (210 X 297 public love) 2004222 93 A7 ____ B7 V. Description of the invention (31) The compound of formula (Π) is the starting point for the preparation of a variety of products. The product is prepared from the primary amine functional group of 3-aminoimidazole according to all the general reactions of this functional group, such as ... calcination, tritiation, reduction after reaction with carbonyl derivatives, sulfonation, conversion to urea or carbamate , Arylation (Castrol reaction or Buchwald reaction), and so on. In the general formula (I), when Pr is a trimethylsilylethoxyfluorenyl group, and a derivative of r3 is a fluorene, a boron derivative can be used for reductive amination reaction, such as: using triethylsulfoxy sodium borohydride, In digas methane, in the presence of R1CH0 type aldehyde, under the conditions described in Organic Reactions, ν〇 59, l-714 (E. Baxter, 10 A. Reitz), or use commonly used It is carried out with other reducing agents for reducing imine, and the product is formed into a product, in which r3 is (1-6C) alkyl, aryl (1-6C) alkyl, heteroaryl | ^ i_6C) alkyl, heterocycloalkyl, ring Alkyl or polycycloalkyl, these groups may need to be substituted with one or more substituents selected from halogen, CN, N02, NH2, OH, OR1, C00H, 15 C (0) 0R1, -〇-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1,- 0-S02IU, -S02-0_ R1, aryl, heteroaryl, formamyl, oxo, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethyl Fluoromethoxy or (1-6C) alkyl. 20 The condensation reaction between a derivative of R3 in the general formula (I) and an isocyanate of type 0CNR1 can be specifically described in tetrahydro-squeezing, according to Comprehensive Organic Functional Group Transformations, Vol. 6 (Katritzky, Meth-Cohn, Rees 1995 ) To form a product, in which R3 is CONR1R2 or CSNR1R2, and R1 and R2 are independently -33- This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X297 public «) 2004222 93 Μ B7 V. Description of the invention (32) hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl or heteroaryl, which may itself be substituted with one or more substituents selected from the group consisting of: halogen, (i-6c) Alkyl, (1-6C) alkoxy, CN, NO2, NH2, OH, COOH, COO alkyl, CONH2, formamyl, oxo, trifluoromethyl, or tri 5methoxy. · In the general formula (I), the sulfonation method of R3 is a derivative of fluorene can be performed by RlSC ^ Cl type sulfonium gas in the presence of a base (specifically a tertiary amine, such as: triethylamine, or an aromatic amine , Such as: pyridine), in a general solvent (such as, for example, digas methane) to produce a product, wherein R3 is so2R1, R1 is 10 hydrogen, (1-6C) alkyl, aryl, alkenyl , Alkynyl or heteroaryl, which may be substituted by one or more substituents selected from the group consisting of: from the ordinary, (uc) alkyl, (1-6C) alkyl, CN, No2, NH2 , OH, fcoOH, COO alkyl, CONH2, fluorenyl, oxo, trifluorofluorene f or trifluorofluorenyloxy. 15 The compound of formula (I) can be isolated and purified according to generally known methods, for example, crystallization, chromatography or extraction. Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. Compounds can use inorganic or organic acids as required, and react with these acids in organic solvents (such as alcohols, ketones, ethers or gasification solvents) to convert them into addition salts. These salts also form part of the invention. 20 Examples of pharmaceutically acceptable salts include the following salts: benzenesulfonate, hydroxamate, hydrochloride, citrate, diacetate, fumarate, gluconate, moth Acid salt, maleic acid salt, acetic acid salt, acetic acid salt, methylene bis-5 / 5-oxonaphthyl acid salt, nitrate, oxalate salt, parahydroxynaphthyl salt, phosphate, water Salicylate, succinate, sulfate, tartrate, -34- Applicable to this paper size + θ ® house standard 芈 ㈣S) A4 size (210x297) " y 2004222 93 A7 B7 V. Description of the invention (33) Tea Alkali acetate and p-toluenesulfonate. Compounds of formula (I) are kinase inhibitors and are therefore suitable for the prevention and treatment of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontal and parietal dementia, the cortex Basal degeneration, Pick's disease, stroke, cranial and spinal trauma and peripheral neuropathy, obesity, essential hypertension, arteriosclerotic cardiovascular disease, polycystic ovary syndrome, syndrome X, immune deficiency And cancer ^ activity assay is to determine p protein in adult rat cortical sections Inhibition of acidification. 10 8-10 week old male 0FA rats (iffa-Credo) were printed and killed by decapitation method after printing and killing by Shellfish Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs. μπι cortical slice? The cells were cultured in 5 ml DMEM medium (including pyruvate and glucose 4.5 g / 1) at 37 ° C for 40 minutes. The sections were then washed twice with the medium, aliquoted into micro-tubes (50 μ contained in 500 μΐ medium with or without test compounds), and cultured under Vi 15 incubation. After 2 hours, the reaction was stopped by centrifugation. The sections were lysed, sonicated, and centrifuged at 4 ° C and 18300 g for 15 minutes. According to the Lowry method, a commercially available analytical method (BCa protein analysis method, Pierce Pharmaceutical Factory) was used to determine the protein concentration in the supernatant. Samples were denatured at 70 ° C for 10 minutes, and then separated in an upright position on 12% of the heart in the presence of Mops 20 SDS buffer, and then transferred to a nitrocellulose membrane by electrophoresis. . Immunolabeling was performed using the monoclonal antibody AD2, which specifically recognizes the Ser396 / 404 phosphorylated epitope of the p protein. Adding a secondary antibody directed against mice that is coupled with peroxidase and coupled with chemiluminescence receptors makes immune -35- 2004222 93 __B7 V. Description of the invention (34) Reactive protein can be determined visually. The obtained automatic radiograph was finally measured for ic5G value using GeneTools 1 software (Syngene (GeneGnome, Ozyme)). The compounds of the formula VII have extremely advantageous activities, in particular, some compounds have an IC50 of less than · 100 μM. The following examples illustrate the invention without limiting it. The LC / MS analysis of the products was performed on a Waters Alliance 2695 device with the LC portion measured and the Waters-Micromass Platform II determined the mass portion. 