TWI353978B - Novel aminoindazole derivatives as medicaments and - Google Patents

Description

A7 1353978 B7 V. INSTRUCTION DESCRIPTION (1) The present invention relates to a derivative having the general formula (I): N-R3

Or the use of a pharmaceutically acceptable salt thereof as a kinase inhibitor. Printed by the Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, the purpose of the present invention is to prepare an aminocarbazole derivative of the general formula (I) and a pharmaceutically acceptable salt thereof for the prevention and treatment of abnormal activity of the kinase. Pharmaceutical compositions of diseases such as, for example, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontal dementia, basal cortical degeneration, Pick's disease , stroke, cranial spinal cord injury and peripheral nerve 15 disease, obesity, metabolic disease, type II diabetes, primary high thalamic pressure atherosclerotic cardiovascular disease, polycystic ovarian syndrome, X syndrome, immunodeficiency and A kinase of cancer comprising a novel aminocarbazole derivative and a pharmaceutically acceptable salt thereof, and the present invention relates to the novel aminocarbazole derivative and a pharmaceutically acceptable salt thereof. The present invention relates to a derivative of the formula (I) wherein: R3 is (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl (1) -6C) alkyl, aryl or heteroaryl fused to (1-10C)cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkyne Base, CONR1R2 'CSNR1R2, C00R1, S02R1, the paper scale applies to the China National Standard (CNS>A4 specification (210X 297 mm) 1353978 A7 B7 V. Description of invention (2) C(=NH)R1 or C(=NH An NR1 group; such groups are 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 ' 5 NHS02R1, S02NR1R2 ' C(S)NR1R2 ' NHC(S)R1, -O-S02R1 -S02-0-Rl, aryl, heteroaryl, heterocyclic, indolyl, trifluoromethyl 'trimethylsulfanyl' trifluoroindolyl or (1-6C)alkyl; R5 and R6 is individually selected from the group consisting of halogen, CN, N〇2, NH2, OH, COOH, C(0)0R8, -0-C(0)R8' NR8R9, 10 NHC(0)R8, C(0) NR8R9, NHC(S)R 8, C(S)NR8R9, SR8, S(0}R8 'S02R8, NHS02R8, S02NR8R9, -O-S02R8, -S02-0-R8, trifluoromethyl, trifluoromethoxy' (1-6C) Mercapto, (1-6C) alkoxy, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, heterocyclic, cycloalkyl, alkenyl, Alkynyl, adamantyl 15 or polycycloalkyl; such groups may be optionally substituted with one or more substituents selected from the group consisting of halogen, CN, N〇2, NH2'OH, OR10, COOH, C ( O) OR10, -OC(O)R10, NR10R11, Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, Printed NHC(O)R10, C(O)NR10Rll 'NHC(S)R10, C(S>NR10R11, SR10 'S (O) R10, SO2R10, NHSO2Ri0, 20 SO2NR10Rll '-〇-SO2R10, -SO2-O-R10, aryl, heteroaryl, formamyl, trifluoromethyl 'trifluoromethoxy or (1-6C )alkyl;

Rl, R2 'R8, R9 'R10 and R11 are each independently hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl, heteroaryl, which are themselves selected from the group consisting of 1 or more Substituted by: Substituent: Halogen, (1-6C)alkyl, (1- -4- This paper scale applies to the Guinness Standard (CNS) A4 specification (2丨0 X 297 mm) 1353978 Λ7 B7 V. Invention Description (ο 6C) alkoxy, CN, hydrazine 2, NH2, OH, COOH, COO alkyl, CONH2, methyl-trifluoromethyl, trifluoromethoxy;

Ri and R2 or R8 and R9 or R10 and R11 may form a 5- or 6-membered ring which may or may not have a hetero atom such as fluorene, S or N; 5 and when R3 is a 6-membered aza-containing When aryl or thiazolyl or imidazolyl or oxazolyl, at least one of R5 and R6 is aryl, optionally substituted with one or more substituents selected from the group consisting of halogen, CN, N02, NH2 , OH, ORH), COOH, C(O)OR10, -0-C(0)R10, NR10R11, NHC(O)R10, C(0)NR10R11, NHC(S)R10, 10 C(S)NR10RU, SR10, S(O)R10 'SO2R10, NHSO2R10, SO2NR10Rll, -Q-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifluoromethyl, trifluoromethoxy or (1 -6C)alkyl; relating to its racemates, mirror image or non-image isomers and mixtures thereof, to their tautomers and to their pharmaceutically acceptable salts. 15 The invention relates in particular to a derivative of the general formula (I), wherein: the Ministry of Economic Affairs Intellectual Property Office employee consumption cooperative prints the R3 system as (1-6C) alkyl, aryl, aryl (1-6C) alkane Alkyl, heteroaryl 'heteroaryl(1-6C)alkyl, aryl or heteroaryl fused to (1-10C)cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantane a polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNH1R2, COOIU, S02R1 or 20 C(=NH)NR1 group; such groups are optionally substituted by one or more substituents selected from the group consisting of: Halogen, CN, N02 'NH2 ' OH, OR1 'COOH, C(0)0R1, 〇-C(0)Rl 'NR1R2, NHC(0>R1, C(0)NR1R2, SRI, S(0)R1 , SO2RI, NHSO2RI, S02NR1R2, C(S)NR1R2, NHC(S)R1, -〇-S02Rl, -SO2- This paper scale applies to China's national standard <CNS>A4 specification (210x297 mm) Ministry of Economic Affairs Property Bureau Staff Consumer Cooperatives Printed 1353978 A7 B7 V. INSTRUCTIONS (4) O-Rl, aryl 'heteroaryl, indolyl, azepine, trifluoromethyl, trifluoromethylsulfanyl, three Fluoromethoxy or (1-6C)alkyl: R5 is an aryl group, optionally 1 Or a plurality of substituents selected from the group consisting of halogen, CN, N02, NH2, OH, ORIO, COOH, 5 C(O)OR10, -0-C(0)R10, NR10R11, NHC(O)R10, C (O)NR10Rll 'NHC(S)R10, C(S)NR10RU, SR10, S(O)R10 ' SO2R10 ' NHSO2RIO ' SO2NRIORH ' -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, Mercapto 'trifluoromethyl, trifluoromethyl fluorenyl or (1-6C) alkyl; 10 R6 is halogen, fluorenyl, cyclopropyl, CN, OH 'decyloxy, trifluoromethyl, ethylene . American 'ethynyl, trifluoromethoxy, N02, NH2 or NMe2 groups;

Rl, R2 are each a hydrogen '(1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl group, which itself is optionally substituted by one or more substituents selected from the following substituents: (1-6C)alkyl, (1-6C)alkoxy, CN, N〇2, NH2 'OH, COOH, COO alkyl, CONH2, formamidine, oxy, trifluoromethyl or trifluoro Methoxy; R1 and R2 may form a 5- or 6-membered ring which may or may not have a hetero atom such as 0'S or N; 20 its racemate, mirror image or non-image isomer And mixtures thereof, tautomers thereof and pharmaceutically acceptable salts thereof. A preferred aspect of the invention relates to a derivative of the formula (I) wherein: R3 is (1_6 alkylalkyl 'aryl 'aryl (1-6C) alkyl, heteroaryl-6- paper paper ruler Did not encounter phase T due to solid and private standards (cj^s > A4 specifications (21〇X 297 mm)

1353978 a7 Β7 V. Description of the invention (5) aryl, heteroaryl (1-6C) alkyl, aryl or heteroaryl, (heterocyclic, heterocycloalkyl, naphthenic) Alkanoyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, C0NR1R2, CSNR1R2, COOfU, S02R1 or C(=NH)NR1 groups; such groups are optionally substituted by i or more selected from the following 5 Substitution: halogen, CN, N〇2, NH2, OH, 0R1, 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-R1, aryl, heteroaryl, formazan, oxygen a group, a trifluoromethyl group, a tris-10 fluorodecyl decyl group, a trifluoromethoxy group or a (1-6C) alkyl group; and the R5 group is a phenyl group, optionally substituted by one or more substituents selected from the group consisting of the following substituents; : halogen, CN, N〇2, NH2, OH, OR10, COOH, C(O)OR10, -OC(O>R10, NR10R11, NHC(O)R10, C(O)NR10Rll, NHC(S)R10, C(S)NR10R11, SR10, 15 S(O)R10, SO2R10, NHSO2R10, SO2NRi0Rll ' -O-SO2RIO, -S〇2-O-R10, aryl, heteroaryl, methyl, trifluoromethyl Trifluoromethane Oxygen or (1-6C)alkyl; R6 is printed by the Ministry of Economic Affairs, Intellectual Property Office, and the Consumer Cooperatives are halogen, mercapto, cyclopropyl, CN ' OH, methoxy, trifluoromethyl, vinyl, acetylene a 'trifluoromethoxy, no 2, NH 2 or 20 NMe 2 group;

Rl, R2 are each hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, which itself is optionally substituted by one or more substituents selected from the following halogens ( 1-6C) alkyl, (1-6C) alkane, CN, N02, NH2, OH, COOH 'COO alkyl, CONH2, formazan, aerobic paper scale applicable to Chinese national standard (CNS> A4 specification (210x297 mm) Λ7 1353978 B7 V. Description of the invention (6) Group, trifluoromethyl or trifluoromethoxy; R1 and R2 may form a 5- or 6-membered ring, which may or may not have a hetero atom , such as 0, S or N; racemates thereof, mirror image or non-image isomers and mixtures thereof, tautomers thereof and pharmaceutically acceptable salts thereof. A derivative of the formula (I) wherein: R3 is (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl,heteroaryl(1-6C)alkane Or aryl or hetero 10 aryl, heterocyclic, heterocycloalkyl 'cycloalkyl 'adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2 fused to (1-10C)cycloalkyl , COOR1, S02R1, C(=NH)R1 or C(=NH)NR1 groups These groups are 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, 15 C(0)NR1R2, SRI, S(0)R1, S02R1 'NHS02R1, S02NR1R2, C(S)NR1R2, NHC(S)R1 ' -〇-S02Rl, -S02·O -Rl, aryl, heteroaryl, methyl, trifluoromethyl, trifluoromethylsulfanyl 'trifluoromethoxy or (1-6C) alkyl; M Ministry of Intellectual Property Office employees cooperative cooperative Printed R5 is a stupid base; 20 R6 is a gas;

Rl, R2 are each independently hydrogen, (1-6C)alkyl, aryl, dilute, alkynyl or heteroaryl' which itself is optionally substituted by one or more substituents selected from halogen: -6C)alkyl, (1-6C)alkylhydrazine, CN, N〇2, NH2, OH, COOH, COO alkyl, CONH2, formazan, trifluoro-8- This paper scale applies to China a孓揉Standard (CNS>A4 Specification (210x297)) --- 1353978 Λ7 B7 V. Description of Invention (7) 10 15 Ministry of Economic Affairs Intellectual Property Bureau Bayer Consumer Cooperatives printed « 20 methyl or trifluoromethyl thiol; ''mixture=, non-image isomer or tautomer, and: can be: chain II Si:::::) pit base in a straight chain or branch containing 2 to 6 partial; tied to a straight bond or branch a bond in the bond... one to three conjugated or non-conjugated double bonds; the alkynyl group contains 2 to 6 carbon atoms in the straight or branched chain and - to 3 = ^ non-co-branded bonds; the aryl group It is selected from the group consisting of a stupid base and a (four) feed base; the heteroaryl jin contains 3 to a ring member, and optionally contains __ or a plurality of heteroatoms selected from the group consisting of hydrazine, sulfur and milk, especially a base group, a porphin base, and a feedstock. Base" is more than biting, biting. Nanji, material base, and. K-based, 4-dis-sulphate, hydrazinyl sulphide, H-, iso-(tetra)-iso-indenyl-triazolyl, pyrazolyl or fluorenyl; halogen group is gas, iodine fluoride or bromine, The alkylene group is selected from the group consisting of an adamantyl acridine group, a fluorenyl group, a n-decyl group, a primary alkenyl group or a n-decyl group; the heteroaryl group fused to the (M0C) cycloalkyl group is selected from the group consisting of hydrogen filaments, Heterochroman, chromanyl, 123,4-tetrahydroisodecyl or 1,2,3,4-tetrahydroindenyl; the heterocyclic group containing from i to 2 selected from the group consisting of oxygen 'sulphur or nitrogen a hetero atom, especially a piperidinyl group, a hydrazino group, a pyrrolyl group, an imidazolidinyl group, a pyrazolidine group, an isothiazolidinyl group, a thiazolidinyl group, an isoxazolidinyl group, a oxazolidinyl group, a piperene Alkaloid, azetidinyl ' 2 piperidinium, 3-piperidone, 4-piperidone, 2-pyrrolidone or 3-pyrrolidone. The compound of formula (I) has one or more asymmetric carbons Therefore, there are isomers, antimony, mirror image isomers and non-image isomer forms; the latter is also part of the invention, and the mixture thereof is also

-9- 1353978 Α7 Β7 V. DESCRIPTION OF THE INVENTION (8) In the application of the compound of the formula (I) of the present invention, the following compounds may be mentioned: N-(bicyclo[2.2.1]hept-5-ene-2- Methyl)-6-gas-5-stupyl-1H-indole. Raw-3-amine 5 6-gas·Ν-(3,3-dimethylbutyl>-5-styl-1H-Woxazol-3-amine 6-gas-Ν-(3·phenylpropane Base)-5-stupyl-1Η-pf|σ sit-3-amine 6-gas-Ν-(cyclopropylmethyl)-5-phenyl-1-indole-3-amine 6-gas-N -(cyclopentylmethyl)-5-phenyl-1H-indazol-3-amine 6-gas-N-[3-(indolyl)propyl]-5-phenyl-1H-Wazole- 3-amine 10 6-gas-N-(phenylethyl)-5-phenyl-1H-»» 丨. Sodium-3-amine 6-gas-N-(cyclohexylmethyl)-5-benzene -1-1H-carbazol-3-amine 6-gas-N-propyl-5-stupyl oxa-3-amine 6-gas-N-(2,2,3,3,4,4,4- Heptafluorobutyl b 5 - phenyl-1H-indazole-3-amine hydrate 15 6-gas-N-(4,4,4-trifluorobutyl)-5-phenyl-1H-carbazole- 3-Amine Ministry of Economics Intellectual Property Bureau Staff Consumer Cooperative Printed 6-Gas-N-[(4-methoxyphenyl)methyl]-5-phenyl-1H-indazole-3-amine 6-gas-N -(笨基曱基)-5·Phenyl 丨 丨 -3--3-amine 6-gas-N-[(4- gas-based stupyl) fluorenyl]-5- stupid-lH-e bow 丨 wow - 3-aminoindole-[(4-indolyl)indenyl]_6_gas-5-stupyl-1indole-indazole-3-amine 20 6-gas-indole-[(3-oxooxy) 5-yl-l-yl-indole-3-amine 6-gas-oxime-[[4-(trifluoromethoxy)phenyl]methyl]_5_styl-1Η-carbazole-3- Amine Ν[[4-[[ [6-Gas-5-stupyl-1H-Woxa-3-yl]amino]methyl] phenyl] acetamamine-10- This paper scale applies to Chinese national standards (CNS> A4 specifications (2丨0x297 PCT) 5 10 15 'Inventive description (9) Amine 6-gas-N-[(3,5-diphenyl)methyl b-5-stupyl·1Η_carbazole_3_amine 6-gas- 5-phenylidene trifluoromethyl) stupid base] fluorenyl]_1 carbazole _3 Ministry of Economic Affairs Intellectual Property Bureau employees consumption cooperation Du printing 20 6-gas-Ν-[(4-fluoro stupid) 曱 base _lH, carbazole·3_amine 6-gas-Ν-[3-(4-methylphenoxy)phenylmethyl]methyl]_5 基基_1Η_ ° azole-3-amine Ν-( 2,2,3,3,4,4,4·heptafluorobutyl)_6·gas_5·phenyl-lH-sodium-3-amine 6-gas-5-stupyl-Ν-[[3 ,5-bis(trifluoromethyl)phenyl]mercaptolamine 6-a-5-phenyl-indole-[[3-(trifluoromethyl)]indolyl]-indenyl]-indole _3_amine 6-gas-Ν_[(6-methoxy-2·tea-based) fluorenyl]-5-stupyl azole _3·amine 6-gas-N-[(pentafluorophenyl)methyl] ·5· Stupid]H•carbazole_3_amine 6-gas-Ν-[[4·(methylthio)phenyl]methyl]_5_styl-1H_carbazole_3 amine N-[ (4-AZ-3-fluorophenyl)methyl]_6·Ga-5-phenyl-1H-Woxazol-3-amine 6-Ga-5-By-N-(3,3,3-Tri Fluoropropyl)_1H-吲3-Oxo-6-gas-5-styl-N-(3-thienylmethyl)·ιη-carbazole-3-amine oxime-(a ring [2.2.1]hept-5-dil-2- N-(i,l'-biphenyl-4-ylindenyl}-6-a-5-phenyl -lH-η引»»坐_3-amine 6-gas-N-[[4-(didecylamino)phenyl]methyl b5·stupid·m bucket full _ 3-amine N-( 2,2'-biphenphen-5-ylindenyl)-6-a-5-phenyl-indenyl-3-amine 6-gas-5-phenyl·Ν-[[Κ(笨基基) -iH-imidazole 1 base]methyl b-II- This paper scale applies to Chinese national standards (CNS> A4 specification (210x297 mm) 1353978 A 7 B7 Ministry of Economic Affairs Intellectual Property Bureau Η Consumer Cooperative Printed 5, Invention Description (10 ) 1H-carbazol-3-amine 6_glycolyl-1H-imidazol-2-yl]methyl]-5-phenyl-1H-indazol-3-amine 6-gas-N-[(1 - Mercapto-i H-吲哚·3-yl)methyl]-5-phenyl-1H-吲5 s-triamine 6-gas-Ν-[(5-methyl-2-furyl) A 5--5-phenyl-1-indole-3-amine 6-a-5-phenylpyrrol-2-ylmethyl)·1Η-indazole-3-amine 6-gas-5-phenyl- Ν-[(1Η-imidazol-2-yl)methyl]-1Η-indazol-3-amine 10 6-gas-5_styl-indole-[(1Η-imidazol-4-yl)indenyl]- 1Η-oxazol-3-amine 6-gas-5-stupyl-indole-(1Η-pyrazol-3-ylmethyl)-1Η-oxazol-3-amine 6-gas-Ν-[[2-mercapto-1Η-imidazole-4 -yl]methyl]-5-styl-1Η-indole-azole_3_amine 6-gas-oxime-[(3,5-dimethyl-1-phenyl-4-yl}methyl] -5-phenyl-15-yl-indole-3-indole-3-amine 6-gas-5-styl-indole-[[2-phenyl-1Η-imidazol-4-yl]methyl]-1Η-吲嗤- 3-amine 6-gas-oxime-[[5-(4-gasto)-2-β-fusyl] fluorenyl]_5_stupyl-1Η-phutazole-3·amine 20 6-gas- 5-phenyl-N-[(l-fluorenyl-1H-. ratio.-2-yl)methyl]-1H-indazol-3-amine 4·[5-[[[6-gas-5 -Phenyl-indole- 丨 丨 坐 -3- 基 基 基 胺 胺 ] ] 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿 酿)-1Η-ρ引. Sitting-3-amine.3⁄43⁄4. .订·4

