TW201202215A - Aminopyrimidine derivatives as LRRK2 modulators - Google Patents

Abstract

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R5, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Description

201202215 VI. Description of the Invention: [Technical Field] The present invention relates to a compound which modulates LRRK2 function and is suitable for the treatment of LRRK2-mediated diseases and conditions such as Parkinson's disease. [Prior Art] Millions of individuals suffer from neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and Huntington's disease. Parkinson's disease is a chronic progressive motor system condition in which approximately one in every 1,000 people is afflicted with this disease, and patients with hereditary Parkinson's disease account for 5-10% of all patients. Parkinson's disease is caused by progressive loss of midbrain dopaminergic neurons, impairing the ability of patients to direct and control their movements. The initial symptoms of Parkinson's disease are tremors, stiffness, slow movements, and impaired balance. Many patients with Parkinson's disease also experience other symptoms such as mood changes, memory loss, speech problems, and sleep disorders. The gene encoding the leucine-rich repeat kinase 2 protein (LRRK2) has been identified to be associated with hereditary Parkinson's disease (Paisan-Ruiz et al, Neuron, Vol. 44(4), 2004, pp. 595-600; Zimprich et al. Man, Neuron, Vol. 44(4), 2004, 60^607). In vitro studies have shown that Parkinson's disease-associated mutations result in increased LRRK2 kinase activity and reduced GTP hydrolysis rates compared to wild-type (Guo et al., Experimental Cell Research, Vol. 313(16), 2007, 3658-3670 page). Anti-LRRK2 antibodies have been used to label brain stems and Lewy bodies associated with Parkinson's disease and cortical antibodies associated with Lewy body dementia, suggesting that LRRK2 plays an important role in the formation and pathogenesis of Lewy bodies associated with these diseases ( Zhou et al., Molecular 156325.doc 201202215

Degeneration, 2006, 1:17 doi: 10.1186/1750-1326-l-17). LRRK2 has also identified another gene that is potentially associated with susceptibility to Crohn's disease and increased susceptibility to leprosy (Zhang et al., New England J. Med. Vol. 361 (2009), Page 2609-2618). LRRK2 is also associated with the conversion of mild cognitive impairment to Alzheimer's disease (WO2007/149789); L-dopa induced exercise difficulties (Hurley et al., Eur. J. Neurosci., 26th) Vol., 2007, pp. 171-177); CNS disorders associated with neuronal progenitor cell differentiation (Milosevic et al, Neurodegen, Vol. 4, 2009, p. 25); cancer, such as kidney cancer, breast cancer, prostate cancer, Blood cancer and lung cancer and acute myeloid leukemia (WO2011/038572); papillary renal and thyroid cancer (Looyenga et al, www.pnas.org/cgi/doi/10.1073/pnas.1012500108); multiple myeloma (Chapman et al) Human, Nature, Vol. 471, 2011, pp. 467-472); amyotrophic lateral sclerosis (Shtilbans et al, Amyotrophic Lateral Sclerosis " Early Online 2011, pp. 1-7); rheumatoid arthritis ( Nakamura et al., DNA Res. Vol. 13(4), 2006, pp. 169-183); and ankylosing spondylitis (Danoy et al, PLoS Genetics, Vol. 6(12), 2010, el 001195, 1st) -5 pages). Thus, compounds and compositions that are effective in modulating LRRK2 activity can provide treatment for diseases such as neurodegenerative diseases such as Parkinson's disease and Lewy body dementia; CNS disorders such as Alzheimer's disease and L-dopa induction Difficulties in exercise; cancer, such as kidney cancer, breast cancer, prostate cancer, blood cancer, papillary and lung cancer, acute myeloid leukemia and multiple myeloma; and inflammatory diseases such as leprosy, Crohn's disease, muscular atrophy Lateral cord sclerosis, 156325.doc 201202215 Rheumatoid arthritis and ankylosing spondylitis. In other words, there is a need for compounds having LRRK2 affinity that are more selective for mlrrk2 than other • chymase (such as JAK2) and which provide an effective drug for the treatment of neurodegenerative disorders such as Parkinson's disease. SUMMARY OF THE INVENTION The present invention provides a compound of formula I: R5

Or a pharmaceutically acceptable salt thereof, wherein: m is 0 to 3; X is .-NRa-; or _8(〇)", wherein 1> is 〇 to 2 and 1 is hydrogen or C 1_6 R1 is: Cj.6 院基'· c2.6 alkenyl; c2-6 block; halo-Cu alkyl; Ci-6 alkoxy-Cw alkyl; hydroxy-c26 alkenyl; _Ci6 alkyl 1 ' 6 alkylsulfonyl-Cw alkyl; Ch cycloalkyl-C 3_6 cycloalkyl-Cw alkyl substituted by Ci ό alkyl, as the C 3 6 cycloalkyl moiety The case is substituted by a q.6 alkyl group; tetrahydrofuranyl; tetrahydrofuranyl-C1_6 alkyl; oxetanyl; or oxetane-Cw alkyl; or ^^ together with the atom to which they are attached Up to a six-membered ring, which may optionally include another hetero atom selected from the group consisting of hydrazine, N and S, and which is substituted by a side oxygen 156325.doc 201202215 group, a halogen group or a Cw alkyl group; R2 is a halogen group; Ci-6 Alkoxy group; cyano 'C2-6 fast radical' C2-6 cation, halo-Ci-6 alkyl; halo-Cl-6 alkoxy, C3-6 cycloalkyl' wherein C3.6 ring burn The base moiety is optionally substituted by a C1-6 alkyl group; a C3-6 cycloalkyl group _Cl.6 alkyl group, wherein the C3_6 cycloalkyl moiety is optionally C. w alkyl substituted; tetrahydrofuran-yl; tetrahydrofuranyl-Cw alkyl; ethyl hydrazino; oxetanyl; or oxetane-Cw alkyl; R3: -OR4; halo; cyano; Cw alkyl; halo-Cw alkyl; C3_6 cycloalkyl substituted by <^, 6 alkyl; C3-6 cycloalkyl-Cw alkyl, wherein the C3-6 cycloalkyl moiety, as appropriate Substituted by cN6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Cw alkyl; oxetanyl; or oxetan-C alkyl; R4: Cw alkyl; halo-Cl_6 alkyl; oxy-Cw alkyl; Cw cycloalkyl substituted by ^^6 alkyl or halo; (: 3-6 cycloalkyl-c!-6 alkyl) wherein (: 3 6 cycloalkyl moiety The case is substituted by a Cl_6 alkyl group or a halogen group Q; a tetrahydrofuranyl group; a tetrahydrofuranyl-Cw alkyl group; an oxetanyl group; or an oxetane-Cu alkyl group; R5 is: hydrogen; or a Cl_6 alkyl group; η is 0 or 1; R is hydrogen, Cb6 alkyl; Cl 6 alkoxy _Ci 6 alkyl; hydroxyl a & thio, amino-Cw alkyl; Cw cycloalkyl; C3^ cycloalkyl _Ci 0 alkyl; heterocyclic; or heterocyclyl fluorene; wherein the C36 cyclos, k ring The benzyl-Cw alkyl group, the heterocyclic group and the heterocyclic decyl group are each optionally substituted by one, two or four groups independently selected from the group consisting of C16 alkane 156325.doc 201202215 dentyl-cv6 sleek; Oxyl group; dentate group - alkoxy group; trans group, hydroxy-Cw alkyl group; halo group; nitrile; Ci0 alkyl group - carbonyl group; c) 6 alkene continuation base; b ring alkyl group; a _Ci_6 alkyl group; a c3 6 cycloalkyl group; an amine group, an amine group, or a heterocyclic group; or two such groups together may form a five or six membered ring; the atom or R and R are attached thereto The nitrogen atom-formation includes three to seven-membered rings optionally selected from the group consisting of 〇, N and S(0)n, and the ring is optionally selected from the following, one, two or four Substituent substitution: 〇^-6 alkyl; halo-Cw alkyl; Ci-6 alkoxy; dentyl-Ci6 alkoxy; hydroxy, hydroxy-C].6 alkyl; halo, nitrile; Ci0 alkyl-carbonyl; Cw alkyl_% fluorenyl, C3.6 cycloalkyl; Cw cycloalkyl-Ci.6 alkyl; C3_6 cycloalkyl-carbonyl, amine, or heterocyclic; or two The groups may form a five or six membered ring together with the atoms to which they are attached; Functional group 'Ci_6 burn-yl; CU6 hospital group; a halogen group _ (^ 6-yl burning; group or a halogen group -Cw burn. Furthermore, the invention includes all optical isomers of the compounds of formula I, that is, diastereomers, diastereomeric mixtures 'exo-secure complexes, all/, corresponding enantiomers and/or Isomers are & solvates thereof. The present invention also provides pharmaceutical compositions containing such compounds, methods of using such compounds, and methods of preparing such compounds. [Embodiment] Definitions Unless otherwise stated, the following terms used in the present application (including the specification and the scope of the patent application) have the definitions given below. Note 156325.doc 201202215. The singular forms "a", "the" and "the" . When used alone or in combination with other groups, t: a group _ c=o-ch3 oxime group, when used alone or in combination with other groups, means consisting only of carbon and chlorine atoms and has 1 A monovalent straight or branched chain saturated smog portion of up to 12 carbon atoms. "Low-carbon alkyl" means an alkyl group having from one to six carbon atoms, that is, C!.6 alkyl. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl, t-butyl, t-butyl, pentyl, n-hexyl 'octyl, dodecyl And similar groups. "Alkenyl", when used alone or in combination with other groups, means a linear monovalent hydrocarbon radical having at least one double bond and having 2 to 6 carbon atoms or a branched chain monovalent hydrocarbon radical having 2 to 6 carbon atoms, ie CM alkenyl, such as vinyl 'propenyl and the like. Q "alkynyl" when used alone or in combination with other groups, means a straight-chain monovalent hydrocarbon group having at least one carbon bond and having 2 to 6 carbon atoms or a branched chain monovalent hydrocarbon group having 2 to 6 carbon atoms. That is, a C2 decynyl group such as an ethynyl group, a propynyl group, and the like. "Alkylene", when used alone or in combination with other groups, means a linear saturated divalent hydrocarbon group having up to a carbon atom, or a branched chain saturated divalent hydrocarbon group having 3 to 6 carbon atoms, such as a sub Methyl, ethyl, 2,2-dimethylexylethyl, propyl, 2-methylpropyl, butyl, pentyl and the like. 156325.doc 201202215 Alkoxy/alkyl〇Xy", when used alone or in combination with other groups, is used interchangeably as it is intended to mean a moiety of the formula _R, where r is the alkyl moiety as defined herein. Examples of the alkoxy moiety include, but are not limited to, methoxy, ethoxy, isopropoxy and the like. "Alkoxyalkyl", when used alone or in combination with other groups, means a moiety of the formula Ra-0-Rb- wherein Ra is alkyl and the milk is alkyl as defined herein, eg, Cw alkoxy Base-Cw alkyl. Exemplary alkoxyalkyl groups include, for example, 2-methoxyethyl, 3-methoxypropyl, methyl-2-methoxyethyl, 1-(2-decyloxyethyl)-3- Alkoxypropyl and i_(2-methoxyethyl 3-methoxypropyl. "Alkoxy-oxyl", when used alone or in combination with other groups, means the formula -OR-R' a group wherein r is an alkylene group and R• is an alkoxy group as defined herein. A "alkyl group", when used alone or in combination with other groups, means a moiety of the formula _C(0)-R Wherein R is an alkyl group as defined herein, for example, "alkyl-alkyl". "Alkoxy group", when used alone or in combination with other groups, means a radical of the formula _C(0)-R a group wherein R is an alkoxy group as defined herein, for example, ci6 alkoxy-alkyl. "Alkyl group", when used alone or in combination with other groups, means the formula -RC(0)- a group of R', wherein R is alkylene and R is alkyl as defined herein, for example Cw alkyl-carbonyl-(^.6 alkyl. "Alkoxycarbonylalkyl" is used alone or in combination with When other groups are combined, meaning a group of the formula -RC(0)-R, wherein R is alkyl and R is as defined herein 156325.doc -10- 201202215 alkoxy group, such as Ck alkoxy-carbonyl-Ci6 alkyl. "Alkoxycarbonylalkoxy", when used alone or in combination with other groups, means formula -0-RC a group of (0)-R', wherein R is an alkylene group and R1 is an alkoxy group as defined herein, for example, Cw alkoxy-carbonyl-Ci6 alkoxy. "Hydroxycarbonylalkoxy" is used alone. Or in combination with other groups, a group of the formula -R-C(0)-〇H, wherein R is alkyl as defined herein, for example, -Ci_6 alkoxy-carbonyl-〇H. "Alkylaminocarbonylalkoxy", when used alone or in combination with other groups, means a group of the formula -〇-RC(〇)-NHR', wherein R is alkyl and is as defined herein Alkyl. "A monoamine-based alkoxy group", when used alone or in combination with other groups, means a group of the formula -0-RC(0)-NR, R, wherein r is a stretch. Alkyl and R, and R" are alkyl as defined herein. "Acetylamino alkoxy" when used alone or in combination with other groups, means a group of formula -0-R-NHR' Wherein R is an alkylene group and R is an alkyl group as defined herein. "Hyperylamino-alkyloxy" when used alone or in combination with other groups, means a group of the formula -OR-NR'R' wherein R is an alkylene group and RI and RM are as "Alkylsulfonyl", when used alone or in combination with other groups, means a moiety of the formula -S〇2_R, wherein R is alkyl as defined herein, for example, a C6 alkyl group "Alkyl-heterocyclyl", when used alone or in combination with other groups, means a moiety of the formula C!.6 alkyl-R, wherein R is heterocyclyl as defined herein, 156325.doc -11- 201202215 WCw alkyl-heterocyclic group. "Alkylsulfonylalkyl", when used alone or in combination with other groups, means a moiety of the formula -R'-S〇2_R'', wherein R is alkyl and R, as defined herein. The base of the base is, for example, 匚丨-6 烧基基醯基_ζ^·6 yard base. "Alkylsulfonylalkoxy", when used alone or in combination with other groups, means a radical of the formula -0-RS〇2_R' wherein R is alkyl and R is an alkane as defined herein. base. "Amine", when used alone or in combination with other groups, means a moiety of the formula _NRR, wherein R and R are each independently hydrogen or a leuco group as defined herein. "Amine" thus includes "homo-based amine group" (wherein R and R, one of which is a hospital base and the other is hydrogen) and "dialkylamine group" (wherein the ruler and the ruler are both alkane) base). "Aminocarbonyl", when used alone or in combination with other groups, means a radical of the formula -C(0)-R, wherein R is an amine group as defined herein. "Huansterylamino", when used alone or in combination with other groups, means a moiety of the formula -NR-OR' wherein R is hydrogen or alkyl and R1 is a succinyl group as defined herein. "Acetylthio", when used alone or in combination with other groups, means a moiety of the formula _SR wherein R is alkyl as defined herein. "Aminoalkyl", when used alone or in combination with other groups, means a group -RR' 'wherein R' is an amine group and R is a stretching group as defined herein, eg, an amine group -C]_6 base. The "aminoalkyl group" includes an aminomethyl group, an aminoethyl group, a 1-aminopropyl group, a 2-aminopropyl group, and the like. The amine moiety of the "aminosyl" group may be substituted once or twice with an alkyl group to produce "alkylaminoalkane 156325.doc 12·201202215 base" and "dihydrolamine group", respectively. The "alkylamino group" includes methylaminomethyl, methylaminoethyl, methylaminopropyl, ethylaminoethyl and the like. The "dialkylaminoalkyl group" includes a di-, 2-aminomethyl group, a dimethylaminoethyl group, a dimethylaminopropyl group, an N-methyl-N-ethylaminoethyl group, and the like. "Amine alkoxy", when used alone or in combination with other groups, means the group -OR_R' where R' is an amine group and R is an alkylene group as defined herein. The "calcinyl amide" group, when used alone or in combination with other groups, means a moiety of the formula -NR'S〇2_R where the sizing is an alkyl group and R is a hydrogen or an alkyl group. "Aminocarbonyloxyalkyl" or "amine-mercaptoalkyl", when used alone or in combination with other groups, means a group of the formula _r_〇_c(〇)_nr,r,, wherein The oxime is an alkyl group and R', R" are each independently hydrogen or an alkyl group as defined herein. Alkynyl alkoxy", when used alone or in combination with other groups, means a radical of the formula -O-R-R' wherein R is alkyl and R is alkynyl as defined herein. ◎ "Aryl", when used alone or in combination with other groups, means a monovalent cyclic aromatic hydrocarbon moiety consisting of a monocyclic, bicyclic or tricyclic aromatic ring. The aryl group can be substituted as described herein. Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, nonyl, decyl, benzyl, pentyl, decyl, oxydiphenyl such as phenyl, fluorenyl diphenyl, amine Diphenyl, diphenylthio, diphenyl sulfonyl- phenylidene isopropyl, benzodioxanyl, benzofuranyl, benzodioxy, benzo. Bicyl, benzoxanthyl, benzoxazinone, benzobenzyl, stupid and stimulating, stupid and carbyl, stupid and morphine, methylenedioxyphenyl Ethyl dioxyphenyl and its analog group 156325.doc •13·201202215, which may be substituted as defined herein. "Arylalkyl" and "aralkyl", when used alone or in combination with other groups, are used interchangeably to refer to a radical of the meaning -RR, wherein Ra is a stretching group and Rb is an aryl group as defined herein. For example, an example of a phenylalkyl group such as a benzyl group, a phenethyl group, a 3-(3-chlorophenyl)-2-methylpentyl group, and the like is an arylalkyl group. "Arylsulfonate", when used alone or in combination with other groups, means a radical of the formula -S〇2_R, wherein R is aryl as defined herein. "Aryloxy", when used alone or in combination with other groups, means a radical of the formula __, wherein R is aryl as defined herein. "Aralkyloxy", when used alone or in combination with other groups, means a radical of the formula _ 〇-R-R| wherein R is alkyl and R is aryl as defined herein. "Carboxy" or "hydroxycarbonyl" is used interchangeably when used alone or in combination with other groups, which means a group of the formula -C(0)-0H. "Cyanoalkyl", when used alone or in combination with other groups, means the moiety of formula R, wherein R| is alkyl as defined herein and R is cyano or nitrile. "Cycloalkyl" When used alone or in combination with other groups, it means a monovalent saturated carbocyclic ring composed of a monocyclic or bicyclic ring, such as #c36 cycloalkyl. The particular cycloalkyl group is unsubstituted or substituted with an alkyl group. A cycloalkyl group can be substituted as defined herein, as appropriate. Unless otherwise defined, a cycloalkyl group may be optionally substituted with — or = substituents, wherein each substituent is independently employed, an alkyl group, an oxo group, a halo group, an i-form group, an amine group, a single-chamber amine. A base or a dialkylamino group. Rings 156325.doc • 14-201202215 Examples of alkyl moieties include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, decyl, cycloheptyl, and the like, including partial unsaturation thereof (ring Alkenyl) derivative. "裱alkylalkyl", when used alone or in combination with other groups, means a moiety of the formula -R'-R" which, R, is an alkylene group and R " is a cycloalkyl group as defined herein. For example, C3.6 cycloalkyl-Ck alkyl. "Cycloalkylalkoxy", when used alone or in combination with other groups, means a radical of the formula -0-R-R., wherein R is alkyl and R is cycloalkyl as defined herein. "Cycloalkylcarbonyl", when used alone or in combination with other groups, means a moiety of the formula -C(0)-R, wherein R is cycloalkyl as defined herein, for example. 3-6 soil base - several groups. "Heteroaryl", when used alone or in combination with other groups, means a monocyclic or bicyclic group having at least one aromatic ring and having 5 to 12 ring atoms, which contains one, two or three selected from N, 〇 or S ring heteroatoms, the remaining ring atoms are C, with the restriction that the point of attachment of the heteroaryl will be on the aromatic ring. The heteroaryl ring can be optionally substituted as defined herein. Examples of heteroaryl moieties include, but are not limited to, optionally substituted imidazolyl, oxazolyl, isotinosyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyrazinyl, Thienyl, stupid, thiophenyl, furyl, piperidyl. Pyridyl, tonyl, oxazolyl, pyrimidinyl, quinolyl, isoquinolyl, benzofuranyl, benzothienyl, benzothiopyranyl, benzimidazolyl, benzoxazolyl , benzoxanthyl, benzoxazolyl, benzoxadiazolyl, benzoxanyl, fluorenyl, isodecyl, triazolyl, triazinyl, quinoxaline, 156325 .doc -15- 201202215 嗓吟基'啥 琳 琳 喧, 喧 基 & & 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓Each of them may be substituted as appropriate as defined herein. When a human "heteroaryl" or "heteroaryl" is used alone or in combination with another group, it means a radical of the formula -RR, wherein the radical ''in the base is an alkyl group and r• is as defined Heteroaryl. "基基基基", when used alone or in combination with other groups, means a group of the entire formula S〇2_R, wherein R is a heteroaryl group as defined herein. "Heteroaryloxy", when used alone or in combination with other groups, means a radical of the formula - wherein, R is heteroaryl as defined herein. "Heteroaralkyloxy", when used alone or in combination with other groups, means a radical of the formula _O-R-R", wherein R is alkylene and RM is aryl as defined herein. The terms "halo", "halogen" and "halide" are used interchangeably when used alone or in combination with other groups and refer to a substituent of fluorine (F), chlorine (C1), bromine (8 =) or (I). . "Haloalkyl" when used alone or in combination with other groups, means that one or more hydrogens have been replaced with an alkyl group, as defined herein, of the same or different halo, such as halo-Ci.6 alkyl. In particular, it is a fluorine-Ci_6 alkyl group. Exemplary haloalkyl groups include -CHzCl, -C^CF3, -CHKCh, perfluoroalkyl (e.g., _CF3) and the like. 'Silver-based base', when used alone or in combination with other groups, means a moiety wherein R is a haloalkyl moiety as defined herein, for example, _yl-Ci-6 alkoxy. An exemplary haloalkoxy group is a difluorodecyloxy group. 156325.doc -16- 201202215 "Heterocyclic amine group" when used alone or in combination with other groups, means a saturated ring wherein at least one of the ring atoms is N, NH or N-alkyl and the remaining ring atoms form an alkylene group. . "Heterocyclyl" when used alone or in combination with other groups, means a monovalent saturated moiety consisting of one to three rings and incorporating one, two, three or four heteroatoms (selected from nitrogen, oxonium sulphur). A heterocyclyl ring can be as defined herein, as appropriate

generation. Examples of heterocyclyl moieties include, but are not limited to, as appropriate, substituted thiophene, sulfanyl, morphinyl, thiomorphinyl, azoxy, pyridyl, azetidin A group, a tetrahydrofuranyl group, a tetranitrocarbamate group, an oxetan group, and the like. The heterocyclic group may be as defined herein as a morpholinyl group, a piperidinyl group, an octahydropyridinium [...] pyrazinyl group, a diheterocyclic ketone group, a (tetra) group, a ridge group. , BTS base: diazepane, nitric acid, 2-oxa 6 heterooxa _3_aza-bicyclo[3.2.1] octyl. Specifically] heptyl, (tetra) and oxetane _ ke, piperidine _4 λ " m ^ Qin · 1 · base m bite small 4 · base, dinitrogen four: = ^ ^ miscellaneous, ring Γ 8 _ base, 2_oxa-5-nitro[2·2.1]heptane_5_yl-milk-5-aza epoxide heteroxyloxa _3_aza·bicyclo[3.2.1] 辛1 Base, 2_ base. #-螺叫庚-6-基, (四)-5-基和气环丁烧.3_ 156325.d〇, 17- 201202215 "Heterocyclylalkyl" when used alone or in combination with other groups means Part of the formula -R-oxime, wherein R is alkylene and R' is heterocyclyl as defined herein, eg, heterocyclyl-Cw alkyl. "Heterocyclyloxy", when used alone or in combination with other groups, is intended to be a moiety of the formula -OR, wherein R is heterocyclyl as defined herein. "Heterocyclylalkoxy", when used alone or in combination with other groups, is intended to be a moiety of the formula -OR-R| wherein R is alkyl and R' is heterocyclyl as defined herein. "Hydroxy", when used alone or in combination with other groups, means the group -OH. "Hydroxyalkoxy", when used alone or in combination with other groups, means a moiety of the formula -OR wherein R is hydroxyalkyl as defined herein. "Hydroxyalkylamino", when used alone or in combination with other groups, means a moiety of the formula -NR-R/ wherein R is hydrogen or alkyl and R; is a thiol group as defined herein. "Hydroxyalkylaminoalkyl", when used alone or in combination with other groups, means a moiety of the formula -R-NR'-R'', wherein R is alkylene, R' is hydrogen or alkyl, and R" is a hydroxyalkyl group as defined herein. "Hydroxycarbonylalkyl" or "carboxyalkyl" when used alone or in combination with other groups, means a radical of the formula -R-(CO)-OH, wherein R is a stretching group as defined herein. "Hydroxycarbonylalkoxy", when used alone or in combination with other groups, means a radical of the formula -0-R-C(0)-0H, wherein R is alkylene as defined herein. "Phenyloxy-based thiol" or "transalkyloxyalkyl" 156325.doc -18- 201202215 When used alone or in combination with other groups, the meaning _rc(〇)_ 〇r〇H2 groups, wherein each R is a stretching base and may be the same or different.

"Hydroxyalkyl" S, alone or in combination with other groups, means a thiol moiety as defined herein substituted by one or more (eg, one, two or three) hydroxy groups. - A broken atom does not carry more than one radical, such as a hydroxy-Cw alkyl group. Representative examples include, but are not limited to, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, hydrazine-(hydroxymethyl)-2-methylpropyl, 2-butyl 3, butyl, 4-butyl, 2,3-dipropyl, hydroxy-1-hydroxymethylethyl)-3-propyl. 2,3-Dihydroxybutyl, 3,4-dihydroxybutyl and 2-(hydroxy "carbocyclyl", when used alone or in combination with other groups, means a cycloalkyl moiety as defined herein. , one, two or three hydrogen atoms in the fluorene ring have been replaced by hydroxy substituents. Representative examples include, but are not limited to, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl or 4-hydroxycyclohexyl, and A similar group. "Alkoxy hydroxyalkyl" and "hydroxyalkoxyalkyl" are used interchangeably, alone or in combination with other groups, which means at least one substitution with a hydroxy group and at least one substitution with an alkoxy group. An alkyl group as defined herein. Thus, "alkoxyhydroxyalkyl" and "hydroxyalkoxyalkyl" encompass, for example, 2-hydroxy-3-methoxy-propan-1yl and the like. "Urea" or "ureido", when used alone or in combination with other groups, means a group of the formula "foot'-(:(〇) with 11'|11''', 11, 11, , and 111|, each independently hydrogen or alkyl. "Amino acid group" when used alone or in combination with other groups means 156325.doc •19- 201202215 Formula-0-C(0) -NR|R& A group in which Ri and R" are each independently hydrogen or an alkyl group. A "stable group", when used alone or in combination with other groups, means a group of the formula _0_c(0)_OH. 'Arylamino", when used alone or in combination with other groups, means a radical of the formula -S〇2_NR'R", wherein RI and the ruler, each independently hydrogen or alkyl. "Substituted as appropriate" When used in combination with an "aryl", "phenyl", "heteroaryl", "cycloalkyl" or "heterocyclyl" moiety, it means that the moiety is unsubstituted (ie, all open valence states are Substituted by a hydrogen atom or substituted with a specific group as referred to herein. "Leaving group" means a group having the meaning usually associated with its synthetic organic chemistry, that is, a substitutable atom or group under the substitution reaction conditions. Examples of leaving groups include, but are not limited to, _, alkanesulfonyloxy or arylsulfonyloxy, such as f alkanesulfonyloxy, ethanesulfonyloxy, thiomethyl , phenoxy, f phenyloxy and phenoxy, bis-aryl, optionally substituted f-oxy, isopropoxy, decyloxy and the like "Modulator" means the interaction with the target _ (but not limited to) agonists, antagonists and their two: nitrile or "cyano" as defined herein, alone or in combination with When the group is combined, it means that the group -C three N., "as appropriate" means that the subsequent events or circumstances mentioned in the stomach can occur but are not necessarily present, and the description includes the occurrence of the event or situation and the The event or situation does not occur. 156325.doc -20- 201202215 The condition and "disease condition" means any disease, condition, symptom, condition or indication. "Inert organic solvent" or "inert solution" % '明The bath is inert under the reaction conditions with which it is described as 5 strokes, including, for example, benzene, "benzene, acetonitrile, tetrahydrofuran, heart two?" Mercaptoamine, chloroform, dioxane, di-ethane, diethyl ether, ethyl acetate, acetone, methyl ethyl ketone, alcohol, ethanol, propanol, isopropanol, third _ drunk-cardane , pyridine and the like

Things. The inventive solvent is used unless otherwise stated. The solvent used in the context is "pharmaceutically acceptable" means that it can be used to prepare a pharmaceutical combination which is generally safe, non-toxic and which is biologically or otherwise undesirable and which is acceptable for veterinary and human medical use. The "pharmaceutically acceptable salt" of the composition means a salt which is pharmaceutically acceptable as defined herein and which has the desired pharmacological activity of the compound. It should be understood that All references to acceptable salts include solvent addition forms (solvates) or crystalline forms (polymorphs) as defined herein for the same acid addition salt. Suitable salts are produced with inorganic and organic acids. Examples are (but not limited to) acetic acid, citric acid, formic acid, fumaric acid, hydrochloric acid, lactic acid, maleic acid, malic acid, methanesulfonic acid, nitric acid, phosphoric acid, p-toluenesulfonic acid Sulfuric acid, sulphuric acid, tartaric acid, trifluoroacetic acid and the like, preferably citric acid, trifluoroacetic acid and hydrochloric acid. The term "pharmaceutically acceptable carrier" and "pharmaceutically Acceptable 156325.doc 21-201202215, such as a diluent or auxiliary substance, means a carrier and auxiliary substance which is compatible with the other ingredients of the formulation. The term "pharmaceutical composition" or "composition" A product comprising a predetermined amount or proportion of the specified ingredients, as well as any product obtained directly or indirectly from the combination of the ingredients, preferably the ingredients, preferably comprising - or a plurality of active ingredients and optionally a carrier (including a product of the inert component) and any combination or combination of any two or more components, or decomposed by - or a plurality of components, or directly or indirectly derived from other types of reactions or interactions of one or more components. Product. "Protecting group" means selectively blocking one of the polyfunctional compounds in a meaning generally associated with its synthetic chemistry such that the chemical reaction can be selectively carried out at another unprotected reaction site. Certain processes of the invention rely on protecting groups to block reactive nitrogen and/or oxygen atoms present in the reactants. The terms "amino protecting group" and "nitrogen protecting group" are used interchangeably herein and refer to such organic groups that are intended to protect the nitrogen atom from undesirable reactions during the synthetic procedure. Including, but not limited to, trifluoroethenyl, etidinyl, benzyl (Bn), benzyloxycarbonyl (CBZ), p-methoxybenzyloxycarbonyl, p-nitrooxyl, and third butoxy Carbonyl (BOC) and the like. Those skilled in the art will understand how to select a group for ease of removal and resistance to subsequent reactions. Solvates are meant to contain stoichiometric or non-stoichiometric amounts of solvent. a solvent addition form. Some compounds have a tendency to capture a solvent molecule that fixes a molar ratio in a crystalline solid state, thereby forming a solvate. If I56325.doc -22·201202215 1 is a solvent complex formed by κ贝] The substance is a hydrate; when the solvent is an alcohol, the cold composition is an alcoholate. The hydrate is formed by grouping one or more water molecules with a substance in which the water maintains the molecular state of H2, and the combination can form - or a plurality of hydrates. "Parkinson's disease" means damage to motor skills, speech and/or cognitive function, the central nervous system, and the degenerative system of the work system. Symptoms of Parkinson's disease can include, for example, muscle stiffness, tremors, slowing of body movements (slowness of movement), and loss of physical activity (exercise of movement). Lewy body disease is also known as "Leuphysical Abandonment", "Diffuse Lewy Body Disease", and "Cortical Lewy Body Disease", which means an anatomically characterized neurodegenerative disorder in the brain. "Individual" means mammals and non-mammals. Mammals mean any member of the Mammalia, including but not limited to humans; non-human primates such as black and other baboons and monkeys selling carp; farm animals such as cattle, horses, pontoon, goats And pigs; livestock, such as rabbits, dogs and drawings; experimental animals, sputum (four) dentate animals such as rats, mice and guinea pigs; and the like. Examples of non-mammals include, but are not limited to, birds and the like. The term "individual" does not indicate a particular age or gender. 'The term "half the maximum inhibitory concentration" is called. ) indicates the concentration of the specific compound required to obtain 50% inhibition of the in vitro biological process. The logarithm of 1〇50 is converted to the A5〇 value (-1〇g IC50), where the higher value indicates the exponentially larger efficiency. The IC5Q value is absolute, but depends on the experimental conditions used (10) such as concentration. The ic5G value can be used in the Cheng_Prus〇ff equation (then. _

Pharmac〇1. (1973) 22:3099) is converted to an absolute inhibition constant (5)). 156325.doc •23- 201202215 The language inhibitory constant (Ki) indicates the absolute binding affinity of a particular inhibitor to the receptor. It is measured using a competitive binding assay and is equal to the concentration at which a particular inhibitor will occupy 5% of the receptor in the absence of a competing ligand (e.g., a radioligand). The Ki value can be logarithmically transformed into a pKi value (i) ogKi), where a higher value indicates an exponentially large potency. By "therapeutically effective amount" is meant an amount of a compound which, when administered to an individual to treat a disease condition, is sufficient to effect treatment of the condition of the disease. The "therapeutically effective amount" will vary depending on the compound, the condition being treated, the severity of the condition being treated, the age and relative health of the individual, the route and form of administration, the judgment of the attending physician or veterinary practitioner, and other factors. When referring to a variable, the terms "as defined herein" and "as used herein" are used to encompass a broad definition of the variable and the preferred, preferred, and best definitions that may be present. The term "tetrahydrofuranyl-C1_6 alkyl", when used alone or in combination with other groups, means an alkyl-linked tetrahydrofuranyl group, as defined herein. The term "tetramethylenepyranyl-C1_6 alkyl" when used alone or in combination with other groups, is meant to mean a tetrahydrourethane group attached via a thiol group, as defined herein. When the π-oxaxyl-butane-Cl-6 alkyl group is used alone or in combination with other groups, it is intended to be a therapeutically effective amount of oxetane I as defined herein. The amount of a compound that is administered to an individual to treat a disease condition for a month to achieve treatment of the condition of the disease. "Treatment of the amount of treatment" will depend on the compound, the condition of the disease being treated, the degree of shouldering of the disease being treated, the age and relative health of the individual, the route of administration and the form, 156325.doc -24- 201202215 Attending physician or veterinarian The judgment of the industry and other factors change. When referring to a variable, the terms "the ones defined above" and "the ones defined in the text" are intended to cover the broad definition of the variables and the specific definitions that may exist. "Treatment" of a disease condition includes, inter alia, inhibiting the disease condition, i.e., preventing the development of the disease condition or its clinical symptoms, and/or alleviating the disease condition, i.e., causing the disease condition or its clinical symptoms to temporarily or permanently resolve.

❹ When referring to a chemical reaction, the terms "treatment", "contact" and "reaction" mean the addition or mixing of two or more reagents under appropriate conditions to produce the designated and/or desired product. It will be appreciated that the reaction to produce the specified and/or desired product may not necessarily be produced directly from the combination of the two agents initially added, that is, there may be one or more intermediates produced in the mixture which ultimately form the designation and/or Or the desired product. Nomenclature and Structure In general, the nomenclature and chemical names used in this application are based on CambridgeSoftTM's Chembi〇〇fficeTM. Any open valence state appearing on the carbon, H or nitrogen atom in the structure herein unless otherwise indicated indicates the presence of a hydrogen atom. If a heteroaryl ring containing nitrogen exhibits an open h @ such as Ra, Rb or Re on the nitrogen atom, the variables are displayed on the heteroaryl ring, and the variables may be combined or linked to the open valence gas. If there is a palm center in the structure but no specific stereochemistry is exhibited for the pair of palm centers, then the two enantiomers associated with the palmar phase are covered by the structure. The right γ U彳# is shown in the right text, and the structure can exist in multiple tautomeric forms, and all such tautomers are covered by the structure. The structure presented in this paper is 156325.doc -25- 201202215 The atom is now intended to cover all of these naturally occurring isotopes. Thus, for example, the enthalpy of the present invention is intended to include strontium and barium, and the carbon atom is intended to include the C13 and C14 isotopes. In this paper, the article (4) and the case of the public case are included in this article. Compounds of the Invention The present invention provides compounds of formula I:

Or a pharmaceutically acceptable salt thereof, wherein: m is 0 to 3; X is .-NR -,; or _8 (〇\_, wherein ^ is 〇 to 2 and ... is Ck alkyl; oxygen R is · <^.6 alkyl; C26 dilute; c26 alkynyl; halo Gw alkyl;

Cm alkoxy-Cl_6 alkyl; hydroxydecenyl; amine-Ci6 alkyl; ο, alkyl group _Cl-6 alkyl; C3·6 ring burned soil substituted by ^6 alkyl group as the case _ 3 6 alkylene-C κ, wherein the C3·6 cycloalkyl moiety is optionally substituted by C丨·6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Ci·6 alkyl; tetrahydropyran Tetrahydropyranyl-C1_6 alkyl; oxetanyl; or oxetane-Ci.6^; 156325.doc •26·201202215 or “and!^ together with the atom to which it is attached A three to six membered ring may be formed, which may optionally include another hetero atom selected from the group consisting of hydrazine, N and S, and substituted with a pendant oxy group, a dentate group or a Ci-6 alkyl group; R2 is a halo group; Cw alkane Oxy; cyano; c26 alkynyl; C26 alkenyl; halo-Cw alkyl; halo-C!.6 alkoxy; c36 cycloalkyl, wherein the C36 cycloalkyl moiety is optionally Cw alkyl Substituted; c3_6 cycloalkyl-Cw alkyl, wherein the C3.6 cycloalkyl moiety is optionally substituted with a C.6 alkyl group; tetrahydrofuranyl, tetrahydrofuranyl-C1-6 alkyl; ethyl hydrazino; oxetane An alkyl group; or an oxetane-Cw alkyl group; R3 is: -OR4; a halogen group; a cyano group; Cl_6 alkyl; halo-Cl6 alkyl; CM cycloalkyl substituted by MCw alkyl as appropriate; c3-6 cycloalkyl-Cw alkyl' wherein the C3-6 cycloalkyl moiety is optionally substituted by Cl-6 alkyl; Hydrofuranyl; tetrahydrofuranyl-Ci-6 alkyl; oxetanyl; or oxetane-Cw alkyl; R4: hydrogen; Cw alkyl; halo-Cw alkyl; Cw alkane Oxy-Cl 6 alkyl; optionally substituted by a ^6 alkyl or halo C3-6 cycloalkyl; c3_6 cycloalkyl-Cl-6 alkyl wherein the C:3·6 cycloalkyl Partially substituted by Cl6 alkyl or dentate; tetrahydrofuranyl; tetrahydrofuranyl-C!-6 alkyl; oxetan; or oxetane-Cm alkyl; R: hydrogen; or Ck Alkyl; η is hydrazine or 1; R6 is: hydrogen; Cw alkyl; Cw alkoxy-Cw alkyl; hydroxy-Cl 6 alkyl 'amino-Ci_6 alkyl; C3·6 cycloalkyl; 3.6 cycloalkyl-Cw alkyl; heterocyclyl; or heterocyclyl 6 alkyl; wherein the C3·6 cycloalkyl, c36 naphthenic 156325.doc -27-201202215 f-cw alkyl, heterocyclic and The heterocyclyl-Cw alkyl group may each be substituted with one, two or four groups independently selected from the group consisting of c]_6 alkyl; Base-c^alkyl; Ck6 alkoxy; dentate _Ci6 alkoxy, perylene, light-based -Cl.6 alkyl; dentate; nitrile, · C. 6.6 alkyl-based; Cl .6 alkyl group _ sulfonyl; c3-6 cycloalkyl '· c 3-6 cycloalkyl _Ci-6 alkyl; C 36 cycloalkyl-carbonyl, amine, or heterocyclic; or two of these The group may form a five- or six-membered ring together with the atom to which it is attached; or R and R together with the nitrogen atom to which it is attached may form three to optionally include another hetero atom selected from the group consisting of 〇, N and S(0)n. a seven-membered ring, and the ring is optionally substituted with one, two, three or four groups independently selected from the group consisting of: ci 6 alkyl; halo-C!.6 alkyl; Cl.6 alkoxy; south Alkyl-Ci_6 alkoxy; hydroxy; hydroxy-Cw alkyl; halo; nitrile; Ci 6 alkyl-carbonyl; Cw alkyl sulfonyl; C3.6 cycloalkyl; Cw cycloalkyl _cN0 alkyl Cw cycloalkyl-carbonyl; amine; Cw alkyl·heterocyclyl; Cl-6 alkoxy_Ci_6 alkyl or heterocyclic; or two such groups together with the atom to which they are attached may form five or six A member ring; and 'R7 is: halo; Cw alkyl; Cw alkoxy; halo-Ci 6 alkyl; or halo-Cw alkoxy. The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof, wherein: m is 0 or 1, X is:, NRa- or -0-, wherein Ra is hydrogen; R1 is: Cw alkyl; halo- Cw alkyl; (^_6 alkoxy _(^-6 alkyl. Ci·6-based thiol-Cm alkyl; optionally substituted by c1-6 alkyl -28- 156325.doc 201202215 alkane a C3-6 cycloalkyl-C:·6 alkyl group, wherein the c3 6 cycloalkyl moiety is optionally substituted with a tetrahydrofuranyl group; tetrahydrofuranylalkyl; tetrahydropyranyl; tetrahydropyranyl-( : 丨 _ 6 alkyl; or R 1 and Ra together with the atom to which they are attached may form a three to six membered ring, which may optionally include another hetero atom selected from fluorene and N; R 2 is: halo; C! 6 alkoxy; cyano; Cl_6 alkynyl; halo-Cw alkyl; c: 3·6 cycloalkyl; ο: 3.6 cycloalkyl-Cl6 alkyl, wherein the c36 cycloalkyl moiety is optionally Indenyl substitution; ® R is: -OR4; halo; Cl 6 alkyl; cycloalkyl; R is hydrogen, C!·6 alkyl; halo-Ci 6 alkyl; optionally via c3 6 ring Alkyl-C -6 alkyl substituted (33.6 cycloalkyl; R5 is: hydrogen or Cw alkyl; η is 0 or 1; R is hydrogen, Cw alkyl; Cw alkane _C 6 alkyl; hydroxy-Ci 6 alkyl; amino-Cw alkyl; (: 36 cycloalkyl; C 3 6 cycloalkyl-Ci 6 alkyl; hetero Q fluorenyl, or heterocyclyl _Cl a 6 alkyl group; wherein the c3_6 cycloalkyl group, <:3-6 cycloalkyl-Cw alkyl group, heterocyclic group and heterocyclic group -Ci ealkyl group may each be one, one, two or four Substituents independently selected from the group consisting of Ci_6 alkane-yl; ifi-based and nitrile; or R5 and R6, together with the nitrogen atom to which they are attached, form, as the case may be, three to one selected from the group consisting of hydrazine and another hetero atom of N. a seven-membered ring, and the ring is optionally substituted with one, two, three or four groups independently selected from the group consisting of: CM alkyl; _ yl-Cl. 6 alkyl; Ci. 6 alkoxy; hydroxy; hydroxy -Cl_6 alkyl; dentate; nitrile; Cw alkyl-carbonyl; Ci_6 alkyl sulfonyl; cw cycloalkyl, cw ring 156325.doc -29· 201202215 alkanoyl-c^.6 alkyl; The atom of the heterocycle - which may form a penta or hexaalkyl-carbonyl group; a Ci.6 alkyl-heterocyclyl group; a c group; or two such groups to which a ring is attached; and R is a halo group or Ci -6 alkoxy. A scientifically acceptable salt thereof. The present invention provides a compound of formula I or a physician thereof Medium: m is 〇 or 1, X is -NH- or -Ο-, R is C 1 _6 alkyl; R is halo, cyano or halo-C1-6 alkyl; R3 is -4 ft 4 or R is a Ci.6 alkyl group; R is chlorine; η is hydrazine; R6 is an alkyl group; or R and R together with the nitrogen atom to which they are attached form an N-morpholinyl ring; and R7 is a halogen group or Ci_6 Alkoxy. The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof wherein: m is hydrazine or 1, X is -NH- or -〇-, R is methyl or ethyl; R2 is Cl, CN or trifluoromethyl R3 is C1, methoxy, ethoxy or isopropoxy; 156325.doc • 30. 201202215 R5 is hydrogen; n is 0; R6 is a tertiary butyl group; or R5 and R are attached to the nitrogen The atoms together form an N-morpholinyl ring; and R7 is F or a decyloxy group. - The invention further provides a compound of formula I: R5

Or a pharmaceutically acceptable salt thereof, wherein: m is 0 to 3; X is: -NRa-; ; or _s(〇)r•, wherein to 2 and the ruler & is hydrogen or

Ci_6 alkyl, R1 is: Ck alkyl; C26 alkenyl; c26 alkynyl; halo 6 alkyl; Cu alkoxy-Cw alkyl; hydroxy-C26 alkenyl; amine-Ci 6 alkyl; *6 Alkyl-Cw alkyl; Cw cycloalkyl substituted by C1-6 alkyl; C3-6 cycloalkyl-Cl.6 alkyl, wherein the C36 cycloalkyl moiety is as appropriate (: a 6-alkyl group; tetrahydrofuranyl; tetrahydrofuranyl-C1-6 alkyl; oxetanyl; or oxetane-C1,6 alkyl; or R1 and Ra together with the atom to which they are attached a three- to six-membered ring, which optionally includes another hetero atom selected from the group consisting of hydrazine, N and S, and which is substituted with a side oxygen 156325.doc • 31-201202215 group, a halo group or an alkyl group; R2 is a leuco group; C 1 - 6 1 1 oxy 'nitro group, 〇 2-6 fluorenyl group, C 2-6 azo group; halo-Ck alkyl group; halo-Cw alkoxy group; 〇 3-6 cycloalkyl group C3.6 The cycloalkyl moiety is optionally substituted by Ci.6 alkyl; <:3·6 cycloalkyl-Cw alkyl, wherein the C3-6 cycloalkyl moiety is optionally substituted by Ck alkyl; tetrahydrofuranyl; Hydroquinone-Cl-6 leucoyl; acetate; oxetan; or oxetane-Cuane R3 is: -OR4; halo; cyano; Ci.6 alkyl; halo-Cw alkyl; C3·6 cycloalkyl substituted by ^^6 alkyl; C36 cycloalkyl_Ci_6 ^基' wherein the C3·6 cycloalkyl moiety is optionally substituted by Cw alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C-6 alkyl; oxetanyl; or oxetane- Ci-6 alkyl; R4 is · CK6 alkyl; halo-Cw alkyl; Cl_6 alkoxy-Cm alkyl; optionally substituted by 31_6 alkyl or halo (: 3-6 cycloalkyl; c3 .6cycloalkyl-alkyl, wherein the C:3·6 cycloalkyl moiety is optionally substituted with a C 6 alkyl or halo group; tetrahydrofuranyl; tetrahydrofuranyl-C16 alkyl; oxetanyl; or oxygen Heterocyclic butane-Cw alkyl; R5 is: hydrogen; or Cw alkyl; η is 0 or 1; R6 is hydrogen; c!.6 alkyl; Cw alkoxy_Cl 6 alkyl; Ci 6 alkyl; amino-Cw alkyl; c3-6 cycloalkyl; c36 cycloalkyl-Ci 6 alkyl; hetero- or di-hetero-C!-6 alkyl; wherein (33_6 ring The alkyl group, the c3_6 cycloalkyl-C!.6 alkyl group, the heterocyclic group and the heterocyclic group -Ci 6 alkyl group may each independently be selected from the following by one, two, three or four Group substitution: C16 alkane 156325.doc • 32- 201202215 2 halo c "6 alkyl '. "alkoxy; halo _c " alkoxy, hydroxy: ke-Cl-6 yard; teeth a nitrile; a Ci6 alkyl group, a benzyl group, a C3.6 cycloalkyl group; a C34 alkyl ruthenium group; a ring-based base, an amine group, an amine group; or a heterocyclic group; or two such groups The group may form a five or six member ring; the atom or R and R and the nitrogen atom to which it is attached __(iv) optionally include three selected from the group consisting of ruthenium, one N and S (0> Up to seven members of the ring, and the situation

Substituted by two, three or four groups independently selected from the following: · Cl.6 炫基;; _ base _ €: 1-6 alkyl; Cl · 6 morphoxy; dentate - Cw courtyard oxygen hydroxyl-silk-Cw alkyl; self-based; nitrile; Ci6 alkyl group; cw syllabary _ «yl; cardinyl; C3_6 I base% base; & cycloalkyl-based Or an amine group; or a heterocyclic group; or two such groups together with the atom to which they are attached may form a five or six membered ring; and R is a halo group; a Cw alkyl group; a Cl 6 alkoxy group; _Ci6 alkyl; or halo-c _6 alkoxy. In certain embodiments of Formula I, η is 〇. In certain embodiments of Formula I, n is one. In certain embodiments of Formula I, Ri and ... together with the atoms to which they are attached may form a three to six membered ring optionally including another hetero atom of hydrazine, N&s, and may optionally be side oxygen Substituted, functional group or Ci6 alkyl substituted. In certain embodiments of Formula I, R1 and 1^ together with the atom to which they are attached form a five or six membered ring. In certain embodiments of the formula ’, R1 and Μ together with the atoms to which they are attached form a ratio of a bite, a bite, or a 唆. 156325.doc • 33· 201202215 In certain embodiments of Formula 1, R 2 is ethyl hydrazide. In certain embodiments, the compounds of the invention have the formula II:

Or a pharmaceutically acceptable salt thereof, wherein X, m, R1, r2, R3, R5 and R7 are as defined in formula I. In certain embodiments, the compounds of the invention have the formula II:

Or a pharmaceutically acceptable salt thereof, wherein: m is 0 to 3; X is · _NR _ ; or -s(〇)r-, wherein r is 0 to 2 and Ra is a hydrogen bite C 1-6 alkyl group 3 R1 is .Cw alkyl; C26 alkenyl; C26 alkynyl; halo-Cw alkyl; Cl-6 alkoxy_Cl.6 alkyl; hydroxy-C2-6 alkenyl; amino-Cw alkyl; Ci 6 alkylsulfonyl-C!·6 alkyl; cycloalkyl substituted by €16 alkyl as appropriate; C3-6 cycloalkyl-Cl 6 alkyl group, wherein the C3 6 cycloalkyl moiety is optionally Substituted by Cw alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Cw alkyl; oxetane, or oxetane-Ci-6 alkyl; 156325.doc -34· 201202215 R2 is: halo; Ci .6 gas-burning group, cyano group; C2-6 fast group; C2-6 thin group; halo-Ci.6 alkyl group; halo-Cw alkoxy group; C3-6 cycloalkyl group, wherein the c3.6 The cycloalkyl moiety is optionally substituted by Cw alkyl; C3-6 cycloalkyl-Cw alkyl, wherein the C3-6 cycloalkyl moiety is optionally substituted by Cw alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C !·6 alkyl; oxacyclobutane; or oxetane-Cw alkyl; R3 is: -OR4; halo; cyano; optionally substituted by Ci-6 alkyl group, C ring burn C3·6 cycloalkyl-Ci_6 leuco, wherein the C3_6 cycloalkyl moiety is optionally substituted by C!·6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Cu alkyl; oxetanyl; or oxa Cyclobutane-Cn.6 alkyl; ft. (31-6 alkyl, halo-(31.6 alkyl; (^1-6 calcination 1 oxy-匸1-6 alkyl; depending on the situation) _6 alkyl substituted (: 3-6 cycloalkyl; C3. 6 cycloalkyl-Ck alkyl, wherein the C3-6 cycloalkyl moiety is optionally substituted by Cl-6 alkyl; tetrahydromanganyl; tetrahydrofuranyl-Cw Alkyl; oxetanyl; or oxetan-Ci_6 alkyl; R5: hydrogen; or Cw alkyl; R6: hydrogen; Cw alkyl; (^.6 alkoxy_cN6 alkane alkyl-cK6-form; C3.6 cycloalkyl; C3-6 cycloalkyl-Cl-6 alkyl; heterocyclyl; or heterocyclyl-Ck alkyl; wherein <:3_6 cycloalkyl, The CM cycloalkyl-Cl_6 alkyl group, the heterocyclic group and the heterocyclic group-Cw alkyl group may each be optionally substituted by one, two or three groups independently selected from the group consisting of Ci0 alkyl; halo-Ci· 6 alkyl; Cu alkoxy; halo-Cl_6 alkoxy; hydroxy; hydroxy-Ci_6 alkyl; halo; nitrile; cN6 alkyl-subunit Ci 6 alkyl group; c3_4 alkyl group; C3-6 cycloalkyl-Cw alkyl group; G: 36 cycloalkyl group-carbonyl group; amine group; or heterocyclic ring 156325.doc • 35-201202215 can form five Or a hexa group; or two of the atoms to which the group is attached; and 'and R and the nitrogen atom to which it is attached are formed as appropriate, including another one selected from the group consisting of, N and S(0)n a three to seven-membered ring of an atom, and the ring is optionally substituted by one or two groups of two genomic groups: c丨-6 alkyl 1 group 4-6 alkyl; c "6 oxygenated Base; tooth base 々6 alkoxy; base group base; self-base; nitrile; & burnt base- Li; Ci6 base _ only eat soil C3.6J clothing base, c3 j yard base _c "6 alkyl; c% 6 cycloalkyl-mono-amino" or heterocyclic; < two base groups together with the atom to which they are attached form a five or six membered ring; and a halo group, Cl • 6 alkyl; C!. 6 alkoxy; halo-c1-6 alkyl; or halo-Ck alkoxy. In certain embodiments of Formula 1, when R1 is (: 3-6 cycloalkyl or c3-6 cycloalkyl-Ck alkyl, then 乂 is _〇_. In certain embodiments of Formula I, when R1 is When cyclopropyl, cyclobutyl, cyclopropyl-Cualkyl or cyclobutyl-Cw alkyl, X is _〇_. In certain embodiments of formula I or formula II, the melon is 〇 to 2 In certain embodiments of Formula I or Formula II, 111 is 〇 or 1. In certain embodiments of Formula I or Formula II, @ is 〇. In certain embodiments of Formula I or Formula II, 111 is 1. In certain embodiments of Formula I or Formula II, r is 〇. In certain embodiments of Formula I or Formula II, r is 2. In certain embodiments of Formula 1 or Formula 11. X is -NRa- or -0-. In certain embodiments of Formula I or Formula II, X is _NRa_. 156325.doc • 36 - 201202215 In certain embodiments of Formula 1 or Formula 11, x In some embodiments of Formula 1 or Formula 11, X is -s(o)n-. In certain embodiments of Formula 1 or Formula 11, X is -NH- or -0- In certain embodiments of Formula I or Formula II, Ra is hydrogen. In certain embodiments of Formula I or Formula II, Ra is Ci 6 alkyl. In certain embodiments of Formula I or Formula II , Ri is: Cl-6 alkyl; halo-Cw alkyl; Cl-6 alkoxy_Ci6 alkyl; amine-Ci6 alkyl; Ci6 alkyl Q aryl-Cl-6 alkyl; C3-6 naphthenic Or a C3-6 cycloalkyl-Cw alkyl group. In certain embodiments of Formula I or Formula II, R1 is: Cl-6 alkyl; optionally substituted by a Cl.6 alkyl group; or c3_6 a cycloalkyl-Cl-6 alkyl group wherein the C:3-6 cycloalkyl moiety is optionally substituted with a Ci6 alkyl group. In certain embodiments of Formula I or Formula II, it is: a cl 6 alkyl group; _Cw alkyl; Cw alkoxy _Cl6 alkyl; amine _Ci6 alkyl; ci6 alkyl fluorenyl-C!-6 alkyl; tetrahydrofuranyl; tetrahydrofuranylalkyl; oxetanyl Or oxetane-C16 alkyl. In certain embodiments of formula I or formula 11, R1 is: Cw alkyl; i-group-