10 Intermediate production method 6,7-difluoro-1H- called Diyin: Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs and adding 0.32 cm3 of hydrazine monohydrate to 0.46 cm. 2,3,4 -Sodium phenyl cyanide in 10 cm3 of absolute ethanol. After the reaction medium was heated at about 75 ° CT for 17 hours, 10 cm3 of ethyl acetate, 5 cm3 of tetrahydrofuran, and 5 cm3 of distilled German water were added. After the phases were separated, the organic phase was separated, washed with 10 cm3 of distilled water, and then washed with 10 cm3 of a saturated aqueous sodium carbonate solution. After the phases were separated, the organic phase was separated, dehydrated with magnesium sulfate, filtered and concentrated under reduced pressure to dryness (2 kPa; 50 C). The residue obtained was purified by silica gel column chromatography at 50 kPa under argon pressure ( The particle size was 40-60 μm; diameter 1.5 cm), and the mixture was dissolved with cyclohexane / ethyl acetate 20 (50/50 Zhao product ratio). The fractions containing the desired product were combined and evaporated under reduced pressure (2kPa; 40 ° C); after drying (90Pa; 40 ° C), 100 mg of 6,7-difluoro-fluorene · indene was obtained. Sit-3-amine is a white solid with a flash point of i83 ° C. 4 NMR spectrum (300 MHz, (CD3) 2SOd6, SPpm) ··· 5 · 57 (Unresolved complex: 2Η); 6.93 (mt: 1Η); 7.52 (ddd, J = 8 · 5-4 · 5 And 1Ηζ: -36- This paper size applies Chinese national standard, (CNS) A4 specification (21 × 297 mm) 2004222 93 __ B7 V. Description of the invention (35) 1H); 12 · 01 (Unresolved compound: 1H). Ν " (6,7-difluoro-lH-indole. Sit-3-yl) butyridine: Add 0.61 cm3 of butyridine gas to the above-mentioned 6,7-difluoro-1H-indazole-3- In 15 cm3 of pyridine of amine, after cooling to about 3 ° C, the mixture was allowed to stand at room temperature for 5 hours and 76 hours. The reaction medium was concentrated under reduced pressure (2kPa; 40 ° C), and the residue was dissolved in 25 cm3 of ethyl acetate and 25 cm3 of water. The organic phase was washed sequentially with 25 cm3 of distilled water and 25 cm3 of a saturated sodium gaseous aqueous solution. After dehydration with magnesium sulfate, filtration and concentration under reduced pressure (2 kPa; 40.0), the obtained residue was purified by silica gel column chromatography under 50 kPa argon pressure (particle size 40-60 / xm; diameter 3 10 cm ), Dissolve with dioxane / methanol mixture (98/2 volume ratio). Combine the fractions containing the desired product and evaporate under reduced pressure (2 kPa; 40 ° C); after drying (90 Pa; 40 ° C) ) To obtain 596 11 ^] ^-(6,7-difluoro-111-indazol-3-yl) butanamide, as a white solid, melting point 19Γ (:. 4 NMR spectrum (300 MHz, (CD3) 2SO (16, δρριη): 0 · 97 (t, J = 15 7.5 Hz: 3H); 1.67 (mt: 2H); 2.40 (t, J = 7 Hz: 2H); 7.10 (mt: 1H); 7.63 (Wide dd, J = 9 and 4.5 Hz: 1H); 10.47 (Wide unresolved complex: 1H); 13.35 (Wide unresolved complex: 1H). Printed by Shellfish Consumer Cooperative, Intellectual Property Bureau, Ministry of Economic Affairs -"6,7-difluoro small ΓΓ2 彳 trimethylsilyl group) ethoxy group Γmethyl 1-1H-indazole-3-some 1 butylammonium amine 20 was added dropwise over a period of 3 hours containing 1.1 g of the above Wo-cm3 dimethylformamide solution of N- (6,7-digas-1H-indazol-3-yl) butyramine prepared to 50 containing 1.65 g of sodium hydride (contained in 60% oil) cm3 Methyl Yue Amides of the reaction medium is concentrated to dryness under reduced pressure, dissolved in 250 cm3 of ethyl acetate and 200 cm3 of water; the phases are separated, the organic phase was separated, washed in 150 cm3 of water, dried over -37-

This paper size is in accordance with Chinese National Standard (CNS) A4 specifications (21 × 297 male FJ 2004222 93 B7 V. Description of the invention (36) magnesium sulfate is dehydrated, filtered and concentrated under reduced pressure to dryness (2 kPa; 500c). The crude product was purified by silica gel column chromatography (particle size 4060 μιη; diameter 6 cm) under a pressure of 50 kPa argon, and then dissolved in a cyclohexane / ethyl acetate mixture (80/2 / volume ratio). The fractions containing the desired product were combined and evaporated under reduced pressure (2 kpa; 5 50 ° C) to yield 7.3 g of [6,7_difluorosmall! ^-(Trimethylsilyl) ethoxy] methyl ] _1Η-σ 弓 布 坐 -3-yl] Butanamine as a yellow oil. H NMR spectrum (300,112, (〇〇3) 28〇 (16,300111): -0.99 (8: 911) 0.82 (t5 J = 8 Hz: 2H); 0.96 (t, J = 7.5 Hz: 3H); 1.67 (mt: 2H); 2.41 (t, J = 7 Hz: 2H); 3.56 ( t, J = 8 Hz: 2H); 5.66 (s: 10 2H); 7.22 (ddd, J = 11_9 and 7 Hz · 1H); 7.69 (wide dd, J = 9 and 4.5 Hz: 1H); 10 · Bee (unresolved complex: 1H). Mass spectrometry: M = 369 difluoro-2-Γ2- (trimethylsilane) ethyl gas, a methylamine ρΐ η is called external — 3 _ %% Ding Li face 15 added 〇. 87cm3 pyridine To lg containing the above-prepared] sf- [6,7-difluoro printed by the Intellectual Property Bureau of the Ministry of Economics and Shellfish Consumer Cooperative, printed by [[2_ (trimethylsilyl) ethoxy] methyl HH-indazol-3-yl ] Butylamine in 30 cm aerosol, then 0.56 cm3 of Mo was added, and the mixture was refluxed overnight. 50 cm3 of digas methane and 50 cm3 of 10% aqueous sodium thiosulfate solution were added to the reaction medium. After stirring for 10 minutes, Filter through frit glass to remove insoluble 20 'organic phase washed with 50 cm3 water and 50 cm3 saturated gasified sodium solution. After layer separation, separate the organic phase, dehydrate with magnesium sulfate, filter and concentrate to dryness under reduced pressure. (2%? 45%. The crude product (17) was purified by Shixi gel column chromatography (particle size 40-60 / xm; diameter 3 cm) under 5 (^? & Argon pressure) to Cyclohexane / ethyl acetate mixture (90/10 volume ratio) dissolves. Combined with the required -38- This paper size applies to China Plant Standard (CNS) A4 specification (210x297 public love) 2004222 93 ___ B7 V. Description of the invention ( 37) Dissolved fractions of product, evaporated under reduced pressure (2 kPa; 50. 