This paper scale applies to the Chinese standard (CNS> A4 specification (210x297 mm) 1353978 Α7 Β7 5. Invention description (11) 6-gas-5-stupid-N-[[2- stupid-1H-flavor Wow-4-yl]methyl]·ιη-吲. Sodium-3-amine 2-[[[6·气-5·笨基-1Η·»»引嗤-3-yl]amino] sulfhydryl] ·5·(Methylthio)-1Η-imidazole-4-carboxylic acid ethyl ester 6-gas-5-stupyl·Ν-[[5-[4-(trifluoromethyl)phenylidene 2·furanyl ]曱基]-1Η-吲》坐-3-amine 10 6-gas-5-phenyl-N-[2-(l-piperidinyl)ethyl]-1Η-carbazole_3_amine 6- Gas-Ν·[2-(4-homofolinyl)ethyl]-5-phenyl-1Η,|azole-3·amine oxime-(6-a-5-phenyl-1Η-carbazole- 3-yl)-indole,-(3,5-di-phenylphenyl)urea-(6-a-5-phenyl-1-indole-3-yl)-indole,-(2-propenyl) Urea Ν-(6·Ga-5-stupyl-1Η-oxazol-3-yl)-Ν,·((基基基)) Ν-(6-Ga-5-phenyl-1Η-”5丨Saliv-3-yl)-Ν'-(4-phenoxyphenyl) adenine-(6-gas·5-stupyl-1Η-»1 引唾-3-yl)-Ν'-(4·甲Oxygen stupid) Jiamei] Lunar urinary 15 Urea Ν-(6-gas-5-stupid-1Η-bow sitting-3-yl)-Ν'-[4-(trifluoromethyl)benzene Intellectual Property Office Staff Consumer Cooperative 20 Ν-(6-Gapent-5-phenyl-1Η-吲 -3--3-yl)-Ν'-(4-methoxyphenyl) adenine-(6_气-5-笨基-1Η-吲嗤-3-yl)-Ν'-cyclohexyl adenine _(6·气-5-本基-1Η-叫丨0坐-3-yl)-Ν'-propyl Ν-(6-gas- 5-phenyl-1 - oxoxazol-3-yl) · Ν '- (4-gas base) Ν Ν - (6 - gas-5-bens-1 Η-ρ 引. sit-3-yl )~Ν'·(4-Fluoro-based) Ν-[6-Ga-5-Ben-1Η- **引. Sit-3-yl]-Ν'-(Tricyclo[3 3 γ j3·癸)-1-ylurea N-(6-a-5-phenyl-1H-indazol-3-yl)-Ν'-(4·methylphenyl) monthly urine-13- This paper size is applicable The country of the park is & € € 认 4 4 specifications (210x297 mm) 1353978 Λ7 B7 V. Invention description (12) *" N~[6-gas_5·Stupid-1H-, azole _3_ base] _4_曱-stupyl sulfonamide-5-stupyl-1H-Woxazol-3-yl]-methanesulfonamide Ν-[6-gas-5-stupyl-JlH-carbazol-3-yl ]-2-propanolamine 6-gas-5-stupyl-111-oxazol-3-yl]-2,2,2-tri-1ethanesulfonamide 5 N-[6-gas·5 - Stupid-1H-carbazole-3-yl]-2 - phenothione oxime [6-gas-5-stupyl-1H-indole. -3--3-yl]-benzenesulfonamide Ν·[6-gas-5·stupyl-1Η·oxazol-3-ylbu 4-(trifluoromethyl)benzenesulfonamide Ν[[6-gas- 5-phenyl-1 - oxazol-3-yl]-5-(3-iso-indenyl)-2-nonylsulfonamide 10 N-[6-gas-5-stupyl-1H-carbazole -3-yl]-4-fluoromethanesulfonamide N-[6-gas-5-stupyl-1H-indole-3-yl]-4-methoxysulfonamide Ν-[6·gas- 5. Stupid-1 Η-oxazol-3-yl] benzoyl sulfonamide Ν-[6-gas-5-styl-1 Η-oxazol-3-yl]-1-fyl-1 Η-imidazole- 4-sulfonamide 15 NH gas-5-phenyl-1H-indazol-3-yl]-4-(1,1-dimethylethyl) oxasulfonamide N-[4-[[(6 · gas stupid base-1H-Wazole _3_ base) amine base] 醯 base] stupid base acetamide economic department intellectual property bureau employee consumption cooperative printed N-[6- gas · 5 · stupid · ih -Wazole-3_yl]wintermethyl alum sulfonamide 20 6-gas-oxime-(pentafluorophenyl)-5-phenyl-1 - oxazol-3-amine 6-gas-N-( 3,4-difluorophenyl)-5-phenyl-1H-carbazol-3-amine 6-a-5-phenyl-N-(2,3,5,6-tetrafluorophenyl>- 1Η-carbazol-3-amine 6 di-5-phenyl-indole·(2,4,6-trifluorophenyl&sodium-3-amine 6-gas-N-(4-fluorophenyl) -5-phenyl-1H-indazole-3-amine-14- This paper scale applies to Chinese national standard <CNS&gt ;A4 size (210 X 297 mm) 1353978

6-gas-N-[3-(trifluoromethyl)phenyl]·5•styl·1Η_ϋ3·amine 6-gas-ν·[4-(三敦methyl) stupid base 5_stupid· 1H_m·amine

6_gas_N_[3-gas_5·(trifluoromethyl> stupid base)5•stupyl · out. lead W amine 6-gas-Ν·(4-nitro stupyl)-5· stupid基_1H•oxazolamide 6·gas-Ν·(3-nitrophenyl)-5-phenyl-1H-carbazole-3-amine 6-gas-N-(3-methoxyphenyl)- 5-phenyl_1H_carbazole_3_amine 6-gas-N-(4-methylindole)-5-styl·1 η-carbazole·3·amine 6-gas-Ν, 5-二笨基-1Η·»»引唾_3-amine 6-gas than bite base)-5·stupid-1Η-»» cited. Sodium-3-amine 6-gas-oxime-(2-0 to bite)·5_stupyl_ΐΗ-<» 丨 丨 -3--3-amine its isomer, its mixture 'its racemate, Mirror isomers, non-image isomers or tautomers, and pharmaceutically acceptable oximes thereof, especially the following compounds: Ν-butyl-6-gas-5-stupyl·1Η-〃引》 3-amine 3-(6-gas-5-stupyl-indole-deca--3-ylamino) porphin·2·moon 耷 (6-gas-5-stupyl-1H-Wazole-3 ·()pyridin-2-yl)amine (6-gas_5_styl-1Η-carbazol-3-yl)(5-nitropyridin-2-yl)amine Ministry of Economic Affairs Intellectual Property Bureau Staff Consumption Cooperative Printing (6-Gapent-5-stupyl-1H--azol-3-yl)(6-oxopyridin-2-yl)amine N-(6-Ga-5-stupyl-1H-carbazole -3-yl)-Ν'-stupyl 6-gas-5-stupyl-1Η-carbazole-3·yl)-3-(4-ethoxyphenyl)-n-(6-gas-5 · Stupid-1H-carbazol-3-yl)-3-(3,4-dioxaphenyl) monthly urine 3-[3-(6·g-5-stupyl-1H-carbazole-3- Urinyl] decyl propionate M6-gas-5-stupyl-1H-carbazol-3-yl)-3-(4-(dimethylamino)phenyl) -15- This paper size is suitable for use Solid time sample ^ (CNS> A4 specification (2丨0 x 297 public Chu) 1353978 Α7 -----__ V. Description of invention (ι·0 urea 1-(6-gas-5-phenyl-1Η-carbazole_3_yl)_3_isopropylurea 1-(6-gas-5-styl-1H-carbazole·3 _ base)_3_cyclohexylurea 1-(6-gas-5-styl-1H-carbazole_3_yl)_3·(3-(trifluoromethyl)phenyl) May urine 1-(6 -chloro-5-styl-1?-carbazole_3_yl)_3_(2_(thiophene-2-yl)ethyl)urea 1-(1,3-phenyl-dioxole·5_ Base)··3_(6_气_5_笨基_1Η-carbazol-3-yl) monthly urine 10 1-(6_气_5-笨基-1仏吲„坐_3_基)-3 -(3,5-dimercaptopurine 嗤 4-yl)urea 1-benzyl-3-(6-a-5-phenyl)-indolyl-3-yl)urea 1-(6 -Chloro-5-stupyl-1Η-吲Salt_3_yl)-3-(stupylethyl) sulfur moon urine 1-(6-gas-5-phenyl-indole-%.sitting_3_yl) _3-[3-(4-methyl. chen〇丼-1·yl) 15 propyl] monthly urine 1-(6-gas-5-phenyl-1Η-»引《«坐_3_基)- 3-(3-(米"坐-U-based) propyl) urinal Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed 1-(6-chloro-5-stupyl. sit-3-yl)-3 -(2-Phenylethyl) maibu (6-gas-5-stupyl 〇 · ·3·基)-3·[3-(4-曱基略“«井-1-基) 20 丙Base] urea ° ° ° each burning 1-retestosteric acid (6-gas-5-stupyl-111-'^丨. Sodium-3-yl > Stearamine (6-Gapent-5-phenyl-1-indole-3-yl}methyl carbamate (6-gas-5-stupyl-1?-carbazole-3- Base) Urine (6-gas-5-stupyl-1Η-carbazol-3-yl) benzyl carbamate-16- This paper scale is applicable to China National Standard (CNS> A4 specification (210x297 public; g ) Λ7 Β7 1353978 V. INSTRUCTIONS () (6-Gapent-5-phenyl-1H-indazol-3-yl) carbamic acid allyl ester (6-Ga-5-phenyl-1H-4 azole- 3-(amino)aminobutyl isobutylate piperidine-1-carboxylic acid (6-chloro-5-phenyl-1H-indazol-3-yl) decylamine 1-(3-(cyclohexadiene) -Bu)propyl)-3-(6-Ga-5-phenyl-1H-indole-5oxa-3-yl)urea 1-(6-Ga-5-phenyl-1H-indazole-3- Benzyl-3-(3-propylpropyl)urea 1-(6,7-dioxa-5-styl-lH-bine. Sodium-3-yl)-3-(3-(**米17 Sodium 1 -yl)propyl)urea 1-(3-aminopropyl)-3-(6-a-5-phenyl-1-oxazol-3-yl)urea 10 1-(6-chloro -5-本基-111-»>引|1 sits-3-yl)-3-[4-(4-(0-bit-3-yl)indol-1-yl)-butyl] Moon urine 5--5-bengi-1H-*pyridin-3-yl)-3-(2-( «*比洛炫-1-yl)ethyl)urea 2,5-dimercaptopyrazine -1- after 8 Man (6-gas-5-phenyl-111-carbazole-3-15 )-Indoleamine Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed N-(6-chloro-5-benyl-1Η-β5丨 -3--3-yl) Ethylamine-(6-Ga-5-stupyl) -1Η-carbazol-3-yl}-6-methoxypyrazine-1 -carboxyindole-(6-gas-5-stupyl-1Η-»»弓丨吐-3-基)辛月东Ν~( 6-gas-5-stupyl-1Η-吲吐-3-yl) 〇 啶 -2- -2- 缓 缓 缓 缓 缓 缓 缓 ( ( ( ( ( ( ( ( ( ( ( ( ( 6 6 6 6 6 6 6 6 6 6 6 3-methoxysulphonamide, an isomer thereof, a mixture thereof, a racemate thereof, a smectomer, a non-k-isomer or a tautomer, and a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising a derivative of the general formula (I) as an active main component, wherein the -17- paper size is suitable for the "1 r four-family sample" <CNS> A4 specification (21〇χ297 public Chu) ---- 1353978 • A7 B7 V. INSTRUCTIONS (1(5) R3 is (U6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl (1- 6C) alkyl, aryl or heteroaryl fused to (丨-10C)cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl , C0NR1R2, CSNR1R2, C00R1, S02R1 5 C(=NH>R1 or C(=NH>NR1 group: these groups are optionally substituted by 1 or more substituents selected from CN, N〇2, NH2, OH, ORi 'COOH , C(0)0R1 > -0-C(0)Ri, NR1R2, NHC(0)R1, C(0)NR1R2, SRI, S(0)R1, S02R1, NHS02R1, S02NR1R2, C(8)NR1R2, NHC(S) R1, -O-10 SO2RI, -SO2-O-RI, aryl, heteroaryl, heterocyclic, aryl-trifluoromethyl, trifluoromethylthio, trifluoromethoxyalkyl or 1-6C) Alkyl; Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed R5 and R6 are individually selected from the following groups: halogen, CN, N〇2, NH2, OH, COOH, C(0)0R8 ' -0- C(0)R8, NR8R9, NHC(0)R8, C(0)NR8R9, NHC(S)R8, C(S}NR8R9 ' 15 SR8 ' S(0)R8, S02R8 ' NHS02R8 ' S02NR8R9, -O- S02R8, -S02-0-R8, trifluoromethyl, trifluoromethoxy, (1-6C)alkyl, (1-6C) alkoxy, aryl, aryl (1-6C) alkyl, Heteroaryl, heteroaryl (1-6C)alkyl, heterocyclic, cycloalkyl, alkenyl, alkynyl, adamantyl or polycycloalkyl; such groups may optionally be selected from one or more Substituted by the following substituents 20: halogen, CN, N〇2, NH2 OH ' OR10, 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, NHSO2R10, SO2NR10Rli, -o.so2rio, -SCVO-RIO 'Aryl, hetero-aryl-18- This paper scale applies to China National Standard (CHS> A4 Specification (210X 297 mm) 1353978 A7 B7 V Description of the invention (π) group 'fluorenyl, trifluoromethyl, trifluoromethoxy or (1-6C) alkyl; IU, R2 'R8, R9, R10 and R11 are hydrogen, (1- 6C) an alkyl, aryl, alkenyl, alkynyl 'heteroaryl group, which itself is optionally substituted with 1 or more substituents selected from halo, (1-6C)alkyl, (1-5) 6C) alkoxy 'CN, Ν02, NH2, OH, COOH, C00 alkyl, conh2, methyl-trifluoromethyl, trifluoromethoxy; R1 and R2 or R8 and R9 or R10 and RU can form a 5- or 6-membered ring which may or may not have a hetero atom such as anthracene, S or N; and when R3 is a 6-membered nitrogen-containing heteroaryl or thiazolyl or imidazolyl or hydrazinozolyl At least one of R5 and R6 is an aryl group, optionally taken by one or more substituents selected from the group consisting of the following substituents Generation: halogen, CN, N02, NH2 'OH, OR10, COOH, C(O)OR10, -OC(O)R10 'NRlORli, NHC(O)R10, C(O)NR10Rll, NHC(S)R10, C (S) NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10 '15 SO2NR10Rll, -O-SO2R10, -SO2-O-R10, aryl 'heteroaryl'-carbenyl, trifluoromethyl, trifluoro Methoxy or (1-6C>alkyl; racemate, mirror image or non-image isomer thereof and mixtures thereof, tautomers thereof and pharmaceutically acceptable salts thereof. The invention relates to a pharmaceutical composition comprising a derivative of the formula (I) as a main component of a living composition, wherein: R3 is (1-6C) alkyl, aromatic Alkyl, aryl(1-6C)alkyl 'heteroaryl'heteroaryl(1-6C)alkyl' fused to an aryl or heteroaryl group of a (1-10C)cycloalkyl group, heterocyclic, hetero Cycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl 'alkynyl, CONR1R2, CSNR1R2, COOR, S02Ri or -19- This paper scale uses Chinese national sample (CNS> A4 specification ( 21〇χ 297 公发) 1353978 Λ7 Β7 5. Inventive Note (18) C(=NH)NR1 group; these groups are optionally substituted by one or more substituents selected from the group consisting of halogen, CN, N 〇2, NH2 'OH ' 0R1, COOH, C(0)0R1, -0-C(0)Rl ' NR1R2, NHC(0)R1, C(0)NR1R2, SRI, S(0)Ri ' S02R1 ' NHS02R1, 5 S02NR1R2 ' C(S)NR1R2 ' NHC(S)R1 ' -0-S02Rl ' -S02-O-Rl, aryl, heteroaryl, formyl, oxy, trifluoromethyl, tri Fluoromethylsulfanyl, trifluoromethoxy or (1-6C)alkyl; R5 is aryl, optionally 1 or more Substituted from the following substituents: halogen, CN, N〇2, NH2, OH, ORiO, COOH, 10 C(O)OR10 '-OC(O)R10, NR10R11, NHC(O)R10, C(O) NR10RU, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10 'SO2R10 'NHSO2RIO ' SO2NRIORII ' -O-SO2R10, -SO2-O-R10, aryl 'heteroaryl, formazan , trifluoromethyl 'trifluoromethoxy or (1-6C) alkyl; 15 R6 is halogen, methyl, cyclopropyl, CN, OH, methoxy, trifluoromethyl, vinyl, acetylene Base, trifluoromethoxy, no2, nh2 or NMe2 group; printed by the Ministry of Economic Affairs Intellectual Property Office employee consumption cooperative