Cw alkyl, Cw alkoxy-Cl6 alkyl; amine-Ci6 alkyl; or Cw alkylsulfonyl-CN6 alkyl. In certain embodiments of formula I or formula II, R1 is Ci 6 alkyl. In certain embodiments of formula I or formula II, R1 is haloalkyl. In certain embodiments of Formula I or Formula II, Han 1 is a 〇16 alkoxy-Ci 6 alkyl group. In certain embodiments of formula I or formula II, R1 is amino-Ci6 alkyl. In certain embodiments of formula I or formula II, R1 is optionally substituted by Ci6 alkyl, -37-156325.doc 201202215, Ck alkyl fluorenyl-Cw alkyl. In certain embodiments of formula I or formula II, R1 is c3_6 cycloalkyl substituted by Ci.6 alkyl as appropriate. In certain embodiments of formula I or formula II, ... is a 6 cycloalkyl group, wherein the C3-6 cycloalkyl moiety is optionally substituted with a ci 6 alkyl group. In certain embodiments of formula I or formula II, R1 is tetrahydrofuranyl. In certain embodiments of formula I or formula II, R1 is tetrahydrofuranyl-C丨6 alkyl; oxetane. In certain embodiments of formula I or formula II, R1 is oxetane-(^^alkyl. In certain embodiments of formula Ϊ or formula II, Ri is: fluorenyl; ethyl; Propyl; isopropyl; isobutyl; 3,3-dimethylpropyl; cyclopropyl; cyclobutyl; cyclodecyl; cyclohexyl; cyclopropyl fluorenyl; cyclobutylmethyl; cyclopentyl hydrazine a group; a cyclopropylethyl group; a methoxyethyl group; an oxetanyl group; or a tetrahydrofuryl fluorenyl group. In certain embodiments of formula I or formula II, 'R1 is: methyl; ethyl; Propyl; isopropyl; isobutyl; 3,3-dimethylpropyl; cyclopentyl; cyclohexyl; cyclopropylmethyl; cyclobutylmethyl; cyclopentyl fluorenyl; cyclopropylethyl; Methoxyethyl; oxetanyl; or tetrahydrofuranylmethyl. In certain embodiments of Formula I or Formula II, Ri is: methyl; ethyl; n-propyl, isopropyl, iso Butyl; 3,3-dimethylpropyl; cyclopentyl; cyclohexyl; cyclopentylmethyl; methoxyethyl; oxetanyl; or tetrahydrofuran 11-n-methyl. In certain embodiments of Formula I or Formula II, ' Ri is: fluorenyl; ethyl; n-propyl 156325.doc - 38· 201202215, isopropyl; or isobutyl. In certain embodiments of formula I or formula II, R1 is methyl or ethyl. In certain embodiments of formula I or formula II, R1 is In certain embodiments of Formula I or Formula II, R1 is ethyl. In certain embodiments of Formula I or Formula II, R1 is: cyclopropyl; cyclobutyl; cyclopentyl; Hexyl; cyclopropylmethyl; cyclobutylhydrazino; cyclopentylfluorenyl; or cyclopropylethyl. In certain embodiments of formula I or formula II, R1 is: cyclopentyl; cyclohexyl; Or cyclopentylmethyl. In certain embodiments of Formula I or Formula II, R2 is: halo; Cw alkoxy, dentate-Ci-6 alkyl; dentate-Ci.6 alkoxy a C3-6 cycloalkyl group, wherein the c3.6 cycloalkyl moiety is optionally substituted by a Cw alkyl group; C3.6 cycloalkyl-C, Λalkyl' wherein the C3·6 cycloalkyl moiety is optionally Cw alkyl substituted; tetrahydrofuranyl; tetrahydrofuranyl-Cu alkyl; oxetanyl; or oxetan-Ci_6 alkyl. In certain embodiments of formula I or formula II, R2 is: halo Base; Cy alkoxy, functional group - Ci-6 alkyl; aryl, C2-6 fast radical, C2-6 thin base, C3-6 ring Or C3.6 cycloalkyl-Cl.6. In some embodiments of formula I or formula II, R2 is: halo; Cm alkoxy; halo-Ci.6 alkyl; cyanide a C3-6 cycloalkyl group; or a C3-6 cycloalkyl group, A-decyl group. In certain embodiments of Formula I or Formula II, R2 is: halo; C1-6 alkoxy; halo Alkyl-Ci.6 alkyl; C3.6 cycloalkyl; or C3-6 cycloalkyl-Cw alkyl. In certain embodiments of Formula I or Formula II, 'r2 is: halo; halo-Cy Alkane 156325.doc 39·201202215 base; or cyano group. In style! Or in some embodiments of the formula, the inverse 2 is: a group; or a dentate a group. , R is a halogen group. 'Alkoxy. 'R2 is i-Cw alkoxy. 'R2 is a halo-CN6 alkyl group. 'R2 is a C3-6 cycloalkyl group. R is a C3-6 peralkyl-Ci.6 hospital in certain embodiments of Formula I or Formula II in certain embodiments of Formula I or Formula II in certain embodiments of Formula I or Formula II. Certain embodiments of Formula I or Formula II are in certain embodiments of Formula I or Formula II in certain embodiments of Formula I or Formula II. In certain embodiments of Formula J or Formula, R 2 is a tetrachabitanyl group. In certain embodiments of Formula Ϊ or Formula II, 2 * 卜 - r R is tetrahydrofuranyl-Cualkyl. In certain embodiments of formula I or formula, R2 is oxetanyl. In style! Or in certain embodiments of the formula, R 2 is oxetane 6 burned R 2 is halo, trifluoromethyl or cyanide R 2 is chloro, trifluoromethyl or cyanide in certain of formula I or formula II In the examples, the base. In certain embodiments of Formula I or Formula 11, base 0 In certain embodiments of formula I or formula II, R2 is fluoro, chloro or bromo. In certain embodiments of Formula I or Formula II, r2 is chloro. In certain embodiments of formula I or formula II, R2 is fluoro. In certain embodiments of Formula I or Formula II, r2 is indifferent. 156325.doc • 40-201202215 In certain embodiments of formula I or formula II, R2 is trifluoromethyl. In certain embodiments of formula I or formula II, R2 is methoxy. In certain embodiments of formula I or formula II, R2 is cyano. In certain embodiments of formula I or formula II, R2 is C2_6 alkynyl. In certain embodiments of formula I or formula II, R2 is a C2_6 dilute group. In certain embodiments of Formula I or Formula II, R3 is _0R4. In certain embodiments of formula I or formula II, 'R3 is: Cl 6 alkyl; or halo-Ci-6 alkyl. In certain embodiments of formula I or formula II, R3 is: halo; or -OR4. In certain embodiments of formula I or formula II, R3 is: halo; Cl.6 alkoxy; dentyl-hydrazine-6 alkoxy; C3-6 cycloalkoxy; or c3.6 naphthenic Base-Cw alkoxy. In certain embodiments of Formula I or Formula II, 'R3 is: Cl-6 alkoxy; halo-C!-6 alkoxy; C: 3·6 cycloalkoxy; or C: 3·6 naphthenic Alkyl-Ci6 alkoxy group. In certain embodiments of Formula I or Formula II, R3 is: halo; Cl-6 alkoxy, cyano, or halo-C!.6 alkoxy. In certain embodiments of Formula I or Formula II, R3 is halo; Cl-6 alkoxy, or halo-Ci.6 alkoxy. In certain embodiments of formula I or formula II, R3 is: methoxy; halo; trifluoromethoxy; difluoromethoxy; 2-halo-ethoxy or 2,2,2- Tri-based ethoxy group. In certain embodiments of formula I or formula II, R3 is: methoxy; or halo. In certain embodiments of formula I or formula II, R3 is: methoxy; chloro; or fluoro. 156325.doc -41- 201202215 In certain embodiments of formula I or formula II, r3 is methoxy. In certain embodiments of Formula I or Formula II, R3 is a gas. In certain embodiments of Formula I or Formula II, ' R3 is fluoro. In certain embodiments of Formula I or Formula II; or -oxy. 4. CM Emulsion, Cyanide In some embodiments of Formula I or Formula II, the oxy group. Oxy; or halogen R3 is cK6 alkoxy. R3 is a decyloxy group. R is a cyano group. R3 is a c3_6 cycloalkyl group. R is a C3.6 cycloalkyl group. In certain embodiments of Formula I or Formula II, in certain embodiments of Formula I or Formula II, in certain embodiments of Formula I or Formula II, in Formula I In some embodiments of the formula or formula, in some embodiments of Formula I or Formula II. In certain embodiments of η, 'r3 is tetrahydrofuranyl. In certain embodiments of formula 或 or formula, r3 is tetrahydroc-butyl 4 alkyl. In certain embodiments of the formula or formula, R3 is a heterocyclic butanyl group. In certain embodiments of Formula 1 or Formula 11, R3 is an oxocyclohexyl group. In certain embodiments of Formula I or Formula II, Han 4 is a U-storm;

Ci• and base; Cl_6 methoxy-Cl·6 alkyl; h cycloalkyl; 3·6瓖 for base-Ci.6 alkyl. In certain embodiments of Formula I or Formula II, R 4 is ···Cl 6 alkane; —碁—C—-6 alkyl; or (: 3-6 cycloalkyl. Certain embodiments of Formula I or Formula II In certain embodiments, R4 is C1 6 burned. 156325.doc -42· 201202215 t In some embodiments of Formula 1 or Formula, R4 is a dentate to a burnt group. In certain embodiments of Formula 或 or Formula U In certain embodiments of Formula 1 or Formula U, 〜3-6cycloalkyl. In certain embodiments of Formula or Formula, R4 is a cycloalkyl group. In certain embodiments of the formula, R4 is tetrahydrofuranyl.

In style! Or in the formula: in some embodiments of the alpha, tetrachlorosinhosyl 6 alkyl. In certain embodiments of Formula I or Formula, Han 4 is an oxetan group. In certain embodiments of formula I or formula, R4 is oxetane. In certain embodiments of formula I or formula U, the ruler 4 is: methyl; ethyl; isopropyl; cyclopropyl; cyclobutyl; cyclopropylcyclobutylmethyl; 2-functional ethyl; Or 2,2,2-trihaloethyl. In certain embodiments of formula I or formula II, R4 is methyl. In certain embodiments of Formula I or Formula II, R5 is a gas. In certain embodiments of Formula I or Formula π, r5 is Ci 6 alkyl. In certain embodiments of formula I or formula II, R5 is methyl. In certain embodiments of Formula I or Formula II, R5 is ethyl. In certain embodiments of Formula I or Formula II, R6 is a gas. In certain embodiments of Formula I or Formula π, r6 is ci 6 alkyl. In certain embodiments of Formula I or Formula II, ' R6 is a Cl-6 alkoxy_Cl-6 alkyl group. I56325.doc • 43- 201202215 In certain embodiments of formula I or formula II, R6 is hydroxy-C16 alkyl. In certain embodiments of formula I or formula II, R6 is amino-C16 alkyl. In certain embodiments of Formula I or Formula II, R6 is C3 6 cycloalkyl, which is optionally substituted with one, two or three groups independently selected from the group consisting of: dentyl-Cw亮基;Cl_6 alkoxy; halo-Ci 6 alkoxy, hydroxy 'light group-C!.6 alkyl; _ group; nitrile; c16 alkyl _ group; Ci6 yard _ sulfonyl; Cw cycloalkyl; C: 3 6 cycloalkyl-Ci 6 alkyl; c36 cycloalkyl-carbonyl; amine; or heterocyclic; or two such groups together with the atom to which they are attached may form five or Six-member ring. In certain embodiments of formula I or formula II, R6 is c3 6 cycloalkyl- to 16 alkyl wherein the C3-6 cycloalkyl moiety is taken as one, two or two separate groups as appropriate a group; a halogenated alkoxy group, a south base-Cu alkoxy group; a mesogenic m_Ci6 group; a halogen group; a nitrile 'Cu alkyl group · (4); a Ci6 alkyl group; a gamma group; a h ring group; a C3j group CL6 hospital base; C3.6 cycloalkyl group _ a few base; position; or heterocyclic group; or rain these groups and their connected atoms - can form five or six in the formula! Or in the examples of the formula, wherein the heterocyclic group, the heterocyclic ring, cyclobutanyl group, the base group, the bottom bite group, the sulfinyl group; the molybdenum 'Marlinyl; 3 · oxa-8-nitrogen Hetero-bicyclo[3·2 u-xin 8 US· 2_ == ring [2.2.1] heptyl I-[oxa]-diazepine is in the doped; as defined herein, it is optionally substituted. f is the formula of the heterozygous base! Or in an embodiment of formula η, the heterocycloalkyl...pyrrolidyl;piperidinyl;piperazinyl; or < 〆- as defined herein is optionally substituted, ie, lenyl' = 1 ° 杂 % 基 鲹 鲹 156325.doc • 44· 201202215: one or two groups independently selected from the following: c " alkane, -Cl · 6 alkyl; Cw alkoxy; dentate - Ci6 Alkoxy; hydroxy; alkoxy; alkyl; alkyl; a hydrazide; a hydrazin; a hydrazine; a hydrazine; a hydrazine; a hydrazine; .6 cycloalkyl-(^-6 alkyl; C3.6 cycloalkylcarbocarbyl 'amine, or heterocyclyl; or two such groups may form a five or six membered ring from the atom to which they are attached And R&lt One-line oxy group; dentate base alkoxy group; hydroxyf'-group-Cl.6 alkyl group; dentate group; nitrile; Cb6 alkyl group-singly group; Cl_6 alkyl group _ κ if, C3·6 Cw cycloalkyl-Cw alkyl; c3 6 cycloalkyl-carbonyl, amine, or heterocyclic; or two such The group may form a five- or six-membered ring together with the atom to which it is attached. In the embodiment of Formula 1 or Formula II which is a heterocyclic-Cl.6 alkyl group, the heterocyclic knives may be azetidinyl;洛洛唆基;派咳基;β辰嗓, porphyrin; thiomorpholinyl; 3-oxa-8-aza-bicyclo[3.2.1] xin-8-yl, 2-oxo_ 5-aza-bicyclo[221]heptyl-5-yl; or 8-oxax-3-azabicyclo[3.2.1]oct-3-yl; each of which is optionally substituted as defined herein The heterocyclyl moiety is optionally substituted with one, two or three groups independently selected from the group consisting of: Ci6 alkyl; functional group - Ci6 alkyl; Ci-6 alkoxy group - Ck alkoxy; hydroxyl; hydroxy-Ci6 alkyl; halo; nitrile; Cw alkyl-based; Ci. 6 alkyl-sulfonyl; c36 cycloalkyl; c3-6 cycloalkyl ci-6; C3-6 cycloalkyl ; an amine group; or a heterocyclic group; or two s and the like, together with the atom to which they are attached, may form a five or six membered ring. 156325.doc •45· 201202215 The formula of a heterocyclic group-Cl_6 in R6 { Or the formula „ base moiety can be: azetidinium ... W group; = its = base; or morphine; each - as defined herein In some embodiments of Formula I or Formula II, R6 is a heterocyclic group. The heterocyclic moiety of the ring is optionally selected from one, two aluminas, and one independently selected from one another. The following earth mass replaces .Cl 6 alkyl; halo-C16 alkyl 匕 1-6 alkoxy, halo = lactyl H via _C1.6 alkyl; dentate; nitrile; ~ burnt soil, C, .6 alkyl-continuous base; C36 cycloalkyl; C36 cycloalkyl _CH 炫, C3.6 cycloalkyl; silk; amine; or heterocyclic; or two of these groups attached thereto The atoms together form a five or six-membered ring. In certain embodiments of formula I or formula II, R6 is: hydrogen; methyl; ethyl; isopropyl, or cyclopropyl. In certain embodiments of formula I or formula II, R6 is: hydrogen; fluorenyl; ethyl; isopropyl; 2-amino-propyl; oxetane _3-yl; 2-methoxy 2-ethyl; 2-trans-ethyl-ethyl; cyclopropyl; π-decyl _4-yl; benzyl-bistidine _4_yl; tert-butyl; 2-trans-based 2-methyl-propyl ; cyclobutyl; 1-methyl-cyclobutyl; 2-trans-propyl-propyl; 1-cyano-cyclopropyl; 3,3-di-cyclobutyl; cyclopropylmethyl; 3- Fluoro-cyclobutyl; or 2,2-difluoroethyl. In certain embodiments of formula I or formula II, r6 is nitrogen. In certain embodiments of Formula I or Formula II, r6 is methyl. In certain embodiments of Formula I or Formula II, r6 is B. In certain embodiments of Formula I or Formula II, R6 is isopropyl. In certain embodiments of Formula I or Formula II, R6 is 2-aminopropyl. In certain embodiments of Formula I or Formula II, R6 is oxetane_3_yl 156325.doc-46 - 201202215 In certain embodiments of Formula I or Formula II, Ruler 6 is 2-methoxy-ethyl. In certain embodiments of Formula I or Formula II, 'r6 is 2-trans-ethyl-ethyl. In certain embodiments of formula I or formula II, R6 is cyclopropyl. In certain embodiments of Formula I or Formula II, R6 is piperidinyl-4. In certain embodiments of formula I or formula II, the ruler 6 is κ-mercapto-piperidinyl-4-yl. In certain embodiments of formula I or formula II, r6 is a third butyl group. In certain embodiments of formula I or formula II, R6 is 2-hydroxy-2-methylpropyl. In certain embodiments of Formula I or Formula II, 'r6 is cyclobutyl. In certain embodiments of formula I or formula II, r6 is 1-methyl-cyclobutyl. In certain embodiments of Formula I or Formula II, Ruler 6 is a 2-hydroxy-propyl group. In certain embodiments of formula I or formula II, R6 is cyano-cyclopropyl. In certain embodiments of formula I or formula II, R6 is 3,3-difluorocyclobutyl. In certain embodiments of Formula I or Formula II, r6 is cyclopropylindenyl. In certain embodiments of formula I or formula II, R6 is 3-fluoro-cyclobutyl. In certain embodiments of formula I or formula, R6 is 2,2-difluoroethyl. In certain embodiments of Formula I or Formula II, R5&R6, together with the nitrogen atom to which it is attached, form as appropriate a two to seven member ring selected from the other hetero atom of 〇, s(〇)n2 and the ring The situation is substituted by one, two or three groups independently selected from the group consisting of C1-6 alkyl, halo-c16 alkyl, alkoxy, halo-C!6 alkoxy, hydroxy , hydroxy-Ci6 alkyl, halo, nitrile, Cw alkyl-carbonyl, Cl.6 alkyl sulfonyl, c36 cycloalkyl, c3-6 cycloalkyl-Cm alkyl, <:3·6 naphthenic A carbonyl or heterocyclic group, or two such groups, together with the atom to which they are attached, may form a five or six membered ring. 156325.doc •47- 201202215 The R and R together with the gas atom to which they are attached form an equation or a formula η including a three to seven-membered ring of another hetero atom selected from Ο, N and S(0)n. In the examples, 'the ring can be azetidinyl; the base bit; the pyridyl; the piperazinyl; the morpholinyl; the thiomorpholinyl; the nitrogen group; the 3 oxa _8-nitrogen Hetero-bicyclo[3.2.1]octyl; 2-oxa-5-hetero-bicyclo[2.2.1]hept-5-yl; or 8-oxax-3-aza-bicyclo[3_2'1]octine _3_base; each is replaced as defined herein. In the embodiment in which the gas atoms to which R and R are connected are formed together, including the three- to seven-membered ring of the other-hetero atom selected from Ο, Ν, and S(0)n, or the formula η, The ring may be: azetidinyl; pyrrolidinyl; piperidinyl; piperazinyl, or morpholinyl; each as appropriate as defined herein. In certain embodiments of Formula I or Formula II, Rule 5 and Rule 6 together with the nitrogen atom to which they are attached form a morpholinyl group, which is optionally substituted once or twice with a group independently selected from: Cw alkane , _yl-〇16 alkyl, 6 alkoxy, dentate-Cw alkoxy, carbyl, hydroxy-Ci6 alkyl, halo, nitrile, &alkyl-carbonyl, Cl.6 alkyl- Sulfonyl, C36 cycloalkyl, C36 cycloalkyl-Ci6 alkyl, C3_6 cycloalkyl-carbonyl, amine or heterocyclic group, or the two groups together with the atom to which they are attached may form five or six members ring. In certain embodiments of Formula I or Formula II, Han 5 and Caliper 6 together with the nitrogen atom to which they are attached form a piperidinyl group, which is optionally substituted once or twice with a group independently selected from: C1_6 alkane , halo-c10 alkyl, c16 alkoxy, halo-Cw alkoxy, hydroxy, hydroxy-Ci_6 alkyl, halo, nitrile, ^16 alkyl-carbonyl, C!.6 alkyl-sulfonate Anthracenyl, C36 cycloalkyl, cycloalkyl-Cw alkyl, C3-6 cycloalkyl-carbonyl, amine or heterocyclic or the atom to which the two groups are attached to 156325.doc -48 - 201202215 Together, a five or six-member ring can be formed. In certain embodiments of formula I or formula II, R5&R6, together with the nitrogen atom to which they are attached, form a piperazinyl group, which is optionally substituted once or twice with a group independently selected from the group consisting of Cw alkyl, Tooth group _Cl_e alkyl, 6 alkoxy, halo-c _6 alkoxy, hydroxy, hydroxy-Cl0 alkyl, benzyl, nitrile, Ci6 alkyl-carbonyl, Cw alkyl-sulfonyl, C3 · 6 cycloalkyl, c36 cycloalkyl _Ci-6

A decyl group, a Cw cycloalkyl-carbonyl group, an amine group or a heterocyclic group, or the two groups together with the atom to which they are attached may form a five or six membered ring. In certain embodiments of Formula I or Formula II, Rule 5 and Rule 6 together with the nitrogen atom to which they are attached form a pyrrolidinyl group which is optionally substituted once or twice with a group independently selected from: C1· 6 alkyl, _yl·C1_6 alkyl, C16 alkoxy, i-Cw alkoxy, hydroxy, hydroxy-Ci_6 alkyl, halo, nitrile, Cm alkyl-carbonyl, Cl-6 alkyl-sulfonyl , C: 3·6 cycloalkyl, c3_6 环美美-c" alkyl, C3_6 cycloalkyl, amino or heterocyclic group, or the two groups together with the atom to which they are attached may form five or Six-member ring. In certain embodiments of Formula I or Formula II, RW, together with the gas atom to which it is attached, forms a group selected from the group consisting of morpholine-4-yl; 4-hydroxy-piperidine-yl; octahydro-indole幷 幷 义 义 比 _2 _2 _ 2 ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; Hydroxydi-methyl-ethyl-anthracene + group; 3-carbyl group _b-pyrrolidine + group; 4_mercapto-bite-ι-yl-m-di-heterocycline-based group; 3-methyl-decyl group; 4-methoxy- lysine]-yl; 3,3-difluoro-piperidin-1-yl; 4-cyano "chen bite-i• base; Small base; 3·methoxy _ 旅 丨 丨 基 基; 4_ethyl _ alkazine small base; 4 _ 乙 基 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 0 bottom 0 -1- group; 4-窠-卞杜气Τ Lane Dibutyl-piperidin-1-yl; 2-hydroxy-ethyl-mouth 唪-1-yl; 2-methyl- η ratio. Each of the oxime 1 is I-l-hexan-1-yl; 4-hydroxymethyl-piperidin-1-yl; 2-methyl-pyridinyl-buyl, pyrrolidinyl; 4-nonanesulfonyl- Nitrozin small group, 3-difluoromethyl group than beer]_ base; 4_(2,2,2_three gas_ethyl)_派派_ 1-yl; 2-methyl-? a .0 < swallowing, 2,6-dimethyl-morpholin-4-yl; 2,2-diethyl-nor--4-yl; 3-trans-methyl-T-['morpholine- 4-yl; 2-isobutyl-morphin-4-yl; 2-methyl-oxalin-4-yl.1. Preparation of '3,3-dimercapto-morpholin-4-yl; 4-indolyl·pyryl-2-yl; 4-isopropyl, 矣0矣, R Qin-1-yl; piperazine -1-yl; 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; w, 2 ro # (S)_3-methyl-morpholin-4-yl; 2-oxo Hetero-5-aza-bicyclo[2.2.1]hept-5-yl·β prepared, this, 8-oxa-3-aza-bicyclo; (R)-3-methyl-? j土' 4-i 衣丙炫基基_旅嘻_ι_基; 4- (1-hydroxy-1-methyl-ethyl), , 唆-l-yl; 4-cyclobutyl-piperazine -1-yl;, eu ' 4 oxetan-3-yl-piperazin-1-yl; 3-morpholin-4-yl-azetidin, w 夂-1·yl; 4 -(1-indolyl-piperidin-4-yl)-piperazin-1-yl; 3,3-difluoro-aza: heteroperbutan-1-yl; 4-diguanylamino-piper Pyridin-1-yl, 4-piperidinyl-4-yl-piperidine 4, its red-branched, 4,4-difluoro-piperidine small group; 3-morpholine-external oxime-gas heterocyclic butyl. ^ ς ^ _ 土' 2~oxa-6-aza-spiro[3·3]hept-6-yl; 2-oxa-5-oxa-bis(1)4]oxazapine; 4_ Methoxy decyl _1 yl; yl; 3 ', hexeptane-4~yl; (2R, 6S)-2,6-dimethyl-morpholine-4-x'-yl' nitrogen heterocycle Ding Yi _1 Gan ^ One A Its 'base, 3-cyanobiha.定-1-基;3,5-一T巷-呢唪-〗 . pyridine.s soil '(3R,5S)-dimercapto-piperazin-1-yl; 3-fluoro-pyrrolidine- 1-yl (.) / - gas "Bilo. Dingqiji; pilazine_1_yl; 3,3_difluoropyridinyl base; 2 '3 2-1 1 azetidine-1- 2,2,6,6-tetrafluoro-m-methoxymethyl-.pyrrolidin-1-yl;(S)-2-methoxyindolyl-156325.doc •5〇, 201202215 0比β-1-yl; Difluoroβ is more specific than B, σ1 _l_ group; 3,4-difluoro π piroxime-l-yl; and 3-decyloxypyrrolidinyl. In some embodiments of formula or formula 'R5 and R6 together with the nitrogen atom to which they are attached form a group selected from the group consisting of the following groups: morphine-4-yl; 4-predominant-branched-l-yl; octa-d-d ratio bite [1,2- a ] ° ratio ° Qin-2-yl, 2-cysyl-trans- -1-yl, 4,4-dimethyl-bunken-1-yl, 3,5-dimercapto-bite-1 -yl; 1-yl-1-methyl-ethyl-piperidin-1-yl; 3-hydroxy-pyrrolidinyl-indoleyl; 4-methyl-piperidin-1-yl; piperidine-1 -yl;azetidin-1-yl; 4,4-difluoro-piperidin-1-yl; 3-methyl-piperidin-1-yl; 4- Oxy-piperidin-1-yl; 3,3-difluoro-piperidin-1-yl; 4-cyano-piperidine-K; 4-fluoro-piperidin-1-yl; 3-oxo 4-piperidin-1-yl; 4-ethyl-piperazine-1-yl; 4-ethylindolyl-piperazin-1-yl; 3-trifluoromethyl-piperidin-1-yl, · 4 - tert-butyl-piperidin-1-yl; 2-hydroxy-ethyl-piperazin-1-yl; 2-mercaptopyridin-1-yl; 4-hydroxymethyl-piperidine-1- 2-methyl-piperidin-1-yl; °pyrrolidyl; 4-methanesulfonyl-piperazin-1-yl; 3-trifluoromethylidene ratio 11 pyridine-1-yl; 4 -(2,2,2-trifluoro-ethyl)-piperazin-1-yl; 2-methyl-nor--4-yl; 2,6-dimethyl-morpholine-4-yl; , 2_diethyl-morphin-4-yl; 3-hydroxymethyl·morpholine_4_yl; 2-isobutyl-morpholine_4_yl; 2-hydroxymethyl-morpholine-4- 3,3-dimercapto-morpholine_4_yl; 4-methyl-piperazin-1-yl; 4-isopropyl-piperazine-indenyl; piperazinyl; 3-oxa _8_aza-bicyclo[3.2.1]oct-8-yl; (8)_3_methyl-morpholine_4_yl; 2_oxa_5_aza-bicyclo[2.2.1]g 5-yl; 8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl; (r)-3-indolyl-morphin-4-yl; 4-cyclopropanecarbonyl-piperazine -1-yl; 4-(1-hydroxy-1-methyl-ethyl)-piperidine-1-yl 4-cyclobutyl-piperazin-1-yl; 156325.doc •51· 201202215 (R)-3-hydroxy-pyrrolidine 3-Merline I-nitro nitrogen heterocycle; _ household'; " oxygen heterocycle丁心如终]-Base '· ♦ -1-yl; 3 3 - Μ * ^ base, 4_(didecyl-piperidin-4-yl)-pipenene, 3-fluoroxanthene. s. Butane; 4-di-f-aminopiperidinyl, and 4-piperidine-4-yl-piperazinyl. In certain embodiments of Formula I or Formula II, r^r6 is taken together with the nitrogen atom to which it is attached. In some embodiments of Formula 1 or Formula 11, R5 and R6 are attached thereto. The nitrogen atoms together form a 4-hydroxy-piperidinyl group. In certain embodiments of Formula 1 or Formula 11, R5 together with the nitrogen atom to which it is attached form an octahydropyridinium [Ha]pyrazinyl group. In certain embodiments of formula I or formula, r\r6, together with the nitrogen atom to which it is attached, forms a 2-hydroxy-piperidinyl group. In certain embodiments of Formula I or Formula II, Han 5 and Rule 6 together with the nitrogen atom to which they are attached form a 4,4-dimercapto-piperidinyl-yl group. In certain embodiments of Formula I or Formula II, Rule 5 and Rule 6 together with the nitrogen atom to which they are attached form a 3,5-dimercapto-piperidinyl group. In certain embodiments of Formula I or Formula II, and Rule 6 is taken together with the nitrogen atom to which it is attached to form 1-hydroxy-1-methyl-ethyl-piperidinyl. In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 3-butyryl-n-l-l-yl group. In certain embodiments of Formula I or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form 4-mercapto-piperidin-1-yl. In certain embodiments of Formula I or Formula II, 'R5 and R6 together with the nitrogen atom to which they are attached form an n-bottom-1 group. 156325.doc -52- 201202215 In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form azetidin-1-yl. In certain embodiments of Formula I or Formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 4,4-difluoro-β-beta-1-yl group. In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 3-indolyl-pi-l-yl group. In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 4-decyloxy-piperidin-1-yl group. In certain embodiments of Formula I or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form a 3,3-difluoro-pyridin-1-yl group. In certain embodiments of Formula I or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form a 4-cyano-β-bottom-1-yl group. In certain embodiments of formula I or formula, R5 and R6, together with the nitrogen atom to which they are attached, form a 4-fluoro-indiyl-1-yl group. In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 3-methoxy-π-pin-1-yl group. In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form a 4-ethyl-π-indolyl-yl group. In certain embodiments of Formula I or Formula II, R5 and r6 together with the nitrogen atom to which they are attached form a 4-ethylindolyl-π-indol-1-yl group. In certain embodiments of formula I or formula, trans 5 and trans 6 together with the gas atom to which they are attached form a 3-trifluoromethyl-piperidine-indenyl group. In certain embodiments of formula I or formula II, r5&r6, together with the I atom to which it is attached, form a 4-tert-butylpiperidine-i- group. 156325.doc -53- 201202215 In certain embodiments of Formula I or Formula II, and Ruler 6 is formed with the nitrogen atom to which it is attached. In certain embodiments of formula I or formula II, R5 and R6, together with the gas atom to which they are attached, form a 2-trans-ethyl-cyanoazinyl group. In certain embodiments of formula I or formula, R5&R6, together with the nitrogen atom to which they are attached, form a 2-mercapto-pyrrolidin-1yl group. In certain embodiments of formula I or formula II, R5&R6, together with the nitrogen atom to which they are attached, form a 4-methyl-l-n-l-yl group. In certain embodiments of formula I or formula II, R5&R6, together with the nitrogen atom to which they are attached, form 2-mercapto-piperidin-1-yl. In certain embodiments of Formula I or Formula II, ... and Ruler 6 together with the nitrogen atom to which they are attached form 11 to 11 each 0^-1-yl. In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 4-indole-xanthine-pyrazine-1-yl group. In certain embodiments of Formula I or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form a 3-trifluoromethyl-pyrrolidinyl-yl group. In certain embodiments of Formula I or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form 4-(2,2,2-trifluoro-ethyl)-piperazinyl. In certain embodiments of formula I or formula II, rW, together with the nitrogen atom to which it is attached, form a 2-methyl-morpholin-4-yl group. In certain embodiments of Formula Ϊ or Formula II, R5 and R6 together with the nitrogen atom to which they are attached form a 2,6-dimercapto-morpholin-4-yl group. In certain embodiments of Formula I or Formula II, Rule 5 and Rule 6 together with the nitrogen atom to which they are attached form 2,2-diethyl-morpholin-4-yl. 156325.doc -54- 201202215 In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form a 3-hydroxymethyl-morpholin-4-yl group. In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form a 2-isobutyl-morphin-4-yl group. In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form a 2-hydroxymethyl-morpholin-4-yl group. In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form a 3,3-dimethyl-morpholin-4-yl group. f) In certain embodiments of Formula 1 or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form 4-mercapto-piperazin-1-yl. In certain embodiments of formula I or formula II, R5 and R6, together with the nitrogen atom to which they are attached, form a 4-isopropyl-[alpha]-heptyl group. In certain embodiments of Formula I or Formula II, 'R5 and R6, together with the nitrogen atom to which they are attached, form a pi-azine group. In certain embodiments of Formula 1 or Formula 11, R5 and R6 together with the nitrogen atom Q to which they are attached form a 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl group. In certain embodiments of Formula 1 or Formula 11, 'R5 and R6, together with the nitrogen atom to which they are attached, form (S)-3-indolyl-oxalin-4-yl. In certain embodiments of Formula 1 or Formula 11, 'R5 and R6, together with the nitrogen atom to which they are attached, form a 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl group. In certain embodiments of Formula I or Formula II, 'R5 and r6 together with the nitrogen atom to which they are attached form an 8-oxa-3-aza-bicyclo[3.2.1]octyl-3-yl group. In certain embodiments of Formula II, R5 and R6, together with the nitrogen atom to which they are attached, form (R)-3-methyl-nor--4-yl. 156325.doc -55- 201202215 In certain embodiments of Formula I or Formula II, Rule 5 and Rule 6 together with the nitrogen atom to which they are attached form a 4-cyclopropanecarbonyl-piperazinyl group. In certain embodiments of formula I or formula II, R5&R6, together with the nitrogen atom to which they are attached, form 4-(1-hydroxy-1-indolyl-ethyl)-piperidine-indenyl. In certain embodiments of Formula I or Formula II, Rule 5 and Rule 6 together with the nitrogen atom to which they are attached form a 4-cyclobutyl-piperazinyl group. In certain embodiments of Formula I or Formula II, R5&R6, together with the nitrogen atom to which it is attached, form a (R)-3-hydroxy-pyrrolidinyl-yl group. In certain embodiments of formula I or formula II, R5&R6 together with the nitrogen atom to which they are attached form a 4-oxetane-3-yl-piperazinyl group. In certain embodiments of Formula I or Formula, "and" together with the nitrogen atom to which it is attached, form a 3-morpholin-4-yl-azetidinium-yl group. In certain embodiments of Formula I or Formula II, ... and " together with the nitrogen atom to which they are attached form a 4-(1-methyl-piperidin-4-yl)-piperazine-indenyl group. Or in certain embodiments of Formula II, R5&R6, together with the nitrogen atom to which they are attached, form a 3,3-difluoro-azetidinium-yl group. In certain embodiments of Formula I or Formula II , 艮5 and 尺6 together with the nitrogen atom to which they are attached form a 4-diamino-piperidinyl group. In certain embodiments of Formula I or Formula II, R5&R6 together with the nitrogen atom to which they are attached form 4 -piperidin-4-yl-piperazine-b-based. In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form 4,4-difluoro-piperidine-indole In certain embodiments of Formula I or Formula II, "and Ruler 6 together with the nitrogen atom to which it is attached form a 3-morpholin-4-yl-azetidinium-yl group. 156325.doc -56· 201202215 In certain embodiments of Formula I or Formula II, Rule 5 and Han 6 together with the nitrogen atom to which they are attached form 2-oxa-6-aza-spiro[3·3]g _6_ base. In certain embodiments of Formula I or Formula II, Rule 5 and " together with the nitrogen atom to which they are attached form a 2-oxa-5-aza-bicyclo[2_21]heptan-5-yl group. In some implementations of Formula or Formula II, the nitrogen atom to which it is attached forms a 4-decyloxy-piperidin-1-yl group. Ο

In certain embodiments of Formula 1 or Formula 11, R5 and R6 together with the nitrogen atom to which they are attached form a [1,4]oxazepan-4-yl group. In certain embodiments of Formula I or Formula II, r^r6, together with the atomic atom to which it is attached, forms a (2R,6S)-2,6-dimercapto-morpholine-4-yl group. In certain embodiments of formula I or formula, r^r6, together with the nitrogen atom to which it is attached, forms a 3-hydroxy- azetidinyl group. In certain embodiments of Formula I or Formula II, r^r6, together with the nitrogen atom to which it is attached, forms a 3-cyanopyrrolidine-yl group. In certain embodiments of Formula 1 or Formula 11, R5 and R6 together with the nitrogen atom to which they are attached form a 3,5-dimethyl-π-pyridazine group. In certain embodiments of Formula 1 or Formula, R5 and R6 together with the nitrogen atom to which they are attached form a (3R,5S)-dimethyl-piperazine-s group. In certain embodiments of the formula or formula π, r^r6, together with the nitrogen atom to which it is attached, forms a 3-fluoro ratio and a bite. In certain embodiments of Formula I or Formula, r^r6, together with the gas atom to which it is attached, forms a (S)-3-fluoro- 嘻 嘻 base. In certain embodiments of Formula I or Formula II, r5&r6 together with the nitrogen atom to which they are attached form a piperazine-1-yl group. 156325.doc 57- 201202215 A certain 4b of formula I or formula II will form a certain one in formula I or formula II + / _ $ . 霄 例 _, R5 and R6 connected to it The nitrogen atoms together form a 3,3-difluoroseprobutan-1-yl group. In the formula 4 or a certain 4b^+A of the formula, - in the example, R5 and R6 together with the nitrogen atom to which they are attached form a 2,2,6,6-tetraqi_?lin_4_ group. In the 4b of the formula I or the formula II, in the t-actual example, R5 and R6 together with the nitrogen atom to which they are attached form a 2-methoxy group of methyl | i methyl "Bilo-1-yl. In certain embodiments of formula I or formula II, R5 and R6 together with the nitrogen atom to which they are attached form a (S)-2-methoxymethyl-pyrrolidin-1-yl group. In certain embodiments of Formula II, RW forms a (1S,4S)_2-oxacapine heterobicyclo[221]heptan-5-yl group with the nitrogen atom to which it is attached. Some of Formula 1 or Formula 11 In the examples, the nitrogen atom to which they are attached forms (3S, 4S)_3, 4_H core groups; 3,4_dioxidine-1-yl, and 3-decyloxypyrrolidine-yl group. In certain embodiments of Formula I or Formula ,, ... is a dentate group. R is (^.6 alkyl. R7 is CV6 alkoxy. R7 is i-Cw alkyl. R7 is halo-Cw alkane R7 is halo or methoxy" R7 is fluoro, chloro or methoxy. R7 is fluoro or chloro. r7 is decyloxy. In certain embodiments of formula I or formula II in formula I or Certain embodiments of Formula I or Formula II in certain embodiments of Formula I or Formula II in certain embodiments of Formula II or Formula II, in certain embodiments of Formula II or Formula II In certain embodiments of Formula I or Formula II, in certain embodiments of Formula I or Formula II, in certain embodiments of Formula I or Formula II, 156325.doc -58-201202215 is in Formula I or Formula II. In certain embodiments, r7 is chloro. In certain embodiments of Formula I or Formula II, R7 is fluoro. Formula I or Formula II wherein R5 and R6 form a three to six membered ring together with the nitrogen atom to which they are attached In the examples, 'the compound of the invention can be represented by the formula:

ρ is 0 to 2; when Ρ is 1 or 2, Υ is:; _s(〇)r_ ; _NRi〇; or _criir12_ : and when ρ is 0, Y is -CRnR12-; R8 and R9 are independently Is: hydrogen; Cl.6 alkyl; halo-Ck alkyl; Cl Λ 1-6 alkoxy, halo-Ci·6 alkoxy; trans-group; hydroxy-(^_6 alkyl; halo; Nitrile; Cw alkyl-aryl; Cw alkyl-sulfonyl; C3-6 cycloalkyl; (: 3-6 cycloalkyl-Cm alkyl; c3-6 cycloalkyl-carbonyl; amine; or heterocyclic; Or R8 and R9 together with the atom to which they are attached form a five or six membered ring; R is 虱; Ck 院基; thio-Cw alkyl; halo-Ck alkyl; trans-Cw alkyl; C! 6 alkyl-carbonyl; Cw alkyl-sulfonyl; c3.6 cycloalkyl; C3·6 cycloalkyl-(^.6 alkyl; c3-6 cycloalkyl-carbonyl; heterocyclic; a cyclic group -C^alkyl; or one of R8 and R9 together with rig and the atom to which it is attached form a five or six membered ring; R" is: hydrogen; c!-6 alkyl; or halo; 156325 .doc -59- 201202215 R12 is: hydrogen; Ci_6 alkyl; halo-Cl 6 alkyl; Cu alkoxy; halo-Cw alkoxy; hydroxy; hydroxy-Ck alkyl; halo; nitrile; cN6 Alkyl-single base; Cw Hyun a sulfhydryl group; a c3-6 cycloalkyl group; a c3.6 cycloalkyl-Cw alkyl group; a C3_6 cycloalkyl-carbonyl group; an amine group; a heterocyclic group; or a heterocyclic group-(:16 alkyl group; R11 and R12 together with the atom to which they are attached may form a three to six membered ring optionally comprising a hetero atom selected from the group consisting of ruthenium, N and S; or one of R8 and R9 may form a five or six a ring of atoms; together form one of five or R8 and R9 and R!2 and its attached or six-membered ring; and R/ in certain embodiments of formula 111 in certain embodiments of formula III In certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in Formula 111 In certain embodiments of Formula III, R3 and R7 are as defined herein, 卩 is 0 or 1. 卩 is 0. P is 1. p is 2. Y is -Ο-; NR1.; or _cri1r12 Ύ" is -Ο-. Y is -NR10- 〇' Y is -S(0)r-. In certain embodiments of formula III, R8 is hydrogen. In an embodiment, R9 is hydrogen. In certain embodiments of Formula III, R8 and R9 are 156325.doc -60- 201202215 In certain embodiments of the formula, R« and R9 are hydrogen, CM alkyl or a south group. In certain embodiments of Formula III, ... and the 9 and the atom to which it is attached - Form a five or six member ring. In some embodiments of the formula, one of the ruler 8 and the ruler 9 forms a five or six member ring with R10 and the atoms to which it is attached.某些 某些 In some embodiments of the formula, one of R8 and R9 forms a five or six membered ring with Rlz and the atoms to which it is attached. In certain embodiments of Formula III, Rio is chlorine. R is a C 1_6 alkyl group. R1() is a hydroxy-C1-6 alkyl group. R is a halo-Cw alkyl group. R is a phono-Ci_6 alkyl group. R is ^^ 烧基- 叛基. RlG is a CN6 alkyl-sulfonyl group. R is a c3.6 cycloalkyl group. R is a C3.6 cycloalkyl group - Ci-6 alkyl group R is a C3.6 cycloalkyl group-single group. R1() is a heterocyclic group. Rl° is a heterocyclic-Ci-6 alkyl group. R" is hydrogen or Cw alkyl. Rl1 and R12 are hydrogen. R11 is hydrogen. R is c!.6 base. In some embodiments of Formula III, in certain embodiments of Formula ,, in certain embodiments of Formula ,, in certain embodiments of Formula III, in certain embodiments of Formula III, In some embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula 111, in certain embodiments of Formula III, In certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, 156325.doc -61 - 201202215 In certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in Formula III In some embodiments, in certain embodiments of Formula III, in certain embodiments of Formula 111, in certain embodiments of Formula 111, in certain embodiments of Formula 111, in Formula III In certain embodiments, in certain embodiments of Formula III, in certain embodiments of Formula III, in certain embodiments of Formula III, in Certain Formula III In certain embodiments, in certain embodiments of Formula III, in certain embodiments of Formula III, R11 is halo. R12 is hydrogen. ^^ is 匚 "alkyl. R12 is halo-Ci-6 alkyl. R12 is Cw alkoxy. R12 is halo-Cw alkoxy. R12 is hydroxy. R12 is hydroxy-Cw alkyl. R12 is R12 is a nitrile. R is a Ci_6 alkyl-based group. R is a Ci_6 alkyl-organic group. R12 is a (:3-6 cycloalkyl group. R is a C3-6 cycloalkyl group-〇1.6 alkyl group. Is a C3-6 cycloalkyl-alkyl group. R12 is an amine group. In certain embodiments of Formula III, r12 is a diammonium group. In certain embodiments of Formula III, R12 is heterocyclyl. In the embodiment of the formula III wherein R1Q is a heterocyclic group, the heterocyclic group may be an anthracene group; "Bilo;base; brittle base; phenyl group: morphine. morpholinyl; Oxa-8-aza-bicyclo[3.2.1]oct-8-yl; 2_oxo 5 hetero-bicyclo[2.2.1]hept-5-yl·, or 8-oxa-3-aza _bicyclo[321] octyl; each optionally substituted by one, two or three independently selected from the group consisting of Cw alkyl; _yl-Cm alkyl; Cl.6 alkoxy; 156325 .doc -62- 201202215

Cw alkoxy; hydroxy; hydroxy_Cl_6 alkyl; halo; nitrile; Ci6 alkyl _ aryl, Cw alkyl-continuation; C: 3·6 cycloalkyl; C3_6 ring-based _cK6 alkyl 'C: 3-6 cycloalkyl-carbonyl; an amine group; or a heterocyclic group; or two such groups together with the atom to which they are attached may form a five or six membered ring. In an embodiment wherein R is a heterocyclic group, the heterocyclic group can be: azetidinyl; pyrrolidinyl; piperidinyl; piperazinyl; or morpholinyl; each as herein The definition is superseded as appropriate. Ο ❹ In the embodiment wherein R1G is a heterocyclic group of _Cl_6 alkyl, the heterocyclic moiety may be: azetidinyl; pyrrolidinyl; piperidinyl; piperazinyl; morpholinyl Thiomorpholyl; 3_oxa-8-aza-bicyclo[321]octyl-8-yl; 2-oxaza-bicyclo[221]hept-5-yl; or 8_oxa-3 _ aza-bicyclo[3.2.1]octyl; each as appropriate as defined herein. In the examples of the formula wherein R1G is a heterocyclic-C1-6 alkyl group, the heterocyclic moiety may be: azetidinyl; pyrrolidinyl; piperidinyl; piperazinyl; or morpholinyl' Each is optionally substituted with one, two or three groups independently selected from the group consisting of: Cl_6 alkyl; group _Ci4; &alkoxy; dentyl 々 6 alkoxy; hydroxy; hydroxy _Ci_6 alkyl; i group; nitrile; Cl_6 cwm group; & cycloalkyl 4 (f) group; c3-6 cycloalkyl group; amine group; or heterocyclic group; or two of these groups The connected atoms together form a five or six member ring. In the embodiment wherein the R12 is a heterocyclic group of the formula m, the heterocyclic group may be: a smectic smear: a money: a ketone; a (iv) group; a (iv) group; a thiol group: a 3 oxa group _ azabicyclo[3.21]octyl; 2_oxa-5-nitro" again%[2.2.1]hept-5-yl; or 8-oxa-3-aza-bicyclo[3.2.1] Oct-3- 156325.doc • 63 - 201202215, each of which is optionally substituted as defined herein. In the embodiment wherein R12 is a heterocyclic group of formula m, the heterocyclic group may be: azetidine Burning base, · Luo Luosi; Niang bite base; Niang „Qinji; or 琳琳基,········———————————————————————————————————————————————————————————————————————————————————————————————————————————————— 6 alkyl; south base _Ci base; Ci 6 methoxy, · Nanji A 6 methoxy; base; _-Cl_6 alkyl; functional; nitrile; Ci 6 炫 - base · heart ^ Alkyl group; C3_6 cyclodextrin; a. 6 cycloalkyl group _c "6 alkyl; "cycloalkyl" amino group; or heterocyclic group; or '^ these groups are attached thereto The atoms together form a five or six-membered ring. In the embodiment of the formula m wherein R 2 is a heterocyclic group -Ci_6 alkyl, the heterocyclic moiety may be: azetidinyl; indolyl; fluorenyl; olynyl; porphyrin 'Thomamorpholinyl; 3_oxa-8-aza-bicyclo[3.2.1]octyl-8-yl: 2-oxa-5-aza-bicyclo[2.21]hept-5-yl; Oxa_3_gas _ Bicyclo[3.2.1 ] 辛_其.甘tb β @土' where the s-hetero-based moiety is optionally substituted by a group selected from the following: Cw alkyl Halo-1-6 alkyl, (^6 alkoxy; _yl-q.6 alkoxy; hydroxy; hydroxy-Ci_6 = fluorenyl, nitrile, Cl-6 alkyl-carbonyl; C丨-6 Alkyl-sulfonyl; C3-6 cycloalkyl; cw fluorenyl-Ci-6 alkyl; C3-6 cycloalkyl aryl; amine; or heterobasic; or two such groups The atom to which it is attached may form a five- or six-membered ring. Λ f Rl2 is a heterocyclic group of the formula III, and the heterocyclic group may be an azetidinyl group; A base; a base; or a linalyl; each as defined herein is replaced by I. In some embodiments of formula HI, Rll and r12 are connected to the original A 156325.doc -64 - 201202215 optionally together form a three to n comprises a heteroatom selected from square, N and s - A In certain embodiments, the compounds of the present invention may be more specific words: wherein ⑽ R1, ❹ Yi

X

Show: In certain embodiments, the compounds of the invention may be more specific s from the formula V, R1, 〇 where defined.

X

Shown herein, in certain embodiments, the compounds of the invention may be more specifically made by Formula VI.

156325.doc -65- 201202215 where m, X, Rl, R2, r3, R7, R8, as defined in the text. In certain embodiments, the compounds of the invention may be represented by the formula νπ as R, R11 and R12 are more specifically:

R1, X

The text is defined. In certain embodiments, the compounds of the invention may be more specifically represented by:

VII R11 and R12 are as defined in the formula VIII

Where m, p, X, γ, R2, R4, r7 are defined. In certain embodiments, the compounds of the invention may be more specifically:

VIII R and R9 are as defined herein by the formula IX 156325.doc -66- 1 201202215

Wherein m, X, R1, R2, R4, R8 & r9 are as defined herein. In certain embodiments, the compounds of the invention may be further described by the formula:

definition. In certain embodiments, the compounds of the invention may be more specifically described by the formula.