〇. After drying (90 Pa; 45.0), 230 mg of N- [5-bromo-6,7-difluoro small [[2- (trisylsilyl) ethoxy] methyl HH-indazol-3-yl ] Butanidine as a colorless oil. NMR spectrum (300 MHz, (CD3) 2SO d6, δρρηι) ··-〇〇〇8 (s: 5 9Η); 0.82 (t, J -8 Hz: 2H) ; 0.96 (t? J = 7.5 Hz: 3H); 1.67 (mt: 2H); 2.42 (t5 J-7 Hz: 2H); 3.55 (t5J = 8 Hz: 2H); 5.66 (s: 2H); 8 · 08 (dd, J = 6 and 2 Hz: 1H); 10.72 (unresolved complex: 1H). Mass spectrum: M = 447 10 difluoro-5-benzyl-pyrene "2_ (trimethylsitridyl) ethane" 1-methyl 1-methyl-3-benzylamine Butanamine, Intellectual Property Bureau, Ministry of Economic Affairs, Shellfish Consumer Cooperative, 30 cm3 of water containing 469 mg of benzyl dihydroxyboric acid, 760 mg of sodium carbonate, and 379 mg of triphenylphosphine (triphenylphosphine) ) To hl5g containing n_ [5_ > odor_6,7 · Dixiang-1-[[2_ (trisylsilyl) ethoxy] methyl] _1Hindazole_3_yl] 15 but The mixture was refluxed in 150 cm3 of dioxane for 4 hours. The reaction medium was diluted with 100 cm3 of ethyl acetate and 75 cm3 of water, and filtered through frit glass filled with Yin's salt. The phases were separated and separated. The organic phase was washed with cm3 water and 75 cm3 saturated sodium gas solution, dehydrated with magnesium sulfate, filtered and concentrated under reduced pressure to dryness (2 kPa; 50. 0), yielding 2 g of crude product as a black oily crude product of 20 substances. Purified by crushed gel column chromatography (particle size 40-60 μηι; diameter 3.5 cm) under 50 kPa argon pressure, and dissolved with cyclohexane / ethyl acetate mixture (85/15 volume ratio). The product's fractions were evaporated under reduced pressure (2 1 ^ &50; 0 and dried (90-145. 0, yielding 1.4 cold [6,7-difluoro-5-benzyl small [[2_ (trimethylsilane Group) ethoxy] methyl] · 丨 indenazolyl] -39- This is from a to 乂 w + Tian "豕 科 (CNS) A4 成 定 （21〇χ 297 a ------- -2004222 93 B7 V. Description of the invention (38) Butamidine 'is a yellow oil. 4 NMR spectrum (300MHz, (CD3) 2SO d6, δρριη):-0.05 (s: 9Η); 0.84 (t? J = 8 Hz: 2H); 0.95 (t, J = 7.5 Hz: 3H); 1.66 (mt: 2H); 2.43 (t, J = 7 Hz: 2H); 3.59 (t, J = 8 Hz : 2H); 5.69 (s: 5 2H); from 7.40 to 7.65 (mt ·· 5H); 7.82 (width d, J = 7 Hz: 1H); 10 · 64 (unresolved complex: 1H ). Mass spectrum: M = 445 Benzyl small "Γ2- (trimethylsilane, π hydrogen, 1 methyl, 1-1, 1-indazol-3-amine, printed by the Employees' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 10 sequentially added 1.1 cm3 ethanolamine With 1.50 g of potassium carbonate to contain L6g of N- [6,7 · difluoro · 5-phenyl-1-[[2_ (trimethylsilyl) hexyl] methyl] -1Η-indazole-3 -Methyl] -butylamidine 50 cm3 of dimethylmethaneamine ψ, the mixture was refluxed for one week, the reaction medium was concentrated to dryness under reduced pressure, dissolved in 150 μl of 3 ethyl acetate and 75 cm3 of water. After the phases were separated, The organic phase was separated and washed sequentially with 75 15 Cin water and 50 cm3 brine. The organic phase was dehydrated with magnesium sulfate, filtered and concentrated under reduced pressure to dryness (2 kPa; 50 ° C). The resulting oily crude product was under 50 kPa argon pressure Purified by silica gel column chromatography (particle size 40-60 μιη; diameter 4cm) with a cyclohexane / ethyl acetate mixture (80/20 volume ratio) under reduced pressure. The fractions containing the desired product were combined. , Evaporated under reduced pressure (2 kpa; 500c). After drying 20 (90 Pa; 45.0), 0.32 g of 6,7-difluoro-5_phenyl-1-[[2- (triamidine Shi Xi alkyl) ethoxy] methyl] -1H-indazol-3-amine. Cai-1H-Pg Bu Sit-3-amine: Add 1.1ml of 2N HC1 to 661mg of 6,7-difluoro-5-phenyl-l-[[2- (monomethyllithium) ethoxy] fluorenyl] indazole | Amine in methanol. -40-2004222 93 B7 V. Description of the invention (39) Reaction in a microwave oven at 140 ° C for 3 minutes. After hydrolysis with saturated KH2P04 solution, it was extracted with methane, and the solvent was evaporated. Chromatography on silica gel (digas methane / ethyl acetate) yielded 314 mg of 6,7-difluoro-5-phenyljun_3_amine. 5 Yipan_ 丄: hexahydropyridine small carboxylic acid (6,7 -Difluoro-5-phenyl-1H-indazol-3-yl) hydrazone Step 1 Sequentially add 131μ1 pyridine and 154μ1 ethyl formate to 10 387.8mg (6,7_difluorophenyl-1_ [[2 · (Trimethylpyridyl) ethoxy] ethoxy] methyl 1 吲 -indazole-3-amine chemistry # 8 in digas methane. After 75 minutes, the reaction is complete. After hydrolysis, extraction and -After evaporation, 840 mg of crude (6,7-difluoro-5-phenyl-1S-indazol-3-yl) carbamate is obtained. Step 2 15 Add 184 mg of hexahydropyridine to 161 mg of crude product (6,7-difluoro-5-phenyl-1H-indazol-3-yl) carbamate in 2.5 ml of trifluorobenzene, and the reaction was carried out in a microwave oven at 200 ° C for 20 minutes. After purification by preparative LC / MS (acetonitrile / pH 9 buffer), 80 mg of hexahydropyridine small carboxylic acid (6,7- printed difluorophenyl_1-[[2 -(Trimethylsilyl) ethoxy] methyl] _1H-indazolyl) 20 hydrazine. Step 3 Take 80 mg of hexahydropyridine small carboxylic acid (6,7-difluoro-5-phenyl small [[2- (trimethysyl) -ethoxy] methyl] -1H-ind. 3-Methanol) 2.5 ml of methanol was treated with 0.82 ml of 2N HC1 under reflux for 1 hour. After evaporation, the paper is prepared-41- This paper size applies to Chinese National Standard (CNS) A4 Hu; Grid (210 X 297 public love) 2004222 93 A7 B7 V. Description of the invention (40) LC / MS (acetonitrile / pH 9 buffer) (Liquid)) to obtain 11 mg of hexahydropyridine-1-carboxylic acid (6,7-difluoro-5-phenyl-1H-indazol-3-yl) amidamine. Mass spectrum: Retention time: 3.99; 357 = [M + Hf hH NMR spectrum (300 MHz, (DMSO-d6, δρρπι): 1.50 (m, 5 4H); 1.58 (m, 2H); 3.45 (m , 4H); 7.42 (m, 1H); 7.51 (m, 5H); 9.16 (s? 1H); 13.20 (bs, 1H) Example 2: pyrrolidine small carboxylic acid (6,7-difluoro -5-Phenyl-1H-indazol-3-yl) -fluorenamine 10 Step 1 Add 154mg of pyrrolidine to 161mg of (6,7-difluoro-5-phenyl-1H -....