Rl 'R2 is independently hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, which itself is optionally substituted by one or more substituents selected from the group consisting of: halogen, ( 1-6C)alkyl, (1-6C)alkoxy, CN, N〇2, NH2 'OH, COOH, COO alkyl, CONH2, fluorenyl 'oxy, trifluoromethyl or trifluoromethyl Alkyl; R1 and R2 may form a 5- or 6-membered ring which may or may not have a hetero atom such as hydrazine, S or N; -20- This paper scale applies to the Chinese National Standard <CNS>A4 specification (210 X 297 mm) 1353978 A7 B7 V. INSTRUCTIONS (19) The racemates are mirror image or non-image isomers and mixtures thereof, tautomers thereof and pharmaceutically acceptable salts thereof. A preferred aspect of the invention relates to a pharmaceutical composition comprising a derivative of the formula (1) as an active main component, wherein: 5 R3 is (1-6C)alkyl, aryl, aryl (1-6C) Alkyl, heteroaryl, heteroaryl (1-6C)alkyl, aryl or heteroaryl fused to (1-10C)cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, diamond An alkyl, polycycloalkyl, alkenyl, alkynyl, C0NR1R2, COORJ, S02IU, C(=NH)R1 or C(=NH)NR1 group; such groups are optionally selected from one or more selected from the group consisting of Substituted by 10 substituents: dentate, CN, N〇2 'NH2, OH, OR1 'COOH, C(0)ORl, -0-C(0>Rl, NR1R2, NHC(0)R1, C(0) NR1R2, SRI, S(0)R1, S02R1, NHS02R1, S02NRiR2, C(S)NR1R2, NHC(S)R1, -0-S02Rl, -S〇2-O-Rl, aryl, heteroaryl, A Sulfhydryl, trifluoromethyl, trifluoromethylsulfanyl 15 alkyl, trifluoromethoxy or (1-6C)alkyl; R5 is stupid; R6 is gas; Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative Printed

Rl, R2 are each independently hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, which are themselves optionally substituted by one or more substituents selected from the group consisting of: halogen' ( 1-6C)alkyl, (1-6C)alkoxy, CN, N〇2 'NH2, OH, COOH, COO alkyl, CONH2, formamyl 'trifluoromethyl or trifluoromethoxy; Isomers, mixtures thereof 'its racemates, mirror image isomers, non-image isomers or tautomers, and pharmaceutically acceptable salts thereof. -21- This paper scale applies to Chinese national standards (CNS>A4 specification (210 X 297 public) 1353978 A7 A7 B7 5. Inventive Note (2〇) The present invention also relates to an amine-based carbazole derivative of the general formula (I) For pharmaceutical applications, wherein R3 is (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, fused to ( 1-10C) aryl or heterocyclic 5 aryl, heterocyclic, heterocycloalkyl, cycloalkyl 'adamantyl, polycycloalkyl, alkenyl, alkynyl, C0NR1R2, CSNR1R2, C00R1, S02R1 , C(=NTH)Ri or C(=NH)NRi groups; such groups are optionally substituted with one or more substituents selected from CN, N〇2, NH2, 0H 'OR1, COOH , C(0)0R1, -0-C(0)Rl, NR1R2, 10 NHC(0)R1, C(0)NR1R2, SRI, S(0)R1, S02R1 'NHSO2RI, S02NR1R2 ' C(S)NR1R2 'NHC(S)R1, -O-S02R1, -S02-0-Rl, aryl, heteroaryl, heterocyclic, indolyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy Base or (1-6C)alkyl: Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperatives Printed R5 and R6 are individually selected from the following groups: Halogen, CN, N〇2 15 NH2 ' OH ' COOH ' C(0)0R8 ' -0-C(0)R8 ' NR8R9 ' NHC(0)R8, C(0)NR8R9, NHC(S)R8, C(S)NR8R9, SR8 &gt ; S(0)R8 ' S02RS ' NHSO2R8 ' S02NR8R9 ' -O-S02R8, -S02-0-R8, trimethylmethyl, trifluoromethoxy, (1-6C) pit, (1-6C) alkane Oxyl, aryl, aryl (1-6C) alkyl, heteroaryl, hetero 20 aryl (1-6C) alkyl 'heterocyclic, cycloalkyl, alkenyl 'alkynyl, adamantyl or many a cycloalkyl group; such groups may be optionally substituted with one or more substituents selected from the group consisting of halogen, CN 'N02, NH2, OH, OR10, COOH, C(O)OR10, -OC(O)R10, NR10R11, NHC(O)R10, C(O)NR10Rll, NHC(S)R10, -22- This paper scale is applicable to Chinese national standard (CNS>A4 specification (2丨Ox 297 mm) 1353978 A7 B7 V. Invention Description (21) C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10Rll, -O-SO2RIO, -S〇2-O-R10, aryl, heteroaryl, carbaryl 'three Fluoromethyl, trifluoromethoxy or (1-6C)alkyl;

Rl, R2, R8, R9, R10 and RU are each hydrogen '(i_6C) 5 leumino, aryl 'alkenyl' alkynyl, heteroaryl, which itself is optionally substituted by one or more selected from the following Substituted by: halogen, (1_6C) alkyl, (1-6C) alkoxy, CN, N〇2, NH2, OH 'COOH, C00 alkyl, CONH2, methyl S, trifluorodecyl, three a gas oxime; R1 and R2 or R8 and R9 or R10 and R11 may form a 5- or 6-1〇 ring, which may or may not have a hetero atom such as ruthenium, S or N; and when R3 is When a 6-membered nitrogen-containing heteroaryl or thiazolyl or imidazolyl or oxazolyl group, then at least one of R5 and R6 is an aryl group, optionally substituted with one or more substituents selected from the group consisting of hydrazine: 'CN ' N〇2, NH2, OH, ORIO, COOH, C(O)OR10, -OC(O)R10, 15 NR10-R11, NHC(O)R10, C(O)NR10Rll, NHC(S) R10, C(S)NRiORll, SR10, S(O)R10, S02RiO, NHSO2R10, SO2NR10Rll '-〇-SO2R10, -SO2-O-RIO, aryl 'heteroaryl, formamyl, trifluoromethyl, Trifluorodecyloxy or (i-6C)alkyl; the Ministry of Economic Affairs, the Intellectual Property Office, the Consumer Cooperative, which prints its racemates, mirror image isomers or 20 enantiomers and mixtures thereof, their tautomers and their pharmaceutically acceptable salts. The invention relates in particular to an aminocarbazole derivative of the formula (I) for use as a medicament, wherein: R3 is (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl Base, heteroaryl (1-6C) alkyl, aryl fused to (ui〇C) cycloalkyl or hetero-23- This paper waviness is suitable for medium solid national standard (CNS> A4 specification (210x297 public Chu) A7 B7 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed 1353978 V. Inventive Note (22) Aryl, heterocyclic, heterocyclic leucoyl 'cyclohexyl, adamantyl, polycycloalkyl, alkenyl, alkynyl , CONR1R2, CSNR1R2, C00R1, S02R1 or C(=NH)NR1 groups; such groups are optionally substituted by one or more substituents selected from the group consisting of halogens 'CN, N〇2, NH2, OH, OR1, 5 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, -〇-S02Rl, -S02_O-Rl, aryl, heteroaryl, fluorenyl, oxy, trifluoromethyl, trifluoromethylsulfanyl, three Fluoromethoxy or (1-6C)alkyl; 10 R5 is aryl, optionally 1 or more selected from the group consisting of Substituted by halogen: CN, N〇2, NH2, OH, OR10, COOH, C(O)OR10, -OC(O)R10, NR10R11, NHC(O)R10, C(O)NR10Rll, NHC ( S) R10, C(S)NR10R11, SR10, S(0)R10, S02R10, NHS02R10, S02NR10R11, -0-15 so2rio '-so2-o-rio, aryl 'heteroaryl, fluorenyl, trifluoro Mercapto 'trifluorodecyloxy or (1-6C)alkyl; R6 is halogen, methyl, cyclopropyl, CN, OH, methoxy, trifluoromethyl, vinyl, ethynyl, trifluoro a methoxy group, a N02 'NH2 or NMe2 group; 20 Rl 'R2 are each hydrogen, (1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, which may itself be one or more Substituted from the following substituents: halogen '(1-6C)alkyl, (1-6C)alkoxy, CN, N〇2, NH2, OH, COOH, COO alkyl, CONH2, fluorenyl, Oxyl, trifluoromethyl or trifluoromethoxy; -24- This paper size applies to China National Standard (CNS) A4 specification (210x297 mm)

1353978 A7 B7 V. INSTRUCTIONS (23) R1 and R2 may form a 5- or 6-membered ring which may or may not have a hetero atom such as 0, S or N; its racemate, mirror image isomer or Non-image isomers and mixtures thereof, tautomers thereof, and pharmaceutically acceptable salts thereof. 5 preferred aspects of the invention relate to the use of an aminocarbazole derivative of the formula (I) as a pharmaceutical, wherein: R3 is (1-6C)alkyl, aryl, aryl (1-6C) Alkyl, heteroaryl, heteroaryl (1-6C)alkyl, aryl or heteroaryl fused to (N10C)cycloalkyl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl a polycycloalkyl, 10 alkenyl, alkynyl, CONR1R2 'COOR1, S02R1, C(=NH)R1 or C(=NH)NR1 group; such groups are optionally substituted by one or more selected from the group consisting of Substituted by: dentate, 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, 15 S02NR1R2, C(S)NR1R2, NHC(S)R1 '-0-S02Rl, -S02-〇-Ri, aryl, heteroaryl 'carbamyl, trifluoro Methyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C)alkyl; R5 is phenyl; Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed R6 gas; 20 Rl, R2 Individual is hydrogen '(1-6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, which itself is optionally substituted by one or more substituents selected from the group consisting of Generation: halogen, (1-6C)alkyl, (1-6C) alkoxy, CN 'N02 ' nH2 ' OH, COOH, COO alkyl, CONH2, formamidine, trifluoromethyl or trifluoromethoxy Base; its isomers, mixtures thereof, racemates thereof, mirrors-25- This paper scale applies to China's solid standard specifications (21〇x297 mm) 1353978 A7 B7 V. Description of invention (24) Like isomers' Non-image isomers or tautomers, and pharmaceutically acceptable salts thereof. The derivative of the formula (I) can be obtained from the corresponding 3-amino derivative (V), wherein the nitrogen in the 1-position is optionally protected with the group Pr. The pr is a 5-trimethylsulfonium alkylethoxymethyl group, a methanesulfonyl group, a sulfonyl group or a benzyl group, or a group known to protect an NH group of an aromatic heterocyclic ring, such as TW Greene , Protecive Groups in Organic Synthesis, J. Wiley-Inte.rscience Publication (1999) 10

Printed by the Intellectual Property Office of the Ministry of Economic Affairs, Employees' Consortium 15 The 3-amino 1H-carbazole having the general formula (II) can be hydrolyzed by 2-fluorobenzonitrile or hydrazine hydrochloride in ethanol or n-butanol type alcohol. , reacted under reflux for 2 to 18 hours' and according to Rf Kaltenbach, Bi〇org. Med. Chem. Lett. £(15), 2259-62 (1999): 20

Ηη2νη2·η2〇 alcohol reflux (ethanol, butanol)

N NH, -26-

1353978 A7 B7 V. INSTRUCTIONS (25) R5 and R6 are each selected from the group consisting of hydrogen, halogen, CN, N〇2 'NH2, OH, COOH, C(0>OR8,-0-C(0) )R8 ' NR8R9 , NHC(0)R8 , C(0)NR8R9 , NHC(S)R8 ' C(S)NR8R9, SR8, S(0)R8, S02R8, NHS02R8 ' Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative 5 S02NR8R9 '-0-S02R8, -S02-0-R8, trifluoromethyl, tri-l-oxyl, (1-6C)alkyl, (1-6C) alkoxy, aryl, aryl ( 1-6C) alkyl, heteroaryl, heteroaryl (1-6C) alkyl, cycloalkyl, alkenyl, alkynyl or adamantyl; such groups may optionally be selected from one or more selected from the group consisting of Substituents substituted: halogen, CN ' N02, NH2, OH, ORIO, COOH, 10 C(〇K)R10 ' -OC(O)R10 ' NR10RU, NHC(O)R10, C(O)NR10Rll, NHC( S) R10, C(S)NR10R11, SR10, S(O)R10 ' S02R1〇' NHSO2RIO ' SO2KRIORII ' -O-SO2R10, -so2-o-rio, aryl, heteroaryl, fluorenyl, trifluoro Methyl, trifluoromethoxy or (1-6C)alkyl; obtainable from the corresponding halogenated derivative by reaction 15 involving palladium chemistry: Suzuki (A. Suzuki, Pure Appl. Chem ., 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, Synthesis, 777 (1977)), Buckwald (SL Buckwald, Acc. Chem. Re., M., 20 805 (1998)), in which case The reactive functional groups are protected. Therefore, the OH, SH, COOH and NH2 functions are protected prior to coupling. The protecting groups are introduced according to any method known to those skilled in the art, especially TW Greene in Protecive Groups in Organic Synthesis, J_ -27- This paper scale applies to Chinese national standards (CNS>A4 gauge (2丨0x297 mm) 1353978 Α7 Β7 5. Inventions (26)