Rl, R2, R4, R7, R8 wherein m, X, and text are defined. XI R9, R11 and R12 are as in some embodiments, the compounds of the invention may be more

The formula XII 156325.doc -67- 201202215 means: where m is defined

X, R1, R2, R4, R7, R8, R9, R" and Rl2 are as in the present examples, the compounds of the invention may be represented by formula XIII:

XIII where p, x, Y, R1, R2, R3, R7, R8 and R9 are as defined herein as any of R, R2, R3, R4, R5, R6, r7, r8, r9, Rll and r12 When an alkyl group or an alkyl moiety is included, the alkyl group is preferably a lower alkyl group, i.e., a C!-6 alkyl group, and in many embodiments may be a 4 alkyl group. In certain embodiments, the invention provides a compound as described herein, selected from the group consisting of 5-chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino) _2_methoxy-benzylamine, 5-chloro-4-(5-gas-4-methylamino-theranodine:ylamino-yl-ethyl)-2-methoxy-tuberamine, 156325.doc •68· 201202215 5-Chloro-N-cyclopropyl-2-methoxy_4_(4·methylamino-5-trifluoromethyl-pyrimidin-2-ylamino nodal amine, ( (2S,6R)-2,6-: f-based (10)morpholinyl))(2-say-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidine _2_ylamino)phenyl)methanone, (15'43)-2-oxa-5-azabicyclo[221]heptan-5-yl (2_fluoro_3_methoxy-4 -(4-(Methylamino)-5-(trifluoro-t-yl)(1Midine-2-amino)phenyl)methyl g, (1S,4S)_2_oxa-5-azabicyclo [2.2.1] Heptane-5-yl (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-decyloxyphenyl) )曱U _, (2,6-dimethyl-morpholine_4_yl)_[3_methoxy_4_(4_methylaminotrifluoromethyldept-2-ylamino)-benzene (]), (2-ethoxy-5-fluoro-4-(4-(methylamino)·5_(trifluoromethyl)pyrimidine_2_ Amino)phenyl)(fluorene-morphinyl)fluorenone, (2-fluoro-3-isopropoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidine-2-ylamine Phenyl)p-(morpho-morpholinyl)fluorenone, hydrazine (2 bis 3-isopropoxy _4_(4-(methylamino)-5-(tri-II fluorenyl) hydrazin-2-ylamine Base) phenyl)(Ν-吗琳基)曱 steel, (2-fluoro-5-methoxy·4·(4_(2_methoxyethoxy))5 (three gas methyl dense-bite- 2-Aminoamino)phenyl)(indolyl-morpholinyl)methanone, .(2-fluoro-5-methoxy_4_(4-(methylamino)-5-(trifluoromethyl)pyrimidine_2 (3-amino)phenyl)(3-methoxypyrrolidin-1-yl)fluorenone, (3-methoxy-4-(5-methoxy-4-(methylamino)pyrimidine_2 (基-amino)phenyl)(Ν-morphinyl)fluorenone, (4-(4-(ethylamino)_5_(trifluoromethyl)pyrimidine-2-ylamino)_2_fluoro_3_ Oxygen 156325.doc -69- 201202215 phenyl)(N-morphinyl)fluorenone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino) _2_Fluoro_3_isopropoxyphenyl)(N-morphinyl)methanone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)_3_( Trifluoromethoxy)phenyl)(N-morphinyl)methanone , (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)_3_(trifluoromethoxy)phenyl)(N-morpholinyl)methanone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl-amino)-3-isopropoxyphenyl)(N-morpholinyl)methanone, (4-( 4-(ethylamino)-5-(trifluoromethyl)pyrimidine-2-ylamino)_3_isopropoxyphenyl)(N-morphinyl)fluorenone, (4-(4-( Ethylamino)-5-(trifluoromethyl)pyrimidine-2-ylamino)_5_fluoro-2-methoxybasyl)(N-morphinyl) brewing|, (4-(4-( Methylamino)-5-(trifluoromethyl)pyrimidine-2-ylaminotrifluoromethoxy)carbyl)(N-morphinyl)methanone, (4-(5-bromo-4-pyrene) Oxypyrimidin-2-ylamino)_3_methoxyphenyl)(3_(trimethyl)methylpyrrolidone-1 -yl)曱, (4-(5-chloro-4-(曱) Amino)pyrimidine-2-ylamino)_3_nonylphenyl)(fluorenyl-morpholinyl)methanone, (4-(5-aero-4-(methylamino)pyrimidin-2-ylamino) )_3_methylphenyl)(4-hydroxypiperidin-1-yl)methanone, (4-(5-Ga-4-(piperidin-1-yl)pyrimidin-2-ylamino)_3_曱oxyphenyl)(Ν-morpholinyl)methanone, (4-(5-Gas-4-(pyrrolidinyl)pyrimidine_2_ Amino)_3_methoxy phenyl 156325.doc *70- 201202215 base) (N-morpholinyl)methanone, (4-(5-gas-4-methoxypyrimidin-2-ylamino)_3 _Methoxy phenyl)(π-pyridin-1-yl)methanone, (4-(5-cyclopropyl-4-methoxypyrimidin-2-ylamino)_3_decyloxyphenyl (Ν-Merlinyl) anthrone, (4-{5-chloro-4-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-2-ylamino}-3-曱oxy·phenyl)-morpholin-4-yl-methyl-, (4-{5-chloro-4-[(tetrahydro-furan-3-ylmethyl)-aminopyrimidine-2-yl) Amino}-3-decyloxy-phenyl)-morpholin-4-yl-methyl-, (4-diamino-yl-piperidine-1-ylmethoxy_4_(4-amino) 5-trifluoromethyl-carto-2-ylamino)-phenyl]-methanone, (4-tert-butyl-piperidin-1-yl)_[4_(5_气_4_曱Amino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-methanone, (5-gas-2-methoxy-4-(4-(methylamino)-5-(trifluoro) Mercaptopyrimidin-2-ylamino)phenyl) (full deuterated (Ν·morpholinyl))methanone, (5-Gas-2-methoxy-4-(4-(methylamino)) -5_(trifluoromethyl)β-Bite_2_ylamino)phenyl)(3-methoxypyrrolidin-1-yl)methanone, (5-chloro-4-(5- -4-(decylamino)pyrimidin-2-ylamino)_2-methoxyphenyl)(fluorene-morphine)fluorenone, (5-fluoro-2.methoxy-4-(4- (Methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(indolyl-morpholinyl)fluorenone, [2-chloro-4-(5-chloro-4-methyl) Amino-pyrimidin-2-ylamino)5-methoxyphenyl]- cylin-4-yl-methanone, [2- gas-5-methoxy-4-(4-methoxy) -5-trifluorodecyl-pyrimidin-2-ylamine 156325.doc -71 · 201202215 yl)-phenyl]-morpholin-4-yl-methanone, [2-chloro-5-methoxy-4 -(4-Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone, [2-fluoro-3-methoxy-4 -(4-Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-oxalin-4-yl-carbamidine [2-fluoro-5-methoxy-4 -(4-曱amino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone, [2-fluoro-5-methoxy-4 -(4-Methylamino-5-trifluorodecyl-pyrimidin-2-ylamino)-phenyl]-((S)-2-methyllacyl fluorenyl-°Bilobit-1-yl) -曱嗣, [3-(2-Fluoro-ethoxy)-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morphine-4 -yl-methyl hydrazine' [3-bromo-4-(4-methylamine) -5-trifluorodecyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone, [3 -> odor-4-(5-murine-4-guanamine) -°Bitter-2-ylamino)-phenyl]-morphine-4_yl-ketone, [3-chloro-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2- Amino)-phenyl]-morpholin-4-yl-methanone, [3-chloro-4-(5-chloro-4-decyloxy-naphtho-2-ylamino)-phenyl ]- 吓 _ _ 4-yl-ketone, [3-chloro-4-(5-chloro-4-hydrazino-indolyl-2-ylamino)-phenyl]-morphin-4-yl - anthrone, [3-diazetyl 4-(4-methylamino-5-dimethyl-methyl). Ding-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone, [3-cyclobutylmethoxy-4-(4-decylamino-5-trifluoromethyl-pyrimidine-2 -ylamine 156325.doc -72- 201202215 yl)-phenyl]-morpholin-4-yl-fluorenone, [3-3⁄4 propyl- 4-(4-methylamino-5-dioxanyl-密密定-2-ylamino)-phenyl]-Merlin _ 4 -yl-曱嗣' [3 - 哀 propyl methoxy-4-(4-amido-5-di-milk Mercapto-mouth. -2 -ylamino)-phenyl]-morpholin-4-yl-methanone, [3-ethoxy-4-(4-methylamino-5-disindolyl) - succinyl-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone, [3-isopropoxy-4-(4-methylamino-5-dioxanyl) - Mouth. Benz-2-ylamino)-phenyl]-?? ^^_4-基-甲嗣' [3 -methyllacyl-4-(4-methyllacyl-5-propan-1- fast Base-mouth bite-2-ylamino)-phenyl]-? scare ^ 4 -yl-曱嗣' [3-methoxy-4-(4-decyloxy-5.trifluoromethyl)- Pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone, [3-mercapto-4-(4-amido-5-propan-1-yl-yl) -2--2-ylamino)-phenyl]-?? ^^_ 4-yl-carboquine' [3 - decyloxy-4-(4-methylamino-5-disindolyl-mouth 唆- 2-ylamino)-phenyl]-morpholin-4-yl -methanone, [3 - fluorenyl-4-(4-methylamino-5-dioxamethyl-. dimethyl-2-ylamino)-phenyl]-(8-oxa-3 -aza-bicyclo[3.2.1]oct-3-yl)-fluorenone, [3-methoxy-4-(4-guanidino-5-dimethyl-methyl-n-but-2-yl) Amino)-phenyl]-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl)-fluorenone, [3-methoxy-4-(4-amidino) 5-5-methoxy-4-(4-decylamine) -5-5-di-gas methyl-σ-dense-2-ylamino)-benzene 156325.doc -73- 201202215 】][4-(2,2,2-three-ethyl)- oxime Azin-i-yl]-methanone, [3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-(4-A Oxy-α-Bottom-1-yl)-methanone, [3-methoxy-4-(4-pyrrolidinyl)-yl-5-trifluoromethyl-pyrimidin-2-ylaminophenyl ]-Molin-4-yl-methyl-j, [4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)_2_fluoro_5_decyloxy-phenyl ]-Merlin-4-yl-methylhydrazine, [4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)_2_fluoro_5_decyloxy-phenyl] -((S)-2-methoxymethyl_D than 洛ι_ι_基)_曱鲷, [4-(5-bromo-4-ethoxy-pyrimidin-2-ylaminomethoxy-phenyl]morpholin-4-yl-fluorenone, [4-(5-bromo-4-iso) Propoxy-pyrimidin-2-ylamino)-3-indolyl-phenyl]-morpholin-4-yl-fluorenone, [4-(5-bromo-4-methoxy-pyrimidine_2 _ ylamino)-2- _5_methoxy-phenyl], morpholin-4-yl-fluorenone, [4-(5-bromo-4-methoxy-pyrimidin-2-ylamine) )-)-fluoro-5-methoxy-phenyl-phenyl-cyano-4-yl-fluorenone, [4-(5-> odor-4-methoxy-3⁄4, -2-amino) )-3-cyclobutoxy-phenyl]-morphin-4-yl-oxime, [4-(5-/odor 4-methoxy-penetrating 2-amino)-3 -cyclopropoxy-phenyl]-morpholin-4-yl-methanone, [4-(5-bromo-4-indolyl-pyrimidin-2-ylamino)-3-ethoxy-benzene []-morpholin-4-yl-methanone, [4-(5-bromo-4-methoxy-pyrimidin-2-ylamino)-3-isopropoxy-phenyl; 156325.doc •74· 201202215 Lin-4-yl-methanone, [4-(5-bromo-4-methoxy-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-((R) - 2.2- Di-deutero-3-indolyl-morpholin-4-yl)-methanone, [4-(5-bromo-4-methoxy-pyrimidin-2-ylamino)-3-methyl Oxy-phenyl]-((S)-2.2-di-deutero-3-methyl-morpholin-4-yl)- Ketone, : [4-(5-bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-intimidation - 4 -yl-gas-misc Butyrate-1 -yl)-methylammonium I, [4-(5->odor-4-methoxy-π-deni-2-ylamino)-3-methoxy-phenyl]-( 4,4_ ^Difluoro-piperidin-1-yl)-fluorenone, [4-(5->Smell-4_曱乳基密定-2-ylamino)-3-decyloxy- Phenyl]-(4-ethyl-Benqin-l-yl)-fluorenone, [4-(5-bromo-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy -phenylindole 4-(1-hydroxy-1-methyl-ethyl)-piperidin-1-yl]-fluorenone, [4-(5-> odor-4-methoxy- 唆-2 -Aminoamino)-3-decyloxy-phenyl]-infrared- 4 ·yl-曱嗣' [4-(5-> odor-4-nonylamine). Ding-2-ylamino)-3-methoxy-phenyl]-morphin-4-yl-methanone, [4-(5-> odor-4-mercapto--. 2-Aminoamino)-3-decyloxy-phenyl]-[4_(1 _ rosinyl-1 -indolyl-ethyl). -1 -yl]-曱嗣' [4-(5 ->odor-4-methylamino- dimethyl-denyl-2-ylamino)-3-decyloxy-phenyl]-(3 -Trifluoromethyl-pyrrolidin-1-yl)-fluorenone, [4-(5->odor-4-methylamino- ̄3⁄4唆-2-ylamino)-3-decyloxy -phenyl]-(4-cyclobutyl-piperazin-1-yl)-fluorenone, [4-(5-> odor-4-mercapto-milami-2-ylamino)-3曱oxy-phenyl]-[4_ 156325.doc -75- 201202215 (2,2,2-trifluoro-ethyl)-[beta]-1-yl]-methanone, [4-(5-bromo) 4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methoxy-piperidin-1-yl)-methanone, [4-(5- Bromo-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-((R)-3-carboxy-0-habita-1-yl)--, [4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-oxetan-3-yl-piperazine-1 -yl)-methanone, [4-(5-bromo-4-methylamino-pyrimidin-2-ylamino)-5-chloro-2-methoxy-phenyl]-morphine-4-yl - beryllium copper [4-(5-chloro-4-cyclobutylamino-pyrimidin-2-ylamino)-3-methoxy-phenylμ? 4-yl-indole, [4-( 5-chloro-4-cyclohexylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl μ? -基-曱§同' [4-(5-Gas-4-cyclopentylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl-μ-line-4-yl-copper , [4-(5-Gas-4-ethoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-?咐*-4-yl-carbamidine, [4-(5 -4--4-aminoamino-pyrimidin-2-ylamino)-2-fluoro-5-decyloxy-phenyl-μ- 4-yl-branched|, [4-(5-gas-4 -ethylamino-pyrimidin-2-ylamino)_3_methoxy-phenyl], morphine-4-yl-carbamidine, [4_(5-(a)-4-isobutylamino-pyrimidine_ 2·ylamino)_3_methoxy-phenyl ph-lin-4-yl-fluorenone, [4-(5-gas-4-isopropoxy-pyrimidin-2-ylamino)_3_曱oxy_phenyl]_?156325.doc -76 - 201202215 Lin-4-yl-oxime, methoxy-phenyl], -methoxy-phenyloxy-phenyl]-?[4 -(5-Gas-4-Isopropylamino-pyrimidinylamino)_3Callin-4-yl-carbamidine, [4_(5_(a)--4-methoxy-pyrimidin-2-ylamino 」 吗 -4 -4 -4 -4 - 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4-

[4_(5_气_4_Methylamino-mouth bite_2_ylamino)_2_气吗-4-基-曱, 5-methoxy-phenyl; 1- [4-( 5-air-4-methylamino-carto-2-ylamino 3 J (2,2,2-trifluoro-ethoxy)-phenyl]-morphin-4-yl-fluorenone,

[4-(5-Chloro-4-methylamino benzoyl-2-ylamino)_3v_ A (hamethetane-3-yloxy)-phenyl]-morpholin-4-yl-indole Ketone, [4-(5-gas-4-famino-indolyl-2-ylamino)-3-cyclobutoxy-phenyl]-morpholine-4-yl-ketone, Ο [4 -(5-gas-4-methylamino-pyrimidin-2-ylamino)-3-cyclopentyloxy-phenyl]-(2-oxa-6-aza-spiro[3.3]hept-6 -yl)-methanone, [4-(5-Ga-4-indole-pyrimidin-2-ylamino)-3-cyclopentyloxy-phenyl]-morpholine-4-yl-ketone , [4_(5-Gas-4-methylamino-pyrimidin-2-ylamino)_3_cyclopropoxy-phenyl]•Mulline-4-yl-fluorenone, [4-(5-chloro -4-nonylamino-pyrimidin-2-ylamino)-3-cyclopropyl-phenyl]-morphin-4-yl-fluorenone, [4-(5-gas-4-methylamino)- Pyrimidine_2-ylamino)-3-difluoromethoxy-phenyl]- 156325.doc -77- 201202215 morpholin-4-yl-fluorenone, [4-(5-chloro-4-methylamine) Base-σ-Bite-2-ylamino)-3-difluoromethoxy-phenyl] stomach (4-hydroxychen-1-yl)-fluorenone, [4-(5-chloro-4- Methylamino-ytyl-2-ylamino)-3-ethoxy-phenyl]-morphin-4-yl-methanone, [4-(5-chloro-4-nonylamino-yl) Amino)-3-3⁄4yl-phenyl]-morphine-4-yl-fluorenone, [4-(5 - gas-4-methylamino-. dimethyl-2-ylamino)-3-isopropyllacyl-phenyl]-morpholin-4-yl-fluorenone, [4-(5-gas-4) -Amidinolide-2-ylamino)-3-decyloxy-phenyl]-oxalin-4-yl-methanone, [4-(5-chloro-4-methylamino----- Ding-2-ylamino)-3 -indolyl-phenyl]-(4-carbyl-piperidin-1-yl)-fluorenone, [4-(5-chloro-4-methylamino)- Pyrimidin-2-ylamino)-3-methoxy-phenylindole octahydrogen ratio. [幷,[l,2-a]u is more than 嗓-2-yl)-methanone, [4-(5-gas-4-methylamino-mouth-2-ylamino)-3-decyloxy -phenyl]·(2-light-sigma-1 -yl)-carboxamidine [4·(5-chloro-4-methylamino-------------- Lacto-phenyl]-(4,4-didecyl-σ-decyl-1 -yl)-indole, [4-(5-murine-4-methylamino-.-denyl-2-ylamino) -3 -Methoxy-phenyl]-(3,5-dimercapto-piperidin-1-yl)-methanone, [4-(5-gas-4-methylamino- 鸣定定-2- Amino)-3-methoxy-phenyl]-[4-(1-hydroxy-1-methyl-ethyl)-piperidin-1-yl]-methanone, [4-(5-qi 4-曱Amino-N-amino-2-ylamino)-3-decyloxy-benzyl]-(3 - 156325.doc •78-201202215-pyrrolidin-1-yl)-A Ketone, [4-(5-gas-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-indolyl-α-beta-1-yl)- Methyl ketone, [4-(5-Ga-4-indoleyl-mouth-2-ylamino)-3-methoxy-phenyl]-pyridin-1-yl-methanone, [4- (5-disc-4-amino-indot-2-ylamino)-3-methoxy-phenyl]-(4,4-difluoro-α-decyl-1-yl)-oxime , [4-(5-lacty-4-methylaminopyridin-2-ylamino)-3-methoxy-phenyl]-(3 -曱^ yl-piperidin-1-yl ketone, [4-(5-gas-4-methylamino-σ-dept-2-ylamino)_3-methyllacyl-phenyl]-(4 -decyloxy-predomin-1-yl)-methanone, [4-(5-chloro-4-methylamino-σ-pyridin-2-ylamino)-3-methoxy-phenyl] -(3,3_二气-旅17定-1-基)-曱嗣5 [4-(5-Aza-4-methylamino- σ-denyl-2-amine-amino)-3-anthracene -Phenyl]-(4-fluoro-pyridin-1-yl)-indole, 0 [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy -phenyl]-(3-decyloxy-piperidin-1-yl)-methanone, [4-(5·murine-4-methylaminopyridin-2-ylamino)-3-oxime -Phenyl]-(4-ethyl-based-pyridin-1-yl)-fluorenone, [4-(5-murine-4-nonylamino-but-2-ylamino)-3-曱lacyl-phenyl]-(3-difluoroindolyl-ninnyldin-1-yl)-曱明, [4-(5-murine-4-methylamino-denyl-2-amino) -3 -decyloxy-phenyl]-[4_(2-propionyl-ethyl)-tour 嗓-1-yl]-曱嗣' [4-(5-Ga-4-methylamino-pyrimidine- 2-Aminoamino)-3_decyloxy-phenylindole 2-indole 156325.doc -79- 201202215 ke-°Piloate-1 -yl)·曱嗣, [4-(5-chloro_4_ Methylamino-pyrimidin-2-ylamino)_3_methoxy-phenyl]_(4_hydroxyl - pie. Ding-1-yl)·曱, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl b (2-methyl-pyrene- 1-based)-A, [4-(5-aero-4-methylamino-pyrimidin-2-ylamino)_3_indolyl-phenyl]-n-pyrrolidin-1-yl-ketone , [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)_3_methoxy-phenyl]_(4_甲烧石黄醢基-π底唤-1-yl)- A class, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-trimethyl fluorenyl) )-a copper, [4-(5-gas-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]_[4_ (2,2,2-trifluoro-B (2-)-[2-(5-gas-4-methylamino-pyrimidin-2-ylamino)oxyl-phenyl]-(2-methyl-吗琳-4-yl)-曱嗣> [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)_3_decyloxyphenyl]-(2,6-dimethyl -Morline-4 -yl)-brewed j, [4-(5-aero-4-methylamino-pyrimidin-2-ylamino)_3_methoxy_phenyl]_(2,2_ 2 Ethyl-morphine-4-yl)-methyl iq, [4-(5-aero-4-methylamino-pyrimidin-2-ylamino)_3_methoxy_phenyl b (3_hydroxyl) Base-Merlin-4-yl)-A class, [4-(5-chloro-4-methylamine) -pyrimidin-2-ylamino)_3_foxy-phenyl]-(2-isobutyl-morpholin-4-yl)-methanone, [4-(5-a-4-phenylamino-pyrimidine) _2_ylamino)_3_methoxy_phenyl]_(2_hydroxy 156325.doc •80· 201202215 fluorenyl-morpholin-4-yl)-fluorenone, [4-(5-gas- 4-Methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3,3-dimethyl-morpholin-4-yl)-methanone, [4-(5 - gas-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methyl'yl-piperazin-1-yl)-methanone, ; (5-Gas-4-Methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4-isopropyl-Ben-qin-1-yl)-methanone, [ 4-(5-Gatro-4-indolyl-mouth 13-yl-2-ylamino)-3-decyloxy-phenyl]-Lv oxazin-1-yl-methanone, [4-(5 - gas-4-methylamino--densyl-di-2-ylamino)-3-decyloxy-phenyl]-(3-oxa-8-aza-bicyclo[3.2.1]xin- 8-yl)-methanone, [4-(5-gas-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-((S)-3-methyl -Methyl-4-yl)-fluorenone, [4-(5-gas-4-methylamino-feeding 11-denyl-2-ylamino)-3-methoxy-phenyl]-(2 - Oxa-5-aza-bicyclo[2.2.1]hept-5-yl)-methanone, [4-(5-qi-4-曱) Amino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(8-oxaindole-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone, [4-(5-Gas-4-Methylamino- σ-Bitter-2-ylamino)-3-methoxy-phenyl]-((R)_. 3-Methyl-morpholine-4 -yl)-methanone, [4-(5-murine-4-mercapto- lymidyl-2-ylamino)-3-decyloxy-phenyl]-(4-cyclopropanecarbonyl- Piperazine-1-yl)-fluorenone, [4-(5-a 4-amino-4-ylamino- σ-Butyl-2-ylamino)-3-decyloxy-phenyl]-(3-? [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy-- Phenyl]-[4- 156325.doc -81- 201202215 (1 methyl-°chen. 4-yl)-cyanozin-1-yl]-methanone, [4_(5-(4-carb-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]_ (3,3-difluoro-fluorenylbutane-1-yl)-methanone, [4, gas + methylamino-pyridin-2-ylamino)_3_methoxyphenyls Methylamino 'Bottom-1-yl)-methanone, [4 (helium-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]-(4-piperidyl疋4 base-π bottom 嗓_ι_ base) _ ketone, [4 (5~ gas-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2 -oxa 6-aza-spiro[3.3]heptan-6-yl)-methanone, [4 (5-chloro-4-methylamino-pyrimidin-2-ylamino)_3_trifluoromethoxy_ Phenyl^morpholin-4-yl-fluorenone, [4 (5-a-cyclo-4-propoxy-pyrimidin-2-ylamino)_3_methoxy-phenyl]-morpholin-4-yl , ketone, [4 (5-a 4-phenylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]-morphine-based fluorenone, [4 (5-cyclobutyl) 4--4-oxo-pyrimidin-2-ylamino)_3_methoxy-phenyl]-morpholinyl-fluorenone, [4 (5-cyclobutyl-4-methylamino-pyrimidine-2 -ylamino)_3_decyloxy-phenyl]-morpholin-4-yl-methanone, [4-(5-cyclopropyl-4-methylamino-pyrimidin-2-ylamino)_3_曱oxy-benzene []-morpholin-4-yl-methanone, [4~(5-cyclopropyl-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-morpholine '4-yl-fluorenone, [4_(S-fluoro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-?156325.doc -82- 201202215 】 4-yl-ketone, [4-(5-Ga-4-amino-pyroo-2-amino)-3_decyloxy-phenyl]-(4-%-piperidine- 1-yl)-methanone, [4-(5-indole-4-indolyl-sulphonyl-2-ylamino)-3-methoxy-phenyl]-writing' porphyrin_4_yl • ketone, [4-(5-indole-4-nonylamino-bitter-2-ylamino)-3-decyloxy-phenyl]-morpholine-4-yl-fluorenone, [4 -[5-Gatro-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-(2,2,2, fluorene trifluoro-ethoxy)-phenyl] -morpholin-4-yl-fluorenone, [5-chloro-2-ethoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl] - 吓 * 4-yl-carbamidine, [5-gas-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl ]-派 ° Qin-1-yl-indole, [5-gas-2-oxo-4-(4-methylamino-5-trimethyl-pyrimidin-2-ylamino)-benzene ]]-(2,6-dimercapto-morpholin-4-yl)-methanone, ◎ [5-Ga-2-indoxy-4-(4- Amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morphin-4-yl-fluorenone, [5-gas-4-(4-ethylamino-5-) Trifluoromethyl-pyrimidin-2-ylamino)-2-oxo-yl-phenyl]-oxalin-4-yl-methylhydrazine, • [5_ gas-4-(5-gas_4_ Ethylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]·morpholin-4-yl-methanone, gas _4-(5-chloro-4-methoxy-pyrimidine _ 2_ylamino)_2_methoxy-phenyl]-morpholin-4-yl-methanone, [5-chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamine) ))_2_methoxy_phenyl]_ 156325.doc •83- 201202215 morpholin-4-yl-methanone, [5-gas- 4- (5-gas-4.methylamino sigma- 2-Aminoamino)-2-indolyl-phenyl]-(4,4-difluoro-pred-1-yl)-fluorenone, [5-chloro-4-(5-gas-4- Methylamino-Nandrolactyl-2-ylamino)-2-methoxy-phenyl]-pyrazin-1-yl-ketone, [5-gas-4-(5-chloro-4-methyl) Amino-pyrimidin-2-ylamino)·2-methoxy-phenyl]-(4-dimethylamino-piperidin-1-yl)-fluorenone, [5-rat-4 - (5 - chaos _ 4 - amidino-dipyl-2 -ylamino)-2 -indolyl-phenyl]_(3 -yl-pyridylpyrazine-1 -yl)-carboquine[ 5-Gas- 4- (5-Gas-4-Methylaminopyrrolidine-2-ylamino) )-2 -曱-milyl-phenyl]_ indoprozol-1 -yl-fluorenone, [5-gas- 4- (5-gas-4-methylamino-mouth). Des-2-ylamino)-2-methoxy-phenyl]-(4-trans-yl-pyridyl-1-yl)-indole_, [5-random-4-(5-gas-4) -nonylamino-ylamino)-2-indolyl-phenyl]-(2-hydroxymethyl-morpholin-4-yl)-fluorenone, [5-wind*-4-(5-disorder -4-Methylamino-- dimethyl-2-methylamino)-2-methoxy-phenyl]-[1,4]oxazepan-4-ylindolone, [ 5-Gas- 4-(5-Gas-4-Amino-thio-l-ylamino)-2-indolyl-phenyl]_((2R,6S)-2,6- Dimercapto-morpholin-4-yl)-fluorenone, [5-lactal-4-(5-a)-4-mercapto-milami-2-ylamino)-2-mercapto-phenyl ]·(3-Hydroxy-azetidin-1-yl)-fluorenone, [5-milk- 4-(5-disorder-4-methylamino-β-denyl-2-amine) -2 - oxime-phenyl]_((3R,5S)-dimercapto-piperazin-1-yl)-methanone, [5-ethoxy-2-fluoro.4-(4-曱Amino-5-trifluorodecyl-pyrimidin-2-ylamine 156325.doc -84· 201202215 base)·phenyl]-? scare ^ _ 4 -yl-曱嗣' [5-ethoxy- 4- (4-ethylamino-5-dioxadecyl-mouth-2-ylamino)-2_gas-phenyl]-oxalin-4-yl-methylhydrazine 9 {4-[5-> stinky -4-(2-decyloxy-ethoxy)-[Methoxy-2-ylamino]-3-methoxy -Phenyl}-intimidation - 4 -yl-indole S, {4-[5-> odor-4-(2-methoxy-ethylamino)- ̄ ° 定 - - 胺]-2-Ga-5-methyllacyl-phenyl}-Merlin-4-yl-曱嗣' {4-[5->Smelly-4-(2-decyloxy-ethylamino)- 1111定-2-ylamino]-3-ethoxy-phenyl}- 吓 & - - - -4 - 基 -甲晒 9 {4-[5-> Base-ethylamino)-.密定-2-ylamino]-3-isopropoxy-phenyl}_?-line-4-yl-曱S with 5 {4-[5-> odor-4-(2-methoxy -ethylamino)-cyclohexyl-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone, {4-[5-chloro-4-(1) -mercapto-cyclobutylamino)-pyrimidine-2-ylamino]-3-methoxy-phenyl}-oxalin-4-yl-methylhydrazine* {4-[5-乱乱-4- (2, 2, 2 - 2 - Ethyl) - Xiao. -2--2-ylamino]-3-methoxy-phenyl}-morphine-4-yl-曱Sl^J ' {4-[5-gas-4-(2,2-digas-B Amino)-0-denyl-2-ylamino]-3-decyloxy-phenylmorpholin-4-yl-fluorenone, {4-[5-rat-4-(2-platinum-propyl) -Ethylamino)-Mouth sigma-2-ylamino]-3-indolyl-phenyl}-oxalin-4-yl-methylhydrazine* {4-[5-gas-4- (2 - 曱 石 黄 - - ethylamine) - ϋ ϋ -2 - 2 - ylamino] - 3 - decyloxy - phenyl} - morpholin-4-yl-methanone, {4 · [5 - Chloro-4-(2-methoxy-ethoxy)-pain-2-ylamino]-3-cyclobutoxy 156325.doc • 85 - 201202215 phenyl-phenyl}-morpholin-4- Keto-ketone, {4-[5-chloro-4-(2-methoxy-ethoxy)-mouth bite_2_ylamino]_3_decyloxy-phenyl}-Merlin-4 -yl-carboquine' {4-[5-chloro-4-(2-methoxy-ethylamino)-] ηη定-2-ylamino]-3-cyclobutoxy-phenyl Morpholin-4-yl-fluorenone, {4-[5-chloro-4-(2-decyloxy-ethylamino)-penetrating _2-ylamino]-3-decyloxy-phenyl }-morpholin-4-yl-methanone, {4-[5-gas_4_(2-methoxy-propylamino)-» 密_2-ylamino]_3_methoxy-phenyl }-morpholin-4-yl-fluorenone, {4-[5-chloro-4-(cyclobutylindolyl-amino)-pyrimidine啶_2_ylamino]_3_methoxy-phenyl}-morpholin-4-yl-methanone, {4-[5-gas-4-(cyclopentylmercapto-amino)-pyrimidine -2_ylamino]_3_decyloxy-phenyl}-morpholin-4-yl-methanone, {4-[5-gas-4-(cyclopropylmethyl-amino)-pyrimidine_ 2_ylamino]_3_methoxy-phenyl}-morpholin-4-yl-methanone, {4-[5-gas- 4- (tetrahydro-σf0-n--3-ylamino) )-Blowing _2_ylamino]_3_methyllacyl-phenyl}-?--4-yl-曱嗣' {4-[5-chloro-4-(tetrahydro-pyran-3-) Amino group)-. Bite 2_ylamino]_3_methoxy-phenyl}-morpholin-4-yl-methanone, {4-[5-gas-4-(tetrahydro-pyran-4-yloxy) Base)-°Bite 2-amino-amino]_3·•methoxy-phenyl}-morpholin-4-yl-fluorenone, Κ4_(5_演_4_methoxy mouth bite_2_ Aminoamino)_3_methoxyoxanyl) piperidine_ 4-carbonitrile, 1-[2-fluoro-5-decyloxy-4-(4-guanidino-5-trifluoromethyl-. Density. _2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 5--5-trifluoromethyl-pyrimidine-2-ylamino)-benzylindolyl-piperidin-4-indrene, 1-[4-(5->odor-4-nonylamino-^密定-2-ylamino)-3-methyllacyl-carboxenyl]·Lvdian-4-carbonitrile, 1-[4-(5-Gas-4-methylamino--] -2-ylamino)·3·decyloxy-branched base]_ Brigade σ定-4-甲猜, 1_[5_Chloro-2-indole-based 4-(4-amidinoyl_5 _二气曱基-响17定-2·ylamino)-benzylbenzyl]pyrrolidine-3-carbonitrile, 1-[5-chloro-4-(5-chloro-4-nonylamino)-喷. -2- 基 基 基 基 基 基 基 基 基 ] ] ] ] ] 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- -σ-Bitter-2-ylamino)-2-methyllate--independent group]-σBilo定-3 - 曱 guess, 1-{2-[2-methoxy-4-(?-*4-mono)-anilino]-4-indolyl----------- • 嗣' 1- {4-[4·(5-Gas-4-Amino-Nandrolidine-2-ylamino)-3-methyllacyl-throki]-piperazine-l- }--ethanone, 2-(2-methoxy-4-(2,2,6,6-tetrafluoromorpholin-4-carbonyl)anilino)-4-(decylamino)pyrimidine-5- Nitrile, 2-(2-indolyl-4-(norpoline-4-propenyl)anilino)-4-(nonylamino). _5_carbonitrile, 2-(4-((33, 43)-3,4-Difluoropyrrolidine-1-carbonyl)-2-oxoanilino)-4-(decylamino)pyrimidine-5-carbonitrile, 2-(4-(4,4) -difluoropiperidine-1-carbonyl)-2-methoxyanilino)-4-(methylamine 156325.doc -87- 201202215 base) °Bite 5-carbonitrile, 2-[2,5- Dimethoxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-1-morphin-4-yl-acetamidine, 2-[2 -曱-oxy-4-(oxalin-4-yl)-anilino]-4-indolyl-mouth bite-5 _ carbonitrile, 2-[2-methoxy-4-(piperidine- 1-carbonyl)-anilino]-4-methylamino-pyrimidine-5-carbonitrile, 2-[2-decyloxy-4-(pyrrolidin-1-carbonyl)-anilino]-4-decylamine Base-pyrimidine-5-phthalonitrile, 2-[3.methoxy-4-( 4-Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-1-morpholin-4-yl-ethanone, 2-[4-((211,68)- 2,6-diamidino-morpholine-4-carbonyl)-5-fluoro-2-methoxy-anilino]-4-indolyl-pyrimidine-5-carbonitrile, 2-[4-(( 211,68)-2,6-diamidino-morpholin-4-carbonyl)-5-fluoro-2-indolyl-anilino]-4-ethylamino-pyrimidine-5-indolecarbonitrile, 2- [4-((R)-3-fluoro-η-pyridyl-oxime-carbonyl)_2•decyloxy-anilino]-4-indolyl- thyridine-5-indolecarbonitrile, 2-[4- ((8)-3-Fluorine_.比 咯 - 卜 卜 羰 羰 羰 羰 羰 羰 羰 羰 羰 羰 羰 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 )-2-methoxy-anilino]-4_nonylamino-pyrimidine carbonitrile, 2-Γ4-Γ3 3-- ^ '- 虱-pyrrolidine-1-carbonyl)-2-methoxy-aniline 4-ylamino---[M-[4-(3-fluoro, _, oxetane-1-carbonyl)-2-nonyloxy-anilino] -4-曱156325.doc • 88 · 201202215 Amino-pyrimidine-5-carbonitrile, 2-[4-(5-bromo-4-methoxy-bine-2-amino)-3_ Methoxy-phenyl l·1-morphin-4-yl-ethyl-, 2-[4-(5-xi-4-ylamino-pyrazine-2-aminol)-2,5- Dimethoxy-phenyl]-1-oxalin-4-yl-ethyl-, 2-[4-(5-gas-4-methoxy-feeder-2-aminocarbyl)_2,5_ Dimethoxy-phenyl]-1-morphin-4-yl·ethanone, 2-[4-(5-gas-4-methoxy-τ»密咬_2_ylamino)_3- Methoxy-phenyl]-1-morphin-4-yl-ethyl g, 2-[4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2,5 -dimethoxy-phenyl]-1 -morphine- 4 -yl-ethyl copper, 2-[4-(5-a-4-amino-amino-actino-2-ylamino)-3- Methoxy-phenyl]-1-intimidation _4-yl-acetamidine, 2-[4-( Gasocyclic heterocyclic ketone-1-yl)_2-methoxy-anilino]-4-famino-pyrimidine-5-indolecarbonitrile, 2-[5-fluoro-2-methoxy-4-( Morpholine-4-carbonyl)-anilino]methylamino-pyrimidine-5-carbonitrile, 2-fluoro-5-methoxy-N-(2-methoxy-ethyl)-N-methyl- 4-(4-Amidino-5-dimethylmethyl-3-broth-2-ylamino)-tubular amine 2-fluoro-5-methoxy-N-methyl-4-(4- Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylamine, 2-fluoro-N-(2-hydroxy-2-methylpropyl)-5-methoxy-N- Mercapto-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino) decylamine, 3-methoxy-4-(4-methylamino-5 -trifluoromethyl-pain-2-ylamino)-N-oxygen 156325.doc •89- 201202215 Heterocyclobutane-3-yl-benzylamine, 3_methoxy- 4-(4- Amidino-5-dioxamethyl-indolyl-2-ylamino)-indole-(1-decyl-piperidin-4-yl)-nodal amine, 3-methoxy-N-(2 -decyloxy-ethyl)-4-(4-methylamino-5-dioxamethyl-pyrimidin-2-ylamino)-nodal amine, 3-decyloxy-N-(2-A Oxy-ethyl)-N-indolyl-4-(4-methylamino-5-trifluorodecyl-pyrimidin-2-ylamino)-benzylamine, 4-(4-ethylamino- 5-trifluoromethyl-pyrimidine-2- Amino)-2-fluoro-5-decyloxy-N-(2-decyloxy-ethyl)-N-indolyl-benzylamine, 4-(4-ethylamino-5-difluoromethyl Kimi-2-ylamino)-3-methoxy-phenyl]-morphin-4-yl-methanone, 4-(4-ethylamino-5-trifluoromethyl-pyrimidine-2 -ylamino)-3-methoxy-N-(2-methoxy-ethyl)-N-indolyl-benzylguanamine, 4-(5-chloro-4-(decylamino)pyrimidine- 2-ylamino)-N,N,3-trimethylbenzylamine, 4-(5-chloro-4-methylamino-n-dimethyl-2-ylamino)-3-anthracene- Brewing amine '4-(5-chloro-4-methylamino-feeding). 4-(Aminoamino)-3-indenyl-N-(tetrazine-birth sigma-3-yl)-inosine' 4-(5-chloro-4-methylamino-pyrimidine-2 -ylamino)-3-methoxy-oxime, fluorenyl-dimercapto-benzylguanamine, 4-(5-chloro-4-nonylamino-.stimin-1-ylamino)-3 -nonyloxy-fluorenyl-mercapto-carboxamide, 4-(5-chloro-4-indolyl- σ-mercapto-2-ylamino)-3-decyloxy-oxime-oxadol Alkyl-3-yl-benzamide, 156325.doc -90- 201202215 4-(5-chloro-4-indolyl-oxo-di-2-amino-)-Ν_ί哀propyl-3 - methyl milk Base-benzylamine, 4·(5-chloro-4·decylaminoguanidino-2-ylamino)-indole-ethyl-3-hydrazinyl-nodal amine, 4-(5-chloro- 4-曱amino-- dimethyl-2-amino-amino)-indole-isopropyl-3-hydranyl benzyl benzylamine, 4-(5-murine-4-ethylamino- σ- -2-2-Amino)-2-a-5-methoxy-indole, Ν-dimercapto-nodal amine, 4-(5-alkyl-4-nonylamino------ -ylamino)-2-a-5-indoleyl-indole, indole-dinonyl-benzylamine, 4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)- 3_曱-oxy-indole, fluorenyl-dimercapto-benzylguanamine, 4-(5-alkyl-4-indenyl-salt-2-ylamino)-3-methyllacyl-N- Mercapto-benzazole , 4-(5-oxy-4-methylaminoammonium-2-ylamino)-indole-(2,2-di-ethyl-ethyl)-3-methoxy-haloxime, 4- (5 - 乱 曱 -4- 曱 - ° ° 密 -2- 基 基 基 基 Ν ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( -(5-alkyl-4-methylamino-whistamin-2-ylamino)-indole, indole-diethyl-3-indolyloxy-benzylamine, 4-(5-carbyl- 4 - amidino-^^-2-ylamino)-hydrazinyl-propyl-decyl-l-decyloxy-benzylamine, 4-(5-ranyl·4·decylamine-^密定定_2_基胺基)-Ν-ethyl-3-hydrazine-based benzylamine, 156325.doc •91 · 201202215 4-(5-cyano-4-methylamino-pyrimidine-2 -ylamino)_N_ethyl_3_methoxy_N-methyl-nodalamine, 4-(5-cyano-4-indenyl-pyrimidin-2-ylamino)_N_B _N_isopropyl_ 3-decyloxy-benzylamine, 4-(5-cyano-4-methylaminocarbyl-2-ylamino)_N_isopropyl_3_oxime Base-tubergic amine, 4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)_N_isopropyl_3_methoxy-N-methyl-benzylamine, 4 _ethylamino-2-[5-fluoro-2-methoxy-4-(morphin-4-ylcarbonyl)-anilino]-pyrimidine-5-carbonitrile, 4-methoxy-2-[2 -methoxy-4-(? _4-arginyl)-anilino]_Bite- 5-carbonitrile, 5-chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamine Base)-N-(lf-yl-piperidine-4-yl)-benzylamine, 5-chloro-2-indolyl-4-(4-methylamino-5-trifluoromethyl-pyrimidine_2 _ ylamino)_N-oxetan-3-yl-benzylamine, 5-chloro-2-methoxy-N,N-dimethyl-4-(4-methylamino-5 -Trifluoromethyl-pyrimidin-2-ylamino)benzamide, chloro-4-(4-ethylamino-5-trifluoromethyl-mouth. _2_2_ylamino)_2_曱oxy_ Ν·(2-decyloxy-ethyl)-benzylamine, 5-chloro-4-(5-chloro-4-methoxypyrimidine-2 -ylamino)-2-decyloxy-N-mercaptobenzylamine, 5-murine-4-(5-gas-4-methylamino-mouth succinyl-2-ylamino)-2-曱oxy-oxime, Ν-dimethyl-benzylamine, 156325.doc • 92· 201202215 5 - gas-4-(5-gas-4-methylamino-salt-2-ylamino)- 2-曱-lactyl-N-(2·decyloxy-ethyl: l·benzylamine, 5·gas-4-(5-chloro-4-famino-indole-2-ylamino )-2-methyllacyl-N-mercapto-peptidylamine, 5-gas- 4-(5-a-4-pyramino-methylidene-2-diamino)-2-methoxy Ν-Ν-oxa; cyclobutane-3-yl-benzylamine, 5-chloro-4-(5-chloro-4-famino-feed-2-ylamino)_2_decyloxy -Ν-(1· decyl-piperidin-4-yl)-benzylguanamine, 〇5-chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2- Methoxy-indole-(2-methoxy-ethyl)-indole-methyl-benzylamine, 5-air-4-(5-milk-4-methylamino--succinyl-2- Aminomethyl)-2-methyllacyl-indole-(1 _indolyl-cyclobutyl)-benzylguanamine, 5-chloro-4-(5-chloro-4-methylaminocarbazin-2-yl Amino)-N-(l-carbyl-3⁄4propyl)-2-methoxy- Indoleamine, 5-air-4-(5-aza-4-methylamino- cytidine-2-ylamino)-indole-(2-lightyl-2-indolyl-propyl)- 2-decyloxy-n-butylamine 5 〇5-gas-4-(5-disorder-4-hydrazino-.-densyl-2-aminoamino)-fluorene-(2-carbyl-ethyl -2_methoxy-oxime-methyl-benzylamine, -5-gas-4-(5-a-4-amino-amino-amino-amino)-Ν-(2 -transyl-propyl-yl)-2-decyloxy-peptidylamine, 5-air- 4-(5-disorder-4-nonylamino-salt-2-ylamino)·Ν- 哀Propyl-2-decyloxy-nodal amine, 5-chloro-N-(l-muryl-cyclopropyl)-2-methoxy-4_(4-aminoamine-5-dione) -pyrimidin-2-ylamino)-benzylguanamine, 156325.doc -93- 201202215 5-chloro-N-(1-cyano-cyclopropyl)-2-methoxy-4_(4- decylamine —- _ 二 二 - - - - - - - - - , , 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 (4_Methylamine, $trifluoromethyl-pyrimidin-2-ylamino)-benzylamine, 5-chloro-N-(2-transyl-2-methylpropyl)-2-decyloxy -n.曱4 (4Methylamino-5-trifluoromethyl-deni-2-ylamino)-nodal amine, 5-chloro-indole-cyclopropyl-4-(4-ethylamino) -5-trifluoromethyl-sound bite _2 mesamine)-2-methoxy-benzylamine, II heterocyclobutan-1-yl-[4-(5-chloro-4-nonylamino-n-bcc-2-aminoamine) 3 methoxy-phenyl]-fluorenone, Ν-(3,3-difluoro-cyclobutyl)-3-decyloxy-4-(4-methylaminotrifluoromethyl)pyrimidine-2- Aminoamine)-nodal amine, Ν-(3-aminopropyl)-4-(5-gas-4-(methylamino)anthracene-2-ylamino)_3_decyloxy nodal Amine, Ν-(3-amino-propyl)-4-(5-chloro-4-indolyl). Ding-2-ylamino)-3-decyloxy-nodal amine, Ν-(3-amino-propyl)-5- -4-(5-chloro-4-methylamino-mouth bite -2-ylamino)-2-methoxy-oximeamine, Ν-(4,4-difluoro-cyclohexyl)-3-methoxy-4-(4-guanidino-5-trifluoro Sulfhydryl-mouth-2-ylamino)-tuberculin, hydrazine, hydrazine-diethyl-3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidine-2 -ylamino)-benzylamine, hydrazine-ethyl-2-fluoro-5-methoxy-indole-(2-methoxy-ethyl)-4-(4-amidino-5-three Fluorinyl-pyrimidin-2-ylamino)-benzylamine, 156325.doc •94· 201202215 N-ethyl-3-methoxy_N_indenyl_4_(4-methylamino-5 _Trifluoromethyl-pyrimidin-2-ylamino)-Heptaamine, N-ethyl-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2 _Fluoryl-5-oxime-N-(2-decyloxy-ethyl)-benzylamine, N-tert-butyl-4-(5-cyano-4-indenyl-pyrimidine-2- Amino)-3_methoxy-tuberamine, and N-second butyl chloride_4-(5-a-4-aminoamine-0-denyl-2-ylamino)_2_ Methoxy-benzylamine, or a pharmaceutically acceptable salt thereof. In certain embodiments, the invention provides a compound as described herein, selected from the group consisting of: [3-methoxy-4-(4-T-amino-5-trifluoromethyl-pyrimidine- 2-Aminoamino)-phenyl]-? 1- 4-yl-methyl-, (5-Gas-2-indolyl-4-(4-(decylamino)-5-(trifluoromethyl)pyrimidine 2-ylamino)phenyl)(full deuterated (N-morphinyl))fluorenone, (5-fluoro-2-indolyl-4-(4-(decylamino)-5-() Trifluoromethyl)pyrimidin-2-ylamino)phenyl)(N-morphinyl)methyl-, [2-fluoro-3-methoxy-4-(4-nonylamino-5-trifluoro) Methyl-pyrimidin-2-ylamino)-phenyl]-morphin-4-yl-indole, [3- gas-4-(5-ox-4-indole-pyrimidin-2-ylamine) ()phenyl]-morpholin-4-yl-fluorenone, [3-isopropoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamine basic group] - 吓 ^ ^ - 4 - yl-methyl hydrazine, [4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)_2_fluoro_5-methoxy 156325.doc -95 · 201202215 phenyl-phenyl]-oxalin-4-yl-carboxamidine, [4-(5-gas-4-methoxyt-butyl-2-ylamino)·3-methoxy-phenyl] _ 琳琳-4-yl-ketone, [5-wind-2-曱-lacyl-4-(4-methylamino-5-difluoromethyl-mouth _2_2_1 Amino)-phenyl]-morphin-4-yl-indole, [5-chloro-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)_2_曱oxy-phenyl]-morphin-4-yl-methane|, [5-ethoxy-2-fluoro-4-(4-decylamino-5-difluoromethyl-sound bite_2 -ylamino)-phenyl]-morphin-4-yl-carboxamidine, 2-(2-decyloxy-4-(morpholin-4-carbonyl)anilino)-4-(methylamino) Pyrimidine _5_phthalonitrile, and hydrazine-tert-butyl-4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-benzylamine, or its medicinal An acceptable salt. In certain embodiments, the present invention provides a composition comprising: (a) a pharmaceutically acceptable carrier; and (b) a compound of claim 1. In certain embodiments Medium: A compound of an active substance. The present invention is used as a treatment as described herein. In certain embodiments, the present invention provides a method for the treatment of the following diseases from a*? Huntington's disease, Lewy body dementia, Alzheimer's kidney: 乂: Bar: Difficulty in movement, cancer or proliferative disorders (such as Zhao: white: two adenocarcinoma, gray cancer, papillary or lung cancer, acute bone bone Tumor), or an inflammatory disease (such as leprosy, 156325.doc • 96-201202215 Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, and ankylosing spondylitis), which involves An individual is administered an effective amount of a compound as described herein. In certain embodiments, the invention relates to the use of a compound as described herein for the manufacture of a medicament for the therapeutic and/or prophylactic treatment of Parkinson's disease, Huntington's disease, and Lewy body. Dementia, Alzheimer's disease, L-dopa-induced motor difficulties, cancer or proliferative disorders

Such as kidney cancer, breast cancer, prostate cancer, blood cancer, papillary or lung cancer, acute myeloid leukemia or multiple myeloma, or inflammatory diseases (such as leprosy, Crohn's disease, muscular atrophy (four) hardening, rheumatoid Arthritis and ankylosing spondylitis] In the present invention, 'the present invention provides a compound for use as a therapeutically active substance as described herein' for the therapeutic and/or prophylactic treatment of the following diseases: Parkinson's disease Disease, Huntington's disease, Lewy body dementia, Alzheimer's disease: disease, L-dopa-induced exercise difficulties, cancer or proliferative disorders (such as kidney cancer, breast cancer, prostate cancer, blood cancer, papillary cancer or lung cancer, Acute myeloid leukemia or multiple myeloma), or inflammatory disease (such as leprosy, 5's amyotrophic lateral sclerosis, rheumatoid arthritis, and ankylosing spondylitis). In certain embodiments, the present invention provides a method of treating Parkinson's disease, Huntington's disease, dementia, Alzheimer's disease, or l. dopa, which is difficult to achieve. The individual is administered an effective amount of a compound as described herein.本中 'The present invention relates to a compound as described herein 156325.doc •97-201202215 疒,上" is used to manufacture therapeutic and/or prophylactic treatment of Parkinson's disease 7 tonton's disease, Lewy body A drug that is difficult to exercise in dementia, Alzheimer's disease, or L-dopa. In certain embodiments, the present invention provides for the incorporation of "ΛΤ, /ΰ I soil delta, as described herein, for the therapeutic and/or prophylactic treatment of Parkinson's disease 7 Tinton's disease. , Lewy body dementia, Alzheimer's disease or L_dopa induced exercise difficulty. In a certain embodiment, the present invention provides a method for treating Parkinson's disease, which comprises injecting to an individual in need thereof An effective amount of a compound as described herein. Certain embodiments make the invention in relation to a compound as described herein for use in the manufacture of a medicament for the therapeutic and/or prophylactic treatment of Parkinson's disease. In certain embodiments, the invention is described as a compound for use as a therapeutic active, as described herein, for use in, <RTIgt; Also provided is a method of treating a disease or condition mediated by or otherwise associated with the LRRK2 receptor, the method comprising administering to a subject in need thereof an effective amount of a compound of the invention. Can be a neurodegenerative disease, such as Parkin Disease, Huntington's disease or Lewy body dementia. The disease can be a CNS condition, such as A (four) Mohs disease and L. dopa-induced exercise difficulties. 5 Hei disease can be cancer or hyperplasia, skin, puerperium f illness, such as kidney cancer, breast cancer, forefront 156325.doc • 98. 201202215

Adenocarcinoma, gray pain, sputum 5S squamous cell carcinoma or lung cancer, acute myeloid leukemia or multiple myeloma. The disease can be a Han Chinese disease such as leprosy, Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis and ankylosing spondylitis. The invention also provides a method of enhancing cognitive memory comprising administering an effective amount of a compound of the invention to a subject in need thereof. Representative compounds of the methods of the invention are shown in the experimental examples below. Synthesis 0 The compounds of the present invention can be prepared by a variety of methods as described in the illustrative synthetic reaction schemes shown and described below. Starting materials and reagents for the preparation of such compounds are generally commercially available from commercial suppliers, such as Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art and following the procedures set forth in the references. ; literature such as Fieser and Fieser, Reagents for Organic

Synthesis; Wiley & Sons: New York, 1991, Volumes 1-15; Q R〇dd, Chemistry of Carbon Compounds, Elsevier Science

Publishers, 1989, vol. 1-5 and supplements; and 〇rganic Reacti〇ns, Wiley & S_: New York, 1991, vol. 1-40. The following synthetic reaction schemes merely illustrate some of the methods by which the compounds of the present invention can be synthesized, and various modifications can be made to the synthetic reaction schemes, and those skilled in the art will appreciate that such modifications are included in the present application. The disclosure. Where necessary, the starting materials and intermediates of the synthetic reaction scheme can be isolated and purified using conventional techniques including, but not limited to, filtration, distillation, crystallization, chromatography, and the like. These materials can be characterized using conventional means, including physical numbers 156325.doc -99-201202215 and spectral data. Unless otherwise stated to the contrary, the reactions described herein can be carried out under an inert atmosphere at atmospheric pressure at from about -78 ° C to about 150. (or (e.g., about 〇 ° C to about 125 ° C) or preferably at about room temperature (or ambient temperature) (e.g., about 20 ° C). Scheme A below illustrates one that can be used to prepare a particular formula. Or a synthetic procedure for a compound of formula π, wherein X, m, R1, R2, R3, R5, R6 and R7 are as defined herein.

In the first step of Scheme A, the dichloropyrimidine compound a is reacted with the reagent b to produce a pyrimidine compound c. The reaction of step 1 can be carried out under polar solvent conditions. In the examples of the present invention, when X is (reagent b is an alcohol), the step reaction can be carried out in the presence of the test. In step 2, the pyrimidine compound is reacted with the aminobenzoic acid compound d to produce the aminopyridine compound e. The reaction of Step 2 can be carried out in a polar protic solvent and in the presence of an acid such as HCl. 156325.doc 100·201202215 The indoleamine coupling reaction is carried out in step 3, wherein compound e reacts with amine f to produce a compound of formula I or formula II of the present invention. The chiral amine coupling reaction of Step 3 can be carried out using various well-known indole coupling reagents, such as carbodiimide (such as DCC, in the presence or absence of a stupid triterpene derivative such as HOBt, HOAt, DhbtOH, and the like). DIC, EDC, and the like), ammonium salts (such as HATU, HBTU, TBTU, and the like) or scale salts (such as BOP, PyBOP, and the like). In other embodiments, an acid chloride or anhydride intermediate (not shown) can be used to form the guanamine. Many variations on the Process A procedure are possible and should be understood by those skilled in the art. Specific details for the manufacture of the compounds of the invention are described in the Examples below. Administration and Pharmaceutical Compositions The present invention includes pharmaceutical compositions comprising at least one compound of the present invention or an individual isomer, isomer thereof, racemic or non-racemic mixture or pharmaceutically acceptable salt or solvent. And at least one pharmaceutically acceptable carrier and, optionally, other therapeutic and/or prophylactic ingredients. As usual. The compounds of the invention will be administered in a therapeutically effective amount by any of the accepted modes of administering a medicament that provides a similar utility. The appropriate dosage range depends on many factors, usually 1-500 mg of horsepower, such as daily 1-3 0 mg, and 兮 蓉 蓉 阳 ,, „„ g ° Factors such as the severity of the disease to be treated, the age of the individual and the relative phase health, the efficacy of the compound used, the route and form of administration, the indications for the investment in the hospital and the preferences and experience of the physician concerned. Those who are generally accustomed to 4 μ 4 of the disease do not need to experiment too much and rely on personal knowledge and this application – the content of the inventive compound can be determined for the therapeutically effective amount of the established disease. The term "pharmaceutically acceptable excipients" and any ingredient that is non-toxic, such as for the preparation of a medical product, a therapeutically active mixture, a filler, a solvent, a buffer, a tonicity agent, a disintegrating agent, a viscosity Agent' surfactant or lubricant. Stabilizers, Antioxidants When the palmitic carbon is present in the chemical structure, all stereoisomers are covered by the structure. ~ for dry carbon related = pharmaceutical compositions of the above compounds, methods of use thereof, and all individual embodiments can be combined. The compound of the present invention may be in the form of a pharmaceutical formulation. The fly 4 is also suitable for, and is suitable for, the mouth (including the buccal and sublingual), the rectum, the nasal, the ^ ^. d. ^ the nasal part, the transpulmonary, Inhaled or parenteral (including intramuscular, intra-arterial, intra-orbital, intraoperative, intra-, subcutaneous, and intravenous y-ghost administration by inhalation or insufflation. The specific mode of administration is generally based on the degree of illness. Suitable parental dosage regimen for oral administration. The compound of the invention and or a plurality of conventional adjuvants, beta or diluent may be formulated into a pharmaceutical composition and unit dosage form. Formulations of conventional ingredients are included in the parental formula and the unit dosage form can contain any suitable effective amount of the active ingredient corresponding to the intended range of dosages to be used. The pharmaceutical composition can be used in the form of solids, Such as a lozenge or a capsule filled with a half-mouth, a powder, a performance release formulation; or a liquid, such as a solution, suspension, lotion, tincture or filling capsule for oral use; or for straightening Or 156325.doc •102· 201202215 Suppositories for vaginal administration; or sterile injectable solutions for parenteral use. Therefore, each tablet contains about 4 grams of active ingredient or, more broadly, about 1 mg to about 1 G0 mg. The formulation of the active ingredient is a suitable representative unit dosage form.

〇 The compounds of the present invention can be formulated into a variety of oral administration forms. The pharmaceutical compositions and dosage forms may comprise one or more compounds of the invention or a pharmaceutically acceptable salt thereof as the active ingredient. Pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, lozenges, pills, capsules, cachets, suppositories, and dispersible granules. The solid carrier can be one or more substances which may also act as a diluent, a flavoring agent, a solubilizer, a lubricant, a suspending agent, a binder, a preservative, a tablet disintegrating agent or an encapsulating material. The granules in the powder are generally finely divided solids mixed with the finely divided active ingredient. In lozenges, the active component will generally be mixed in a suitable ratio with the carrier having the necessary binding strength and compressed into the desired shape and size. Powders and lozenges may contain from about 1% to about 7% by weight of active compound. Suitable carriers include, but are not limited to, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, sulfhydryl cellulose, sodium carboxymethylcellulose, Low refining rings, cocoa butter and the like. The term "formulation" is intended to include a formulation of the active compound with the encapsulating material as a carrier, and a capsule in which the active component (with or without a carrier) is surrounded by a carrier associated therewith. Similarly, it is included as a gel and an ingot. Tablets, powders, capsules, pills, troches, and buccal tablets may be in a solid form suitable for oral administration. Other suitable forms for oral administration include liquid form preparations, including emulsions, syrups, elixirs, aqueous solutions, aqueous suspensions, or solid forms of 156325.doc-103-201202215, which are intended to be converted to liquid form prior to use. preparation. The emulsion may be prepared, for example, in a solution of an aqueous solution of propylene glycol or may contain an emulsifier such as lecithin, sorbitan monooleate or gum arabic. The aqueous solution can be prepared by dissolving the active set of knives in the water and adding suitable color formers, flavoring agents, stabilizers and thickening agents. Aqueous suspensions can be prepared by dispersing the finely divided active component in water using a viscous material such as natural or synthetic oxime, resin, sulfhydryl cellulose, slow methylcellulose, and other well known suspending agents. Solid 2 formulations include solutions, suspensions and emulsions, and may contain, in addition to the active component, coloring agents, flavoring agents, stabilizers, buffers, artificial and natural sweeteners, dispersing agents, thickening agents, solubilizing agents, and Its analogues. The compounds of the invention may be formulated for parenteral administration (e.g., by injection, such as bolus injection or continuous infusion) and may be presented in unit dosage form in ampoules! : In a true-filled syringe, a small-volume infusion set, or in a multi-month 1 I bar with added preservatives. The composition may be in the form of a suspension, solution or emulsion, such as an aqueous solution of polyethylene glycol, in an oily or aqueous medium. Examples of the oil L or the carrier, diluent, solvent or vehicle include propylene glycol, vegetable oil (for example, eucalyptus oil), and at. ) the main organic ester (for example, ^ ^ (4) wetting agent, Emulsifiers or suspensions, or 'active ingredients can be obtained from the powder-free type 7 obtained by autolysis of Donggan, for recovery by a suitable medium before use. Halogen-free pyrogen water) The compounds of the invention may be formulated for topical administration to the epidermis in a soft or transdermal patch. The ointment or lotion form can be formulated with an aqueous or oily base with a suitable thickening and/or gelling agent, for example, at 156325.doc 201202215. Lotions may be formulated with an aqueous or oily base and will generally contain one or more emulsifiers, stabilizers, dispersing agents, suspending agents, builders or colorants. Formulations suitable for topical administration in the mouth include buccal tablets containing the active agent in a flavoring base (usually sucrose and gum arabic or tragacanth); tablets containing such as gelatin and glycerin or sucrose and arabic An active ingredient in an inert matrix of gum; and an elixir comprising the active ingredient in a suitable liquid carrier. The compounds of the invention may be formulated for administration as a suppository. The low melting wax such as a mixture of fatty acid glycerides or cocoa butter is first melted and the active component is uniformly dispersed, for example, by stirring. The molten homogeneous mixture is then poured into a mold of suitable size which is allowed to cool and solidify. The compounds of the invention may be formulated for vaginal administration. Pests, tampons, creams, gels, pastes, foams or sprays containing such carriers as known in the art, in addition to the active ingredient, are suitable. The compounds of the invention may be formulated for nasal administration. The solution or suspension is applied directly to the nasal cavity by conventional means (e.g., using a dropper, pipette or spray). Formulations may be provided in single or multiple doses. In one condition after the dropper or pipette, this can be accomplished by administering to the patient a suitable predetermined volume of solution or suspension. In the case of a nebulizer, this can be achieved, for example, by means of a metered atomizing spray pump. The compounds of the invention may be formulated for aerosol administration, especially to the respiratory tract and include intranasal administration. The compound will generally have a small particle size of, for example, about 5 microns or less. The particle size can be obtained, for example, by micron sizing, by the method of 156325.doc - 105 · 201202215 known in the art. Active Λ 适 适 适 适 丨丨 r r r ’ ’ ’ 舌 舌 舌 舌 舌 舌 舌 舌 舌 舌 舌The pressurized package A, the propulsion rrFrv/sr ^ agent is such as a gas fluorocarbon (CFC) (for example, dichlorodifluoromethane, sulphur, sulphuric acid, or sulphur tetrafluoroethane) == Suitable gas. The aerosol may also contain, for example, (iv) a lipid which may be provided in the form of a dry powder, for example, a compound in a suitable powder matrix in the form of a bis-compound which is such as lactose, a powder, a starch derivative (as far as a propylmethyl group). Cellulose) and polyvinyl ketone (PVP). The powder carrier will form a gel in the nasal cavity. The powder composition may be presented in unit dosage form, e.g., in a capsule or cartridge, such as a gelatin or blister pack, which can be administered by means of an inhaler. If desired, the formulations may be prepared with enteric coatings which are suitable for sustained or controlled release administration of the active ingredient. For example, the compounds of the invention may be formulated in a transdermal or subcutaneous drug delivery device. Such delivery systems are advantageous when sustained release of the compound is necessary and when patient compliance with the treatment regimen is critical. Compounds in transdermal delivery systems are often attached to skin adhesive solid supports. The compound of interest may also be combined with a penetration enhancer such as azone (1-12 doxacycloheptan-2-one). The sustained release delivery system is inserted subcutaneously into the subcutaneous layer by surgery or injection. The subcutaneous implant encapsulates the compound in a lipid soluble membrane (e.g., polyoxyxene rubber) or a biodegradable polymer (e.g., polylactic acid). The pharmaceutical preparations can be in unit dosage form. In this form, the preparation is subdivided into unit doses containing appropriate quantities of the active ingredient. The unit dosage form can be a package preparation such as a packaged lozenge, a capsule and a vial or an ampoules containing a discrete formulation of 156325.doc -106 - 201202215. The unit dosage form can also be a capsule, lozenge, troche or lozenge itself, or it can be any one of these unit dosage forms in a suitable number of packages. Other suitable pharmaceutical carriers and formulations thereof are described in Remington: The Science and Practice of Pharmacy 1995, Ew Heart Coffee, 'MaCk Pub Hshing ComPany, 19th Edition, Easton, Pennsylvania. Representative pharmaceutical formulations containing a compound of the invention are described below. 〇C Utility The compounds of the invention are generally suitable for treating diseases or conditions mediated by an individual in need thereof, including neurodegenerative diseases such as Parkinson's disease. , Lewy body dementia and Huntington's disease, and is suitable for enhancing the cognitive memory of individuals in need. EXAMPLES The following preparations and examples are given to enable those skilled in the art to clarify the self-explanation and practice of the present invention, which are not to be construed as limiting the invention, but are merely illustrative and representative of the invention. Unless otherwise specified, all temperatures including the melting point (i.e., Mp) are degrees Celsius (rc). It will be appreciated that the reaction to produce the designated and/or desired product may not necessarily result directly from the combination of the two agents initially added, that is, there may be one or more intermediates produced in the mixture which ultimately form the designation and/or Or the desired product. The following abbreviations are used in the preparation and examples. Abbreviation table

Ac0H acetic acid 156325.doc •107- 201202215

AIBN Atm. (B0C)20 DCM DIAD DIPEA DMAP DME DMF DMSO DPPF Et20 EtOH EtOAc HATU HBTU HOBT HPLC RP HPLC i-PrOH LCMS MeOH MW 2,2'-azobis(2-methylpropionitrile) Atmospheric dicarbonate Third butyl ester, dichlorodecane azodicarboxylate diisopropyl ester, diisopropylethylamine, 4-dimethylaminopyridine, 1,2-dimethoxyethane hydrazine, hydrazine-dimercaptocarboxamide Dimethyl hydrazine 1, hydrazine-bis(diphenylphosphino) ferrocene ether ethyl acetate ethyl hexafluorophosphate 2-(1Η-7-azabenzotriazol-1-yl)-1,1,3 , 3-tetrazine, amidoxime salt, hexafluorophosphate, benzotriazol-1-yl-N,N,N'W-tetradecyl-hydroxybenzotriazole, high pressure liquid chromatography, reverse phase high pressure Liquid Chromatography Isopropyl Alcohol Liquid Chromatography/Mass Spectrometry Analysis of Sterol Microwave 156325.doc • 108 · 201202215 NBS N-Bromobutadienimide NMP 1-Methyl-2-pyrrolidone PSI Pounds per square inch RT room temperature TBDMS tert-butyl dimethyl fluorene TFA trifluoroacetic acid THF tetrahydrofuran TLC thin layer chromatography preparation 1: 2-chloro-5-fluoro-N-mercaptopyrimidine-4-amine

To a 250 mL round bottom flask equipped with a stir bar was added 9.0 g of a 5-fluoro-2,4-dichloro-indole, 4〇1111^methanol, and 15 1111^8\1 guanamine in ethanol. The reaction was warmed (slightly exothermic) and allowed to stir at room temperature for about 30 minutes. A complete reaction was shown by TLC (1:1 EtOAc: heptane) and LCMS. The ruthenium was concentrated to give 9.77 g of crude material. The crude material was purified eluting with EtOAc EtOAc EtOAc EtOAc - gas - N - sulfhydryl shunt - 4 amine. The compounds shown in Table 1 below were prepared using the same method using the commercially available substituted 2,4-dichloro-pyrimidines and amines. HN〆 I 1 2-chloro-5-gas-N-mercaptopyrimidine-4-amine 156325.doc -109- 201202215

156325.doc -110- 201202215

G

15 2,5-di-gas-N,N-dimethylpyridin-4-amine Y 16 4-(azetidin-1-yl)-2,5-diaziridine 0 °txcl 17 2, 5-dioxa-4-(pyrrolidin-1 -yl)pyrimidine 18 2,5-dioxa-4-(piperidin-1 -yl)pyrimidine 0 CtXe, 19 2,5-diox-4-(2 -(decyloxymethyl)piperidinyl)pyrimidine. , ctxc, 20 2,5-dioxa-4-(4-(decyloxyindolyl)piperidin-1-yl)pyrimidine c'txc, 21 2,5-diox-N-(cyclopropylhydrazine Pyrimidine-4-amine Cl 22 22,5-di-gas-N-(cyclobutylindenyl)pyrimidine-4-amine Cl 23 2,5-dichloro-N-(cyclopentylmethyl) Pyrimidine-4-amine 24 2-chloro-N-mercaptopyrimidine-4-amine HN〆 (I 156325.doc • 111 - 201202215 25 2,5-di-gas-N-(2-decyloxyethyl)pyrimidine -4-amine "Λ, human Cl Table 1 Preparation 2: 2,5-di-gas-4-methoxypyrimidine

CI

NaOMe Et^O~

Cl To a 250 mL round bottom flask equipped with a stir bar was added 1 g of 5-chloro-2,4-dichloro-pyrimidine and 1 5 mL of diethyl ether. The mixture was cooled to hydrazine in an ice bath. Oh, and

Subsequently, 1 equivalent of sodium methoxide in methanol (prepared by reacting 120 mg of sodium with 4 mL of methanol at room temperature) was slowly added. The reaction was stirred overnight at room temperature and checked by LCMS. The white precipitate was filtered and the solid was washed with cold 771 EtOAc. 0.98 g of pure 2,5-dichloro-4-hydrogen|present T-pyridylpyrimidine was obtained after drying, and the material was used without further purification. ,--虱-pyrimidine, use phase

The compounds shown in Table 2 below were prepared using the appropriate commercially available alcohols and the appropriate methods of substitution. 156325.doc 112· 201202215

Table 2

Preparation 3: 4-(5-fluoro-4-(methylamino)pyrimidin-2-ylamino)-3-decyloxybenzoic acid

4-amino-3-indolyl benzoic acid n-BuOH, MW, 120〇C, 40 minutes

50 mg of 2-chloro-5-fluoro-N-fluorenyl is dense. a mixture of 4-amine, 57 mg 4-amino-3-methoxybenzoic acid, 0.1 mL of 4 N HCl in 1,4-dioxane and 1 mL of n-butanol was placed in a 10 mL gland In a snap-top microwave bottle (CEM Corp.), and microwave heating to 120 ° C for 40 minutes. The reaction was monitored by LC/MS. The precipitated solid was filtered to give 80 mg of 4-(5-fluoro-4-(methylamino)pyrimidin-2-ylamino)-3-decyloxybenzoic acid. The compound shown in Table 3 below was prepared in the same manner using the appropriate amine and the appropriately substituted 2-chloropyrimidine. 1 4-(5-Gas-4-(methylamino)pyrimidin-2-ylamino)- CI, Tl N 1 3-decyloxybenzoic acid NT V Η T /Ο 156325.doc -113 - 201202215

2 4-(5-Chloro-4-(decylamino)pyrimidin-2-ylamino) benzoic acid ΗΝ^ 0 Η 3 3-methoxy-4-(5-decyloxy-4-(曱Amino)pyrimidin-2-ylamino)benzoquinone hydrazine|/ 0 /ΟΟ矿Η 5 4-(5-gas-4-propoxy-oxo-2-ylamino)-3-oxime Benzophthalic acid H /Ϊ 7 4-(5-gas-4-isopropyllacylate-denyl-2-ylamino)_3-methoxybenzoic acid cltxN^0H 8 4-(5-gas 4--4-oxopyrimidin-2-ylamino)-3-indolyl benzoic acid HJ 10 4-(5->odor-4-(nonylamino)p-deni-2-ylamino -3-oxooxybenzoic acid HN^ O Vi 11 4-(5->odor-4-methyllacyl σ-mercapto-2-ylamino)-3_decyloxybenzoate ϋ 12 3- Methoxy-4-(4-(decylamino)pyrimidin-2-ylamino)benzoic acid HN^ OHJ 13 4-(5-峨-4-曱-milyl thiophene-2-ylamino )-3_ methoxybenzoic acid HI 156325.doc -114- 201202215

制备 Preparation 4: 4-(5-Gas-4-(nonylamino)pyrimidin-2-ylamino)->(difluoromethoxy)benzoic acid

To a cooled solution of 1 g of decyl 3-hydroxy-4-nitrobenzoate and 3.31 g of carbonic acid in 20 mL of DMF was carefully added to 15 equivalents of difluoroiodomethane. The reaction was allowed to warm to room temperature and was followed by TLC. After completion of the reaction, the mixture was concentrated and purified by EtOAc EtOAc (EtOAc). Methyl 3-(difluoro-toxy)-4-nitrobenzoate (〇·9 g) was placed in a 25 圆 round bottom flask and dissolved in 30 mL of ethanol. Pd/c (〇i5 g 1 0/° Pd) was carefully added and the hydrogen balloon was attached to the flask. Stir the reaction violently. 156325.doc •115· 201202215 Night. After checking by TLC, the reaction was filtered and concentrated with EtOAc EtOAc EtOAc (EtOAc) 4-Amino-3-(-methoxymethoxy)benzoic acid benzyl ester (70 mg), 2,5-dichloro-N-methylpyrimidin-4-amine, 0.1 mL 4 N HC1/dioxane And 1 mL of n-butanol was placed in a microwave vial. The reaction was heated at 150 °C for 3 min and monitored by LCMS. The mixture was concentrated and purified by silica gel chromatography to give 4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-(difluoromethoxy)benzene. Methyl formate. Dissolve methyl 4-(5-vapor-4-(methylamino)pyridin-2-ylamino)-3-(difluorodecyloxy)benzoate (5 〇0 mg) in 5 mL THF And 5 mL of water. After dissolution, 234 mg of lithium hydroxide was added and the reaction was stirred at room temperature overnight. The mixture was checked by LCMS and then carefully acidified with 1 n HCl and partitioned with EtOAc. The organic layer was condensed and purified by gel-break chromatography to obtain 2 5 〇mg 4_(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-(difluoromethoxy) Benzoic acid 0 is prepared analogously: 1 4-(5-Gas-4-(decylamino)pyrimidin-2-ylamino)·3-ethoxybenzoic acid~ΝΗ 0 Cl ΗH 2 4- (5-Gatro-4-(decylamino)pyrimidin-2-ylamino)-3-cyclobutoxybenzoic acid 'νη 0 CltV^H _Η °^ο I56325.doc -116- 201202215

3 4-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-3-(2,2,2-trifluoroethoxy)benzoic acid, NH 〇YIN ore Η V Instance 1 (4-(5-fluoro-4-(decylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(N-morpholinyl)methanone

1 〇〇 mg of 4-(5-fluoro-4-(methylamino)pyrimidin-2-ylamino)-3-indolyl benzoic acid, 47 pL of morpholine, 205 mg HATU, at room temperature A mixture of 188 mL of diisopropylethylamine in 1 mL of dimethyl decylamine was overnight. The reaction was checked by LCMS and found to be complete. The reaction was diluted with EtOAc and EtOAcq. The organic layer was concentrated and purified by preparative reverse phase HPLC to give 12 mg (4-(5-fluoro- 4-(methylamino)pyrimidin-2-ylamino)-3-methoxyphenyl) (N) - morpholinyl) fluorenone.

Compounds prepared using the above procedure, together with proton NMR and LRRK2 Ki (micromolar) data for selected compounds as determined by the assays described below, are shown in Table 4 below. EXAMPLES Name Structure 4 NMR Ki 1 [4-(5-Gas-4-Amino-amino-3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-?#-4-yl-fluorenone ~NH 0 NMR (400 MHz, DMSO) δ 8.46 (d, 1H), 7.89 (d, 1H), 7.56 (d, 2H), 7.04 (s, 1H), 7.00 (d, 1H), 3.90 (s, 3H), 3.58 (d, 4H), 3.52 (s, 3H), 2.90 (t, 3H). 0.0708 156325.doc -117- 201202215 Example Name Structure ^NMR Ki 2 [4-(5-Fluoro-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-(4 - thiol- cytosole-1-yl)-fluorenone~ΝΗ Ο h /° *HNMR (400 MHz, DMSO) δ 8.43 (d, 1H), 7.89 (d, 1H), 7.55 (d, 2H) , 7.00 (s, 1H), 6.96 (d, 1H), 4.77 (d, 1H), 3.90 (s, 3H), 3.73 (dd, 2H), 3.23-3.12 (m, 2H), 2.89 (d, 3H ), 1.74 (s, 2H), 1.36 (d, 2H). 0.0446 3 [4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-morpholin-4-yl-fluorenone~ΝΗ Η Η /〇 ^NMR (400 MHz, DMSO) δ 8.41 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.32 (d, 1H), 7.05 (s, 1H), 7.01 (d, 1H) , 3.90 (s, 3H), 3.56 (d, 8H), 2.90 (t, 3H). 0.0041 4 4-(5-Gas-4-Aminoamino hydrazin-2-ylamino)-3-methoxy-indole, fluorenyl-dimercapto-benzylguanamine ~NH Ο Η /〇'HNMR( 400MHz, DMSO) δ 8.39 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.05 (s, 1H), 7.00 (d, 1H), 3.87 (d , 3H), 2.97 (s, 6H), 2.91 (d, 3H). 0.0061 5 4-(5-Galo-4-indolyl-mole-2-ylamino)-Ν-ί 丙基propyl-3-methoxy-benzylamine ^NH 0 H /° !ΗΝΜΚ( 400 MHz, DMSO) δ 8.43 (d, 1H), 8.28 (s, 1H), 7.97 (s, 1H), 7.70 (s, 1H), 7.46 (d, 2H), 7.35 (d, 1H), 3.93 ( s, 3H), 2.91 (d, 3H), 2.82 (d, 1H), 0.75-0.62 (m, 2H), 0.56 (d, 2H). 0.0024 6 [4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4-yl-l-decyl-1-yl)- Anthrone 0 H /〇^NMR (400 MHz, DMSO) 5 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.01 (s, 1H), 6.96 (d, 1H), 4.77 (d, 1H), 3.88 (d, 3H), 3.73 (d, 2H), 3.18(t, 2H), 2.91 (d, 3H), 1.74 (s, 2H), 1.36 (d, 2H). 0.0173 156325.doc -118- 201202215

Example name structure ^NMR Ki 7 [4-(5-Gas-4-indole-pyrimidin-2-ylamino)-3-difluorodecyloxy-phenyl]-morphin-4-yl-A Ketone Ο A〆0 Η Α丫FF *ΗΝΜΚ(400ΜΗζ, DMSO) δ 8.34 (d, 1H), 8.07 (s, 1H), 7.95 (s, 1H), 7.29 (ddd, 3H), 3.56 (d, 8H ), 2.98-2.83 (m, 3H). 00049 8 [4-(5-Ga-4-indoleyl-°3⁄4唆-2-ylamino)-3-decyloxy-phenyl]-(octa-nitrogen 嗓幷[1,2-巳] °Bin-2-yl)-indolone^ΝΗ 0 c,A^nco H i /〇'HNMRC^OMHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H ), 7.32 (d, 1H), 7.02 (d, 1H), 6.97 (dd, 1H), 3.91 (d, 3H), 2.91 (d, 3H), 2.81-2.61 (m, 3H), 2.12-1.89 ( m, 2H), 1.81 (t, 1H), 1.76-1.36 (m, 4H), 1.34-0.97 (m, 2H). 0.0035 9 [4-(5-Ga-4-indoleyl-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-(2-amino-1 chenyl-1-yl )-fluorenone ~NH 0 OH H /〇*HNMR (400 MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.04 ( s, 1H), 6.98 (d, 1H), 4.91 (s, 1H), 3.91 (d, 3H), 3.51 (s, 2H), 3.11 (s, 1H), 2.91 (d, 3H), 1.86 (s , 1H), 1.70 (s, 1H), 1.41 (s, 2H). 0.0028 10 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-phenyl]-(4,4-dimercapto-piperidin-1-yl )-fluorenone ~NH OH /° *HNMR (400MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 6.98 (d, 1H ), 6.94 (d, 1H), 3.89 (s, 3H), 3.39 (d, 1H), 3.24 (d, 2H), 2.91 (d, 3H), 1.54 (s, 2H), 1.44-1.33 (m, 2H), 0.87 (s, 6H). 0.0037 11 [4-(5-Gas-4-Amino-Acryl--2-ylamino)-3-decyloxy-phenyl]-(3,5-dimethyl·piperazine v^-l -Based - Brewing I ^NH 0 H /° 1 *HNMR (400MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.00 (d, 1H), 6.99-6.91 (m, 1H), 3.91 (d, 3H), 2.90 (d, 3H), 1.95-1.71 (m, 2H), 1.67-1.49 (m, 0.0062 156325.doc - 119- 201202215 Instance name structure! hnmr Ki 2H), 1.43 (t, 1H), 1.00-0.68 (m, 7H). 12 [4-(5-Gas-4-methylaminobutyridyl-2-ylamino)-3-methoxy-phenyl]-[4-(1-hydroxy-1-indolyl-ethyl) - slightly biting-1-yl]-methanone, ΝΗ Ο αχΧ ore cv H OH *HNMR (400 MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.01 (d, 1H), 6.96 (dd, 1H), 4.14 (s, 1H), 3.90 (s, 3H), 2.91 (d, 3H), 1.71 (s, 2H), 1.44 ( t, 1H), 1.24-1.08 (m, 2H), 1.04 (s, 6H). 0.0017 13 [4-(5-Ga-4-indoleyl-°3⁄4 ate-2-ylamino)-3-methoxy-phenyl]-(3-radio-π-ha-0 0 1-yl )-fluorenone ^NH 0 n H /〇'HNMR (400 MHz, DMSO) δ 8.40 (d, 1H), 7.97 (s, 1H), 7.68 (s, 1H), 7.32 (d, 1H), 7.14 ( d, 2H), 4.97 (s, 1H), 4.28 (d, 1H), 3.92 (d, 3H), 3.72-3.39 (m, 3H), 2.90 (t, 3H), 1.89 (dd, 2H). 0.0041 14 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4-indolyl-predyl-1-yl)-indole Ketones ^NH OH /° *HNMR (400 MHz, DMSO) δ 8.38 (d, 1H), 7.95 (s, 1H), 7.66 (s, 1H), 7.31 (d, 1H), 7.00 (d, 1H), 6.95 (dd, 1H), 3.91 (d, 3H), 2.91 (d, 4H), 1.62 (d, 3H), 1.08 (q, 2H), 0.94 (t, 3H). 0.0028 15 [4-(5-Chloro-4-indenylamino)-3-indolyl-phenyl]-brazidin-1-yl-fluorenone^NH 0 CIA Mine H /0 JHNMR( 400MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.66 (s, 1H), 7.31 (d, 1H), 7.00 (d, 1H), 6.95 (dd, 1H), 3.89 (s , 3H), 3.41 (d, 4H), 2.91 (d, 3H), 1.62 (d, 2H), 1.51 (s, 4H). 0.0025 16 azetidin-1-yl-[4-(5-chloro-4-hydrazino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-fluorenone~NH 0 CIA Mine 0 H /〇'HNMRC^OMHz, DMSO) δ 8.44 (d, 1H), 7.97 (s, 1H), 7.70 (s, 1H), 7.34 (d, 1H), 7.26-7.20 (m, 2H) , 4.35 (s, 2H), 4.03 (s, 2H), 3.91 (s, 3H), 2.91 (d, 3H), 0.0052 156325.doc 120· 201202215 Example name structure ^NMR Ki 2.30-2.20 (m, 2Η) . 17 [4-(5-Ga-4-indoleyl-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-(4,4-difluoro-piperidine-1- Base)-A_0 Η /〇'HNMR (400 MHz, DMSO) 6 8.41 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.33 (d, 1H), 7.09 (d, 1H), 7.04 (dd, 1H), 3.91 (s, 3H), 3.60 (s, 4H), 2.91 (d, 3H), 2.11-1.97 (m, 4H). 0.0030 18 [4-(5-Chloro-4-indenyl- lysyl-2-ylamino)-3-indolyl-phenyl]-(3-methyl-π-dept-1-yl )--ketone-ΝΗ Ο Η /〇々NMR (400 MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.00 (d , 1H), 6.95 (dd, 1H), 3.89 (s, 3H), 2.90 (d, 3H), 1.78 (d, 1H), 1.70-1.50 (m, 2H), 1.42 (d, 1H), 1.22- 1.08 (m, 1H), 0.84 (s, 3H). 0.0045 19 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-phenyl]-(4-decyloxy-Nanthene-1-yl)-嗣 ΝΗ ΝΗ ΝΗ ° / ° 1 JHNMR (400 MHz, DMSO) 6 8.39 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.02 (d, 1H ), 6.97 (dd, 1H), 3.90 (s, 3H), 3.49-3.39 (m, 2H), 3.26 (s, 3H), 3.22 (d, 2H), 2.91 (d, 3H), 1.84 (s, 2H), 1.44 (d, 2H). 0.0029 20 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(3,3-disorgano-pyridin-1-yl) - ketone^ΝΗ 0 cf 矿 〇 /〇*HNMR(400MHz, DMSO) δ 8.43 (d, 1H), 7.97 (s, 1H), 7.70 (s, 1H), 7.33 (d, 1H), 7.04-6.96 (m, 2H), 3.90 (s, 3H), 3.84 (s, 2H), 3.53 (s, 2H), 2.91 (d, 3H), 2.18-2.01 (m, 2H), 1.70 (s, 2H). 0.0026 21 1-[4-(5-Chloro-4-indenyl- ̄3⁄4 ate-2-ylamino)-3-decyloxy-benzylic acid]-slightly β-1,4-carbonitrile 0 /0 1HNMR (400MHz, DMSO) 6 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.05 (d, 1H), 6.99 (dd, 1H) ), 3.89 0.0027 156325.doc -121 - 201202215 Instance name structure ^NMR Ki (d, 3Η), 3.72 (s, 2Η), 3.20-3.09 (m, 1H), 2.91 (d,3H), 1.90 (s, 2H), 1.81-1.67 (m, 2H). 22 [4-(5-Gas-4-Amino-Stymidine-2-ylamino)-3-indolyl-phenyl]-(4-a-piperidin-1-yl)-indole Ketones ΝΗ 0 Η /〇*HNMR (400 MHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.05 (d, 1H) , 7.00 (dd, 1H), 5.02-4.81 (m, 1H), 3.90 (s, 3H), 3.68-3.37 (m, 4H), 2.91 (d, 3H), 2.00-1.80 (m, 2H), 1.73 (s, 2H). 0.0021 23 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(3-methoxy-n-din-1-yl)- Anthrone, ΝΗ 0 ι Η /〇iHNMR (400 MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.03 (s, 1H) ), 6.97 (d, 1H), 3.90 (s, 3H), 3.41 (d, 2H), 2.90 (d, 3H), 1.86 (s, 1H), 1.63 (d, 2H), 1.42 (s, 1H) . 0.0056 24 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-(4-ethyl-pyrene-!--yl)-曱 ΝΗ ΝΗ ΝΗ ' 〇 〇 ' ' 'HNMR (400 MHz, DMSO) 5 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.02 (d, 1H), 6.97 (dd, 1H), 3.90 (s, 3H), 3.50 (s, 4H), 2.91 (d, 3H), 2.35 (dd, 6H), 1.00 (t, 3H). 0.0020 25 1-{4-[4-(5-Gas-4-methylamino-pyrazin-2-ylamino)-3-decyloxy-benzylidene]-Pymidine-1--1-yl Ethyl ketone ~ ΝΗ 0 c, A^or Η ^0 0 lU NMR (400 MHz, DMSO) δ 8.42 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.33 (d, 1H) , 7.07 (d, 1H), 7.02 (dd, 1H), 3.91 (s, 3H), 3.51 (d, 8H), 2.91 (d, 3H), 2.02 (s, 3H). 0.0034 156325.doc -122- 201202215

Example Name Structure ^NMR Ki 26 [4-(5-Gas-4-Aminoamino-11-deni-2-ylamino)-3-methoxy-phenyl]-(3-trifluoromethyl- Piperidin-1-yl)-methanone~ΝΗ 0 F ρ Η /〇*ΗΝΜΚ(400ΜΗζ, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.69 (s, 1H), 7.32 (d , 1H), 7.05 (d, 1H), 7.03-6.97 (m, 1H), 3.90 (s, 3H), 2.97 (d, 2H), 2.89 (t, 3H), 2.67 (s, 1H), 1.99 ( d, 1H), 1.72 (s, 1H), 1.65-1.44 (m, 2H). 0.0028 27 (4-Tertiary-t-piperidin-1-yl)-[4-(5-Gas-4-methylamino-α-denyl-2-ylamino)-3-methoxy-benzene ]]- ketone ~ ΝΗ 0 乂人矿 h / ° ' 1H NMR (400MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.01 (d, 1H), 6.96 (dd, 1H), 3.89 (s, 3H), 2.92 (t, 3H), 1.67 (s, 2H), 1.33-1.03 (m, 3H), 0.85 (s, 9H) . 0.0073 28 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy-phenylindole 4-(2-trans-ethyl-ethyl)-派°秦-1 -yl]-methanone ^NH OH /〇, *HNMR (400MHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.02 ( d, 1H), 6.97 (dd, 1H), 4.42 (t, 1H), 3.90 (s, 3H), 3.50 (dd, 6H), 2.91 (d, 3H), 2.41 (t, 6H). - 29 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-(2-indolylpyrylene-1-yl)-indole Ketone, NH 0 , n H /〇*HNMR (400MHz, DMSO) δ 8.39 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.11 (s, 2H) ), 4.17-4.05 (m, 1H), 3.90 (s, 3H), 3.54 (s, 1H), 3.48-3.36 (m, 1H), 2.90 (t, 3H), 2.07 (td, 1H), 1.87 ( s, 1H), 1.70 (s, 1H), 1.59-1.46 (m, 1H), 1.24(s, 2H). 0.0038 30 [4-(5-Chloro-4-indenylamine 2 -ylamino)-3-decyloxy-phenyl]-(4-methyl-α-deposited-, IH 0 / O OH IHNMR (400MHz, DMSO) δ 8.38 (d, 1H), 7.96 (s, 1H), 7.66 (s, 1H), 7.31 (d, 1H), 7.00 (d, 1H), 6.95 (dd, 1H) , 4.49 0.0027 156325.doc -123- 201202215 Example name structure ^NMR Ki 1-yl)-fluorenone (t, 1Η), 3.89 (s, 3H), 3.28 (t, 2H), 2.91 (d, 4H), 1.66 (s, 3H), 1.09 (q, 2H). 31 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-indolyl)-fluorenone, ΝΗ 0 1 Η / 〇'HNMR (400 MHz, DMSO) δ 8.37 (d, 1H), 7.95 (s, 1H), 7.66 (s, 1H), 7.30 (d, 1H), 6.98 (d, 1H), 6.93 (dd, 1H) ), 4.39 (s, 1H), 3.89 (s, 4H), 2.97 (t, 1H), 2.90 (d, 3H), 1.73-1.28 (m, 6H), 1.20 (d, 3H). 0.0022 32 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]pyrrolidin-1-yl-曱"^ΝΗ 0 Υχ r ^O Η /〇iHNMRGOOMHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.18-7.11 (m, 2H), 3.90 (s , 3H), 3.47 (d, 4H), 2.91 (d, 3H), 1.83 (s, 4H). 0.0047 33 [4-(5-Gas-4-Aminoamino)-3-methoxy-phenyl]-(4-nonanesulfonyl-piperazin-1-yl)-methanone ~ΝΗ 0 Η J 0^0 lU NMR (400 MHz, DMSO) 5 8.43 (d, 1H), 7.97 (s, 1H), 7.69 (s, 1H), 7.33 (d, 1H), 7.09-6.99 (m , 2H), 3.91 (s, 3H), 3.62 (s, 4H), 3.17 (s, 4H), 2.91 (d, 6H). 0.0036 34 [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(3-trifluoromethyl-0-pyridin-1- ))- ketone~ΝΗ 0 α A Ν Ν Η /〇'H NMR (400 MHz, DMSO) 6 8.46-8.39 (m,1H), 7.95 (d, 1H), 7.69 (s, 1H), 7.33 ( d, 1H), 7.16 (dd, 2H), 3.91 (s, 3H), 3.76 (dt, 1H), 3.60 (dd, 3H), 2.91 (d, 3H), 2.17(s, 1H), 2.05-1.95 (m, 1H). 0.0051 35 [4-(5-Gas-4-Amidinosyl-2-ylamino)-3-methoxy-phenyl]-[4-(2,2,2-difluoro-ethyl )-嗓嗓小基]-曱酮~ΝΗ 0 Η /〇f4"FF JH NMR (400 MHz, DMSO) δ 8.40 (d, 1H), 7.95 (d, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.03 (d, 1H), 6.98 (dd, 1H), 3.89 (d, 3H), 3.52 (s, 4H), 3.28-3.13 (m, 2H), 2.90 (t, 3H), 2.64 (s, 0.0023 156325.doc -124- 201202215

Instance Name Structure !hnmr Ki 4H). 36 [4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morphin-4-yl-methanone^NH 0 Η /〇* ΗΝΜΚ(400ΜΗζ, DMSO) δ 8.40 (d, 1H), 8.04 (s, 1H), 7.68 (s, 1H), 7.14 (d, 1H), 7.05 (d, 1H), 7.01 (dd, 1H), 3.90 (s, 3H), 3.56 (d, 8H), 2.90 (d, 3H). 0.0013 37 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-phenyl]-(2-indolyl-morphin-4-yl)-indole Ketone^ΝΗ 0 Mine cr Η /〇1HNMR (400MHz, DMSO) δ 8.41 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.32 (d, 1H), 7.05 (d, 1H) , 7.00 (dd, 1H), 3.90 (s, 3H), 3.79 (s, 1H), 3.48 (ddd, 2H), 2.91 (d, 3H), 1.08 (s, 3H). 0.0053 38 [4-(5-Galo-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-phenyl]-(2,6-diamidino-morpholin-4-yl - ketone ~NH 0 H /〇1 1H NMR (400MHz, DMSO) δ 8.41 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.32 (d, 1H), 7.04 (d, 1H), 7.00 (dd, 1H), 3.90 (s, 3H), 3.54 (ddd, 2H), 2.89 (t, 3H), 1.07 (s, 6H). 0.0070 39 [4-(5-Gas-4-Aminoamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2,2-diethyl-morphin-4-yl ) 曱 ketone ~ NH OH / 〇 ^ NMR (400 MHz, DMSO) δ 8.41 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.32 (d, 1H), 7.01 (dd, 2H), 3.90 (s, 3H), 3.69-3.36 (m, 6H), 2.91 (d, 3H), 1.47 (d, 4H), 0.75 (s, 6H). 0.0055 40 [4-(5-Chloro-4-methylamino] 13 dimethyl-2-ylamino)-3-decyloxy-phenyl]-(3-hydroxymethyl-morpholin-4-yl )--ketone, NH 0 |^〇HH /° iHNMR (400 MHz, DMSO) δ 8.39 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.08 (s, 1H), 7.02 (d, 1H), 4.92 (s, 1H), 3.90 (s, 3H), 3.88-3.44 (m, 6H), 2.91 (d, 3H). 0.0044 156325.doc -125- 201202215 Example Name Structure ^NMR 41 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2- Isobutyl-oxo-4-yl)-indolone~NH 0 C,ii^cnr Η /〇*Η NMR (400 ΜΗζ, DMS0) δ 8.41 (d, 1Η), 7.96 (s, 1Η), 7.68 (s, 1H), 7.32 (d, 1H), 7.06 (d, 1H), 7.00 (dd, 1H), 3.90 (s, 3H), 3.76 (d, 1H), 3.44 (dd, 3H), 2.91 ( d, 3H), 1.69 (s, 1H), 1.36 (s, 1H), 1.18 (s, 1H), 0.86 (s, 6H). 0.0042 42 [4-(5-Gas-4-methylamino-°3⁄4 ate-2-ylamino)-3-methoxy-phenyl]-(2- thiol-?#-4-yl )-曱 ketone ~ ΝΗ 0 c, A^nCT0H Η /〇jH NMR (400 MHz, DMSO) δ 8.41 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.32 (d, 1H ), 7.06 (d, 1H), 7.01 (dd, 1H), 4.78 (s, 1H), 3.90 (s, 3H), 3.85 (d, 1H), 3.42 (ddd, 4H), 2.91 (d, 3H) . 0.0048 43 [4-(5-Ga-4-indoleyl-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-(3,3-dimethyl-?"^ -4-yl)-remanent\|ΜΗ 0, /αΑ矿& Η /〇'H NMR (400 MHz, DMSO) δ 8.44-8.37 (m, 1H), 7.96 (s, 1H), 7.68 (s , 1H), 7.33 (d, 1H), 7.04 (dd, 2H), 3.91 (s, 3H), 3.73-3.63 (m, 2H), 3.39 (d, 2H), 2.91 (d, 3H), 1.41 ( d, 6H). 0.0082 44 [4-(5-Gas-4-Amino-α-D-D-yl-2-ylamino)-3-methoxy-phenyl]-(4-indole-piperazine-1-yl)-曱 ΝΗ ΝΗ H 〇 /〇!H NMR (400 MHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.02 (d, 1H), 6.97 (dd, 1H), 3.90 (s, 3H), 3.50 (s, 4H), 2.89 (t, 3H), 2.31 (s, 4H), 2.21 (d, 3H). 0.0023 45 [4-(5-Gas-4-Aminoamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-isopropyl-D-Chenazine-1-yl) - fluorenone ~ ΝΗ 0 NMR (400 MHz, DMSO) 6 8.39 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.32 (d, 1H), 7.02 (s, 1H), 6.97 (d, 1H), 3.90 (s, 3H), 3.44 (d, 4H), 2.91 (d, 3H), 2.74-2.60 (m, 1H), 2.44 (s, 4H), 0.97 (d, 6H). 0.0011 156325.doc -126- 201202215

实例 Example name structure XHNMR Kj 46 [4-(5--; odor-4-methoxy-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-morphin-4-yl -methyl ketone oxime / oxime 1H NMR (400MHz, DMSO) δ 8.38 (s, 1H), 8.31 (s, 1H), 8.15 (d, 1H), 7.08 (d, 1H), 7.02 (dd, 1H), 3.98 ( s, 3H), 3.89 (s, 3H), 3.56 (d, 8H). 0.0037 47 [4-(5-Gas-4-Aminoamino- σ-Bist-2-ylamino)-3-decyloxy-phenyl]-piperidinyl-11-yl-yl-pyrene~ΝΗ 0 Η /〇^NMRC^OMHz, DMSO) δ 8.42 (d, 1H), 7.96 (s, 1H), 7.69 (s, 1H), 7.33 (d, 1H), 7.06 (d, 1H), 7.05-7.00 ( m, 1H), 3.91 (s, 3H), 3.59 (s, 4H), 2.97 (s, 4H), 2.90 (t, 3H). 0.0028 48 [4-(5-Gatro-4-indolyl-pyrimidin-2-ylamino)-3-difluorodecyloxy-phenyl]-(4-trans-based-σ-嗔 ·_1·yl )_甲嗣0 Η ά 丫F 】HNMR (400 MHz, DMSO) δ 8.30 (d, lH), 8.06 (s, 1H), 7.95 (s, 1H), 7.37-7.14 (m, 3H), 3.74 ( s, 2H), 2.88 (dd, 3H), 1.75 (s, 2H), 1.37 (s, 2H). 0.0037 49 [4-(5-Gas-4-Methylamino-.Ment-11-ylamino)-3-ethoxy-phenyl]-morpholin-4-yl-fluorenone~ΝΗ 0 lHNMR (400MHz, DMSO) · 8.44 (d, J=8.3 Hz, 1H), 7.96 (s, 1H), 7.65 (s, 1H), 7.33 (d, J=4.5 Hz, 1H), 7.04 (d, J = 1.4 Hz, 1H), 7.00 (d, /=8.3 Hz, 1H), 4.16 (q, /=6.9 Hz, 2H), 3.55 (d, J=35.7Hz, 8H), 2.92 (d, J=4.6 Hz, 3H), 1.45-1.33 (m, 3H). 0.0043 50 [3-Methoxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl·anthrone F ^ΝΗ 0 Η /〇iHNMR (400 MHz, DMSO) δ 8.31 (d, lH), 8.19 (s, 1H), 8.07 (s, 1H), 7.21 (d, 1H), 7.07 (s, 1H), 7.02 (d , 1H), 3.90 (s, 3H), 3.56 (d, 9H), 2.92 (d, 3H). 0.0027 156325.doc •127- 201202215 Example Name Structure*Η NMR Kt 51 4-(5-Gas-4-Amidino-°3⁄4 ate-2-ylamino)-3-decyloxy-benzylguanamine NH 0 CA^NH2 Η /〇*HNMR (400ΜΗζ, DMSO) δ 8.47-8.39 (m, 1Η), 7.97 (s, 1H), 7.83 (s, 1H), 7.69 (s, 1H), 7.51 (d, 2H), 7.32 (d, 1H), 7.16 (s, 1H), 3.93 (s, 3H), 2.92 (d, 3H). 0.0051 52 4-(5-Gas-4-methylamino-♦ ketone-2-ylamino)-N-ethyl-3-methoxy-benzyl octaamine\νη 0 Η /〇XH NMR (400 MHz , DMSO) δ 8.46-8.41 (m, 1H), 8.30 (t, 1H), 7.96 (d, 1H), 7.69 (s, 1H), 7.48 (t, 2H), 7.32 (d, 1H), 3.91 ( d, 3H), 2.92 (d, 3H), 1.12 (t, 3H). 0.0031 53 4-(5-Gas-4-methylamino-feeding-2-ylamino)-N-isopropyl-3-oxooxy-benzylamine \κΐΗ 0 Η /〇*H NMR ( 400 MHz, DMSO) δ 8.44 (d, 1H), 8.03 (d, 1H), 7.97 (s, 1H), 7.69 (s, 1H), 7.53-7.45 (m, 2H), 7.32 (d, 1H), 4.10 (dq, 1H), 3.94 (s, 3H), 2.92 (d, 3H), 1.17 (d, 6H). 0.0020 54 4-(5-Chloro-4-indenyl-°®唆-2-ylamino)-3-methoxy-N-methyl-benzylamine, ΝΗ 0 CA^'H Η /〇 !H NMR (400 MHz, DMSO) δ 8.43 (d, J = 8.2 Hz, 1H), 8.27 (d, J = 4.2 Hz, 1H), 7.97 (s, 1H), 7.69 (s, 1H), 7.46 ( d, J=8.2 Hz, 2H), 7.32 (d, ./=4.2 Hz, 1H), 6.48 (s, 1H), 3.93 (s, 3H), 2.92 (d, J-4.5 Hz, 3H), 2.78 (d, J = 4.4 Hz, 3H). 0.0104 55 [4-(5-Gas-4-propoxy-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-morphin-4-yl-fluorenone 0 Η /〇'H NMR (400 MHz, DMSO) δ 8.31 (s, 1H), 8.26 (s, 1H), 8.13 (d, 1H), 7.07 (s, 1H), 7.02 (d, 1H), 4.35 (t, 2H), 3.88 (s, 3H), 3.56 (d, 8H), 1.76 (d, 2H), 0.97 (t, 3H). 0.0060 156325.doc -128- 201202215

EXAMPLES Name Structure NMR Ki 56 [4-C5-Gas-4-Ethylamino-Wwound-2-ylamino)-3-decyloxy-phenyl]-indol-4-yl-fluorenone HN〆 ^ 0 H /° *ΗΝΜΚ(400ΜΗζ, DMSO) δ 8.37 (d, 1Η), 7.96 (s,1Η), 7.66 (s, 1Η), 7.29 (t, 1H), 7.05 (s, 1H), 7.02- 6.97 (m, 1H), 3.90 (s, 3H), 3.64-3.48 (m, 7H), 3.48-3.40 (m, 2H), 1.17 (t, 3H). 0.0025 57 [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3_oxa-8-aza-bicyclo[3.2.1 ] 辛-8-yl)-fluorenone oxime|/ 0 Η /〇'H NMR (400 MHz, DMSO) δ 8.43 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.31 ( d, 1H), 7.11 (d, 2H), 3.92 (s, 3H), 3.67 (d, 2H), 3.59 (s, 2H), 2.91 (d, 3H), 1.87 (s, 4H). 0.0025 58 [4-(5-Gas-4-ethoxy-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-morphin-4-yl-fluorenone oxime / NMR ( 400 MHz, DMSO) δ 8.31 (s, 1H), 8.25 (s, 1H), 8.14 (d, 1H), 7.08 (s, 1H), 7.02 (d, 1H), 4.45 (q, 2H), 3.89 ( s, 3H), 3.56 (d, 8H), 1.36 (t, 3H). 0.0077 59 [4-(5-Gas-4-isopropoxy-°® dimethyl-2-ylamino)-3-decyloxy-phenyl]-oxalin-4-yl-fluorenone η /° 'H NMR (400 MHz, DMSO) δ 8.30 (s, 1H), 8.25 (s, 1H), 8.11 (d, J=8.2Hz, 1H), 7.43-7.32 (m, 1H), 7.08 (d, J =1.4 Hz, 1H), 7.02 (d, /=8.2 Hz, 1H), 5.34 (dt, /=12.3, 6.2 Hz, 1H), 3.88 (s,3H), 3.56 (d,J=38.0Hz, 8H ), 1.35 (d, /=6.2 Hz, 6H) ° 0.0130 60 [4-(5-Gas-4-methylamino-penetidine-2-ylamino)-3-decyloxy-phenyl]- ((S)-3-indolyl-Mulline-4-yl)-曱嗣ΗΝ〆0 ι Η /〇*H NMR (500 MHz, DMSO) δ 8.40 (d, 1H), 7.95 (s, 1H) , 7.66 (s, 1H), 7.29 (s, 1H), 7.02 (s, 1H), 6.98 (d, 1H), 3.91 (s, 3H), 3.83-3.78 (m, 3H), 3.63-3.59 (m , 1H), 3.57-3.53 (m, 1H), 3.42-3.34 (m, 0.0027 156325.doc -129- 201202215 Instance name structure *ΗΝΜΗ Kj 2Η), 2.91 (d, 3Η), 1.26 (d,3H); [4-(5-Chloro-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-oxalin-4-yl-曱阙H /° 1H NMR (400 MHz, DMSO) δ 8.32 (s, 2H), 8.15 (d, 1H), 7.08 (d, 1H), 7.02 (dd, 1H), 3.99 (s, 3H), 3.89 (s, 3H), 3.56 (d 8H). 0.0104 62 [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-oxa-5-aza-bicyclo[2.2. 1]hept-5-yl;)-fluorenone HN|/ 0 Η /〇'HNMRC^OMHz, DMSO) δ 8.44 (d, 1H), 7.97 (s, 1H), 7.70 (s, 1H), 7.36 ( d, 1H), 7.24-7.05 (m, 2H), 4.63 (dd, 3H), 3.93 (d, 3H), 3.67 (ddd, 3H), 2.91 (d, 2H), 1.83 (t, 2H). 0.0045 63 [4-(5-Chloro-4-methylamino-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-(8-oxa-3-aza-bicyclo[ 3_2'1] octyl-3-yl)-methanone ΗΝ〆" 0 Η /〇iHNMR (400 MHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.34 (d, 1H), 7.03 (d, 1H), 6.98 (dd, 1H), 4.28 (s, 3H), 3.90 (s, 3H), 2.91 (d, 3H), 1.72 (d, 5H). 0.0020 64 [4-(5-Gas-4-Methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-((R)-3-methyl-morpholin-4- ))-methanone ΗΝ^ 0 = Η /〇^NMR (500 MHz, DMSO) δ 8.40 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.33 (d, 1H), 7.02 (d, 1H), 6.97 (d, 1H), 3.90 (s, 3H), 3.84-3.73 (m, 3H), 3.61 (d, 1H), 3.54 (d, 1H), 3.42-3.35 (m, 2H) ), 2.90 (d, 3H), 1.25 (d, 3H) 0.0042 65 N-(3-Amino-propyl)-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino) -3-methoxy-nodal amine 0 Η /〇, Η2 0.0023 66 [4-(5-cyclopropyl-4-methylamino-pyridin-2-ylamino)-3-methoxy- Phenyl]-oxalin-4-yl- Λ ΗΝ〆0 Η /〇1HNMR (400 MHz, DMSO) .8.39 (d, J=8.2, 1H), 7.93 (s, 1H), 7.82 (s, 1H) , 7.07 (s, 1H), 7.02 (d, 0.0359 156325.doc -130· 201202215

Instance name structure!hnmr Ki 曱 Η 1Η), 3.97 (s, 3Η), 3.91 (s, 3Η), 3.56 (m, 8H), 1.80-1.71 (m, 1H), 0.86-0.78 (m, 2H), 0.69-0.61 (m, 2H) 67 [4-(5-Gas-4-isobutylamino-pyrimidin-2-yl)]-methoxy-phenyl]- 淋 -4- Base - 曱嗣0 H / ° * ΗΝΜΚ (400 ΜΗζ, DMSO) δ 8.36 (d, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.39 (s, 1H), 7.05 (s, 1H) , 6.98 (d, 1H), 3.90 (s, 3H), 3.68-3.42 (m, 8H), 3.21 (t, 3H), 1.98 (dt, 1H), 0.90 (d, 6H) 〇0.0040 68 [4- (5-Gas-4-propylamino-catridin-2-ylamino)-3-methoxy-styl]-morpholin-4-yl-fluorenone 0 c,AV〇Η /〇^NMR^ OOMHz, DMSO) δ 8.36 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.35 (dd, 1H), 7.05 (s, 1H), 6.99 (d, 1H), 3.90 (s , 3H), 3.56 (d, 8H), 1.68-1.51 (m, 2H), 0.90 (t, 3H). 0.0019 69 [4-(5-Gas-4-Isopropylaminocarbyl-2-ylamino)-3-decyloxy-phenyl]-?#-4-yl-methanone 0 Η /〇'HNMR (400 MHz, DMSO) δ 8.34 (d, 1H), 7.97 (s, 1H), 7.67 (s, 1H), 7.05 (s, 1H), 7.00 (d, 1H), 6.89 (d, 1H), 4.38 -4.21 (m, 1H), 3.90 (s, 3H), 3.56 (d, 8H), 1.22 (d, 6H). 0.0072 70 [4-(5-Gatro-4-indolyl-mouth-2-ylamino)-3-indolyl-phenyl]-(4-cyclopropanecarbonyl-piperazin-1-yl) -methanone ΗΝ〆* Ο 〇Η /. Δ 1H NMR (400MHz, DMSO) δ 8.42 (d, 1H), 7.97 (s, 1H), 7.69 (s, 1H), 7.33 (d, 1H), 7.08 (d, 1H), 7.03 (dd, 1H), 3.88 (d, 3H), 3.63 (d, 8H), 2.91 (d, 3H), 1.97 (s, 1H), 0.81-0.66 (m, 4H). 0.0022 71 [4-(5-Bromo-4-indenyl- ̄3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-[4-(1-pyridyl-1-anthracene) ^ Ο Η J hJS 'HNMR (400MHz, DMSO) δ 8.38 (s, 1H), 8.29 (s, 1H), 8.12 (d, 1H), 7.04 (s, 1H), 6.98 (d, 1H), 4.13 ( s, lH), 3.98 (s, 0.0024 156325.doc -131 - 201202215 Instance name structure ^ NMR Ki-ethyl) _ mother. -1--1-] fluorenone 3H), 3.88 (s, 3H), 1.42 (m, 2H), 1.18 (m, 2H), 1.05 (s, 6H). 72 [4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-trifluorodecyl-0-pyridin-1-yl )--ketone ΗΝ^ Ο n H /° 'H NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.31 (s, 1H), 8.18 (d, 1H), 7.17 (m, 2H), 3.99 (s, 3H), 3.90 (s, 3H), 3.77 (m, 1H), 3.62 (m, 3H) 0.0064 73 1-[4-(5-bromo-4-indolyl-pyrimidin-2-ylamine ))-3-methoxy-benzylindenyl]· 咬 曱-4-曱carbonitrile HN/ o /0 NMR (400 MHz, DMSO) δ 8.38 (s, 1H), 8.30 (s, 1H) „ 8.15 ( d, 1H), 7.08 (s, 1H), 7.01 (d, 1H), 3.98 (s, 3H), 3.89 (s, 3H), 3.15 (m, 2H), 1.90 (m, 2H), 1.75 (m , 2H) 0.0041 74 [4-(5-Bromo-4-indolyl-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-cyclobutyl-piperazine-1- Base)-fluorenone HN^ O t ore H /0 ^ 'H NMR (400 MHz, DMSO) δ 8.4 (s, 1H), 8.35 (s, 1H), 8.2 (d, 1H), 7.1 (s, 1H ), 6.99 (d, 1H), 3.9 (s, 3H), 3.8 (s, 3H), 3.5 (m, 4H), 2.69 (m, 1H), 2.25 (s, 4H), 1.98 (m, 2H) , 1.75 (m, 2H), 1.62 (m, 2H) 0.0023 75 [4-(5-溪-4-曱amino-mouthed-2-ylamino)-3-methoxy-phenyl]- [4-(2,2,2-Trifluoro-ethyl)-pyrylo-l-yl]-methanone HIS|/ 0 HJAF F 0.0038 76 [4-(5-Bromo-4-indenyl- ̄3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-(4-decyloxy-piperidin-1- Base)--ketone HN|/ OH /〇1 'H NMR (400 MHz, DMSO) δ 8.38 (s, 1H), 8.29 (s, 1H), 8.13 ((1,/=8.2,1H), 7.05 ( s, 1H), 6.99 (d, J=8.2, 1H), 3.98 (s, 3H), 3.88 (s, 3H), 3.50-3.38 (m, 1H), 3.26 (m, 4H), 1.85 (m, 2H), 1.45 (m, 2H). 0.0024 156325.doc -132- 201202215

Example name structure ^NMR Ki 77 [4-(5-indipro-4-amino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((R)-3-yl-- ° 比洛 bit-1-yl)-methanone HN"^ 0 Yx rro---'〇H n Η /〇'HNMR (400MHz, DMSO) δ 8.38 (s, 1H), 8.29 (d, J=7.7 , 1H), 8.14 (d, /=8.2, 1H), 7.06 (s, 1H), 7.00 (d, J=8.3, 1H), 4.54 (m, 2H), 4.44 (m, 2H), 3.98 (s , 2H), 3.88 (s, 2H). 0.0051 78 [4_(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-oxebutan-3-yl-indole 17 Qin-1 -yl)-methanone HN^ 0 1H NMR (400MHz, DMSO) δ 8.38 (s, 1H), 8.29 (d,J=7.7, lH), 8.14 (d, J=8.2, 1H), 7.06 ( s, 1H), 7.00 (d, J=8.3, 1H), 4.54 (t, /=6.5, 2H), 4.44 (t, /=6.1, 2H), 3.98 (s, 2H), 3.88 (s, 2H) ). 0.0080 79 [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-3-isopropoxy-phenyl]-morphin-4-yl-methanone HN|/ 0 clx ^N^o Η Y lHNMR(400MHz, DMSO) · 8.47 (d, /=8.3 Hz, 1H), 7.96 (s, 1H), 7.61 (s, 1H), 7.33 (d, J=4.5 Hz, 1H) , 7.06 (s, 1H), 6.99 (d, J=8.3Hz, 1H), 4.73 (dt, /=12.0, 6.0 Hz, 1H), 3.55(d, J=36.7Hz, 8H), 2.93 (d, J = 4.6 Hz, 3H), 1.33 (d, J = 6.0 Hz, 6H). 0.0156 80 {4-[5-Gatro-4-(cyclopropylindolyl-amino)-Spoken-2-ylamino]-3-indolyl-phenyl}-morpholin-4-yl- Methyl ketone hn"^V7 it H /〇1HNMR (400MHz, DMSO) δ 8.34 (d, /=8.3 Hz, 1H), 7.97 (s, 1H), 7.68 (s, 1H), 7.38 (s, 1H), 7.05 (s, 1H), 6.99 (d, J = 8.2 Hz, 1H), 3.90 (s, 2H), 3.56 (d, J = 33.7 Hz, 8H), 1.15 (s, 1H), 0.46-0.37 (m , 2H), 0.26 (d, /=4.6 Hz, 2H). 0.0027 156325.doc 133- 201202215 Example Name Structure!Η NMR Kj 81 [4-(5-Gas-4-cyclobutylamino-pyridin-2-ylamino)-3-methoxy-phenyl] -morpholin-4-yl-fluorenone oxime-^^ Ο Η /〇*HNMR (400ΜΗζ, DMSO) δ 8.35 (d, J=S.2 Hz, 1H), 7.98 (s, 1H), 7.68 (s , 1H), 7.35 (d, J=7.1Hz, 1H), 7.04 (dd, 7=11.1, 4.9 Hz, 2H), 4.52 (dd, J=16.1, 7.9 Hz, 1H), 3.90 (s, 3H) , 3.56 (d, J = 35.5 Hz, 8H), 2.26 (d, J-2.9Hz, 2H), 2.21-2.07 (m, 2H), 1.75-1.60 (m, 2H). 0.0015 82 [4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-heptyl-phenyl]-oxalin-4-yl·anthracene ΗΝ〆" 0 OH JH NMR (400 MHz, DMSO) δ 8.18 (d, J = 8.3 Hz, 1H), 7.95 (s, 1H), 7.86 (s, 1H), 7.32 (d, 7=4.6 Hz, 1H), 6.92-6.80 ( m, 2H), 3.54 (d, J-36.7 Hz, 8H), 2.91 (d, •7=4·6 Hz, 3H). 0.0289 83 [4-(5-Bromo-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-(4-ethyl-π- bottom-methyl-1-yl) -曱 ketone Η /〇1 *H NMR (400 MHz, DMSO) 5 8.38 (s, 1H), 8.29 (s, 1H), 8.14 (d, J = 8.2, 1H), 7.05 (d, J = 1.4, 1H), 6.99 (d, J=8.2,1H), 3.98 (s, 3H), 3.88 (s, 3H), 3.50 (s, 4H), 2.35 (m, 6H), 1.00 (t, J=7.1, 3H). 0.0025 84 [4-(5-Chloro-4-indenyl-pyrimidin-2-ylamino)-2-lacto-5-decyloxy-phenyl]-morpholin-4-yl-fluorenone ΗΝ^ F Ο Η /〇'H NMR (400 MHz, DMSO) δ 8.37 (d, J = 12.4 Hz, 1H), 8.01 (s, 1H), 7.74 (s, 1H), 7.42 (d, J = 4.3 Hz, 1H), 6.99 (d, J=6.2 Hz, 1H), 3.89 (s, 3H), 3.64 (m, 4H), 3.55 (m, 4H), 2.92 (d, J=4.5 Hz, 3H). 0.0055 85 [4-(5-Bromo-4-indolyl-♦ oxa-2-ylamino)-3-3⁄4 butyloxy-phenyl]- 吓 * -4--4-yl-fluorenone cr° ' H NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.24 (s, 1H), 8.19 (d, J = 8.3 Hz, 1H), 7.01 (d, J = 8.2 Hz, 1H), 6.88 (s) , 1H), 4.90-4.75 (m, 0.0028 156325.doc -134- 201202215 Instance name structure! hnmr Ks 1Η), 4.00 (s, 3Η), 3.55 (m, 8Η), 2.43 (m, 2H), 2.21- 2.04 (m, 2H), 1.80 (m, 1H), 1.72-1.55 (m, 1H). 86 [4-(5-Galo-4-indolyl-carto-2-ylamino)-3-cyclobutoxy-phenyl]-morphin-4-yl-methanone ΗΝ〆" 0 If *ΗΝΜΚ(400ΜΗζ, DMSO) δ 8.44 (d, J=8.3 Hz, 1H), 7.96 (s, 1H), 7.64 (s, 1H), 7.33 (d, J=4.5 Hz, 1H), 7.00 (d , J=8.3 Hz, 1H), 6.86 (s, 1H), 4.90-4.69 (m, 1H), 3.55 (m, 8H), 2.92 (d, J=4.6 Hz, 3H), 2.50-2.36 (m, 2H), 2.14 (m, 2H), 1.82 (m, 1H), 1.68 (m, 1H). 0.0028 87 [4-(5-Gas-4-Ethylamino-mouth-2-ylamino)-2-fluoro-5-decyloxy-phenyl]-morpholin-4-yl-fluorenone F Ο 〇 /〇iHNMR (400 MHz, DMSO) δ 8.34 (d, J = 12.5 Hz, 1H), 8.01 (s, 1H), 7.73 (s, 1H), 7.43 (t, 1H), 6.99 (d, • /=6.2 Hz, 1H), 3.89 (s, 3H), 3.59 (m, 8H), 3.49-3.39 (m, 2H), 1.18 (t, 3H). 0.0025 88 [4-(5- Desert-4-Alkoxy-Bitter-2-ylamino)-3-decyloxy-phenyl]-(3-?-------- 4-A-azetidine Alkyl-1-yl)-fluorenone 1H NMR (400 MHz, DMSO) δ 8.41 (s, 1H), 8.30 (s, 1H), 8.22 (d, J = 8.9, 1H), 7.27 (d, J = 6.8, 2H), 4.36 (s, 2H), 4.17(s, 1H), 4.05 (s, 1H), 3.99 (s, 3H), 3.91 (s, 3H), 3.88 (s, 1H), 3.59 (t, J =4.4, 4H), 3.19-3.09 (m, 2H), 2.33 (s, 5H). 0.0050 89 [4-(5-Gas-4-Aminoamino-11-denyl-2-ylamino)-3-decyloxy-phenyl]-(3-morphin-4-yl-azacyclo) Butyr-1-yl)-fluorenone Hls|/ 0 1HNMR (400 MHz, DMSO) δ 8.45 (d, J = 8.2, 1H), 7.98 (s, 1H), 7.71 (s51H), 7.34 (dd, J =8.2,4.1, 1H), 7.25 (d, J=9.3, 2H), 4.45-4.31 (m, 1H), 4.23-4.11 (m, 1H), 4.02 (dd, 0.0027 156325.doc -135- 201202215 Examples Name structure *Η NMR Ki J=14.9, 9.3, 1Η), 3.92 (s, 3Η), 3.86 (dd, J=9.8, 7.5,1H), 3.59 (t, J=4.3, 3H), 3.17-3.08 ( m, 1H), 2.92 (d, J=4.6, 3H), 2.32 (s, 4H). 90 [4-(5-Gas-4-cyclopentylamino-pyrazin-2-ylamino)-3-indolyloxy-phenyl]•吗吓*-4-yl-methanone Ο Η / 〇'H NMR (400 MHz, DMSO) δ 8.36 (d, J = 8.3 Hz, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 7.05 (d, J = 1.5 Hz, 1H), 7.00 (d, J=8.3 Hz, 1H), 6.93 (d, J=12 Hz, 1H), 4.36 (dd, J=14.2, 7.1 Hz, 1H), 3.90 (s, 3H), 3.56 (d, J- 33.8 Hz, 8H), 1.97 (d, J=l 1.7 Hz, 2H), 1.72 (s, 2H), 1.59 (m, J=11.5, 7.5 Hz, 4H). 0.0039 91 {4-[5-Gas-4-(1-indolyl-cyclobutylamino)-°3⁄4]-2-ylamino]-3-indolyloxy-phenyl}-Nuprin-4 -基-甲嗣>〇Ο CIA Mineο Η /〇'H NMR (400 MHz, DMSO) δ 8.21 (d, J=8.2 Hz, 1H), 7.95 (s, 1H), 7.65 (s, 1H) , 7.09-6.88 (m, 3H), 3.88 (s, 3H), 3.56 (d, J=37.1Hz, 8H), 2.32 (d, J=11.8Hz, 2H), 2.07 (s, 2H), 1.78 ( d, J = 6.7 Hz, 2H), 1.52 (s, 3H) 〇 0.0024 92 [4-(5-chloro-4-cyclohexylamino-pyridin-2-ylamino)-3-decyloxy- Phenyl]-morpholin-4-yl-fluorenone oxime CIA ο Η /〇]H NMR (400 MHz, DMSO) δ 8.33 (d, J = 8.3 Hz, 1H), 7.96 (s, 1H), 7.70 (s, 1H), 7.05 (d, /=1.4 Hz, 1H), 6.98 (d, J=8.3 Hz, 1H), 6.86 (d, J=7.8 Hz, 1H), 3.90 (s, 3H), 3.56 (d, /=34.3 Hz, 8H), 1.83 (dd, /=48.5, 11.4 Hz, 4H), 1.65 (d, J=12.7 Hz, 1H), 1.48-1.22 (m, 4H), 1.14 (d, J = 12.6 Hz, 1H). 0.0061 156325.doc -136- 201202215

实例 Instance name structure ^NMR Ki 93 (4-{5-gas-4-[(tetrazol chew-3_ylmercapto)-amino]-pyrazin-2-ylamino}-3-oxime --phenyl)- 吓 _ _ 4- ketone ketone Hhj / 0 H / ° 'HNMR (400 MHz, DMS0) δ 8.33 (d, J = 8.3 Hz, 1H), 7.97 (s, 1H), 7.71 (s, 1H), 7.49 (s, 1H), 7.05 (s, 1H), 6.99 (d, /=8.3 Hz, 1H), 3.90 (s, 3H), 3.75 (dd, /=13.8, 7.9 Hz, 1H), 3.67-3.44 (m, 8H), 3.38 (t, J=6.6Hz, 2H), 2.63 (s, 2H), 1.93 (dd, J=12.4, 5.8 Hz, 2H), 1.63 (dd, / =12,3, 5.4 Hz, 2H). 0.0141 94 [4-(5-Iodo-4-indolyl-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-fluorenone Η〆0 Η /〇 1HNMR (400 MHz, DMSO) δ 8.46 (s, 1H), 8.23 (s, 1H), 8.18 (d, 1H), 7.08 (s, 1H), 7.02 (d, 1H), 3.95 (s, 3H), 3.89 (s, 3H), 3.56 (m, 8H) 0.0008 95 [4-(5-Bromo-4-isopropoxy-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl] -Mallin-4-yl-methylhydrazine/〇*HNMR (400MHz, DMSO) δ 8.36 (s, 1H), 8.26 (s, 1H), 8.10 (d, 1H), 7.08 (d, 1H), 7.02 (dd, 1H), 5.32 (sept, 1H), 3.88 (s, 3H), 3.66-3.44 (m, 8H), 1.34 (d, 6H) 0.0039 96 [4-(5-bromo-4-ethoxy) Bite-2-ylamino)-3-decyloxy-phenyl]-morphin-4-yl-methanone Η /〇^NMR (400 MHz, DMSO) δ 8.38 (s, 1H), 8.26 ( s, 1H), 8.13 (d, 1H), 7.08 (d, 1H), 7.02 (dd, 1H), 4.44 (q, 2H), 3.88 (s, 3H), 3.70-3.43 (m, 8H), 1.36 (t, 3H) 98 [4-(5-Bromo-4-indolyl-°® dimethyl-2-ylamino)-3-decyloxy-phenyl]-(4,4-difluoro-peripiped啶-1-yl)-methanone Η /〇^NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.30 (s, 1H), 8.16 (d, 1H), 7.12 (s, 1H), 7.06 (d, 1H), 3.98 (s, 3H), 3.89 (s, 3H), 3.61 (s, 4H), 2.14-1.94 (m, 4H) 0.0045 156325.doc -137- 201202215 Example name structure ^NMR Ki 99 (4-{5-gas -4-[(tetrazine-bit 11 Nan-2-ylmethyl)-amino]-pyrazin-2-ylamino}-3-methoxy-phenyl)-oxalin-4-yl- Ketone eve. . 〇Η^〇Η /〇iHNMR (400ΜΗζ, DMSO) δ 8.32 (d, /=8.3 Hz, 1H), 7.98 (s, 1H), 7.71 (s, 1H), 7.23 (t, J=5.8Hz, 1H) , 7.05 (d, J=1.4 Hz, 1H), 6.98 (d, J=8.3 Hz, 1H), 4.13-4.05 (m, 1H), 3.90 (s, 3H), 3.78 (dd, J-13.9, 7.0 Hz, 1H), 3.65-3.47 (m, 8H), 3.47-3.41 (m, 2H), 1.96-1.74 (m, 3H), 1.70-1.53 (m, 1H). 100 {4-[5-Chloro-4-(cyclobutylmethyl-amino)-°3⁄4 ate-2-ylamino]-3-decyloxy-phenyl}-morpholin-4-yl-fluorenone Η /〇lU NMR (400 MHz, DMSO) δ 8.36 (d, J = 8.3 Hz, 1H), 7.95 (s, 1H), 7.67 (s, 1H), 7.32 (s, 1H), 7.05 (d, J =1.5 Hz, 1H), 6.98 (d, J=8.3 Hz, 1H), 3.90 (s, 3H), 3.56 (d, 7=34.2 Hz, 8H), 3.47-3.41 (m, 2H), 2.72-2.59 (m, 1H), 1.98 (d, J=8.3 Hz, 2H), 1.82 (dd, /=13.9, 6.2 Hz, 2H), 1.74 (dd, /-18.4, 7.4 Hz, 2H) ° 101 [4- (5-iodo-4-oxime-°3⁄4.din-2-ylamino)-3-decyloxy-phenyl]-morpholin-4-yl-methanone Η /〇0.0021 102 [4- (5-Cyclobutyl-4-indolyl-pyrazin-2-ylamino)-3_decyloxy-phenyl]-?--*-4-yl-fluorenone^y ΗΝ|/ 0 Η /〇1H NMR (400 MHz, DMSO) δ 8.39 (d, 1H), 7.93 (s, 1H), 7.82 (s, 1H), 7.07 (s, 1H), 7.02 (d, 1H), 3.97 (s, 3H), 3.91 (s, 3H), 3.56 (m, 8H), 1.80-1.71 (m, 1H), 0.86-0.78 (m, 2H), 0.69-0.61 (m, 2H) 0.4275 156325.doc -138· 201202215 o 〇Instance 103 104 105 106 Name Structure

ONMR

Ki [4-(5-cyclopropyl-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-morpholin-4-yl-fluorenone {4-[ 5-Actyl-4-(2-cyclopropyl-ethylamino)-°3⁄4 ate-2-ylamino]-3-methoxy-phenyl}-morphin-4-yl-曱_ {4 -[5-Gatro-4-(2-decyloxy-ethylamino)-[3⁄4唆-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone {4-[5-Gatro-4-(cyclopentylmethyl-amino)-°3⁄4 ate-2-ylamino]-3-decyloxy-phenyl}-morphin-4-yl-A Gang

Iz,s, ,m hpj /IV \ly /IV ? , MfH),.03H),m.56H),2H)3H) 00.60l,7,il,.7,3,13,,, (48 @ H)(d=4H)(d(nl(nlH) ^07,0 1,82^,507·^^7·^'^2·-2-1'^ N^llxolx5-2-4Hwff4H59H302 -E 1 1 6 2 2 ΉΝΜΕΙ(400ΜΗζ, DMSO) δ 8.36 (d, /=8.3 Hz, 1H), 7.95 (s, 1H), 7.67 (s, 1H), 7.31 (s, 1H), 7.05 (d, J =1.4Hz, 1H), 6.99 (d, J=8.2Hz, 1H), 3.90 (s, 3H), 3.65-3.43 (m, 8H), 1.49 (dd, /=14.6, 7.1 Hz, 2H), 0.71 (s, 1H), 0.47-0.34 (m, 2H), 0.06 (d, J = 3.8 Hz, 2H). *ΗΝΜΚ(400ΜΗζ, DMSO) δ 8.32 (d, J=8.3 Hz, 1H), 7.98 (s , 1H), 7.71 (s, 1H), 7.24 (d, J=5.5 Hz, 1H), 7.05 (s, 1H), 6.98 (d, J=8.2 Hz, 1H), 3.90 (s, 3H), 3.66 -3.45 (m, 12H), 3.26 (d, J = 9.4 Hz, 3H). 'HNMRC^OMHz, DMSO) δ 8.37 (d, /=8.3 Hz, 1H), 7.95 (s, 1H), 7.67 (s , 1H), 7.38 (t, /=5.4 Hz, 1H), 7.05 (s, 1H), 6.97 (d, J=8.3 Hz, 1H), 3.90 (s, 3H), 3.56(d, J=34.6Hz , 8H), 2.35-2.24 (m, 1H), 1.73-1.44 (m, 6H), 1.29 (dd, /=11.7, 7.1 Hz, 2H). 0.0895 0.0018 0.0094 0.0039 156325.doc •139- 201202215 Instance Name Structure *HNMR Kj 107 [4-(5-bromo) 4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((R)-2,2-di-deutero-3-methyl-morpholin-4- Methyl ketone H / ° 0.002 108 [4-(5-chloro-4-methylamino-benzo-2-ylamino)-3-(2,2,2-trifluoroi-ethoxy )-phenyl]-morpholin-4-yl-fluorenone HN〆" 0 α 灰 ο Η Ηρ *Η NMR (400 MHz, DMSO) δ 8.40 (d, J=8.3 Hz, 1H), 7.96 ( s, 1H), 7.65 (s, 1H), 7.34 (d, /=4.7 Hz, 1H), 7.23 (s, 1H), 7.12 (d, J-8.4 Hz, 1H), 4.92 (q, J=8.8 Hz, 2H), 3.56 (m, 8H), 2.91 (d, J=4_5 Hz, 3H). 0.0004 109 [4-[5-Chloro-4-(2-methoxy-ethylamino)-°3⁄4 bite 2-ylamino]-3-(2,2,2-tris-ethoxy) )-phenyl]- 吓 · -4- ke ketone ΗΝ*^^0, 0 Η o^k; 'H NMR (400 MHz, DMSO) δ 8.31 (d, J = 8.3 Hz, 1H), 7.98 (s, 1H), 7.70 (s, 1H), 7.27 (m, 1H), 7.22 (s, 1H), 7.09 (d, J=8.3 Hz, 1H), 4.92 (m, 2H), 3.52 (m , 12H), 3.26 (s, 3H). 0.0096 110 [4-(5-Bromo-4·decyloxy-pyrimidin-2-ylamino)-2-a-5-methoxy-phenyl]-morphin-4-yl-methanone oxime / 〇lU NMR (400 MHz, DMSO) δ 8.46 (s, 1H), 8.34 (s, 1H), 8.16 (d, /=12.0 Hz, 1H), 7.04 (d, J=6.1 Hz, 1H), 4.01 ( s, 3H), 3.89 (s, 3H), 3.60 (m, 8H). 0.0110 111 [4-(5-Bromo-4-indolyl-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-((S)-2,2-di-deuterated -3-Methyl-morpholin-4-yl)-fluorenone ΗΝ〆0 Η /〇112 [4-(5-Ga-4-indoleyl-°3⁄4 ate-2-ylamino)-3-曱oxy-phenyl]-[4-(1-methyl-piperidine- ΗΝ^ 0 Η /〇^Ν, 156325.doc •140· 201202215

Example name structure XH NMR Ki 4-yl)-〇底"Qin-1-yl]-methanone 113 [4-(5-Ga-4-indoleyl-°3⁄4pred-2-ylamino)- 3-trifluorodecyloxy-phenyl]-morphin-4-yl-indole 114 F 114 [4-(5-d-butyl-4-yloxy)-biting-2-ylamine ))-3-曱-oxy-phenyl]- 吓 * -4- -4- ketone ketone /0 115 [3- gas -4- (5- -4- 4-amino-pyridin-2- Aminoamino)-phenyl]-infrared>-4-yl-methanone oxime ^ 0 Cl 0.006 116 [4-(5- desert-4-methoxy-mouth-2-ylamino ethoxylate) · 苯基 ] -4- -4- -4- -4- -4- -4- -4- ' ' ' ' ' ' ' 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 39 4.15 (q, J = 7.0 Hz, 2H), 3.99 (s, 3H), 3.55 (d, J = 37.7 Hz, 8H), 1.37 (t, /=6.9 Hz, 3H). 117 [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(3,3-difluoro-heterocyclobutane-1- ))-fluorenone HN^ 0 c,AVn〇tf H /° NMR NMR (400 MHz, DMSO) 5 8.64 (d, J=6.7 Hz, 1H), 8.47 (d, /=8.5 Hz, 1H), 7.98 (s, 1H), 7.73 (s, 1H), 7.55-7.42 (m, 2H), 7.35 (d, J = 4.5 Hz, 1H), 4.38-4.15 (m, 1H), 3.94 (s, 3H), 3.00 - 2.92 (m, 1H), 2.93 (d, J = 5.0 Hz, 3H), 2.85-2.59 (m, 2H). 118 {4-[5-Bromo-4-(2-decyloxy-ethylamino)-oryl-2-ylamino]-3-ethoxy-phenyl}-?HN^^0, 0 XH NMR (400 MHz, DMSO) δ 8.33 (d, J = 8.3 Hz, 1H), 8.06 (s, 1H), 7.68 (s, 1H), 7.07-6.93 (m, 3H), 4.16 (q, , /=6.9 Hz? 156325.doc -141 - 201202215 Example name structure JH NMR oxa-4-yl-fluorenone 2H), 3.69-3.38 (m, 12H), 3.28 (s, 3H), 1.39 (t, J= 6.9 Hz, 3H). 119 [4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-(4-didecylamino-piperidin-1-yl)-曱 ΗΗ ΗΗ ^ Ο H /0 1 'H NMR (400 MHz, DMSO) 5 8.39 (d, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.31 (d, 1H), 7.05 (s , 1H), 7.00 (d, 1H), 3.87 (d, 3H), 2.97 (s, 6H), 2.91 (d, 3H). 120 4-(5-Chloro-4-indolyl-Bitterbit 2-ylamino)-3-decyloxy-N-oxetan-3-yl-peptidylamine HN^ 0 H / ° ° 'H NMR (400 MHz, DMSO) δ 8.93 (d, J = 6.4 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.73 (s, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.51 (s, 1H), 7.35 (d, /=4.6 Hz, 1H), 5.00 (dt, J=13.9, 7.0 Hz, 1H), 4.78(t,J =6.9Hz, 2H), 4.60 (t, J=6A Hz, 2H), 3.95 (s, 3H), 2.92 (d, J=4.5 Hz, 3H) 〇121 4-(5-Gas-4-methylamine Base - contiguous 2-ylamino group >3-decyloxy>-N-(tetraz-c-amyl-3-yl)-nodal amine HN^ 0 H /° 'H NMR (400 MHz, DMSO) δ 8.45 (d, J=8.5 Hz, 2H), 8.04 (d, J=7.6 Hz, 1H), 7.98 (s, 1H), 7.71 (s, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.47 (s, 1H), 7.35 (d, J=4.2 Hz, 1H), 3.94 (s, 3H), 3.79 (t, 2H), 3.15 (t, 2H), 2.92 (d, J=4.5 Hz, 3H), 1.91 (m, 1H), 1.70 (m, 2H), 1.63-1.58 (m, 2H). 122 {4-[5-gas-4-(tetrahydro-pyr. south-3-yl) Amino)-pyrimidin-2-ylamino]-3-decyloxy-phenyl}-morpholin-4-yl-fluorenone j〇〇HN 0 H /〇*H NMR (400 MHz, DMSO) 6 8.29 (s, 1H), 8.27 (s, 1H), 8.00 (s, 1H), 7.76 (s, 1H), 7.05 (s, 1H), 6.98 (d, J-8.3Hz, 1H), 6.82 (d, J=8.0 Hz, 2H), 4.09 (m, 156325.doc ~ 142- 201202215

Example name structure *HNMR Ks 2Η), 3.90 (s, 3Η), 3.86-3.74 (m, 3Η), 3.56 (m, 8Η), 3.46-3.11 (m, 64H), 1.93 (s, 1H), 1.77- 1.52 (m, 3H). 123 {4-[5-Gas-4-(2-decyloxy-ethylamino)-] dimethyl-2-ylamino]-3-cyclobutoxy-phenyl}-morpholine-4- Base-ketone HN^^0, 0. Huan Mine 0. iHNMRGOOMHz, DMSO) δ 8.35 (d, J-8.3 Hz, 1H), 7.98 (s, 1H), 7.67 (s, 1H), 7.25 (t, J=52 Hz, 1H), 6.97 (d, J=8.3 Hz, 1H), 6.86 (s, 1H), 4.87-4.72 (m, 1H), 3.68-3.35 (m, 12H), 3.28 (s, 3H), 2.48-2.36 (m, 2H), 2.13 (m, 2H), 1.81 (m, 1H), 1.74-1.56 (m, 1H). 124 {4-[5-Bromo-4-(2-decyloxy-ethylamino)-°3⁄4 ate-2-ylamino]-3-cyclobutoxy-phenyl}- 淋 -4- Base - 曱 _ 乂. Hr° 1H NMR (400MHz, DMSO) δ 8.34 (d, J=8.3 Hz, 1H), 8.06 (s, 1H), 7.68 (s, 1H), 7.02 (t, J=5.5 Hz, 1H), 6.97 (d , J=8.4 Hz, 1H), 6.86 (s, 1H), 4.90-4.67 (m, 1H), 3.67-3.41 (m, 12H), 3.27 (s, 3H), 2.41 (m, 2H), 2.26- 2.04 (m, 2H), 1.81 (m, 1H), 1.68 (m, 1H). 125 [4-(5-Gas_4_ 曱Amino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4-°Bite-4-yl-Nantazin-1-yl )-fluorenone ο Η /〇^νη 126 {4-[5-Gas-4-(2,2,2-tris-ethylamino)-pyrimidin-2-ylamino]-3-decyloxy -phenyl}-morpholin-4-yl-methanone HN^^Cp 0 Η /〇]HNMR (400MHz, DMSO) δ 8.20 (d, •7=8.3 Hz, 1H), 8.10 (s, 1H), 7.92 (s, 1H), 7.80 (t, J=6.4 Hz, 1H), 7.06 (s, 1H), 6.97 (d, J=8.2 Hz, 1H), 4.28-4.12 (m, 2H), 3.89 (s , 3H), 156325.doc -143- 201202215 Instance name structure ^NMR Ki 3.56 ((1,/=36.1 Hz, 8Η). 127 {4-[5-chloro-4-(2,2-digas-B Amino)-n-butyl-2-ylamino]-3-decyloxy-phenyl}-oxalin-4-yl-ketone HN^^|^F 0 Η /〇'HNMR (400 MHz, DMSO) δ 8.22 (d, J=8.3 Hz, 1H), 8.05 (s, 1H), 7.91 (s, lH), 7.58 (s, 1H), 7.06 (s, 1H), 6.97 (d, /=8.3 Hz, 1H), 6.39-6.03 (m, 1H), 3.86 (d, J=19.1 Hz, 3H), 3.87-3.69 (m, 2H), 3.56 (d, /=35.6 Hz, 8H). 128 [4 -(5-bromo-4-methoxy·. shout. _2_2 amino-amino)-3-isopropoxy-phenyl]- cylin-4-yl-fluorenone oxime 'HNMR (400 MHz, DMSO) 5 8.40 (s, 1H) , 8.23 (d, J=8.3 Hz, 1H), 8.13 (s, 1H), 7.08 (s, 1H), 7.00 (d, /=8.3 Hz, 1H), 6.73 (s, 1H), 4.81-4.61 ( m, 1H), 4.00 (s, 3H), 3.55 (d, J = 39.2 Hz, 8H), 1.32 (d, J = 6.0 Hz, 6H). 129 [3-bromo-4-(5-gas-4) -Amidino-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone ΗΝ^ 0 Br lU NMR (400 MHz, DMSO) δ 8.21 (d, /=8.5 Hz , 1H), 8.06 (s,lH), 7.94 (s, 1H), 7.67 (d, J=1.6Hz, 1H), 7.44-7.39 (m, 1H), 7.35-7.29 (m, 1H), 3.67- 3.38 (m, 8H), 2.87 (d, /=4.6 Hz, 3H). 130 [4-(5-Bromo-4-decyloxy-oxyl-2-ylamino)-3-decyloxy-phenylindole 4-(1-hydroxy-1-indolyl-ethyl)- 0 1-yl]-fluorenone 0\ ΟΗ 'HNMR (400 MHz, DMSO) δ 8.38 (s, 1H), 8.29 (s, 1H), 8.12 (d, 1H), 7.04 (s, 1H), 6.98 ( d, 1H), 4.13 (s, 1H), 3.98 (s, 3H), 3.88 (s, 3H), 1.51-1.32 (m, 2H), 1.17 (d, 2H), 1.05 (s, 6H). 156325.doc 144- 201202215

Example name structure ^NMR Ki 131 (4-(5-bromo-4-pyridylpyrimidin-2-ylamino)-3-methoxyphenyl)(3-(trifluoromethyl)pyrrolidin-1 -based) fluorenone ν ν Η 〇, *HNMR (400 MHz, DMS0) δ 8.39 (s, 1H), 8.31 (s, 1H), 8.18 (d, 1H), 7.17 (d, 2H), 3.99 (s , 3H), 3.90 (s, 3H), 3.77 (dd, 1H), 3.60 (d, 3H). 132 1-(4-(5-Butoxy-4-pyridylpyrimidin-2-ylamino)-3-methoxybenzyl)piperidine-4-carbonitrile oxime, 1H NMR (400 MHz, DMSO) δ 8.38 (s, 1H), 8.30 (s, 1H), 8.14 (d, 1H), 7.08 (s, 1H), 7.01 (d, 1H), 3.98 (s, 3H), 3.89 (s, 3H), 3.15 ( s, 2H), 1.90 (s, 2H), 1.80-1.67 (m, 2H). 133 (3-methoxy-4-(5-decyloxy-4-(decylamino)pyrimidin-2-ylamino)phenyl)(N-morpholinyl)anthrone ΗΝ^ 0 Η /〇 iHNMR (400 MHz, DMSO) δ 8.56 (d, 1H), 7.58 (s, 1H), 7.32 (s, 1H), 7.06-6.95 (m, 3H), 3.92 (d, 3H), 3.75 (d, 3H) ), 3.65-3.46 (m, 8H), 2.86 (d, 3H). 0.259 134 N-(3-Aminopropyl)-4-(5-vapor-4-(methylamino)pyrimidin-2-ylamino)-3-decyloxyguanamine ΗΝ^ 0 Η /〇 135 [3-曱-oxy-4-(4-decylamino-5-propan-1-yl-yl)-phenyl]-phenyl]-morpholin-4-yl-fluorenone \ ΗΝ^ 0 Η /〇lHNMR(400MHz, DMSO) δ 8.46 (d, J=8.3, 1H), 7.93 (s, 1H), 7.66 (s, 1H), 7.05 (s, 1H), 7.00 (d, J=7.9, 2H), 3.90 (s, 3H), 3.60 (s, 4H), 3.52 (s, 4H), 2.91 (d, J=4.6, 3H), 2.08 (s, 3H). 136 [3-decyloxy-4-(4-methoxy-5-propan-1-yl)-phenyl]-phenyl]-stimulus*-4-yl-indole Ketooxime / 〇lHNMR (400MHz, DMSO) δ 8.28 (s, 2H), 8.20 (d, J=8.2, 2H), 7.08 (s, 1H), 7.02 (d, J=8.0, 2H), 3.95 (s , 3H), 3.89 (s, 3H), 3.61 (s, 4H), 3.52 (s, 4H), 2.05 (s, 0.400 156325.doc -145- 201202215 Example name structure *H NMR 3H). 137 [5-Chloro-4-(5-chloro-4-methylamino-pyrazin-2-ylamino)-2-decyloxy-phenyl]-oxalin-4-yl-fluorenone ΗΝ^ 0 〇 CI * H NMR (400 MHz, DMSO) 5 8.11 (s, 1H), 7.99 (s, 1H), 7.97 (s, 1H), 7.38 (m, 1H), 7.29 (s, 1H), 3.82 (s, 3H), 3.60 (s, 4H), 3.52 (t, J = 4.3, 2H), 3.17 (s, 2H), 2.92 (d, J = 4.6, 3H). 139 {4-[5-Bromo-4-(2-decyloxy**ethyl lactyl)-σ-denyl-2-ylamino]-3-decyloxy-phenyl}-morpholin-4- Base-indolone oxime. βΛ^ο Η /〇'H NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.31 (s, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.08 (s, 1H), 7 -02 (d, /=8.2 Hz, 1H), 4.53-4.49 (m, 2H), 3.88 (s, 3H), 3.72-3.67 (m, 2H), 3.64-3.46 (m, 8H). 0.0057 140 5-Gas-4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-oxime, Ν-dimethyl-benzylamine ~NH \〇0 Cl 'H NMR (400 MHz, DMSO): δ 8.09 (s, 1H), 8.03 (s, 1H), 7.98 (s, 1H), 7.40 (d, J = 5.3 Hz, 1H), 7.25 (s, 1H) ), 3.81 (s, 3H), 2.95 (s, 3H), 2.92 (d, J=4.5 Hz, 3H), 2.79 (s, 3H). 0.0118 141 5-Gas-4-(5-Ga-4-indolinyl-pyrimidin-2-ylamino)-2-decyloxy-peptidylamine~ΝΗ 'Ο 0 Cl lH NMR (400 MHz, DMSO ): δ 8.27 (s, 1H), 8.02 (s, 2H), 7.87 (s, 1H), 7.59 (d, J = 13.4 Hz, 2H), 7.47 (d, J = 5.4 Hz, 1H), 3.93 ( s, 3H), 2.94 (t, J = 2.2 Hz, 3H). 0.0093 142 5-Gas-4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-indole-(2-trans-ethyl)-2-methoxy-dodecylamine\ Nh, 0 0 Cl OH *H NMR (400 MHz, DMSO): δ 8.27 (s, 1H), 8.20 (t, J = 5.5 Hz, 1H), 8.02 (d, J = 6.9 Hz, 2H), 7.88 ( s, 1H), 7.47 (d, J=5.3 Hz, 1H), 4.81 (s, 1H), 3.94 (s, 3H), 3.51 (t, J=5.9Hz, 2H), 3.40-3.35 (m, 2H) ), 2.95-2.88 (m, 3H). 0.0110 156325.doc -146- 201202215 Example Name Structure ^NMR Ki 143 5-Gas-4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-2-decyloxy-N-( 2-methoxy-ethyl)-benzylguanamine ~ ΝΗ, 0 0 c, Av S ci d), 1H NMR (400 MHz, DMSO): δ 8.28 (s, 1H), 8.20 (s, 1H), 8.02 ( d, J=6.8 Hz, 2H), 7.87 (s, 1H), 7.47 (d5 J=5.1 Hz, 1H), 3.94 (s, 3H), 3.47-3.43 (m, 5H), 2.96-2.88 (m, 5H). 0.01533 144 5-Gas-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-decyloxy-N-methyl-benzylamine ^nh, 〇0 ciyS i^ Sr^SH, in! Cl ^ NMR (400 MHz, DMSO): δ 8.24 (s, 1H), 8.11 (d, J = 5.5 Hz, 1H), 8.03 (d, J = 10.5 Hz, 2H), 7.84 ( s, 1H), 7.48 (d, J=5.5 Hz, 1H), 3.92 (s, 3H), 2.94 (d, J=2.3 Hz, 3H), 2.81 (d, J=4.6 Hz, 3H) 〇0.0113 145 5-AZ-4-(5-Ga-4-indole-pyrimidin-2-ylamino)-N-cyclopropyl-2-decyloxy-benzylamine ^NH, 0 0 Cl丫r^ Y^NH VNV λ Cl iHNMRGOOMHz, DMSO): δ 8.21 (s, 1H), 8.02 (d, J=8.4 Hz, 3H), 7.75 (s, 1H), 7.45 (d, J=5.3 Hz, 1H), 3.89 (s, 3H), 2.92 (t, J=4.5 Hz, 3H), 2.82 (tq, J=7.4, 3.7 Hz, 1H), 0.73-0.66 (m, 2H), 0.59-0.53 (m, 2H) . 0.01003 146 [5-gas-4-(5-gas-4-methylamino-pyrimidin-2-ylamino)-2-decyloxy-phenyl]-(4,4-digas-° bottom咬-1-yl) 曱 ketone ~NH, 0 0 Cl ^HNMRGOOMHz, CDC13): δ 8.47 (s, 1H), 7.96 (s, 1H), 7.52 (s, 1H), 7.28 (s, 1H), 5.40 (d, J=5.8 Hz, 1H), 3.99 (s, 1H), 3.87 (s, 3H), 3.79 (s, 1H), 3.47 (s, 1H), 3.38 (s, 1H), 3.12 (d , J=4.9 Hz, 3H), 2.06 (d, J=17.3 Hz, 2H), 1.94 (s, 2H). 0.0078 147 [5-Chloro-4-(4-ethylamino-5-trifluorodecyl-σ-deni-2-ylamino)-2-methoxy-phenyl]-morpholin-4-yl -fluorenone F ^NH , 0 0 Cl 1H NMR (400MHz, CDC13): 5 8.38 (s, 1H), 8.22 (d, J=ll Hz, 1H), 7.64 (s, 1H), 7.31 (s, 1H) , 5.19 (s, 1H), 3.87 (s, 3H), 3.78 (d, J=l 1.5 0.0034 156325.doc •147- 201202215 Example name structure ^NMR Ki Hz, 4H), 3.66-3.56 (m, 4H) , 3.32 (s, 2H), 1.30 (t, J = 7.3 Hz, 3H). 148 5-lacyl-N-propaffin-4-(4-ethylamino-5-trifluoromethylidene-2-ylamino)-2-decyloxy-benzylamine F ^ ΝΗ , 0 0 CI 'HNMR (400MHz, CDC13): δ 8.48 (s, 1H), 8.25-8.22 (m, 2H), 7.81 (s, 1H), 7.75 (s, 1H), 5.19 (s, 1H), 3.98 ( s, 3H), 3.61 (qd, J=7.3, 5.2 Hz, 2H), 2.92 (tq, J=7.1, 3.7 Hz, 1H), 1.30 (t, J-7.3 Hz, 3H), 0.89-0.83 (m , 2H), 0.60-0.55 (m, 2H). 0.0035 149 5-Gas-4-(4-Ethylamino-5-trifluoromethyl-noise 2,ylamino)-2-methoxy-indole-(2-methoxy-ethyl) -benzylamine F ^ ΝΗ , 0 0 Cl 0 \ 1H NMR (400 MHz, CDC13): δ 8.49 (s, 1H), 8.24 (s, 2H), 8.12 (s, 1H), 7.75 (s, 1H), 5.19 (s, 1H), 4.00 (s, 3H), 3.69-3.55 (m, 6H), 3.41 (s, 3H), 1.30 (t, J = 7.3 Hz, 3H). 0.0093 150 [5-Gatro-4-(5-chloro-4-methylamino-pyrazin-2-ylamino)-2-decyloxy-phenyl]-Brigade-1 _yl-fluorenone^ NH 〇0 c'tx^〇H Cl Ή NMR (400 MHz, DMSO): δ 8.08 (s, 1H), 8.03 (s, 1H), 7.97 (s, 1H), 7.40 (d, J=5.3 Hz , 1H), 7.26 (s, 1H), 3.81 (s, 3H), 3.51 (d, J=17.9 Hz, 2H), 3.08 (s, 2H), 2.92 (d, J=4.5 Hz, 3H), 2.70 (t, J = 5.2 Hz, 2H), 2.60 (s, 3H). 0.0089 151 [5_Gas-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-decyloxy-phenyl]-(4-didecylamino-α辰u定-1 -yl)-fluorenone \nh, o ο H Ϊ, I Ή NMR (400 MHz, DMSO): δ 8.08 (s, 1H), 8.03 (s, 1H), 7.97 (s, 1H), 7.40 (d, J=5.2 Hz, 1H), 7.30 (s, 0.5H), 7.23 (s, 0.5H), 4.43 (s, 1H), 3.80 (s, 3H), 2.92 (d, J=4.5 Hz , 3H), 2.80-2.66 (m, 1H), 2.35 (d, J=12.5 Hz, 3H), 2.19 (s, 6H), 1.81 (s, 0.0028 156325.doc -148- 201202215

Example Name Structure JHNMR Ki 1H), 1.67 (s, 1H), 1.32 (s, 2H). 152 [5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(3-hydroxypyrobitone-1 -yl ) - fluorenone ~ ΝΗ, 0 0 Η ί丨0 Η 1H NMR (400 MHz, DMSO): δ 8.10 (d, J = 4.1 Hz, 1H), 8.05-7.97 (m, 2H), 7.40 (d, J = 5.2 Hz, 1H), 7.26 (s, 1H), 4.98 (s, 1H), 4.32 (s, 1H), 4.21 (s, 1H), 3.81 (s, 3H), 3.49 (dd, J=9.9, 5.4 Hz , 2H), 3.00 (d, J = 11.2 Hz, 1H), 2.93-2.86 (m, 3H), 1.98-1.80 (m, 1H), 1.78-1.71 (m, 1H). 0.0086 153 5-Gas-4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-2_decyloxy-N-oxadiazepine-3-yl-benzylamine ΝΗ , 0 0 , human κ V cold Cl 〇 1H NMR (400 MHz, DMSO): δ 8.67 (d, 3 = 63 Hz, 1H), 8.29 (s, 1H), 8.06 (d, J-9.2 Hz, 2H), 7.79 (s, 1H), 7.50 (d, J=5.3 Hz, 1H), 5.04-4.96 (m, 1H), 4.86-4.76 (m, 2H), 4.64-4.57 (m, 2H), 3.97 (s, 3H), 2.97 (d, J=4.6 Hz, 3H). 0.0274 154 5-Gas-N-cyclopropyl-2-decyloxy-4-(4-amidino-5-trifluoromethyl- σ-denyl-2-ylamino)-nodal amine F ^ NH \〇0 Cl 'HNMR (400MHz, CDC13): δ 8.54 (s, 1H), 8.26 (d, J=6.2 Hz, 2H), 7.82 (d, J=14.2 Hz, 2H), 5.32 (s, 1H ), 4.00 (s, 3H), 3.15 (d, J = 4.7 Hz, 3H), 2.97-2.91 (m, 1H), 0.91-0.84 (m, 2H), 0.64-0.58 (m, 2H). 0.0052 155 5-Chloro-4-(5-vapor-4-methylamino-pyrimidin-2-ylamino)-2-decyloxy-N-(l-methyl-πchen-4-yl) -benzylamine amine ~NH, 0 0 rS H Cl ψ 1 iHNMR (400 MHz, CDC13): δ 8.54 (s, 1H), 8.20 (s, 1H), 7.97 (s, 1H), 7.75 (d, J= 8.0 Hz, 1H), 7.62 (s, 1H), 5.40 (d, J=5.7 Hz, 1H), 4.07-3.94 (m, 4H), 3.12 (d, J=4.9 Hz, 3H), 2.76 (s, 2H), 2.31 (s, 3H), 2.32-2.11 (m, 0.0045 156325.doc -149- 201202215 Example name structure ^NMR Kj 2H), 2.04 (d, J=12.5 Hz, 2H), 1.68 (s, 2H ). 156 [5-Chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-decyloxy-phenyl]-. Bilolide-1-yl-fluorenone \nH \〇0 CI WNMRWOOMHz, CDC13): δ 8.44 (s, 1H), 7.96 (s, 1H), 7.54-7.48 (m, 1H), 7.30 (s, lH ), 5.37 (s, 1H), 3.87 (s, 3H), 3.62 (t, J-7.0 Hz, 2H), 3.29 (t, J=6.7 Hz, 2H), 3.12 (d, J=4.9Hz, 3H ), 1.98-1.81 (m, 4H). 0.0074 157 N-Secontabutyl-5-chloro-4-(5-chloro-4-indolylpyrimidin-2-ylamino)-2-decyloxy-nodal amine\νη \〇0 CINj ^^N Cl 1HNMR (400MHz, CDC13): 6 8.51 (s, 1H), 8.20 (s, 1H), 7.97 (s, 1H), 7.76 (s, 1H), 7.60 (s, 1H), 5.38 (s , 1H), 3.98 (s, 3H), 3.12 (d, J = 4.9 Hz, 3H), 1.45 (s, 9H) 0.0282 158 5-chloro-2-methoxy-wind > 1-didecyl- 4-(4-Amidino-5-trimethylsulfonyl-mouth-2-ylamino)-benzylamine F ~NH, 0 0 Cl JHNMR (400 MHz, CDC13): δ 8.41 (s, 1H ), 8.22 (s, 1H), 7.66 (s, 1H), 7.29 (s, 1H), 5.30 (s, 1H), 3.87 (s, 3H), 3.15-3.06 (m, 6H), 2.93-2.85 ( m, 3H). 0.0068 159 5-Chloro-4-(5-Ga-4-indole-pyrimidin-2-ylamino)-2-methoxy-N-(2-decyloxy-ethyl)-N-indole - 醯 ^ ~ NH NH NH ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 7.26 (d, J=2.2 Hz, 1H), 3.83 (d, J=4.7 Hz, 3H), 3.59-3.56 (m, 2H), 3.33 (s, 2H), 3.19(S, 2H), 2.99 (s , 3H), 2.94 (s, 2H), 2.86 (s, 2H) 0.01151 160 5 -Gas-4-(5-Gas-4-Amino-pyrimidin-2-ylamino)-N-(2- Hydroxy-2-methyl-propyl)-2-decyloxy-nodal amine ~NH, 0 0 H Cl 丨 'HNMRC^O MHz, DMSO): δ 8.30 (s, lH), 8.16 (t, J =5.6 Hz, 1H), 8.04 (d, J=10.5 Hz, 2H), 7.90 (s, 1H), 7.47 (d, J=5.1 Hz, 1H), 4.68 (s, 1H), 3.96 (s, 3H ), 3.29 (d, J=5.6Hz 0.01179 156325.doc -150- 201202215 Example name structure ^NMR K 2Η), 2.95 (d, J=3.8 Ηζ, 3Η), 1.13 (s, 6Η). 161 [5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)_2-decyloxy-phenyl]-(4-carbyl-n-butyl-1- Base)-methanone Cl 'HNMRC^OMHz, DMSO): δ 8.08 (s, 1H), 8.03 (s, 1H), 7.98 (s, 1H), 7.40 (d, J=5.0 Hz, 1H), 7.26 ( s, 1H), 4.77 (d, J=4.0 Hz, 1H), 4.01 (s, 1H), 3.81 (s, 3H), 3.72 (d, J=7.5 Hz, 1H), 3.01 (s, 2H), 2.93 (d, J=4.5 Hz, 3H), 1.77 (s, 1H), 1.67 (s, 1H), 1.36 (d, J=11.6Hz, 2H), 1.33-1.20 (m, 1H). 0.0036 162 [5-Gatro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(2-hydroxyindole-Merlin- 4-yl)-fluorenone~ΝΗ 0 Cl ΗΟ^ !ΗΝΜΚ(400ΜΗζ, DMSO): 5 8.14(d, J=3.1 Hz, 1H), 8.09-7.98 (m, 2H), 7.43 (s, 1H), 7.34 (d, J=15.4 Hz, 1H), 4.86 (t, J=5.6 Hz, 1H), 4.74 (s, 1H), 4.46 (d, J=13.2 Hz, 1H), 4.33 (d, J=12.8 Hz, 1H), 4.00-3.90 (m, 1H), 3.85 (s, 3H), 3.39-3.49 (m, 3H), 3.19-3.30 (m, 2H), 2.96-2.83 (m, 3H). 0.0069 163 5-Gas-4-(5-Gatro-4-phthalamido-pyrimidin-2-ylamino)-N-(2-trans-ethyl)-2-indolyl-N-indenyl -benzylamine ΝΗ, 0 0 Cl ΟΗ 1H NMR (400MHz, DMSO): δ 8.15-8.03 (m, 2H), 8.00 (s, 1H), 7.42 (d, J = 5.3 Hz, 1H), 7.28 (d , ]=7.7 Hz, 1H), 4.76 (dt, J=16.0, 5.4 Hz, 1H), 3.83 (d, J=5.5 Hz, 3H), 3.61 (d, J=6.2 Hz, 1H), 3.42-3.51 (m, 1H), 3.15 (s, 1H), 3.03-2.82 (m, 7H) 0.0078 156325.doc -151 - 201202215 Example Name Structure ^NMR Ki 164 5-Chloro-4-(5-chloro-4-曱Amino-pyrimidin-2-ylamino)-2-decyloxy-N-(l-methyl-cyclobutyl)-nodal amine 'NH \〇? ci V 'HNMR (400 MHz, DMSO): δ 8.27 (s, 1H), 8.06-8.03 (m, 3H), 7.81 (s, 1H), 7.49 (d, J=5.1 Hz, 1H), 3.96 (s, 3H), 2.97 (d, J=4.5 Hz , 3H), 2.41-2.29 (m, 2H), 2.06-1.98 (m, 2H), 1.89-1.79 (m, 2H), 1.50 (s, 3H). 0.01308 165 [5-Chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-decyloxy-phenyl]-[1,4]oxaza heterocycle Heptan-4-yl-methanone ^NH, 0 0 Cl 'HNMR (400 MHz, DMSO): δ 8.12 (s, 1H), 8.06 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H) , 7.42 (d, J=5.4 Hz, 1H), 7.31 (s, 1H), 3.93-3.71 (m, 4H), 3.79-3.58 (m, 5H), 3.59 (s, 2H), 2.95 (d, J =4.5 Hz, 3H), 1.89 (s, 1H), 1.72 (s, 1H). 0.0057 166 [5-Chloro-4-(5-chloro-4-indolyl-pyridin-2-ylamino)-2-indolyl-phenyl]-((2R,6S)-2,6 - dimethyl-morpholin-4-yl)-fluorenone ''', 0 Ο Cl ▲ 1H NMR (400 MHz, DMSO): S8.16 (s, 1H), 8.03 (d, J = l3.9 Hz , 2H), 7.44 (d, J=5.1 Hz, 1H), 7.32 (d, J=12.3 Hz, 1H), 4.40 (d, J=13.0 Hz, 1H), 3.84 (s, 3H), 3.55 (m , 1H), 3.21 (m, 1H), 2.88-2.74 (m, 4H), 2.73 (d, J = 15.3 Hz, 1H), 2.44 (m, 1H), 1.19-1.09 (m, 3H), 1.03 ( s, 3H). 0.02613 167 1-[5-Gas-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-methoxy-benzylindolyl]-piperidine-4-indoleonitrile\ Νη, 0 0 Cl *ΗΝΜΚ(400 MHz, DMSO): δ 8.04 (s, 1H), 7.96 (s, 1H), 7.91 (s, 1H), 7.31 (t, J = 10.1 Hz, 1H), 7.22 ( s, 1H), 3.88 (m, 1H), 3.75 (d, J=9.5 Hz, 3H), 3.22 (m, 1H), 3.07 (s, 2H), 2.86 (d, J=4.5 Hz, 3H), 1.86-1.61 (m, 5H). 0.0033 156325.doc -152- 201202215 Example Name Structure ^NMR Ki 168 5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-(2-light-based-propene ) 曱 曱 J 曱 曱 V V V 曱 曱 曱 曱 8. 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 7.96 (d, J=8.5Hz, 2H), 7.81 (s, 1H), 7.40 (d, J=5.2 Hz, 1H), 4.79 (s, 1H), 3.87 (s, 3H), 3.75-3.67 (m , 1H), 3.13-3.04 (m, 1H), 2.87 (d, J = 4.0 Hz, 3H), 1.01 (d, J = 6.2 Hz, 3H). 0.01026 169 [5-Chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-decyloxy-phenyl]-(3-hydroxy-azetidine -1-yl)-methanone~ΝΗ, 0 0 Cl JHNMR (400MHz, DMSO): δ 8.17 (s, 1H), 8.03 (d, J = 7.5 Hz, 2H), 7.45 (d, J = 5.4 Hz, 1H), 7.38 (s, 1H), 5.77 (s, 1H), 4.49 (d, J=6.4 Hz, 1H), 4.21 (t, J=8.5 Hz, 1H), 4.09 (t, J=8.1 Hz, 1H), 3.87 (s, 3H), 3.74 (t, J = 6.6 Hz, 2H), 2.98-2.92 (m, 3H). 0.0054 170 5-Gas-4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-N-(1-ranylcyclopropyl)-2-indolyl-benzylamine NH, 0 0 Cl 'HNMRC^OMHz, DMSO): δ 8.83 (s, 1H), 8.30 (s, 1H), 8.07 (d, J = 13.6 Hz, 2H), 7.83 (s, 1H), 7.51 (d , J = 5.2 Hz, 1H), 3.94 (s, 3H), 2.97 (d, J = 4.5 Hz, 3H), 1.61-1.55 (m, 2H), 1.35-1.25 (m, 2H). 0.0139 171 1-[5-Gas-4-(5-chloro-4-hydrazino-indenyl-2-ylamino)-2-methoxy-benzylindolyl]-pyrrolidine-3-indolecarbonitrile ~NH, 0 0 ci \ ^NMR (400 MHz, DMSO): δ 8.05 (d, J = 6.3 Hz, 2H), 7.93 (d, J = 2.0 Hz, 1H), 7.42 (s, 1H), 7.26- 7.22 (m, 1H), 3.78-3.64 (m, 4H), 3.55-3.19 (m, 4H), 2.88-2.81 (m, 3H), 2.28-2.00 (m, 2H) ° 0.0045 156325.doc -153- 201202215 Example name structure ^NMR Ki 172 [5-chloro-4-(5-chloro-4-indenylamino, guan-2-ylamino)-2-decyloxy-phenyl]-((3R,5S ) - dimethyl base ° Qin-1-yl)-fluorenone \νη, 0 0 H Cl * JHNMRGOOMHz, DMSO): δ 8.14 (s, 1H), 8.02 (t, J = 13.3 Hz, 2H), 7.43 (d, J-5.2 Hz, 1H), 7.30 (s, 1H), 4.42 (d, J=12.5 Hz, 1H), 3.83 (s, 3H), 3.22 (m, 2H), 2.83-2.53 (m, 7H), 1.08 (d, J = 6.2 Hz, 2H), 1.02 (s, 2H), 0.92 (s, 2H). 0.0333 173 5-Chloro-2-indolyl-4-(4-methylamino-5-trifluoromethyl-pyridin-2-ylamino)-N-(l-methylpiperidin-4- Base) - Β Β F F amine NH ~ 0 0 0 0 0 0 0 0 0 0 (s, lH), 7.36 (d, J = 5.2 Hz, 1H), 3.94 (s, 3H), 3.79 (m, 1H), 2.95 (d, J=4.3 Hz, 3H), 2.74 (s, 2H) , 2.24 (s, 3H), 2.16-2.09 (m, 2H), 1.84 (d, J = 12.2 Hz, 2H), 1.66-1.54 (m, 2H). 0.0015 174 5-Gapent-2-oxo-4-(4-guanidino-5-trifluoromethyl-pyridin-2-ylamino)-oxime-oxetan-3-yl- Benzoylamine F ~NH, 0 0 Cl 〇!H NMR (400 MHz, DMSO): δ 8.73 (d, J = 6.4 Hz, 1H), 8.64 (s, 1H), 8.26 (s, 1H), 8.06 ( s, 1H), 7.78 (s, 1H), 7.37 (d, J=5.1 Hz, 1H), 5.06-4.96 (m, 1H), 4.79 (t, J=6.9 Hz, 2H), 4.60 (t, 3 =6.4 Hz, 2H), 3.95 (s, 3H), 2.96 (d, J=4.3 Hz, 3H). 0.0041 175 5-Chloro-indole-(2-hydroxy-2-methyl-propyl)-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidine-2- Aminobenzyl)-benzylamine F ^NH , 0 0 Cl OH *H NMR (400 MHz, DMSO): δ 8.63 (s, 1H), 8.28 (s, 1H), 8.16 (m, 1H), 8.10 ( s, 1H), 7.92 (s, 1H), 7.37 (s, 1H), 4.68 (s, 1H), 3.97 (s, 3H), 3.29 (d, J=5.8 Hz), 2H), 2.95 (s, 3H), 1.16 (s, 6H). 0.0079 156325.doc -154- 201202215 Example name structure ^ NMR Ki 176 [5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethylidene-2-ylamino)- Phenyl]-pyrazin-1-yl-ketone F ^ ΝΗ , 0 0 Cl 1H NMR (400MHz, CDC13): δ 8.43 (s, 1H), 8.24 (d, J=ll Hz, 1H), 7.69 (s , 1H), 7.30 (d, J=l 1.0 Hz, 1H), 5.32 (s, 1H), 3.89 (s, 3H), 3.84-3.69 (m, 2H), 3_30(d, J=15.4Hz, 3H ), 3.14 (d, J = 4.7 Hz, 3H), 2.95 (s, 2H), 2.82 (s, 2H). 0.0041 177 1-[5-Gas-2-oxo-4-(4-methylamino-5-trifluorodecyl-U-Methoxy]-2-ylamino)-benzylindenyl]-pyrrolidine -3-carbonitrile F, 'NH, '0 0 c, ^ NMR (400 MHz, DMSO): δ 8.66 (s, 1H), 8.24 (s, 1H), 7.94 (d, J = 6.7 Hz, 1H) , 7.36 (s, 1H), 7.31 (s, 1H), 3.88-3.75 (m, 4H), 3.63-3.49 (m, 4H), 2.94 (t, J=3.9 Hz, 3H), 2.37-2.10 (m , 2H). 0.0029 178 1-[2-Fluoro-5-methoxy-4-(4-amidino-5-trifluoromethyl-D-denyl-2-ylamino)-benzylindenyl]-pyrrole bite- 3-anthracene F ^NH F 0 H /〇^ *H NMR (400 MHz, DMSO): δ 8.38 (dd, J = 12.4, 3.9 Hz, 1H), 8.29 (s, 1H), 8.17 (s, 1H) ), 7.41 (s, 1H), 7.08 (d, J=6.2 Hz, 1H), 3.93 (d, J=1.6 Hz, 3H), 3.67 (d, J=23.8Hz, 2H), 3.58 (t, J = 8.9 Hz, 2H), 3.50-3.43 (m, 1H), 2.98 (dd, J=4.3, 2.3 Hz, 3H), 2.39-2.13 (m, 2H). 0.0018 179 [5-Chloro-2-ethoxy-4-(4-decylamino-5-trifluoromethyl- σ-amyl-2-ylamino)-styl]-morpholin-4-曱-fluorenone F ''"NH 0 Cl JH NMR (400 MHz, CDC13): δ 8.39 (s, 1H), 8.22 (d, J=ll Hz, 1H), 7.65 (s5 1H), 7.32 (s , 1H), 5.29 (s, 1H), 4.10(s, 2H), 3.76 (s, 4H), 3.67 (s, 1H), 3.61 (s, 1H), 3.37 (s, 1H), 3.29 (s, 1H), 3.11 (d, J = 4.7 Hz, 3H), 1.43 (t, J = 7.0 Hz, 3H). 0.02472 156325.doc -155- 201202215 Example name structure *Η NMR Ki 180 2-fluoro-5-decyloxy-N-mercapto-4-(4-methylamino-5-trifluoromethyl-pyrimidine-2 -ylamino)-benzylamine F ~NH F 0 Η /〇iHNMR (400ΜΗζ, DMS0): δ 8.37 (d, J = 13.4 Hz, 1 Η), 8·30 (s, lH), 8.18 (s, 1H), 8.07 (s, 1H), 7.42 (d, J=5.1 Hz, 1H), 7.30 (d, J=6.7 Hz, 1H), 3.94 (s, 3H), 2.98 (d, J=4.2 Hz, 3H), 2.82 (d, J=4.5 Hz, 3H). 0.0047 181 5-Chloro-N-(2-hydroxy-2-methyl-propyl)-2-methoxy-N-indenyl-4-(4-guanidino-5-trifluoromethyl-pyrimidine -2-ylamino)-benzylamine F "^NH, 0 0 H Cl HO Ή NMR (400 MHz, CDC13): δ 8.44 (s, 1H), 8.22 (s, 1H), 7.68 (s, 1H), 7.32 (s, 1H), 5.31 (s, 1H), 4.08 (s, 1H), 3.95 (s, 3H), 3.58 (s, 2H), 3.13 (d, J=4.6 Hz, 3H), 3.01 (s, 3H), 1.32 (s, 6H). 0.0063 182 (4-(5-Cyclopropyl-4-decyloxypyrimidin-2-ylamino)-3-methoxyphenyl XN-morpholinyl)methanone H /〇1H NMR (400 MHz, DMSO) δ 8.60 (d, 1H), 7.74 (s, 1H), 7.41 (s, 1H), 7.03 (s, 1H), 7.00 (d, 1H), 6.50 (d, J=4.7, 1H), 3.91 (s, 3H), 3.56 (m, 8H), 2.87 (d, 3H), 2.35-2.27 (m, 2H), 2.02-1.91 (m, 3H), 1.24 (s, 2H) 0.0895 183 1-{2 -[2-decyloxy_4-(morphin-4-carbonyl)-anilino]-4_methylamino-pyrazin-5-yl}_acetoxime 0 ~NH 0 H /〇1H NMR (400 MHz, DMSO) δ 9.21-9.05 (m, 1H), 8.71 (s, 1H), 8.35 (d, J=8.2, 1H), 8.25 (s, 1H), 7.09 (s, 1H), 7.03 (d, J-8.3, 1H), 3.90 (s, 3H), 3.56 (s, 8H), 2.99 (d, J=4.8, 3H), 2.45 (s, 3H). 0.0682 184 {4-[5-Gas-4-(2-methoxy-ethoxy)-moutate-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl - ketone oxime 0. Η /〇lU NMR (400 MHz, DMSO) δ 8.32 (m, 2H), 8.11 (d, J = 8.2 Hz, 1H), 7.08 (s, 1H), 7.02 (d, J = 8.2 Hz, 1H), 4.60-4.41 (m, 2H), 3.88 (s, 3H), 3.74-3.65 (m, 2H), 3-56 (m, 8H). 0.01819 156325.doc -156- 201202215

Example name structure *HNMR Ki 185 {4-[5-bromo-4_(2-decyloxy-ethylamino)indol-2-ylamino]-2_fluoro-5-decyloxy-phenyl}- Horror - 4-base-fluorenone 'F. ° Η /〇lHNMR (400MHz, DMSO) δ 8.27 (d, J = 12.3 Hz, 1H), 8.11 (s, 1H), 7.78 (s, 1H), 7.12 (t, J = 5.5Hz, 1H), 7.01 (t, J = 10.3 Hz, 1H), 3.89 (s, 3H), 3.57 (m, 12H), 3.27 (s, 3H). 0.0069 186 {4-[5-Bromo-4-(2-decyloxy-ethylamino)-pyrimidin-2-ylamino]-3-isopropoxy phenyl}-morphin-4-yl曱 network βγΧλν^Ο Η.丫1HNMR (400MHz, DMSO) δ 8.37 (d, /=8.3 Hz, 1H), 8.06 (s, 1H), 7.64 (s, 1H), 7.15-7.00 (m, 2H), 6.96 (d, J=8.3 Hz, 1H), 4.72 (dt, J = 12.0, 6.0 Hz, 1H), 3.71-3.40 (m, 12H), 3.28 (s, 3H), 1.33 (d, 6H). 0.0135 187 {4-[5-Gas-4-(2-decyloxy-ethoxy)-°3⁄4 ate-2-ylamino]-3-cyclobutoxy-phenyl}-Merlin-4 -Base-曱酉同/0\. Η °\3 ^ NMR (400 MHz, DMSO) δ 8.34 (s, lH), 8.24 (s, 1H), 8.13 (d, J = 8.2 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H) , 6.88 (s, 1H), 4.93-4.73 (m, 1H), 4.59-4.47 (m, 2H), 3.78-3.66 (m, 2H), 3.55 (m, 8H), 2.43 (m, 2H), 2.25 -2.00 (m, 2H), 1.80 (m, 1H), 1.74-1.47 (m, 1H). 0.0143 188 [4-(5-Gatro-4-indenyl-dean-2-ylamino)-3-cyclodecyloxy-phenyl]-(2-oxa-6-aza-spiro[3 ·3]g·6_yl)_methanone^ΝΗ 0 0Ό> 'HNMR(400MHz, DMSO) δ 8.43 (d, /=8.3 Hz, 1H), 7.95 (s, 1H), 7.59 (s, 1H) , 7.33 (d, J=4.3 Hz, 1H), 7.03 (s, 1H), 6.99 (d, J=8.3 Hz, 1H), 4.96 (m, 1H), 3.56 (dm, 8H), 2.92 (d, J = 4.5 Hz, 3H), 2.00-1.85 (m, 2H), 1.73 (m, 6H). 0.0063 156325.doc -157- 201202215 Example Name Structure *HNMR Ki 189 [4-(5-Gas-4-Methylaminoamino)-3-cyclopentyloxy-phenyl]-Merionine- 4-Base - ketone^ΝΗ 0 Η °Χ> 1HNMR (400MHz, DMSO) δ 8.43 (d, J=8.3 Hz, 1H), 7.95 (s, 1H), 7.59 (s, 1H), 7.33 (d, /=4.3 Hz, 1H), 7.03 (s, 1H), 6.99 (d, /=8.3 Hz, 1H), 4.96 (sm, 1H), 3.56 (dm, 8H), 2.92 (d, J=4.5 Hz, 3H), 2.02-1.85 (m, 2H), 1.73 (tm, 6H) ° 0.01260 3 190 [4-(5-Ga-4-amino-pyrimidin-2-ylamino)-3-decyloxy-phenyl ]-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-fluorenone~ΝΗ 0 Η 〇, *HNMR(400 MHz, DMSO) δ 8.45 (d, J=8.9 Hz, 1H), 7.98 (s,lH), 7.71(3, 1H), 7.34 (d, J=4A Hz, 1H), 7.23 (d, 2H), 4.69 (s, 4H), 4.53 (s, 2H), 4.19(s, 2H), 3.92 (s, 3H), 2.92 (d, J=4.5 Hz, 3H). 0.0063 191 2-(2-Methoxy-4-(2,2,6,6-tetrafluoromorphin-4-yl)anilino)-4-(decylamino)pyrimidine-5-carbonitrile, ΊΜΗ 0 Η /〇FF 1HNMR (400 MHz, DMSO) δ 8.37 (s, 1H), 8.33 (d, J=8.1 Hz, 1H), 7.13-7.07 (m, 2H), 4.32 (t, J=8.6 Hz , 4H), 3.91 (s, 3H), 2.90 (s, 3H) 0.0208 192 2-(4-(4,4-dioxene-1-aryyl)-2-nonyloxyanilino)-4- (Amino) pyrimidine-5-indoleonitrile~ΝΗ Ο Η /0 F 1H NMR (400 MHz, DMSO) δ 8.36 (s, 1H), 8.35 (s, 1H), 8.18 (d, J = 8.2 Hz, 1H), 7.79 (d, J=4.3 Hz, 1H), 7.12 (s, 1H), 7.05 (d, J=9.1 Hz, 1H), 3.88 (s, 3H), 3.59 (brs, 4H), 2.88 ( d, J=4.4 Hz, 3H), 2.12-1.96 (m, 4H) 0.0149 193 [4-(5-Gas-4-Amino-Symidine-2-ylamino)-3-cyclopropyl -Phenyl]-morpholin-4-yl-fluorenone ΗΝ^ 0 aAfo 'H NMR (400 MHz, DMSO) 5 8.19(s, 1H), 8.05 (d, J=8.4 Hz, 1H), 7.91 (s , 1H), 7.26-7.18 (m, 2H), 7.07-7.03 (m, 1H), 3.66-3.41 (m, 8H), 2.88 (d, J=4.6 Hz, 3H), 2.06-1.97 0.0239 156325.doc -158- 201202215

Example Name Structure ^NMR Ki (m, 1Η), 0.99-0.91 (m, 2H), 0.63-0.57 (m, 2H). 194 4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-(3,3-difluoro-cyclobutyl)-3-decyloxy-benzylguanamine H/ 〇X ^ NMR (400 MHz, DMSO): δ 8.69 (d, J = 6.6 Hz, 1H), 8.36 (s, 1H), 8.33 (s, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.80 (m, 1H), 7.41 (m, 2H), 4.37-4.19 (m, 1H), 3.92 (s, 3H), 3.06-2.84 (m, 5H), 2.84-2.63 (m, 2H). 0.0065 195 4-(5-Cyano-4-indenyl-pyrimidin-2-ylamino)-N-cyclopropylindolyl-3-indolyl-oximeamine ^NH 0 ΆνΧ Η /〇ν 'HNMRC^OMHz, DMSO): δ 8.46 (t, J=5.6 Hz, 1H), 8.35 (s, 1H), 8.33-8.17 (m, 2H), 7.78 (s, 1H), 7.51 (d, J= 7.1 Hz, 2H), 3.92 (s, 3H), 3.15 (approx. t, J=6.2 Hz, 2H), 2.90 (d, J=2.0Hz, 3H), 1.21-0.90, m, 1H), 0.64-0.35 (m, 2H), 0.30-0.12 (m, 2H). 0.0042 196 2-[4-((S)-3-Fluoro-pyrrolidine-1-carbonyl)-2-decyloxy-anilino]-4-methylamino-°3⁄4 咬-5-曱carbonitrile^ΝΗ 0 ΝΥχ rr^o ν ν ^ Η /° F ^NMRGOOMHz, DMSO): δ 8.35 (s, 1H), 8.31 (s, 1H), 8.21 (d, J = 8.2 Hz), 1H), 7.75 (m, 1H), 7.22-7.14 (m, 2H), 3.89 (s, 3H), 3.84-3.54 (m, 5H), 2.89 (d, J = 4.5 Hz, 3H), 2.27-2.00 (m, 2H). 0.0060 197 4-(5-Cyano-4-indenylamino)-3-methoxy-N-indenyl-benzylamine ΝΗ 0 Η /〇1H NMR (400 MHz, DMSO): δ 8.43- 8.27 (m, 3H), 8.24 (d, J=8.4 Hz, 1H), 7.77 (m, 1H), 7.51-7.45 (m, 2H), 3.91 (s, 3H), 2.89 (d, J=4.5 Hz , 3H), 2.78 (d, J=4.5 Hz, 3H). 0.0066 156325.doc -159- 201202215 Example name structure NMR Ki 198 4-(5-ranyl-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N,N-dimethyl -benzylamine ~NH 0 Η /〇^NMRC^O MHz, DMS0): δ 8.33 (s, 1H), 8.31 (s, 1H), 8.15 (d, J=8.2 Hz, 1H), 7.73 (m, 1H), 7.07 (d, J=1.4 Hz, 1H), 7.00 (dd, 3=8.2, 1.5 Hz, 1H), 3.87 (s, 3H), 2.97 (s, 6H), 2.85 (d, J=3.6 Hz, 3H). 0.01240 199 4-(5-Cyano-4-indenyl-pyrimidin-2-ylamino)-N,N-diethyl-3-indolyl-benzylamine, -ΝΗ 0 1 Η /° *H NMR (400 MHz, DMSO): δ 8.32 (s, 1H), 8.30 (s, 1H), 8.13 (d, J = 8.2 Hz, 1H), 7.71 (m, 1H), 7.00 (d, J= 1.3 Hz, 1H), 6.93 (dd, J=8.2, 1.5 Hz, 1H), 3.87 (s, 3H), 3.42-3.30 (m, 4H), 2.87 (s, 3H), 1.11 (t, J=6.8 Hz, 6H). 0.0068 200 4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-isopropyl-3-indole-benzylamine ΝΗ 0 Η /〇NMR (400 MHz , DMSO): δ 8.35 (s, 1H), 8.30 (s, 1H), 8.25 (d, J=8.6 Hz, 1H), 8.09 (d, J=7.7 Hz, 1H), 7.76 (m, 1H), 7.51 (s, 1H), 7.49 (s, 1H), 4.10 (dq, J=13.5, 6.7Hz, 1H), 3.92 (s, 3H), 2.90 (d, J=4.1 Hz, 3H), 1.17(d , J=6.6 Hz, 6H). 0.0044 201 2-[2-Methoxy-4-(pyrrolidin-1-carbonyl)-anilino]-4-indolyl-pyrimidine-5-indoleonitrile~ΝΗ 0 Ν Vl Jpr^O ν ν Η / 〇^ NMR (400 MHz, DMSO): δ 8.34 (s, 1H), 8.30 (s, 1H), 8.18 (d, J = 8.2 Hz, 1H), 7.74 (m, 1H), 7.17 (d, J = 1.3Hz, 1H), 7.13 (dd, J=8.3, 1.5 Hz, 1H), 3.88 (s, 3H), 3.46 (t, J-6.6 Hz, 4H), 2.89 (d, J=3.3 Hz, 3H) , 1.92-1.78 (m, 4H). 0.01467 156325.doc -160- 201202215

Example name structure ιΗ NMR Kj 202 2-[4-(3-Fluoro-azetidin-1-carbonyl)-2-decyloxy-anilino]-4-indenyl- σ-Bite-5-曱 ΝΗ ΝΗ F 0 F * HNMR (400 ΜΗζ, DMSO): δ 8.36 (s, 1 Η), 8.31 (s, 1H), 8.27 (d, J = 8.5 Hz, 1H), 7.79 (m, 1H), 7.27 ( Dd, 5=4.2, 2.6 Hz, 2H), 4.75-4.00 (m, 5H), 3.91 (s, 3H), 3.29 (m, 2H), 2.90 (d, J=2.0 Hz, 3H). 385 Ν 乙基 N 400 MHz, DMSO): 5 8.40-8.33 (m, 2H), 8.30 (s, 1H), 8.20 (d, J=8.2 Hz, 1H), 7.78 (m, 1H), 7.50 (s, 1H), 7.48 (s, 1H), 3.89 (s, 3H), 3.30 (m, 2H), 2.93 (s, 3H), 1.13 (t, J = 7.2 Hz, 3H). 6 6 0.009 曱 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 0.009 NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR , DMSO): 5 8.32 (s, 1H), 8.31 (s, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.72 (m, 1H), 7.03 (d, J = 1.4 Hz, 1H), 6.96 (dd, J=8.2, 1.4 Hz, 1H), 3.87 (s, 3H), 3.45 (br s, 4H), 2.88 (d, J=4.5 Hz, 3H), 1.68-1.45 (m, 6H). 0.0033 205 4-(5-Cyano-4-methylamino-oxo-2-ylamino)-indole-(2,2·difluoro,ethyl)-3-methoxy·benzylamine ~ ΝΗ 0 Η /〇F NMR (400 MHz, DMSO): δ 8.76 (t, J = 5.8 Hz, 1H), 8.36 (s, 1H), 8.33 (s, 1H), 8.29 (d, J = 8.8 Hz, 1H), 7.80 (m, 1H), 7.55 (s, 1H), 7.53 (d, J=1.6 Hz, 1H), 6.25-5.97 (m, 1H), 3.92 (s, 3H), 3.82-3.56 (m , 2H), 2.90 (s, 3H). 0.0121 206 Ν-Tertibutyl-4-(5-cyano-4-methylamino _ σ-Bitter-2-ylamino)-3-methoxy-benzylamine ~ ΝΗ 0 Η /〇* H NMR (400 MHz, DMSO): δ 8.35 (s, 1H), 8.29 (s, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.78 (m, 1H), 7.63 (s, 1H), 7.51-7.44 (m, 2H), 3.93 (s, 0.0046 156325.doc 161 - 201202215 Example name structure *Η NMR Kj 3Η), 2.90 (s, 3Η), 1.39 (s, 9Η). 207 4-(5-Cyano-4-methylamino-°3⁄4 ate-2-ylamino)-N-ethyl-N-isopropyl-3-methoxy-benzylamine, ·ΝΗ 0 I Η /〇'Η NMR (400 MHz, DMS0): δ 8.32 (s, 1Η), 8.31 (s, 1Η), 8.12 (d, J=8.2Hz, 1H), 7.71 (m, 1H), 6.97 (d, J=1.2Hz, 1H), 6.90 (d, J=8.2 Hz, 1H), 4.10-3.88 (m, 3H), 3.87 (s, 3H), 2.87 (d, J=4.5 Hz, 3H ), 1.15 (m9H). 0.0054 208 2-[4-(3,3-Difluoro-0 to 0°°-1-decyl)-2-decyloxy-anilino]_4_methylaminocarbonitrile 0 H /° F ' H NMR (400 MHz, DMSO): δ 8.35 (s, 1H), 8.31 (s, 1H), 8.24 (d, J = 8.2 Hz, 1H), 7.77 (m, 1H), 7.23-7.14 (m, 2H) ), 3.91 (s, 3H), 4.00-3.84 (m, 2H), 3.74 (t, J=7.1 Hz, 2H), 89 (d, J=4.2 Hz, 3H), 2.54-2_37 (m, 2H) . 0.0081 209 2-[4-(3,3-Difluoro-azetidin-1-yl)-2-methoxyanilino]-4-methylamino-pyrimidine-5-carbonitrile^NH 0 Η /〇'H NMR (400 MHz, DMSO): δ 8.37 (s, 1H), 8.33 (s, 1H), 8.30 (d, J = 8.3 Hz, 1H), 7.80 (m, 1H), 7.38-7.27 (m, 2H), 4.90-4.40 (m, 4H), 3.92 (s, 3H), 2.90 (d, J=4.5 Hz, 3H). 0.02382 210 2-[4-((R)-3-Fluoro-perylpyrazine-1 - anthracenyl)-2-nonyloxy-anilino]-4-nonylamino-σδσ--5-曱onitrile, "ΝΗ 0 Ν Υχ jc/o Η /0 F 'H NMR (400 MHz, DMSO): 6 8.35 (s, 1H), 8.31 (s, 1H), 8.21 (d, J = 8.2 Hz, 1H), 7.75 (m, 1H), 7.23-7.12 (m, 2H), 3.89 (s, 3H), 3.85-3.49 (m, 5H), 2.89 (d, J=4.5 Hz, 3H), 2_22-l_95 (m, 2H). 3 3 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I Η /〇lH NMR (400 MHz, DMSO): δ 8.33 (s, 1H), 8.31 (s, 1H), 8.14 (d, J-8.2Hz, 1H), 7.72 (m, 1H), 7.03 (s, 1H), 6.97 (d, 0.01700 156325.doc -162- 201202215

Instance name structure *Η NMR Kj J=8.2 Hz, 1Η), 3.87 (s, 3H), 3.50-3.20 (m, 2H), 2.93 (s, 3H), 2.88 (d, J=4.4 Hz, 3H), 1.11 (t, J=6.9 Hz, 3H). 212 2-[4-(azetidin-1-yl)_2-decyloxy-anilino]-4-methylamino-pyrimidine-5-indolecarbonitrile~ΝΗ 0 Η /〇*H NMR ( 400 MHz, DMSO): δ 8.35 (s, 1H), 8.30 (s, 1H), 8.23 (d, J=8.3 Hz, 1H), 7.77 (m, 1H), 7.26-7.20 (m, 2H), 4.34 (br s, 2H), 4.04 (br s, 2H), 3.90 (s, 3H), 2.89 (d, J = 4.5 Hz, 3H), 2.36-2.18 (m, 2H). 0.0264 213 4-(5-Cyano-4-indenylamino 2,2-ylamino)-N-isopropyl-3-indolyl-N-methyl-benzylamine ~ ΝΗ 0 η / 〇JH NMR (400 MHz, DMSO): δ 8.32 (d, J = 4.6 Hz, 1H), 8.31 (s, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.72 (m, 1H), 7.02 (s, 1H), 6.95 (d, J=8.1 Hz, 1H), 4.10-3.88 (m, 1H), 3.87 (s, 3H), 2.88 (d, J=4.5 Hz, 3H), 2.79 (s, 3H), 1.13 (d, J=6.7 Hz, 6H) ° 0.0068 214 {4-[5-Gas-4-(tetrachloro-α-furan-3-ylamino)-°3⁄4 ate-2-ylamine ]]-3-decyloxy-phenyl}-morpholin-4-yl-methanone k. Η /° *H NMR (400 MHz, DMSO) δ 8.29 (d, J = 8.3 Hz, 1H), 8.00 (s, 1H), 7.76 (s, 1H), 7.16 (d, J = 6.3 Hz, 1H) , 7.03 (dd, /=15.4, 4.8 Hz, 2H), 3.96-3.78 (m, 5H), 3.73 (d, J=6.2Hz, 1H), 3.58 (t, /=21.4 Hz, 8H), 2.20 ( Dd, /-12.8, 6.7 Hz, 2H), 2.11-1.90 (m, 2H). 0.0184 215 [3-Isopropoxy-4-(4-amidino-5-trifluoromethyl-mouth 0-ylamino)-phenyl]-? Ketone F ^ ΝΗ 0 Η Υ XH NMR (400 MHz, DMSO) δ 8.40 (d, /=8.3 Hz, 1H), 8.19 (s, 1H), 7.95 (s, 1H), 7.26 (d, J = 4.2 Hz , 1H), 7.08 (s,1H), 7.00 (d, J=8.3 Hz, 0.0094 156325.doc -163- 201202215 Instance name structure *HNMR Ki 1H), 4.73 (dt, /=12.1, 6.1 Hz, 1H) , 3.55 (d, J-38.1 Hz, 8H), 2.94 (d, J=4.3 Hz, 3H), 1.33 (d, /=6.0 Hz, 6H). 216 [3-Ethoxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-infrared-4-yl-fluorenone F ~ΝΗ 0 4 NMR (400 MHz, DMSO) δ 8.35 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H), 7.24 (s, 1H), 7.06 (s, 1H), 7.01 (d, / =8.2 Hz, 1H), 4.16(q, J=7.0 Hz, 1H), 3.55 (d, J=38.1 Hz, 8H), 2.93 (d, /=4.3 Hz, 2H), 1.39 (t, J=6.9 Hz, 3H). 0.0042 217 [4-(5-Chloro-4-indenylamino)-3-cyclopropoxy-phenyl]-morpholin-4-yl-methanone~ΝΗ 0 H °v 'H NMR ( 400 MHz, DMSO) δ 8.39 (d, J=8.3 Hz, 1H), 7.94 (s, 1H), 7.56 (s, 1H), 7.32 (s, 2H), 7.03 (d, J=8.3 Hz, 1H) , 3.98 (s, 1H), 3.57 (d, J = 33.3 Hz, 8H), 2.91 (d, J = 4.5 Hz, 3H), 0.88-0.69 (m, 4H). 0.0020 218 [4-(5-Bromo-4-indolyl-pyrimidin-2-ylamino)-3-cyclopropanyl-phenyl]-infrared·4_yl-fluorenone^NH 0 °v * H NMR (400 MHz, DMSO) δ 8.37 (s, 1H), 8.22 (s, 1H), 8.13 (d, /=8.2 Hz, 1H), 7.35 (s, 1H), 7.05 (d, J = 8.3 Hz , 1H), 3.98 (s, 3H), 3.57 (d, /=36.5 Hz, 8H), 0.87-0.70 (m, 4H). 0.0025 219 {4-[5-Gas-4-(2-decanesulfonyl-ethylamino)-Bistyl-2-ylamino]-3-methoxy-phenyl}-? - ketone ketone 0 H / 〇 'H NMR (400 MHz, DMSO) 6 8.30 (d, J = 8.3 Hz, 1H), 8.02 (s, 1H), 7.83 (s, 1H), 7.47 (s, 1H ), 7.06 (s, 1H), 7.01 (d, J=8.2 Hz, 1H), 3.90 (s, 3H), 3.82 (d, J=6.8 Hz, 2H), 3.56 (d, /=34.4 Hz, 8H ), 3.44 (t, J=7.l Hz, 2H), 0.0264 156325.doc •164· 201202215 Instance name structure ^NMR Kt 3.03 (s, 3Η). 220 2-[4-(5-Bromo-4-indolyl-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1 - stimuli *-4-yl-B Ketone\νη, 〇Γ^0 Η 〇\ iHNMR (400 MHz, DMSO) 5 8.14(s, 1H), 8.00 (s, 1H), 7.56 (s, 1H), 7.11 (d, /=4.5 Hz, 1H ), 6.79 (s, 1H), 3.79(s, 3H), 3.73 (s, 3H), 3.56 (s, 2H), 3.49 (dd, /=24.0, 5.0 Hz, 8H), 2.94 (d, J= 4.5 Hz, 3H). 0.0034 221 2-[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1-infrared>-4-yl - ethyl ketone \ ΝΗ \〇Η 〇 \ 1H NMR (400MHz, DMSO) 6 8.15 (s, 1H), 7.93 (s, 1H), 7.55 (s, 1H), 7.29 (d, /=4.4 Hz, 1H), 6.79 (s, 1H), 3.79 (s, 3H), 3.73 (s, 3H), 3.56 (s, 2H), 3.49 (dd, /=24.0, 5.2 Hz, 8H), 2.94 (d, J=4.6 Hz , 3H). 0.0087 222 2-[4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-phenyl]-1-infrared>-4-yl-B, ΝΗ Γ^0 Η 〇, *HNMR(400MHz, DMSO)5 8.18(d, /=8.2 Hz, 1H), 7.90 (s, 1H), 7.54 (s, 1H), 7.22 (s, 1H), 6.88 ( s, 1H), 6.77 (d, J=8.5 Hz, 1H), 3.83 (s, 3H), 3.66 (s, 2H), 3.51 (d, J=19.1 Hz, 8H), 2.88 (d, J=4.5 Hz, 3H) ° 0.0090 223 2-[3-methoxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-1-morphin- 4-yl-ethanone F ^ ΝΗ Γ ^, 0 ^ ΙΧΤΤ ° 〇 〇, iHNMR (400 MHz, DMSO) 5 8.13 (s, lH), 8.05 (d, J = 8.2 Hz, 1H), 7.99 (s, 1H), 7.12 (s, 1H), 6.90 (s, 1H), 6.79 (d, /=8.7 Hz, 1H), 6.65 (s, 1H), 3.82 (s, 3H), 3.68 (s, 2H), 3.51 (d, /=17.5 Hz, 8H), 2.88 (d, J=4.2 Hz, 3H). 0.0052 156325.doc -165- 201202215 Example Name Structure ^ NMR Ki 224 2-[4-(5-Chloro-4-methoxy-°3⁄4 ate-2-ylamino)-2,5-dimethoxy -Phenyl]-1 - 吓 * -4- -4- ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke ke , 6.83 (s, 1H), 4.01 (s, 3H), 3.78 (s, 3H), 3.73 (s, 3H), 3.58 (s, 2H), 3.49 (d, J = 28.3 Hz, 8H). 0.02113 225 2-[4-(5-chloro-4-methyllacyl-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-1 -morphin-4-yl-ethanone Η 〇 \ 'H NMR (400 MHz, DMSO) 5 8.22 (d, /=16.9 Hz, 2H), 7.88 (d, J=8.2 Hz, 1H), 6.91 (s, 1H), 6.80 (d, J= 8.2 Hz, 1H), 3.95 (s, 3H), 3.81 (s, 3H), 3.69 (s, 2H), 3.51 (d, J = 17.2 Hz, 8H). 0.01133 226 2-[4-(5-Bromo-4-indolyl-°3⁄4 ate-2-ylamino)-3-decyloxy-phenyl]-1 -morphin-4-yl-ethanone eArrr° Η 〇, 'H NMR (400 MHz, DMSO) δ 8.31 (s, 1H), 8.22 (s, 1H), 7.87 (d, J=8.1 Hz, 1H), 6.91 (s, 1H), 6.80 ( d, J = 7.9 Hz, 1H), 3.94 (s, 3H), 3.81 (s, 3H), 3.69 (s, 2H), 3.50 (t, J = 12.7 Hz, 8H). 0.0056 227 2-[2,5-Dimethoxy-4-(4-amidino-5-dioxamethyl-°3⁄4唆-2-ylamino)-phenyl]-1 -Merline- 4-yl-ethanone F ~NH , 0 Γ""", 0 H 〇\ Ή NMR (400 MHz, DMSO) δ 8.16 (s, 1H), 8.04 (s, 1H), 7.94 (s, 1H ), 7.20 (s, 1H), 6.82 (s, 1H), 3.79 (s, 3H), 3.73 (s, 3H), 3.58 (s, 2H), 3.49 (d, J=24.9 Hz, 8H), 2.96 (s, 3H). 0.0037 228 N-(3-Amino-propyl)-5-gas-4-(5-vapor-4-hydrazino-pyrimidin-2-ylamino)-2-methoxy-benzylguanamine^ NH, 0 0 Cl ^nh2 0.0038 156325.doc -166 - 201202215

Example name structure ^NMR Ki 229 {4-[5-bromo-4-(2-decyloxy-ethylamino)-°3⁄4 ate-2-ylamino]-3-decyloxy-phenyl}- Morpholin-4-yl-methanone. Η /〇0.0041 230 {4-[5-Gas-4-(2-decyloxy-propylamino)-°3⁄4 ate-2-ylamino]-3-methoxy-phenyl}--- 4-Base-A-〆〇丫, SIH 0 c, A^o Η /〇0.0096 231 4-(5-Gas-4-(nonylamino)pyrimidin-2-ylamino)-N,N,3 -tridecylbenzylamine ~ ΝΗ 0 232 (4-(5-Gas-4-(methylamino)pyrimidin-2-ylamino)-3-indolylphenyl)(N-morpholinyl) A Ketone^ΝΗ 0 c,A^o 0.0074 233 (4-(5-Gas-4-(decylamino)pyrimidin-2-ylamino)-3-indolylphenyl)(4-hydroxy-bite-1 -yl) ketone to oxime 0 0.0061 234 (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-(trifluoromethoxy)phenyl (N-morpholinyl)fluorenone F 0 °yff 0.0032 235 (4-(4-(decylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-(trifluoro) Methoxy)phenyl)(N-morphinyl) formazan F ΗΝ^ 0 0.0112 156325.doc -167- 201202215 Example name structure *Η NMR Ki 236 (5-gas-2-methoxy-4-( 4-(decylamino)-5-(trifluorodecyridin-2-ylamino)phenyl)(full deuterated (N-morphinyl))fluorenone F ^NH , 0 ODd 0.0042 237 (5 -fluoro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamine Phenyl)(N-morpholinyl)methanone f, 〇o F 0.0048 238 (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)- 5-fluoro-2-decyloxyphenyl)(N-morpholinyl)fluorenone F HN''''', 0 0 F 0.0014 239 [2-Fluoro-5-decyloxy-4-(4 -曱Amino-5-trifluoromethyl ketone-2-ylamino)-phenyl]-morphin-4-yl-fluorenone F ^NH F 0 F^x^o 0.0029 240 4- (5 -Cyano-4-ethylamino-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-indole, Ν·dimercapto-nodal amine ^NH F 0 H /〇0.0098 241 ( 4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-indolylphenylhydrazine-morpholinyl)fluorenone FOH /〇 0.0018 242 (lS,4S)-2-oxa-5- azabicyclo P.2.1]heptane-5-yl(4-(4-(ethylamino)-5-(trifluoromethyl)°3⁄4 Pyridin-2-ylamino)-2- -3--3-O 0 0 / 〇 0.0028 156325.doc • 168- 201202215 Example name structure XH NMR Ki methoxy phenyl) ketone 243 (lS, 4S)-2 -oxa-5-azabicyclo[2.2.1]heptane-5-yl(2-fluoro-3-oxooxy-4-(4-(decylamino)-5-(trifluoromethyl) °密密-2-ylamino)phenyl) ketone F Η〆0 Η /〇0.0114 244 5-气-4-(5 -chloro-4-methoxypyrimidin-2-ylamino)-2-decyloxy-N-methylbenzylamine\〇,〇0 Γ Cl 0.0709 245 2-(4-((3 S,4S) )-3,4-difluoro-pyrrolidine-l-l-yl)-2-methoxyanilino)-4-(decylamino)pyrimidine-5-indoleonitrile Η /0 F 0.0135 246 (5 -Chloro-2-indolyl-4-(4-(decylamino)-5-(trifluoromethyldept-2-ylamino)phenyl)(3-oximeoxy 0 to 0 each 0 -1-yl)fluorenone F ΗΝ^ , 0 0 Η Cl /° 0.0050 247 (2-fluoro-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)° 3⁄4pred-2-ylamino)phenyl)(3-decyloxy. Ratio 11 each bite -1 base) fluorenone F HN^ F 0 H 0, /° 0.0027 248 2-fluoro-N-(2-hydroxy-2-mercaptopropyl)-5-methoxy-N- Methyl-4-(4-(decylamino)-5-(trifluoromethyl) aceto-2-ylamino)benzylamine F HN^ F 0 /0 OH 0.0092 156325.doc -169- 201202215 Instance name structure! hnmr Ki 249 ((2S,6R)-2,6-diindenyl (N-morphinyl)) (2-dan tau 5-decyloxy-4-(4-(decylamino)- 5-(Trifluoromethyl)pyrimidin-2-ylamino)phenyl)methanone F HN^ F 0 Η /0 1 0.0080 250 Fluoro-5-methoxy-4-(4-(2-methoxy) Ethyloxy)-5-(trifluoromethyl) guanidine-2-ylamino)phenyl)(indolyl-morpholinyl)anthone 1 FF 0 Η 〇\ 0.0553 251 (2-ethoxyl -5-fluoro-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(indolyl-morpholinyl)indanone F Η〆/' '"Ο 0 F 0.0193 252 (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-isopropoxyphenyl)(Ν-? Phenyl) ketone fo HY 0.0045 253 (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-isopropoxyphenyl (Ν-morpholinyl) anthrone F 0 HY 0.206 254 (4-(5-chloro-4-(piperidin-1-yl) σ dense 2-yl) -3-methoxyphenyl Yue) (Ν · morpholinyl) Yue-one o. c,A^o H 〇\ 0.0121 156325.doc -170- 201202215 Instance name structure ^NMR Ki 255 (4-(5-chloro-4-(mouth-pyridin-1-yl)pyridin-2-ylamine (3-methoxyphenyl) (N-morpholinyl) anthrone. °\0.0179 Table 4 Example 2 [4-(5-Cyclopropyl-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-intimidation-4-yl-A嗣

D^BF3K / \ Pd(OAc)2 vi Ό XPhos CS2CO3 H L H2〇 PhMe 140 °C

Add (4-(5-bromo-4-(decylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(N-loryl) Brewing 1 (56 mg) to a microwave tube , 0·13 mmol), cyclopropyltrifluoro-potassium (39 mg, 0.27 mmol), carbonic acid (0·13 g, 0.40 mmol), toluene (1.8 mL) and water (0.2 mL). The mixture was degassed by bubbling nitrogen for 15 minutes. Then XPhos (6.4 mg, 0.013 mmol) and acetic acid (2 mg, 0.01 mmol) were added. The reaction was heated in a Biotage microwave at 140 °C for 20 minutes. The reaction mixture was filtered and concentrated. The crude product was purified by EtOAc EtOAc (EtOAc) Other compounds prepared using the above procedure are shown in Table 4 above. Example 3 (4-(5-Cyclobutyl-4-(decylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(N-morpholinyl)methanone 156325.doc -171 - 201202215

^V-bf3k

Pd(OAc)2 XPhos CS2CO3

H2o PhMe 140 °C Add to the microwave tube (4-(5-bromo-4-(methylamino)pyrimidin-2-ylamino)_3, decyloxy) (N-rheptyl) 曱_( I〇〇mg, 0.24 mmol), potassium cyclobutylidene trifluoroborate (177 mg, 1.1 mmol), carbonic acid (0.23 g, 0.71 mmol), toluene (2.9 mL) and water (0.3 mL). The mixture was degassed by bubbling nitrogen for 15 minutes. Subsequently, bis-(^adamantyl)-n-butylphosphine (19f\mg, 0.053 mmol) and palladium acetate (2.6 mg, 0.026 mmM) were added. The reaction was sealed and heated at 11 C for 2 hours. The reaction mixture was filtered and concentrated. The crude product was purified by EtOAc (EtOAc) eluting Other compounds prepared using the above procedure are shown in Table 4 above. Example 4: 1-{2-丨2-methoxy-4-(morpholin-4-carbonyl)-anilino]_4_methylamine--snack--5-yl}-acetamidine

(PPh3) 4Pd PhMe 110°C

SnBu-a OEt

Stirring in a sealed tube at 110 ° C (4_(5_bromo-4-(indolyl)pyrimidin-2-ylamino)-3-decyloxyphenyl)(N_morpholinyl)fluorenone (1〇〇mg, 〇24 mmol), Pd(PPh3)4 (36 mg, 〇.〇3 mmol) and tributylethoxyvinyltin (0·16 mL, 0.47 mmol) in toluene Mixture [hours. The reaction mixture was filtered and concentrated. The crude product was obtained via a silicone pad (using 庚 丨〇〇〇 〇 〇 156325.doc - 172 - 201202215 in heptane. Others prepared by reverse phase using the above procedure

The reaction mixture was filtered, EtOAc (EtOAc) Compounds are shown in Table 4 above. 1-ynyl-pyrimidin-2-yl Example 5: [3-methoxy-4·(4-methylamino-5-propylamino)-phenyl]-morphin-4-yl-methyl

Stirring (4_(5-bromo-4-yl)-pyrimidin-2-ylamino)-3-decyloxyphenyl)(N-morpholinyl)fluorenone in a sealed tube at 110 °C 14 〇 mg, 〇 233 mmol), Pd(PPh3) 4 (50 mg, 0,04 mmol) &tributyl(propynyl)stannane (0·20 mL, 0.66 mmol) in toluene (5 mL) The mixture in 1 hour. The reaction mixture was filtered and concentrated. The crude product (9 mg '10%) was purified by reverse phase HPLC. Other compounds prepared using the above procedure are shown in Table 4 above. Q Example 6: [4-(5-Gas_4_Methylamino-pyrimidin-2-ylamino)-3-cyclopropyl-phenyl] -吗淋-4-基-甲网

KOAc Νθ2〇〇3

MeCN/H2〇140 °C [3-Bromo-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone (0.0500 g, 0.117 mmol), potassium acetate (0.0172 g, 0.176 156325.doc -173- 201202215 mmol), sodium carbonate (0.0186 g, 0.176 mmol) and 1, bismuth-bis(diphenylphosphino)ferrocene palladium chloride A mixture of (11) (0.00478 g, 0.00585 mmol) was weighed and added to a microwave vial equipped with a stir bar. Acetonitrile (0.94 mL, 18 mmol) and degassed water (0_3 mL, 20 mmol) were then added and the mixture was degassed with nitrogen for 4 min and then heated to 140 ° C under microwave irradiation for 80 min. The mixture was then filtered through celite with EtOAc (EtOAc)EtOAc. The crude product was purified by reverse phase HPLC. Example 7: 5-Gas-2-methoxy-4-N,N-dimethyl-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylguanamine f3c

Pd2(dba)3 Xantphos CS2〇〇3 l,4-dioxin

4-Amino-5-chloro-2-indolyl-N,N-dimercaptobenzylamine (110 mg, 0.48 mmol), 2-ox-4-(nonylamino)-5- Trifluoromethylpyrimidine (50 mg, 0.23 mmol), ginseng (diphenylidene acetonide) di I bar (11 mg, 0.012 mmol), xantphos (14 mg, 0.024 mmol) and carbolic acid (235 mg, 0.72 mmol) The mixture in 1,4-two ° methane was degassed for 5 minutes and then heated to 100 ° C for 2 hours. The mixture was diluted with EtOAc (EtOAc)EtOAc. The residue was triturated with EtOAcqqqqqqq Other compounds prepared using the above procedure are shown in Table 5 below. 156325.doc -174- 201202215

Example name structure *HNMR Ki 256 [4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-decyloxy-phenyl]-?咐&gt ;-4-yl-ketone F ^NH F 0 Η 〇, 1H NMR (400MHz, CDC13): δ 8.44 (d, J = 12.3 Hz, 1H), 8.20 (s, 1H), 7.84 (s, 1H), 6.91 (d, J=5.9Hz, 1H), 5.21 (s, 1H), 3.92 (s, 3H), 3.80 (d, J=9.1 Hz, 4H), 3.71-3.54 (m, 4H), 3.44 (s , 2H), 1.33 (t, 5=1.2 Hz, 3H). 0.002 257 4-(4-Ethylamino-5-trifluoromethyl-transfer-2-ylamino)-3-methoxy-phenyl]-oxalin-4-yl-fluorenone F ^NH 0 H 〇, 1H NMR (400MHz, CDC13): δ 8.54 (d, J=8.2 Hz, lH), 8.19 (s, 1H), 7.81 (s, 1H), 7.04-7.00 (m, 2H), 5.15 (s , 1H), 3.94 (s, 3H), 3.70 (s, 7H), 3.65-3.55 (m, 3H), 1.31 (t, J = 7.2 Hz, 3H). 0.002 258 [5-Gatro-4-(5-Ga-4-ethylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-oxalin-4-yl-methanone^NH , 0 O Cl, less than H Cl 1H NMR (400 MHz, CDC13): δ 8.41 (s, 1H), 7.96 (s, 1H), 7.49 (s, 1H), 7.30 (s, 1H), 5.35-5.25 ( m, 1H), 3.87 (s, 3H), 3.77 (d, J=11.6Hz, 4H), 3.59 (dt, J=13.4, 7.2Hz, 4H), 3.32 (d, J=18.3 Hz, 2H), 1.31 (t, J = 7.3 Hz, 3H). 0.005 259 [4-(5-Chloro-4-methoxy-carto-2-ylamino)-2-fluoro-5-decyloxy-phenyl]-morpholin-4-yl-fluorenone "〇Η 〇\ 'H NMR (400 MHz, CDC13): δ 8.37 (d, J = 12.2 Hz, 1H), 8.20 (s, 1H), 7.81 (s, 1H), 6.93 (d, J=5.9 Hz, 1H), 4.10 (s, 3H), 3.94 (s, 3H), 3.80 (d, J=8.5 Hz, 4H), 3.68 (s, 2H), 3.44 (s, 2H). 0.0192 260 [5-Gas-4-(5-Ga-4-indoxy-pyrimidin-2-ylamino)-2-methoxy-phenyl]-oxalin-4-yl-oxime, 0 'Ο 0 Cl 'H NMR (400 MHz, DMSO): δ 8.88 (s, 1H), 8.31 (s, 1H), 7.70 (s, 1H), 7.32 (s, 1H), 398 (s, 1H), 3.80 (s, 3H), 3.61 (m, 4H), 3.53 (m, 2H), 3.17 (m, 2H). 0.047 261 [3-Ga-4-(5-Ga-4-indoxy-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone Cl !H NMR (400 MHz, DMSO): δ 9.03 (s,1H), 8.28 (s, 1H), 7.92 (d, J=8.3,1H), 7.55 (s,1H), 7.39 (d, J=9.8,1H), 3.95 (m , 3H), 3.56 (m, 8H). 0.047 156325.doc -175- 201202215 Example name structure ^ NMR Ks 262 [2-Chloro-5-methoxy-4-(4-decyloxy-5-tris-methyl-pyrimidin-2-ylamino) -phenyl]- 吓 _ _ 4- ketone ketone F, 0 CI 〇 F ^ x ^ 〇 H / ° lHNMR (400MHz, DMSO) δ 8.98 (s, 1H), 8.56 (s, 1H), 8.15 ( s, 1H), 7.10 (s, 1H), 4.01 (s, 3H), 3.87 (s, 3H), 3.73-3.48 (m, 6H), 3.23 - 3.15 (m, 3H). 0.024 263 [3-Methoxy-4-(4-decyloxy-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-?咐'-4-yl-曱明F^ Xr/on H /〇0.020 264 {4-[5-Gas-4-(tetrazole-β-bottom 0-N--4-yloxy)-pyrimidin-2-ylamine °a0. Yx r/onn H 〇, 'H NMR (400 MHz, DMSO): δ 8.32 (m, 2H), 8.06 (d, J = 8.2, 1H), 7.08 (s, 1H), 7.02 (d, J = 8.2 , (H, 5H), 3.26 (m, 6H), 2.05 (m, 2H), 1_68 (m, 2H). Table 5 Example 8: 5-Gas-N-(2-hydroxy-2-methyl-propyl)-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidine-2 ·Amino group)_-acid amide HN〆f3c

P-toluenesulfonic acid 1,4-two blessing f3c

Cl

Stirring 4-amino-5-chloro-2-indolyl-N-(2-methyl-propan-2-ol)-benzylguanamine (95 mg, 0.35 mmol), 2- at 100 °C Chloro-4-(decylamino)-5-trifluoromethyl D-bite (5 〇 mg ' 〇 _ 23 mmol) and monohydrate p-benzoic acid (49 mg, 0.26 mmol) in 1,4- A mixture of dioxane (5 ml) was used for 18 hours. The solvent was removed by vacuum evaporation and the residue was partitioned between DCM and EtOAc. The organic phase was separated, EtOAc (EtOAc m. in. Example 9: (3-(2-Fluoroethoxy)_4_(4-(methylamino)-5•(trifluoromethyl)-pyridylamino)phenyl)(N-morpholinyl)methyl

F '''NH

Stir 2-O-N-indenyl-5-(trifluoromethyl)pyrimidine-4-amine (〇·1〇g' 0.47 mm〇1), (4_Amino_3_(2_1 ethoxy) at 95C a mixture of methyl hydrazine (0.13 g ' 〇 · 47 mmol), trifluoroacetic acid (〇〇 7 mL, 0 9 mmol) in 2-methoxylethanol (2.5 mL) hour. Concentrate the reaction. The crude product was purified by reverse phase HPLC to give the title compound (61 mg, 29%). Other compounds prepared using the above procedure are shown in Table II below.

Example 10: (2-Fluoro-3-methoxy_4-(4-(methylamino)-5-yl-2-ylamino)phenyl)(fluorene-morphine)fluorene (trifluoromethyl) Pyrimidine

Add to the suspension of 2-fluoro-3-decyloxy-4-nitrosomic acid (18 〇, 〇97 _(10) 156325.doc -177- 201202215 DCM (8 mL) (0·1 7 The mixture was stirred at room temperature for 18 hours. The reaction was diluted with water and extracted with DCM (3x). Drying over Na2SO4, filtered and concentrated. EtOAcqqqqqqqqqQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQ , 83%). Under nitrogen, give (2-gas-3-decyloxy-4 - lyobylphenyl) (N-morphinyl) anthrone (0.20 g) and palladium/carbon (0_1 g) , 10% by weight of a suspension in ethanol for 18 hours. The reaction was then filtered through celite and concentrated to give (4-amino-2-fluoro-3-methoxyphenyl) (N-morpholinyl) Ketone. Stirring (4-amino-2-fluoro-3-methoxyphenyl)(N-morpholinyl)methanone (0·18 g, 0-72 mmol) and 2-chloro- at 95t N-Methyl-5-(trifluoromethyl)pyrimidin-4-amine (0.10 g, 0.47 mmol) in 2-methoxyethanol (2 mL) and TFA (0.055 mL) The reaction was concentrated for 2 hours. The reaction was concentrated and purified by reverse phase HPLC to give the title compound. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> The other compounds prepared using the procedures described above are shown in Table 6. Example name structure XH NMR Kj 265 5-chloro-N-(l- Cyano-3⁄4 propyl)_2_methoxy-4-(4-decylamino-5-trifluoromethyl dimethyl-2-ylamino)-benzylamine F ^NH , 0 0 CI NMR NMR (400 MHz, DMSO): δ 8.88 (s, 1H), 8.64 (s, 1H), 8.27 (s, 1H), 8.08 (s, 1H), 7.82 (s, lH), 7.39 (d, J-5.1) Hz, 1H), 3.93 (s, 3H), 2.95 (t, J=4.3 Hz, 3H) 1.61-1.55 (m, 2H), 1.35-1.29 (m, 2H). 0.0042 156325.doc -178- 201202215

Example name structure *H NMR Ki 266 5-chloro-N-(l-cyano-3⁄4propyl)-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidine-2 -Aminoamine)-Hydroxylamine F ~NH, 0 0 Γ C! ^NMR (400 MHz, DMSO): 6 8.62 (s5 1H), 8.26 (s, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.05 (s, 1H), 7.87 (s, 1H), 7.36 (d, J=5.1 Hz, 1H), 3.94 (s, 3H), 2.95 (d, J=4.4 Hz, 3H), 2.84 ( d, J = 4.6 Hz, 3H). 0.0046 267 [5-Gas-2-indolyl-4-(4-amidino-5-trifluoroindolyl-2-ylamino)-phenyl]-(2,6-dimethyl?啉-4-yl)-fluorenone F ^NH , 0 0 H Cl 1 'H NMR (400 MHz, DMSO): δ 8.64 (s, 1H), 8.24 (s, 1H), 7.92 (s, 1H), 7.37 (s, 1H), 7.31 (t, J=5.5 Hz, 1H), 4.40 (d, J=13.1 Hz, 1H), 3.84 (s, 3H), 3.55 (s, 2H), 3.21 (m, 1H) ), 2.93 (d, J=4.4 Hz, 3H), 2.82-2.70 (m, 1H), 2.45 (m, 1H), 1.17 (d, J=6.1 Hz, 3H), 1.03 (d, J=6.3 Hz) , 3H). 0.0080 268 [3-Alkyloxy-4-(4-°Bido-1-yl-5-trifluoromethyl]d-densole-2-aminocarbyl)-phenyl]-morpholin-4- Base-fluorenone F. Br * NMR (400 MHz, DMSO): δ 8.34 (s, 1H), 8.27 (d, J = 8.2, 1H), 8.06 (s, 1H), 7.08 (s, 1H), 7.03 (d, J = 8.2, 1H), 3.90 (s, 3H), 3.56 (m, 12H), 1.93 (m, 4H). 0.019 269 [3-Cyclobutoxy-4-(4-guanidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone F ^ NH 0 f^xn^O *H NMR (400 MHz, DMSO) 5 8.36 (d, J = 8.3 Hz, 1H), 8.19 (s, 1H), 8.02 (s, 1H), 7.25 (s, 1H), 7.01 (d, J=8.3Hz, 1H), 6.88 (s, 1H), 4.81 (dd, J=14.2, 7.0 Hz, 1H), 3.55 (dm, 8H), 2.93 (d, /=4.3 Hz, 3H ), 2.45 (m, 2H), 2.24-2.02 (m, 2H), 1.81 (m, 1H), 1.66 (m, 1H). 0.0025 270 N-(3,3-Difluoro-cyclobutyl)-3-methoxy-4-(4-nonylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzyl hydrazine F ^NH 0 H 〇\ NMR (400 MHz, DMSO) δ 8.69 (d, /=6.4 Hz, 1H), 8.41 (d, J = 8.3 Hz, 1H), 8.21 (s, 1H), 8.11 (s, (H, 2H) m, 4H), 2.77 (br, 2H). 271 3-methoxy-4-(4-methylamino-5-trifluorodecyl-°3⁄4 B-but-2-ylamino)-N-oxetan-3-yl-benzylguanamine F ~ ΝΗ 0 H / ° ° 'H NMR (400 MHz, DMSO) δ 8.98 (d, / = 6.3 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.21 (s, 1H), 8.11 (s, 1H), 7.59-7.47 (m, 2H), 7.27 (s, 1H), 5.01 (dd, 1H), 4.78 (t, J = 6.8 Hz, 2H), 4.60 (t, J=6A Hz, 2H), 3.94 (s, 3H), 2.93 (d, J=4.2 Hz, 3H) 0.0037 272 [3-methoxy-4-(4-methylamino-5-trifluoromethyl-°® bite- 2-Aminoamino)-phenyl]-(8-oxa-3-aza-bicyclic guanidine 2.1] oct-3-yl)-fluorenone F ~NH 0 H 〇, Ή NMR (400 MHz, DMSO ) δ 8.31 (d, J=8.3 Hz, 1H), 8.19 (s, 1H), 8.07 (s, 1H), 7.23 (s, 1H), 7.05 (s, 1H), 6.99 (d, J=8.3Hz , 1H), 4.30 (m, 6H), 3.90 (s, 3H), 2.92 ((1, /=4.3 Hz, 3H), 1.73 (m, 4H). 0.0017 273 [3-曱oxy-4-( 4-nonylamino-5-trifluoromethyl-pyridin-2-ylamino)-phenyl]-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl) - ketone F ~NH 0 H 〇\ *H NMR (400 MHz, DMSO) 5 8.34 (d, J = 8.3 Hz, 1H), 8.20 (s, 1H), 8.08 (s, 1H), 7.17 (m, 3H), 4.63 (m, 2H), 3.91 (s, 3H), 3.88-3.41 (m, 4H), 2.92 (d, J = 4.2 Hz, 3H), 1.97-1.65 (m, 2H). 0.0033 274 [3-methoxy-4-(4-decylamino-5-trifluorofluorene) -β3⁄4 淀-2-ylamino)-phenyl]-. piroxidin-1-yl-fluorenone F ^NH 0 nnn 0.0041 275 Ν, Ν-diethyl-3-decyloxy-4 -(4-Amidino-5-trifluoromethyldept-2-ylamino)-benzylamine F ~ΝΗ 0 F^xr/cnn °\ *H NMR (400 MHz, DMSO) δ 8.26 (d , J=8.1 Hz, 1H), 8.18(s, 1H), 8.07 (s, 1H), 7.20 (s, 1H), 7.00 (s, 1H), 6.94 (d, J=8.3 Hz, 1H), 3.89 (s, 3H), 2.91 (d, /=4.2 0.0033 156325.doc -180- 201202215 Instance name structure *HNMR Ki Hz, 3H), 1.12 (s, 6H). 276 (4-Diaminoamino-piperidin-1-yl)-[3-decyloxy-4-(4-indolyl-5-trifluoromethyl-pyrimidin-2-ylamino)-benzene ]]-ketone F ~NH 0 η 〇, 1 JHNMR (400 MHz, DMSO) δ 8.28 (d, /=8.2 Hz, 1H), 8.19 (s, 1H), 8.07 (s, 1H), 7.22 (s , 1H), 7.04 (s, 1H), 6.98 (d, J=8.3 Hz, 1H), 3.89 (s, 3H), 2.92 (m, 7H), 2.32 (s, 1H), 2.18 (s, 6H) , 1.76 (s, 2H), 1.34 (m, 2H) 〇0.0008 277 (2,6-diamidino-morphin-4-yl)-[3-methoxy-4-(4-anthrylamino)- 5-3 曱 -03 -03 -03 -03 -03 基 基 基 基 基 基 ^ ^ ^ ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 8.19(s, 1H), 8.08 (s, 1H), 7.23 (s, 1H), 7.07 (s, 1H), 7.01 (d, J=8.3 Hz, 1H), 3.89 (s, 3H), 3.55 (s , 2H), 2.92 (d, J=4.1 Hz, 3H), 1.08(s, 6H). 0.0049 278 1-[3-曱-oxy-4-(4-indole- 5- tris(J-methyl-pyrimidin-2-ylamino)-benzylindenyl]- 派-4--4- ^NH OH 〇, N 'HNMR (400MHz, DMSO) δ 8.30 (d, /=8.2 Hz, 1H), 8.19 (s, 1H), 8.08 (s, 1H), 7.22 (s, 1H), 7.07 (s , 1H), 7.01 (d, /=7.9 Hz, 1H), 3.90 (s, 3H), 3.72 (s, 2H), 3.36 (s, 2H), 3.15 (s, 1H), 2.92 (d, J= 4.2 Hz, 3H), 1.90 (s, 2H), 1.75 (m, 2H) ° 0.0017 279 [3-methoxy-4-(4-amido-5-trifluoromethyl-°3⁄4 bite-2 -ylamino)_phenylH4-(2,2,2-trifluoro-ethyl)-0- bottom 0-methyl-1-yl]-fluorenone F ^NH 0 H 〇, 'HNMRC^OMHz, DMSO) 6 8.31 (d, J=8.3 Hz, lH), 8.19(s, 1H), 8.08 (s, 1H), 7.23 (s, 2H), 7.05 (s, 1H), 6.99 (d, J=8.2Hz, 1H), 3.89 (s, 3H), 3.52 (s, 4H), 3.23 (m, 2H), 2.92 (d, 3H), 2.65 (s, 4H). 0.0020 156325.doc -181 - 201202215 Example name structure ^NMR Ki 280 [3-曱oxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzene HH4-decyloxy-pyridin-1 -yl)-fluorenone F ^NH 0 Η 〇\ 1 *Η NMR (400 ΜΗζ, DMSO) δ 8.28 (d, J=8.3 Hz, lH), 8.19 (s , 1H), 8.07 (s, 1H), 7.22 (s, 1H), 7.05 (s, 1H), 6.98 (d, J=8.0Hz, 1H), 3.89 (s, 3H), 3.75 (m, 4H) , 3.44 (s, 1H), 3.26 (s, 3H), 2.91 (d, J-4.1 Hz, 3H), 1.84 (s, 2H), 1.46 (s, 2H). 0.0016 281 3-decyloxy-N-(2-decyloxy-ethyl)-4-(4-decylamino-5-trifluoromethyl-noise-2-ylamino)-benzylguanamine F ~ ΝΗ 0 Η 0, 0, lU NMR (400 MHz, DMSO) δ 8.56-8.30 (m, 2H), 8.21 (s, 1H), 8.09 (s, 1H), 7.51 (m, 2H), 7.26 ( s, 1H), 3.93 (s, 3H), 3.44 (m, 2H), 3.27 (m, 5H), 2.93 (d, J = 4.2 Hz, 3H). 0.0023 282 3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyridin-2-ylamino)-N-(l-fluorenyl-piperidin-4-yl)- Benzalamide F ^ ΝΗ 0 1 * H NMR (400 MHz, DMSO) δ 8.37 (d, / = 8.4 Hz, 1H), 8.20 (s, 1H), 8.16-8.01 (m, 2H), 7.51 (m, 2H), 7.27 (s, 1H), 3.93 (s, 3H), 3.74 (s, 1H), 2.93 (d, J=4.2 Hz, 3H), 2.78 (d, 2H), 2.17 (s, 3H), 1.94(t, 2H), 1.76 (m, 2H), 1.60 (m, 2H). 0.0006 283 N-(4,4-Dilacyl-cyclohexyl)-3-decyloxy-4-(4-decylamino-5-trifluoromethylpyrimidin-2-ylamino)-benzylguanamine F ^ ΝΗ 0 * H NMR (400 MHz, DMSO) δ 8.38 (d, / = 8.4 Hz, 1H), 8.29-8.11 (m, 2H), 8.09 (s, 1H), 7.63-7.39 (m, 2H) , 7.27 (s, 1H), 3.99 (m, 1H), 3.93 (s, 3H), 2.93 (d, J=4.1 Hz, 3H), 2.06 (s, 4H), 1.88 (m, 2H), 1.65 ( m, 2H). 0.0011 284 [4-(5-Chloro-4-indolyl-^^-2-ylamino)-3·(oxetan-3-yloxy)-phenyl]-? 4-yl-fluorenone 0 〇Να 0.0128 156325.doc -182- 201202215 Example name structure *HNMR Ki 285 [3-cyclopropylmethoxy-4-(4-decylamino-5-trimethylmethyl-嗔 嗔-2-ylamino)-phenyl]-morphin-4-yl-fluorenone F0 Η 'HNMRC^OMHz, DMSO)5 8.37 (d, J=8.2 Hz, 1H), 8.20 (s, 1H ), 8.03 (s, 1H), 7.30 (d, J=AA Hz, 1H), 7.05 (s, 1H), 7.04-6.98 (m, 1H), 3.95 (d, J-7.0 Hz, 2H), 3.55 (dm, 8H), 2.93 (d, J=4.4 Hz, 3H), 1.37-1.20 (m, 1H), 0.66-0.55 (m, 2H), 0.37 (q, /=4.5 Hz, 2H). 0.00646 286 [3-Cyclobutylphosphonium-4-(4-amidino-5-difluoroindolylpyrimidin-2-ylamino)-phenyl]-infrared*-4-yl-A Ketone F ^NH 0 H 'ΗΝΜΚ(400 MHz, DMSO)5 8.31 (d, J=8.2 Hz, 1H), 8.19 (s, 1H), 8.01 (s, 1H), 7.27 (d, /=4.3 Hz, 1H), 7.08 (d, J=1.4 Hz, 1H), 7.02 (d, J=8.2 Hz, 1H), 4.07 (d, J=6.5 Hz, 2H), 3.56 (dbr, 8H), 2.91 (d, J=4.3 Hz, 3H), 2.78 (dd, 1H), 2.18-1.99 (1X1, 2H), 1.89 (m, 4H). 0.00519 287 N-Ethyl-3-decyloxy-N-indenyl 4- 4-(4-aminoamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylamine F ~NH OH /〇288 [4-(5-Bromo-4-indenylamino)-5-chloro-2-yloxy-phenyl]-morphin-4-yl-fluorenone^NH, 0 0 Cl iHNMR (400MHz, DMSO): 5 8.10 (s, 1H), 8.05 (s, 1H), 7.99 (s, 1H), 7.29 (s, 1H), 7.18 (s, 1H), 3_81 (m, 3H), 3.56 (m, 6H), 3.18 (m, 2H), 2.92 (m, 3H). 0.0026 289 [3-Cyclopropyl-4-(4-amidino-5-trifluoromethyl-pyridin-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone F XNH 0 f^jC^O 'HNMRC^OMHz, DMSO): δ 8.71 (s, 1H), 8.14 (s, 1H), 7.86 (d, J=7.8,1H), 7.22 (d, J=8.0, 1H) , 7.02 (s, 2H), 6.65 (s, 1H), 3.59 (m, 4H), 3.48 (m, 4H), 2.86 (m, 3H), 2.04 (m, 1H), 0.93 (m, 2H), 0.61 (m, 2H). 0.0200 156325.doc -183- 201202215 Example Name Structure ^NMR Ki 290 [3-溪-4-(4-Methylamino-5-trifluoromethyl-indolyl-2-ylamino)-phenyl]-琳林-4-yl-ketone F ^NH 0 Br •HNMRC^OMHz, DMSO): δ 8.64 (s, 1H), 8.16 (s, 1H), 8.00 (d, J=8.3,1H), 7.69 ( s, 1H), 7.42 (d, J=8.3, 1H), 7.15(d, J=3.4, 1H), 3.55 (m, 8H), 2.86 (d, J=4.2, 3H) 〇0.0075 291 [3- Chloro-4-(4-amido-5-tris-decyl-pyrimidin-2-ylamino)-phenyl]-infrared·_4-yl-ketone F ^NH 0 Cl 'HNMRC^OMHz, DMSO): δ 8.83 (s, 1H), 8.17 (s, 1H), 8.02 (d, J=8.4, 1H), 7.55 (s, 1H), 7.39 (d, J-7.6, 1H), 7.22 (s , 1H), 3.60 (s, 4H), 2.86 (d, J=4.2, 3H). 0.017 292 [2-Chloro-5-decyloxy-4-(4-amidino-5-trifluoromethyl-σ-deni-2-ylamino)-phenyl]-morpholin-4-yl -曱Μ F ~NH Cl 0 H 〇\ 'HNMR (400 MHz, DMSO) 5 8.51 (s, 1H), 8.24 (s, 1H), 8.12 (s, 1H), 7.32 (d, J=4.0, 1H ), 7.06 (s, 1H), 3.89 (s, 3H), 3.71-3.49 (m, 6H), 3.24-3.15 (m, 2H), 2.94 (d, J=4_3, 3H). 0.0020 293 [2-Chloro-4-(5-chloro-4-nonylamino-pyrazin-2-ylamino)- 5-methoxy-phenyl]-oxalin-4-yl-methanone~ NH Cl 0 H /〇'HNMR (400 MHz, DMSO) 5 8.58 (s, 1H), 8.00 (s, 1H), 7.71 (s, 1H), 7.40 (m, 1H), 7.02 (s, lH), 3.90 (s, 3H), 3.70-3.60 (m, 4H), 3.60-3.48 (m, 2H), 3.23-3.15 (m, 3H), 2.92 (d, J=4.5, 3H). 0.0027 294 [4-(5- Desert-4-Methoxy-p-denyl-2-ylamino)-2-a-5-methoxy-phenyl]-oxalin-4-yl-fluorenone , 0 Cl 0 Av ° H /〇^NMR (400 MHz, DMSO) δ 8.44 (s, 1H), 8.36 (s, 1H), 8.30 (s, 1H), 7.06 (s, 1H), 4.00 (s, 3H), 3.88 (s, 3H), 3.72-3.59 (m, 4H), 3.56 (d, J = 3.9, 2H), 3_23-3.14 (m, 2H). 0.0094-295 (5-Chloro-4-(5-gas-4-(decylamino))pyridin-2-ylamino)-2-methoxyphenyl)(N-morpholinyl)methanone CIV ^nc'y^An^ 1 H | ^NMR (400 MHz, DMSO) δ 8.11 (s, 1H), 7.99 (s, 1H), 7.97 (s, 1H), 7.38 (dd, J-9.2, 4.6, 1H), 7.29 (s, 1H), 3.82 (s, 3H), 3.60 (s, 4H), 3.52 (t, J=4.3, 2H), 3.17 (s, 2H), 2.92 (d, 0.0060 156325.doc -184- 201202215

Example Name Structure ^NMR Kj J=4.6, 3H). 296 [5-Gas-2-oxo-4-(4-decylamino-5-trifluoromethyl)-phenylammonium-2-ylamino)-phenyl]-oxalin-4-yl- Anthrone F ^ ΝΗ , 0 0 F^x^o Cl ^ NMR (400 MHz, DMSO) δ 8.59 (s, 1H), 8.20 (s, 1H), 7.88 (s, 1H), 7.32 (s, 1H) , 7.25 (dd, J=12.0, 7.5, 1H), 3.81 (s, 3H), 3.60 (s, 4H), 3.53 (t, J-4.4, 2H), 3.17 (s, 2H), 2.90 (d, J=4.3, 3H). 0.0020 297 [2-Fluoro-3-indolyl-4-(4-methylamino-5-trifluoromethyl-°3⁄4 ate-2-ylamino)-phenyl]-oxalin-4-yl -曱嗣F0 Η 〇\ ^NMR (400 MHz, DMSO) δ 8.49 (s, 1H), 8.20 (s, 1H), 8.11 (d, J=8.5, 1H), 7.25 (d, J=3.6, 1H ), 7.08 (t, J=7.8, 1H), 3.91 (s, 3H), 3.59 (m, 6H), 2.91 (d, J=4.2, 3H). 0.0145 298 [3-(2-Fluoro-ethoxy)-4-(4-guanidino-5-trifluoromethyl-[3⁄4]-2-ylamino)-phenyl]-m-lin-4 -基-曱Μ F ~ΝΗ 0 F^X^O ^NMR (400 MHz, DMSO) δ 8.38 (d, J=8.3, 1H), 8.19(s, 1H), 8.07 (s, 1H), 7.24 ( d, J=4.3,1H), 7.13 (s, 1H), 7.05 (d, J=8.3,1H), 4.91-4.83 (m, 1H), 4.80-4.72 (m, 1H), 4.47-4.39 (m , 1H), 4.39-4.29 (m, 1H), 3.56 (d, J = 37.5, 8H), 2.93 (d, J = 4.4, 3H). 0.0024 299 (4-(5-Ga-4-indoxyoxyl-2-ylamino)-3-decyloxyphenyl) (pyrrolidin-1-yl)methanone Yx r/ o NNH 〇, 1H NMR (400MHz, DMSO) 5 8.32 (s, 1H), 8.26 (s, 1H), 8.16 (d, J-8.2Hz, 1H), 7.18(s, 1H), 7.15 (d, J= 8.3 Hz, 1H), 4.00 (s, 3H), 3.89 (s, 3H), 3.46 (t, J=6.6 Hz, 4H), 1.83 (s, 4H) 0.006 300 [5·ethoxy-2_fluoro- 4-(4-Amidino-5-trifluoromethyl-oxo-2-ylamino)-phenyl]-oxalin-4-yl-曱F ~NH F 0 F^v^o 】ΗΝΜΙΙ (400ΜΗζ, DMSO) δ 8.34 (d, /=12.2 Hz, 1H), 8.24 (s, 1H), 8.04 (s, 1H), 7.35 (d, J=4.3 Hz, 1H), 7.02 (d, J= 6.2 Hz, 1H), 4.15 (q, J=6.9 Hz, 2H), 3.59 0.009 156325.doc -185- 201202215 Instance name structure 'hnmr Kj net (m, 6H), 2.95 (d, J-4.4 Hz, 3H ), 1.39 (t, J = 6.9 Hz, 3H). 301 3-decyloxy-N-(2-methoxy-ethyl)-N-indolyl-4-(4-methylamino-5-trifluoromethyl-pyridin-2-ylamino) -benzylamine F ~NH 0 H /0 0 NMR (400 MHz, DMSO) δ 8.27 (d, J = 8.2 Hz, 1H), 8.18 (s, 1H), 8.06 (s, 1H), 7.19 (d , J=4.3 Hz, 1H), 7.07 (s, 1H), 7.03-6.95 (m, 1H), 3.88 (s, 3H), 3.51 (s, 4H), 3.26 (s, 3H), 2.98 (s, 3H), 2.91 (d, J=4.4 Hz, 3H). 0.0051 302 4-(4-Ethylamino-5-trifluoromethylsulfanyl-2-ylamino)-3-methoxy-N-(2-methoxy-ethyl)-N-indenyl -benzylamine F HN'''-'' 0 H /0 〇, NMR (400 MHz, DMSO) δ 8.21 (d, /=8.2 Hz, 1H), 8.18(s, 1H), 8.06 (s, lH ), 7.19 (t, /=5.4 Hz, 1H), 7.07 (s, 1H), 6.98 (dd, J=8.2, 1.5 Hz, 1H), 3.88 (s, 3H), 3.62-3.40 (m, 6H) , 3.25 (s, 3H), 2.98 (s, 3H), 1.14 (t, J = 7.1 Hz, 3H). 0.0023 303 2-Fluoro-5-decyloxy-N-(2-decyloxyethyl)-N-indolyl-4-(4-methylamino-5-trifluoromethyl-Mickey-2- Aminoguanyl)-benzylamine F ~NH F 0 H /0 0\ 'H NMR (400 MHz, DMSO) δ 8.34-8.25 (m, 1H), 8.24 (s, 1H), 8.09 (s, 1H) , 7.3 l(s, 1H), 6.98 (t, J=6.3 Hz, 1H), 3.88 (d, J=6.9 Hz, 3H), 3.65-3.52 (m, 2H), 3.44-3.33 (m, 2H) , 3.21-3.15 (m, 2H), 3.02-2.89 (m, 6H). 0.0059 304 4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-N-(2-indole-ethyl)- N-Mercapto-benzylamine F HN·^^ F 0 H /0 0\ XH NMR (400 MHz, DMSO) δ 8.28-8.19 (m, 2H), 8.09 (s, 1H), 7.33 (d, J = 4.9 Hz, 1H), 6.98 (t, J = 6.3 Hz, 1H), 3.88 (d, J = 7.0 Hz, 3H), 3.65-3.33 (m, 6H), 3.29-3.15 (m, 3H), 2.96 (d, J-29.9 Hz, 3H), 1.17 (t, J-7.0 Hz, 3H). 0.0016 156325.doc -186- 201202215

Example Name Structure ^NMR Ki 305 [2-Fluoro-5-methoxy-4-(4-methylamino-5-trifluorodecyl-°3⁄4 ate-2-ylamino)-phenyl]-( (S)-2-decyloxymethyl group 嘻-1-yl)-fluorenone F ~NH F 0 Η °\ /〇*ΗΝΜΚ(400 MHz, DMSO) δ 8.34-8.26 (m, 1H), 8.24 (s, 1H), 8.09 (s51H), 7.31 (s, 1H), 7.07-6.96 (m, 1H), 4.22 (s, 1H), 3.63-3.53 (m, 1H), 3.44-3.35 (m, 1H), 3.30 (s, 2H), 3.22 (s, 1H), 3.09-3.00 (m, 2H), 2.94 (d, /=4.3 Hz, 3H), 2.06-1.65 (m, 5H) 〇 0.0030 306 [ 4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-decyloxy-phenyl]-((S)-2-methoxyindole -Pyrrolidin-1-yl)-fluorenone FF 0 H °\ /〇'HNMR (400MHz, DMSO) δ 8.29-8.20 (m, 2H), 8.12-8.06 (m, 1H), 7.38-7.30 (m , 1H), 7.07-6.96 (m, 1H), 4.27-4.17 (m, 1H), 3.63-3.34 (m, 4H), 3.30 (s, 2H), 3.27-3.20 (m, 1H), 3.13-2.99 (m, 2H), 2.04-1.64 (m, 5H), 1.17 (t, J = 7.0 Hz, 3H). 0.0006 307 N-Ethyl-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-decyloxy-N-(2-methoxy -ethyl)-benzylamine FF 0 IH /0 〇, 1H NMR (400MHz, DMSO) δ 8.27-8.20 (m, 2H), 8.09 (s, 1H), 7.33 (t, J = 5.5 Hz, 1H), 6.96 (d, J = 6.2 Hz, 1H), 3.88 (s, 3H), 3.63-3.32 (m, 8H), 3.27-3.13 (m, 3H), 1.20-0.98 (m, 6H). 0.0014 308 N-Ethyl-2-indole-5-methoxy-indole-ρ-methoxy-ethyl)-4-(4-decylamino-5-trifluoromethyl-°3⁄4 bite-2 -ylamino)-benzylamine F ~NH F 0 IH /° °\ 】HNMR (400 MHz, DMSO) δ 8.32-8.25 (m, 1H), 8.24 (s, 1H), 8.09 (s, 1H) , 7.34-7.27 (m, /=4.2 Hz, 1H), 6.96 (d, J-6.2 Hz, 1H), 3.88 (s, 3H), 3.62-3.15 (m, 9H), 2.93 (d, /=4.4 Hz, 3H), 1.18-0.97 (m, 3H). 0.0035 309 [5-Ethoxy-4-(4-ethylamino-5-trifluoromethyl-pyridin-2-ylamino)-2-phenyl]-morphin-4-yl-indole Ketone F HN^^ F 0 1H NMR (400MHz, DMSO) δ 8.29 (d, .7 = 12.2 Hz, 1H), 8.23 (s, 1H), 8.04 (s, 1H), 7.37 (t, J = 5.3 Hz, 1H), 7.02 (d, /=6.2 Hz, 1H), 4.15 (q, /=6.9 Hz, 2H), 3.71-3.44 (m, 9H), 1.38 (t, J=6.9Hz, 3H), 1.18 ( t, J = 7.1 Hz, 3H). 0.0021 156325.doc •187- 201202215 Example Name Structure ^NMR Ki 310 (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl-amino)-3-isopropyloxy Phenyl phenyl XN-morpholinyl fluorenone f 〇V 'H NMR (400 MHz, DMSO) δ 8.38-8.31 (m, 1H), 8.21-8.17 (s, 1H), 7.97-7.92 (s, 1H) , 7.30-7.23 (t, J=5.4Hz, 1H), 7.10-7.06 (d, J=l .6 Hz, 1H), 7.02-6.96 (dd, J=8.3, 1.6 Hz, 1H), 4.79-4.66 (m, 1H), 3.64-3.56 (m, 4H), 3.57-3.41 (m, 6H), 1.35-1.29 (d, /=6.0 Hz, 6H), 1.21-1.09 (t, J=7.1 Hz, 3H ). 0.0045 311 (2-Fluoro-3-isopropoxy-4-(4-(decylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl XN-morpholinyl) A Ketone F ΗΝ^ Ο V Ή NMR (400 MHz, DMSO) δ 8.22-8.20 (s, 1H), 8.20-8.14 (m, 2H), 7.32-7.27 (M, 1H), 7.13-7.06 (dd, J= 8.4, 7.3 Hz, 1H), 4.46-4.32 (m, 1H), 3.67-3.59 (m, 4H), 3.57-3.51 (m, 2H), 3.29-3.23 (m, 2H), 2.95-2.86 (d, J-4.4 Hz, 3H), 1.35-1.24 (d, J=6.l Hz, 6H) ° 0.206 312 (4-(4-(ethylamino)-5-(trifluoromethyl)°3⁄4 bite- 2-Aminoamino)-3-(trifluoromethoxy)phenyl)(N-morpholinyl)methanone f 〇 十 F *H NMR (400 MHz, DMSO) 6 9.20-9.11 (s, 1H) , 8.19-8.11 (s, 1H), 8.07-7.98 (d, J=8.9 Hz, 1H), 7.45-7.38 (m, 2H), 7.22-7.12 (t, J=5.6 Hz, 1H), 3.66-3.56 (m, 4H), 3.59-3.41 (m, 4H), 3.42-3.35 (m, 2H), 1.14-1.02 (t, J = 7.0 Hz, 3H). 0.028 313 (2-Fluoro-3-isopropoxy-4-(4-(methylamino)-5-(difluoromethyl)pyrimidin-2-ylamino)phenyl;) (N-morpholine) (), fluorenone F ΗΝ〆Ο f^xnjO^O pV 'H NMR (400 MHz, DMSO) δ 9.20-9.08 (s, 1H), 8.20-8.14 (s, 1H), 8.13-8.06 (d, J= 8.9 Hz, 1H), 7.46-7.38 (m, 2H), 7.23-7.15 (m, 1H), 3.68-3.57 (m, 4H), 3.57-3.37 (m, 4H), 2.89-2.82 (d, J= 4.4 Hz, 3H). 0.206 Table 6 156325.doc -188- 201202215 Example 11: 2-[2-Methoxy-4-(morpholin-4-carbonyl)-anilino]-4-methylamino-pyrimidine-5-indoleonitrile ^ Ο

Zn(CN)2 Pd2(dba)3 DPPF DMF

搅拌 Stirring (4-(5-bromo-4-(decylamino)pyrimidin-2-ylamino)-3-methoxyphenyl) (N-morpholine) in a pressure tube at 105 ° C. Ketone (80 mg, 0.19 mmol), zinc cyanide (50 mg, 0.42 mmol), ginseng (diphenylidene propyl), gemini (9 mg, 0.09 mmol) 'DPPF (11 mg, 0.02 mmol) The mixture in DMF (3 mL) was 18 h. The reaction mixture was filtered and concentrated. The crude product was purified by EtOAc (EtOAc) Other compounds prepared using the above procedure are shown in Table 7, below. Example name structure ^NMR Kt 314 2-(2-methoxy-4-(morpholin-4-carbonyl)anilino)-4-(methylamino)pyrimidine-5-indolecarbonitrile kl HN〆HJ Ο ΉΝΜΚ (400ΜΗζ, DMSO) δ 8.34 (s, 1Η), 8.33 (s, 1H), 8.18(d, J=8.2, 1H), 7.81-7.70 (m, 1H), 7.08(d, J=1.5, 1H) , 7.01 (m, 1H), 3.88 (s, 3H), 3.60 (s, 4H), 3.51 (s, 4H), 2.88 (d, J=4.5, 3H) 0.0024 315 4-decyloxy-2-[ 2-methoxy-4-(Merlin-4·yl)-anilino]-°3⁄4 曱 曱 曱 H H H H H H H H H H H H H H H H H H 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 9. 9. s, 1H), 7.85 (d, J=7.9,1H), 7.11 (s, 1H), 7.02 (d, J=7.9, 1H), 3.98 (s, 3H), 3.85 (s, 3H), 3.56 ( m, 8H). 0.138 156325.doc -189- 201202215 Example name structure ^NMR Kj 316 4-ethylamino-2-[5-fluoro-2-methoxy-4-(oxalin-4-yl)-anilino]- Pyrimidine- 5-carbonitrile^NH F 0 Η /〇1HNMR (400MHz, DMSO) δ 8.39 (s, 1Η), 8.32 (s, 1H), 8.17 (d, y = 12.0 Hz, 1H), 7.96-7.90 ( m, 1H), 7.04 (d, /=6.2 Hz, 1H), 3.88 (s, 4H), 3.70-3.49 (m, 8H), 3.48-3.38 (m, 3H), 1.17(t,J=7.1 Hz , 4H). 0.0065 317 2-[5-Fluoro-2-methoxy-4-(morpholin-4-carbonyl)-phenylamino]-4-indolyl-pyrimidine-5-carbonitrile F 0 Η /〇^NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.31 (s, 1H), 8.22 (d, J = 11.9 Hz, 1H), 7.88 (d, J = 3.8 Hz, 1H), 7.04 (d, J =6.2 Hz, 1H), 3.88 (s, 4H), 3.69-3.50 (m, 8H), 2.91 (d, J=4.5 Hz, 4H). 0.0112 318 2-[4-((2R,6S)-2,6-Dimercapto-infrared'-4-yl)-5-fluoro-2-methoxy-anilino-H-nonylamino- Pyrimidine-5-phthalonitrile~ΝΗ F 0 Η /0 * iHNMR (400 MHz, DMSO) δ 8.40 (s, 1H), 8.32 (s,1H), 8.23 (d,J=12.0 Hz, 1H), 7.89 ( s,1H), 7.03 (d, J=6.2 Hz, 1H), 4.40 (d, J=13.1 Hz, 1H), 3.88 (s, 3H), 3.52 (s, 2H), 3.40-3.33 (m, 7 = 10.8 Hz, 1H), 2.92 (d, J=3.9 Hz, 3H), 2.81 (t, /=11.8 Hz, 1H), 2.46 (d, J-12.1 Hz, 1H), 1.20-0.95 (m, 6H) ). 0.0368 319 2-[4-((2R,6S)-2,6-Dimethyl-morphin-4-yl)-5-fluoro-2-indolyl-anilino]-4-ethylamino -pyrimidine-5-indolecarbonitrile ΝΗ F 0 Η /° 4 ΉΝΜΚ (400 MHz, DMSO) δ 8.40 (s, 1H), 8.33 (s, 1H), 8.17 (d, J = 12.0 Hz, 1H), 7.98 -7.90 (m, 1H), 7.03 (d, J=6.2 Hz, 1H), 4.40 (d, /=12.9 Hz, 1H), 3.88 (s, 3H), 3.60-3.48 (m, 2H), 3.48- 3.39 (m, 2H), 3.39-3.34 (m, 1H), 2.81 (t, /=11.9 Hz, 1H), 0.0194 156325.doc -190- 201202215 Example name knot^S— *ΗΝΜΚ Ki 2.49-2.42 (m , J=12.0 Hz, 1H), 1.21-0.97 (m, 9H) ° 320 4- (5-Cyano-4-indenyl-°3⁄4 bite-2- 5-decyloxy-N,N-II曱-benzyl benzamide ^NH pn ^ NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.30 (s, 1H), 8.19 (d, J = 11.9 Hz, 1H), 7.90-7.83 (m, 1H), 7.01 (d, 7=6.2 Hz, 1H), 3.87 (s, 4H), 2.99 (s, 3H), 2.91 (d, J=4.5 Hz, 3H), 2.89 (s, 3H). 7

The corresponding pharmaceutically acceptable salts of hydrazine and acid formation can be obtained by standard methods known to those skilled in the art, for example by dissolving the formula in a suitable solvent such as dioxane or THF and adding the appropriate amount. Acid to get. The product can usually be isolated by filtration or by chromatography. The compound can be converted to a pharmaceutically acceptable salt formed with the base by the use of a compound of formula I. A possible method of forming the salt is, for example, by adding an equivalent basic salt such as M(〇H)n, wherein M=metal or ammonium cation and ^anion anion number to the compound in a suitable solvent (eg ethanol) In a solution in ethanol, water mixture, tetrahydroanhydride-water mixture, and solvent is removed by evaporation or drying. Particular salts are the hydrochloride, formate and trisodium acetates. Especially the hydrochloride salt. Where the preparation of the compound of formula I and all intermediates is not described in the examples, it can be prepared according to analogous methods or according to the methods described herein: starting materials are commercially available, known or available in the art. It is prepared by methods known in the art or analogous thereto. It will be appreciated that the compounds of the present invention may be provided in the functional group at 126325.doc -191 - 201202215 to provide derivatives which are capable of reconversion into the parent compound in vivo. Pharmacological Tests The compounds of formula I and their pharmaceutically acceptable salts have important pharmacological properties. The compounds of the invention have been found to be involved in the regulation of LRRK2 activity. These compounds were studied according to the tests given below. Example 12 In Vitro LRRK2 LabChip Assay This assay was used to determine the potency of a compound to inhibit LRRK2 activity by measuring Kiapp, IC50 or percent inhibition values. In a polypropylene plate, LRRK2, a fluorescently labeled peptide substrate, ATP, and a test compound were incubated. Using LabChip 3000 (Caliper Life Sciences), the receptors were divided into two populations by capillary electrophoresis after the reaction: phosphorylated receptors and unphosphorylated substrates. The relative amount of each population was quantified by fluorescence intensity. LRRK2 Ki is determined according to the following equation: Y=V〇x(l-((x+Kix(l + S/Km)+Et)/(2xEt)-(((x+Kix(l+S/Km)+Et ) 2-(4xEtxx))°.5)/(2xEt))). The Ki values in Table 4 and elsewhere herein are shown in μΜ. The verification conditions and materials used are as follows: Final verification conditions: 5.2 nM (Invitrogen batch number 567054A) 11 nM (Invitrogen batch number 567054A) 15 nM (Invitrogen batch number 500607F) 25!1]^1 (11^11 (^611 lot number 43594) 1 μΜ LRRK2 G2019S in 5 mM MgCl2: LRRK2G2019S in 1 mM MnCl2 · LRRK2 wild type in 5 mM MgCl2: LRRK2 I2020T in 5 mM MgCl2 : Substrate: ATP : 156325.doc -192- 201202215 Kinase reaction time: 2 hours Temperature: Ambient temperature Total volume: 20 μΐ ATPapp Kms : G2019S in 5mMMgCl2 : 130 μΜ G119S in 1 mMMgCl2t : 1 μΜ in 5 mM MgCl2 _ wild type: 80 μΜ in 5 mM MgCl2 After 2020: 14 μΜ

Materials · Solid Support · Black 50 μm Volume Polypropylene 384-well Plate (MatriCal Cat. No. MP101-1-PP) Kinase: LRRK2 G2019S (Invitrogen Cat. No. PV4882) LRRK2 Wild Type (Invitrogen Cat. No. PV4874) Substrate: 5FAM- GAGRLGRDKYKTLRQIRQ-CONH2 Unbonded Plate: 384-well transparent V-bottom polypropylene plate (Greiner Cat. No. 781280) ATP : 10 mM ATP (Cell Signaling Cat. No. 9804)

Triton X-100 · Triton X-100

Brij-35 : Brij-35 (Pierce Cat. No. 20150) Coating Reagent #3 : Coating Reagent #3 (Caliper) DMSO : DMSO (Sigma Cat. No. 34869-100ML)

Complete reaction buffer: H20/25 mM Tris, pH 8.0/5 mM

MgC12/2 mM DTT/0.01% Triton X-100 Stop solution: H20/100 mM HEPES, pH 7.2/0.015% Brij- 156325.doc -193- 201202215

3 5/0.2% Coating Reagent #3/20mMEDTA Separation Buffer: H20/100 mM HEPES, pH 7.2/0.015% Brij-35/0.1% Coating Reagent #3/1:200 Coating Reagent #8/10 mM EDTA/5% DMSO Compound Plate Preparation: For serial dilutions, add 34.6 μM DMSO to rows 3-24. For the assay control, add 37.5 μΐ DMSO to rows 1 and 2 of columns A and P, and add 50 μΐ 25 μΜ G-02883 1 (Staurosporine) to rows 1 and 2, column B. For samples: start at 100 μΜ, add 37.5 μΐ DMSO to rows 1 and 2, then add 12.5 μΐ 10 mM compound; start with 10 μΜ, add 78 μΐ DMSO to rows 1 and 2, then add 2 μΐ 10 mM compound And starting with 1 μΜ, add 25 μM compound (2 μΐ 10 mM compound + 798 μΐ DMSO) to blank lines 1 and 2. 1:3.16 serial dilution ("PLK-BM-serial_halflog") was performed using a precision instrument. ATP preparation: ATP was diluted to 282.1 μΜ ° in complete kinase buffer (final concentration 130 μΜ) and blank control preparation: The substrate was diluted to 4 μΜ in complete reaction buffer. Equal volumes of complete reaction buffer and 4 μΜ substrate were combined to obtain a blank control. Equal volumes of complete reaction buffer and 4 μΜ substrate were combined and 2 χ final concentration LRRK2 was added to the pooled solution. Verification procedure: Manually add 5 μl/well buffer/substrate to a 156325.doc -194- 201202215 blank well into a 50 pL polypropylene plate. The kinase reaction ("PLK SAR 23 ATP") was initiated using Biomek FX. Add the following material to the appropriate wells: 2 μΐ compound + 23 μΐ ATP; 5 μl/well of compound/ATP in assay plates; 5 μl/well of kinase/substrate in assay plates; plates were incubated for 2 hours in the dark. The kinase reaction ("PLK Stop") was stopped using Biomek FX and 1 〇 microliter/well stop solution was added to the assay plate. The results were read using the LabChip 3000. Ο

Lab Chip 3000 Solution: Operate the LabChip 3000 with the job "LRRK2 IC50" and the following operating settings: Pressure: -1.4 psi

Downstream voltage: -500 V

Upstream voltage: -2350 V After sample buffer suction time: 75 seconds after dye buffer suction time: 75 seconds Final delay time: 200 seconds Example 13 In vitro LRRK2 Lanthascreen binding assay This assay is determined by Kiapp, IC50 or inhibition Percent values are used to determine the potency of a compound to inhibit LRRK2 activity. LRRK2, Eu-anti-GST antibody, Alexa Fluor® kinase tracer 23 6 and test compound were incubated in 384-well proxiplates F black well plates. The binding of the Alexa Fluor® "trace" to the kinase was detected by the addition of an Eu-labeled anti-GST antibody. The combination of the tracer and antibody with the kinase causes a high degree of 156325.doc -195 - 201202215 FRET, while displacement of the tracer with a kinase inhibitor causes FRET loss. The assay conditions and materials used are as follows: GST-LRRK2 G2019S 10 nM Eu-anti-GST antibody 2 nM Kinase tracer 23 6 8.5 nM Kinase reaction time: 1 hour Temperature: Ambient temperature Total volume: 15 μΐ DMSO 1% Material = 384-well proxiplates F black shallow well Perkin Elmer Cat. No. 6008260 Kinase: LRRK2 G2019S Invitrogen Cat. No. PV4882 (batch 567054A) Eu-labeled anti-GST antibody Invitrogen Cat. No. PV5594 Alexa Fluor® Kinase Tracer 236 Invitrogen Cat. No. PV5592 TRIS-HC1 Sigma Cat. No. T3253 EGTA Sigma Cat. No. E3889 Brij-35 Sigma Cat. No. B4184 (30% w/v) DMSO Sigma Cat. No. D8418 MgC12 Sigma Cat. No. M9272 Reaction Buffer: H2O/50 mM Tris, pH 7.4/10 mM MgC12/ l mM EGTA/0_01% Brij 35. Compound plate preparation: 156325.doc -196- 201202215 The test compound (10 mM stock solution) was serially diluted with 1:100% (20 μl + 43.2 μM) in 100% DMSO. 12-point curve. Each concentration was diluted with 1:33.3 (3 μl + 97 μΐ) using reaction buffer. Take 5 μΐ to the assay plate. The final maximum test concentration is 10 0 μΜ. Preparation of all and blank controls: In reaction buffer, 5 μΐ DMSO (3%) was added to all and blank wells and 5 μΐ Eu-labeled anti-GST antibody (6 nM) was added to the blank wells. Assay procedure: Add 5 μΐ LRRK2 (30 nM)/Eu labeled anti-GST antibody (6 nM) mixture to the compound and all wells. Add 5 μΐ kinase tracer (25.5 nM) to all wells. The plates were incubated for 1 hour at room temperature on a plate shaker (slightly shaken). The HTRF protocol was read using a Perkin Elmer EnVision reader. Data processing: Calculated ratio: (665/620) χ 10000. The average background value is subtracted from all data points. Calculate the % control of each test value. The % of the control relative to the concentration of the compound is plotted. Calculate the Ki value (xlfit curve fit - Morrison equation) 〇 The result is expressed as Κί(μΜ). Ki equation: Y=V〇x(l-((x+Kix (l + S/Km)+Et)/(2xEt)-(((x+Kix(l + S/Km)+Et)2-(( 4xEtxx))05)/(2xEt)))

Wherein Et = 4 nM 1 &lt;;&lt; 1 (inverted) =: 8.5 11] \1 shows the vertical concentration (S) = 8.5 nM. Example 14 Animal Model of Parkinson's Disease 156325.doc -197- 201202215 Parkinson's disease can be achieved by administering 1-mercapto-4-phenyltetrahydro. ratio. Ding (MPTP), a selective nigrostriatal dopaminergic neurotoxin that causes loss of the striatum dopamine (DA) neuroenda marker, replicates in mice and primates. The effectiveness of the compounds of the invention in the treatment of Parkinson's disease can generally be assessed using MPTP-induced neurodegeneration according to the protocol described by Saporito et al., J. pharmacology (1999) Vol. 288, pp. 421-427. Briefly, MPTP was dissolved in pbs at a concentration of 2_4 mg/ml, and mice (male C57 weighing 20-25 g) were given a subcutaneous injection of 20 to 40 mg/kg. The compound of the present invention was solubilized with polyethylene glycol hydroxystearate and dissolved in PBS. Mice were administered a 10 ml/kg compound solution by subcutaneous injection 4 to 6 hours prior to MPTP administration, and then administered daily for 7 days. Mice were sacrificed on the day of the last injection and the midbrain was blocked and then fixed in the trimeric furfural. The striatum was cut, weighed and stored at -70 °C. As described by Sonsalla et al., J. Pharmacol. Exp. Ther. (1987) Vol. 242, pp. 850-857, dopamine in the striatum thus collected and its properties were evaluated by HPLC and electrochemical detection. Metabolites dihydroxyphenylacetic acid and high vanillic acid content. Okunu et al., Anal Biochem (1987) Vol. 129, pp. 405-411, tyrosine hydroxylase assay 'by measurement with tyrosine hydroxylase-mediated labeled tyrosine conversion The striatum was evaluated for L-dopa-related 14c〇2 escape. Can be used separately, such as White et al, Life

Monoamine oxidase-B assays described in Sci. (1984), vol. 35, pp. 827-833 and as assessed by monitoring dopamine uptake as described in Saporito et al., (1992) Vol. 260, pp. 1400-1409. Shape. Although the present invention has been described with reference to the specific embodiments thereof, it is understood that the skilled artisan will be able to make various changes without departing from the true spirit and scope of the present invention. Alternative equivalent. In addition, modifications may be made to adapt a particular situation, material, composition of matter, method, and method steps to the objective spirit and scope of the invention. All such modifications are intended to be within the scope of the accompanying claims. Pharmaceutical Compositions The compounds of formula I and pharmaceutically acceptable salts are useful as therapeutic actives, for example in the form of pharmaceutical preparations. Such pharmaceutical preparations can be administered orally, for example, in the form of tablets, coated tablets, dragees, hard gelatin capsules and soft gelatin capsules, solutions, emulsions or suspensions. However, administration can also be carried out, e.g., in the form of a suppository, or parenterally, e.g., in the form of an injectable solution. The pharmaceutically acceptable salts and pharmaceutically acceptable salts thereof can be treated with a pharmaceutically inert inorganic or organic carrier to prepare a pharmaceutical preparation. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like can be exemplified as such carriers for use as lozenges, coated lozenges, dragees and hard gelatin capsules. Suitable carriers for soft gelatin capsules are, for example, vegetable oil 1, fat, semi-solid and liquid polyols and the like. However, depending on the nature of the active substance, it is generally not necessary to use a carrier in the case of a soft knee capsule. Suitable carriers for the preparation, liquid dispersion and syrup are, for example, water, polyols, glycerol, vegetable oils and the like. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like. In addition, 'medical preparations may contain pharmaceutically acceptable auxiliary substances such as preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, 156325.doc •199· 201202215 Colorants, flavoring agents, change infiltration Salt, buffer, masking agent or antioxidant. It may also contain other therapeutically valuable substances. The invention also provides a medicament comprising a compound of formula I, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier, and a process for the manufacture thereof, which comprises one or more compounds of formula I and/or pharmaceutically acceptable thereof The salt and one or more other therapeutically valuable substances may be required to form a galenical administration form together with one or more therapeutically inert carriers. The dosage can vary within wide limits and will of course have to be adjusted to individual needs in each particular case. In the case of oral administration, the adult dosage will vary from about 0,01 mg to about 1000 mg of the compound of formula I or the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dose may be administered in a single dose or in divided doses, and may additionally exceed the upper limit when found to be needed. The following examples are described without limiting the invention, but are merely representative. The pharmaceutical preparation preferably contains from about 1 to 500 mg, preferably from 1 to 100 mg, of a compound of formula I. Examples of compositions of the invention are:

Example A A tablet of the following composition was prepared in the usual manner: Ingredient mg/bonding agent 5 25 100 500 Compound of formula I 5 25 100 500 Anhydrous lactose DTG 125 105 30 150 Sta-Rx 1500 6 6 6 60 Microcrystalline cellulose 30 30 30 450 Magnesium stearate 1 1 1 1 Total 167 167 167 831 Table 8: Possible lozenge composition 156325.doc • 200- 201202215 Procedure 1. Mix ingredients 1, 2, 3 and 4 and pelletize with pure water. 2. Dry the granules at 50 °C. 3. Pass the particles through a suitable grinding device. 4. Add ingredient 5 and mix for three minutes; compress on a suitable press. Example B-1 A capsule of the following composition was made: Ingredient mg/capsule 5 25 100 500 Compound of formula I 5 25 100 500 Aqueous lactose 159 123 148 - Corn starch 25 35 40 70 Talc 10 15 10 25 Magnesium stearate 1 2 2 5 Total 200 200 300 600 Table 9: Possible Capsule Composition Composition Manufacturing Procedure 1. Mix ingredients 1, 2 and 3 in a suitable mixer for 30 minutes. 2. Add ingredients 4 and 5 and mix for 3 minutes. 3. Fill into a suitable capsule. The compound of formula I, lactose and corn starch are first mixed in a mixer and subsequently mixed in a pulverizer. The mixture is returned to the mixer; talc is added to it and thoroughly mixed. The mixture is filled into suitable capsules (e.g., hard gelatin capsules) by machine. Example B-2 A soft gelatin capsule of the following composition was made: 156325.doc • 201 · 201202215 Ingredient mg/capsule I Compound 5 Astragalus 8 Hydrogenated soybean oil 8 Partially hydrogenated vegetable oil 34 Soybean oil 110 Total 165 Table ίο: Possible soft gelatin Capsules Ingredients mg/capsule gelatin 75 Glycerin 85% 32 Karion 83 8 (dry matter) Dioxide demon 0.4 Iron oxide yellow 1.1 Total 116.5 Table 11: Possible soft gelatin capsule composition manufacturing procedure Dissolve the compound of formula I in other ingredients The hot melt is filled and the mixture is filled into soft gelatin capsules of appropriate size. The filled soft gelatin capsules are processed according to common procedures.

Example C A suppository of the following composition was made: Ingredient mg/suppository Compound of formula I 15 Suppository base 1285 Total 1300 Table 12: Possible suppository compositions Manufacturing procedure The suppository base was melted in a glass or steel vessel, thoroughly mixed and cooled to 45 °C. A fine powder of the compound of formula I is then added thereto and stirred until it is completely dispersed 156325.doc -202 - 201202215. The mixture is poured into a suppository mold of suitable size to allow it to cool; the suppository is then removed from the mold and individually dispensed in wax paper or foil.

Example D An injection solution of the following composition was prepared: Ingredient mg/injection solution Compound I of formula I 3 Polyethylene glycol 400 150 Acetic acid was adjusted to pH 5.0 The injection solution was adjusted to 1.0 ml with water. Table 13: Possible injection solution composition Manufacturing procedure I The compound is dissolved in a mixture of polyethylene glycol 400 and water for injection (partial). The pH was adjusted to 5.0 by acetic acid. Adjust the volume to 1 .〇 ml by adding the remaining amount of water. The solution was filtered and filled into vials with appropriate spillage and sterilized.

Example E A sachet of the following composition was made: Ingredient mg / sachet I compound 50 Fine powdered lactose 1015 microcrystalline cellulose (AVICELPH 102) 1400 sodium carboxymethyl cellulose 14 polyvinylpyrrolidone K 30 10 stearic acid Magnesium 10 Flavouring Additive 1 Total 2500 Table 14: Possible Pouch Composition 156325.doc -203- 201202215 Manufacturing Procedure Mixing Compounds of Formula I with Lactose, Microcrystalline Cellulose and Sodium Carboxylic Cellulose, and Using Polyvinylpyrrolidone The mixture in water is granulated. The granules are mixed with magnesium stearate and a flavoring additive and filled into the sachet. 156325.doc -204·

Claims (1)

201202215 VII. Patent application scope: 1. A compound of formula I, Rv X 6 R RIN Q R3 i or a pharmaceutically acceptable salt thereof, ο G wherein: m is 0 to 3; X is: -NRa- ; -Ο-; or -S(0)r-, wherein r is 〇 to 2 and Ra Is hydrogen or CN6 alkyl; R is .Cw alkyl, C2-6 dilute, C2_6 alkynyl; halo; C!6 alkoxy-C1-6 alkyl; trans-C2.6 alkenyl Amino-cl6 alkyl; C!_6 alkyl-CW-based; C3-6-cycloalkyl substituted by c1-6, C3-6 cycloalkyl-C]·6 a group wherein the cycloalkyl moiety is optionally substituted with a C 丨 6 alkyl group; a tetrahydro β-fanyl group; a tetramethylpyranyl jf alkyl group; a tetrahydropyranyl group; a tetrahydropyranyl group _ Ci 6 alkyl; anthracene ketone; or oxetane-Cw alkyl; or ... and ^ together with the atom to which they are attached may form a three to six membered ring, which may optionally include an O' N and Sy—hetero atom, and which is substituted by a pendant oxy group, a halogen group or a Ck alkyl group; R 2 is: —yl; c, -6 alkoxy group, cyano group; C26 alkynyl group; a dilute group; -6 alkyl; i-yl-Cl.6 oxo; cardinyl, 156325.doc 201202215 wherein the Cw cycloalkyl moiety is optionally substituted by Ci 6 alkyl; C 3 6 cycloalkyl _ Cl_6 alkyl among them The C3.6 cycloalkyl moiety is optionally substituted by C!-6 alkyl; tetrahydroc-butyl; tetrahydrofuranyl-c16 alkyl; ethyl hydrazino; oxetan; or oxetane-c16 R3 is: -〇R4; dentate; cyano; Ci6 alkyl; halo-〇16 alkyl; c3_6 cycloalkyl substituted by ^^6 alkyl; C3_6 cycloalkyl_Ck Wherein the c3 6 cycloalkyl moiety is optionally substituted by Cm alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Ci 6 alkyl; oxetanyl; or oxetane-Ci 6 alkyl R is oxygen, 匚1_6 alkyl; dentyl-〇1_6 alkyl, 〇1-6 oxy-(!11.6 alkyl; optionally C3-6 naphthenic substituted by Cl-6 alkyl or halo a C3-6 cycloalkyl-C!-6 alkyl group, wherein the c3_6 cycloalkyl moiety is optionally substituted by a Cw alkyl group or a hydryl group; a tetrahydrofuranyl group; a tetrahydrofuranyl-Cw alkyl group; an oxetane group; Or oxetane-cN6 alkyl; R5 is: hydrogen; or alkyl; η is 0 or 1; R6 is: hydrogen; Cy alkyl; Cw alkoxy-Cw alkyl; hydroxy-Cw Amino-Cw alkyl; hydrazine: 3-6 cycloalkyl; c3-6 cycloalkyl-Cw alkyl; heterocyclic; or heterocyclic-Ck And wherein the C3_6 cycloalkyl group, the C3_6 cycloalkyl-C!-6 alkyl group, the heterocyclic group and the heterocyclic group _cN6 alkyl group are each independently selected from the group consisting of one, two, three or four Group substitution: C1_6 alkyl; halo-Cw alkyl; Cw alkoxy; halo-Cm alkoxy; hydroxy; hydroxy-Cw alkyl; halo; nitrile; d_6 alkyl-cut; c! -6 alkyl-contiguous fluorenyl; C3·6 cycloalkyl; c36 cycloalkyl-Cl 6 alkyl; c3_6 cycloalkane 156325.doc 201202215 benzyl-aryl; amine ' or heterocyclic; or two The groups may form a five or six membered ring together with the atom to which they are attached; or R5 and R6 together with the nitrogen atom to which they are attached form optionally including another hetero atom selected from the group consisting of 〇, N and S(0)n. a three to seven membered ring, and the ring is optionally substituted with one, two, three or four groups independently selected from the group consisting of: Cw alkyl; dentyl-Cl-6 alkyl; Ci-6 alkoxy; Alkoxy, hydroxy; hydroxy-Cw alkyl; halo; nitrile; Ci6 alkyl-carbonyl; ^Ch alkyl-sulfonyl; C3 6 cycloalkyl; 〇3·6 cycloalkyl 6 alkyl; C3 -6 cycloalkyl-carbonyl; amine; c10 alkyl-heterocyclyl; c16 alkane a group of -C 6 alkyl or heterocyclic groups; or two such groups together with the atom to which they are attached may form a five or six membered ring; and R is a 'halo" C!-6 alkyl group, C!- 6 alkoxy; halo-Cw alkyl; or south-Ci-6 alkoxy. 2. A compound of formula I as claimed in claim 1, ο RIN Or a pharmaceutically acceptable salt thereof, wherein: m is 0 to 3; X is: -NRa-; ; 4_S(〇)n· ' wherein η is 〇 to 2 and RaA hydrogen or C ι 6 burning group; 156325. Doc 201202215 R is · Ci-6 alkyl; C2-6 alkenyl; C2-6 alkynyl; halo-Cj.6 alkyl; Ci-6 alkoxy-Cw alkyl; hydroxy-C2.6 alkenyl Amino-Ck alkyl, C!_6 alkyl thiol-Cj^6 alkyl; C. 6 cycloalkyl substituted by ^^^ alkyl; C3·6 cycloalkyl-C! a 6 alkyl group, wherein the c:3·6 cycloalkyl moiety is optionally substituted by a C 1 -6 alkyl group; a tetrahydroanthyl group; a tetrahydrocarbamate group _C, a 1'6 alkyl group; a cyclobutane group; or an oxetane_Cl_6 alkyl group; or R1 and 1^ together with the atom to which they are attached may form a three to six membered ring, which may optionally include another impurity selected from the group consisting of ruthenium, N and S. An atom, and which is substituted by a pendant oxy group, an i group or a Cw alkyl group; 2 R is: a halogen group; a Cu alkoxy group; a cyano group; a c2-6 alkynyl group; a c2-6 azide group; a halogen group-C!. 6 alkyl; halo-Cw alkoxy; CM cycloalkyl, wherein the C3·6 cycloalkyl moiety is optionally substituted by a Cl.6 alkyl; C3·6 cycloalkyl, C!·6 alkyl Where the Gw ring The phenyl moiety is optionally substituted with a C 4 alkyl group, 'tetrahydrofuranyl group; tetrahydrofuranyl-C 丨 6 alkyl group; ethyl hydrazino group; oxetan group; or oxetane-Cw alkyl group; R 3 is: -or 4 Halogen; cyano; Cl-6 alkyl; halo-Ci 6 alkyl; CM cycloalkyl substituted by ^^6 alkyl; Gw cycloalkyl _ c! · 6 alkyl The Gw cycloalkyl moiety is optionally substituted by c10 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Cw alkyl; oxetanyl or oxetane-Cl6 alkyl; R is: Cl-6 alkyl ; halo-Ci-6 alkyl; Ci-6 alkoxy-Ci6 alkyl; optionally C3-6 cycloalkyl substituted by 1_6 alkyl or halo; c3_6 cycloalkyl-Ch, wherein The C36 cycloalkyl moiety is optionally substituted by a Ci 6 alkyl or a benzyl group, a tetrahydroanthracene group; a south group; a tetraflavyl-Cl. 6 alkyl group; an oxa group 156325.doc 201202215 a cyclobutane group; Cyclobutanealkyl; R5 is: hydrogen; or CK6 alkyl; η is 0 or 1; R6 is: hydrogen; k-alkyl; Ci_6 alkoxy_c&quot;alkyl;hydroxyl-based; amine-Cl a group; a cycloalkyl group; a c3-6 cycloalkyl group; a heterocyclic group; or a heterocyclic group Wherein the cw-deactivating group, ❹ G-alkyl group _Cl_6 alkyl group, heterocyclic group and heterocyclic group 4 alkyl group are each: substituted by one, two, three or four groups independently selected from the group consisting of: ^ Halo-C丨-6 alkyl; cN6 oxy-oxan. South A fluorenyl, halo-C丨_6 alkoxy; surface group; trans-C1·6 alkyl; dentate; nitrile; k alkyl group-single group; C16 base group - sulphate group; ~ ring-yard group; C3.6 cycloalkyl group _Ci 6 yard group; c36 ring = yl-yl group; amine group; or heterocyclic group; The material group may form a five- or six-membered ring together with the atom to which it is attached; or R5 and R6 together with the nitrogen atom to which it is attached may form, as the case may be, another hetero atom selected from the group consisting of ruthenium, N and S(〇)n. a three to seven-membered ring, and the ring is optionally substituted with one, two, three or four groups independently selected from the group consisting of: k-alkyl; ke-Cl.6 alkyl; Ci-6 oxo; halogen &amp;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; alkyl-Ci6 alkyl; C3-6 cycloalkyl-carbonyl; amine; or heterocyclic; or two such groups The atoms together may form a five or six membered ring; and R7 is: halo; Ck alkyl; Cl-6 alkoxy; halo CM alkyl; or halo-Cw alkoxy. 3. As claimed in claim 1 A compound according to any one of 2, wherein the compound has the formula 156325.doc 201202215 II: Or a pharmaceutically acceptable salt thereof, wherein: m is 0 to 3; X is .-NRa-; ; or -S(〇)n-, wherein 1 is 〇 to 2 and ][^ is gas or C, _6 alkyl; R is a decyl group; c2-6 alkenyl; c2_6 alkynyl; halo-cl6 alkyl; Cw alkoxy-C1-6 alkyl; hydroxy-C2·6 alkenyl; An alkyl group, a Ci_6 alkyl group, a sulfonyl group, a C3-6 ring-based base substituted by a Ci 6 alkyl group, and a C3·6 cycloalkyl-Cw alkyl group, wherein The alkyl moiety is optionally substituted with C!-6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Cl6 hexyl; oxetane; or oxetane-Cw alkyl; 2R is: halo; Ci-6 alkoxy; cyano; C2-6 alkynyl; (: 2-6 alkenyl; dentyl-hydrazine alkyl; halo-Cw alkoxy; C3-6 cycloalkyl, wherein the C3·6 The cycloalkyl moiety is optionally substituted with a c16 alkyl group; c3_6 cycloalkyl-Cl.6 alkyl group wherein the C3-6 cycloalkyl moiety is optionally substituted with a CN6 alkyl group; tetrahydrofuranyl; tetrahydrofuranyl-c16 alkyl; Oxetane, or oxetane-C!-6 alkyl; R is: -〇R4; halo; cyano; optionally substituted by 匕6 alkyl C: 3·6 ring C36 cycloalkyl-c16 alkyl, wherein the (:3-6 cycloalkyl moiety 156325.doc 201202215 is optionally substituted by Ci 6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-Ci-6 alkyl; oxyheterocycle Butanyl; or oxetanealkyl; R is .4.6 alkyl; halo-Cw alkyl; Ci6 alkoxy-decane-yl; C3.6 optionally substituted by Cw alkyl a cycloalkyl group; a c3-6 cycloalkyl-Cl-6 alkyl group, wherein the Cw cycloalkyl moiety is optionally substituted by a Ci-6 alkyl group; a tetrahydrofuranyl group; a tetrahydrofuranyl-Cm alkyl group; an oxetane group; Oxetane-Cl6 alkyl; 〇R5 is: hydrogen; or Cw alkyl; R6 is: hydrogen; c-6 alkyl; Cl-6 alkoxy_Ci6 alkyl; amine-Ci6 alkyl; C3·6 cycloalkyl; C3_6 cycloalkyl-Ci·6 alkyl; heterocyclic group; or heterocyclic group-Cm-institution; in the oxime, the C3-6 cycloalkyl, C36 ring-form 々6 alkyl, The heterocyclic group and the heterocyclic ruthenium each may be optionally substituted by one, two or three groups independently selected from the group consisting of: 'alkyl group; functional group _ Cl_6 alkyl group; Cm alkoxy group; -Gw alkoxy; hydroxy; hydroxy _ C]-6 炫, · from base; nitrile; C I6alkyl group; &amp; calcination group - continued 醯Ο C3_6 cycloalkyl-cycloalkyl 4-6 alkane &amp; c3_6 cycloalkyl-alkyl, amino, or heterocyclic; or two The group may form a five- or six-membered ring together with the atom to which it is attached; " or R and R, together with the nitrogen atom to which they are attached, form three other heteroatoms, optionally including ruthenium, N and S(〇)n. Up to seven-membered ring, and the ring is replaced by one, two or three groups independently selected from the group consisting of: Cl·6 alkyl, 1 base_c〗 6 courtyard; Cl6; oxy; halogen基-Ci6 group; via group '· base group; dentate group; nitrile; CM group Cl-6 alkyl-sulfonyl group; Cw cycloalkyl group; C3·6 cycloalkyl group _Cl·6 alkyl group; ' 156325.doc 201202215 C3-6 cycloalkyl-carbonyl; amine; or heterocyclic; or two such groups together with the atom to which they are 7 may form a five or six membered ring; and: halo, Cl_6 Affiliation; Cl, 6 alkoxy; halo-Ck alkyl; or _yl-C alkoxy. 4. A compound of the formula 3, wherein m is hydrazine or 1 〇 5. A compound of the formula 3, wherein X is -NRa- or -Ο-. 6·如. The compound of claim 3, wherein X is _NRa. 7. A compound of claim 3, wherein R1 is a Cu alkyl group. 8. A compound of claim 3, wherein ^ is: a functional group; a dentate base -6 alkyl group; or a cyano group. 9. The compound of claim 3, wherein r2 is: chloro, trimethyl or nitrogen. 1〇· For example, the compound of claim 3, wherein R3 is: a functional group; or _〇R4. U. The compound of claim 3 wherein R3 is: -yl; CN6alkoxy; or halo-Ci-6alkoxy. 12. The compound of claim 3, wherein R3 is: decyloxy; chloro; or fluoro. The compound of the term 3, wherein m is 1 and R7 is halo or methoxy. 14. The compound of claim 3, wherein R5 and R6 together with the nitrogen atom to which they are attached form, as the case may be, three to one member I selected from the other hetero atom of 〇, N and S, and the Two or three groups independently selected from 'substituents. Cu alkyl, halo-Cl.6 alkyl, ^6 alkoxy, dentate-C!.6 alkoxy, hydroxy, hydroxy-Cl_6 Alkyl, dentate, nitrile 匚1_6 phenanthrenyl, Cw alkyl-transyl, C3·6 cycloalkyl, c3 6 decyl-Ci 6 alkyl, Cw cycloalkyl-carbonyl, amine Or a heterocyclic group, or 156325.doc 201202215 Two members of the 5 hai group and the like are connected to them. Four /, /, depending on the atom, can form five or six rings. The compound of claim 3, wherein R4R6, together with the nitrogen atom to which it is attached, forms a morphyl group, which is optionally substituted with a group selected from the group consisting of -C.6 alkyl, halo-Cl 6 alkyl, Ci 6 alkoxy, dentyl hydrazine 6 alkoxy, meridyl, thiol-Ci6 alkyl, dentyl, guess, alkyl-carbonyl, Cl. 6 alkyl-sulfonyl, Cm ring Alkyl, c36 cycloalkyl-Cm alkyl, Gw cycloalkyl-carbonyl, amine or heterocyclic, or the two groups together with the atom to which they are attached may form a five or six membered ring. 16. The compound of claim 3, wherein the compound has sin: III where: P is 0 to 2; although P is 1 or 2, Y is:; _s(〇)n_ ; _NRio ; or _criiri2_ : and when p is 0, γ is _CRUR12-; R and R9 are Independently: hydrogen; Cu alkyl; halo-Ci 6 alkyl; G·6 alkoxy; halo-Cl. 6 alkoxy; hydroxy; hydroxy-Ci6 alkyl; halo, nitrile; Cw alkyl-carbonyl; Cw alkyl-sulfonyl; c36 cycloalkyl; C3. 6 cycloalkyl-C 6 alkyl; eg 6 cycloalkyl aryl; amine; or heterocyclyl; or R 8 and R 9 together with the atom to which they are attached form a five or six membered ring; 156325. Doc 201202215 R is. Hydrogen; Ci-6 alkyl; via -C!-6 alkyl; halo-匸16 alkyl, hydroxy-Cw alkyl, Cw alkyl-carbonyl; c16 alkyl sulfonyl; C3·6 ring Base, C3. 6 ring alkyl-Cw alkyl; C3. 6 Cyclocarbyl ketone; cyclyl; or heterocyclyl-Cl-6 alkyl; or one of R8 and R9 together with the ruthenium (7) and the atom to which it is attached form a five or six membered ring; R11 is : hydrogen; Ci-6 alkyl; or halogen; R12: hydrogen; Cw alkyl, halo-Cl_6 alkyl; alkoxy; halo-C!-6 alkoxy; hydroxy; hydroxy-c ]_6 alkyl; halo; guess; base - several groups; C!. 6 alkyl-sulfonyl; C3-6 cycloalkyl; c36 cycloalkyl.   C!-6 alkyl; C3_6 cycloalkyl-carbonyl; amine; heterocyclic; or heterocyclyl Ck alkyl; can be formed as appropriate or R11 and R12 and the atom to which they are attached are selected from 0, N And a three- to six-membered ring of a hetero atom of S; the sub-forms form one of five or R8 and R9 with Ri〇 and its original or six-membered ring; and R12 and its attached or R8 and R91 One or six member rings; and the atoms together form five 17.  18.  19.  20.   For example, m'n, X, Ri, and R2HR7 are the compounds of item 3 as claimed herein, wherein 卩 is jade. A compound of claim 3, such as the compound of claim 3, wherein Y is -0-. A compound according to any one of claims 1 to 2, defined or -CRnR12- which is selected from the group consisting of 156325. Group of doc -10- 201202215: 5-chloro-4-(5-chloro-4-methylamino-indolyl-2-ylamino)-2-decyloxy-benzylamine, 5-air-4 -(5-Galo-4-indenyl dimethyl-2-ylamino)-N-(2-trans-ethyl)-2-methoxy-benzylamine, 5-chloro-N-cyclo Propyl-2-methoxy-4-(4-amidino-5-trifluoromethyl-carcinoma π-denyl-2-ylamino)-tuberamine, ((2S,6R)-2,6 -Dimethyl(indole-morpholinyl))(2-fluoro-5-decyloxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino) Phenyl) anthrone, (18,43)-2-oxa-5-azabicyclo[2. 2. 1]Heptane-5-yl(2-fluoro-3-indolyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)indole Ketone, (lS, 4S)-2-oxa-5-azabicyclo[2. 2. 1]Heptane-5-yl(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-indolylphenyl) hydrazine (2,6-Dimercapto-morpholin-4-yl)-[3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -Phenyl]-methylnet, (2-ethoxy-5-fluoro-4-(4-(decylamino)-5-(trifluoromethyl)-anthracene-2-ylamino)phenyl) (N -Merlinyl) formazan, (2-fluoro-3-isopropoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl) ( N-Merlenyl) A-, (2-fluoro-3-isopropoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl) (N-Merline) A-, (2-fluoro-5-methoxy-4-(4-(2-methoxyethoxy)-5-(trifluoromethyl) 156325. Doc • 11 - 201202215 pyrimidin-2-ylamino)phenyl)(N-morpholinyl)fluorenone, (2-fluoro-5-methoxy-4-(4-(methylamino)-5-) (trifluoromethyl)pyrimidinylamino)phenyl)(3-methoxypyrrolidin-1-yl)anthone, (3-methoxy-4-(5-methoxy-4-(oxime) Amino) oxy-2-ylamino)phenyl)(N-morphinyl)methanone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidinyl) 2-fluoro-3-methoxyphenyl)(N-morpholinyl)methanone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidine-2-ylamino) _2_Fluoro_3_isopropoxyphenyl)(N-morphinyl)fluorenone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidine-2-ylamine) —(3-(trifluoromethoxy)phenyl)(N-morpholinyl)fluorenone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidine-2-yl) Amino) 3-(trifluoromethoxy)phenyl)(N-morphinyl)indole, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidinyl-amino) )_3_isopropoxyphenyl)(N-noryl)methanone, (4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)_3_ Isopropoxyphenyl)(N-morpholinyl)methanone, (4-(4-(ethylamine) -5-(Trifluoromethyl)pyrimidine-2-ylamino)-5-fluoro-2-indoxyphenyl)(N-morpholinyl)methanone, (4-(4-(methylamine)) -5-(Trifluoromethyl)pyrimidine-2-ylamino)_3_(trifluoromethoxy)phenyl)(N-morphinyl)fluorenone, (4-(5-bromo-4-)曱 嘧啶 _2 _ _ _ ) ) ) ( 3 3 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (Methylamino)pyrimidine_2-ylamino)_3_nonylphenyl)(]^_?156325. Doc -12- 201202215 吓基)甲甲,(4-(5-Gas-4-(4-Amino)pyrimidin-2-ylamino)-3-indolylphenyl)(4-hydroxypiperidine- 1-yl)methanone, (4-(5-chloro-4-(piperidin-1-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)(N-morpholinyl)- Ketone, (4-(5-chloro-4-(-pyrrolidin-1-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)(N-morphinyl)methanone, ( 4-(5-Vethyl-4-methoxypyrimidin-2-ylamino)-3-methoxyphenyl)indole-1-butyr-1-yl)methanone, (4-(5-cyclopropyl) _4_曱-oxypyrimidin-2-ylamino)-3-methoxyphenyl)(N-morpholinyl)methanone, (4-{5-chloro-4-[(tetrahydro-furan-) 2-ylmethyl)-amino]-pyrimidin-2-ylamino}-3-methoxy-phenyl)-morpholin-4-yl-methanone, (4-{5-chloro-4- [(tetrahydro-furan-3-ylmethyl)-amino]-pyrimidin-2-ylamino}-3-methoxy-phenyl)-L- _4-yl-ketone, (4- Dimethylamino-piperidine-1_yl)-[3_decyloxy_4-(4-methylamino-5-trifluoromethylpyrimidin-2-ylamino)-phenyl]•曱Ketone, (4-tert-butyl-piperidine-1-yl)-[4·(5-gas_4_methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl] - fluorenone, (5-Chloro-2-indolyl-4-(4-(decylamino)·5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl) (full deuterated (Ν-morpholinyl) )) A, (5-chloro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(3-methoxy Pyrrolidine_1-yl)methanone, (5-chloro-4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)_2_methoxybenzene 156325. Doc -13· 201202215 base)(N-morpholinyl)fluorenone, (5-fluoro-2-decyloxy_4_(4_(decylamino)_5_(tri-methyl) mouth bite_2_ylamine Phenyl)(N-morphinyl)fluorenone, [2-ethane-4-(5-aero-4-methylamino-pyrimidin-2-ylamino)_5_decyloxy-phenyl] - 淋-4-yl-indole, [2-chloro-5-methoxy-4-(4-decyloxy-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl] -Merlin-4-yl-carbamidine, [2-chloro-5-methoxy-4-(4-methylamino-5-trifluoromethyl-penetrating 2-amino)-phenyl ]-Molin-4 -yl-methyl copper' [2_fluoro-3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyridin-2-ylamino)-benzene []]-morpholin-4-yl-fluorenone, [2- gas-5-methoxy-4-(4-methylamino-5-trifluoromethyl- sylphidine-2-amino) -phenyl]-morpholin-4-yl-fluorenone, [2-fluoro-5-methoxy-4-(4-methylamino-5-trifluoromethyl-pentidine-2-ylamine) ))-phenyl]-((S)-2-decyloxymethylpyrrolidine-1-yl)-fluorenone '[3-(2-fluoro-ethoxy)_4_(4-methylamino) -5-trifluoromethyl-deni-2-ylamino)-phenyl]-morpholine-4-yl-methanone, [3-bin-4-(4-methylamino-5-trifluorofluorene) Base-pyrimidine_2-ylamino)-phenyl]_ -4-yl-methanone '[3_,; odor-4-(5-chloro-4-methylamino-octylamino)-phenyl]-oxalin-4-yl-fluorenone, [3 _Chloro_4_(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-oxalin-4-yl-methanone, [3 - gas - 4- (5 -Chloro-4-methoxy_°D-D-2-ylamino)-phenyl]-Merline Μ • 14- ι 56325. Doc 201202215 base-fluorenone, [3-chloro-4-(5-chloro-4-methylaminoindol-2-ylamino)-phenyl]-morphin-4-yl-ketone, [3- Cyclobutoxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone, [3-cyclobutylmethoxy 4-(4-amido-5-trifluoromethyl guanidino-2-ylamino)-phenyl]]morpholin-4-yl-fluorenone [3-cyclopropyl-4- (4-Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone, [3-cyclopropylmethoxy-4-( 4-nonylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-fluorenone, [3-ethoxy-4-(4-decylamine) 5--5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-infrared--4-yl-methylhydrazine [3-isopropoxy-4-(4-methylamino)- 5-trifluorodecyl-pyrimidin-2-ylamino)-phenyl]-morphin-4-yl-fluorenone, [3-methoxy-4-(4-methoxy_5_propyl- 1-alkynyl-pyrimidin-2-ylamino)-phenyl]-morphin-4-yl-enthalin|, [3-methoxy-4-(4-methoxy-5-trifluoromethyl) _-pyrimidine_2•ylamino)phenyl]- 吓-4-yl-methyl-, [3-methoxy-4-(4-f-amino-5-propynyl-pyrimidine) 2_ylamino)) phenyl]-? -基-甲酿], [3-methoxy-4-(4-amidino-5-trifluoromethyl]pyrimidin-2-ylamino)phenyl]- Ketofluorenone, [3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzene 156325. Doc •15- 201202215 base]-(8-oxa-3-aza-bicyclo[3. 2. 1] oct-3-yl)-fluorenone, [3-methoxy-4-(4-methylamino-5-difluoromethyl-methyl)-phenyl-2-ylamino)-phenyl ]-(2-oxa-5-aza-bicyclo[2. 2. 1]hept-5-yl)-fluorenone, [3-methoxy-4-(4-methylamino-5-disindolyl-mouth-2-ylamino)-phenyl]-.比明〇-1 -yl-曱嗣, [3 -methoxy-4-(4-methylamino-5-di-methyl- σ-D-amino-2-yl)-phenyl] -[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-methanone, [3-methoxy-4-(4-methylamino-5-dioxa) Benzyl succinyl-2-ylamino)-phenyl]-(4-methoxy-piperidin-1-yl)-methanone, [3-methoxy-4-(4-pyrrolidine-1 -yl-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morphine-4-yl-carbamidine [4-(4-ethylamino-5-trifluoromethyl-) Pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]·•morpholin-4-yl-fluorenone, [4-(4-ethylamino-5-dimethylmethyl) - σ-Butyl-2-ylamino)-2-a-5-methoxy-phenyl]-((S)-2-methoxymethylpyrrolidin-1-yl)-methanone, [4-(5 -> odor-4 -ethoxy-^-Butyl-2-ylamino)-3-decyloxy-phenyl]-oxalin-4-yl-indole, [4- (5 -> odor-4 -isopropoxy- lysyl-2-ylamino)-3-methoxy-phenyl]-morphin-4-yl-fluorenone, [4-(5 -bromo-4-indolyl-pyrimidin-2-ylamino)-2-chloro-5-decyloxy-phenyl]-morpholin-4-yl-fluorenone, [4-(5-bromo- 4-decyloxy-pyrimidin-2-ylamino)-2-fluoro-5-decyloxy-phenyl]-morpholine- 4-yl-fluorenone, [4-(5-&gt; odor-4-曱乳-σ 密-2-ylamino)-3-3⁄4 butyloxy-phenyl]- 156325. Doc -16- 201202215 琳林-4-yl-fluorenone, [4-(5-bromo-4-methoxy-pyrimidin-2-ylamino)-3-cyclopropoxy-phenyl]-? Lin-4-yl-fluorenone, [4-(5- desert-4-methyl-based-D-densyl-2-ylamino)-3-ethoxy-phenyl]- Keto-ketone, [4-(5-&gt; odor-4-oxime-sigmine-2-ylamino)-3-isopropoxy-phenyl]- morphin-4-yl- Anthrone, [4-(5 -" odor-4-曱乳-°3⁄4唆-2 -ylamino)-3-methoxy-phenyl]_ ❹ ((R)-2,2-di -deuterated-3-methyl-morpholin-4-yl)-indolone, [4-(5-bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-benzene Base]-((S)-2,2-di-aryl-3-indolyl-morphin-4-yl)-anthracene [4-(5-&gt;odor-4-methoxy-. Bite-2-ylamino)-3-decyloxy-phenyl]-(3-morpholin-4-yl-azetidin-1-yl)-fluorenone, [4-(5-bromo) -4-decyloxy-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4,4-di-n-yl-1-yl)-carboxamidine, [4-(5 -&gt; odor-4-oxime _ lymid-2-ylamino)-3-decyloxy-phenyl]-(4_ethyl-tour 嗓 1 -yl)- formazan, [4 -(5-bromo-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-[4-(1-light Base · 1-mercapto-ethyl) - brig. Ding-1 -yl]-brewing I '[4-(5 -&gt; odor-4-methoxy-. dimethyl 17-yl-2-ylamino)-3-methoxy-phenyl]- Lin-4-yl-methanone, [4-(5-bromo-4-indolyl-pyrimidin-2-ylamino)-3-indolyloxy-phenyl]-intimidation - 4 ·yl-A嗣5 [4-(5-Bromo-4-indolyl-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-[4- 156325. Doc -17- 201202215 (1_Phenyl-1 -methyl-ethyl)-Liaodian-1_基]&quot;曱嗣, [4-(5 -&gt; Odor-4-Methylamino-. Ding-2-ylamino)-3-decyloxy-phenyl]-(3-trifluorodecyl-pyrrolidin-1-yl)-methanone, [4-(5-&gt;odor-4 Methylamino-mercapto-2-ylamino)-3-indolyl-phenyl]-(4-cyclobutyl-piperazin-1-yl)-fluorenone, [4-(5-&gt; 4-Methylamino-.Methoxy-2-ylamino)-3-decyloxy-phenyl]-[4-(2,2,2-digas-ethyl)-Brigade-1- [4-(5-bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-decyloxy-piperidine-1 -yl)-methanone, [4-(5-&gt; odor-4-anthranyl-bine-2-ylamino)-3-hydrazino-phenyl]_((R)-3- Rhodamine-σ ratio 定.-1 -yl)-A-side I ' [4-(5 -&gt;odor-4 -nonylamino-.succinyl-2-ylamino)-3-decyloxy -phenyl]-(4_oxetan-3-yl-piperazin-1-yl)-fluorenone, [4-(5-bromo-4-indolyl-pyrimidin-2-ylamino) -5-chloro-2-indolyl-phenyl]-morphine-4-yl-methyl-3 with '[4-(5-gas-4-3⁄4 butylamino--methion-2-ylamine) ))-3-methoxyphenyl]-? scare ^ - 4 -yl-曱嗣[4-(5-Gas-4-3⁄4-hexylamino-indolyl-2-ylamino)-3-methyllacyl-phenyl]-Nolidine-4-yl-曱嗣^ [4-(5 - 鼠-4 - 哀 戊 yl ylamino-. succinyl-2-ylamino)-3 - fluorenyl-phenyl]- 吓 ^ ^ - 4 - yl- 曱 明 5 [4-(5 - gas-4 -ethoxy-. dimethyl-2-ylamino)-3-hydrazino-phenyl]-morpholin-4-yl-methanone, [4-(5-gas-4 -ethylamino-N.-denyl-2-ylamino)-2-rat-5-methoxy-benzene 156325. Doc -18- 201202215 base]-morpholin-4-yl-methanone, [4-(5-chloro-4-ethylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl; Μmorpholin-4-yl-methanone, [4-(5-gas-4-isobutylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-morpholine-4 -yl-ketone, [4-(5-gas-4-isopropoxy-pyrimidin-2-ylamino)-3.nonyloxy-phenyl]-morpholin-4-yl-methanone, [4-(5-Chloro-4-isopropylamino-pyrimidin-2-ylamino)-3-decyloxy-phenylindolomorph-4-yl-methanone, [4-(5-chloro- 4 - 曱 基 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -曱oxy-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-morpholine-4-yl-methanone, [4-(5-Ga-4-indole-pyrimidine- 2-ylamino)-2-fluoro-5-decyloxy-phenyl]-morpholin-4-yl-methanone, q [4-(5-chloro-4-nonylamino-pyrimidin-2- Amino)-3-(2,2,2-trifluoro-ethoxy)-phenyl]-morphine-4-yl-indene|, [4-(5-a. -pyrimidin-2-ylamino)-3-(oxetan-3-yloxy)-phenyl]-morpholin-4-yl-fluorenone, [4-(5-qi-4-曱) Amino-pyrimidin-2-ylamino)-3-cyclobutoxy-phenyl]- Phenyl-4-yl-fluorenone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-3-cyclopentyloxy-phenyl]-(2-oxa-6 -aza-spiro[3·3]hept-6-yl)-fluorenone, [4-(5-a-4-nonylamino-pyrimidin-2-ylamino)-3-cyclopentyloxy- Phenyl]- 156325. Doc . 19- 201202215 Morpholin-4-yl-methanone, [4·(5-lacty-4-methylamino- η-Minidine-2-ylamino)-3-3⁄4-propyl-phenyl]- Morpholin-4-yl-methanone, [4-(5-chloro-4-indolyl-σ-amyl-2-ylamino)-3-thysyl-phenyl]-morpholine-4 -yl-fluorenone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-3-difluoromethoxy-phenyl]-morpholin-4-yl-fluorenone , [4-(5-chloro-4-indolyl- σ-amyl-2-ylamino)-3-dimethoxymethyl-phenyl]-(4-trans-radical-yl-yl) )--ketone, [4-(5-a, 4-aminoamino-^^-2-ylamino)-3-ethyllacyl-phenyl]-morphin-4-yl-fluorenone, [ 4-(5-Gas-4-methylamino-σ-denyl-2-ylamino)-3-carbo-phenyl]-morphine*~ 4-yl-fluorenone, [4-(5- Chloro-4-indolyl-.denidyl-2-ylamino)-3-isopropoxy-phenyl]_ 兮木-4-yl-indole, [4-(5-chloro- 4-nonylamino-.denyl-2-ylamino)-3-methyllacyl-phenyl]-morphin-4-yl-fluorenone, [4-(5-gas-4-decylamine) --ρ密定定-2-ylamino)-3-decyloxy-phenyl]-(4-carbyl-Nymidine-1 -yl)-fluorenone, [4-(5-gas- 4-nonylamino-t-densidine 2-amino-amino)-3-methoxy-phenyl]- (octahydro-pyridinium [1,2-a]pyrazine-2-yl)-methanone, [4-(5-murine-4-methylamino-mouth succinyl-2-ylamino)-3 -heteroyl-phenyl]-(2-hydroxy-piperidin-1-yl)-methanone, [4-(5-a -4-aminoamino-α-succinyl-2-ylamino) -3 -decyloxy-phenyl]_ 156325. Doc -20- 201202215 (4,4-Dimethyl-Big 定-1-yl)-fluorenone' [4-(5-Gas-4-methylamino-pyrimidin-2-ylamino)-3 -nonyloxy-phenyl]-(3,5-dimercapto-piperidin-1-yl)-methanone [4-(5-chloro-4-indenylamino)-2-ylamino )-3-methoxy-phenyl]-[4-(1-hydroxy-1-indolyl-ethyl)-piperidin-1-yl l-methanone [4-(5-gas_4_) Methylamino-pyrimidin-2-ylamino)-3-methoxyphenyl]-(3-hydroxy-pyrrolidin-1-yl)-methanone, [4-(5-chloro-4-methyl) Amino-°3⁄4°-2-ylamino)-3-decyloxy-phenyl]-(4-indolyl-piperidin-1-yl)indolone, [4-(5-gas- 4-曱Amino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-piperidin-1-yl-fluorenone, [4-(5-chloro-4-ylamino-pyrimidine) -2-ylamino)-3-methoxy-phenyl]-(4,4-difluoro-derivative-1-yl)-carboxamidine, [4-(5·gas-4-methylamine) -Pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(3-indolyl-piperidin-1-yl)-anthracene, [4-(5-Ga-4-indoleamine) -pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-decyloxy-piperidinyl-1-yl)-methanone, [4-(5-chloro-4_- Amino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3,3-difluoro-piperidine-indenyl)-A Ketone, [4-(5-chloro-4-ylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4-fluoro-nivine. _, [4-(5-Gas_4_Methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-methoxycindin-1-yl)- Ketone, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-(4- 156325. Doc -21 · 201202215 Ethyl-Broadenol-1 -yl)-anthracene, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_methoxy-phenyl] _(3_Trifluorodecyl-Brigade-1-yl)-methanone, [4-(5-chloro-4-indolyl-pyridin-2-ylamino)_3_methoxy-phenyl ]_[4_(2-Phenyl-ethyl)-η- bottom 嗓-1-yl]-fluorenone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_曱oxy_phenyl phenyl (2_ fluorenyl-D than fluoren-1-yl)-methyl, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_A Oxy-phenyl]-(4_ thiol-Octo-1-yl)-methanone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_曱Oxy-phenyl]-(2_ fluorenyl-ninnium-1 -yl)-indole, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_decyloxy _Phenyl] than ^^-1-yl-methanone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_decyloxy-phenyl]_(4_ A烧石黄醯基-11底唤-1 -基)_甲甲, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy_phenyl]_(3_ Trimethyl-methyl-0 to ^^-1-yl)-methanone, [4-(5-aza-4-nonylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]_ [4-(2,2,2-trifluoro-ethyl) Peptazine-i-yl]-fluorenone, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-methyl-吗琳-4-yl)-曱嗣, [4-(5-chloro-4-hydrazino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]-(2,6-dimethyl (4-(5-chloro-4-hydrazino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]- 156325. Doc •22- 201202215 (2,2-Diethyl-morphin-4-yl)-A, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_A Oxy-phenyl]-(3_ fluorenyl hydrazin-4-yl)-A class, [4-(5-Ga-4-indole-pyrimidin-2-ylamino)_3_methoxy -Phenyl]-(2-isobutyl-morpholin-4-yl)-methanone, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)_3_methoxy _Phenyl]-(2-hydroxymethyl-morphin-4-yl)-methanone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_decyloxy_ Phenyl]_ I1 (3,3-dimercapto-morpholin-4-yl)-methanone, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)_3_A Oxy-phenyl]-(4-methyl-piperazin-1-yl)-methanone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_methoxy _Phenyl]-(4_isopropyl-p-but-1-yl)-曱明, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)_3_methoxybenzene Base]_piperidinyl-1-yl_brew I, Q [4-(5-chloro-4-methylamino-indolyl-2-ylamino)-3-methoxy-phenyl]- (3-oxa-8-aza-bicyclo[3. 2. 1] octyl-8-yl)-methanone, [4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((S)- 3-methyl-morphin-4-yl)-methanone, [4-(5-a-4-phenylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-( 2-oxa-5-aza-bicyclo[2_2. 1]heptyl-5-yl)-methanone, [4-(5-aza-4-nonylamino-pyrimidin-2-ylamino)_3_decyloxy-phenyl]_(8_oxa-3 -aza-bicyclo[3. 2. 1] oct-3-yl)-methyl-, [4-(5-chloro-4-hydrazino-pyrimidin-2-ylamino)_3_methoxy-phenyl]- 156325. Doc •23· 201202215 ((R)-3-methyl-Mouth _4·yl)_methanone, [4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)_3 A Oxy-phenyl]-(4-cyclopropanecarbonyl-piperazine-indolyl)-methanone, [4-(5-gas-4-methylamino-pyrimidin-2-ylamino)_3 methoxy -phenyl]-(3_morphinyl-azetidin-1-yl)-methanone, [4-(5-lacty-4-methylamino-pyrimidin-2-ylamino)_3_A Oxy-phenyl]-[4_(1-methyl-piperidin-4-yl)-piperazin-1-yl]-indolone, [4-(5-chloromethylamino-pyrimidin-2-ylamine) Alkyloxy-phenyl]-(3,3-difluoro-indolebutan-1-yl)-methanone, [4-(5-chloro-4-methylamino-pyrimidin-2-yl) Amines &gt; 3_decyloxy-phenyl]-(4-dimethylamino-piperidin-1-yl)-fluorenone, [4_(5-chloro, 4-methylaminopyrimidin-2-yl) Amino)-3-indolyl-phenyl]-(4-piperidinyl-4-yl, piperazin-1-yl)-fluorenone, [4_(5-('-' 4-methylamino-pyrimidine- 2-ylamino)-3-indolyl-phenyl]-(2-oxa-6-aza-spiro[33]heptyl-6-yl)-anthrone, [4-(5-armor) Amino-pyrimidin-2-ylamino)_3_trifluoromethoxy-phenyl]-oxalin-4-yl-fluorenone, [4-(5-chloro, 4-propoxy-pyrimidine) _基胺基)_3_曱_Phenyl]? Lin-4-yl-methyl-j, [4-(5-chloro-4-propylamino-pyrimidin-2-ylamino)-3-decyloxy-phenyl]-?淋-4-yl-methyl-, [4-(5-cyclobutylmethoxy-pyrimidin-2-ylamino)_3_decyloxy-phenyl]-Nol-4, ketone-ketone, [4 -(5-Cyclobutyl-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-benzene 156325. Doc -24- 201202215 base]-morpholine_4-yl-ketone, [4-(5-3⁄4propyl-4-methylamino-mouth.dent-2-ylamino)-3 -anthracene -phenyl]-oxalin-4-yl-propene, [4-(5-3⁄4propyl-4-methylamino-s-amyl-2-ylamino)-3-methoxy-phenyl ]-morpholin-4-yl-fluorenone, [4-(5-a 4-amino-amino-anthracene-2-ylamino)-3-decyloxy-phenyl]-morpholine- 4-yl-fluorenone, [4-(5-aza-4-nonylaminomercapto-2-ylamino)-3-indolyl-phenyl]-(4-^hydroxy-piperidine-1 -yl)-fluorenone, [4-(5-indol-4-yloxy-.succinyl-2-ylamino)-3-methoxy-phenyl]-?咐^ - 4 -yl - 曱西同, [4-(5-峨-4-Methylamino) dimethyl-2-ylamino)-3-methyllacyl-phenyl]-morphin-4-yl-fluorenone, [ 4-[5-Chloro-4-(2-decyloxy-ethylamino)-° dense. -2--2-ylamino]-3-(2,2,2·trifluoro-ethoxy)-phenyl]-?-lin-4-yl-methyl-Ten 0 [5· disorder-2-ethoxy 4-(4-amidino-5-dimethylhydrazinyloxyl-2-ylamino)-phenyl]-morpholin-4-yl-methanone, [5-chloro-2-indole Oxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-pyridinium-9-yl-methanone[5-gas-2-曱L--4-(4-amido-5-disorganinyl-.denyl-2-ylamino)-phenyl]-(2,6-dimethyl-morpholine-4- ())-fluorenone, [5-gas-2-methoxy-4-(4-amidino-5-dioxamethyl-)-denyl-2-ylamino)-phenyl]- Phenyl-4-yl-methanone, [5-gas-4-(4-ethylamino-5-dioxamethyl- thio-diethylamino)-2 -hydrazine 156325. Doc -25- 201202215 base-phenyl]-? scare ^ - 4 -yl-曱嗣' [5·gas-4-(5-gas_4_ethylamino-min.din-2-ylamino) -2·methoxy-phenyl]-morpholin-4-yl-fluorenone, [5-gas-4-(5-gas-4-hydrazino-]-denyl-2-ylamino) -2-decyloxy-phenyl]-oxalin-4-yl-fluorenone, [5-chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-曱oxy-phenyl]- 吓 * * - 4 -yl-indole, [5 - qi-4-(5 - qi-4- oxime--- sigma- 2 -ylamino)-2 -methoxy-phenyl]-(4,4-difluoro-piperidin-1-yl)-fluorenone, [5-gas-4-(5-gas-4-methylamino--dense- 2-aminoamino)-2-indolyl-phenyl]-piperazin-1-yl-fluorenone, [5-gas-4-(5-a-4-pyramino-------- 2-aminoamino)-2-indolyl-phenyl]-(4-diguanylamino-piperidin-1-yl)-fluorenone, [5-gas-4-(5.murine-4-曱 基 - 定 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 5 5 5 [ [ 5 [ [ 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-2-methoxy-phenyl]-. Ratio of -1 -yl-carboquine' [5-gas-4-(5-azino-4-nonylamino succinyl-2-ylamino)-2-methoxy-phenyl]-( 4-罗坐基-略.定-1-基)-曱嗣' [5-Gas-4-(5-Ga-4-indole-- dimethyl-2-ylamino)-2- Methoxy-phenyl]-(2-hydroxyindolyl-morpholin-4-yl)-fluorenone, [5-gas-4-(5-gas-4-hydrazino-mouth] Amino)-2-methoxy-phenyl]-[1,4]oxazepan-4-yl-fluorenone, [5-gas-4-(5-gas-4-A) Amino-.M. 17-denyl-2-ylamino)-2-methoxy-benzene 156325. Doc -26- 201202215 base]-((2R,6S)-2,6-diamidino-morpholin-4-yl)-fluorenone, [5-chloro-4-(5-chloro-4-methylamine) -pyrimidin-2-ylamino)-2-decyloxy-phenyl]-(3-hydroxy-azetidinyl)-methanone, [5-gas-4-(5- Chloro-4-indolyl-pyrimidin-2-ylamino)-2-indolyl-phenyl]-((3R,5S)-diindolyl-piperazin-1-yl)-methanone, [ 5-ethoxy-2-fluoro-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morphin-4-yl-methyl-, [ 5-ethoxy-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2- phenyl-phenyl]-morphin-4-yl-methyl, { 4-[5-bromo-4-(2-methoxy-ethoxy)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morphin-4-yl-methanone, {4-[5-Bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-2-fluoro-5-decyloxy-phenyl}-morpholin-4- Keto-one, {4-[5-bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-ethoxy-benton}-? -yl-methyl, {4-[5-bromo-4-(2-decyloxy-ethylamino)-pyrimidin-2-ylamino]_3_isopropoxy-benyl]-- -4 -yl-indene copper, {4-[5-bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamine ]-3-methoxy-benzyl}-morphine-4-yl-ylamine, {4-[5-chloro-4-(1-methyl-cyclobutylamino)pyrimidine-2-yl Amino]_3_decyloxy-phenyl}-oxalin-4-yl-indole, {4-[5-chloro-4-(2,2,2-trifluoro-ethylamino)-pyrimidine_ 2_ylamino]_3_曱lacyl-phenyl]·- 吓 & -4- -4--4-yl-曱嗣, Η-[5-gas_4_(2,2-difluoro-ethylamino)· Mouthidine 2_ylamino]-3-methoxy 156325. Doc -27- 201202215 基-本基}-? scare ^ - 4 -yl-brew I, {4-[5-chloro-4-(2-cyclopropyl-ethylamino)-pyrimidine_2-yl Amino]_3_methoxy-benyl}-morphin-4-yl-carboxamidine, {4-[5-chloro-4-(2-methane hydrazino-ethylamine)-pyrimidine_2_ Amino group]_3_methyllacyl-benzyl}-nor-p--4-indolone, {4-[5-chloro-4-(2-decyloxy-ethoxy)-pyrimidine_2-yl Amino]_3_cyclobutoxy&quot;benzin}-Merlin·4-yl-carbamidine, {4-[5-gas-4-(2-methoxy-ethoxy)-pyrimidine_2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Aminoamino]-3-cyclobutoxy-benyl}-nor--4-yl-indole, {4-[5-chloro-4-(2-foxy-ethylamino)-pyrimidine _2_ylamino]_3_decyloxy-benzyl]-morphine-4-yl-indole, {4-[5-chloro-4-(2-methoxy-propylamino)-n-density . _2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ . _2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _密-_2-ylamino]-3-decyloxy-benyl}-morphine-4-yl-曱嗣' {4-[5-chloro-4-(cyclopropyldecyl-amino) -Mouth π定_2_ylamino]]3-methoxy-phenyl}-morphin-4-yl-fluorenone, {4-[5-gas- 4- (tetrahydro-β-f. 3-aminoamino)-. Bite 2_ylamino]_3_decyloxy-phenyl}-morphin-4-yl-ketone, {4-[5-chloro-4-(tetrahydro-σ bottom. South-3 - Amino group)-t&gt; dense bite 2_ylamino group]_3_曱156325. Doc -28- 201202215 oxy-phenyl}- 吓 - 4 -基-曱嗣 {4-[5 - 鼠- 4- (four mice - britan-4 - yloxy) - σ 密 - 2-aminoamino]-3-methoxy-phenyl}-morpholin-4-yl-fluorenone, 1-(4-(5-bromo-4-methoxypyrimidin-2-ylamino) -3-oxoxybenzyl) piperidine-4-carbonitrile, &quot; 1-[2-fluoro-5-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidine- 2-ylamino)-benzylindenyl]pyrrolidin-3-indrene, 1-[3-decyloxy-4-(4-methylamino-5-trifluorodecyl-pyrimidin-2-yl Amino)- 〇^ benzhydryl]-piperidine-4-carbonitrile, 1-[4-(5-bromo-4-indolyl-pyrimidin-2-ylamino)-3-methoxy- Benzyl hydrazide]-bite-4-carbonitrile, 1-[4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-benzylindolyl]- .定-4-section guess 1-[5-chloro-2-indolyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylindenyl] ratio L-bromo-3-indene nitrile, 1-[5-nitro-4-(5-wind-4-nonylamino-α-mercapto-2-ylamino)-2-methoxy-indenyl]- Piperidine-4-indene nitrile, 1-[5-chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-benzyl aryl]-π ratio洛咬-3-甲猜, — 1-{2-[2-methoxy-4-(morpholin-4-carbonyl)-anilino]-4-methylamino-pyrimidin-5-yl} - 乙,1_{4-[4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-indolyl-benzylindolyl]-pyrene-1 -yl}- Ethyl 2-(2-methoxy-4-(2,2,6,6-tetrafluoromorpholin-4-carbonyl)anilino)-4- 156325. Doc -29- 201202215 (Methylamino)pyrimidine-5-carbonitrile, 2-(2-decyloxy-4-(morpholin-4-carbonyl)anilino)_4_(decylamino)pyrimidine_ 5-A Nitrile, 2-(4-((3 S,4S)-3,4-difluoropyrrolidine β1-carbonyl) decyloxyanilino)-4-(methylamino)° cleavage-5-carbonitrile, 2-(4-(4,4-Difluoropiperidin-1-carbonyl)_2-methoxyanilino)_4_(methylamino)pyrimidine-5-carbonitrile, 2-[2,5-dimethoxy 4-(4-methylamino-5-trifluoromethyl-pain-2-ylamino)-phenyl]-1-morphin-4-yl-acetamidine, 2-[2-anthracene Oxy- 4-(morphin-4-yl)-anilino]_4-methylaminosuccinyl-5-carbonitrile, 2-[2-decyloxy-4-(Benter-1-carbonyl) )_anilino]_4_decylamine-bense-5-carbonitrile, 2-[2-methoxy-4-0-pyridyl-1-carbonyl)-anilino]_4_decylamine-pyrimidine _ 5 - Jiachao, 2-[3-decyloxy-4-(4-decylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-1-influenza-4 -yl-acetamidine, 2-[4-((2R,6S)-2,6-didecyl-morphin-4-yl)-5-fail-2-methyl-1-amino-anilino]- 4-Methylamino-pyrimidine-5-carbonitrile, 2-[4-((2R,6S)-2,6-dimethyl-morpholin-4-carbonyl)-5-fluoro-2-methoxy -anilino]-4-B -Pyridine-5-carbonitrile, 2-[4-((R)-3-fluoro-pyrrolidine-1-carbonyl)-2-methoxy-anilino]-4-methylamino-pyrimidine-5 -phthalonitrile, 2-[4-((S)-3-fluoro-indolyl-1-carbonyl)-2-methoxy-anilino]-4-methyl 156325. Doc • 30- 201202215 Amino-pyrimidine-5-carbonitrile, 2_[4_(3,3-difluoro-azetidin-1-carbonyl)-2-methoxy-anilino]·4-A Amino-η密定定_5_甲猜, 2-[4-(3,3-Difluoro-pyrrolidinium bcarbonyl)_2-methoxy-anilino]_4_decylamino-pyrimidine-5- Nitrile, 2-[4-(3-gas-azetidine+carbonyl)_2-methoxy-anilino]_4_methylamino-pyrimidine-5-indolecarbonitrile, 2-[4-(5- -4--4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl; μ 1-infrared-4-yl-ethanone, 2-[4-(5-bromo-4 -曱Amino-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]_ 1_?, scare, - 4 -yl-ethyl,|2-[4-(5-gas 4-methoxy-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1 -morphine-4-yl-acetamidine, 2-[4_(5-chloro- 4-decyloxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-1-oxa-4-yl-ethanone, 2_[4_(5- -4-pyramino) -pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1-morphin-4-yl-ethanone, 2-[4_(5-a 4-aminoamine- Pyrimidin-2-ylamino)-3-indolyl-phenyl]-1 -morphin-4-yl-ethanone, 2-[4-(azetidin-1-carbonyl)_2_曱Oxy-anilino]_4_methylamino -pyrimidine-5-carbonitrile, 2-1&gt;fluoro-2-methoxy_4-(morpholine-4-ylcarbonyl)-anilino]_4_nonylamino-pyrimidine-5-carbonitrile, 2-fluoro _5-Methoxy-indole-(2-methoxy-ethyl)-fluorenyl-mercapto-4-(4-methylamine 156325. Doc •31 - 201202215 yl-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylamine, 2-fluoro-5-methoxy-N-mercapto-4-(4-methylamino) -5-trifluoromethyl-pyrimidin-2-ylamino)-benzylamine, 2-fluoro-N-(2-hydroxy-2-methylpropyl)-5-methoxy-N-methyl 4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzamide, 3-methoxy-4-(4-amido-5-III Fluorinyl-pyrimidin-2-ylamino)-N-oxetan-3-yl-peptidylamine, 3-methoxy-4-(4-methylamino-5-trifluoromethyl -pyrimidin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-nodal amine, 3-methoxy-N-(2-methoxy-ethyl)-4 -(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylguanamine, 3-methoxy-N-(2-decyloxy-ethyl)-N- 4-(4-methylamino-5-trifluorodecyl-pyrimidin-2-ylamino)-nodal amine, 4-(4-ethylamino-5-disorganomethyl-°°° Di-2-ylamino)-2-a-5-indole-N-(2-methoxy-ethyl)-N-methyl-benzylamine, 4-(4-ethylamino- 5- 乱 甲基 - - 。 。 。 。 。 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- Trifluoromethyl-pyrimidine-2- Amino)-3-decyloxy-N-(2-decyloxy-ethyl)-N-methyl-benzylamine, 4-(5-chloro-4-(decylamino)pyrimidin-2- Amino, N,N,3-trimethylbenzylbenzylamine, 4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-3-methoxy-benzylamine, 4-(5-Chloro-4-indenyl-.-denyl-1-ylamino)-3-methyllacyl-N-(tetra-m-pyran-3-yl)-benzylguanamine, 156325 . Doc -32- 201202215 4-(5-Chloro-4-indolyl-pyrimidin-2-ylamino)-3-methoxy-indole, indole-dimercapto-benzylamine, 4-(5- Chloro-4-nonylamino-α-mercapto-2-ylamino)-3-methoxy-indole-indenyl-nodal amine, 4-(5-chloro-4-methylamino-pyrimidine-2 -ylamino)-3-methoxy-oxime-oxo-butan-3-yl-benzylamine, 4-(5-chloro-4-methylamino-.-Bite---amine ))-Ν-ί^propyl-3-methyllacyl — benzalkonium, 4-(5-chloro-4-indenyl-°3⁄4 0-diylamino)-indole-ethyl- 3-methyllacyl-nodalamine, 4-(5-chloro-4-indolyl-pain. 1,4-ylamino)-indole-isopropyl-3-methyllacyl-benzylamine, 4-(5-ranyl-4-ethylamino-ylamino)-2 -a-5-methyllacyl oxime, fluorenyl-dimercapto-benzylamine, 4-(5-enyl-4 - 曱 基 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Amino-pyrimidin-2-ylamino)-3-decyloxy-oxime, fluorene-dimethyl-benzylamine, 4-(5-enyl-4-pyridylamine-denyl-2-yl Amino)-3-methoxy-N-methyl- 'benzyl benzamide, 4-(5-carbyl-4-indolyl-sigmine-2-ylamino)-indole-(2, 2-diqi-ethyl)-3-A -benzylamine, 4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)-indole-(3,3-difluoro-cyclobutyl)-3-methoxy- Benzoylamine, 156325. Doc -33- 201202215 4-(5-Cyano-4-indolyl-pyrimidin-2-ylamino)-N,N-diethyl-3-methoxy-benzylamine, 4-(5 -Cyano-4-methylamino-pyrimidin-2-ylamino)-N-cyclopropylmethyl-3-decyloxy-benzylamine, 4-(5-murine-4-nonylamino - 1,4-β-ylamino)-N-ethyl-3- methoxy-benzylamine, 4-(5-murine-4-oxime-yl-. ))-Ν-ethyl-3-methoxy!-yl Ν-mercapto-benzylamine, 4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)-oxime-B Base-oxime-isopropyl-3-methoxy-benzylamine, 4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)-indole-isopropyl-3-indole Oxy-benzylamine, 4-(5-ranyl-4-indenyl- lysyl-2-ylamino)-indole-isopropyl-3-oxo-N-methyl- Benzylamine, 4-ethylamino-2-(5-Ga-2-oxo- 4-(?-lin-4-luyl)-anilino]_ αα定-5 -曱carbonitrile, 4- Methoxy-2-[2-indolyl-4-(morpholin-4-carbonyl)-anilino]-pyrimidine-5-indolecarbonitrile, 5-chloro-2-indolyl-4-(4- Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-N-(l-fluorenyl-piperidin-4-yl)-benzylamine, 5-azino-2-indole- 4-(4-amido-5 - succinylmethyl- lysyl-2-ylamino)-hydrazine-oxetan-3-yl-benzylamine, 5-chloro-2-indolyl-indole, fluorenyl-difluorenyl 4-(4-Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-nodal amine, 156325. Doc -34- 201202215 5-Chloro-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-decyloxy-N-(2-indolyl-B Base)-branched amine ' 5-chloro-4-(5-chloro-4-methoxypyrimidin-2-ylamino)-2-methoxy-N-methylbenzylamine, 5-chloro- 4-(5-Ga-4-indole-pyrimidin-2-ylamino)-2-methoxy-indole, indole-dimercapto-benzylamine, 5-Q-4-(5-gas 4-曱Amino-σ 咬2-ylamino)-2-methyllacyl-indole-(2-decyloxy-ethyl)-benzylamine, 5-chloro-4-(5-chloro 4-曱Amino-°Bitter-2-ylamino)-2-methoxy-oxime-methyl-benzylamine, 5-chloro-4-(5-chloro-4-nonylamino)- Mouth bit-2-ylamino)-2-decyloxy-oxime-oxetan-3-yl-benzylamine, 5-chloro-4-(5-chloro-4-methylamino-° Dimethyl-2-ylamino)-2-methyllacyl-N-(l-methyl-piperidin-4-yl)-benzylamine, 5-chloro-4-(5-chloro-4-methyl Amino-based succinyl-2-ylamino)-2-methoxy-indole-(2-methoxy-ethyl)-indenyl-benzyl-benzylamine, 5-chloro-4-(5-chloro 4-曱Amino-indole. Benz-2-ylamino)-2-decyloxy-N-(l-methyl-cyclobutyl)-benzylamine, 5-air-4-(5-gas -4-nonylamino-.Methoxy-based-2-ylamino)-N-(1-^l - propyl)-2-methoxy-benzylamine, 5-chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-N-(2-hydroxy-2 -Methyl-propyl)-2-decyloxy-benzylamine, 5-Nerve-4-(5-Gas-4-methylamino-.succinyl-2-ylamino)-N-( 2-hydroxy-ethyl)-2-methoxy-N-indenyl-benzylamine, 156325. Doc -35- 201202215 5 -Gas-4-(5-chloro-4-methylamino-β-deni-2-ylamino)-N-(2-propionyl-propyl)-2-methoxyl - decylamine, 5-chloro-4-(5-chloro-4-indolyl-pyrimidin-2-ylamino)-N-cyclopropyl-2-methoxy-nodalamine, 5-chloro -N-(l-cyano-cyclopropyl)-2-decyloxy-4-(4-methylamino-5-trifluorodecyl-pyrimidin-2-ylamino)-benzylguanamine, 5 - gas-N-(l-cyano-cyclopropyl)-2-methoxy-4-(4-guanidino-5-trifluoromethyl-mouth-2-amino)-branched Amine, 5-gas-N-(2-carbo-2-methyl-propyl)-2-decyloxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-yl Amino)-benzylamine, 5-chloro-N-(2-carbo-2-methyl-propyl)_2-methoxy-N-methyl-4-(4-methylamino-5- Dioxomethyl-penetrating-2-ylamino)_tuberamine, 5-gas-N-cyclopropyl-4-(4-ethylamino-5-trifluoromethyl-pyrimidine-2-yl Amino)-2-decyloxy-nodal amine, azetidin-1-yl-[4-(5-a-4-phenylamino-pyrimidin-2-ylamino)- 3 -A Oxy-phenyl]-indole, N-(3,3-fluoro-cyclobutyl)_3_methoxy_4_(4-nonylamino-5-trifluoromethyl guanidin-2-yl Amino)-tuberamine, N-(3-aminopropyl)- 4-(5-chloro-4-(decylamino)pyrimidin-2-ylamino)-3-oxooxybenzylamine, N-(3-amino-propyl)-4-(5-qi 4-曱Amino-pyrimidin-2-ylamino)-3-methoxy-tuberamine, N-(3-amino-propyl)-5_chloro_4_(5_chloro_4_ Methylamino-pyrimidin-2-ylamino)-2-indolyl-benzylamine, 156325. Doc -36- 201202215 c N-(4,4-Difluoro-cyclohexyl)-3-decyloxy-4-(4-nonylamino-5-trifluoromethyl-pyrimidin-2-ylamino) - decylamine, hydrazine, hydrazine-diethyl-3-methoxy-4-(4-amidino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzylguanamine, hydrazine- Ethyl-2-a-5-methoxy-indole-(2-methoxy-ethyl)-4-(4-amido-5-dimethylmethyl D-butylamino) )-N-ethyl-3-methoxy-N-mercapto-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-nodal amine , N-ethyl-4-(4-ethylamino-5-disindolyl-σ-stimuli-2-ylamino)-2- gas_ 5-oxime-oxime-(2-oxime Oxy-ethyl)-benzylamine, Ν-t-butyl-4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)-3-decyloxy-benzylamine , and Ν-di-dibutyl-5-gas- 4- (5-wind-4-methylamino-(dimethyl-2-methylamino)-2-methoxy-benzamide, or its pharmaceutical A salt that is acceptable for learning. O 21- A compound according to any one of claims 1 to 2, which is selected from the group consisting of: [3-methoxy-4-(4-amido-5-disorganomethyl-) Ding-2-ylamino)-phenyl]-oxalin-4-yl-fluorenone, (5-chloro-2-indolyl-4-(4-(methylamino)-5-(three Fluorinyl)pyrimidin-2-ylamino)phenyl)(full deuterated (Ν-morpholinyl))fluorenone, (5-fluoro-2-indolyl-4-(4-(methylamino) -5-(Trifluoromethyl)pyrimidin-2-ylamino)phenyl)(indolyl-morpholinyl)methanone, [2-fluoro-3-indolyl-4-(4-decylamino) -5-trifluoromethyl-pyrimidin-2-ylamine 156325. Doc -37- 201202215 yl)-phenyl]-morphin-4-yl-methyl-, [3-a-4-methylamino-2-ylamino)-phenyl bromide I-indenone, [3-isopropoxy ortho-methylamino-5-trifluoromethyl-indol-2-yl)-phenyl]-morphin-4-yl-methyl, [4-(4-B Amino-5-triterpene^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ , [4-(5-random-4-decyloxy·mouthcoat 〇glycan-2-ylamino)_3_decyloxy-phenyl]-morpholin-4-yl-methanone, [ 5-Chloro-2-methoxy-4-(4-methylad; Gan. 1Methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-Merlin-4-基-甲|同, [5-Gas-4_(4-ethylamino-5-dioxa-gas T-pyrimidine-2-ylamino)_2_decyloxy-phenyl]-Merlin-4 -yl-carbamyl, [5-ethoxy-2-fluoro- 4-(4-methylacetoin ^ w VT amine ·5_trifluoromethyl-pyrimidin-2-ylamino)-ben ]]-Molin-4-yl-A-, 2-(2-decyloxy-4-(inhaly 4 Α 3 -4--4-carbyl)anilino)_4_(methylamino)pyrimidine _ 5 -carbonitrile, and hydrazine-tert-butyl-4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)_3_decyloxy-benzyl Amine, or a pharmaceutically acceptable salt thereof. twenty two.  a composition comprising: (a) a pharmaceutically acceptable carrier; and (b) a compound of claim 1. twenty three.  A compound of any one of claims 1 to 2 for use as a therapeutic activity 156325. Doc -38- 201202215 Substance. twenty four.  Use of a compound of formula I according to any one of claims 1 to 21 for the manufacture of a medicament for the therapeutic and/or prophylactic treatment of Parkinson's disease. 25.  A compound of formula I as claimed in claims 1 to 2 for use as a therapeutically active substance for the therapeutic and/or prophylactic treatment of Parkinson's disease. 156325.doc -39- 201202215 IV. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 5. If there is a chemical formula in this case, please reveal the best display. Chemical formula of the inventive feature: 156325.doc