- 'in Azol-3-yl) aminoammonium ethyl acetate in 2.5 ml trifluorobenzene, in a microwave oven 200T: 20 minutes in a microwave oven. The product was purified by a silica gel column to give 75 mg of pyrrolidine small carboxylic acid (6,7 -Difluoro-5-phenyl small [[2- (trimethylsilyl) ethoxy 15-yl] methyl] -1H-indazol-3-yl) fluorenamine. Step 2 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Preparation of 75 mg pyrrolidine-containing small carboxylic acid (6,7-difluoro-5-phenyl small [[2- (trisylsilyl) -ethoxy] methyl] -1Η-indazol-3-yl) 3 ml of fluorenamine was treated with 0.82 ml of 2N HC1 under reflux for 1 hour. After evaporation, it was purified by preparative 20 LC / MS (acetonitrile / pH 9 buffer) to obtain 36 mg of pyrrolidine small carboxylic acid (6,7- Difluoro-5-phenyl-1H-indazol-3-yl) fluorenamine. Dwell time 3.72 minutes; 343 = [M + H] + W NMR spectrum (300 MHz, (DMSO-d6, δ ppm): 1.86 (m, 4H); 3.40 (m, 4H); 7.42 (m (1H); from 7.45 to 7.54 (m, 4H); -42- This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 2004222 93 _ B7 V. Description of the invention (41) 7 -63 (bd, J = 7 Hz, 1H); 8.84 (s, 1H); 13.20 (bs, 1H). -¾: 3- (4-methylhexahydro ° specificity) as in Example 2- 1-yl) propylamine is reacted as a starting material to produce 1- (6,7-difluoro-5-phenyl-5 1H-indazol-3-yl) -3- [3- (4-methyl -Hexahydro-17Big-1--1-yl) propyl] gland. LH NMR spectrum (300 MHz, (DMSO-d6, δριη): 1.92 (m, 2H); 2.82 (s, 3H); by 3 · 01 to 3.75 (m, partially shaded, 12 Η); 7.43 (m, 1Η); from 7.47 to 7.56 (m, 4Η); 7.71 (t, J = 7 Ηζ, 10 1H); 8.05 (dd? J = 1.5 -7 Hz, 1H); 9.61 (s, 1H) Mass spectrum: retention time 157 minutes; 429 blue [M + H] + according to the pharmaceutical composition of the present invention is a compound of formula ⑴ Or salts of these compounds, which are pure substances or are medically compatible with any other inert or physiological activity Compatibility of the active ingredient composition into compositions. The medicine according to the present invention can be administered by 15 oral administrations, parenteral administrations, rectal or topical administrations. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. The solid dosage forms for oral administration can be made into tablets, pills, powders (hard gelatin capsules, pill packs) or granules. In these compositions, the active ingredient according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under an argon stream. These compositions may also contain materials other than 20 dilutions, such as: one or more lubricants, such as: stearic acid or talc 'coloring agents, coating agents (sugar coating :) or brighteners. Liquid compositions for oral use can be made into pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs, which contain inert diluents such as water, ethanol, glycerol, vegetable oil or liquid paraffin. These compositions may contain thinner-43- This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 2004222 93 V. Description of the invention (42) Other than 10, for example: humidifier , Sweetener, thickener, flavoring or stabilizer. The parenteral sterile composition is preferably an aqueous or non-aqueous solution, suspension or emulsion. Water, propylene glycol, polyethylene glycol, vegetable oils, specifically olive oil, organic esters for injection, such as ethyl oleate, or other suitable organic solvents can be used as a solvent or vehicle. These compositions may also contain adjuvants, specifically wetting agents, isotonicity agents, emulsifiers, dispersants and stabilizers. There are several ways to kill g, such as: sterile filtration, adding a fungicide to the composition, irradiation or heating. It can also be made in the form of a sterile solid composition which is dissolved in sterile water or any other sterile medium for injection when used. 15 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 Rectal compositions are suppositories or rectal capsules, which contain excipients in addition to the active product, such as cocoa butter, semi-synthetic glycerides or polyethylene Diol. ° Topical pharmaceutical compositions may be, for example: creams, lotions, ophthalmic drops, mouthwashes, nasal drops or aerosols. The subject matter of the present invention is the amidoindazole compound of the formula 与其 and its pharmaceutically acceptable Salt, and its derivatives in the preparation of pharmaceutical compositions for the prevention and treatment of diseases caused by abnormal kinase activity, such as those involving neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, forehead Dementia, Cortical Basal Degeneration, Pick's Disease, Stroke, Spine Trauma and Peripheral Neuropathy, Obesity, Metabolic Diseases, Type H Diabetes, Normal South Blood Pressure, Arteriosclerotic Cardiovascular Diseases, and more Cystic ovary syndrome, syndrome X, immunodeficiency and cancer. '-44- This paper is disgusted by the general national standard (CNS) A4 specification (21〇χ297α) 2004222 93 _ B7 V. Description of the invention (43 Abnormal kinase activity can be mentioned, for example: PI3K, AkT or GSK3 /? Abnormal activity of CDKs, etc. In human therapy, the compounds according to the present invention are particularly suitable for treating / preventing neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontal and parietal dementia, cortex Basal degeneration, Pick, disease, stroke, cranial and spinal trauma and peripheral neuropathy, obesity, metabolic disease, type II diabetes, intrinsic high blood pressure, arteriosclerotic cardiovascular disease, polycystic ovary Syndrome, Syndrome X, Immune Deficiency and Cancer. 10 The dosage depends on the required effect, the length of treatment period and the route of administration. The daily oral dose for adults is usually between 5mg and 1000mg. Unit doses range from 1 mg to 250 mg of the optional ingredient. Usually the physician will know the appropriate dose based on the age, weight and all other specific factors of the patient being treated.