As described by Wiley-Interscience Publication (1999). It is preferred to protect the nitrogen at the [- position] using, for example, a third butoxycarbonyl or an anthracene derivative. It is preferred to select a third butyl dimethyl fluorenyl alkyl or a triisopropyl carboxy fluorenyl alkyl group (which may be removed using a fluoride anion or with acetic acid), especially using 5 trimethyl methacrylate alkyl ethoxylate. Sulfhydryl group (which can be refluxed in a solvent such as tetrahydrofuran or dioxinane and removed by tetrabutylammonium fluoride. 1^11丨11,10% Chem., 51, 1891 (1986); BH Lipshutz, Tetrahedron Lett. 4095 (1986) or excised with 2N hydrochloric acid under reflux in methanol or ethanol). 10 1-position is protected with a trimethylsulfonium alkyl ethoxymethyl group by using the starting compound and trimethylsulfonium alkyl ethoxymethyl chloride in the presence of sodium hydride in a solvent (such as two In methyl decylamine, the reaction is carried out at ambient temperature (JP Whitten, J. Org. Chem., 51, 1891 (1986); MP Edwards, Tetrahedron, 42, 3723 (1986)). 15 Similarly, the 1-NH nitrogen functional group of the carbazole can be protected by a group such as a decyl derivative, a benzyl 'carbamate or a tosyl group. For example, 'When it is desired to coordinate with the 6-positioned toothed derivative, it is necessary to protect the nitrogen in the position (X=Cb Br or I) as follows: Printed by the Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative

20

R5 X -28- This paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1353978 A7 B7 V. Description of invention (27) Deprotection is carried out according to methods known to those skilled in the art. It is described by TW Greene in Protective Groups in Organic Synthesis, J. Wiley-Interscience Publication (1999). For example, if the protecting group at the 1-position is trimethyldecyl ethoxymethyl, it can be deprotected by reaction with tetrabutylammonium fluoride as follows:

SiMej Ministry of Economics, Intellectual Property, Employees, Co., Ltd., Co., Ltd., when one of the coupled R5 or R6, which involves the use of the chemistry of palladium itself, contains a reactive functional group (such as a hydroxyl group, an amine, a thiol or an acid) or generally includes 15 For heteroatoms, the latter also needs to be protected prior to coupling with palladium. Thus, for example, a phenolic functional group will be introduced from a gasification derivative in a protected form (e.g., hydrazine-benzyl), and the nitrogen in the 1-position will be protected as previously described:

-29- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 λ·297 mm) 1353978 A7 B7 V. Inventive Note (28) The benzyl group can then be used in acetonitrile, for example, under reflux. It is removed by hydrazine-based iodine treatment. It can also be protected by a trimethyl hydrazinoalkyl ethoxy group. It can be removed by refluxing tetrabutyl fluoride in a solvent such as tetrahydrofuran or dioxane (Jp Whitten, J. Org. Chem ., 51, 1891 5 (1986); BH Lipshutz, Tetrahedron Lett. 4095 (1986)) or by 2N hydrochloric acid in methanol or ethanol under reflux. When R5 and R6 are aryl and dentate, The aryl functional group is introduced into the brominated position by self-coupling, and the nitrogen in the 3-position is suitably protected. Pr is preferably a trimethylcarbinylethoxymethyl group and Pr' represents a n-butylcarbonyl group which forms n-butyldecylamine with nitrogen. The deprotection phase of the amine is carried out in DMF for one week under reflux in the presence of ethanolamine. This excision can also be carried out using stannous vaporized gas in ethanol (R J. Griffm, J. Chem. Soc. Perkin I, 1992, 1811-1819) or using methanol in decyl alcohol (丫.卩111 > 11 |<; said 3, (]; 116111. 15 Pharm· Bull·, 1968, 16, 1076) or using any other alkoxide in the corresponding alcohol.

Ministry of Economic Affairs, Intellectual Property Bureau, employee consumption cooperative, printing

The compound of the formula (II) is the starting point for preparing various products by the reaction of the 3-aminocarbazole monoamine functional group in the conventional reaction of the functional group, -30- The paper scale is applicable to the Chinese national standard (CNS) A4 size (210 X 297 mm) 1353978 A7 B7 V. Description of invention (29) Such as: alkylation, deuteration, reduction after carbonyl derivative reaction, sulfonation, conversion to urea or amino phthalate, Arylation (Castro reaction or Buchwald reaction)' and its class. The reductive amination of the derivative of the formula (I) wherein R3 is H, when the Pr system is a trimethyl sulfonium 5 alkyl ethoxymethyl group, may be a boron derivative such as sodium triethoxy borohydride ), in dioxane in the presence of an R1CH0 type aldehyde, under the conditions described in Organic Reactions, Vol. 59, 1-714 (E. Baxter, A. Reitz), or by other means for reducing the imine The reducing agent is carried out to form a product, wherein R3 is (1-6C)alkyl, aryl(1-6C)alkanyl,heteroaryl(1-6C)alkyl,heterocycloalkyl,cycloalkyl Or polycycloalkyl., such groups are optionally substituted by one or more substituents selected from the group consisting of: ' CN ' Ν〇 2 ' ΝΗ 2 ' 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, 15 NHC(S)R1 , -0-S02Rl, -S02-0-Rl 'aryl, heteroaryl, methionyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (i-6C) . The Ministry of Economic Affairs, the Intellectual Property Bureau, the Bayer Consumer Cooperative, printed the derivative of the general formula (I) (wherein R3 is H) and the OCNR1 type isocyanate condensation, especially in tetrahydrofuran according to Comprehensive 20 Organic Functional Grout Transformations, Vol. 6 (Katritzky, Meth-Cohn, Rees 1995) is carried out to form the product (wherein R3 is CONR1R2, and R1, R2 are each hydrogen '(1-6C)alkyl, aryl, alkenyl, alkynyl or A heteroaryl group, which itself is optionally substituted with one or more substituents selected from the group consisting of halogen, (1-6C)alkyl, (1-6C) alkane. The paper size is applicable to China National Standard (CNS>A4 specification). (210x297 mm) 1353978 7 A7 B7 V. INSTRUCTIONS (3〇) oxy, CN, N〇2, NH2, OH, COOH, C00 alkyl, CONH2 'mercapto-trifluoromethyl or trifluoromethyl The sulfonation of a compound of the formula (I) wherein R3 is H can be used in conventional solvents such as, for example, dioxane, in bases (especially tertiary amines such as triethylamine) or aromatic In the presence of a amide such as pyridine, a 'formation product' is formed from R1S02C sulfonium sulfonium, wherein R3 is S02R1, and R1 is hydrogen, ( 1-6C) Hyunyl, aryl 'alkenyl, alkynyl or heteroaryl, which itself is optionally substituted by one or more substituents selected from the group consisting of halogen '(1-6C)alkyl, (1) -6C) alkoxy group, CN 'N02, NH2, OH, COOH, COO alkane 10 group, CONH2, fluorenyl, trifluoromethyl or trifluoromethoxy. Compound IV (where Pr is trimethyl hydrazine)矽Alkyl ethoxylated) is 3-amino-5-phenyl-6-chlorotrimethyldecyl ethoxycarbonyl) oxazole and is prepared in the following manner. -5-Phenyl-6-gas-l-[(2-trimethylformamidoethoxy)methyl]oxazole 15 1.63 cm 3 of ethanolamine and subsequent 2.24 g of potassium carbonate added to the Ministry of Economic Affairs Intellectual Property Bureau employees The consumer cooperative printed 2.4 g of N-[5-phenyl-6-gas-i-[(2-trimethylformamidoethoxy)indolyl] in 75 cm 3 of dimethylformamide The mixture was heated under reflux for 1 week in the azole 3 -yl]butanamine (described below). The reaction medium was concentrated to dryness under reduced pressure and dissolved in ethyl acetate (250 cm) and water (1 cm). 20 Separate the organic phase by sedimentation' continuously wash with 2 times 100 cm 3 of water and 75 cm 3 of sodium carbonate solution The organic phase was dried over magnesium sulfate, filtered, and then concentrated under reduced pressure (2 kPa, 50 〇 dry to dryness. The crude oil was obtained under a argon pressure of 50 kPa on a ruthenium tube column (particle size 40 to 60 μm) ; 4 cm in diameter), purified by chromatography, mixed with cyclohexane/ethyl acetate (80/20 by volume) -32- This paper scale is applicable to China National Standard <CNS) A4 size (210x297 mm) ΓΙ353978 A7 V. Description of the invention (3 溶 溶 ' ' collection of each 35 cm 3 "raised. Combine the fraction containing the expected product, and evaporate under reduced pressure (2 kPa; 50 〇. dry (9 〇 Pa; 45. 〇 after 'obtained 0.43 g of yellow oil in the form of 3-amino stupyl -6 gas b [ 2-trimethylmethyl sulphate ethoxy) sulfhydryl] 弓bui. 5 HN.MR spectrum (3 〇〇 MHz, (CD3) 2SO, S expressed in ppm). -0.05 (s, 9H), 0.83 (t, J = 8 Hz, 2H), 3·52 (t, j. 8 2H), 5.49 (s, 2H), 5.75 (wide peak s, 2H), from 7.30 to 7 55 (mt' 5H )' 7.77 (s, 1H), 7.81 (s, 1H). ' ' 10 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed N-[5-phenyl-6-ammonia-l-[(2-trimethyl)曱矽alkyl 氡 氡) methyl] oxazole _3 · yl] butyl amide is prepared in the following manner: soil 821 mg phenyl citric acid, 克 14 g sodium carbonate in 30 cm 3 distilled water, and finally 347 mg of tetrakis(triphenylphosphine) palladium is added to 2 g of N-[5-bromo-6-gas-^[(2-trimethylformamidinylethoxy) in 18 〇 15 m 3 ) methyl indol-3-yl]butanamine (described below). The mixture is heated under ^90 minutes and then returned to 20«>c' to add ι〇〇厘米 acetate Ethyl vinegar and 100 cm 3 of distilled water. The organic phase was washed with a saturated aqueous solution of sodium carbonate (1 cm 3 ), separated by sedimentation and dried over magnesium sulfate. After filtration through a fritted glass funnel, the filtrate was concentrated and dried under reduced pressure (2) Kpa; 50 ° C). The residue was purified by chromatography on a ruthenium column (particle size 4 〇 to 6 〇 micron: diameter 4 cm) under argon pressure of 50 kPa to cyclohexane/ethyl acetate (80/ 20 parts by volume) The mixture was dissolved, and each 35 cm 3 fraction was collected. The mixture containing the expected product was evaporated under reduced pressure (2 kPa; 50 ° C). 20 -33-

This paper size is applicable to the S-sample (CNS) A4 specification (210x297 mm) 1353978 A7 B7 V. Inventive Note (32) After drying (90 Pa; 45 ° C), 2 g of N-[5-phenyl is obtained. a yellow oil of -6-gas-l-[(2-tridecylmethyl decyl ethoxy) fluorenyl] 11 oxazole-3-yl]butanamine. iHN.MR spectrum (300 MHz, (CD3) 2SO, 5 in ppm): 5 -0.05 (s, 9H), 0.85 (t, J = 8 Hz, 2H), 0.92 (t, J = 7.5 Hz, 3H ), 1.63 (mt, 2H), 2.38 (t, J = 7.5 Hz, 2H), 3.56 (t, J = 8 Hz, 2H), 5.70 (s, 2H), from 7.30 to 7.55 (mt, 5H), 7.91 (s,1H), 7.99 (s,1H), 10.59 (wide peak s, 1H). 10 N-[5-bromo-6-chloro-l-[(2-tridecylfluorenyl ethoxylate) )methyl]carbazole-3-yl]butanamine is prepared in the following manner: Employees of the Intellectual Property Office of the Ministry of Economic Affairs, a cooperative copy of 0.22 cm 3 of pyridine added to N-[ in 15 cm 3 chloroform] 6-Gas-l-[(2-trimethyldecyl ethoxy)methyl]oxazol-3-yl]butanamine (described below), followed by the addition of 0.14 cm 3 of bromine. The mixture was stirred at 20 ° C for 15 hours, after which 50 cm 3 of dichloromethane and 50 cm of a saturated aqueous solution of sodium sulfate were added. After stirring for 10 minutes, the insoluble material was filtered off through a sintered glass funnel, and the organic phase was washed with a saturated aqueous solution of sodium carbonate (50 cm). The organic phase was separated, dried over magnesium sulfate, filtered and evaporated to dryness (2 kPa; The residue was purified by chromatography on a silica gel column (particle size 40 to 60 μm; diameter: 3.5 cm) at 50 kPa argon pressure, and dissolved in a mixture of ethyl acetate/cyclohexane (20/80 by volume). 3 cents per 3 cents. The fractions containing the expected product were combined and evaporated under reduced pressure (2 kPa; 50 ° C). After drying (90 Pa; 45 ° C), 0.94 g of N-[5-bromo-6-gas-l-[(2-trimethyldecyloxy)methyl]-34- China National Standards (CNS) A4 specifications (210x297 public «) 『1353978 at B7 V. Inventions (33) 丨 丨 0 sit -3- base] butyl amine white solid, dazzle 130 ° C. iHN.MR first spectrum (300 MHz, (CD3) 2s 〇, 5 in ppm): -0.08 (s, 9H), 0.82 (t, J = 8 Hz, 2H), 〇95 (t, J = 7.5 Hz) , 3H), 5 1.66 (mt, 2H), 2.40 (t, J = 7.5 Hz, 2H), 3.52 (t, J = 8 Hz, 2H), 5.66 (s, 2H), 8.13 (s, 1H), 8.34 (s, 1H), 10.67 (wide peak s' 1H). 10 N-[6-Chloro-l-[(2-tridecylmethyl decyl ethoxy)methyl]p-triazol-3-yl The butylamine is produced in the following manner: The Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, printed 3 grams of (6-chloro-111-oxazol-3-yl)butanamine in 40 cm 3 dimethylformamide The solution in the amine was added to 606 mg of 60% sodium hydride in 20 cm 3 of dimethylformamide. After cooling to about 5 ° C, 2.68 cc of 15 m 3 of 2-(trimethylformamidinyl)ethoxy oxo chloride in 10 cm 3 of dimethylformamide was added. The temperature was returned to about 21 ° C and the mixture was stirred for 2 hours. The reaction medium was then evaporated under reduced pressure (2 kPa; 45 〇. The residue was dissolved in 200 cm 3 of ethyl acetate and 100 cm 3 of distilled water. Two portions of 100 cm 3 distilled water were used again and saturated with 100 cm 3 was used. The sodium aqueous solution 20 was washed. The organic phase was dried over magnesium sulfate. The mixture was filtered through a fritted glass funnel, and then evaporated under reduced pressure (2 kPa; 50 ° C). The residue was applied to a silica gel column under a pressure of 5 kPa argon (particle size 40). Up to 60 μm; diameter 4.5 cm) on chromatographic purification 'dissolved in a mixture of cyclohexane/ethyl acetate (80/20 by volume) to collect a fraction of 100 cm of the parent. Combine the fraction containing the desired product. Subtract -35- This paper size is applicable to the state of the country (CNS) A4 specification (210 X 297 public « ) rI353978 A7 B7 V. Description of invention (34) Evaporation under pressure (2 kPa; 50 ° C). Drying (90 After Pa; 45 ° C), 3 g of a yellow oil of 6-gas-i-[(2-tridecylmethyl decyl ethoxy)methyl]oxazol-3-yl]butanamine was obtained. 5 hN.MR spectra (300 MHz, (CD3) 2SO, S in ppm): -0.08 (s, 9H), 0.83 (wide peak t, J = 8 Hz, 2H), 0.96 (t, J = 7) 5 Hz, 3H), 1.67 (mt, 2H), 2.40 (t, J = 7.5 Hz, 2H), 3.53 (t, j ^ 8 Hz, 2H), 5.66 ( s, 2H), 7.16 (dd, J = 9 to 2 Hz, 1H) , 7.86 (d J = 2 Hz, 1H), 7.88 (d, J = 9 Hz, 1H), 10.53 (unionized peak ' 10 1H). ' N-(<5-chloro-1Η-carbazole- 3-Base) Butylamine Ministry of Economics Intellectual Property Bureau Staff Consumer Cooperative Printed 0.47 cm 3 Butyl chloride was cooled in the reaction medium to about, after which it was added to 75 mg of 3-amino-6 in 10 cm of 3 pyridine. - Gas-1H - Borax 15 in. The medium was subsequently returned to 19 using 14 hours. (: The reaction medium was evaporated to dryness under reduced pressure (2 kPa; 40. (:). The residue was dissolved in 50 cm of acetic acid. Ethyl acetate, 50 cm 3 of tetrahydrofuran and 5 cm 3 of distilled water. The organic phase was washed with 50 cm 3 of distilled water and 5 cm 3 of saturated aqueous sodium carbonate solution, dried over magnesium sulfate, filtered through a fritted glass funnel, and decompressed. The mixture was steamed for 20 times. The residue obtained was purified by chromatography on a silica gel column (particle size 4 〇 to 6 〇 micron; diameter 2.5 cm) under argon pressure of 50 kPa, with cyclohexane/ethyl acetate (70/30 volume). For the dissolution, collect 25 cm 3 of each portion. The knot contains the fraction of the expected product and is evaporated under reduced pressure (2 kpa; 4 Torr). ^ Dry (9〇Pa; 45. After ,, get 2〇〇 mg N-(6-gas-1H-carbazole-3-36-- This paper scale applies to the τ country S standard (CNS) A4 specification (210 X 297 ----------- 1353978 A7 B7 V. Description of the invention (35) Base) White solid of butaamine, melting point 230 ° C. HN.MR spectrum (300 MHz, (CD3) 2SO, S is expressed in ppm): 0.98 (t, J = 7 Hz, 3H), 1.67 (mt, 2H), 2.40 (t, J = 7 Hz, 2H), 5 7.08 (dd, J = 9 and 2 Hz, 1H ), 7.52 (d, J = 2 Hz, 1H), 7.84 (d, J = 9 Hz, 1H), 10.39 (undeached peak, 1H), from 12.50 to 13.00 (wide peak unseparated peak, 1H) 10 3-Amino-6-a-5-phenyl-1H-carbazole is obtained from 3-amino-5-phenyl-6-gas-l-[(2-trimethylformamidinyl) Ethoxy)methyl]-oxazole. 300 μl of 2hi HCl added to 108.3 mg of compound 3-amine-5-phenyl-6-chloro-l-[(2-trimethylmethyl) in 4.7 ml of methanol The reaction was placed in a microwave at 140 ° C for 150 15 seconds. The Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative printed the mixture and poured it onto a saturated KH2P04 solution using AcOEt. Extraction. Organic Drying with anhydrous MgS04, filtration and concentration. The obtained crude product was purified by cerium chloride to give 63.5 mg of compound 3-amino-6- ethane-5-phenyl-1H-carbazole. a compound which can be purified by a generally known method such as crystallization, chromatography or extraction. The compound of the formula (I) can be used in an organic solvent such as an alcohol, a ketone, an ether or a gasification solvent, optionally using inorganic or The organic acid is converted into an addition salt by the action of the acid. These salts also form part of the invention. -37- This paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1353978 A7 B7 V. INSTRUCTIONS (36) Examples of pharmaceutically acceptable salts which may be mentioned are the following salts: besylate, hydrobromide, hydrochloride, citrate, ethanesulfonate, counter-butyl Oleic acid salt, gluconate, iodate, maleate, isethionate, methanesulfonate, fluorenylene bis-yg-hydroxynaphthate, nitrate, oxalic acid 5 salt , pamoate, phosphate, salicylate, succinate, sulfate, tartrate, tea base acetate and The compound of the formula (I) is a kinase inhibitor and can therefore be used for the prevention and treatment of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontal parietal bone. Dementia 10, basal cortical degeneration, Pick's disease, stroke, head spinal cord trauma and peripheral neuropathy, obesity, essential hypertension, arteriosclerotic cardiovascular disease, polycystic ovarian syndrome, X Symptoms 'immune insufficiency and cancer. Its activity is determined by measuring its ability to inhibit the phosphorylation of tau-protein 15 in adult cortical sections. Printed by the Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, a cortical slice 300 microns thick was prepared from a 10 to 10 week old 0FA male (Iffa-Credo) killed by decapitation. It was incubated at 37 ° C for 40 minutes in 5 ml of DMEM medium containing 4.5 g / liter of pyruvate and glucose. Sections were then washed twice with the medium, dispensed into traces of 20 tubes (50 microliters in 500 microliters of medium with or without test compound), and incubated at 37 °C with agitation. After two hours, the experiment was terminated by centrifugation. The sections were lysed, sonicated, and centrifuged at 18300 g for 15 minutes at 4 °C. The protein concentration in the supernatant is based on the BCA Protein Assay, Pierce -38- This paper scale applies to the Chinese B standard (CNS) A4 specification (210 x 297 mm). 1353978 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed Α7 Β7 V. Invention description (37) Determination. The sample was denatured at 70 ° C for 10 minutes, separated in a 4 to 12% Bis-Tris vertical gel in the presence of K10PS-SDS buffer, and electrotransferred onto a nitrocellulose membrane. Immunolabeling was carried out using the monoclonal antibody AD2 (Ser396/404 specifically phosphorylating the epitope of the 5 τ protein). The immunologically active protein is visualized by the addition of a second antibody and chemiluminescent substrate that is directed to mouse IgGs and conjugated to peroxidase. The resulting autoradiographs were finally quantified using Syngene's "GeneTools" software (GeneGnome, Ozyme) to determine 10 IC50 values. The compound of the formula (I) has a very high activity, in particular a part of the compound has a value of less than 100//M (: 5 () value 〇 by LC/MS analysis of the product in the LC part of the Waters Alliance 2695 The mass is produced on the device and the mass fraction is produced on the Waters-15 Micromass Platform II. The following examples illustrate the invention without limitation. AfeLAI: N-butyl-6-gas-5-stupyl-m- Oxazole _3-amine oxime / latent thin: 24 mg n-butyraldehyde and 113 mg sodium triethoxy hydride borohydride added to 100 mg 3-amino-5-stupyl-6 qi-^[(2— Trimethylformamidine 20 alkyl ethoxy)methyloxazole in a solution of 5 cm 3 of di-methane. After 3 hours at ambient temperature, the reaction medium is hydrolyzed and then extracted with di-methane. Drying over magnesium sulfate, filtration and evaporation. The crude product was purified eluted eluted eluted elute Gas _5·phenyl small (2_(trimethyl)

-39- Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed 1353978 A7 B7 V. Inventive Note (38) Base) Ethoxymethyl-1H-indazol-3-yl)amine (yellow solid). Mass Spectrum: 432 [M+H]+, retention time: 5.26 min. 'H NMR [d6-DMSO]: 7.83 (1H, s), 7.73 (1H, s), 7.35-7.50 5 (5H, m), 6.25 (1H, t, J = 6 Hz), 5.49 (2H, s ), 3.52 (2H, t, J = 8 Hz), 3.24 (2H, m), 1.60 (2H, m), 1.39 (2H, m), 0.91 (3H, t, J = 7 Hz), 0.81 (2H , t, J = 8 Hz), -0.07 (9H, s). 10 茗 麿 :: 0.7 ml 2N HC1 added to 21 mg butyl [6-gas-5-phenyl-1-(2-(three) Methyl decyl) ethoxymethyl-1H-indazol-3-yl)amine in a solution of 0.3 cm 3 of methanol. The reaction medium was stirred at ambient temperature for 48 hours, refluxed for 1 hour and then evaporated. The solid obtained was dried under vacuum to give 16 mg of N-butyl-6-hexane-5-phenyl-1H-indazole-3-amine (yellow 15 color solid). Mass Spectrum: 300 [M+H]+, retention time: 4.25 min. *H NMR [d6-DMSO]: 7.52 (1H, s), 7.95 (1H, s), 7.35-7.50 (5H, m), 3.30 (2H, t, J = 7 Hz), 1.61 (2H, m) , 1.40 (2H, m), 20 0.92 (3H, t, J = 7 Hz). Example A2: 3-(6-Ga-5-phenyl-1H-indazol-3-ylamino)thiophene- 2-nitrile 38 mg 2-dicyclohexylphosphino-2'-(N,N-dimethylamino) biphenyl, 20 mg Pd2dba3 (tris(dibenzylideneacetone) dipalladium (〇)), 52 mg 2-Cyan-40- This paper size applies to China National Standard (CNS) A4 specification (210 x 297 mm)

Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperatives printed number 1353978 A7 B7 V. Description of the invention (3 mercapto-3-bromothiophene and 23 mg of sodium butoxide) added to 0.5 ml of NMP (1-mercapto-2-pyrrolidone) 52 mg of the compound 3-amino-5-phenyl-6-gas-l-[(2-trimethyldecyloxy)indolyl]carbazole. The reaction was placed at M0 °C. After 3 minutes under microwave treatment, the crude product was treated with a 2N HCl solution to yield 8.4 mg of 3-(6-chloro-5-phenyl-1H-indazol-3-ylamino). Thiophene-2-ride. Mass Spectrum: 351 [M+H]+, retention time: 4.19 min. 'H NMR [d6-DMSO]: 7.40 (1H, m), 7.48 (2H, m), 7.53 (3H, 10 m), 7.81 (1H, s), 8.09 (1H, s), 8.27 (1H, d, J = 5.5 Hz), 8.91 (2H, s),. Examples A3 to A5 15 The following examples are based on A2 Obtained in the same way.

N. Name Starting material retention time / ΓΜ + ΗΓ NMR d6_DMSO, unless otherwise stated A3 (6-gas-5-phenyl-1H-carbazol-3-yl)(pyridin-2-yl)amine 2-bromo" Specific bite 2.89/321 7.07 ppm (b, 1H), from 7.36 ppm to 7.50 ppm (m, 5H), 7.55 ppm (b, 1H), 7.67 ppm (s, 1H), 7.87 ppm (s, 1H), 7.95 Ppm (1, 1H), 8.21 ppm (b, 1H) at MeOD -41- This paper scale applies to China Difficult Standard (CNS) A4 specification (210x297 mm)

Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumer Cooperatives, Printing 1353978 A7 B7 V. Description of Invention (40) A4 (6-Gapent-5-Strepyl-1H-carbazol-3-yl) (5-Nitropyridin-2-yl) Amine 2- > odor-5· Exact σ ratio bite 4.58/ 366 from 7.42 to 7.52 ppm (m, 5H), 7.63 ppm (s, 1H), 7.65 ppm (s, 1H), 7.94 ppm (d, J - 9 Hz, 1H), 8.43 ppm (dd, J = 2.5 and 9 Hz, 1H), 9.13 ppm (d, J = 2.5 Hz, 1H), 7.77 ppm (bs, 1H), 9.55 ppm (bs, 1H A5 (6-Gapent-5-styl-1H-indazol-3-yl)(6-methoxypyridin-2-yl)amine 2-bromo-6-methoxypyridine 3.87 ppm (s, 3H), 6.31 ppm (d, J = 7.5 Hz, 1H), 7.36 ppm (bd, J = 7.5 Hz, 1H), from 7.35 to 7.50 ppm (m, 5H), 7.36 ppm (t, J = 7.5 Hz, 1H), 7.54 ppm (s, 1H), 7.69 ppm (bs, 1H) on CDC13 Example B1: N-(6-chloro-5-phenyl-1H-indazol-3-yl)-indole-phenylurea No: 39 μl of phenyl isocyanate was added to 102.2 mg of 3-amino-5 5-phenyl-6-chloro-1-[(2-trimethylformamido ethoxy)methyl] The azole is in a solution of 2.5 cm 3 in tetrahydrofuran. The reaction medium was stirred at ambient temperature for 24 hours and then evaporated. The crude product was purified by chromatography on silica gel (solvent: methylene chloride / acetone (98/2, ν / ν) to give 122.5 mg of 1-[6-gas-5-stupyl-1-(2- Trimethyldecyl ethoxymethyl)-1 Η-oxazol-3-yl]-3-10 phenylurea (colorless solid). Mass Spectrum: 493 [Μ+Η]+, retention time: 6.02 min. This paper size applies to the Chinese National Standard (CNS) A4 specification (210x297 mm)

Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed 1353978 A7 B7 V. Description of Invention (4〇NMR[d6-DMSO]: 9.89 (1H, wide peak s), 9.86 (1H, wide peak s), 8.20 (1H , s), 8.07 (1H, s), 7.35-7.50 (5H, m), 5.81 (2H, s), 3.66 (2H, t, J = 8 Hz), 0.92 (2H, t, J = 8 Hz) , -0.12 (9H, s),. 5 茗2麿: 1 ml of 2N HC丨 added to 106 mg of 1-[6-chloro-5-phenyl-1·(2-tridecylfluorenyl ethoxylate) a solution of -1 - oxazol-3-yl]-3-phenylurea in 12 cm of methanol. The reaction medium was stirred at ambient temperature for 48 hours, stirred under reflux for 5 hours and then evaporated. 10 Dry under vacuum to give 82 mg of N-(6-a.sup.5-phenyl-1H-carbazol-3-yl)-indole-phenylurea (colorless solid). Mass Spectrum: 363 [Μ+Η]+, Retention time: 5.15 minutes. lH NMR [d6-DMSO]: 12.64 (1H, broad peak s), 9.70 (1H, 15 broad peak s), 9.59 (1H, broad peak s), 8.07 (1H, s ), 7.64 (1H, s), 7.50 (7H, m), 7.30 (2H, m), 7.0 (1H, m). Example B2: 1-(6-Ga-5-phenyl-1H-carbazole -3-yl)-3-(4-ethoxyphenyl) 20 urea 36.4 mg 4-ethoxyphenyl isocyanate added 80 mg of 3-amino-5-phenyl-6-gas-l-[(2-trimethylcarbamimidyloxy)methyl] in 1 ml of THF is called oxazole. Heating at °C for 1 hour, then hydrolyzed in saturated KH2P04 solution, extracted with di-methane. Dry and evaporated -43- This paper scale is applicable to China National Standard (CNS) A4 specification (210 X 297 mm)