The following examples illustrate the composition according to the invention 15 f Example A Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 Prepare hard gelatin capsules according to general technology, the composition of which is as follows: 50 mg active ingredient,-compound of formula (I) 50 mg-cellulose 18 mg-lactose 55 mg-colloidal silica lmg-endometridium sodium powder-talc 10 mg 10 mg-magnesium stearate 1 mg -45- This paper is applicable to the national standard + CNS A4 specifications (210x297 public love) 2004222 93 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (44) Example B A tablet was prepared according to general technology with a dosage of 50mg of active ingredient, and its composition is as follows: (I) Compound 50 mg-lactose 104 mg-cellulose 40 mg-polyvinylpyrrolidone 10 mg-sodium carboxymethyl starch 22 mg 10-talc 10 mg-magnesium stearate 2 mg-colloidal lithotripsy 2 mg-hydroxyamidine Mixture of cellulose, glycerol and titanium oxide (72 / 3.5 / 24.5) in an appropriate amount to make a finished coating 15 Example C. Suspicious agent is equivalent to 245 mg. An injection solution is prepared according to general techniques, with a dose of 10 mg of the active ingredient, which The formula is as follows: 20 • Compound of formula (I) 10 mg-Phenylic acid 80mg-Benzyl alcohol 0.06 ml-Sodium benzoate 80 mg-95% ethanol 0.4 ml -46- This paper size applies to China National Standard (CNS) A4 (210x297 mm) 2004222 93 A7 B7 V. Description of the invention (45 Sodium hydroxide propylene glycol printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 24 mg 1.6 ml appropriate amount, added to 4 ml This invention is related to prevention and treatment involving τ-protein The method for the disease of phosphorylation reaction is to administer the compound of formula (I) and its pharmaceutically acceptable salt. 0 This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210x297 mm)

Claims (1)

2004222 93 A8 B8 C8 D8 VI. Patent application scope A compound of formula (I), its racemate, enantiomer or diastereomer and its mixture, its tautomer and its pharmaceutically acceptable salt : N ^ r3 N (I) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 101520 where R3 is (1-6C) alkyl, aryl, aryl (14C) alkyl, heteroaryl, heteroaryl (1-6C) alkane Base, aryl or heteroaryl fused with (MOC) cycloalkyl, heterocycle, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, C00R1, S02R1, C (= NH) R1 or C (= NH) NR1 groups; these groups may optionally be substituted with one or more substituents selected from the group consisting of dentin, cn, no2, nh2, oh, ori, cooh, c (o) ori, -o- C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SR1, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S ) NR1R2, NHC (S) R1, -O-SO2RI, -S02-0-R1, aryl, heteroaryl, heterocyclic, fluorenyl, trifluoromethyl, trifluorofluorenylsulfanyl, trifluoro Ethoxy or (1-6C) alkyl; R5, R6 and R7 are each independently selected from the group consisting of halogen, CN, N02, NH2, OH, COOH, C (0) 0R8, -0-- 48-The size of the paper is applicable to the Chinese National Standard (CNS) A4 (21〇 297 public love) 92411B 2004222 93 A8 B8 C8 D8 VI. Application Patent scope C (0) R8, NR8R9, NHC (0) R8, C (0) NR8R9, NHC (S) R8, C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0 -S02R8, -S02-0-R8, trifluorofluorenyl, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl5, aryl (1-6C) alkyl, Heteroaryl, heteroaryl (1-6C) alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, adamantyl, or polycycloalkyl; these groups may be selected from one or more members as required The following substituents are substituted: halogen, CN, N02, NH2, OH, ORIO, COOH, C (O) OR10, -0-C (0) R1〇, NR10R11, NHC (O) R10, 10 C (O) NR10Rll , NHC (S) R10, C (S) NR10R11, SR10, S (0) R10, S02ja〇, NHS02R10, S02NR10Rll < -0-SO2RIO, -S〇2-〇-R10, aryl, heteroaryl, fluorene Bake, trifluoromethyl, trifluoro * methoxy or (1-6C) alkyl; PJ, R2, R8, R9, R10 and R11 are printed independently as hydrogen, ( i-6C) 15 alkyl, aryl, alkenyl, alkynyl, heteroaryl, which may be substituted by one or more substituents selected from halogen, (1-6C) alkane Group, 〇6C) alkoxy, CN, No2, NH2, OH, COOH, COO alkyl, CONH2, methylamino, trifluoromethyl, trifluoromethyloxy; R1 and R2 or R8 and R9 or R10 and Rll may form a 5- or 6-membered 20 ring, which may or may not contain heteroatoms, such as: 0, S or N; and when R3 is a 6-membered nitrogen-containing heteroaryl or thiazolyl or imidazolyl or In the case of an oxazolyl group, at least one of R5 and R6 is an aryl group, and it may be optionally substituted with one or more substituents selected from the group consisting of halogen, CN, N02, NH2, OH, OR10, COOH, and C (0). 〇R1〇, -〇- -49-This paper size applies to China National Standard (CNS) A4 (210x297 public love) 2004222 93 C (O) R10, NR10R11, NHC (0) R1〇, C (0) NR10R11, NHC (S) R10, C (S) NR10R11, SR10, S (0) R1〇, SO2R10, NHSO2R10, S02NR1. R11, -0-SO2R10, -S02-O-R10, aryl, heteroaryl, formamyl, trifluorofluorenyl, trifluoromethoxy or (1-6C) alkyl. 2 · —A compound of formula ，, its racemate, enantiomer or diastereomer, its structure, its tautomer and its pharmaceutically acceptable salt: (I) Order 15 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 where R3 is (1-6C) alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1- 6C) Alkyl, aryl or heteroaryl fused with (1-10C) cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2 , CSNR1R2, COOR1, S02R1, C (= NH) R1 or C (= NH) NR1 groups; these groups can be optionally substituted with one or more substituents selected from the group consisting of prime, CN, N02, NH2 , 0H, 0Rl, C00H, C (0) 0Rl, -0-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SR1, S (0) R1, S02R1, NHS02R1, S02NR1R2, -50 This paper size is applicable to China National Standard (CNS) A4 specification (210x297 mm) 2004222 93 C8 D8 VI. Patent application scope C (S) NR1R2, NHC (S) R1, -O-SO2RI, -S02-0- R1, aryl, heteroaryl, heterocyclic, methylfluorenyl, trifluorofluorenyl, trifluorofluorenylsulfanyl, trifluorofluorenyloxy or (1-6C) alkyl; R5 and R6 are independently selected From the following groups: functins, CN, 5 NO! ·, NH2, OH, COOH, C (0) 0R8, -0-C (0) R8, NR8R9 NHC (0) R8, C (0) NR8R9, NHC (S) R8, C (S) NR8R9, SR8, S (0) R8, S02R8, NHS02R8, S02NR8R9, -0-S02R8, -SCV0-R8, trifluoro Methyl, trifluoromethoxy, (1-6C) alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) 10 alkyl, heteroaryl, heteroaryl (1- 6C) alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, desandyl, polycyclic alkyl; these groups may be optionally substituted with one or more substituents selected from the group consisting of CN, N02, NH2, OH, OR10, COOH, C (O) OR10, -〇-C (O) R10, NR10R11, NHC (O) R10, 15 C (O) NR10Rll, NHC (S) R10, C (S) NR10R11, SR10, S (O) R10, SO2RIO, NHS02R1〇, S02NR1〇R11, -〇-SO2R10, -SO2-O-R10, aryl, heteroaryl, formamyl, trifluoromethyl, trifluoromethyl