1353978 A7 B7 V. INSTRUCTION DESCRIPTION (42) Thereafter, the crude product was purified on cerium oxide using an AcOEt/hexane mixture. The product obtained was deprotected in 2 ml of a 1 / 1 MeOH / 2N HCl mixture for 3 hours under reflux. 62.5 mg of 1-(6-gas-5-phenyl-1H-indazol-3-yl)-3-(4-ethoxyphenyl)urea were obtained. 5 Mass Spectrum: 407 [M+H]+, retention time: 4.36 min. *H NMR [d6-DMS0]: 1.3 (3H, t, J = 7 Hz), 3.98 (2H, q, J = 7 Hz), 6.87 and 7.36 (AA'-BB% 4H), 7.36-7.50 (5H , m), 7.63 (1H, s), 8.08 (1H, s), 9.53 (2H, s), 12.53 (1H, s). 10 Examples B3 to B12: Products B3 to B12 are identical to product B2 The method was produced by the Ministry of Economic Affairs, the Intellectual Property Bureau, and the employee consumption cooperative. Name Starting material retention time / ΓΜ + Η] + NMR d6-DMS0 B3 1-(6-gas-5-phenyl-1H-indazol-3-yl)-3-(3,4-dichlorophenyl Urea isocyanate 3,4-dioxa ester 4.75/ 407 [Μ-Η] From 7.38 to 7.48 ppm (m, 6H), 7.53 ppm (d, J = 8.5 Hz, 1H), 7.66 ppm (s, 1H), 7.90 ppm (d, J = 2.5 Hz, 1H), 8.01 ppm (s, 1H), 9.70 ppm (s, 1H), 9.84 ppm (s, 1H), 12.72 ppm (bs, 1H) -44- This paper scale applies to China's B standard (CNS) A4 specification (210x297 mm) 1353978 A7B7 Five invention descriptions (43 Ministry of Economic Affairs Intellectual Property Bureau employees consumption cooperatives printed B4 gas-5-bens-1H-called | azole-3 -yl)-ureido]-propionate propionate phenethyl isophthalate 3.71 / 373 2.56 ppm (t, J = 6.5 Hz, 2H), 3.44 ppm (m, 2H), 3.61 (s, 3H), from 7.36 to 7.50 ppm (m, 5H), 7.58 ppm (s, IH), 7.81 (b, 1H), 8.08 ppm (s, 1H), 9.48 ppm (s, 1H), 12.52 ppm (bs, 1H) (two Methylamino) cumin 3.26/ 406 3·10 ppm (s, 6H), from 7.38 to 7.50 ppm (m, 5H), 7.64 (b, 4H), 7.66 ppm (s, 1H), 8.03 ppm (s, 1H), 9.70 ppm (s, 1H), 9.95 ppm (s, IH), 12.72 ppm (bs, 1H) B5 1-(6-gas-5-stupyl-1 Η · 丨" sit-3-yl)-3·(4-dimethylamino stupyl) m 3.95 329 1.16 ppm (d, J = 6.5 Hz, 6H), 3.85 ppm (m, 1H), from 7.38 to 7.50 Ppm (m, 5H), 7.58 ppm (b, 1H), 7.60 ppm (s, 1H), 8.10 ppm (s, 1H), 9.36 ppm (s, IH), 12.48 ppm (bs, 1H) B6 1-( 6-gas-5-phenyl-1H-oxime-3·yl)·3-isopropylurea B7 1-(6-gas-5-stupyl-1H· 引峻·3-yl)-3- Cyclohexylureaisophthalic acid cyclohexyl ester 4.37/ 369 from 1.3 to 1.9 ppm (m, 10H), 3.58 ppm (m, lH), from 7.38 to 7.49 ppm (m, 5H), 7.57 ppm (s, 1H), 7.68 ppm (bd, J = 5.5 Hz, 1H), 8.10 ppm (s, 1H), 9.38 ppm (s, 1H), 12.48 ppm (bs, IH) -45- (CNS) A4 size (210x297 mm) 1353978 A7 B7 V. Description of invention (44) B8 - (6-gas-5-stupid-1 Η-bow 1 &quot; sit-(tri-base)-3-( 3-(Trifluoromethyl)phenyl) phthalic acid 3-indole methyl stupid 6| 4.61/ 431 7.34 ppm (bd, J = 8 Hz, IH), 7.38 to 7.49 ppm (m, 5H), 7.53 Ppm (t, J = 8 Hz, 1H), 7.66 ppm (s, 1H), 7.69 ppm (bd, J = 8 Hz, 1H), 7.98 ppm (bs, 1H), 8.03 ppm (s, 1H), 9.71 Ppm (s , 1H), 9.96 ppm (s, 1H), 12.76 ppm (bs, 1H)_ B9 1-(6-gas-5-phenyl-1H- 4 &quot;Ke-(3-yl)-3-(2 -(thiophen-2-yl)ethyl)isophthalic acid 2-°S phen-2-yl)ethyl ester 4.2/ 397 3.02 ppm (t, J = 7 Hz, 2H), 3.46 ppm (m, 2H) , 6.92 ppm (dd, J = 1.5 and 3.5 Hz, 1H), 6.95 ppm (dd, J = 3.5 and 5 Hz, 1H), 7.32 ppm (dd, J = 1.5 and 5 Hz, IH), from 7.37 To 7.49 ppm (m, 5H), 7.58 ppm (s, 1H), 7.80 ppm (bt, J = 6 Hz, 1H), 8.08 ppm (s, 1H), 9.50 ppm (s, 1H), 12.48 ppm (bs , 1H)_ B10 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing (1,3-benzodioxan-5-yl)-3-(6-gas·5-stupyl·1Η- &lt; » 〇 〇 -3- ) 腺 腺 腺 1,3- 1,3- 1,3- 1,3- 1,3- 1,3- - - - - - - - - - - 5.97 / 407 5.97 ppm (s, 2H), 6.81 ppm (dd, J = 2.5 and 8.5 Hz, 1H), 6.84 ppm (d, J = 8.5 Hz, 1H), 7.22 ppm (d, J = 2.5 Hz, 1H), from 7.35 to 7.50 ppm (m, 5H), 7.65 ppm (s, 1H), 8.05 ppm (s, 1H), 9.56 ppm (s, 1H), 9.6 ppm (s, 1H), 12.65 ppm (bs, 1H) -46- This paper size applies to the China Standard (CNS) A4 specification (210 x 297 mm) 135 3978 A7 V. INSTRUCTIONS (45) B11 1-(6-Gas-5-stupyl-1H-°5丨"Guide-3-yl)-3-(3,5-Dimethylisoxazole-4 -Base) 3,5-Dimethylisoxazole-4-ester of isocyanate 3.76/ 382 2.13 ppm (s, 3H), 2.29 ppm (s, 3H), from 7.36 to 7.50 ppm (m, 5H) , 7.64 ppm (s, 1H), 8.03 ppm (s, 1H), 8.75 ppm (s, 1H), 9.74 ppm (s, 1H), 12.68 ppm (bs, 1H) B12 1-octyl-3-(6 - Benzene-5-phenyl-1H-carbazole _3_ carbamic acid benzyl isocyanate 4.2/ 377 4.43 ppm (d, J = 6 Hz, 2H), from 7.20 to 7.50 ppm (m, 10H), 7.58 Ppm (s, 1H), 8.10 ppm (bs, 2H), 9.57 ppm (s, 1H), 12.50 ppm (s, 1H) B13 1-(6-gas-5-stupid-1H-bow 丨 -3-3 -yl)-3-(p-ethyl) thiourea isothiononanoate 2.96 ppm (t, J = 7.0 Hz, 2H), 3.86 ppm (dt, J = 5.5 and 7.0 Hz, 2H), from 7.15 to 7.35 ppm (m, 5H), from 7.35 to 7.50 ppm (m, 5H), 7.64 ppm (s, 1H), 8.37 ppm (s, 1H), 10.14 ppm (t, J = 5.5Hz, 1H ), 10.97 ppm (s, 1H), 12.73 ppm (s, 1H) Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed Example __CX · 1-(6-chloro-5-stupid-1Η-» bow vomit -3-yl)-3-[ 3-(4-Methyl ** well-1-yl)-propyl] vein 5 Agricultural/grinding section: 62 μl of pyridine and 125 μl of ethyl chloroformate were continuously added in 2 ml of dioxane 387.8 mg of 3-amino-5-stupyl-6-gas _ 1-[(2-tridecyl fluorite ethoxy) methyl]u was introduced into the saliva. The reaction was completed after 75 minutes. After the hydrolysis, it was extracted and evaporated to give 571 mg of crude carbamic acid ester (6- </RTI> <RTIgt; -47- The paper size applies to the national standard (CNS) A4 specification (210 x 297 mm). Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed 1353978 A7 V. Invention description (46) # 2麿: 377 mg 4- (3-Aminopropyl)-1-methylpiped was added to 106 mg of the aforementioned urethane in 2.5 ml of trifluoromethyl, and the reaction was carried out under microwave irradiation at 200 ° C for 20 minutes. After purification by preparative LC/MS (acetonitrile / pH = 9 buffer), 60 mg of 1-[6-gas-5-phenyl-1-5(2-tridecylalkyl)-ethoxycarbonyl] was obtained. -1H-carbazol-3-yl)-3-[3-(4-mercaptopiperidin-1-yl)propyl]urea.茗3麿: The above compound was dissolved in 2 ml of 1/1 MeOH/2N HCl mixture and refluxed for 3 hours. 10 *H NMR [d6-DMSO]: 1.63 (2H, m), 2.18 (3H, s), 2.33 (10H, m), 3.21 (2H, m), 7.36-7.48 (5H, m), 7.58 (1H , s), 7.66 (1H, t, J = 5.5 Hz), 8.08 (1H, s), 9.37 (1H, s), 12.70 (1H, s). Examples C2 to C19 15 Products C2 to C19 The product C was obtained in the same manner as N. Name Starting material retention time / [Μ + ΗΓ NMR d6-DMSO C2 1-(6-gas-5-phenyl-1H-indazol-3-yl)-3-(3-(imidazol-1-yl) Propyl) 3-(imidazol-1-yl)propylamine 3/ 395 2.05 ppm (m, 2H), 3.24 ppm (m, 2H), 4.25 ppm (t, J = 6 Hz, 2H), from 7.38 To 7.49 ppm (m, 5H), 7.61 ppm (s, 1H), 7.69 ppm (bs, 1H), 7.76 ppm (d, J = 5.5 Hz, 1H), 7.83 ppm (bs, 1H), 8.08 ppm (s , 1H), 9.19 ppm (s, 1H), 9.53 ppm (s, 1H), 12.53 ppm (bs, 1H) -48- This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm)

1353978 A7B7 77 Explanation of invention (47) Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, printed C4 1·(6-Ga-5-stupyl-1Η-oxazol-3-yl)-3-(2-hydroxyethyl) Ureaethanolamine 3.36/331 3.27 ppm (m, 2H), 3.49 ppm (t, J = 6.5 Hz, 2H), from 7.38 to 7.50 ppm (m, 5H), 7.59 ppm (s, 1H), 7.83 ppm (b, 1H), 8.10 ppm (s, 1H), 9.49 ppm (s, 1H), 12.50 ppm (bs, 1H) C5 1-(6-Ga-5-phenyl-1H-indazol-3-yl)-3 -[3-(4-methyl D-bottom&quot;well-1-yl)propyl]urea 3-(4-methyl-° bottom 4 -1 -yl)propylamine 2.52/ 427 C6 pyrrolidine-1 -carboxylic acid (6-a-5-phenyl-1H-indazol-3-yl)-alanpyrrolidine 4/ 340 1.84 ppm (m, 4H), 3.37 ppm (m, 4H), from 7.37 to 7.49 ppm (m, 5H), 7.61 ppm (s, 1H), 7.72 ppm (s, 1H), 8.80 ppm (s, 1H), 12.62 ppm (s, 1H) C7 (6 - gas-5-stupid ~ 1H- Oxazol-3-yl)carbazate methyl ester methyl formate 4.1/ 302 3.66 ppm (s, 3H) from 7.33 ppm to 7.49 ppm (m, 5H), 7.65 ppm (s, 1H), 7.78 ppm ( s, 1H), 10.1 ppm (s, 1H), 12.80 ppm (s, 1H) C8 (6-gas _5·phenyl-1H-port -3-ethyl) aqueous urea solution 3.39/287 6.89 ppm ( Bs , 2H), from 7.37 ppm to 7.49 ppm (m, 5H), 7.59 ppm (s, 1H), 8.09 ppm (s, 1H), 9.37 ppm (s, 1H), 12.51 ppm (bs, 1H) C9 (6 -5-phenyl-1H-p-indol-3-yl)-carbamic acid benzyl acetate benzyl formate 4.5/ 378 5.14 ppm (s, 2H), from 7.29 to 7.49 ppm (m, 10H), 7.65 Ppm (s, 1H), 7.76 ppm (s, 1H), 10.08 ppm (bs, 1H), 10.77 ppm (bs, 1H) -49- This paper size applies to the Chinese National Standard (CNS) A4 specification (210x297 mm) 1353978 A7 B7 ft. » V. INSTRUCTIONS (48) C10 (6-gas-5-stupyl-1H-carbazol-3-yl)amine ruthenium citrate Allyl carbamate 4.4/ 328 4.61 ppm (dl, J = 5 Hz, 2H), 5.21 ppm (dl, H = 11 Hz, 1H), 5.34 ppm (dl, J = 17.5 Hz, 1H), 5.96 ppm (m) , 1H), from 7.39 to 7.49 ppm (m, 5H), 7.65 ppm (s, 1H), 7.78 ppm (s, 1H), 10.06 ppm (bs, 1H), 12.76 ppm (bs, 1H) C11 (6- Gas-5-stupyl-1H-indazol-3-yl)isobutyl carbazate isobutylate 4.55/ 344 0.90 ppm (d, J = 6.5 Hz, 6H), 1.90 ppm (m, 1H) , 3.86 ppm (d, J = 6.5 Hz, 2H) from 7·38 ppm to 7 .49 ppm (m, 5H), 7.66 ppm (s, 1H), 7.79 ppm (s, 1H), 9.93 ppm (bs, 1H), 12.93 ppm (bs, 1H) C12 piperidine-1-carboxylic acid (6 -Gas-5-phenyl-1H. Oral -3-yl) decylamine 3.92/ 355 1.40 ppm (m, 4H), 1.60 ppm (m, 2H), 3.43 ppm (m, 4H), from 7.37 to 7.50 ppm (m, 5H), 7.61 ppm (s, 1H), 7.62 ppm (s, 1H), 9.07 ppm (s, 1H), 12.62 ppm (s, 1H) C13 1-(3-(azetidine) Diisopropyl-1-yl)propyl)-3-(6_gas-5-styl-1H-indazol-3-yl)urea azacyclobutadiene (secondary addition) 1.50 ppm (m, 2H) , 2.02 ppm (m, 1H), 3.20 ppm (m, 2H), 2.54 ppm (masked, 2H), 3.27 ppm (masked, 4H), from 7.35 ppm to 7.50 ppm (m, 5H), 7.59 ppm ( s, 1H), 7.72 ppm (bt, J = 6 Hz, 1H), 8.09 ppm (s, 1H), 9.44 ppm (s, 1H), 12.50 ppm (s, IH) -50-

II.订·线_ This paper scale applies to China National Standard (CNS) A4 specification (210x297 mm) 1353978 A7 B7 V. Invention description (49) Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed C14 1-(6- Gas-5-phenyl-1H-indazol-3-yl)-3-(3-a-propyl)urea azetidinal (HCL open loop) 4.26/ 363 1.94 ppm (m, 2H), 3.30 ppm (masked, 2H), 3.60 ppm (t, J = 6.5 Hz, 2H), from 7.38 ppm to 7.50 ppm (m, 5H), 7.58 ppm (s, 1H), 7.60 ppm (bt, J = 6 Hz) , 1H), 8.07 ppm (s, 1H), 9.40 ppm (s, 1H), 12.41 ppm (s, 1H) C15 1-(6,7-difluoro-5-phenyl-1H-indazole-3- 3-(3-(imidazol-1-yl)propyl)urea 3-(imidazol-1-yl)propylamine 1.94 ppm (m, 2H), 3.18 ppm (q, J = 6.5 Hz, 2H ), 4.02 ppm (t, J = 6.5 Hz, 2H), 6.89 ppm (s, 1H), 7.21 ppm (s, 1H), 7.42 ppm (bt, J = 7.5 Hz, 1H), 7.50 ppm (bt, J =7.5 Hz, 2H), 7.55 ppm (bd, J = 7.5 Hz, 2H), 7.65 ppm (s, 1H), 7.73 ppm (bt, J = 6.5 Hz, 1H), 8.05 ppm (d, J = 6.0 Hz) , 1H), 9.58 ppm (s, 1H) C16 1-(3-Aminopropyl)-3-(6-Gas-5-Phenyl-1H-indazol-3-yl)urea 3-AminopropylAmine 2.74/ 344 1.77 ppm (m, 2H), 2.81 ppm (m, 2H), 3.28 ppm (m, 2H), from 7.38 ppm to 7.50 ppm (m, 5H), 7.60 ppm (s, 1H), 7.81 ppm (m, 3H), 8.08 ppm (s, 1H), 9.54 ppm (s, 1H), 12.54 ppm (s, 1H), -51- This paper size applies to the National Standard (CNS) A4 specification (210x297 mm) 4 1353978 A7 B7 V. INSTRUCTIONS (50) Employees of the Ministry of Economic Affairs, Intellectual Property Bureau, Consumer Cooperation, Printed CI7 1-(6-Ga-5-Benyl-1H-carbazol-3-yl)-3-[4_ (4-( π-precipitate-3-yl)imidazolium-mercapto)butyl]urea 4-(4-(indolyl-3-yl)imidazol-1-yl)butylamine 2.95/ 486 1.51 ppm ( m, 2H), 1.90 ppm (m, 2H), 3.26 ppm (m, 2H), 4.23 ppm (t, J = 7 Hz, 2H), from 7_37 ppm to 7.49 ppm (m, 5H), 7.58 ppm (s , 1H), 7.75 ppm (m, 2H), 8.08 ppm (s, 1H), 8.37 ppm (d, J = 2 Hz, 1H), 8.47 ppm (m, 1H), 8.69 ppm (dd, J = 1.5 and 5Hz, 1H), 9.00 ppm (bs, 1H), 9.12 ppm (d, J = 2 Hz, 1H), 9.48 ppm (s, 1H), 12.40 ppm (bs, 1H) C18 1-(6-gas-5 - Stupid-1H-吲w-3-yl)-3-(2-pyrrolidin-1-yl)ethyl)urea 2-(indolepyr-1-yl)ethyl)amine 2.8/ 384 1.83 Ppm (m, 2H ), 1.99 ppm (m, 2H), 3.03 ppm (m, 2H), 3.28 ppm (m, 2H), 3.56 ppm (masked, 4H), from 7.36 ppm to 7.49 ppm (m, 5H), 7.61 ppm (s , 1H), 7.80 ppm (bt, J = 5.5 Hz, 1H), 8.08 ppm (s, 1H), 9.65 ppm (s, 1H), 10.02 ppm (bs, 1H), 12.62 ppm (bs, 1H) C19 2 ,5-di-P-pyrrolidine-1-carboxylic acid (6-gas-5-phenyl-1H-indazol-3-yl)guanamine 2,5-dimethyl-pyrrolidine 4.08/ 369 1.10 and 1.21 ppm (d, J = 7 Hz, 6H), 1.50 and 1.61 ppm (m, 2H), 1.99 and 2.12 ppm (m, 2H), 4.03 and 4.15 ppm (m, 2H), from 7.36 to 7-49 ppm (m, 5H), 7.60 ppm (s, 1H), 7.67 and 7.69 ppm (s, lH), 8.52 and 8.66 ppm (s, 1H), 12.60 ppm (bs, 1H) -52- This paper size applies China National Standard (CNS) A4 Specification (210 X 297 mm) 1353978 A7 B7 V. Description of Invention (51) Example Dl: N'(6-Gapent-5-Strepyl-1H-carbazol-3-yl) Ethylhydrazone 33 mg of acetaminophen was added to 50 mg of 3-amino-6-a-5-phenyl-1H-carbazole in 3 ml of acetonitrile and 12 mg of acetic acid. The reaction was allowed to stand under microwave irradiation at 5 180 ° C for 5 minutes. After general treatment and purification by cerium oxide, 35 mg of N-(6-gas-5-styl-1H-indazol-3-yl)

&quot;1 I Example D2 to D4 Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed 10 The following products were obtained in the same manner as D1. N. Name Starter Material Retention Time / Γμ+ηΓ NMR D2 N-(6-Ga-5-stupyl-1H-carbazol-3-yl)-6-oxime O-pyrene-2-thiol-methoxy- 11 than chlorinated 2-carboxyindoleimine ethyl ester 3.61 / 379 4.08 ppm (s, .3 Η), from 7.40 to 7.50 ppm (m, 5H), 7.68 ppm (s, 1H), 7.93 ppm (s, 1H), 8.24 ppm (bs, 1H), 8.43 ppm (s, 1H), 8.69 ppm (bs, 1H), 9.27 ppm (s, 1H), 12.80 ppm (bs, 1H) D3 N-(6-gas - 5-phenyl-1H-carbazol-3-yl)-benzylidene benzidine iodide ethyl ester 3.42/ 347/ from 7.36 ppm to 7.50 ppm (m, 8H), 7.64 ppm (s, 1H), 7.80 ppm (s, 1H), 8.12 ppm (m, 2H), 8.24 ppm (bs, 1H), 8.76 ppm (bs, 1H)5 12.60 ppm (bs, 1H) -53- set. 4 This paper size applies to troubled countries Standard (CNS) A4 Specification (210x297 mm) 1353978 V. INSTRUCTIONS (52) D4 N-(6-Gapent-5-Pyridine-2-carboxylate from 7.35 to 7.50 ppm (m, yl-1H-carbazole-醯iminoethyl 5H), 7.54 ppm (dd, J = 5.0 3 -yl)·σ ratio bite-2 - ester and 7.5 Hz, 1H), 7.67 ppm Carboxylic acid (s, 1H), 7.87 ppm (s, 1H ), 7.94 ppm (dt, J = 1.5 and 7.5 Hz, 1H), 8.30 ppm (bs, 1H), 8.58 ppm (d, J = 7.5 Hz, 1 H), 8.64 ppm (bs, 1H), 8.58 ppm (dd, J = 1.5 and 5.0 Hz, 1H), 12.70 ppm (bs, 1H) Example Ei: N-(6-chloro-5-phenyl-1H -oxazol-3-yl)-3-methoxybenzenesulfonamide 5 茗7麿: 0.236 33 pyridine and 26.5 mg of 3-methoxyphenyl sulfonium chloride added to 54.1 mg of 3-amino-5 -Phenyl-6-gas-l-[(2-trimethylformamidoethoxy)mercaptocarbazole in 2 ml of dioxane. The reaction medium was stirred at ambient temperature for 24 hours and then evaporated. The crude product was purified by chromatography on cerium chloride (solvent: dioxane/acetone (98/2, 10 v/v)) to give 70 mg of 1 Ν-[6-chloro-5-phenyl--1- (2-(Trimethyl decane Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing base) ethoxymethyl)-1 Η-oxazol-3-yl]-3-methoxy sulfoxamide (colorless foam) . Mass Spectrum: 546 [M+H]+, retention time: 4.24 min. 15 'H NMR [d6-DMSO]: 10.96 (1H, s), 7.37 (1H, s), 7.58 (1H, s), 7.30-7.55 (8H, m), 7.17 (1H, dd), 5.63 (2H , s), 3.74 (3H, -54- This paper size applies to national standard (CNS) A4 specification (210x297 mm) 1353978 4 A7 B7 V. Description of invention (53) s), 3.38 (2H, t, J =8 Hz), 0.74 (2H, t, J=8 Hz), -0.12 (9H, s). 茗2麿 Thin: 1 cm 3 of 2N HC1 added to 10.8 mg of lN-[6-gas-5-benzene A solution of -1-(2-(trimethyldecyl)ethoxymethyl)-1 oxazol-3-yl]-3-methyl-5-oxosulfonamide in 1 cm of methanol. The reaction medium was stirred at ambient temperature for 48 hours and at reflux for 1 hour before evaporating. The resulting solid was dried under vacuum to give &lt;RTI ID=0.0&gt;&gt;&gt;&&&&&&&&&&&& Mass Spectrum: 414 [M+H]+, retention time: 4.04 min. 10 4 NMR [d6-DMSO]: 12.90 (1H, broad peak s), 10.74 (1H, broad peak s), 7.67 (1H, s), 7.31-7.56 (10H, s), 7.20 (1H, dd ), 3.77 (3H, s). 15 The pharmaceutical composition of the present invention comprises a compound of the formula (I) or a salt of the compound, which is in a pure state or is compatible with any other medicinal product (may be inert) Or physiologically active) combined with the form of the compound. The medicine of the invention can be used for oral, parenteral, rectal or topical use. The solid composition of the Ministry of Economic Affairs, the Intellectual Property Bureau, the employee consumption cooperative, which can be used for oral administration, can be used for tablets, pills, powders 20 (hard gelatin capsules, beans) Capsule) or granules. In such compositions, the active principal component of the present invention is mixed with one or more inert diluents such as starch, cellulose, sucrose, lactose or cerium oxide under a stream of argon. 'These compositions may also contain substances other than diluents, such as one or more lubricants (such as magnesium stearate or talc), colorants, coatings (coatings) or glazes -55- for paper grades China National Standard (CNS) A4 Specification (210x297 mm) Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed 1353978 A7 B7 V. Description of Invention (54) (glaze) Liquid composition for oral administration can be used in medicine Accepted solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oil or liquid. These compositions may contain materials other than diluents, such as wetting agents 'sweeteners' thickeners, flavoring agents or stabilizers. The sterile composition for parenteral administration is preferably a solution, suspension or emulsion in aqueous or non-aqueous form. As the solvent or adjuvant, water, propylene glycol, polyethylene glycol, vegetable oil (especially eucalyptus oil) 'injectable organic ester 10 (e.g., ethyl oleate) or other suitable organic solvent can be used. These compositions may also contain adjuvants, especially wetting agents, isotonic agents, emulsifying agents, dispersing agents and stabilizers. Sterilization can be carried out in several ways, such as sterilization filtration, incorporating a bactericide, illuminating or heating in the composition. It can also be prepared as a sterile solid composition which can be dissolved in sterile water or any other injectable sterile medium. The rectal pharmaceutical compositions are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols. The topical pharmaceutical composition can be, for example, a cream, lotion, ophthalmic drip 20, mouthwash, nasal drop or aerosol. The subject of the present invention is a compound having the aminoguanidine of the formula (1) and a pharmaceutically acceptable salt thereof and use thereof for the preparation of a pharmaceutical composition for preventing and treating a disease caused by abnormal activity of a kinase, Such as, for example, with neurodegenerative diseases, Alzheimer's disease 'Pa-56- This paper scale applies the national standard (CNS) A4 specification (2丨Ox297 mm)

Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumption Cooperative, Printed 1353978 A7 V. INSTRUCTIONS (55) Parkinson's disease, frontal dementia, basal cortical degeneration, Pick's disease, stroke, spinal cord trauma And neuropathy, obesity, metabolic disease, type III diabetes, essential hypertension, arteriosclerotic cardiovascular disease, polycystic ovarian syndrome 'X syndrome 5 ', immune insufficiency and cancer kinase. Abnormal kinase activity may refer to, for example, P13K, AkT or GSK3)S, CDK and the like. In human therapeutic applications, the compounds of the invention are particularly useful for the treatment and/or prevention of neurodegenerative diseases, Alzheimer's 10 disease, Parkinson's disease, frontal osteopathy, basal cortical degeneration. , Pick's disease, stroke, head spinal cord trauma and peripheral neuropathy, obesity, metabolic disease, type III diabetes, essential hypertension, arteriosclerotic cardiovascular disease, polycystic ovarian syndrome, X Symptoms, immune insufficiency and cancer. 15 Dosage depends on the desired effect, duration of treatment, and route of administration; usually adult oral doses are between 5 mg and 1000 mg daily, and unit doses are from 1 mg to 250 mg active. Typically, the physician will determine the appropriate dosage for the age, weight, and all other factors that the patient will treat. 20 The following examples illustrate the compositions of the present invention: Example A A hard gelatin capsule having the following composition was prepared according to the general technique at a dose of 50 mg of active product: - a compound of the formula (I) *··50 mg-57-ben Paper size is applicable to the National Standards (CNS) A4 specification (210x297 mm)

r 1353978 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed A7 B7 V. Invention description (56 ) - Cellulose...18 mg-lactose...5 5 mg-colloidal cerium oxide...1 mg-carboxymethyl starch sodium...10 Mg 5 - talc... 10 mg - magnesium stearate... 1 mg

Example B A tablet having the following composition was prepared according to the general technique at a dose of 50 mils of active product: - a compound of the formula (1) ... 50 mg - lactose ... 104 mg - cellulose ... 40 mg - Polyvidone )··· 10 mg 15-carboxymethyl starch sodium...22 mg-talc...10 mg-magnesium stearate...2 mg-colloidal ceria...2 mg-hydroxymethylcellulose, a mixture of glycerin and titanium dioxide 20 (72/3.5/24.5) the right amount, so that the coated bond is &quot; 245 mg

Example C An injectable solution having the following composition and containing 10 mg of the active product was prepared. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 x 297 mm).

1353978 A7 B7 V. INSTRUCTIONS (57) - Compounds of the general formula (I) ... 10 mg - succinic acid ... 80 mg - octanol - 0.06 ml - sodium octoate ... 80 mg 5 - 95% ethanol ... 0.4 ml - oxidized Sodium "·24 mg-propylene glycol...1.6 ml-water...total amount up to 4 ml The present invention also relates to a method for preventing and treating a disease involving phosphorylation of tau protein, which is administered to a compound of the formula (1) and a pharmaceutical thereof Acceptable salt. Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed on this paper scale applicable to China National Standard (CNS) A4 specification (210x297 mm)

Claims (1)