Oxygen or (1-6C) alkyl; printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, R7 is halogen, fluorenyl, cyclopropyl, CN, OH, methoxy, trifluoro 20 methyl, vinyl, acetylene Group, trifluoromethoxy, N02, NH2 or NMe2, IU, R2, R8, R9, R10 and Can are independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl or Aryl, which may be substituted by one or more substituents selected from the following: halogen, (丨 _6C) -51-This paper size applies to China National Standard (CNS) A4 (210x297 public) 2004222 93 A8 B8 C8 ____D8 _ VI. Patent Application: Alkyl, (1-6C) alkoxy, CN, N02, NH2, OH, COOH, COO alkyl, CONH2, methylamino, trifluoromethyl or trifluoromethyloxy R1 and R2 or R8 and R9 or R10 and RU may form a 5- or 6-membered 5-ring, which may or may not contain heteroatoms, such as: 0, S or N; and when R3 is 6-membered nitrogen When heteroaryl or thiazolyl or imidazolyl or oxazolyl, at least one of R5 and R6 is an aryl group, which may be substituted with one or more substituents selected from halogen, CN, N02, NH2, as required. OH, OR10, COOH, C (O) OR10, _〇-10 C (O) R10, NR10R11, NHC (O) R10, C (O) NR10Rll 'NHC (S) R10, C (S) NR10R11, SRlj) , S (0) R1〇, SO2R10, NHSO2R10, S02NR1〇R11 f-〇-S〇2R1〇, _ S〇2_O-R10, aryl, heteroaryl, formamyl, trifluoromethyl, trifluorofluorene Oxy, or (1-6C) alkyl. 15 3 · —Compounds of formula (I), their racemates, enantiomers or diastereomers and their mixtures, their tautomers and their pharmaceutically acceptable salts: employees of the Bureau of Intellectual Property, Ministry of Economic Affairs Consumption cooperative prints 20 of its R5R6 3 R R7 \) / This paper size is applicable to Chinese National Standard (CNS) A4 specification (2ΐ〇χ297 公 楚) 2004222 93 A8 B8 C8 ___D8 ___ 6. The scope of patent application R3 is (1-6C) alkyl, aryl , Aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, aryl or heteroaryl fused with (1-10C) cycloalkyl, heterocyclic, heterocycloalkyl , Cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, 5 S02R1 or C (= NH) NR1 groups; these groups can be Substituted from the following substituents: halogen, CN, NO2, NH2, OH, OR1, COOH, C (0) 0R1, -0-C (0) R1, NR1R2, NHC (0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, 10 NHC (S) R1, -0-S02Rl, -S02-0-Rl, aryl, heteroaryl, formyl, Oxo, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C) alkyl; R5 is aryl; R6 and R7 are independently halogen, methyl, cyclopropyl , CN, 15 OH, methoxy, trifluoromethyl, vinyl, ethynyl, trifluorofluorenyloxy, N02, NH2 or NMe2 The R1 and R2 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs are independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl or heteroaryl, which can be selected by one or more The following substituents are substituted: halogen, (1-6C) alkyl, (1-6C) alkoxy, 20 CN, No2, NH2, OH, COOH, COO alkyl, conh2, formamyl, oxo Group, trifluorofluorenyl or trifluoromethoxy; R1 and R2 may form a 5- or 6-membered ring, which may or may not contain heteroatoms, such as ·· 0, S or N. 4. The compound according to item 1 of the scope of patent application, which is selected from the following: -53-This paper size is applicable to Chinese national standards (0 ^ Magic 4 specification (21〇x297 mm) 2004222 93 Α8 Β8 C8 D8 Scope of patent application N- (Bicyclo [2.2.1] hept-5-en-2-ylfluorenyl) -6 • Ga-7-fluoro-5-phenyl-1H_ indene * 3-amine 6-Ga-7 _Fluoro-N- (3,3-difluorenylbutyl) -5-phenyl-1H-indazole-3-amine 6-gas-7-fluoro-N- (3-phenylpropyl) -5 Phenyl-1 H-indazole-3-amine 5 6-chloro-7-fluoro-N- (cyclopropylmethyl) -5-phenyl-1H-indazole-3-amine 6-gas-7 _Fluoro-N- (cyclopentylmethyl) -5-phenyl-1H-indazole-3-amine 6-gas-7_fluorosmall_ [3- (fluorenylthio) propyl] -5-benzene 1H-indazole-3-amine 6-Ga-7-fluoro-N · (phenethyl) -5-phenyl-1H-indazole-3-amine 6-Ga-7-fluoro-N- ( Cyclohexylmethyl) -5-phenyl-1H-indazole-3-amine 10 6-Ga-7-fluoro-7N-propyl-5-phenyl-1H-indazole-3-amine 6-Ga- 7-fluoro-N- (2, $ 3,3,4,4,4-heptafluorobutyl)-$ • phenyl-1H-indazole-3-amine hydrate 6-gas-7-fluoro-N- (4,4,4-trifluorobutyl) _5-phenyl-1H-indazole-3-amine 6-gas-7-fluoro-N-[(4-methoxyphenyl) methyl] -5 -Phenyl-1H-indazole-3-15 Member of the Bureau of Intellectual Property, Ministry of Economic Affairs Printed by Consumer Cooperatives 6-Ga-7-Fluoro-N- (phenylmethyl) -5-phenyl-1H-indazole-3-amine 6-Ga-7-fluoro-N-[(4-cyano Phenyl) methyl] -5-phenyl-1H-indazol-3-amine N-[(4-chlorophenyl) fluorenyl] -6-chloro-7 · fluoro-5-phenyl-1H-ind N- [3- (3-methoxyphenyl) methyl] -5-phenyl-1H-pyridine-3-20 Amine 6-Ga-7 -Fluoro-N-[[4- (trifluoromethoxy) phenyl] methyl] -5-phenyl-1fluorene-indazole-3-amine N- [4-[[[6- 气 -7- Fluoro-5-phenyl-1Η-indazol-3-yl] amino] methyl] phenyl] ethanamine-54-This paper is sized to the Chinese National Standard (CNS) A4 (210 X297 mm) 2004222 93 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Ah B8 C8 D8 Sixth, the scope of patent application 6-Ga-7-fluoro-N-[(3,5-Digas phenyl) methyl] -5-phenyl- 1H-indazol-3-amine 6-gas-7-fluoro-5-phenyl-N-[[4- (trifluorofluorenyl) phenyl] fluorenyl] -1H-0. Sat-3-amine 5 6-gas-7-fluoro-N-[(4-fluorophenyl) methyl] -5-phenyl-1H-indazole-3-amine 6-chloro-7-fluoro-N_ [3- (4-methylphenoxy) phenylmethyl] -5-phenyl-1H-indhalan-3-amine (2,2,3,3,4,4,4_heptafluorobutane ) -6-Ga-7-fluoro-5-phenyl-111-indazole-3 · amine 10 6-Ga-7-fluoro-5-phenyl_N _ [(3,5-bis (trifluoromethyl) Phenyl) phenyl] fluorenyl] -1H- indyl-3-amine 6-gas-7-fluoro-5-phenyl-N-[[3-(trifluoromethyl) phenyl] fluorenyl] -1 H-indole-3-amine 6-gas-7-fluoro-N-[(6-fluorenyloxy-2-naphthyl) fluorenyl] -5-phenyl-1H-indazole-15 3-amine 6- GA-7-GA-N-[(pentaphenyl) methyl] -5-phenylbenza-3-amine 6-GA-7-fluoro-N-[[4- (methylthio) phenyl ] Fluorenyl] -5-phenyl-1fluorene-indazole-3-amine N-[(4-gas-3-fluorophenyl) methyl] -6-chloro_7_fluoro-5-phenyl-1fluorene -Indazole-3-20 amine 6-gas-7-fluoro-5-phenyl-N- (3,3,3-trifluoropropyl) -1 hafnium_indazole-3-amine 6-gas-7 -Fluoro-5-benzyl-N- (3-thienylmethyl) -1fluorene-indazol-3-amine N- (bicyclo [2.2.1] hept-5-en-2-ylfluorenyl) -6 -Ga-7-Fluoro-5-phenyl-1Η-indazole-3-amine-55-This paper size applies to China National Standard (CNS) A4 (210 X 297 cm) 2004222 93 A8 B8 C8 D8 VI. Patent application scope N- (1, Γ-biphenyl-4-ylfluorenyl) -6-gas · 7-fluoro-5-phenyl-1H-indazole-3-amine 6 -Ga-7-fluoro-N-[[4- (dimethylamino) phenyl] methyl] -5-benzyl-1'-indazole-3-amine N- (2,2 · -bithiophene (-5-ylmethyl) -6-Ga-7-fluoro-5-phenyl-1H-indazole-3- 5 amine 6-Ga-7-fluoro-5-phenyl-N-[[l- ( Phenylfluorenyl) -1fluorenyl-imidazol-2-yl] fluorenyl] -1fluorenyl-fluorenyl 5-pyridine-3_amine 6-gas-7-fluoro-N-[[l_methyl-1fluorenyl-imidazole-2- [Methyl] methyl] -5-phenyl-1Η-sigmato-3-amine 10 6-gas-7-fluoro-N _ [(l-methyl-1Η-indole-3 · yl) methyl] -5-phenyl-1fluorene-indazole-3_amine 6-gas-7-fluoro-N-[(5-methyl-2-furanyl) fluorenyl] phenyl-1fluorene-indazole-3-amine 6-Ga-7-Ga-5-phenyl-N- (1Η-ϋ 比 洛 -2 · 基 methyl) -1Η-σ 弓 丨 Sial-3-amine 15 6-Ga-7_fluoro-5- Phenyl-N-[(1Η-imidazole_2_yl) fluorenyl] _1 fluorene-indazole-3-amine 6-gas-7-fluoro-5-phenyl-N-ΙχΙΗ-17 m 11 sit-4 -Base) 曱 基] -1Η-β 弓 | 11 Sitting -3 · Printed by 6-Ga-7-Ga-5-phenyl-N- (1Η-σ than 0 sitting -3-ylmethyl) -111-17. Sat-3-amine 20 6-gas-7-fluoro-N-[[2-methyl-1H-imidazole_4-yl] fluorenyl] -5-phenyl-1H-indazole_3 • amine 6 Gas-7_fluoro-N · [(3,5-dimethyl-1 · benzyl-1H_radazol-4-yl) methyl] -5-phenyl-1H-indazole-3-amine 6 -Gas-7-fluoro-5-phenyl-N-[[2-phenyl-1H-imidazol-4-yl] fluorenyl] -lH- -56-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 2004222 93 A8 B8 C8 D8 6. Application scope of patents Indazol-3-amine 6-gas-7-fluoro-N-[[5- (4-gasphenyl) -2-furanyl ] Methyl] -5-phenyl-1H-indazol-3-amine 6-gas-7-gas-5-phenyl-N-[(l-methyllo-2-yl) methyl] -1Η_ 5 Indazol-3-amine 4- [5-[[[6-Ga-7-fluoro-5-phenyl-1} _indazol-3-yl] amino] fluorenyl] -2-furanyl]- Benzylsulfonamide 6-gas-7-fluoro-5-phenyl-N- (3-thienylmethyl) -1fluorene-indazole-3-amine 6-gas-7-fluoro-5-phenyl-N -[[2-phenyl-1Η-imidazol-4-yl] methyl] -1Η-10 indazol-3-amine 2-[[[6-6--7-fluoro-5_phenyl-1Η-indene Azole-3, yl] amino] methyl] -5- (fluorenylthio) -1fluorene-imidazole-4-carboxylic acid ethyl ester 6-gas-7-fluoro-5-phenyl-N-[[5- [4- (trifluorofluorenyl) phenyl] -2-furanyl] fluorenyl] -1H-indazol-3-amine 15 6-Ga-7 · Ga》 -5 -Phenyl-N- [2- (l-hexaaza ^ pyridyl) ethyl] -1Η-ϋ 17ϋ * »3-Printed by 6-Ga-7- Fluoro-N- [2- (4-morpholinyl) ethyl] -5-phenyl-1fluorene-indazole-3-amine N- (6-Ga-7-fluoro-5-phenyl-1fluorene-indole Azole-3-yl) -NΗ3,5-dichlorophenyl) urea 20 Ν- (6-Ga-7-fluoro-5-phenyl-1Η-indazol-3-yl) -Nf- (2-propene ) Urea N- (6-Ga-7-fluoro-5-phenyl-1H-indazol-3-yl) -Nf- (phenylfluorenyl) urea N- (6-Ga-7-fluoro-5 -Phenyl-1H-indazol-3-yl) -N '-(4-phenoxyphenyl) urea N · (6-gas-7-fluoro-5-phenyl-1H-indazole-3- -N · _ (4 · methoxyphenyl) -57-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 200422293 Α8 Β8 C8 D8 VI. Patent application scope methyl group] Urea N- (6-Ga-7-fluoro-5-phenyl_1H-indazol-3-yl) -N44- (trifluoromethyl) phenyl] urea N- (6-Ga-7-Ga- 5-phenyl-1Η · sigma bow | hydrazone-3-yl) -N '-(4-methoxyphenyl) 5 urea N- (6-gas-7-fluoro_5_phenyl-1H- Indazol-3-yl) -N1-cyclohexylurea N- (6-gas-7-fluoro-5-phenyl-1H-indazol-3-yl) -N * -propylurea N- (6- GA-7-fluoro-5-phenyl-1H-indazol-3-yl) -N ·-(4-Gabenzene ) Urea N- (6-Ga-7-fluoro-5-phenyl-1H-indazol-3-yl) -N ·-(4-fluorophenyl) urea 10 Ν- [6-Ga-7-默 _5_phenyl-1Η-ϋ 弓 丨 Jun-3-yl] _Ν '-(Dibad [3 · 3 · 1] dec) -1-ylurea N- (6-qi-7_qi-5 -Phenylsulfan-3-yl) -N *-(4-fluorenylphenyl) gland N- (6-Ga-7-fluoro-5 ^ benzyl-1H-indazol-3-yl) urea N -(6-Ga-7-fluorenyl-5-phenyl-1Η-σ 弓 丨 ϋ-3-yl) gland 15 Ν- (6-Ga-7-cyano-5-phenyl-1Η-in Azole-3-yl) urea Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs N- (6-Ga-7-cyclopropyl-5-phenyl-1Η-indazol-3-yl) urea N- (6- 7-Hydroxy-5-phenyl-1fluorene-indazol-3-yl) urea N- (6-chloro-7-fluorenyl-5-phenyl-1fluorene-indazol-3-yl) urea N -(6-Ga-7-trifluorofluorenyl-5-phenyl-1 弓 -0bone 嗤 -3-yl) gland 20 Ν- (6-Ga-7-trifluoromethoxy-5-phenyl -1Η-indazol-3-yl) urea N- (6-Ga-7 · Songyl-5-phenyl-1 Η-πbow 11 Syl-3 -yl) gland N- (6-Ga-7 -Amino-5-phenyl-1fluorenyl-β5-oxan-3-yl) vein N- (6-Ga-7-difluorenylamino-5-phenyl-1fluorene-indazol-3-yl) urea Ν- (6-Ga-7-ethynyl_5_phenyl-1Η-indazol-3-yl) urea-58-This paper size applies to China National Standard (CNS) A4 (210x297) ) 2004222 93 Αδ B8 C8 D8 VI. Application scope of patent N- [6-Ga-7-deca-5-phenyl-1Η-σ3 | 17x-3-yl] -4-fluorenyl-benzene continued amine N -[6-Ga-7-fluoro-5_phenyl-1fluorene-indazol-3-yl] sulfanilamide N- [6-Ga-7-fluoro-5-phenyl-1fluorene-indazole-3 -Yl] -2-propanesulfonamide N- [6-Ga-7-fluoro-5-phenyl-1fluorene-indazol-3-yl] -2,2,2-trifluoroethanesulfonium 5 amine N_ [6-Ga-7-fluoro-5-phenyl-1fluorene-indazole_3-yl] -2-thiophenesulfonamide N- [6-Ga-7-fluoro-5-phenyl-1fluorene-indazole -3-yl] benzenesulfonamide N- [6-Ga-7-Ga-5-phenyl-1Η_σbowo-3-yl] _4- (difluorofluorenyl) benzene-carbamidine 10 1 ^ _ [6-Ga-7-Ga-5-phenyl-111-. Bow 丨 0-sit-3-yl] -5- (3-iso11-to 11-sityl) -2-thiophene-sulfonamido N_ [6-air-7-fluoro-5-phenyl · 1Η_indazole- 3-yl] -4-fluorobenzenesulfonamidine N- [6-Ga-7-fluoro-5-phenyl-1fluorene-indazol-3-yl] -4-methoxybenzylsulfonamide N- [ 6-Ga-7-Ga-5-phenyl-1Η-σbow | 嗤 -3-yl] benzyl continuous amine 15 N- [6-Ga-7-fluoro-5 · phenyl-1Η-indazole -3-yl] -1-methyl-1fluoren-imidazole-4-sulfonamide N- [6-qi-7-qi-5-phenyl-1fluorene-fluorene 5 | fluorene-3-yl] -4- (1,1-Difluorenylethyl) benzsulfuronamide Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs N- [4-[[(6-Ga-7_Fluoro-5-phenyl-1H-indazole) -3-yl) amino] sulfofluorenyl] 20 phenyl] -acetamidoamine N- [6-qi-7 · xiang-5-phenyl-1Η-σbendol-3-yl] -4- Methylbenzyl methylamine amine 6-gas-7-fluoro-N- (pentafluorophenyl) -5-phenyl-1fluorene-indazole-3-amine 6-gas-7-fluoro-N- (3, 4-difluorophenyl) -5-phenyl-1H-indazole-3-amine 6-chloro-7-fluoro-5_benzyl_N- (2,3,5,6-tetrafluorophenyl) -1Η-Indazole-3-amine-59-This paper size applies to Chinese National Standard (CNS) A4 (210x297 mm) 2004222 93 Α8 Β8 C8 -------- D8 VI. Range of Patent Application _ 7_fluoro-5-phenyl-N- (2,4,6-trifluorobenzene Yl) -1H-indazolamine-7-fluoro_N- (4-fluorophenyl) _5-benzyl-1H_indazol-3-amine gas' 7-fluoro.N- [3- ( Trifluorofluorenyl) phenyl] benzyl-1H.indazolamide-7-fluoro_steam 〇 (trifluoromethyl) phenyl) jbenzyl "3-amine 6-gas- 7-Fluorine | [3-Fluoro-5- (trifluorofluorenyl) benzyl [5_benzyl] η: 嗤 · 3-amine 10 15 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 20 -Fluoro-N- (4-nitrophenyl) -5-phenyl-1H-indazole-3-amine 6-gas-7-fluoro-N- (3-nitrophenyl) -5-phenyl-1H -Indazol-3-amine-7-fluorine (3-methoxyphenyl) -5-phenyl-1H -Methoxyphenyl) -5-phenyl-fluorene-β-α-α_3_amine 6-gas-7-fluoro-N, 5-diphenyl-1H-, sia_3_amine 6-gas- 7-defeated fluorenyl group) -5-phenyl · 1Η-ϋ5 丨 salan-3-amine 6 qi-7-qi ratio octyl group) -5-benzyl_ hydrazone-saccharin-3-amine N- Butyl-6-Ga-7-fluoro-5-phenyl-1fluorene-indazole_3-amine team (6-Gafluoro-5_phenyl-1fluorene-σ3buzu.3-yl) benzyl gland > K6-Ga-7-fluoro-5_phenyl-1fluoren-indazole · 3yl) _3_methoxy its racemates, enantiomers or diastereomers and mixtures thereof, Tautomers Acceptance of salt. 5. Compounds according to item 1 and 2 of the scope of the patent application, the series of ..., Shi Bibu hexahydro. Specific bite-i-sharp (6,7-difluoro-5 · phenyl_1HH3 · yl) brewing amine ° Bihar bite-1-slow acid (6,7-dilept-5-benzyl_ 丨 H • Indazole · 3yl) pyrimidine kisses, 7-two-speaking _5-benzyl · out-〇bow 丨 sialyl) · 3 · [3 (4-fluorenylhexahydrotonium phenyl-1-yl) propyl ] Urea-60-This paper is sized for China National Standard (CNS) A4 (21〇χ 297 mm) 2004222 93 A8 Βδ C8 Its tautomers and their pharmaceutically acceptable salts. 6. The compound according to any one of claims i to 5 of the scope of patent application, which is used for preparing medicine. 7. A pharmaceutical composition 'comprised in a pharmaceutically acceptable medium containing a compound defined according to any one of items 1 to 5 of the scope of the patent application 8. A medicine according to item 7 of the scope of the patent application, which contains at least A compound 10 according to any one of claims 1 to 5 of the scope of the patent application is used for medical purposes for treating diseases in which p-protein phosphorylation occurs. 15 9 · Medicine according to item 6 of the scope of the application, which contains to noisy a compound defined according to any of the items 1 to 5 of the scope of patent application for medical use, for the treatment of neurodegenerative diseases, stroke, Cranial and spinal trauma and peripheral neuropathy, obesity, metabolic diseases, H-type diabetes, hypertension, arteriosclerotic heart disease, polycystic ovary syndrome, syndrome X, immune deficiency and cancer. Printed by Shelley Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs10. Medicine according to item 9 of the scope of patent application, in which neurodegenerative diseases are Alzheimer's disease, Parkinson's disease, frontal and parietal dementia, degeneration of the cortical base Or Pick's disease. 20 11 · —A method for preparing a compound of formula ⑴ according to item 1 of the scope of the patent application, wherein R3 is (1-6C) alkyl, aryl (1-6C) alkyl, heteroaryl (1-6C) alkyl , Heterocycloalkyl, cycloalkyl, or polycycloalkyl; these groups may be optionally substituted with one or more substituents selected from the group consisting of dentin, CN, No2, NH2, OH, OR1, COOH 、 -61 This paper size is in accordance with Chinese National Standard (CNS) A4 (210x297 mm) 2004222 93 A «B8 C8 VI. Application scope of patents C (0) 0R1, -〇-C (0) Rl, NR1R2, NHC ( 0) R1, C (0) NR1R2, SRI, S (0) R1, S02R1, NHS02R1, S02NR1R2, C (S) NR1R2, NHC (S) R1, -0-S02Rl,-SCVO-Rl, aryl, hetero Aryl, formamyl, oxo, trifluorofluorenyl, trifluorofluorenylsulfanyl, trifluoromethoxy or (1-6C) alkyl; and R1 and R2 are each independently hydrogen, (uc ) Alkenyl'aryl, alkenyl, alkynyl or heteroaryl, which may be substituted by one or more substituents selected from the group consisting of halides, (1-6C) alkyl, (1-6C) alkoxy, CN, N02, NH2, OH, COOH, COO alkyl, CONH2, 10 fluorenyl, A substituted group, a trifluorofluorenyl group, and a trifluorofluorenyl group; the product is a derivative of fluorene, R1CHO derivative, and sodium diethylfluorenylborohydride in formula IX, and is reacted in methane gas to obtain the product. If necessary, it can be converted into a pharmaceutically acceptable salt. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 12 · —A method for preparing compound 15 according to the formula (1) defined in item # 1 of the patent scope, where R3 is C (0) NR1R2 or C (S) NR1R2, and R1 and R2 are each independently hydrogen, (1-6C) alkyl, aryl, alkenyl, alkynyl or heteroaryl, which may be substituted by one or more substituents selected from the following: _ prime, (1-6C) alkyl, (1-6C) alkoxy, CN, N02, NH2, OH, COOH, COO alkyl, CONH2, 20 formamyl, oxo, trifluoromethyl, trifluoromethoxy ; It is obtained by reacting OCNR1 and a derivative of R3 in formula (I) with tetrahydrofuran, and the product obtained can be converted into a pharmaceutically acceptable salt if necessary. 13 · —A method for preparing a compound of formula ⑴ as defined in item 丨 of the scope of the patent application, wherein R3 is S02R1; and R1 is hydrogen and (1-6C) alkane-62 (CNS) A4 specification (21G x 297 public 2004222 93 93 A8 B8 C8 __D8 6. Application for a patent scope group, aryl, alkenyl, alkynyl or heteroaryl, which itself may be subject to one or more selected from the following Substituent substitution: halogen, (1-6C) alkyl, (1-6C) alkyloxy, CN, NO2, NH2, OH, COOH, COO alkyl, CONH2, fluorenyl, oxo, trifluorofluorene And tri-5 fluoromethoxy; it is a derivative of sulfonium gas R1SO2001 and R3 in formula ⑴ is a hydrazone derivative, and reacted with dichloromethane in the presence of the test, the resulting product can be converted into Pharmaceutically acceptable salts 14. An intermediate: 10 6,7-difluoro-1fluorene-indazole-3_amine N- (6,7-difluoro-1fluorene-indazol-3-yl) butanamine Ν- [6,7-difluoro-1-[[2- (trimethylsilyl) ethoxy] fluorenyl; yl] 3-yl] butanamide N- [5- Mo_6,7_difluoro Small [[2_ (trimethylsilyl) ethoxy] methylchuan 15 ind. Sit-3-yl] -butanidine Ν- [6,7-difluoro-5-phenyl small [[2- (trimethylsilyl) ethoxy] methyl 1Η-indazol-3-yl] butanamide, Intellectual Property Bureau, Ministry of Economic Affairs, Employee Consumption Cooperative Printed 6,7-difluoro-5-phenyl small [[2_ (trisylsilyl) ethoxy] methyl] _1Η_indazole_3_amine 20 6,7-difluoro-5-phenyl- 1Η-called Buzu-3-amine. .63-This paper size is applicable to the Chinese National Standard (CNS) A4 specification (21〇χ 297 mm) 2004222 93 (0 books? · Running Sun Nose '(2), the representative Brief description of the symbols of the components in the figure: Page 2-2 »