1353978 Announcement A8 B8 C8 D8 Patent Application No. 92丨24408 ROC Patent AppJn. No.92124408 Amended Claims in Chinese - ΕηοΙ.ΠϊΠ Amend Claims in Chinese - ΕηοΙ. Patent Scope (Submitted on May 10, 2011) (Submitted on May 10, 2011) 1. A compound of formula (I) N-R3 Wherein R3 is (1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, heteroaryl(1-6C)alkyl, fused to (1-10C)cycloalkane Aryl or heteroaryl, heterocyclic, heterocycloalkyl, cycloalkyl, adamantyl, polycycloalkyl, alkenyl, alkynyl, CONR1R2, CSNR1R2, COOR1, S02R1 or C(=NH)NR1 a group; such groups are optionally substituted with one or more substituents selected from the group consisting of: 'CN, N〇2, NH2, OH, OR1, COOH, C(0)0R1, -0-C ( 0) Rl, NR1R2, NHC(〇)R1, C(0)NR1R2, SRI, S(0)R1, S02R1, NHS02R1, S02NR1R2, C(S)NR1R2, NHC(S)R1, -0-S02Rl, - SCV O-R1, aryl, heteroaryl, decyl, oxy, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy or (1-6C)alkyl; The R5 system printed by the Property Bureau Staff Consumer Cooperative is a phenyl group, which is substituted by one or more substituents selected from the group consisting of halogen, CN, N〇2, 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, S(O)R10, SO2R10, NHS02R1〇, SO2NRIORII, -C US〇2R1〇, -so2-o_rio, aryl, heteroaryl, methionyl, trifluoromethyl-60 - This paper scale applies to China National Standard (CNS) A4 specification (210x297 mm) 2'~~ Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed 1353978 Α8. Β8 C8 ------- D8____ VI. Patent application scope &quot; ^ base, trifluoromethoxy or (1-6C) alkyl; - R6 is halogen , methyl, cyclopropyl, CN, 0H, methoxy, monomethyl 'ethylglycosyl, ethynyl, trifluoromethoxy, n〇2, nh2 or NMe2 groups; R1, R2 are hydrogen (1_6C)alkyl, aryl, alkenyl, alkynyl or heteroaryl, which itself is optionally substituted with hydrazine or a plurality of substituents selected from the group consisting of dentate, (1-6C) alkyl, (1) -6C) alkoxy, CN, N〇2, NH2, 〇H, COOH, COO 炫, CONH2, formamidine, oxy, trifluoromethyl or trifluoromethoxy; R1 and R2 can form a 5- or 6-membered ring which may or may not have a hetero atom of hydrazine, S or N; a racemate, a mirror image or a non-image isomer thereof, and mixtures thereof, tautomers thereof and Pharmaceutically acceptable salt2. A compound according to claim 1 which is selected from the group consisting of: 〇N-(bicyclo[2.2.1]hept-5-zhen-2-ylindenyl)-6-gas_5- Stupid base_1H丐丨. Sodium-3-amine 6-chloro-N-(3,3-dimercaptobutyl)-5-phenyl-1H-Wazole! Amine 6-gas-N-(3-phenylpropyl)-5-phenyl-1H-carbazole-3-amine 6-|ίΐ-Ν-(cyclopropylindenyl)-5-phenyl-1H -11 cited. 3-Oxo-6-ICL-N-(cyclopentylmethyl)-5-phenylindole-3-amine 6-gas-N-[3-(methylthio)propyl]-5-benzene -1H-bamboo sitting_3-amine 6-gas-N-(phenylethyl)-5-phenyl-1H.carbazole-3-amine 6-gas-N-(cyclohexylfluorenyl)- 5-phenylpyrazine-3-amine -61 - 1353978 A8 B8 C8 D8 VI. Patent Application 6-Gas-N-propyl-5·Phenyl-iH-p 嗤-3-amine 6-Chloro-N-(2,2,3,3 ,4,4,4-heptafluorobutyl)-5-phenyl-1H-indazole-3-amine hydrate 6-gas-N-(4,4,4-trifluorobutyl)_5·phenyl -1H-carbazole-3-amine 6-chloro-N-[(4-indolylphenyl)indenyl]_5_phenyl_1H_P-triazole_3_amine 6-chloro-N-(phenylmethyl -5-phenyl_1H-indazol-3-amine 6-gas-N-[(4-cyanophenyl)methyl]_5_phenyl_1H_carbazole_3_amine N-[( 4-oxophenyl)indenyl]-6-chloro-5-phenyl-1H-indazol-3-amine 6-gas-N-[(3-indolylphenyl)methyl]_5_phenyl- 1H_carbazole-3-amine 6-gas-N-[[4_(trifluoromethoxy)phenyl]indenyl]_5_phenyl_1H-carbazole_3_amine N-[4-[[[ 6-chloro-5-phenyl-1H-Woxazol-3-yl]amino]methyl]phenyl]acetamide 6-gas-N-[(3,5-dichlorophenyl)indenyl] _5_phenyl-1H-carbazole-3-amine 6-gas-5-phenyl-N-[[4-(trifluoromethyl)phenyl]methyl]-1H-indazol-3-amine 6 - gas-N-[(4-fluorophenyl)indolyl]-5-phenyl-1H-indazol-3-amine 6-chloro-N-[3-(4-mercaptophenoxy)phenyl Indenyl]_5_phenyl-1H"-indazole-3-amine 1^-(2,2,3,3,4,4,4-heptafluorobutyl)-6-chloro-5-phenyl-111 -carbazole-3-amine 6-gas-5-phenyl-N-[[3,5-double (Trifluoromethyl)phenyl]methyl]-1H-indazol-3-amine 6-gas_5·phenyl-N-[[3_(tris-decyl)phenyl]methyl]-iH-卜 坐-3-amine 6-chloro-N-[(6-methoxy-2-naphthalenyl)methyl]-5-phenyl-1H-indazole-3-amine 6-gas-N-[( Pentafluorophenyl)indolyl]-5-phenyl-1H-indazol-3-amine 6-chloro-N-[[4-(indolylthio)phenyl]indolyl]-5-phenyl-1H -carbazole-3-amine N-[(4-gas_3_fluorophenyl)indolyl]-6-gas-5-phenyl-1Η-ρ引0--3-amine-62 - paper scale Applicable to China National Standard (CNS) A4 Specification (2丨Ox297 mm) Customized Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed A8 B8 C8 D8 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed 1353978 VI. Patent Application 6- Gas-5-phenyl-N-(3,3,3-trifluoropropyl)-1Η-indazol-3-amine 6-gas-5-phenyl-N-(3-thienylfluorenyl)- 1Η-carbazol-3-amine N-(bicyclo[2.2.1]hept-5-en-2-ylmethyl)-6-chloro-5-phenyl-1H-indazol-3-amine N- (l,l'-biphenyl-4-ylindenyl)-6-a-5-phenyl-1H-indazol-3-amine 6-chloro-N-[[4-(dimethylamino) Phenyl]methyl]-5-phenyl-1H-indazole-3-amine N-(2,2'-bithiophen-5-ylindenyl)-6-chloro-5-phenyl-1H-indole Oxazole-3- 6-Chloro-5-phenyl-N-[[l-(phenylmethyl)-1Η-imidazol-2-yl]indolyl]-1H-indazol-3-amine 6-chloro-N-[[ l-Mercapto-1H-imidazol-2-yl]fluorenyl]-5-phenyl-1H-indazol-3-amine 6-chloro-N-[(l-fluorenyl-1H-indole-3- 5-mercapto]-5-phenyl-1H-indazol-3-amine 6-chloro-N-[(5-methyl-2-furyl)methyl]-5-phenyl-1H-carbazole 3-amine 6-chloro-5-phenylpyrrol-2-ylindenyl)-1 - oxazol-3-amine 6-chloro-5-phenyl-N-[(1H-imidazol-2-yl) Methyl]-1H-indazole-3-amine 6-chloro-5-phenyl-N-[(1H-imidazol-4-yl)methyl]-1H-indazol-3-amine 6-chloro-5 -phenyl-N-(1H-pyrazol-3-ylindenyl)-1 - oxazol-3-amine 6-gas-N-[[2-methyl-1H-imidazol-4-yl]methyl ]-5-phenyl-1H-carbazol-3-amine 6-gas-N-[(3,5-dimercapto-1-phenyl-1H-pyrazol-4-yl)indolyl]-5 -phenyl-1H-called 丨 ° sit-3-amine 6-chloro-5-phenyl-N-[[2-phenyl-1H-imidazol-4-yl]indolyl]-1H-indole-63 - This paper size applies to the Chinese National Standard (CNS) A4 specification (210x297 mm) A8 B8 six _25_____ μ patent range 6' gas-N-[[5-(4-chlorophenyl)-2-furanyl]methyl]-5-phenyl_1H-indole "amine 6' gas Phenyl-N-[(l-methyl-1H-pyrrol-2-yl)methyl]_1H, 丨°生 '3-amine 4'[5-[[[6_chloro-5-phenyl-1H) -oxazol-3-yl]amino]methyl]_2-furan] oxasulfonamide 6~ gas-S-phenyl-N-(3-thienylmethyl)-1Η-indazol-3-amine 6' gas, 5-phenyl-N-[[2-phenyl-1H-imidazol-4-yl]methylindole-5-phenyl-1Η-carbazole-3-yl]amino]methyl] -5_(曱 米 唾 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ , carbazole-3-amine economy Zou wisdom property bureau employee consumption cooperative printing gas ~5 · phenyl-N-[2-(1 - shouting) ethyl]' 1 Hp lead. sitting -3 -amine fluoride ~Κί-[2-(4-Ifosyl)ethyl]-5-phenyl-indole-'1 cis-s--3-amine N'(6-chloro-5-phenyl-1H-carbazole- 3-yl)-N'-(3,5-diphenyl) vein (6-虱-5-phenyl-1Η-ρ?1 ° sit-3-yl)-1^'-(2-propane Dilute base) N~(6U-phenyl-1H-carbazol-3-yl)-Ν'-(phenylmethyl)urea (6·'虱-5-phenyl-1Η-ρ引11 sitting- 3-yl)-indole,-(4-phenoxyphenyl)urea oxime (6~wind-5-phenyl- Η-口引0 sits-3-yl)-Ν'-(4-曱-oxyphenyl)indolyl]urea~(6-chloro-5(phenyl-1Η-,oxazolyl)-Ν,- [4-(Trifluoromethyl)phenylindole (·(6-chloro-5-phenyl-1Η-carbazole·3-yl)-Ν'-(4-methoxyphenyl)urea-(6 -Chloro-5-phenyl-1Η-bamboo--3-yl)-Ν'-cyclohexyl胧-64 - This paper scale applies to China National Standard (CNS) A4 (210x297 mm) AB c D 1353978 VI. Patent application scope N~(6-gas-5-phenyl-1 ° sit-3-yl)-N'-propyl pulse N-(6-chloro-5-phenyl-1H-carbazole- 3-yl)-N'-(4-chlorophenyl)urea N-(6-chloro-5-phenyl-1H-indazol-3-yl)-N'-(4-fluorophenyl)urea N -[6-chloro-5-phenyl-1H-indazol-3-yl]-N,-(tricyclo[3.3.1.13,7]indole-1-ylurea N-(6-chloro-5- Phenyl-1H-indazol-3-yl)-N'-(4-mercaptophenyl)urea N-[6-chloro-5-phenyl-1H-indazol-3-yl]-4-indole -Benzenesulfonamide N-[6-chloro-5-phenyl-1H-indazol-3-yl]-indolesulfonamide N-[6-chloro-5-phenyl-1H-carbazole-3 -yl]-2-propanesulfonamide [6-chloro-5-phenyl-111-oxazol-3-yl]-2,2,2-trifluoroethanesulfonamide N-[6-chloro- 5-phenyl-1-β-β-3-yl]-2 -σ-cepheno-continuous amine Ν-[6-chloro-5-phenyl-1Η-oxazol-3-yl --Benzenesulfonamide-[6-chloro-5-phenyl-1Η-oxazol-3-yl]-4-(trifluoromethyl)benzenesulfonamide N-[6-chloro-5-benzene Base-1H-carbazol-3-yl]-5-(3-isoxazolyl)-2-thiophene yellow-brown amine economic department intellectual property bureau employee consumption cooperative printed N-[6-chloro-5-benzene -1-1H-carbazol-3-yl]-4-fluorobenzenesulfonamide N-[6-chloro-5-phenyl-1H-indazol-3-yl]-4-oxooxybenzenesulfonamide N -[6-chloro-5-phenyl-1H-indazol-3-yl]benzimidamide N-[6-chloro-5-phenyl-1H-indazol-3-yl]-1-oxime N-[6-chloro-5-phenyl-1H-indazol-3-yl]-4-(1,1-dimethylethyl)benzite yellow Amine N-[4-[[(6-Ga-5-phenyl-1H-indazol-3-yl)amino]sulfonyl]phenyl]acetamide-65 - This paper scale applies to Chinese national standards (CNS) A4 size (210x297 mm) 3978 Six patent application scope A8 B8 C8 D8 Ν·[6-chloro-5-phenyl-1H-indazol-3-yl]-4-methylbenzimidamide 6-milk-Ν-(penta-phenyl)-5-phenyl-1Η-bamboo-3-amine 6-milk-Ν-(3,4-«-gas base)-5-phenyl-1 Η -ρ引唾-3-amine 6-chloro-5-benyl-indole-(2,3,5,6-tetrafluorophenyl)_ιη-»引唾_3_amine 6-milk-5-benzen -Ν-(2,4,6-trifluorobenzene )-ΐΗ-«»引嗤_3_amine 6-gas-N-(4-fluorophenyl)-5-phenyl-1H-bamboo-3-amine 6-gas-N-[3-( Trifluoromethyl)phenyl]-5-phenyl·1H_„嗤嗤_3•amine 6-gas seven-[4-(trimethylmethyl)phenyl H-phenyl-1H-called 卜 sitting_3 -amine 6-gas-N-[3-fluoro-5-(trifluoromethyl)phenyl]_5_phenyl-1 private 4 sitting _3_amine 6-milk-N-(4- sure' group Stupid)-5-phenyl-1H-called oxa-3-amine 6-gas-N-(3-nitrophenyl)-5-phenyl-1H-indazol-3-amine 6-rat- N-(3-oxophenyl)-5-phenyl-1H-1b--3-amine 6-chloro-N-(4-methoxyphenyl)-5-phenyl-1H_W 〇3 -amine 6-chloro-N,5-diphenyl-1H-indazol-3-amine 6-gas-N-(l-pyridyl)·5·phenyl-1H-indazol-3-amine 6- Gas-N-(2-«» ratio bite base)-5-phenyl-1Η-ρ 嗤-3-amine economy Zou Intellectual Property Bureau employee consumption cooperative printed matter its racemate, mirror image isomer, Or a non-image isomer and mixtures thereof, tautomers thereof, and pharmaceutically acceptable salts thereof. A compound according to claim 1 which is selected from the group consisting of N/butyl-6-a-5-phenyl-1H-indazol-3-amine 3-(6-chloro-5-phenyl -1H-oxazol-3-ylamino)thiophene-2_ride (6-a-5-phenyl-lH-p-indol-3-yl) (B-but-2-yl)amine (6 -Chloro-5-phenyl-lH-p cited '^-3-yl)(5-nitron ratio _2-yl)amine-66 - This paper scale applies to China National Standard (CNS) A4 specification (210x297 PCT 1653978 Six patent application scope A8 B8 C8 D8 (6-chloro-5-phenyl-indole 丨 丨 NA chloro-5-phenyl-1Hp 引 基 base) (dioxime ° bite · 2- base Amine W6-chloro-5-benzene A m 3_yl)·Ν'·Phenyl urea meal called ethoxy stupid H3-(6-chloro-5-phenyl]H 3 sylylene-3-( 3,4-Dichlorophenyl)urea, carbazole _3_yl)ureido]methyl propionate, chlorobenzene benzophenone-Ht, sitting on the base rushing ^ ah-5-phenyl-heart: sitting Cyclohexylurea H6-chloro-5. Stupid-1Η,^ί (trifluoromethyl)benzene fine oxime, 3·benzodioxan 3_(2-(喧)丝)杂 蛛 5 · -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -3 -(3,5_Dimethylisothene)_下下^-3-(6-Ga-5-phenyl-1Hn3_ Urinary ι', _5_phenyl·1Hm3j)3 (phenethyl) thiourea 1-(6-wind_5-stupyl-1H-o-azol _3_yl)_3_[3_(4_f-based 〇井小基propyl]urea Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed 1 (6 chloro-5_phenyl-ιη·射_3•基)_3·(3_(令坐基)propyl 1- (6·Chloro-5-phenyl]Η.+sitting·34)_3(2_^ylethyl)ureaΗ6-chloro-5-stupidyl-1Η斗_3_基)3_[3·(4曱Base] propyl] genipodone-1-carboxylic acid (6-chloro-5-phenyl-1 fluoren-3-yl) decylamine (6-gas-5-bens-1 Η- »1引. Sodium-3-yl) Amino phthalic acid --67 - This paper scale applies to China National Standard (CNS) A4 specification (2丨Οχ297 mm) 1353978 A8 B8 C8 D8_ VI. Patent application scope ( 6-rat-5-phenyl-1 H-p5l ° sit-3-yl) vein (6-chloro-5-phenyl-1H-indazol-3-yl)aminobenzyl phthalate (6-nitrogen) -5-Heptyl-1 H-p5|.Sodium-3-yl)carbamic acid diisopropyl benzoate (6-chloro-5-phenyl-1H-indazol-3-yl) carbamic acid isobutyl ester Piperidine-1-carboxylic acid (6-a-5-phenyl-1H-indazol-3-yl) decylamine 1-(3-(3-(1)-) -(6-lact-5-phenyl-1 Hp-azol-3-yl)urea 1-(6-chloro-5- Base-1 σ-s--3-yl)-3-(3-chloropropyl)gland-1(6,7-difluoro-5-phenyl-1H-indazol-3-yl)-3-(3 -(imidazol-1-yl)propyl) hide 1 _(3_aminopropyl)-3-(6-a-5-phenyl-1 Hp-induced w--3-yl) vein 1-(6- Chloro-5-phenyl-1H-indazol-3-yl)-3-[4-(4-(pyridin-3-yl)imidazol-1-ylbutyl]urea 1-(6-chloro-5- Phenyl-1H-indazol-3-yl)-3-(2-(pyrrolidin-1-yl)ethyl)urea 2,5-diindenyl 0 to 11 calcined-1 - slow acid (6- Gas-5-Benyl-1Η-ρ弓丨°Sit-3_ Base)-Proline Economics Department Intellectual Property Bureau Staff Consumer Cooperative Printed Ν-(6-Ga-5-phenyl-1Η-carbazole-3- Acetylamine-(6-chloro-5-phenyl-1indole-indazol-3-yl)-6-methoxypyrrol-2-carboxyindole N-(6-chloro-5-phenyl- 1H-carbazol-3-yl)benzylidene N-(6-chloro-5-phenyl-1H-indazol-3-yl)pyridine-2-carboxyramine N-(6-gas-5-benzene a racemate, a mirror image isomer or a tautomer thereof, and a pharmaceutically acceptable salt thereof, of the radical-1H-indazol-3-yl)-3-methoxybenzenesulfonamide. -68 - This paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1353978 A8 B8 C8 D8 VI. Patent scope 4. A method for preventing and treating diseases caused by abnormal activities of kinases A pharmaceutical composition comprising a compound according to any one of claims 1 to 3 in a pharmaceutically acceptable medium. 5. The pharmaceutical composition according to claim 4, which comprises at least one compound according to any one of claims 1 to 3, which is therapeutically used for the treatment of the phosphorylation of tau protein. disease. 6. A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 3, and for medical use in the treatment of neurodegenerative diseases, stroke, head spinal cord trauma and peripheral neuropathy, Obesity, metabolic disease, type II diabetes, essential hypertension, arteriosclerotic cardiovascular disease, polycystic ovarian syndrome, X syndrome, immunodeficiency, and cancer. 7. The pharmaceutical composition of claim 6, wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, frontal osteopathy, basal cortical degeneration or ratio Pick's disease. Ordering Printed by the Intellectual Property Office of the Ministry of Economic Affairs, the consumer cooperatives. This paper scale applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm).