TW200524880A - Pyrimidine compounds - Google Patents

Abstract

The present invention relates to a pyrimidine derivative of the following formula (I) or the pharmaceutical acceptable salt thereof: [wherein, R1: a lower alkyl group etc.; R2: an aryl group etc.; R3: -NHR6 group (wherein, R6 is an aryl group etc.), etc.; R4: H etc.; R5: a heterocyclic group etc.]. These compounds have the exellent MLR inhibiting activity.

Description

200524880 IX. Description of the invention: [Technical field to which the invention belongs] The present invention relates to a pyrimidine derivative or a pharmacologically acceptable salt thereof which has an inhibitory effect on a mixed lymphocyte culture reaction (hereinafter referred to as MLR), and contains a Medicine with active ingredients. [Prior art] The rejection of transplanted tissues, such as bone marrow transplantation and organ transplantation, is the reaction of transplant recipient's autolymphocytes with non-autologous cells in the transplanted tissue, causing lymphocytes to activate and proliferate and produce an aggressive rejection reaction. _ This rejection reaction is a multi-stage response including: 1) identification of non-autologous cells, 2) increased expression of costimulatory molecules on the surface of lymphocytes to produce proliferating cytokinins, 3) activation and proliferation of lymphocytes, 4) proliferation The multi-stage response of lymphocytes to attack of transplanted tissue. Lymphocytes recognize major non-autologous cells via Major Histocompatibility (MHC). According to the difference of MHC, lymphocytes activated by non-autologous cells can be identified to produce cell kinetin called interleukin-2 (hereinafter referred to as IL-2). This IL-2 can proliferate and activate various immune cells. Activated lymph _ The co-stimulatory molecules found on the surface of the membrane can stimulate the proliferation and activation of various immune cells. Proliferated activated T cells, B cells, and killer T cells will attack and exclude transplanted lymphocytes and histiocytes (IMMUNOBIOLOGY 3rd Edition, 67). OMLR is used in this rejection. Autologous lymphocytes can reflect non-autologous lymphocytes. A simple evaluation system for the activation of proliferative responses of spheres is an evaluation system often used in the development of existing immunosuppressive agents. In recent years, it has been apparent that transplantation rejection anti-200524880 should inhibit effective compounds; all of them also show significant inhibitory effects in this system can be clearly expressed (Immunology 3rd edition, 505). Therefore, the compounds having an inhibitory effect in MLR can be expected to be used as a drug to suppress rejection of bone marrow transplantation, organ transplantation, etc., and to maintain long-term implantation of transplanted bone marrow and organs. Also evaluate the MLR test system as a liquid immune function test system that reflects cellular immunity such as lymphocyte proliferation and cytocidal activity, and antibody production. Therefore, agents with MLR inhibitory effects can participate in cellular immune functions and liquid immunity. The following diseases with excess function are effective. That is, the excess of cellular immune function and liquid immune function, chronic rheumatoid arthritis involved in inflammatory diseases, multiple sclerosis of organ-specific autoimmune diseases, inflammatory bowel disease, diabetes, glomerulonephritis, protozoa Primary biliary cirrhosis, chronic hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis, myasthenia gravis, dry addiction and Sjoegren's syndrome, organ non-specific autoimmune diseases, systemic lupus erythematosus , Diseases of allergic rhinitis, asthma, atopic dermatitis [Immunol. Today, Vol, 16, 34-3 8, (1 9 9 5); Science Vol. 260, 547-549, (1 9 9 3 ); Immunity, Vol. 3, 171-174, (1 995); J. Exp. Med., Vol. 1 90, 995- 1003, (1 999); Kidney Int., Vol. 52, 52-29, (1 997); J. Exp. Med., Vol. 185, 65-70, (1 997), Nanshantang Medical Dictionary, 797], so MLR inhibitors have been shown to be effective in the treatment or prevention of the above diseases. Based on the above background, a compound with excellent inhibitory effect on MLR is to be developed 200524880 [Summary of the Invention] As a result of studying the derivative with MLR inhibitory effect, the present inventors found that the pyrimidine derivative of the present invention has excellent MLR inhibitory effect and low cell Toxicity 'can be used as an inhibitor of transplantation tissue rejection in bone marrow transplantation, organ transplantation, cancer cell inhibitors with selective cytocidal activity (such as inhibitors of cancerous lymphocytes), or chronic rheumatoid arthritis of inflammatory diseases , Organ-specific autoimmune diseases (such as multiple sclerosis, inflammatory bowel disease, diabetes, glomerulonephritis, primary biliary cirrhosis, chronic active hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis , Myasthenia gravis, dry addiction or _ Shecklen syndrome), organ non-specific autoimmune diseases (such as systemic lupus erythematosus) or allergic diseases (such as rhinitis, asthma or atopic dermatitis) preventives And / or therapeutic agent (preferably an inhibitor of rejection of transplanted tissues such as bone marrow transplantation or organ transplantation or chronic rheumatism) The agent for preventing arthritis and / or therapeutic agent) effective, thereby completing the present invention. The present invention relates to (1) a pyrimidine derivative of the following formula or a pharmacologically acceptable salt thereof:

[Wherein R1 is a low radical group 'R2 is an aryl group, a heterocyclic group, an aryl group substituted with 1 to 5 groups selected from the substituent group a or a substituted group with 1 to 3 groups selected from the substituent group a Heterocyclic group, A is -NH- or oxygen atom, 200524880 R3 is hydrogen, lower alkyl, aryl, heterocyclic or -NHR6 group (5 has lower alkyl, cycloalkyl, cycloalkyl substitution Alkyl, cycloalkyl substituted with 1 to 3 groups of selective group b, aryl, heterocyclic group, aryl substituted with 1 to 5 groups selected from substituent group b, or 1 of selective group b ~ 3 radicals substituted heterocyclyl), R4 is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, cycloalkane lower alkyl, aryl, heterocyclyl, aralkyl, substituted An aryl group substituted with 5 to 5 bases or a heterocyclic group selected from 1 to 3 of the substituent group b (except when R3 is hydrogen and R4 is hydrogen), R5 is hydrogen, a halogen atom, or a lower alkyl group Group, cycloalkyl group, heterocyclic group, heterocyclic group substituted with 1 to 3 groups of the substituent group b, -NR7R8 group] (R7 and R8 are the same or different, each is a selective hydrogen, a lower alkyl group, a Is selected from 1 to 5 substituted low-alkyl groups, aryl groups of the substituent group c or is a selective substituent group b 1 ~ 5 groups substituted aryl) except for the group in which ζ R6 is a self-substituted aralkyl group, self-substituted group is substituted with a group of b. Group, heterocyclic ring, but

{Wherein T is N or CH, Y is 0, S, SO, S02, Z is any group selected from the substituent group), and the substituent group a is selected from the group consisting of low alkylsulfonyl, sulfamoyl, mono Group, di-lower alkylamine sulfonyl, mono-cycloalkylamine sulfonyl, mono-(^) aminesulfonyl, mono- (carboxylow alkyl) aminesulfonyl, nitrogen-containing sulfonyl, and -S 〇3H group, the auryl group b is selected from the group consisting of a halogen atom, a lower alkyl group, a lower haloalkyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkylsulfinyl group, or NZ (low Aminosulfonic acid (Hydroxylowane saturated heterocyclic ring, low alkoxycarboxyl group, amine 200524880 group, mono-low alkylamino group, di-low alkylamino group, sulfamoyl group, hydroxyl group, aryl group, aryloxy group, heterocyclic ring Group, haloaryl group, haloaryloxy group, 1- (4-methylaminesulfonylphenyl) -ethylene-hydrazinecarbonyl group and tris (methylsulfonylphenyl) -ethylene-hydrazinecarbonyl group, substituent group c is a mono-fluorenylamino group selected from an amino group, a mono-oligoalkylamino group, a di-oligoalkylamino group, a mono-fluorenylamino group, and a fluorenyl group having 1 to 5 groups selected from the substituent group b. , Hydroxy, lower alkoxy, hydroxy lower alkoxy, carboxyl, guanidino, aryl, aryloxy, heterocyclic, selected from Aryl groups substituted with 1 to 5 groups in the substituent group b, aryloxy groups substituted with 1 to 5 groups selected from the substituent group b, and hetero groups substituted with 1 to 3 groups selected from the substituent group b Ring group] In the present invention, it is preferably (2) a pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, wherein R1 is methyl, ethyl, or n-propyl, and (3) such as pyrimidine of (1) A derivative or a pharmacologically acceptable salt thereof, wherein R1 is a methyl group, (4) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (3), wherein R2 is a heterocyclic group or is selected from 1 to 3 substituted aryl groups of substituent group a, (5) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (3), wherein R 2 is pyridyl or is selected from (Low alkanesulfonyl, aminesulfonyl, mono-loweraminesulfonyl, mono-cycloalkylaminesulfonyl and mono- (carboxylowalkyl) aminesulfonyl) Any group substituted at the 4-position Phenyl, (6) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (3), wherein R2 is 4-pyridyl, 4-methanesulfonylphenyl, 4-ethanesulfonyl 200524880 Phenyl, 4-Aminosulfenylphenyl, 4-Methylsulfenylphenyl, 4-Ethyl Sulfophenyl, sulfopropylamine, sulfophenyl, or 4-carboxymethylaminesulfophenyl, (7) selected from the pyrimidine derivatives or pharmacologically acceptable salts thereof according to any one of (1) to (3) R2 is pyridyl, 4-methanesulfenyl phenyl, 4-aminosulfonyl phenyl, 4-methylaminosulfonyl phenyl, o-cyclopropylaminesulfonyl phenyl, or 4-carboxamidinesulfonyl phenyl, (8 ) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (3), wherein R2 is cardiopyridyl, 4-methanesulfonylphenyl, or 4-methylaminesulfonylphenyl, g ( 9) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (8), wherein A is -NH-, and (1〇) is selected from any one of (1) to (9) Pyrimidine derivatives or pharmacologically acceptable salts thereof, wherein R3 is an aryl group, a heterocyclic group, a mono-arylamino group, a mono-heterocyclic amino group or a phenyl moiety selected from (halogen atom, low alkyl group and low alkoxy group 1) Any one or two substituted mono-aniline groups, (11) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (9), wherein R3 is 3-pyridyl, ^ Indolinyl, aniline, 3-D to D amine, or the moieties are selected from (fluorine, Chlorine, methyl and methoxy) 1 or 2 substituted mono-aniline groups, (12) selected from the pyrimidine derivatives or pharmacologically acceptable salts thereof according to any one of (1) to (9), wherein R3 is 3-pyridyl, oxindolinyl, aniline, 3-pyridylamino, 4-fluoroaniline, 2-fluoroaniline, 5-fluoro-2-toluidine or 2-methoxyaniline (13) a pyrimidine derivative or -10- 200524880 pharmacologically acceptable salt selected from any one of (1) to (9), wherein R3 is aniline, 3-pyridylamino, 4-fluoroaniline Or a 2-fluoroaniline group, (14) a chelating derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (9), wherein R3 is a 3__11 amidin and a 1 ^ 丨 0 flower Linyl, aniline, 3-pyridylamino, 2-fluoroaniline, 5-fluorotoluidine or 2-methoxyaniline, (15) selected from any one of (1) to (9) Chewing Ding derivative or a pharmacologically acceptable salt thereof, wherein R3 is 3 -D to Dingyl, aniline, 3 to 3D Dingamidine or 5-fluoro-2-tolylamino, (16) selected from (1 A peak D-determining derivative or a pharmacologically acceptable salt thereof according to any one of (15) to (15), wherein R4 is hydrogen, low fluorene Group, aryl group, heterocyclic group, aromatic group or aryl group substituted with 1 to 5 groups selected from the substituent group b. (17) A dense D selected from any one of (1) to (15) A derivative or a pharmacologically acceptable salt thereof, wherein r4 is hydrogen, lower fluorenyl, phenyl, naphthyl, aromatic heterocyclic, fused bicyclic heteroaryl, benzyl, or selected from (halogen atom, lower alkyl 1 and 2 substituted phenyl groups' (18) and any alkoxy group) (18) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (15), wherein R4 is hydrogen, Phenyl, 1-naphthyl, 3-thienyl, 1,3-benzodifluorenyl-5-yl., 1,4-benzodi-Dfalk-6-yl, benzyl or may be selected from ( Fluorine, chlorine, methyl and methoxy) 1 or 2 substituted phenyl groups, (19) selected from the pyrimidine derivatives or pharmacologically acceptable salts thereof according to any one of (1) to (15), wherein R4 is hydrogen, phenyl, 3.thienyl, benzyl, 4-fluorophenyl, 2-fluorophenyl or 2-tolyl, -11-200524880 (20) selected from any of (1) to (15) A pyrimidine derivative or a pharmacologically acceptable salt thereof, wherein R4 is hydrogen, phenyl, 3-thienyl, 4-fluorophenyl, 2-fluoro Or 2-tolyl, (21) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (1 5), wherein R 4 is hydrogen, lower alkyl, aryl, heterocyclic or An aryl group substituted with 1 to 5 groups selected from the substituent group b, (22) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (15), wherein R4 is hydrogen, Lower alkyl, phenyl, naphthyl, aromatic heterocyclic, fused bicyclic heteroaryl or 1 or 2 substituted with any group selected from (halogen, lower alkyl and lower alkyloxy) Phenyl, (23) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (15), wherein R4 is hydrogen, phenyl, 1-naphthyl, 3-thienyl, 1, 3 -Benzodifluorenylflocene-5-yl, 1,4-benzodifluorenylalkyl or (fluoro, chloro, methyl and methoxy) arbitrary 1 or 2 substituted phenyl groups, (24 ) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (15), wherein R4 is hydrogen, phenyl, 1-naphthyl, 3-thienyl, 1,3-benzodioxin Ceto-5-enyl, 1'benzodioxane-6-yl, 2-fluorobenzyl, 2-tolyl or methoxyphenyl, (25) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (1 5), wherein R4 is hydrogen, phenyl, 3-thienyl, 1,3-benzodifluorenane-5- Group, 2-fluorophenyl group, or 2-tolyl group, (26) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen, a halogen atom, or a cycloalkyl group , Heterocyclic group, a heterocyclic group substituted with 1 to 3 groups selected from the substituent group, -NR7R8 group or -12-200524880 OR7 group (R7 and R8 are the same or different, each is hydrogen, a lower alkyl group, A cycloalkyl group, a lower alkyl group substituted with 1 to 5 groups selected from the substituent group c, an aryl group, a heterocyclic group, or an aryl group substituted with 1 to 5 groups of the substituent group b),

(27) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen, a heterocyclic group, a heterocyclic group substituted with one heterocyclic group, an amine group, The mono-lower alkylamino, di-lower alkylamino, or lower alkyl moiety has 1 to 3 substitutions of an arbitrary group selected from a hydroxyl group, a lower alkoxy group, a hydroxy lower alkoxy group, a heterocyclic group, and a substituent group b. Mono-lower amino or low alkoxy substituted with 1 to 5 groups of aryl,

(28) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen, pyrazolyl, imidazolyl, azetidinyl, 1-pyrrolidinyl, M4-([Eye B fixed base)] 卩 0 0 base, 1- [3_ (Heart B than steep base)] 卩 Bi base, 3-(4-卩 比 卩 定 基)-卩 比比基基, ( 4-hydrazine B) methylamine, amine, methylamine, dimethylamine, hydroxyethylamine, methoxyethylamine, 2- (2-ethoxy) ethylamine, 2- (4 -pyridinyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (pyridinyl) hydroxyethylamino, 2- (1,3-benzodisordinylalkyl) ethyl Amine, 3, 3-dimethoxyphenethylamino, 2- (3 '4-dimethoxyphenyl) tauethylamine, diaminosulfophenylethylamine, or 2- (4-pyridyl) ethyl Oxy '(29) is a chewidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen, 1-pyrazolyl, bimizolyl, bazetidinyl, ^ [4- (4-pyridinyl)] lapinyl, W3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -pyridyl, (cardiopyryl) methylamine Radical, amine radical, Amino group, 2- (2-hydroxyethoxy) ethylamino group, 2- (4-fluorenyl-D-Amino group) -13-200524880 ethylamino group, 3- (4-pyridyl) propylamino group, 2- (4 -Pyridyl) -2-hydroxyethylamino, 2- (1,3-benzodifluorenyl-5-yl) ethylamino, 3,4-dimethoxyphenethylamino, 2- (3 , Cardiac dimethoxyphenyl) -2-hydroxyethylamino, 4-aminosulfophenylethylethyl or 2- (4-pyridyl) ethoxy, (30) selected from (1) to (25) A pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of the above, wherein R5 is hydrogen, prazolyl, 1-imidazolyl, 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -pyrrolyl, (4-pyridyl) methylamino, 2- (4-pyridyl) ethylamino, 3- (4 -Pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 3,4-dimethoxyphenethylamino, 2- (3,4-dimethoxyphenyl) -2 -Via ethylamino or 2- (4-pyridyl), ethoxy, (31) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen , Heterocyclyl, heterocyclyl with 1 heterocyclyl substituent, amine, mono-lower alkylamine The di-lower alkylamine or lower alkyl moiety has 1 to 3 of 1 to 3 substituted aryl groups selected from hydroxy, lower alkoxy, hydroxy lower alkoxy, heterocyclic group and substituent group b. 5 radically substituted mono-lower amino groups' (32) A pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen, prazolyl, 1 -Imidazolyl, 1-Π, 2,3] -triazolyl, 2- [1,2,3] -triazolyl, 1- [1,2,4] -triazolyl, 4- [1, 2,4] -triazolyl, azetidinyl, 1-pyrrolidinyl, 1- [4- (4-pyridyl)] pyrazolyl, (4-pyridyl)] pyrazolyl, amine, methyl Amino, dimethylamino, 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino or lower alkyl sites are selected from 3-pyridyl, Pyridyl, 1 -14.200524880, 3-benzodisordinyl-5-yl, mono-methoxyphenyl, di-methoxyphenyl and sulfamoylphenyl 1 arbitrary substituted mono- Low alkylamine group, (33) a pyrimidine derivative or a pharmacologically acceptable salt thereof selected from any one of (1) to (25), wherein R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, or azetidine Lu Dingji, Budbi Slimidine, 1- [4- (4-pyridyl)] pyridyl, 1- [3- (4-pyridyl)] pyrazolyl, amine, methylamino, dimethylamino , 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridyl) ethylamino, 2- (1,3-benzene Benzodiocene-5-yl) ethylamino, 3,4-dimethoxyphenethylamino, or 4-aminosulfophenylethylethyl, (34) selected from any of (1) to (25) A pyrimidine derivative or a pharmacologically acceptable salt thereof, wherein R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, 1-azetidinyl, 1- [4- (4-pyridyl)] pyrazolyl, amine Group, methylamino group, 2- (2-hydroxyethoxy) ethylamino group, 2- (4-pyridyl) ethylamino group, 2- (1,3-benzodisorocene-5-yl group) Ethylamino, 3,4-dimethoxyphenethylamino, or 4-aminosulfophenylethylamino, (35) A pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, wherein R1 is methyl: R2 is 4-pyridyl, 4-methanesulfonylphenyl, 4-aminosulfonylphenyl, 4-methylsulfonylphenyl, [cyclopropylaminesulfonylphenyl, or 4-carboxmethylsulfonylphenyl, Α is -Nh_, r3 is 3-pyridyl, oxindolinyl, aniline, 3-0 ratio D The amine or phenyl moiety has one or two substituted mono-aniline groups selected from (fluorine, chlorine, methyl, and methoxy), R4 is hydrogen, phenyl, 丨 -naphthyl, 3_ Hexenyl, 1,3-benzobisfluorenyl-5-yl, 1,4-benzodiisopentan-6-yl ', or selected from (fluorine, chlorine, methyl, and methoxy 1) or any 2 substituted phenyl groups, R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, 200524880 1-azetidinyl, 1-pyrrolidyl, 1- [4- (4-pyridine )] Pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -1-pyrrolyl, (4-pyridyl) methylamino, amine, Methylamino, dimethylamino, 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 2- (1,3-benzodisorocene-5-yl) ethylamino, 3 , 4-Dimethoxyphenethylamino, 2- (3,4-dimethoxyphenyl) -2-hydroxyethylamino, 4-aminosulfophenylethylamino, or 2- (4-pyridyl) Ethoxy, (36) a pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, wherein R1 Is methyl, R2 is 4-pyridyl, 4-methanesulfenylphenyl, 4-aminosulfonylphenyl, 4-methylaminesulfonylphenyl, 4-cyclopropylaminesulfonylphenyl, or 4-carboxymethylamine Sulfonylphenyl, A is -NH-, R3 is 3-pyridyl, 1-indololinyl, aniline, 3-H hydradinylamino, 4-aminoaniline, 2-aminoaniline, 5 -Chloro-2 -tolylamino or 2-methoxyaniline, R4 is hydrogen, phenyl, 3-thienyl, benzyl, 4-fluorophenyl, 2-fluorophenyl or 2-tolyl, and R5 is Hydrogen, 1-pyrazolyl, 1-imidazolyl, 1-azetidinyl, W4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4 _Pyridyl) _pyrrolyl, (4-pyridyl®) methylamino, amine, methylamino, 2- (2-hydroxyethoxy) ethylamino, (4-pyridyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (pyridyl) -2-hydroxyethylamino, 2- (1,3-benzodisorcinyl) ethylamino, 3,4-dimethoxybenzene Ethylamino, 2- (3,4-dimethoxyphenyl) hydroxyethylamino, 4-aminosulfophenylethylamino or 2-('pyridyl) ethoxy, (37) (1) Such as the pyrimidine derivative (1) or its pharmacologically acceptable salt, where -16-20 0524880 R1 is methyl, R2 is 4-pyridyl, 4-methanesulfenylphenyl, or 4-methylaminosulfonylphenyl, A is -NH-, R3 is 3-pyridyl, 1-indolinyl, Aniline, 3-pyridylamino, 4-fluoroaniline, 2-fluoroaniline, 5-fluorotoluidine or 1methoxyaniline, R4 is hydrogen, phenyl, 3-thienyl, Ifluorobenzene Group, 2-fluorophenyl or 2-tolyl, R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, butadidinyl, 1- [4- (4-pyridyl)] pyrazolyl, 1 -[3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -1-pyrrolyl, (4-pyridyl) methylamino, amine, methylamino, 2- (2 -Hydroxyethoxy) ethylamino, 2- (4-pyridine ethynyl, 3- (4-pyridyl) pyridyl) propylamino, 2- (4-pyridyl) Amine group, 2- (1,3-benzodifluorenyl-5-yl) ethylamino group, 3,4-dimethoxyphenethylamino group, 2- (3,4-dimethoxyphenyl) 2-Hydroxyethylamino, 4-monthlysulfenylphenylethylamine or 2- (cardiopyridyl) ethoxy, (38) A pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, in which methyl is R2 is 4-pyridyl, 4-methanesulfonylphenyl or 4-methylaminosulfonylphenylhydrazone, and A is- NH-, R3 is aniline, 3-pyridinylamino, 4-benzylidene or 2-fluoroaniline, R4 is hydrogen, phenyl, 3-thienyl, Ifluorophenyl, phenyl or 2 _Tolyl, R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, 1-pyridyl, W4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl) j Ozozozolyl, 3- (4-pyridyl) vi-pyrrolyl, (4-pyridyl) methylamino, limbyl, methylamino, 2- (2-hydroxyethoxy) ethylamino , 2- (4-pyridyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 2- (1,3-benzodi Fluorenyl-5-yl) ethylamino, 3,4-dimethoxyphenethylamino, 2- (3,4-dimethoxyphenyl) -2-hydroxyethylamino, amine dimerase benzene Ethylamino or 2- (4-pyridyl) ethoxy, -17-200524880 (39) Such as the pyrimidine derivative of (1) or its pharmacologically acceptable salt, in which R1 is methyl, R2 is cardiac pyridyl, cardiac Methanesulfonylphenyl or methylaminesulfonylphenyl, A is -NH-, R3 is aniline, 3-pyridylamino, 4-fluoroaniline or 2-fluoroaniline, and R4 is hydrogen, phenyl, 3-thienyl, 4-fluorophenyl, 2-fluorophenyl or 2 -Tolyl, R5 is hydrogen, prazolyl, primizolyl, 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3 -(4-pyridyl) -pyrrolyl, (4-pyridyl) methylamino, 2- (4-pyridyl) ethylamino, 3- (cardipyridyl) propylamino, 2- (4-pyridyl ) -2-hydroxyethylamino, 3,4-dimethoxyphenethylamino, 2- (3,4-dimethoxyphenyl) -2-hydroxyethylamino or 2- (4-pyridyl ) Ethoxy, (40) a pyrimidine derivative or a pharmacologically acceptable salt thereof as in (1), in which is methyl, R2 is a heterocyclic group or an aryl group substituted with 1 to 3 groups selected from substituent group a , A is -NH-, and R3 is aryl, heterocyclic, mono-arylamino, mono-heterocyclic amino or phenyl moiety is selected from (halogen atom, lower alkyl and lower alkoxy) 1 or 2 substituted mono-aniline groups, R4 is hydrogen, lower alkyl, aryl, heterocyclic group or aryl group substituted with 1 to 5 groups of substituent group b, R5 is hydrogen, heterocyclic group, Heterocyclyl, amine, mono-oligoalkylamino, di-oligoalkylamino or low alkyl moiety having 1 substituent of heterocyclic group is selected from the group consisting of hydroxy, oligoalkoxy, hydroxyoligoalkoxy, Heterocyclyl 1 to 5 substituted aryl groups of 1 to 5 substituted mono-lower alkylamino groups of substituent group b, (41) pyrimidine derivatives such as (1) or pharmacologically acceptable salts thereof, where R1 is Methyl, R2 is pyridyl or selected from the group consisting of (lower alkylsulfonyl, aminesulfonyl, mono-lower alkylaminesulfonyl, mono-cycloalkylaminesulfonyl and mono- (carboxylower alkyl) amine Sulfonyl) phenyl substituted with any group at the 4-position, A is -NH-, R3 is -18-200524880 3-pyridyl, 1-indololinyl, aniline, 3-pyridylamino or phenyl moiety There are 1 or 2 substituted mono-aniline groups of any group selected from (fluorine, chlorine, methyl, and methoxy), R4 is hydrogen, lower alkyl, phenyl, naphthyl, aromatic heterocyclic group, thick Heterobicyclic heteroaryl or 1 or 2 substituted phenyl groups selected from (halogen, lower alkyl and lower alkoxy), R5 is hydrogen, prazolyl, bimizolyl, 1- [1,2,3] -triazolyl, 2- [1,2,3] -triazolyl, [[1,2,4] butriazolyl, 4- [1,2,4] -triazole , 1-azetidinyl, 1-pyrrolidinyl, 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, amine, methylamine base Dimethylamino, 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino or lower alkyl moiety is selected from 3-pyridyl, 4-pyridyl , 1,3-Dibenzo-Dflocene-5-yl, mono-methoxyphenyl, di-methoxyphenyl, and sulfamoylphenyl 1 arbitrary substituted mono-lower amino groups, ( 42) A pyrimidine derivative or a pharmacologically acceptable salt thereof as described in (1), wherein R1 is a methyl group, and R2 is a 4-pyridyl group, a 4-methanesulfonylphenyl group, a 4-ethanesulfonylphenyl group, and a 4-sulfamidine Phenyl, 4-methylaminesulfonylphenyl, 4-ethylaminesulfonylphenyl, I-cyclopropylaminesulfonylphenyl or 4-carboxymethylaminesulfonylphenyl, A is -NH-, R3 is 3-pyridine Group, 1-indololinyl, aniline, 3-pyridylamino, 2-fluoroaniline, 5-fluoro-2-tolylamino or 2-methoxyaniline, R4 is hydrogen, phenyl, and naphthyl , 3-thienyl, 1,3-benzodifluorenyl-5-yl, 1,4-benzodifluorenyl, or any one selected from (fluorine, chlorine, methyl, and methoxy) 1 or 2 substituents, R5 is hydrogen, 1-pyrazolyl, bimizolyl, 1-azetidinyl, pyrrolidyl, 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl Amine, methylamino, dimethylamino, 2-hydroxyethylamino, 2-methyl-19- 200524880 oxyethylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridine Group) ethylamino, 2- (1,3-benzodifluorenyl-5-yl) ethylamino, 3, dimethoxyphenylethylamino, or 4-aminosulfophenylethylethyl, (43 ) For example, a pyrimidine derivative or a pharmacologically acceptable salt thereof according to (1), wherein R1 is a methyl group, and R2 is a 4-pyridyl group, a 4-methanesulfonylphenyl group, a 4-aminosulfonylphenyl group, and a 4-methylaminesulfonyl Phenyl, 4-cyclopropylaminesulfonylphenyl or 4-carboxymethylaminesulfonylphenyl, A is -NH-, R3 is 3-pyridyl, 1-indolinyl, aniline, 3-pyridylamine Group, 2-fluoroaniline group, 5-fluoro-2-tolylamino group or 2-methoxyaniline group, R4 is hydrogen, phenyl group, 1-naphthyl group, 3-thienyl group, 1,3-benzoxazone Cetane-5-yl, 1,4-benzodioxane-6-yl, 2-fluorophenyl, 2-tolyl or 3-methoxyphenyl, R5 is hydrogen, 1-pyrazolyl, 1 -Imidazolyl, 1-azetidinyl, 1- [4- (4-pyridyl)] pyrazolyl, amine, methylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4 -Pyridyl) ethylamino, 2- (1,3-benzodifluorenyl-5-yl) ethyl Group, 3,4-dimethoxyphenethylamino group or 4-aminosulfophenethylamino group, (44) A pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, wherein Ri is methyl and R2 is 4 _Pyridyl, 4-methanesulfonylphenyl or 4-methylaminesulfonylphenyl, A is -NH-, R3 is 3-pyridinyl, aniline, 3-pyridylamino or 5-fluoro-2- Tolylamino, R4 is hydrogen, phenyl, 3-thienyl, 1. , 3-benzodifluorenyl-5-yl, 2-fluorophenyl or 2-tolyl, R5 is hydrogen, prazolyl, 1-imidazolyl, 1-azetidinyl, 1- [4- ( 4-pyridyl)] pyrazolyl, amine, methylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridyl) ethylamino, 2- (1,3- Benzodifluorene group) Ethylamino, 3,4-dimethoxyphenethylamino or 4-aminosulfophenylethylamino, -20- 200524880 (45) Pyrimidine derivatives such as (1) Or a pharmacologically acceptable salt thereof, which is N4- [2- (3,4-dimethoxyphenyl) -ethyl] -N2-phenyl-6- [Nf- (pyridin-4-yl-ethylene) ) -Hydrazino] -pyrimidine-2,4-diamine, 5-phenyl-2-anilino-4-pyridin-4-yl-ethylene) -hydrazino] -pyrimidine [4- {N'- [1- (4-Methanesulfonylphenyl) -ethylene] -hydrazinob 6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-2-yl] -aniline, 6 -{1 ^ '_ [1_ (4-methanesulfonylphenyl) -ethylenehydrazineb] ^ 2-phenyl44- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4- Diamine, (4- {1 ^ '-[1- (4-methanesulfonylphenyl) -ethylidene] -hydrazino} -5-phenylpyrimidin-2-yl) -aniline, [4- {N '[1- (4-Methanesulfonylphenyl) -ethylenehydrazine 5-phenyl-6- (2- Pyridin-4-yl-ethylamino) -pyrimidin-2-yl; 1-aniline, N-methyl-4- (1-{[2-phenylamino-6- (4-pyridin-4-yl-pyridine Azol-1-yl) -pyrimidin-4-yl] -hydrazinyl} -ethyl) -benzenesulfonamide, N-methyl-4- (1- {[2-phenylamino-6- (2- Pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -amidinophenylethyl) -benzenesulfonamide, N-methyl-4- {1- [5-phenyl-2-aniline pyrimidine- 4-yl] -hydrazinyl ethyl ethyl benzylsulfonamide, N-methyl-4- {1-[(5-phenyl-2-anilino-6-pyrazol-1-yl-pyrimidine-4- Yl) -hydrazinyl ethyl ethyl benzylsulfonamide, 4- {l-[(6-imidazol-phenyl-5-phenyl-2-phenylaminopyrimidin-4-yl) -hydrazino] -ethyl ethyl N-toluenesulfonamide, N_methyl_4- (1- {[5-phenyl-2-aniline-6- (4-pyridin-4-yl-pyrazole-1- 200524880) -pyrimidine -4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl- 4- (1-{[5-phenyl-2-aniline-6- (2-pyridin-4-yl- Ethylamino) -pyrimidin-4-yl] -amidinophenylethyl) -benzenesulfonamide, N-methyl-4- {1-[(2-anilino-5-thien-3-yl-pyrimidine- 4-yl) -hydrazinyl] -ethylsulfenylsulfonamide, N-methyl-4- (1-{[2-phenylamino-6- (4-pyridin-4-yl-pyrazole-1) -Yl) -5-thiophene-3 -Yl-pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl-4- (1-{[2-phenylamino-6- (4-pyridin-4-yl-pyridine Azole-butyl) -5-o-tolylpyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl-4- (1- {[5-phenyl-2- ( Pyridin-3-ylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, 4- (1- {[5- (2-fluorophenyl) -2-phenylamino-6 -(4-pyrimidin-4-yl-pyrazol-butyl) -pyrimidin-4-yl] -amidinophenylethyl) -N-tosylsulfonamide, phenyl- [4- [化-(1- Pyridin-4-yl-ethylene) -hydrazinyl] -6- (3-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-2-yl] -amine, 4- (1-{[ 5- (4-fluoro-phenyl) -2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyridin-4-yl] -pyridinyl} -ethyl)- N-methyl-phenyl mineral amine, 5- (4-fluoro-phenyl) -6-^ '-[1- (4-methylsulfonyl-phenyl) -ethylidene] -hydrazine}- N2-phenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine, 4- (1 · {[5-benzyl-2-anilino-6- (2 -Pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide, 1- (3,4-dimethoxy-phenyl) -2- (2-aniline-6- {N '-[pyridin-4-yl- Phenyl] -pyridyl-4-methylamino) -ethanol, 4- (1- {[6- (2-hydroxy-2-pyridin-4-yl-ethylamino) -5-phenyl -2-Anilino- -22- 200524880 pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide, 4- (1-{[6- (2-hydroxy-2-pyridine) -4-yl-ethylamino) -2-anilino-pyrimidin-4-yl] -hydrazino} -ethyl) -N-methyl-benzenesulfonamide, 1 ^ methyl-4- [1 -({5-phenyl-2-aniline-6-[(pyridin-4-ylmethyl) -amino] -pyrimidin-4-ylpyrazino) -ethyl] -benzenesulfonamide, 4- (1- {[2- (4-fluoro-aniline) -6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N-formyl -Benzenesulfenylamine, 4- (1- {[2- (4-fluoro-aniline) -5-phenyl-6- (2-pyridin-4-yl-ethylamino) -pyrimidine-4- Glyphosphinoylethyl) -N-methyl-benzenesulfonamide, _N2- (4-fluoro-phenyl) -6- {N '-[1- (4-methylsulfonyl-phenyl) -Ethylene] -hydrazinob 5-phenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine, 4- (1- {[2- (2- Fluoro-aniline) -5-phenyl-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinophenylethyl) -N-methyl-benzenesulfonamide, N-methyl-4- (1-{[5-phenyl-2-aniline -6- (3-pyridin-4-yl-propylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl-4- (1-{[2-phenylamino -6- (3-pyridin-4-yl-pyrrole-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, $ N -methyl-4- (1- {[ 5-phenyl-2-aniline-6- (3-pyridin-4-yl-pyrrole-1-yl) -pyrimidin-4-yl] -hydrazino} -ethyl) -benzenesulfonamide, or N-methyl-4- (Bu [[5-phenyl-2-aniline-6- (2-pyridin-4-yl-ethoxy) -pyrimidin-4-yl] -hydrazinylethyl) -Besylate, (46) a pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, which is N4- [2- (3,4-dimethoxyphenyl) -ethyl] -N2-phenyl -6- [N ·-(l-pyridin-4-yl-ethylidene) -bakeryl] -pentadione-2,4-amine, -23- 200524880 5-phenyl-2-phenylamino- 4- [N '-(1-pyridin-4-yl-ethylene) -hydrazino] -pyrimidine 6_ {N'-[l- (4-methylsulfonylphenyl) -ethylene] -hydrazino N2-phenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine, (4- ^ |-[1- (4-methanesulfonylphenyl) -subline Ethyl] -hydrazinob 5-phenylpyrimidin-2-yl) -aniline, N-methyl-4- (1-{[2-aniline-6- (4-pyridin-4-yl-pyridine Azol-1-yl) -pyrimidin-4-yl ] -Hydrazinophenylethyl) -benzenesulfonamide, N-methyl- 4- (1-{[2-phenylamino-6- (2-pyridin-4-yl-ethylamino) -pyrimidine-4- Phenyl] -hydrazinylethylbenzylsulfonamide, N-methyl-4- {1- [5-phenyl-2-anilinepyrimidin-4-yl] -hydrazinylethylbenzsulfonamide, N-methyl-4- {1-[(5-phenyl-2-anilino-6-pyrazol-1-yl-pyrimidinyl) -hydrazinyl ethyl ethyl benzylsulfonamide, 4- {1- [(6-imidazol-1-yl-5-phenyl-2-anilinepyrimidin-4-yl) -hydrazinyl] -ethylbenzene N-toluenesulfonamide, N-methyl-4- (1- {[5-phenyl-2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N -Methyl- 4- (l-{(5-phenyl-2-aniline-6-. (2-pyrimidin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl- 4- (1- {[2-phenylamino- 6- (4-pyridin-4-yl-pyrazol-1-yl) -5-thiophene_3_yl-pyrimidin-4-ylbazirazinylethyl) -benzenesulfonamide, N-methyl-4 -(1-{[2-anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-o-tolylpyrimidin-4-yl] -hydrazinylethyl) -benzene Sulfonamide, -24- 200524880 N-methyl_4- (Bu [[5-phenyl-2-((pyridin-3-ylamino) -pyrimidinyl] •• hydrazinyl} -ethyl)- Benzsulfonamide, 4- (1-{[5- (2-fluorophenyl) -2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidine-4- Group; I-hydrazinylethyl) -N-tosylsulfonamide, phenyl- [4- [N '-(1-pyridin-4-yl-ethylene) -hydrazino] -6- (3- Pyridin-4-yl-lipidan-1 -yl) -chrysene-2 -yl] -amine, 4- (1-{[5- (4-per-benzyl) -2-benzylamino- 6- (2-bundidin-4-yl-ethenyl) _pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide, 4- (1-{[6- (2-Hydroxy-2-pyridin-4-yl-ethylamino) -5-phenyl-2-aniline- # pyrimidin-4-ylpyrazinylethyl) -N-methyl-benzenesulfonamide , 4- (1-{[6- (2-hydroxy-2 · Pyridin-4-yl-ethylamino) -2-anilino-pyrimidin-4-yl] -pyridinyl ethyl) -N-methyl-phenylphenylamine, N-methyl-4- [l- ({5-phenyl-2-anilino-6-[(pyridin-4-ylmethyl) -amino] -pyrimidin-4-ylbutazidinyl) -ethyl] -benzenesulfonamide, 4 -(1-{[2- (4-fluoro-aniline) -6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylpyridinyl} -ethyl) -N- Methyl-benzylamine, 4- (1- {[2- (4-fluoro-aniline) -5-phenyl-6- (2-pyridin-4-yl-ethylamino)-^ pyrimidine- 4-yl] -amidinophenylethyl) -N-methyl-benzenesulfonamide, 4- (1-{[2- (2-fluoro-aniline) -5-phenyl-6- (2-pyridine -4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl)-. Methyl-benzenesulfonamide, N-methyl- 4- (l-{[5-benzyl-2-aniline-6- (3-pyridine-4-yl-propylidene))- Pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl- 4- (l-{[5-phenyl-2-aniline-6- (3-pyridin-4-yl -Pyrrole-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, or -25-200524880 N-methyl-4- (1-{[5-phenyl-2- Anilino-6- (2-pyridin-4-yl-ethoxy) -pyrimidin-4-yl] -hydrazinylethyl) _benzenesulfonamide, (47) A pyrimidine derivative such as (1) or its Pharmacologically acceptable salt, which is phenyl- [4- [Chuan- (1-pyridin-4-yl-ethylene) -hydrazinob 6- (4-pyridin-4-yl-pyrazol-1-yl) -Pyrimidin-2-yl; I-amine, N2-phenyl-N4- (2-pyridin-4-yl-ethyl) -6- [N '-(1-pyridin-4-yl-ethylene) -Hydrazino] -pyrimidine-2,4-diamine, N4- [2- (3,4-dimethoxyphenyl) -ethyl] -N2-phenyl-6- [N, (1-pyridine- 4-yl-ethylene) -hydrazino] -pyrimidine-2,4-diamine, 4- (2- {2-phenylamino-6- to '-(1-pyridin-4-yl-ethylene) ) -Hydrazine] -pyrimidin-4diylaminobethyl) _benzenesulfonamide, 5-phenyl-2-anilino-4- [N '-(l-pyridin-4-yl · ethylene) -Hydrazine ] -Pyrimidine, 5-phenyl-2-anilino-4_ [N ·-(pyridin-4-yl-ethylene) -hydrazino] -6- (4-pyridin-4-yl-pyrazole- 1-yl) -pyrimidine, (4- {N '-[1- (4-methanesulfonylphenyl) -ethylene] -hydrazinob 5-phenylpyrimidin-2-yl) -aniline, N -Methyl-4- (l-{[2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) _benzenesulfonate Hydrazine, N-methyl-4- (1-{[2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylpyrazolylethyl) -benzenesulfonate Hydrazine, 4- [1- (丨 6- [2- (3,4-dimethoxyphenyl) -ethylaminophenyl 2-aniline-pyridin-4-ylpyrazino) -ethyl] -N-toluenesulfonamide, 4- [2- (2-aniline-6- {N '-[1- (4-methylaminesulfonylphenyl) -ethylene] -hydrazine 200524880 Pyrimidine- 4-ylamino) -ethyl] -benzenesulfonamide, N-methyl- 4- {l- [5-phenyl-2-anilinepyrimidin-4-yl] -hydrazinylethylethylbenzenebenzene Amine, N_methyl_4- {1-[(5-phenyl-2-phenylamino-6-pyrazol-1-yl-pyrimidin-4-yl) -hydrazino] -ethylbenzenebenzenesulfonate Amidoamine, 4- {1-[(6-imidazol-1-yl-5-phenyl-2-phenylpyrimidin-4-yl) -hydrazino] -ethylbenzene N-toluenesulfonamide, 4- {1-[(6- Butidin-1-yl-5-phenyl-2-anilino-pyrimidin-4-yl) -hydrazinyl] -ethyl} -N-toluenesulfonamide, N-methyl-4- (1- {[5-phenyl-2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) _pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, 4 -{1- (6-Amino-5-phenyl-2-anilinepyrimidin-4-yl) -hydrazinyl ethyl ethyl N-toluenesulfonamide, N -methyl-4- {1-[(6 -Methylamino-5-phenyl-2-phenylaminopyrimidin-4-yl) -amidino] -ethylbenzylamine, 4- [1-({6- [2- (2-hydroxyethyl (Oxy) -ethylamino] -5-phenyl-2-phenylaminopyrimidin_4_ylhydrazino) -ethyl] -N-tosylsulfonamide, N-methyl-4- (1-{[ 5-phenyl-2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl-4 -{l-[(2-anilino-5-thien-3-yl-pyrimidin-4-yl) -hydrazino] -ethylbenzsulfuronamide, N_methyl_4- (1- { [2-Anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-thien-3-yl-pyridin-4-yl] -pieridinyl} -ethyl) -The present mineral amine, 4- (1-{[5- (2-Tolyl) -2-aniline-pyrimidin-4-yl] -hydrazinylethyl) -N- -27- 200524880 tosylsulfonamide, N Monomethyl_4 -(l-{[2-anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-o-tolylpyrimidin-4-yl] -hydrazinylethyl) -benzene Sulfonamide, N-methyl-4- (l-{[5 -benzyl-2- (2-pyridin-3-ylamino) -¾'-4-4-yl] -hydrazinyl ethyl ) -Toluenesulfonamide, N-methyl-4- {1-[(5-phenyl-2-pyridin-3-yl-pyrimidin-4-yl) -hydrazino] -ethylbenzylsulfonium Amine, 4- (1-{[5- (2-fluorophenyl) -2-aniline pyrimidin-4-yl] -hydrazinylethyl) -N-toluenesulfonamide, _phenyl- [4- [ 1 ^-(1-pyridin-4-yl-ethylene) -fluorenyl] -6- (3-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-2-yl] -amine, N -Methyl-4- {1-[(5-phenyl-2-anilino-6-pyrrolidin-1-yl-pyrimidin-4-yl) -hydrazino] -ethylbenzylsulfonamide, (4- {N '[1- (4-Methanesulfonylphenyl) -ethylenesulfazinyl 5-phenyl-6-pyrrolidin-1-yl-pyrimidin-2-yl) -aniline, 4- { 1-[(6-dimethylamino-5-phenyl-2-anilinepyrimidin-4-yl) -hydrazino] -ethylbenzene N-toluenesulfonamide, ^ (6-dimethylamino- 4- {N '[1- (4-Methanesulfonylphenyl) -ethylene] -hydrazinob 5-phenyl-pyrimidin-2-yl) -aniline, (6- (2-methoxyethylamine) ) -4- {N '[1- (4-Methanesulfonylbenzene ) -Ethylene] -hydrazinyl 5-phenyl-pyrimidin-2-yl) -aniline, 4- (1-{[5- (3-methoxyphenyl) -2-aniline pyrimidin-4-yl ] -Hydrazinylethyl) -N-toluenesulfonamide, N-methyl-4- {l-[(5-naphthalen-1-yl-2-aniline-pyrimidin-4-yl) -hydrazino ]-Ethyl sulfenilamide, -28- 200524880 4- {l-[(5-Dibenzyl-3-yl-2-phenylamino-¾¾, fluorenyl-4-yl) -pyridinyl] " • Ethyl Bu. Tosylsulfonamide, N-methyl-4- {1-[(2-aniline-5-p-tolylpyrimidin-4-yl) -hydrazinobethyl} -benzenesulfonamide, 4- (1 -{[5- (3-fluorophenyl) -2-anilinepyrimidin-4-yl] -hydrazinylethyl) -N-tosylsulfonamide, N-methyl- 4- (1-{[5- (4-Methanesulfonylphenyl) -2-anilinepyrimidin-4-ylhydrazinobethyl) -benzenesulfonamide, 4- (1-{[5- (2-chlorophenyl) -2-aniline Pyrimidin-4-ylbuazidinyl} -ethyl) -1 tosylsulfonamide, 4- (1-{[5- (2-fluoro-5-tolyl) -2-aniline-6-pyrazole -1-yl-pyrimidin- 4-yl: l · hydrazinylethyl) -N-toluenesulfonamide, 4- (1-{[5- (3-chloro-2-fluorophenyl) -2 · aniline -6-pyrazol-pyridyl-pyrimidin-4-yl] -hydrazinylbuthyl) -N-tosylsulfonamide, 4- (1-{[5- (2,3-xylyl) -2 -Anilino-6-pyrazol-1-yl-pyrimidin-4-yl] -hydrazinylethyl) -N-tosylsulfonamide, 4- (1-{[2- (2,3-dihydroindane Indole-1-yl) -5-phenyl-pyrimidin-4-yl] -hydrazinylethyl) -N-tosylsulfonamide, 4- (1- {[2- (2-fluoroaniline) -5 -Phenylpyrimidin-4-yl] -hydrazinylethyl) -N-tosylsulfonamide, (4- {1-[(5-phenyl-2-aniline-pyrimidin-4-yl)- Phenyl] -ethylbenzylsulfonamido) -acetic acid, (4- {1-[(6-imidazol-1-yl-5-phenyl-2-phenylaminopyrimidin-4-yl) -hydrazino] -Ethylbenzenesulfonamido) -acetic acid, or 200524880 [4- (1-{[5-phenyl-2- (pyridin-3-ylamino) -pyrimidin-4-yl; I-hydrazine Phenylethyl) -benzenesulfonamido] -acetic acid, (48) a pyrimidine derivative such as (1) or a pharmacologically acceptable salt thereof, which is phenyl- [4- [化-(1-pyridin-4-yl- Ethylene) -hydrazino] -6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-2-yl] -amine, N2-benzyl-N4- (2-Ui: t Fluoren-4-yl-ethyl) -6- [N '-(1-Π than hydradin-4-yl-ethylene) -fluorenyl] -pyrimidine-2,4-diamine, 1 ^ 4 -[2- (3,4-dimethoxyphenyl) -ethyl 1-2-phenyl-6- [1 ,,-(pyridin-4-yl-ethylene) -hydrazine]- Pyrimidine-2,4-diamine, 5-phenyl-2-anilino-4- [N '-(1-pyridyl-ethylene) -hydrazinopyrimidine > (4-{] ^'- [1- (4-Methanesulfonylphenyl) -ethylene] -hydrazinob 5-phenylpyrimidin-2-yl) -aniline, N-methyl-4- (1-{[2-aniline -6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-ylbazirazinylethyl) _benzenesulfonamide, N_methyl-4- (b {{2 -Anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -amidinophenylethyl) -benzenesulfonamide, 4- [1-({6- [2- (3,4-di Methoxyphenyl) -ethylamino] -2-anilino-pyridine-4-ylburazinyl) -ethyl] -N-tosylsulfonamide, 4- [2- (2-phenylamino) -6- {Ν ·-[1- (4-methylaminesulfonylphenyl) -ethylene] -hydrazinopyrimidin-4-ylamino) -ethyl] -benzenesulfonamide, Ν_ 甲Methyl-4_ {l- [5-phenyl-2-aniline pyrimidine · 4-yl] -hydrazinophenylethyl} -benzenesulfonamide, N-methyl-4-{[[5-phenyl-2 -Anilino-6-pyrazol-1-yl-pyrimidin-4-yl)-200524880 hydrazinyl ethyl ethyl benzylsulfonamide, 4- {1-[(6-imidazol-1-yl-5-phenyl-5-phenyl -2-Anilinopyrimidin-4-yl) -hydrazinyl] -ethylbenzene N-tosylsulfonamide, 4- {1-[(6-azetidin-1-yl-5-phenyl-2- Aniline-pyrimidin-4-yl) -hydrazinyl] -ethylbenzene N-tosylsulfonamide, 4- {1- (6-amino-5-phenyl-2-anilinepyrimidin-4-yl) -Hydrazinyl ethyl ethyl N-tosyl sulfonamide, N-methyl-4- {l-[(6-methylamino-5-phenyl-2-phenylpyrimidin-4-yl) -hydrazino] -Ethyllbenzamidine, 4- [1-({6- [2- (2-hydroxyethoxy) -ethylamino] -5-phenyl-2-phenylaminopyrimidin-4-yl Buya ) -Ethyl: IN-toluenesulfonamide, N · methyl-4- (1- {[5-phenyl-2-aniline-6- (2-pyridin-4-yl-ethylamino) -Chew amidin-4-yl] -Asianyl bisethyl) " " This finely brewed maid, 4- (1 · {[5- (2-Tolyl) -2-aniline pyridin-4-yl] -Hydrazinylethyl) _N-tosylsulfonamide, N-methyl-4- (1-{[5-phenyl-2- (pyridin-3-ylamino) -pyrimidin-4-yl]- Hydrazinylethyl) -benzenesulfonamide, 4- (1-{[5- (2-chlorophenyl) -2-aniline sulfan-4-yl] -pylidene} -ethyl) -N- Tosyl sulfonamide, phenyl- [4- [N '-(1-fluorenidine-4-yl-ethylidene) -pieyl] -6- (3 -fluorenidine-4-yl- Orbizol-pyridyl) _pyrimidinyl] -amine, 4_ {Bu [(5-biphenyl-3-yl-2-phenylamino-pyrimidin-4-yl) -hydrazinyl] -ethylpyridine -Toluene fluorenamine, N-methyl-4- (l-{[5- (4-methylsulfonylphenyl) -2 -aniline pendidine-4 -yl] -hydrazine-31-200524880 group} • Ethyl) -benzamine, 4- (1-{[5- (3-chloro-2-fluorophenyl) -2-aniline-6-pyrazol-1-yl-pyrimidin-4-yl Hydrazino} -ethyl) -N-toluenesulfonamide, 4- (1-{[5- (2,3-xylyl) -2-aniline-6-pyrazol-1-yl-pyrimidine -4-yl]- Hydrazinylethyl) -N-tosylsulfonamide, 4- (1- {[2- (2,3-dihydroindole · 1-yl) -5-phenyl-pyrimidin-4-yltriazine Ethyl) -N-toluenesulfonamide, 4- (1- {[2- (2-fluoroaniline) -5-phenylpyrimidin-4-yl] -hydrazinyl ethyl) _N_tosylsulfonamide , Lu (4- {1-[(5-phenyl-2-anilino-pyrimidin-4-yl) -hydrazino] -ethylbenzylsulfonamido) -acetic acid, or [4- (1 -[[5-phenyl- 2- (pyridin-3-ylamino) -pyrimidin-4-yl] -hydrazino} -ethyl) -benzenesulfonamido] -acetic acid, (49) a medicine A composition containing a pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of (1) to (48) as an active ingredient, (50) a medicinal composition for inhibiting a mixed lymphocyte culture reaction, containing (1) ) ~ (48) The pyrimidine derivative or its pharmacologically acceptable salt is an active ingredient, (51)-a type of prevention and / or treatment of inflammatory diseases that inhibits rejection of transplanted tissues such as bone marrow transplantation and organ transplantation , Medicinal composition of organ-specific autoimmune disease, organ non-specific autoimmune disease or allergic disease, including in (1) ~ (48) A pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of the active ingredients, (52) — a kind of prevention and / or treatment of chronic rheumatoid arthritis, multiple -32- 200524880 sclerosis, inflammatory bowel disease, diabetes, glomeruli Nephritis, Primary Biliary Cirrhosis, Chronic Active Hepatitis, Malignant Anemia, Hashimoto's Thyroiditis, Atrophic Gastritis, Myasthenia Gravis, Xyphobia, Shekelian's Syndrome, Systemic Lupus Erythematosus, Rhinitis, Asthma or Heterogeneity A pharmaceutical composition for atopic dermatitis, containing the pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of (1) to (48) as an active ingredient, (53) — a pharmaceutical composition for inhibiting cancer cells, Containing a pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of (1) to (48) as an active ingredient (54) A medicinal composition that inhibits cancerous lymphocytes, including the following (1) to (48) Any of the pyrimidine derivatives or pharmacologically acceptable salts thereof as an active ingredient, (55) a pharmaceutical composition for preventing and / or treating chronic rheumatoid arthritis by inhibiting rejection of transplanted tissues such as bone marrow transplantation and organ transplantation, Contained as (1) ~ (48) The pyrimidine derivative or its pharmacologically acceptable salt is an active ingredient, (56) A use for manufacturing a pharmaceutical composition is to use a pyrimidine derivative according to any of (1) to (48) or Its pharmacologically tolerable salt, (57) uses such as (5 6), wherein the pharmaceutical composition is a composition capable of inhibiting mixed lymphocyte culture reaction, (58) uses such as (5 6), wherein the pharmaceutical composition is Prevention and / or treatment of inflammatory diseases, organ-specific autoimmune diseases, organ non-specific autoimmune diseases, or allergic diseases by inhibiting the rejection of transplanted tissues such as bone marrow transplantation and organ transplantation, -33- 200524880 (59) The use of (56), wherein the pharmaceutical composition can prevent and / or treat chronic rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, diabetes, glomerulonephritis, primary biliary cirrhosis, chronic Active hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis, myasthenia gravis, psoriasis, Shekelian's syndrome, systemic lupus erythematosus, rhinitis' asthma or atopic dermatitis, (60) such as (56) use The pharmaceutical composition is a composition capable of inhibiting cancer cells, (61) such as (56) uses, wherein the pharmaceutical composition is a composition capable of suppressing cancerous lymphocytes, (62) such as (56) uses, among which medicines The composition can prevent and / or treat chronic rheumatoid arthritis by inhibiting the rejection of transplanted tissues such as bone marrow transplantation and organ transplantation, (63) a method for inhibiting the rejection of transplanted tissues such as bone marrow transplantation and organ transplantation, It is a pharmacologically effective amount of a pyrimidine derivative such as any one of (1) to (48) or a pharmacologically acceptable salt thereof for administration to a warm-blooded animal, (64) a method for preventing and / or treating a disease by pharmacologically An effective amount of a pyrimidine derivative according to any one of (1) to (4 8) or a pharmacologically acceptable salt thereof is administered to a warm-blooded animal, (65) The method according to (64), wherein the disease is an inflammatory disease, an organ Specific autoimmune disease, organ non-specific autoimmune disease or allergic disease, (66) The method of (64), wherein the disease is chronic rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, diabetes, glomerulus nephritis, -34- 200524880 Primary biliary cirrhosis, chronic active hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis, myasthenia gravis, psoriasis, Shekelian's syndrome, systemic lupus erythematosus, rhinitis, asthma, or heterogeneity Orthotopic dermatitis, (67) The method of (64), wherein the disease is chronic rheumatoid arthritis, (68) — A method of suppressing cancer cells, which is based on a pharmacologically effective amount such as (1) ~ (4 8 ) The pyrimidine derivative or pharmacologically acceptable salt thereof according to any one of (), (69) The method according to (6 8), wherein the cancer cells are cancerous lymphocytes, (70), such as (63) ~ ( 69) The method of any one of the above, wherein the warm-blooded animal is a human. In the present invention, the "low alkyl" may be, for example, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, second butyl, third butyl, n-pentyl, isopentyl , 2-methylbutyl, neopentyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3 , 3-dimethylbutyl, 2 '2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2 C1 ~ 6 straight or branched alkyl such as 3-dimethylbutyl, 1-ethylbutyl or 2-ethylbutyl, preferably CrG alkyl, and also preferably methyl, ethyl or The n-propyl group is more preferably an alkyl group, and particularly preferably a methyl group. In the present invention, the "aryl" may be a C6 ~ 14 aromatic hydrocarbon group such as phenyl, indenyl, naphthyl, phenanthryl, anthracenyl or manganyl, etc., preferably C6-C1G aryl, and also preferably phenyl or Naphthyl is more preferably phenyl or naphthyl, and particularly preferably phenyl. In the present invention, a "heterocyclic group" is a 5- to 7-membered heterocyclic group containing 1 to 4 sulfur atoms, oxygen atoms, or -35-200524880 and nitrogen atoms, such as furyl, thienyl, pyrilyl, and acryl. Butidyl, pyrazolyl, imidazolyl, oxazolyl, iso [Ifazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl'thiadiazolyl, "Aromatic heterocyclic groups" such as pyranyl, pyridyl, daphthyl, pyrimidinyl or pyridyl, tetrahydropyranyl, tetrahydrothienyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, Pyrrolyl, imidazolyl, pyrazolidyl, piperidinyl, piperidyl, oxadiazolyl, isoDfdiazyl, thiazolyl, pyrazolidyl, difluorenylalkyl or diDfalkyl Such partially or completely reduced saturated heterocyclic groups, the above heterocyclic groups may be fused with other rings such as benzene rings ("fused bicyclic hetero · aryl groups"), such as benzothienyl, benzothiazolyl, benzene Benzozolyl, isobenzofuranyl, quinolinyl, 1,3-benzodifluorenylalkyl, benzodifluorenyl, indolyl, isoindolyl, or indolyl, R2 is preferred 6-membered aromatic heterocycle , Preferably pyridyl, more preferably 4-pyridyl, R3 is preferably 3-pyridyl or 1-indololinyl, and is also 3-pyridyl, R6 is preferably 3-pyridyl, and R4 is preferably 2 -Thienyl, 3-thienyl, 1,3-benzodiocorane-5-yl or 1 '4-benzodioxane-6-yl, also preferably 3-thienyl, 1,3- Benzodifluorenyl-5-yl or 1,4-benzodiDfalkyl-6-yl, more preferably 3-thienyl or 1 '· 3-benzodifluorenylfoctan-5-yl , Especially 3-thienyl, R5 is preferably pyrazolyl, 1-imidazolyl, 1-pyrrolyl, 1-[1,2,3] -triazolyl, 1-[1,2,4 ' -Triazolyl, 4- [1,2,4] -triazolyl, 1-azetidinyl, or pyrrolidinyl, preferably 1-pyrazolyl, 1-imidazolyl, propyryl, D-Alkyl or 1-pyrrolidinyl, more preferably 1-pyrazolyl, 1-imidazolyl, propyryl or 1-azetidinyl, particularly preferably 1-pyrazolyl, 1-imidazolyl or pyrrolyl. In the present invention, "cycloalkyl" is cyclopropyl, cyclobutyl, cyclopentyl or cyclo-36-200524880 hexyl, preferably cyclopropyl. In the present invention, the "lower alkyl group substituted with cycloalkyl group" refers to the above-mentioned "cycloalkyl group" combined with the above "lower alkyl group", for example, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl , Cyclobutylmethyl, cyclobutylethyl, cyclobutylpropyl, cyclopentylmethyl or cyclopentylmethyl, preferably cyclopropylmethyl. In the present invention, "aralkyl" refers to a group in which the above "aryl" is combined with the above "low alkyl", such as benzyl, α-naphthylmethyl, Θ-naphthylmethyl, onion methyl, and benzyl , Trityl, 1-phenethyl, 2-phenethyl, naphthylethyl, 2-naphthylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-naphthalene Propyl, 2-naphthylpropyl, 3-naphthylpropyl, 1-naphthylbutyl, 2-naphthylbutyl, 3-naphthylbutyl, 4-naphthylbutyl, 1-naphthylbutyl, 2-naphthylbutyl , 3-naphthylbutyl, 4-naphthylbutyl, 1-phenylpentyl, 2-phenylpentyl, 3-phenylpentyl, 4-phenylpentyl, 5-phenylpentyl, 1-naphthylpentyl, 2 -Naphthylpentyl, naphthylpentyl, 4-naphthylpentyl, 5-naphthylpentyl, 1-phenylhexyl, 2-phenylhexyl, 3-phenylhexyl, 4-phenylhexyl, 5-phenylhexyl, 6-phenylhexyl 1,1-naphthylhexyl, 2-naphthylhexyl, 3-naphthylhexyl, 4-naphthylhexyl, 5-naphthylhexyl, or 6-naphthylhexyl, preferably C7-C1G aralkyl, and preferably benzyl. In the present invention, the "low alkoxy group" refers to the above-mentioned "low alkyl" group combined with an oxygen atom, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, Second butoxy, third butoxy, n-pentyloxy, isopentyloxy, 2-methylbutoxy, 1-ethylpropoxy, 2-ethylpropoxy, neopentyloxy , Hexyloxy, 4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy , 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy or 2,3-dimethylbutoxy, preferably Cl-C4 Alkoxy is preferably Cl-C2alkoxy-37-200524880, and more preferably methoxy. In the present invention, the "halogen atom" is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, and more preferably fluorine. In the present invention, "lower alkylsulfonyl" is the above-mentioned "lower alkyl" combined with sulfonyl, such as methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, butanesulfonyl Fluorenyl, isobutylsulfonyl, second sulfonylsulfonyl, third sulfonylsulfonyl, pentylsulfonyl, isopentylsulfonyl, 2-methylbutylsulfonyl, neopentylsulfonyl, 1 -Ethylpropanesulfonyl, hexamethanesulfonyl, 4-methylpentylsulfonyl, 3-methylpentylsulfonyl, 2-methylpentylsulfonyl, 1-methylpentylsulfonyl, 3 , 3-dimethylbutanesulfonyl, 2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl, 1,2-dimethylbutanesulfonyl, 1,3 -Cl_C6 alkylsulfonyl groups such as dimethylbutanesulfonyl, 2,3-dimethylbutanesulfonyl, or 2-ethylbutanesulfonyl, preferably alkylsulfonyl and CrQ alkylsulfonyl Fluorenyl, more preferably methanesulfonyl. In the present invention, the "mono-lower alkylamine sulfonyl group" is a group of the above-mentioned "low alkyl" combined with an amine group and a sulfonyl group, such as methylamine sulfonyl, ethylamine sulfonyl, and propylamine sulfonyl , Isopropylamine sulfonyl, butylamine sulfonyl, isobutylamine sulfonyl, second butylamine sulfonyl, third butylamine sulfonyl, pentylsulfonyl, isoamylsulfonyl, 2 -Methylbutylaminesulfonyl, neopentylaminesulfonyl, 1-ethylpropylaminesulfonyl, hexylaminesulfonyl, isohexylaminesulfonyl, 4-methylpentylaminesulfonyl, 3-methyl Pentylaminesulfonyl, 2-methylpentaminesulfonyl, 1-methylpentaminesulfonyl, 3,3-dimethylbutylaminesulfonyl, 2,2-dimethylbutylaminesulfonyl Fluorenyl, 1,1-dimethylbutylaminesulfonyl, 1,2-dimethylbutylaminesulfonyl, 1,3-dimethylbutylaminesulfonyl, 2,3-dimethylbutyl Aminesulfenyl, or 2-ethyl-38-200524880 butylaminesulfonyl, preferably mono-CPC4 alkylaminesulfonyl, and also preferably mono-C ^ Ca alkylaminesulfonyl, more preferably methylamine Sulfonyl. In the present invention, "mono-cycloalkylaminesulfonyl" is cyclopropylaminesulfonyl, cyclobutylaminesulfonyl, cyclopentylaminesulfonyl or cyclohexylaminesulfonyl, preferably mono-c3_c4 cycloalkylamine Sulfonyl, and preferably cyclopropylaminesulfonyl. In the present invention, the "mono- (hydroxy-lower alkyl) aminosulfonyl" is a group in which one hydroxyl group is substituted with the "low-alkyl" moiety of the above-mentioned "mono-lower alkylaminesulfonyl", for example, hydroxymethylaminesulfonyl Fluorenyl, 2-hydroxyethylamine sulfonyl, hydroxyethylamine sulfonyl, 3-hydroxypropylamine sulfonyl, 4-hydroxybutylamine sulfonyl, 5-hydroxypentylamine sulfonyl, or 6-hydroxyhexyl The sulfamoyl group is preferably a hydroxyCrG alkylaminosulfonyl group, and also preferably a hydroxyCrCz alkylaminesulfonyl group, and more preferably 2-hydroxyethylaminesulfonyl group. In the present invention, "mono- (carboxy-lower alkyl) aminosulfonyl" is a group in which one carboxyl group is substituted with a "low-alkyl" moiety of the above-mentioned "mono-lower alkylaminesulfonyl", for example, carboxymethylaminesulfonyl Fluorenyl, 2-carboxyethylaminesulfonyl, 1-carboxyethylaminesulfonyl, 3-carboxypropylaminesulfonyl, 4-carboxybutylaminesulfonyl, 5-carboxypentaminesulfonyl, or 6-carboxyl Hexylaminesulfonyl is preferably carboxyalkylaminesulfonyl, more preferably carboxyalkylaminesulfonyl, more preferably carboxymethylaminesulfonyl. In the present invention, the "nitrogen-containing saturated heterocyclic sulfonyl group" is a 3 to 7-membered saturated heterocyclic group containing 1 to 3 nitrogen atoms combined with a sulfonyl group, such as morpholin-1 -yl-sulfonyl, Thiomorpholine-l-yl-sulfonyl, aziridin-1-yl-sulfonyl, azetidin-1-yl-sulfonyl, pyrrolidin-1-yl-sulfonyl, piperidine- 1-yl-sulfonyl, pyrrolin-1-yl-sulfonyl, imidazol-1-yl-sulfonyl, pyrazol-1-yl-sulfonyl, piperidinyl-sulfonyl Sulfonyl, piperidin-1-yl-sulfonyl, isoxazolyl-1 -yl-sulfonyl, thiazolidine-1-yl-sulfonyl, or pyrazolidine-sulfonyl-39-2005- 24550 Amidino is preferably azetidin-1-yl-sulfonyl. In the present invention, “halo-lower alkyl” means that the above-mentioned “low-alkyl” has 5 to 5 same or different substituents as the above-mentioned “halogen atom”, such as trifluoromethyl, trichloromethyl, and difluoromethyl. , Dichloromethyl, dibromomethyl, fluoromethyl, 2,2, trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoro Halo C! -C6 alkyl such as ethyl, 2-ethylethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl or 2,2-dibromoethyl, preferably halogen CrC4 alkyl, More preferably, it is a halogen Ci-C2 alkyl group, and also preferably a fluorine C ^ C: 2 alkyl group or a chlorine CrC2 alkyl group, and most preferably a trifluoromethyl group. In the present invention, the "low alkylthio group" refers to the above-mentioned "low alkyl" group bonded to a sulfur atom, such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, Second butylthio, third butylthio, pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, hexylthio: 4-methylpentylthio, 3-methyl Pentylthio, 2-methylpentylthio, 3,3-dimethylbutylthio, 2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1, 2- C1 ~ 6 straight or branched alkylthio groups such as dimethylbutylthio, 1,3-dimethylbutylthio or 2,3-dimethylbutylthio, preferably Ci-Q alkylthio , More preferably a CrQ alkylthio group, and most preferably a methylthio group. In the present invention, "lower alkylsulfinyl" refers to the above-mentioned "lower alkyl" combined with sulfinyl, such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylidene Sulfonyl, butylsulfinyl, isobutylsulfinyl, second sulfinyl, third sulfinyl, pentylsulfinyl, isopentylsulfinyl, 2-methyl Butylsulfinyl, neopentylsulfinyl, butylsulfinylsulfinyl, hexylsulfinyl, 4-methylpentylsulfinyl, 3-methylpentylsulfinyl, 2--40 -200524880 methylpentylsulfinyl, 1-methylpentylsulfinyl, 3,3-dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinyl, 1,1- Dimethylbutanesulfinyl, 1,2-dimethylbutanesulfinyl, 1,3-dimethylbutanesulfinyl, 2,3-dimethylbutenesulfinyl, or 2- CrCe alkylsulfinyl sulfonyl groups such as ethylbutenesulfinyl sulfonyl are preferably CrQ alkylsulfinyl sulfinyl, but also alkylsulfinyl sulfinyl, and more preferably methylsulfinyl sulfinyl. In the present invention, the "mono-lower alkylamine group" is one of the above-mentioned "low alkyl" bonded amino groups, such as methylamino, ethylamino, propylamino, isopropylamine, butylamine, and isobutylamine Group, second butylamino group, third butylamino group, pentylamino group, isorupentylamino group, 2-methylbutylamino group, neopentylamino group, 1-ethylpropylamino group, hexylamine group, isohexylamine Methyl, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1-methylpentylamino, 3,3-dimethylbutylamino, 2,2-bis Methylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino, or Monoalkylamine groups such as 2-ethylbutylamino are preferably monoalkylamine groups, more preferably monoalkylamine groups, and most preferably methylamine groups. In the present invention, "di-low alkylamino" is the same or different two groups of the above-mentioned "_low alkyl" combined with amine, such as dimethylamino, diethylamino, and ethyl-N-methylamine. Dialkylamino, dipropylamino, dibutylamino, dipentylamino or dihexylamine, etc., are preferably di-Cl_C4 alkylamino, more preferably di_Ci_C 2 amino, most preferably Dimethylamino. In the present invention, "" di-oligoalkylaminesulfonyl "refers to the above-mentioned" di-oligoalkylamine "combined with sulfonyl, such as dimethylaminesulfonyl, diethylaminesulfonyl, N-ethyl -N-methylaminesulfonyl, dipropylaminesulfonyl, dibutylaminesulfonyl, di-41-200524880 di_Ci_C6 alkylaminesulfonyl, such as pentylsulfonyl or dihexylaminesulfonyl, preferably It is a mono-c ^ c: 4-aminosulfamoyl group, more preferably a di-Ci-C2 alkylaminesulfamoyl group, and most preferably a dimethylaminesulfamoyl group. In the present invention, the "" aryloxy group "is a group of the above-mentioned" aryl group combined with an oxygen atom ", for example, a phenoxy group, an indenyloxy group, a naphthyloxy group, a phenanthryloxy group, an onionoxy group, or a diyloxy group" is preferably C6, Cl () aryloxy is also preferably phenoxy or naphthyloxy, and more preferably phenoxy. "Haloaryl" is one to five identical or different, in the present invention

The above-mentioned "aryl" substituted with "dental atom", for example, fluorophenyl, chlorophenyl, perphenyl or difluorophenyl, is preferably 4-fluorophenyl. In the present invention, the "haloaryloxy group" refers to the above-mentioned "aryloxy group" having 1 to 5 same or different "halogen atoms", such as fluorophenoxy group, chlorophenoxy group, and bromophenoxy group. Or difluorophenyloxy, preferably 4-fluorophenoxy. In the present invention, the "mono-fluorenylamino group" is a carbonyl-linked amino group which is a combination of the above-mentioned "low alkyl" or "aryl", such as an ethylamino group and a benzylamino group.

In the present invention, "" hydroxyalkoxy "is a group in which a hydroxy group is bonded to the aforementioned" low alkoxy ", such as hydroxymethoxy, hydroxyethoxy, and hydroxypropoxy, and is preferably hydroxyethoxy. In the present invention, the "substituent group a" is preferably a low alkanesulfonyl group, an amine sulfonyl group, a mono-lower amine sulfonyl group, and a mono-cycloalkylamine sulfonyl group, and also preferably a methanesulfonyl group and an ethyl group. The sulfofluorenyl, sulfamolfenyl, methylaminesulfonyl, ethylaminesulfonyl and cyclopropylaminesulfonyl groups are more preferably methylsulfonyl and methylaminesulfonyl. In the present invention, the "" substituent group b "is preferably selected from halogen atom, lower alkyl group, lower -42-200524880 peroxy group and fluorenyl group. It is also preferably fluorine, chlorine, methyl, methoxy and The 4-fluorene ratio β radical is more preferably a fluorine, methyl, methoxy and 4-D ratio D radical. In the present invention, the "substituent group c" is preferably selected from the group consisting of a hydroxy group, a lower alkoxy group, an aryl group substituted with any one of the lower group oxy group, a heterocyclic ring and a substituent group b. Radical, 2-Ethoxy group, 3-fluorenyl ratio fluorenyl, 4-fluorenyl ratio uryl ", 3-benzodifluorene noctidin-5-yl, mono-methoxyphenyl, di-methoxybenzene More preferably, the sulfamoyl group and the sulfamoyl group are a mesityl group, a 4-pyridyl group, and a 3,4-dimethoxyphenyl group. In the present invention, the "aryl group substituted with 1 to 5 groups of the substituent group a" is the above-mentioned "aryl group" and the group substituted with 1 to 5 groups selected from the arbitrary group of the substituent group a is preferably a substituent An aryl group substituted with 1 to 3 groups of group a, and is preferably (lower sulfofluorenyl, aminesulfonyl, mono-low alkylaminesulfonyl, and mono-cycloalkylaminesulfonyl) Rensyl in the 4-position Substituted phenyl 'is more preferably 4-methylamine phenyl, 4-ethanesulfonyl phenyl, 4-aminosulfonyl phenyl, 4-methylaminesulfonyl phenyl, 4-ethylaminesulfonyl phenyl. Or 4-cyclopropylaminesulfonylphenyl, particularly preferably 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 4-methylaminesulfonylphenyl or 4-cyclopropylaminesulfonylphenyl, most preferably Methanesulfonylphenyl or 4-methylaminosulfonylphenyl. In the present invention, the "heterocyclic group substituted with 1 to 3 groups of the substituent group a" is the above-mentioned "heterocyclic group" which has 1 to 3 groups substituted with any group selected from the substituent group a, and is preferably Any group having a substituent group a. A substituted 6-membered aromatic heterocyclic group. In the present invention, the "cycloalkyl group substituted with 1 to 3 groups of the substituent group b" is the above-mentioned "cycloalkyl group" which has 1 to 3 groups substituted with any group selected from the substituent group b, and is preferably fluorine Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl substituted with 1, 2, chloro, methyl or methoxy, preferably 2-fluorocyclopropyl or 2-methylcyclohexyl-43- 200524880 In the present invention 'The "aryl group substituted by 1 to 5 groups of the substituent group b" is the above-mentioned "aryl group" and is selected from the substituent group! ^ Of any one of the groups substituted with 1 to 5 groups, for example, `` has any group selected from the substituent group b or 2 substituted phenyl groups '', it is preferably a halogen atom, a methyl group, or a methoxy group 1 or 2 Substituted phenyl, R6 is also preferably 4-fluorophenyl, 2-fluorophenyl, 5-fluoro-2-tolyl or 2-methoxyphenyl, more preferably 4-fluorophenyl, 2_ Fluorophenyl or 5-fluorotolyl, particularly 4-fluorophenyl or 2-fluorophenyl, and in r4, 4-fluorophenyl, 2-fluorophenyl, 2-tolyl, or 3-fluorophenyl The methoxyphenyl group is more preferably a fluorophenyl group, a 2-fluorophenyl group, or a 2-fluorenyl 'substituent group c, and also a 3,4-dimethoxyphenyl group. In the present invention, "the heterocyclic group substituted with 3 to 3 groups of the substituent group 13" is the above-mentioned "heterocyclic group" which has 3 groups substituted with any group selected from the substituent group b. Substitute group! Heterocyclic group substituted with 1 group of 3 arbitrary groups, in R5, preferably 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4-radyl)] pyrazolyl Or 3- (4-pyridyl)-^ pyrrolyl, and preferably [4- (4-pyridyl)] pyrazolyl. In the present invention, the "aralkyl group substituted with 1 to 5 groups of the substituent group b" is _ The above "aralkyl group" has a substituted group with 1 to 5 groups selected from any group of the substituent group b, for example, The benzyl group having 1 or 2 substitutions of any group selected from the substituent group b is preferably a benzyl group having 1 or 2 substitutions of a halogen atom, a methyl group or a methoxy group. In the present invention, the "-NHR6 group" is preferably a mono-arylamino group, a mono-heterocyclic amino group or a phenyl moiety having any group i or two substitutions selected from (halogen atom, lower alkyl group and lower alkoxy group). The mono-aniline group is also preferably a cycloalkylamine, aniline group, 3-pyridoxamine group or phenyl moiety having any group selected from (fluorine, chlorine, methyl and methoxy) -44- 200524880 1 or 2 A substituted mono-aniline group, more preferably an aniline group, a% pyrimidinyl group, a 4-fluoroaniline group, a 2-fluoroaniline group, a 5-fluoro-2_toluidine group, or a 2-methoxyaniline group. Preferably it is aniline, 3-pyrimidinyl, 4-fluoroaniline, 2-fluoroaniline or 5-fluoro-2-toluidine, most preferably aniline,% pyridinyl, 4-fluoroaniline Or 2-fluoroaniline. In the present invention, the "mono-acidamino group substituted with 1 to 5 groups of the substituent group b in the fluorenyl group moiety" is the above-mentioned "mono-fluorenylamino group" and has 1 to 5 substitutions of any group selected from the substituent group b. The base is preferably methoxyacetamido or 3,4-dimethoxybenzylamino. _ In the present invention, the “aryloxy group substituted with 1 to 5 groups of the substituent group b” is the above-mentioned “aryloxy group” and has 1 to 5 substituted groups selected from the arbitrary group of the substituent group b. One or two substituted phenoxy groups of any group from the substituent group b are preferably selected from halogen atoms, methyl or methoxy groups, or two substituted phenoxy groups. In the present invention, the "lower alkyl group substituted with 1 to 5 groups of the substituent group c" is the above-mentioned "lower alkyl group" and has 5 or more substituted groups selected from the arbitrary group of the substituent group c. 5-alkyl substituted low alkyl from hydroxy, lower alkoxy, hydroxy lower alkoxy, heterocyclic ring and 3 substituted aryl groups of arbitrary group b), and preferably selected from 2- Hydroxyethyl, 2-methoxyethyl, (2-hydroxyethoxy) ethyl, or (Mono-methoxyphenyl, di-methoxyphenyl, and sulfamoyl)) 1 or 2 substituted lower alkyl groups, more preferably (fpyridyl) methyl, 2-hydroxyethyl , 2, oxyethyl, 2_ (2, ethoxy) ethyl, 2_ (4-pyridinyl) ethyl, 3 · (4 · pyridyl) propyl, 2 _ (* • pyridyl) _- 45-200524880 2-hydroxyethyl, 2- (1,3-benzodifluorenylalkyl) ethyl, 3,4-dimethoxyphenethyl, 2- (3,4-dimethoxyphenyl) ) _2_Hydroxyethyl or 4-Aminosulfophenethyl, especially (4-pyridyl) methyl, 2- (2-hydroxyethoxy) ethyl, 2- (4-pyridyl) ethyl 3-(4, pyridyl ) Propyl, 2- (4-pyridyl) -2-hydroxyethyl, 2- (1,3-phenylhydrazinofluorenyl-5-yl) ethyl, 3,4-dimethoxyphenethyl , 2- (3,4-dimethoxyphenyl) -hydroxyethyl or 4-sulfamophenethyl, most preferably (4-pyridyl) methyl, 2- (4-pyridyl) ethyl , 3- (4-pyridyl) propyl, 2- (4-pyridyl) -2-hydroxyethyl, 3,4-dimethoxyphenethyl, or 2- (3,4-dimethoxyphenyl) ) _2_hydroxyethyl. In the present invention, the "-NR7R8 group" is preferably a mono-low alkylamino di-low alkylamino or low alkyl moiety having a member selected from the group consisting of (hydroxy, low alkoxy, hydroxy low alkoxy, heterocyclic and substituents). Group b arbitrarily 1 to 3 substituted aryl groups) i to 5 substituted mono-low alkylamino groups: also preferably methylamino, dimethylamino, 2-hydroxyethylamino, 2- The methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino or lower alkyl moiety is selected from the group consisting of (hydroxy, 3-pyridyl, cardiac pyridyl, 1,3-benzodifluorenyl- 5 ·, mono-methoxyphenyl, di-methoxyphenyl, and sulfamoyl)) 1 or 2 substituted mono-lower alkylamino groups, more preferably methylamino, dimethylamino (4-pyridyl) methylamino, 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridyl) ethylamino , 2- (1,3-benzodifluorenyl-5-yl) ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 3,4-dimethoxyphenethylamino, 2- (3, I dimethoxyphenyl) -2-hydroxyethylamino or 4-aminosulfophenylethylamino, particularly methylamine, ( 4-pyridyl) methylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (tpyridyl) ethylamino, 2- (1,3-benzodifluorenyl-5-yl) ethylamine 200524880, 3- (4 -Pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 3,4-dimethoxyphenethylamino, 2- (3,4-dimethoxyphenyl) -2 -Hydroxyethylamino or 4-aminosulfophenylethylamine, most preferably (4-pyridyl) methylamino, 2-(4-Π than hydradinyl) ethylamine, 3-(4-fluorene D-Amino) Alanine, 2-(4-O-pyridinyl) -2-hydroxyethylamino, 3,4-dimethoxyphenethylamino, or 2- (3,4-dimethoxyphenyl)- 2-hydroxyethylamine. In the present invention, the "-OR7 group" is preferably a methoxy group, a 2- (2-hydroxyethoxy) ethoxy group, a 2- (4-pyridyl) ethoxy group, or a 2- (1,3-benzo) group. Disuecene-5-yl) ethoxy, 3,4-dimethoxyphenethoxy, or 4-sulfamophenethylethoxy, preferably 2- (4-pyridyl) ethoxy. In the present invention, it is preferred that R1 is methyl, ethyl or n-propyl, and it is also preferred that R1 is methyl. In the present invention, it is preferred that R2 is a heterocyclic group or an aryl group substituted with 1 to 3 groups selected from the substituent group a, and R2 is preferably a pyridyl group or a group selected from , Mono-lower alkylaminesulfonyl, mono-cycloalkylaminesulfonyl and mono- (carboxylow alkyl) aminesulfonyl) any phenyl group substituted at the 4-position, more preferably R2 is 4-pyridine Methyl, 4-methylsulfonylphenyl, 4-ethylsulfonylphenyl, 4-aminosulfonylphenyl, 4-methylsulfonylphenyl, 4-ethylsulfonylphenyl, 4-cyclopropylaminesulfonyl Phenyl or 4-carboxymethylaminesulfonylphenyl, particularly preferably R2 is 4-pyridyl, 4-methylsulfonylphenyl, 4-aminesulfonylphenyl, 4-methylaminosulfonylphenyl, 4-ring Propylsulfenylphenyl or 4-carboxymethylsulfonylphenyl, most preferably R2 is 4-pyridyl, 4-methylsulfonylphenyl or 4-methylsulfanylphenyl. In the present invention, A is preferably -NH-. In the present invention, it is preferred that R3 is an aryl group, a heterocyclic group, a mono-aromatic amino group, a mono-heterocyclic-47-200524880 amino group, or a phenyl group 1 or: Preferably R3 is 3-4-fluoroaniline, particularly preferably Raniline. In the present invention, there may be selected from the group consisting of hydrogen, lower alkyl, benzyl, or 1 or 2 phenyl groups, 1, 3 $ groups, or optionally substituted phenylbenzyl, 2-fluoro, fluorobenzyl In the invention, the soil group and the amine group have a hydroxyl group, a low-b arbitrary group I or a low alkoxypyridyl group, and the 1-pyridine moiety is selected from (halogen atom, low alkyl group, and low alkoxy group) any one of the substituted mono- Aniline, preferably R3 is 3-pyridyl, 1-anilinyl, 3-pyridinyl or phenyl moiety has 1 or 2 substituted mono-aniline groups selected from (fluoro, methoxy) arbitrary groups, more Pyridyl, 1-indololinyl, aniline, 3-pyridylamino, 2-fluoroaniline, 5-fluoro-2-tolylamino or 2-methoxyaniline 3 is aniline, 3-eye D-Amino group, 4-fluoroaniline group or 2-Wei group, preferably R4 is an aryl group substituted by 1 to 5 groups of hydrogen, lower alkyl group, aryl group, heterocyclic group, aralkyl group, b, It is also preferable that R4 is phenyl, naphthyl, aromatic heterocyclic group, and condensed bicyclic heteroaryl. Any group selected from (halogen atom, lower alkyl group and lower alkoxy group): substituted phenyl group, more preferably R4 is Hydrogen, phenyl, 1-naphthyl, 3-thi ... benzodifluorenyl-5-yl, 1,4-benzo Krysene-6-yl, 1 or 2 '(Fluorine, Chlorine, Methyl and Methoxy) arbitrary groups, particularly preferably R4 is hydrogen, phenyl, 3-thienyl, benzyl, 4-fluorophenyl or 2-Tolyl, most preferably R4 is hydrogen, phenyl, 3-thienyl, 2-fluorophenyl or 2-tolyl. 'It is desirable that R5 is hydrogen, heterocyclic group, and hetero substituted with 1 heterocyclic group' mono-low alkylamino, di-low alkylamino or low alkyl moiety, Heterocyclic group and mono-low alkylamino group substituted with 1 to 5 groups selected from the group of substituents ~ 3 substituted aryl groups, and preferably R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, buacidine Slightly 11 amidyl, 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4- -48- 200524880 aliphatic B amidyl)] 卩 than 11 thiol, 3-(4-卩More than 11 amidyl) -1 * pyrrolyl, (4-pyridyl) methylamino, amine, methylamine, dimethylamino, 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino , 2- (1,3-Benzodisuecene-5-yl) ethylamino, 3,4-dimethoxyphenethylamino, 2- (3,4-dimethoxyphenyl) -2 -Hydroxyethylamino, 4-Aminosulfophenylethylamino, or 2- (4-pyridyl) ethoxy 'more preferably R5 is hydrogen, 1-pyrazolyl, 1-imidyl, 1-acyl Ding 卩 dingji, 1-[4-(4-卩 比 卩 定 基)] 卩 比 卩 基基, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -1-pyrrolyl, (4-pyridyl) methylamino, amine, methylamino, 2- (2-hydroxyethoxy Group) ethylamino group, 2- (4-pyridyl) ethylamino group, 3- (4-pyridyl) propylamino group, 2- (4-pyridyl) -2-hydroxyethylamino group, 2 -(1,3-Benzodibenzopentane-5-yl) ethylamino, 3,4-dimethoxyphenethylamino, 2- (3 '4-dimethoxyphenyl) -2-hydroxy Ethylamino, 4-Aminosulfophenethylamino or 2- (4-pyridyl) ethoxy, particularly preferably R5 is hydrogen, 1-pyrazolyl, bimizolyl, W4- (4-pyridyl) ] Pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -1-pyrrolyl, (4-pyridyl) methylamino, 2- (4- Pyridyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 3,4-dimethoxyphenethylamino, 2- (3 , 4-dimethoxyphenyl) -2-hydroxyethylamino or 2- (4-pyridyl) ethoxy. "The pharmacologically acceptable salt" means a salt prepared by reacting an acid with a basic group such as an amine group in the pyrimidine derivative of the formula (I) of the present invention, and reacting with a base when an acidic group such as a carboxyl group is present. Salts of basic group are preferably hydrochloride, hydrobromide, hydroiodate, etc. -49- 200524880, nitrate, perchlorate, sulfate, phosphate and other inorganic acid salts; methanesulfonic acid Salt, trifluoromethanesulfonate, ethanesulfonate and other low-alkane sulfonates, benzenesulfonate, p-toluenesulfonate and other aromatic sulfonates, acetate, malate, fumarate, succinic acid Organic acid salts such as acid salts, citrates, ascorbates, tartrates, oxalates, and maleates; and glycine, lysine, arginate, ornithine, glutamate Amino acid salts such as salts and aspartate salts are most preferably hydrohalide salts, inorganic acid salts or organic acid salts. The salt of the acidic group is preferably an alkali metal salt such as sodium salt, potassium salt, lithium salt, alkaline earth metal salt such as calcium salt, magnesium salt, metal salt such as aluminum salt, iron salt; inorganic salt such as ammonium salt; third octylamine salt , Dibenzylamine salt, molybdenum salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methyl glutamine salt, guanidine salt, diethylamine salt, triethylamine salt 'dicyclohexyl Amine salt, N, N, -dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzylphenylethylamine salt, piperon salt, tetramethylammonium salt, ginseng (Hydroxymethyl) amine salts such as organic methane salts; and amine groups such as glycine, lysine, spermine, guanine, glutamate, aspartate Acid salts, most preferably alkali metal salts. The pyrimidine derivative of formula (I) or its pharmacologically acceptable salt of the present invention may have various isomers due to the presence of asymmetric carbon atoms in the molecule. In the compounds of the present invention, the isomers and isomer mixtures thereof are all represented by a single formula, that is, formula (I). Therefore, the present invention also includes isomers and mixtures of the isomers in any ratio. The pyrimidine derivative of formula (I) or a pharmacologically acceptable salt thereof of the present invention may have geometric isomers due to the presence of a double bond in the molecule. In the compounds of the present invention, the geometric isomers and geometric isomer mixtures thereof are both represented by a single formula, that is, formula (I). Therefore, the present invention also includes geometric isomers and mixtures of geometric isomers in any ratio. -50 · 200524880 The pyrimidine derivative of formula (I) or a pharmacologically acceptable salt thereof of the present invention may be placed in the atmosphere or recrystallized to absorb water, adsorb water, and form hydrates. These hydrates are also included in the present invention. Invention salt. Specific examples of the compound of the formula (I) of the present invention may be the compounds described in Table 1 below, but the present invention is not limited thereto. In Table 1 below, the abbreviations are as follows:

Me: methyl, 4-Py: 4-pyridyl, 4-MeNH S 02C6H4: 4-methylaminesulfonylphenyl,

PhNH: aniline, 3-PyNH: 3-pyridinyl,

Ph (A) NH: 5-fluoro-2-tolylamino, 3-Th: 3-thienyl, 1-Pyra: 1-pyridyl, 1-Imid: 1-imidazolyl, 1-A zt : 1-azetidinyl,

Pyra (A): 1-[4-(4-pyridyl)] pyrazolyl,

EtNH (A): 2- (2-hydroxyethoxy) ethylamino,

EtNH (B) .: 2- (4-pyridyl) ethylamino,

EtNH (C): 2- (1,3-benzodifluorenyl-5-yl) ethylamino, PhCH2CH2NH (A): 3,4-dimethoxyphenethylamino,

PhCH2CH2NH (B): 4-Aminosulfophenethylamine,

Ph (B): 1,3-benzobisocorane-5-yl.

Pyra (B): 1-[3-(4-pyridyl)] pyrazolyl, 200524880 1-Pyrd: 1 -pyrrolidinyl,

EtNH (D): 2-methoxyethylamino, 1-Naph: 1-naphthyl,

Ph (C): 2-fluoro-5-tolyl,

Ph (D): 3-chloro-2-fluorophenyl,

Ph (E) · 2,3-xylyl, 1-Ind: 1 -indolinyl,

Ph (F): 4-carboxymethylaminesulfophenyl, cPr: cyclopropyl,

Et: ethyl,

Pyrr (A): 1-methanesulfonyl-3-pyrrolyl,

EtNH (E): 2- (2-thienyl) ethylamino,

PhCH2CH2NH (C): 2,5-dimethoxyphenethylamine group,

EtNH (F): 2- (5-imidazolyl) ethylamino, l-Tri (A): 1- (1,2,4-triazolyl), l-Tri (B): 1- (1 , 2,3-triazolyl),

Py (A): 5-phenyl-3-pyridyl,

Ph (G): 1,4-benzodioxane-6-yl,

Ph (H): 3- (4-fluorophenoxy) phenyl, cHe X: cyclohexyl,

Ph (I): 2-chloro-6-fluorophenyl,

Pipe (A): 1- {4- [l- (4-methylaminesulfonylphenyl) -ethylene-hydrazinecarbonyl] piperidinyl} group,

Pipe (B): 1- {3- [l- (4-methylaminesulfonylphenyl) -ethylene-hydrazinecarbonyl] -52- 200524880 piperidinyl} group,

Pipe (C): 1- {4- [l- (4-methylsulfonylphenyl) -ethylene-hydrazinecarbonyl] piperidinyl} group,

Pipe (D): 1- {3- [1- (4-methylsulfonylphenyl) -ethylene-fluorenylcarbonyl] piperidinyl}, Tri (C): 4- (1,2,4 -Triazolyl),

Ph (J): 4-hydroxy-3,5-xylyl,

PhCH2CH2NH (D): 2- (3,4-dimethoxyphenyl) -2-hydroxyethylamine,

Ph (K): 4- (2-hydroxyethylaminesulfonyl) phenyl,

EtNH (Η): (tetrahydrofuran-2-yl) methylamino, cB u: cyclobutyl,

Py (B): 2-methoxy-5-pyridyl,

Py (C): 2,6-dimethoxy-3-pyridyl,

PhCH2NH (A): 3,4-dimethoxyphenylmethylamino,

PhCH2CH20 (A): 3,4-dimethoxyphenethoxy,

PhCH2CH2NH (E): 4-ethoxy-3-methoxyphenethylamino, PhCH2CH2NH (F): 3-ethoxy-4-methoxyphenethylamino, PhCH2CH2NH (G) ... 3,4- Dichlorophenethylamine,

Ph (L): 5-methoxy-2-tolyl,

EtNH (I): 2- (morpholin-4-yl) -ethylamino, 2-Th: 2-thienyl,

EtNH (J): 2-([1,3) Difluorenane-2-yl) -ethylamino,

EtNH (K): 2- (1-pyrrolidinyl) -ethylamino, 200524880

EtNH (L): 2- (1-piperidinyl) -ethylamino, iPr: isopropyl,

Pyrr (B) ·· 3-(4-pyridyl) -1-pyrrolyl,

PhCH2NH (B): 6,7-dimethoxy-3,4-dihydro-1H-isoquinolinyl,

Ph (M): 4- (2-hydroxypropylaminesulfonyl) phenyl,

Ph (N): 4- (morpholine-4-sulfonyl) -phenyl,

PhCH2CH2NH (Η): 2- (3,4-dimethoxyphenyl) -2- [1,3]

R4 R2 (I) Compound number R1 R2 A R3 R4 R5 1 Me 4-Py -NH- PhNH HH 2 Me 4-Py-NH- PhNH H 1-Pyra 3 Me 4-Py -NH- PhNH H 1-Imid 4 Me 4-Py -NH_ PhNH H 1-Azt 5 Me 4-Py -NH- PhNH H Pyra (A) 6 Me 4-Py -NH- PhNH H nh2 7 Me 4-Py -NH- PhNH H MeNH 8 Me 4 -Py -NH- PhNH H EtNH (A) 9 Me 4-Py -NH- PhNH H EtNH (B) 10 Me 4-Py -NH- PhNH H EtNH (C) 11 Me 4-Py -NH_ PhNH H PhCH2CH2NH ( A) 12 Me 4-Py -NH- PhNH H PhCH2CH2NH (B) 13 Me 4-Py -NH- PhNH Ph H 14 Me 4-Py -NH- PhNH Ph 1-Pyra 15 Me 4-Py -NH- PhNH Ph 1-Imid 16 Me 4-Py -NH- PhNH Ph 1-Azt -54- 200524880 47 Me 4-Py-NH_ PhNH 2-MeC6H4 PhCH2CH2NH (A) 48 Me 4-Py -NH_ PhNH 2 ~ MeC6H4 PhCH2CH2 legs ⑻ 49 Me 4-Py -NH- 3-PyNH HH 50 Me 4-Py-NH-3-PyNH · H 1-Pyra 51 Me .4-Py -NH- 3-PyNH H 1-Imid 52. Me 4-Py- NH- 3-PyNH H 1-Azt 53 Me 4-Py -NH- '3-PyNH H Pyra (A) 54 Me 4-Py-NH-3-PyNH H nh2 55 Me 4-Py -NH- 3-PyNH H MeNH 56 Me 4-Py-NH- 3-PyNH H EtNH (A) 57 Me 4-Py -NH- 3-PyNH H EtNH (B) 58 Me 4-Py-NH- 3-PyNH H EtNH (C) 59 Me 4-Py-NH- 3-PyNH H PhCH2CH2NH (A) .60 Me 4-Py ~ NH_ 3-PyNH / H PhCH2CH2NH (B) 61 Me 4-Py-NH-3-PyNH Ph .H 62 Me 4-Py -NH- 3-PyNH Ph 1-Pyra 63 Me. 4-Py-NH- 3-PyNH Ph 1-Imid 64 Me 4-Py ~ NH- 3-PyNH Ph 1-Azt 65 Me 4-Py -NH- 3-PyNH Ph Pyra (A ) 66 Me 4-Py ~ NH- 3-PyNH Ph nh2 67 Me 4-Py -NH- '3-PyNH Ph MeNH 68 Me 4-Py -NH- 3-PyNH Ph. EtNH (A) 69 Me 4-Py _NH ~ 3-PyNH Ph EtNH⑻ 70 Me 4-Py -NH- 3-PyNH Ph EtNH (C) 71 Me • 4-Py-NH- 3-PyNH Ph PhCH2CH2NH (A) 72 Me 4-Py -NH- 3- PyNH Ph PhCH2CH2_) 73 Me 4-Py ~ NH * ~ 3-PyNH 3-Th H 74 Me 4-Py-NH- 3-PyNH 3-Th 1-Pyra 75 Me 4-Py-NH-3-PyNH 3- Th 1-Imid 76 Me 4-Py -leg- 3-PyNH 3-Th 1-Azt -55-200524880 17 Me 4-Py -leg- .PhNH Ph Pyra (A) 18 Me 4-Py -NH- PhNH Ph Muscle 19 Me 4-Py-Leg-PhNH Ph Me Re 20 Me 4-Py -NH-. PhNH Ph EtNH (A) 21 Me 4-Py-NH- PhNH Ph EtNH⑻ 22 Me 4-Py-NH- PhNH Ph EtNH (C) 23 Me 4-Py -NH-PhNH Ph PhCH2CH2NH (A) 24 Me 4-Py -NH- PhNH Ph PhCH2CH2NH (B) 25 Me 4-Py _NH-PliNH 3-Th H 26 Me 4-Py.- NH- PhNH 3-Th 1-Pyra 27 M e 4-Py -NH-PhNH 3-Th Hmid 28 Me 4-Py-NH- PhNH 3-Th 1-Azt 29 Me 4-Py -NH-PhNH. 3-Th Pyra (A) 30 Me. 4-Py -NH- PhNH 3-Th nh2 31 Me 4-Py-NH- PhNH .3-Th MeNH 32 Me 4-Py -NH- PhNH 3-Th EtNH (A) 33 Me 4-Py-NH- PhNH 3-Th E-brain 34 Me 4-Py -NH- PhNH 3-Th EtNH (C) 35 Me 4-Py-NH- PhNH 3-Th PhCH2CH2NH (A) 36 Me 4-Py -NH- PhNH 3-Th PhCH2CH2NlKB) 37 Me 4-Py-NH- .PhNH 2-MeC6H4 H 38. Me 4-Py -NH_ PhNH 2-MeC6H4 1-Pyra 39 Me 4-Py -NH- PtiNH 2-MeC6H4 1-Imid 40 Me 4-Py-NH -PhNH 2-MeC6H4 1-Azt 41 Me 4-Py-NH- PhNH 2-MeC6H4 Pyra (A) 42 Me 4-Py -NH-PhNH 2-MeC6H4 nh2 43 Me 4-Py PhNH 2-MeC6H4 MeNH 44 Me 4 -Py-NH- H 2-MeC6H4 EtNH (A) 45 Me 4-Py-NH- PhNH 2-MeC6H4 EtNH (B) 46 Me 4-Py-NH- PhNH 2-MeC6H4 EtNH (C) -56- 200524880 77 Me 4-Py-NH-3-PyNH 3-Th Pyra (A) 78 Me 4-Py -NH- 3-PyNH 3-Th nh2 79 Me 4-Py _NH-3-PyNH 3-Th MeNH 80 Me 4- Py -NH- '.3-Py Li 3-Th EtNH (A). 81 Me 4-Py -NH-' 3-PyNH 3-Th EtNH (B) 82 Me 4-Py-NH- 3-PyNH 3- Th EtNH (C) 83 Me 4- Py .-NH-3-PyNH .3-Th PhCH2CH2NH (A) 84 Me 4-Py-NH- 3-PyNH 3-Th PhCH2CH2NH ⑻ 85 Me 4-Py-NH- 3 ~ PyNH 2-MeC6H4 H 86 Me 4 -Py ~ NH ~ 3-PyNH 2-MeC6H4 1-Pyra 87 Me 4-Py-NH- 3-PyNH 2_MeC6H4 1-Imid 88 Me 4-Py-NH- 3-PyNH 2-MeC6H4 1-Azt 89 Me 4- Py -NH-3-PyNH 2-MeC6H4 Pyra (A) 90 Me 4-Py · -NH- 3-PyNH 2-MeC6H4 • nh2 91 Me 4-Py-NH- 3-PyNH · 2-MeC6H4 MeNH 92 Me 4 -Py -NH- 3-PyNH 2-MeC6H4 • EtNH (A) 93 Me 4-Py-NH- 3-PyNH 2-MeC6H4 E sprinkler 94 Me 4-Py -NH- 3-PyNH 2-MeC6H4 EtNH (C ) 95 Me 4-Py -NH- 3-PyNH 2-MeC6H4 PhCH2CH2NH (A) 96 Me 4-Py -NH- 3-PyNH 2-MeC6H4 PhCH2CH2NH ⑻ 97 Me 4-Py-NH-Ph (A) NH HH 98 Me 4-Py -NH-Ph (A) NH H 1-Pyra 99 Me 4-Py -NH- Ph (A) NH H 1-Imid 100 Me 4-Py-NH- Ph (A) NH H 1-Azt 101 Me 4-Py -NH-Ph (A) NH H Pyra (A) 102 Me 4-Py-NH-Ph (A) NH H nh2 103 Me 4-Py -NH- Ph (A) NH H MeNH 104 Me 4-Py-NH-, Ph (A) NH H EtNH (A) 105 Me 4-Py -NH- Ph (A) NH H * EtNH ⑻, 106 Me 4-Py -NH- Ph (A) NH H EtNH (C) -57- 200524880 107 Me 4-Py ~ NH- Ph (A) N HH PhCH2CH2NH (A) 108 Me 4-Py -NH- Ph (A) NH H PhCH2CH2NH (B) 109 Me 4-Py -NH- Ph (A) NH Ph H 110 Me, 4-Py -NH- Ph (A ) NH Ph 1-Pyra ill Me 4-Py -NH-Ph (A) NH Ph 1-Imid 112 Me 4-Py -NH-Ph (A) NH Ph l "Azt 113 Me 4-Py -NH-Ph ( A) NH .Ph Pyra (A) 114 Me 4-Py -NH-Ph (A) NH Ph nh2 115 Me 4-Py -NH-Ph (A) NH Ph MeNH 116 Me 4-Py -NH-Ph (A ) NH Ph EtNH (A) 117 Me 4-Py-NH- Ph (A) NH Ph Et_) 118 Me .4-Py-NH- Ph (A) NH .Ph EtNH (C) 119 Me 4-Py-NH -Ph (A) NH Ph. PhCH2CH2NH (A) 120 Me 4-Py • -NH- Ph (A) NH. Ph PhCH2CH2NiKB) 121 Me 4-Py -NH-Ph (A) NH 3-Th H 122 Me 4 -Py-NH_ Ph (A) NH J-Th 1-Pyra 123 Me 4-Py-NH-Ph (A) NH 3-Th 1-Imid 124 Me 4-Py-NH-Ph (A) NH 3-Th 1-Azt 125 Me 4-Py-NH-Ph (A) NH 3-Th Pyra (A) 126 .Me 4-Py -NH-Ph (A) NH 3-Th nh2-127 Me 4-Py-NH- Ph (A) NH 3-Th MeNH 128 Me 4-Py-NH- Ph (A) NH 3-Th EtNH (A) 129 Me 4-Py -NH- Ph (A) NH 3-Th EtNH (B) 130 Me 4-Py-NH-Ph (A) NH 3-Th EtNH (C) 131 Me 4-Py -NH-Ph (A) NH 3-Th PhCH2CH2NH (A) 132 Me 4-Py-NH_ .Ph (A ) NH 3-Th Ph CH2CH2NH (B) 133 Me 4-Py-NH-Ph (A) NH 2-MeC6H4 H 134 Me 4-Py -NH-. Ph (A) NH 2-MeC6H4 1-Pyra 135 Me 4-Py-NH- Ph (A) NH 2-MeC6H4 1-Imid 136 Me 4-Py-NH-Ph (A) NH 2-MeC6H4 1-Azt -58- 200524880 137 Me 4-Py -NH-Ph (A) NH 2-MeC6H4 Pyra (A) 138 Me 4-Py -leg- Ph (A) NH 2-MeC6H4 nh2 139 Me 4 ~ Py -Li- Ph (A) NH 2-MeC6H4 140 Me 4-Py -NH ~ Ph (A) NH 2 -MeC6H4 EtNH (A) 141 Me 4-Py -leg- Ph (A) NH 2-MeC6H4 EtNH⑻ 142 Me 4-Py -NH-. Ph (A) NH 2-MeC6H4 EtNH (C) 143 Me 4-Py- NH-Ph (A) NH 2-MeC6H4 PhCH2CH2NH (A) 144 Me 4-Py. -NH- Ph (A) NH 2-MeC6H4 PhCH2CH2NH ⑻ 145 Me 4-MeS02C6H4 -NH- PliNH HH 146 Me 4-MeS02C6H4 -NH -PhNH H 1-Pyra 147 Me 4-MeS02C6H4 -NH- PhNH .H 1-Imid 148 Me 4-MeS02C6H4 -NH- PhNH H 1-Azt 149 Me 4-MeS02C6H4 -NH- PhNH H Pyra (A) 150 Me • 4-MeS02C6H4-ΝΉ- PhNH H 2 151 Me 4-MeS02C6H4 -NH- PhNH. *: H MeNH 152 Me 4-MeS02C6H4-NH- PhNH H EtNH (A) 153 Me 4-MeS02C6H4 -NH- PhNH. H EtNH ( B) 154 Me 4-MeS02C6H4 -NH- PhNH H EtNH (C) 155 Me 4 ~ M6S02C6H4 -NH- PhNH H PhCH2CH2NH (A) 156 Me 4-MeS02C6H4 -NH ~ PhNH H PhCH2CH2NH ⑻ 157 Me 4_MeS02C6H4-NH-PhNH Ph H 158 Me. 4-MeS02C6H4-NH- PhNH Ph 1-Pyra 159 Me 4-MeS02C6H4 ',-PhNH Ph 1 -Imid 160 Me 4-MeS02C6H4 -NH-. PhNH Ph 1-Azt 161 Me 4 ~ MeS02C6H4 -NH- PhNH Ph Pyra (A) 162 Me 4-MeS02C6H4 -NH- PhNH Ph NH2

163 Me 4-MeS02C6H4-NH-PhNH Ph MeNH 164 Me 4-MeS02C6H4 -NH- PhNH Ph EtNH (A) 165 Me 4-MeS02C6H4 -NH- PhNH Ph, EtNH (B) 30 166 Me 4-MeS02C6H4 -NH- PhNH Ph EtNH (C) -59- 200524880 167 Me 4-MeS02C6H4-NH- PhNH Ph. PhCH2CH2NH (A) '168 Me 4-MeS02C6H4 -NH- Ph Ph PhCH2CH2NH (B). 169 Me 4-MeS02C6H4-NH-PhNH 3-Th H 170 Me 4-MeS02C6H4-NH-PhNH 3-Th 1-Pyra 171 Me 4-MeS02C6H4-NH- PhNH 3-Th 1-Imid 172 Me 4-MeS02C6H4-NH- PhNH 3-Th 1-Azt 173 Me 4-MeS02C6H4.-NH- PhNH 3-Th Pyra (A) 174 Me 4-MeS02C6H4-NH- PhNH 3-Th nh2 · 175 Me 4-MeS02C6H4 -NH- PhNH 3-Th MeNH 176 Me 4-MeS02C6H4-NH -PhNH 3-Th EtNH (A) 177 Me 4-MeS02C6H4:-NH- PhNH 3-Th EtNH⑻ 178 Me 4-MeS02C6H4-NH- PhNH 3-Th EtNH (C) 179 Me .4-MeS02C6H4-NH- PhNH 3 -Th PhCH2CH2NH (A) 180 Me 4-MeS02C6H4-NH- PhNH 3-Th PhCH, CH2NH (B) 181 Me 4-MeS02C6H4 -NH- · PhNH 2-MeC6H4 H 182 Me 4-MeS02C6H4-NH-PhNH 2-MeC6H4 1-Pyra 183 Me 4 ~ MeS02C6H4-NH- PhNH 2-MeC6H4 1-Imid 184 Me 4-MeS02C6H4.-NH-PhNH 2-MeC6H4 Azt 185 Me 4-MeS02C6H4-NH-PhNH 2-MeC6H4 Pyra (A) 186 Me 4-MeS02C6H4 -NH- PhNH 2-MeC6H4 nh2 187 Me 4-MeS〇2C6H4-NH- PhNH 2-MeC6H4 MeNH 188 Me 4-MeS02C6H4 -NH-PhNH 2-MeC6H4 EtNH (A) 189 Me 4-Me.S02C6H4-NH- PhNH 2-MeC6H4 EtNH (B) 190 Me 4-MeS02C6H4 -NH- PhNH 2-MeC6H4 EtNH (C) 191 Me 4:-MeS02C6H4-NH-PhNH 2-MeC6H4 PhCH2CH2NH (A) 192 Me 4-MeS02C6H4 -NH- PhNH 2-MeC6H4 PhCH2CH2NH (B) 193 Me 4-MeS02C6H4-NH- 3-PyNH HH 194 Me 4-MeS02C6H NH- 3-PyNH H 1-Pyra 195 Me 4_M6S02C6H4 -NH-3 ~ PyNH H 1-Imid 196 Me 4-MeS02C6H4 -NH-3-PyNH H 1-Az t

Reference -60- 200524880 197 Me 4-MeS02C6H4 -NH- 3-PyNH H Pyra (A) 198 Me.  4-MeS02C6H4 -NH-3-PyNH H nh2 199 Me 4-MeS02C6H4-NH-3-PyNH H MeNH 200 Me 4-MeS02C6H4 -NH- '3-PyNH H EtNH (A) 201 Me 4-MeS02C6H4 -NH-3 -PyNH H EtNH (B) 202 Me 4-MeS02C6H4-3-PyNH H EtNH (C) 203 Me 4-MeS02C6H4 -NH-.  . 3-PyNH H PhCH2CH2NH. (A) 204 Me 4-MeS02C6H4 -NH- 3-PyNH • H PhCH2CH2NH (B) 205 Me 4-MeS02C6H4-NH- 3-PyNH Ph H 206 Me 4-MeS02C6H4-NH- 3-PyNH Ph 1-Pyra 207 Me 4-MeS02C6H4. -NH- 3-PyNH Ph 1-Imid 208 Me 4-MeS02C6H4 -NH- 3-PyNH Ph 1-Az t 209 Me 4-MeS02C6H4 -NH_ 3-PyNH Ph Pyra (A) 210 Me 4-MeS02C6H4-NH-3 -PyNH Ph nh2.   211 Me 4-MeS02C6H4-NH- 3-PyNH Ph MeNH 212 Me 4-MeS02C6H4-NH- 3-PyNH Ph EtNH (A) 213 Me 4-MeS02C6H4-NH- 3-PyNH Ph EtNH (B) 214 Me 4-MeS02C6H4 -NH- 3-PyNH Ph EtNH (C) 215 Me 4-MeS02C6H4-NH- 3-PyNH Ph PhCH2CH2NH (A) 216 Me 4-MeS02C6H4-NH- 3-PyNH Ph PhCH2CH2NH ⑻ 217 Me 4-MeS02C6H4 rNH- 3- PyNH 3-Th H 218 Me 4-MeS02C6H4 -NH-3-PyNH 3-Th l ~ Pyra 219 Me 4-MeS02C6H4 -NH- 3-PyNH 3-Th 1-Imid 220 Me 4-MeS02C6H4-NH-3-PyNH 3-Th 1-Azt 221 Me 4-MeS02C6H4-NH- 3-PyNH 3-Th Pyra (A) 222 Me 4-MeS02C6H4-NH- 3-PyNH 3-Th nh2 223 Me 4-MeS02C6H4 -NH- 3-PyNH 3-Th • MeNH 224 Me 4-MeS02C6H4 -NH- 3-PyNH 3-Th EtNH (A) 225 Me 4-MeS02C6H4-NH-3-PyNH 3-Th EtNH (B) 226 Me 4-MeS02C6H4 • -NH- 3-PyNH 3-Th EtNH (C) -61-200524880 227 Me 4-MeS02C6H4-NH- 3-PyNH 3-Th PhCH2CH2NH (A) 228 Me.  4-MeS02C6H4 -NH- 3-Py Li 3-Th PhCH2CH2NH (B) 229 Me 4-MeS02C6H4 _NH-3-PyNH 2-MeC6H4 H 230 Me 4-MeS02C6H4 -NH- 3-PyNH 2-MeC6H4 1-Pyra 231 Me 4-MeS02C6H4 -NH- 3-PyNH 2-MeC6H4 1-Imid 232 Me 4-MeS02C6H4 -leg- 3-PyNH 2-MeC6H4 1-Azt 233 Me 4-MeS02C6H4 -NH- 3-PyNH 2-MeC6H4 Pyra (A) 234 Me 4-MeS02C6H4-NH-3-P. yNH 2-MeC6H4 nh2 235 Me 4-MeS02C6H4. -NH- 3-PyNH.  2-MeC6H4 MeNH 236 Me 4-MeS02C6H4 -NH- 3-PyNH 2-MeC6H4 EtNH (A) '237 Me 4-MeS02C6H4-NH- 3-PyNH 2-MeC6H4 EtNH (B) 238 Me 4-MeS02C6H4-NH- 3 -PyNH 2-MeC6H4 E Xinjiang 239 Me 4-MeS02C6H4-NH- 3-PyNH 2-MeC6H4 PhCH2CH2NH (A) 240 Me 4-MeS02C6H4 -NH-3-PyNH 2-MeC6H4 PhCH2CH2NH (B) 241 Me 4-MeS02C6H4- NH- Ph (A) NH H. H 24. 2 Me 4-MeS02C6H4 -NH-Ph (A) NH H 1-Pyra 243 Me 4-MeS02C6H4 _NH-Ph (A) NH H 1-Imid 244 Me 4-MeS02C6H4 -NH- 'Ph (A) NH H 1- Azt 245 Me 4-MeS02C6H4 ~ NH- Ph (A) NH H Pyra (A) 246 Me 4-MeS02C6H4 -NH- Ph (A) NH H nh2 247 Me 4-MeS02C6H4-NH- Ph (A) NH H. MeNH 248 Me 4-MeS02C6H4-NH- Ph (A) NH.  H. EtNH (A) 249 Me 4-MeS02C6H4-NH- Ph (A) NH H EtNH ⑻ 250 Me 4-MeS02C6H4 -NH- Ph (A) NH H EtNH '(C) 251 Me 4-MeS02C6H4 -NH-Ph (A ) NH H PhCH2CH2NH (A) 252 Me 4-MeS02C6H4-NH-Ph (A) NH H PhCH2CH2NH (B) 253 Me 4-MeS02C6H4 -NH-Ph (A) NH Ph H 254 Me 4-MeS02C6H4 -NH ~ Ph ( A) NH Ph 1-Pyra 255 Me 4-MeS02C6H4 -NH-Ph (A) NH Ph 1-Imid 256 Me 4-MeS02C6H4-NH-Ph (A) NH Ph 1-Azt -62- 200524880 257 Me 4-MeS02C6H4 -NH- Ph (A) NH Ph Pyra (A) 258 • Me 4-MeS02C6H4 -NH- Ph (A) NH Ph nh2 259 Me 4-M6S02C6H4 -volume-. Ph (A) NH Ph MeNH 260 Me 4-MeS02C6H4 -NH- · Ph (A) NH Ph EtNH (A) 261 Me 4_MeS02C6H4 -NH- Ph (A) NH Ph EtNH⑻ 262 Me 4-MeS02C6H4 ~ NH_ Ph (A) NH Ph EtNH (C) 263 Me 4-MeS02C6H4 -NH-Ph (A) NH Ph PhCH2CH2NH (A) 264 Me 4-MeS02C6H4 -leg- Ph (A) NH Ph PhCH2CH2NH (B) 265 Me 4-MeS02C6H4 -Li- Ph (A) NH 3-Th H 266 Me 4-MeS02C6H4-NH- Ph (A) NH 3-Th 1-Pyra 267 Me 4-MeS02C6H4-NH- Ph (A) NH 3-Th.  1-Imid 268 Me 4-MeS02C6H4 -NH-Ph (A) NH 3-Th l-Azt 269 Me 4-MeS02C6H4 -NH- Ph (A) NH 3-Th Pyra (A) 270 Me 4-MeS02C6H4-NH- Ph (A) NH 3-Th nh2 271 Me 4-MeS02C6H4 -NH- Ph (A) NH. 3-Th MeNH 272 Me 4-MeS02C6H4 -NH- Ph (A) NH 3-Th EtNH (A) 273 Me 4-MeS02C6H4-NH-Ph (A) NH 3-Th EtNH⑻ 274 Me 4-MeS02C6H4 ~ NH_ Ph ( A) NH 3-Th EtNH (C) 275 Me 4-MeS02C6H4-NH- Ph (A) NH 3-Th PhCH2CH2NH (A) 276 Me 4-MeS02C6H4-NH- Ph (A) NH 3-Th PhCH2CH2N1KB) 277 Me 4-MeS02C6H4-NH-Ph (A) NH 2-MeC6H4 H 278 Me 4-MeS02C6H4-NH- Ph (A) NH 2-MeC6H4 1-Pyra 279 Me 4-MeS02C6H4-NH- Ph (A) NH 2-MeC6H4 1-Imid 280 Me 4-MeS02C6H4-NH- Ph (A) NH 2-MeC6H4 l-Azt 281 Me 4-MeS02C6H4 -NH- Ph (A) NH 2 ~ MeC6H4 Pyra (A) 282 Me 4-MeS02C6H4-NH- Ph (A) NH 2-MeC6H4.  nh2 283 Me 4-MeS02C6H4-NH- Ph (A) NH 2-MeC6H4 MeNH 284 Me 4-MeS02C6H4-NH- Ph (A) NH 2-MeC6H4 EtNH (A) 285 Me 4-MeS02C6H4. -NH-Ph (A) NH 2-MeC6H4 EtNH (B) 286 Me 4-MeS02C6H4-NH-Ph (A) NH 2-MeC6H4 EtNH (C) -63- 200524880 287 Me 4_MeS02C6H4 -NH- Ph (A) NH 2-MeC6H4 PhCH2CH2NH (A) 288 Me 4-MeS02C6H4 -NH-Ph (A) NH 2-MeC6H4 PhCH2CH2NH ⑻ 289 Me 4-Me Li S02C6H4-NH-PhNH HH 290 Me 4-MeNHS02C6H4-NH- PhNH H 1-Pyra 291 Me 4-MeNHS02C6H4.  -NH-PhNH H 1-Imid 292 Me 4-MeNHS02C6H4 -NH- PhNH H 1-Azt 293 Me 4-MeNHS02C6H4-NH- PhNH H Pyra (A) 294 Me 4-MeNHS02C6H4-NH- PhNH H nh2 295 Me 4- MeNHS02C6H4-NH-PhNH H MeNH 296 Me 4-MeNHS02C6H4 -NH- PhNH H EtNH (A) 297 Me 4-MeNHS02C6H4 -NH- PhNH H EtNH (B) 298.  Me 4-Me_2C6H4-NH-PhNH H EtNH ⑹ 299 Me 4-MeNHS02C6H4 -NH- PhNH H PhCH2CH2NH (A) 300 Me 4-MeNHS02C6H4-NH-PhNH.  H PhCH2CH2NHKB) 301 Me 4-MeNHS02C6H4 -NH-PhNH Ph H 302 Me 4-MeNHS02C6H4-NH-PhNH Ph 1-Pyra 303 Me 4-MeNHS02C6H4 -NH- PhNH.  Ph 1-Imid 304 Me 4-MeNHS02C6H4 -M-PhNH Ph 1 -Az t 305 Me 4-MeNHS02C6H4 -NH- PhNH Ph Pyra (A) 306 Me 4-MeNHS02C6H4-NH-PhNH Ph nh2 307 Me 4-MeNHS02C6H4 -NH -PhNH Ph MeNH 308 Me 4_MeNHS02C6H4 -NH-PhNH Ph EtNH (A) 309 Me 4-MeNHS02C6H4-NH-PhNH Ph EtNH (B) 310 Me 4-MeNHS02C6H4-NH-PhNH Ph EtNH (C) 311 Me 4-Me_2C6H4 _NH ~ PhNH Ph PhCH2CH2NH (A) 312 Me 4-Me Bribe S02C6H4 -NH- PhNH Ph PhCH2CH2_) 313 Me 4-MeNHS02C6H4-NH-PhNH 3-buth H 314 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th 1-Pyra 315 Me 4-MeNHS02C6H4 -NH-.  PhNH 3-Th 1-Imid 316 Me 4-MeNHS02C6H4 ~ NH ~ PhNH 3-Th 1-Azt -64- 200524880 317 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th Pyra (A) 318 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th Li 2 319 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th MeNH '320 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th EtNH (A) 321 Me 4-MeNHS02C6H4 -Li- PhNH 3-Th E Xinjiang ⑻ 322 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th EtNH (C) 323 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th PhCH2CH2NH (A) 324 Me 4-MeNHS02C6H4 -NH-PhNH 3-Th PhCH2CH2NH (B) 325 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 H 326 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 1-Pyra 327 Me 4-MeNHS02C6H4-NH- PhNH 2-MeC6H4 1-Imid 328 Me '4-MeNHS02C6H4 -NH -PhNH 2-MeC6H4 1-Azt 329 Me 4-MeNHS02C6H4 _NH ~ PhNH 2-MeC6H4 Pyra (A) 330 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 nh2 · 331 Me.  4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 MeNH 332 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 EtNH (A) 333 Me 4-MeNHS02C6H4 '-NH- PhNH 2-MeC6H4 E wake up • 334 Me.  4-MeNHS02C6H4 -NH- PhNH 1 2-MeC6H4 EtNH (C) 335 Me 4-MeNHS02C6H4-NH- PhNH 2-MeC6H4 PhCH2CH2NH (A) 336 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 PhCH2CH2NH4 (B) -MeNHS02C6H4-NH- 3-PyNH HH 338 Me 4-MeNHS02C6H4 _NH-3-PyNH H 1-Pyra 339 Me 4-MeNHS02C6H4 -NH- 3-PyNH H 1-Imid 34. 0 Me 4-MeNHS02C6H4-NH-3-PyNH H 1-Azt 341 Me 4-MeNHS02C6H4-NH- 3-PyNH H Pyra (A) 342 Me 4-MeNHS02C6H4 _NH_ 3-PyNH H nh2 343 'Me 4-MeNHS02C6H4 -NH -3-PyNH H MeNH 344 Me 4-MeNHS02C6H4 -NH- 3-PyNH H EtNH (A) 345 Me 4-MeNHS02C6H4-NH- 3-PyNH H EtNH⑻ 346 Me 4-MeNHS02C6H4 -NH- 3-PyNH H EtNH (C ) -65- 200524880 347 Me 4-MeNHS02C6H4 -NH- 3-PyNH H PhCH2CH2NH (A) 348 Me 4-MeNHS02C6H4 -NH- 3-PyNH H PhCH2CH2_) 349 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph.  H 350 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph 1-Pyra 351 Me 4-MeNHS02C6H4 -NH-.  3-PyNH Ph 1-Imid 352 Me 4-MeNHS02C6H4 -NH- 3-Py Li Ph 1-Azt 353.  Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph Pyra (A) 354 Me 4-MeNHS02C6H4 -NH-3-PyNH Ph nh2 355 Me 4-MeNHS02C6H4 -NH-3-PyNH Ph MeNH · 356 • Me 4-MeNHS02C6H4. _NH- 3-PyNH Ph EtNH (A) 357 Me 4-MeNHS02C6H4-NH-3-PyNH P. h EtNH (B) 358 Me 4-MeNHS02C6H4 -NH-3-PyNH Ph EtNH (C) 359 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph PhCH2CH2NH (A) 360 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph PhCH2CH2_ ) 361 Me 4-MeNHS02C6H4 -NH- 3-PyNH. 3-Th H 362 Me 4-MeNHS02C6H4 -NH- 3-PyNH. 3-Th 1-Pyra 363 Me 4-MeNHS02C6H4-NH- 3-PyNH 3-Th Imid 364 Me 4-MeNHS02C6H4 -NH- 3-PyNH 3-Th 1-Azt 365 Me 4-MeNHS02C6H4-Leg- 3-Py Li 3-Th Pyra (A) 366 Me 4-MeNHS02C6H4 -NH-3-PyNH 3-Th nh2 367 Me 4-MeNHS02C6H4 -NH-3-PyNH 3-Th MeNH 368 Me 4-MeNHS02C6H4-NH-3-PyNH 3 -Th 'EtNH (A) 369 Me 4-MeNHS02C6H4 -NH- 3-PyNH 3-Th EtNH (B) 370 Me 4-MeNHS02C6H4-NH-3-PyNH 3-Th EtNH (C) 371 Me 4-MeNHS02C6H4 -NH -3-PyNH 3-Th PhCH2CH2NH〇 \) 372 Me 4-MeNHS02C6H4 -NH-3-PyNH 3-Th PhCH2CH2_) 373 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 H 374 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 1-Pyra 375 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 1-Imid 376 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 1-Azt -66-200524880 377 Me 4 -Me Re S02C6H4 -NH- 3-PyNH 2-MeC6H4 Pyra (A) 378 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 nh2 379 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 MeNH 380 Me • 4-MeNHS02C6H4 -NH- 3-PyNH 2-MeC6H4 EtNH (A) 381 Me 4-Me Rei S02C6H4-NH- 3-PyNH 2-MeC6H4 Et Rei 382 Me 4-MeNHS02C6H4 -NH- 3 -PyNH 2-MeC6H4 EtNH (C) 383 Me 4-Me Li S02C6H4 -NH- 3-PyNH 2-MeC6H4 PhCH2CH2NH (A) 384 Me 4-MeNHS02C6H4 -NH-3-PyNH 2-MeC6H4 PhCH2CH2NH (B) 385 Me 4 -MeNHS02C6H4-NH- Ph (A) NH HH 386 Me 4-MeNHS02C6H4 -NH- Ph (A) NH H 1-Pyra 387 Me 4-MeNHS02C6H4-NH-Ph (A) NH H 1-Imid 388 Me 4-MeNHS02C6H4 -NH- Ph (A) NH H 1-Azt 389 Me 4-MeNHS02C6H4 -NH_ Ph (A) NH H Pyra (A) 390 Me 4-MeNHS02C6H4 -NH- Ph (A) N. HH nh2 391 Me 4-MeNHS02C6H4 -NH- Ph (A) NH H MeNH 392 Me 4-MeNHS02C6H4 -NH_ Ph (A) NH H EtNH (A) 393 Me 4-MeNHS02C6H4 -NH- Ph (A) NH H EtNH ( B) 394 Me 4-MeNHS02C6H4-NH- Ph (A) NH H EtNH (C) 395 Me 4-MeNHS02C6H4-NH-Ph (A) NH H PhCH2CH2NH (A) 396 Me 4-MeNHS02C6H4 -NH-Ph (A) NH H PhCH2CH2_) 397 Me 4-MeNHS02C6H4-NH- Ph (A) NH Ph H 398 Me 4-Me Band S02C6H4-NH- Ph ㈧ NH Ph 1-Pyra 399 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph 1-Imid 400 Me 4-MeNHS02C6H4-. -Ph (A) NH Ph 1-Azt 401 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph Pyra (A) 402 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph nh2 403 Me 4-MeNHS02C6H4 -NH -Ph (A) NH Ph MeNH 404 Me 4-Me Book S02C6H4 -NH- 'Ph (A) NH Ph EtNH (A) 405 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph EtNH ⑻ 406 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph EtNH (C) -67-200524880 407 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph PhCH2CH2NH (A) 408 Me 4-MeNHS02C6H4 -M- Ph (A) NH Ph PhCH2CH2NH (B) 409 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 3-Th H 410 Me 4-MeNHS02C6H4 -Volume-Ph (A) NH 3-Th 1-Pyra 411 Me 4-MeNHS02C6H4-NH-Ph (A ) NH 3-Th 1-Imid 412 Me 4-MeNHS02C6H4 -leg- Ph (A) NH 3-Th 1-Azt 413 Me 4-MeNHS02C6H4-NH-Ph (A) NH 3-Th Pyra (A) 414 Me 4 -MeNHS02C6H4-NH-Ph (A) NH 3-Th nh2 415 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 3-Th MeNH 416 Me 4-MeNHS02C6H4-NH- Ph (A) NH 3-Th EtNH (A ) 417 Me 4-MeNHS02C6H4-NH- Ph (A) NH 3-Th EtNH (B) 418 Me 4-MeNHS02C6H4-NH- Ph (A) NH 3-Th EtNH (C) 419 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 3-Th PhCH2CH2NH (A) 420 Me 4-MeNHS02C6H4 -NH-Ph (A) NH 3-. Th PhCH2CH2NHKB) 421 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-MeC6H4 H 422 Me 4-MeNHS02C6H4 -NH-Ph (A) NH 2-MeC6H4 1-Pyra 423 Me 4-MeNHS02C6H4 -NH-.  Ph (A) NH 2-MeC6H4 1-Imid 424 Me 4-MeNHS02C6H4-NH-Ph (A) NH 2-MeC6H4 l ~ Az t 425 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-MeC6H4 Pyra (A ) 426 Me 4-MeNHS02C6H4-NH_ Ph (A) NH 2-MeC6H4 nh2 427 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-MeC6H4 MeNH 428 Me 4-MeNHS02C6H4 -NH-Ph (A) NH 2-MeC6H4 EtNH (A) 429 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-MeC6H4 Et_) 430 Me 4-Me Li S02C6H4 -NH- Ph (A) NH 2-MeC6H4 EtNH (C) 431 Me 4-MeNHS02C6H4- NH- Ph (A) NH 2-MeC6H4 PhCH2CH2NH (A) 432 Me 4-MeNHS02C6H4 -NH- Ph (A) Li 2-MeC6H4 PhCH2CH2NH ⑻ 433 Me 4-Py-NH-3-Py HH 434 Me 4-Py- NH- 3-Py H 1-Pyra 435 Me 4-Py -NH- 3-Py H 1-Imid 436 Me 4-Py _NH_ 3-Pv H 1-Azt -68- 200524880 437 Me 4-Py -NH- 3 -Py H Pyra (A) 438 Me 4-Py _NH- 3-Py H nh2 439 Me 4-Py -NH- 3-Py H MeNH 440 Me 4-Py -NH- '3-Py H Et Li (A) 441 Me 4-Py -NH- 3-Py H EtNH (B) 442 Me 4-Py -NH- 3-Py H EtNH (C) 443 Me 4-Ργ -NH- 3-Py H PhCH2CH2NH (A) 444 Me 4-Py -NH- 3-Py H PhCH2CH2NH (B) 445 Me 4-Py -NH- 3-Py Ph H 446 Me 4-Py -NH- 3-Py Ph 1-Pyra 447 Me 4-Py-NH- 3- Py Ph 1-Imid 448 Me 4-Py -NH- 3-Py Ph 1-Azt 449 Me 4-Py -NH-3-Py.  Ph.  Pyra (A) 450 Me 4-Py _NH ~ 3-Py Ph nh2 451 Me 4-Py-NH-3-Py Ph MeNH 452 Me 4-Py -NH-3-Py Ph EtNH (A) 453 Me 4-Py -NH-3-Py Ph EtNH (B) 454 Me • 4-Py-NH- 3-Py Ph EtNH (C) 455 Me 4-Py -leg- 3-Py Ph PhCH2CH2NH (A) 456 Me 4-Py- NH- 3-Py Ph PhCH2CH2NH (B) 457 Me 4-Py -NH-3-Py 3-Th H 458 Me 4-Py -NH- '3-Py 3-Th 1-Pyra 459 Me 4-Py -NH -3-Py 3-Th 1-Imid 460 Me 4-Py-NH-3-Py 3-Th 1-Azt 461 Me 4-Py -NH- 3-Py 3-Th Pyra (A) 462 Me 4-Py -NH-3-Py 3-Th nh2 463 Me 4-Py -NH-3-Py 3-Th MeNH 464 Me 4-Py -NH-3-Py 3-Th EtNH (A) 465 Me 4-Py -NH -3-Py 3-Th EtNH (B) 466 Me 4-Pv -NH- 3-Py 3-Th EtNH (C) -69- 200524880 467 Me 4-Py -M- 3-Py 3-Th PhCH2CH2NH (A ) 468 Me 4-Py -NH- 3-Py 3-Th PhCH2CH2NH (B) 469 Me 4-Py -NH- 3-Py 2-MeC6H4 H 470 Me 4-Py -NH- · 3-Py 2-MeC6H4 1 -Pyra 471 Me 4-Py-NH- 3-Py 2-MeC6H4 1-Imid 472 Me 4-Py-NH-3-Py 2-MeC6H4 1-Azt 473 Me 4-Py-NH- 3-Py 2-MeC6H4 Pyra (A) 474 Me 4-Py -NH- 3-Py 2-MeC6H4 nh2 475 Me 4-Py -leg- 3-Py 2-MeC6H4 MeNH 476 Me 4-Py -Li- 3-Py 2-MeC6H4 EtNH (A) 477 Me 4-Py -NH- 3-Py 2-MeC6H4 EtNH⑻ 478 Me 4-Py -NH-3-Py 2-MeC6H4 EtNH (C) 479 Me 4- Py -NH- 3-Py 2-MeC6H4 PhCH2CH2NH (A) 480 Me 4-Py -NH-3-Py 2-MeC6H4 PhCH2CH2NH (B) 481 Me 4-MeS02C6H4 -NH- 3-Py HH 482 Me 4_MeS02C6H4-NH- 3-Py H 1-Pyra 483 Me 4-MeS02C6H4 -NH-3-Py H 1-Imid 484 Me 4-MeS02C6H4 -NH-3-Py H 1-Azt 485.  Me 4-MeS02C6H4-NH-3-Py H Pyra (A) 486 Me 4-MeS02C6H4 _leg-3-Py H nh2 487 Me 4-MeS02C6H4 -NH- 3-Py H MeNH 488 Me 4-MeS02C6H4 -NH- 3 -Py H Et ㈧ 489 Me 4-MeS02C6H4 -NH- 3-Py H EtNH (B) 490 Me 4-MeS02C6H4 _NH ~ 3-Py H EtNH (C) 491 Me 4-MeS02C6H4 -NH- 3-Py H PhCH2CH2NH (A) 492 Me 4_MeS02C6H4 -NH- 3-Py H PhCH2CH2NH (B) 493 Me 4-MeS02C6H4 -NH ~ 3-Py Ph H 494 Me 4-MeS02C6H4-NH- 3-Py Ph 1-Pyra 495 Me 4-MeS02C6H4 -NH ~ 3-Py Ph 1-Imid 496 Me 4-MeS02C6H4 -NH- 3-Py Ph.  1-Azt -70- 200524880 497 Me 4-MeS02C6H4 -NH- 3-Py Ph Pyra (A) 498 Me 4-MeS02C6H4-NH-3-Py Ph nh2 499 Me 4-MeS02C6H4-NH- 3-Py Ph MeNH 500 Me 4-MeS02C6H4 -NH- 3-Py Ph EtNH (A) 501 Me 4-MeS02C6H4-NH-3-Py Ph EtNH (B) 502 Me, 4-MeS02C6H4 -NH-3-Py Ph EtNH (C).   503 Me 4-MeS02C6H4-NH- 3-Py Ph PhCH2CH2NH (A) 504 Me 4 ~ M6S02C6H4 -NH-3-Py Ph PhCH2CH2NH. ⑻ 505 Me 4-MeS02C6H4 -Li- 3-Py 3-Th H 506 Me 4-MeS02C6H4 -NH- 3-Py 3-Th 1-Pyra 507 Me 4-MeS02C6H4 -NH- 3-Py 3-Th 1-Imid 508 Me 4-MeS02C6H4 -NH- 3-Py 3-Th 1-Azt 509 Me 4-MeS02C6H4-NH-3-Py 3-Th Pyra (A) 510 Me 4 ~ M6S02C6H4. -NH- 3-Py 3-Th nh2 511 Me 4-MeS02C6H4-NH-3-Py 3-Th MeNH 512 Me 4-MeSQ2C6H4-NH-3-Py 3-Th EtNH (A) 513 Me 4-MeS02C6H4 -NH -3-Py 3-Th Et_) 514 Me 4-MeS02C6H4-NH-3-Py 3-Th EtNH (C) 515 Me 4-MeS02C6H4 -NH- 3-Py 3-Th PhCH2CH2NH (A) 516 Me 4 ~ M6S02C6H4 -NH-3-Py 3-Th PhCH2CH2 Lixi 517 Me 4-MeS02C6H4 -NH- 3-Py 2-MeC6H4 H 518 Me 4_MeS02C6H4-NH- 3-Py 2-MeC6H4 1-Pyra 519 Me 4-MeS02C6H4-Li- 3-Py 2_M? C6H4 1-Imid 520 Me 4 ~~ MeS02C6H4 -NH- 3-Py 2-MeC6H4 1-Azt 521 Me 4-MeS02C6H4 -NH- 3-Py 2-MeC6H4 Pyra (A) 522 Me 4_MeS02C6H4 -NH -3-Py 2-MeC6H4 nh2 523 Me 4 ~ * MeS02C6H4 ~ NH_ 3-Py 2-MeC6H4 MeNH 524 Me 4-MeS02C6H4 -NH- 3-Py 2-MeC6H4 EtNH (A) 525 Me 4-MeS02C6H4 -NH- 3 -Py 2-MeC6H4 EtNH (B) 526 Me.  4-MeS02C6H4 -NH- 3-Py, 2-MeC6H4 EtNH (C) -71-200524880 527 Me 4-MeS02C6H4 -NH- 3-Py 2-MeC6H4 PhCH2CH2NH (A) 528 Me 4-MeS02C6H4.  -NH- 3-Py 2-MeC6H4 PhCH2CH2_) 529 Me 4-MeNHS02C6H4 -NH- 3-Py HH 530 Me 4-MeNHS02C6H4 -NH- 3-Py H 1-Pyra 531 Me 4-MeNHS02C6H4 -Li- 3-Py H 1-Imid 532 Me 4-Me Li S02C6H4-NH- 3-Py H 1-Azt 533 Me 4-MeNHS02C6H4 -NH- 3-Py H Pyra (A) 534 Me 4-MeNHS02C6H4 '-NH-. 3-Py H nh2 535 Me 4-MeNHS02C6H4 -NH-3-Py H MeNH 536 Me 4-MeNHS02C6H4 -NH- 3-Py HE sprinkler 537 Me 4-MeNHS02C6H4-NH-3-Py H EtNH (B) 538 Me 4-MeNHS02C6H4 -NH- 3-Py H EtNH (C) 539 Me 4-MeNHS02C6H4 -NH- 3-Py H PhCH2CH2NH (A) 540 Me 4-MeNHS02C6H4 -NH-• 3-Py H PhCH2CH2NH ⑻ 541 Me 4-MeNHS02C6H4 -NH-3-Py Ph H 542 Me 4-M. eNHS02C6H4-NH- 3-Py Ph l ~ Pyra 543 Me 4-MeNHS02C6H4 -NH_ 3-Py Ph 1-Imid 544 Me 4-MeNHS02G6H4 -NH- 3-Py Ph 1-Azt 545 Me 4-MeNHS02C6H4 -NH- 3- Py Ph Pyra (A) 546 Me 4-MeNHS02C6H4 3-Py Ph nh2 547 Me 4-MeNHS02C6H4 -NH- 3-Py Ph MeNH 548 Me 4-MeNHS02C6H4-NH- 3-Py Ph EtNH (A) 549 Me 4-MeNHS02C6H4 -Legs-3-Py Ph EtNH (B). 550 Me 4-MeNHS02C6H4 -NH- 3-Py Ph EtNH (C) 551 Me 4-MeNHS02C6H4 -NH- 3-Py Ph PhCH2CH2NH (A) 552 Me 4-MeNHS02C6H4 -NH-3-Py Ph PhCH2CH2NH (B) 553 Me 4-MeNHS02C6H4 -NH- 3-Py 3-Th H 554 Me 4-MeNHS02C6H4 -NH-3-Pv 3-Th 1-Pyra 555 Me 4-MeNHS02C6H4.  -NH- 3-Py 3-Th 1-Imid 556 Me 4-MeNHS02C6H4 -NH- 3-Py 3-Th 1-Azt -72- 200524880 557 Me 4-MeNHS02C6H4 -NH- 3-Py 3-Th Pyra (A ) 558 Me 4-MeNHS02C6H4 -NH- 3-Py 3-Th nh2 559 Me 4-MeNHS02C6H4-NH- 3-Py 3-Th • MeNH · 560 Me 4-MeNHS02C6H4-NH- 3-Py 3-Th EtNH (A ) 561 Me 4-MeNHS02C6H4 -NH- 3-Py- 3-Th EtNH (B) 562 Me.  4-MeNHS02C6H4 -NH-3-Py 3-Th EtNH (C) 563 Me 4-MeNHS02C6H4-NH-3-Py 3-Th PhCH2CH2NH (A) 564 Me 4-MeNHS02C6H4 -NH-. 3-Py 3-Th PhCH2CH2NH (B) 565 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 H 566 Me 4-MeNHS02C6H4-NH- 3-Py 2-MeC6H4 1-Pyra 567 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 1-Imid 568 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 1-Azt 569 Me 4-MeNHS02C6H4 -NH-3-Py 2-MeC6H4 Pyra (A) 57. 0 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 nh2 571 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 MeNH 572 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 EtNH (A) 573 Me 4-MeNHS02C6H4 -NH- 3-Py 2-MeC6H4 E sprinkler 574 Me 4-MeNHS02C6H4 -NH-.  3-Py 2-MeC6H4 EtNH (C) 575 Me 4-MeNHS02C6H4-NH- 3-Py 2-MeC5H4 PhCH2CH2NH (A) 576 Me 4-MeNHS02C6H4-NH-3-Py 2-MeC6H4 PhCH2CH2NiUB) 577 Me 4-Py _NH ~ PhNH 2-FC6H4 H 578 Me 4-Py-NH-PhNH 2-FC6H4 1-Pyra 579 Me 4-Py -NH- PhNH 2-FC6H4 1-Imid 580 Me 4-Py _NH ~ PhNH 2-FC6H4 1-Azt 581 Me 4-Py -NH-PhNH 2-FC6H4 Pyra (A) 582 Me 4-Py -NH- PhNH 2-FC6H4 nh2 583 Me 4-Py -NH- PhNH 2-FC6H4 MeNH 584 Me 4-Py-NH- PhNH 2-FC6H4 EtNH (A) 585 Me 4-Py -NH- PhNH 2-FC6H4 EiNH (B) 586 Me 4-Py -NH- PhNH 2-FC6H4 EtNH (C) -73- 200524880 587 Me 4-Py- NH- PhNH 2-FC6H4 PhCH2CH2NH (A) 588 Me 4-Py -NH- PhNH 2-FC6H4 PhCH2CH2NH (B) 589 Me 4-Py -Li- 3-PyNH 2-FC6H4 H 590 Me 4-Py -NH-3 -Py Lai 2-FC6H4 1-Pyra 591 Me 4-Py ~ NH ~ 3-PyNH 2-FC6H4 1-Imid 592 Me 4-Py -Lai- 3-PyNH 2-FC5H4 1-Az t 593 Me 4-Py- NH- 3-PyNH 2-FC6H4 Pyra (A) 594 Me 4-Py ~ NH ~ 3-PyNH 2-FC6H4 nh2 595 Me 4-Py -NH- 3-PyNH 2-FC6H4 MeNH 596 Me 4-Py. -NH- 3-PyNH 2-FC6H4 EtNH (A) 597 Me 4-Py -NH-.  3-PyNH 2-FC6H4 EtNH ⑻ 598 Me 4-Py -NH- 3-PyNH 2-FC6H4 EtNH (C) 599 Me 4-Py -NH- 3-PyNH 2-FC6H4 PhCH2CH2NH (A) 600 Me 4-Py- NH-3-PyNH 2-FC6H4 PhCH2CH2NH (B) 601.  Me 4-Py '-NH- Ph (A) NH 2-FC6H4 H 602 Me 4-Py -NH-Ph (A) NH 2-FC6H4 1-Pyra 603 Me 4-Py -NH-Ph (A) NH 2 -FC6H4 1-Imid 604 Me 4-Py -NH- Ph (A) NH 2-FC6H4 1-Azt 605 Me 4-Py-NH- Ph (A) NH 2-FC6H4 Pyra (A) 606 Me 4-Py ~ * NH- Ph (A) NH 2-FC6H4 nh2 607 Me 4-Py -NH- Ph (A) NH 2-FC6H4 MeNH 608 Me 4-Py -NH_ Ph (A) NH 2-FC6H4 EtNH (A) 609 Me 4-Py-NH- Ph (A) NH 2-FC6H4 EtNH ⑻ 610 Me 4-Py. -NH- Ph (A) NH 2-FC6H4 EtNH (C) 611 Me 4-Py _NH_ Ph (A) NH 2-FC6H4 PhCH2CH2NH (A) 612 Me 4-Py -NH-Ph (A) NH 2-FC6H4 PhCH2CH2NH (B).   613 Me 4-MeS02C6H4 -NH- PhNH 2-FC6H4 H 614 Me 4-MeS02C6H4 -NH- PhNH 2-FC6H4 1-Pyra 615 Me 4-MeS02C6H4-NH- PhNH 2-FC6H4 1-Imid 616 Me 4-MeS02C6H,- NH- PhNH 2-FC6H4 1-Azt 200524880 617 Me 4-MeS02C6H4-NH-PhNH 2-FC6H4 Pyra (A) 618 Me 4-MeS02C6H4 -NH-PhNH 2-FC6H4 nh2 619 Me.  4_M6S02C6H4-NH- PhNH 2-FC6H4 MeNH 620 Me 4-MeS02C6H4 -NH- PhNH 2-FC6H4 EtNH (A) 621 Me 4-MeS02C6H4 -NH- PhNH 2-FC6H4 EtNH⑻ 622 Me 4-MeS02C6H4 -NH- PhNH 2-FC EtNH (C) 623 Me 4_MeS〇2. C6H4 -NH- PhNH 2-FC6H4 PhCH2CH2NH (A) 624 Me 4-MeS02C6H4 -NH-PhNH 2-FC6H4 PhCH2CH2NH ⑻ 625 Me 4-MeS02C6H4 -NH-3-PyNH 2-FC6H4 H 626 Me 4-MeS02C6H4 -NH-3 -PyNH 2-FC6H4 1-Pyra 627 Me 4_MeS02C6H4 -NH-3-PyNH. 2-FC6H4 Iraid 628 Me 4-MeS02C6H4 -NH- 3-PyNH 2-FC6H4 1-Azt 629 Me 4-MeS02C6H4 -NH- 3-PyNH 2-FC6H4 Pyra (A) 630 Me 4-MeS02C6H4 -NH- 3- PyNH 2-FC6H4 nh2 631 Me 4-M6S02C6H4-NH-3-PyNH 2-FC6H4 MeNH 632 Me 4-MeS02C6H4-NH-3-PyNH 2-FC6H4 EtNH (A) 633.  Me 4-MeS02C6H4. -NH- 3-PyNH 2-FC6H4 EtMKB) 634 Me 4-MeS02C6H4 -NH- 3-PyNH 2-FC6H4 EtNH (C) 635 Me 4-MeS02C6H4-NH- • 3-PyNH 2-FC6H4 PhCH2CH2NH (A) 636 Me 4-MeS02C6H4-NH_ 3-PyNH 2-FC6H4 PhCH2CH2NH (B) 637 Me 4-MeS02C6H4 -NH- Ph (A) NH 2-FC6H4 H 638 Me 4-MeS02C6H4 -NH-Ph (A) NH 2-FC6H4 1- Pyra 639 Me 4-MeS02C6H4 -NH-Ph (A) NH 2-FG6H4 1-Imid 640 Me 4-MeS02C6H4 -leg- Ph (A) NH 2-FC6H4 1-Azt 641 Me 4-MeS02C6H4 one leg one Ph (A ) NH 2-FC6H4 Pyra (A) 642 Me 4-MeS02C6H4 -NH- Ph (A) NH 2-FC6H4 nh2 643 Me 4-MeS02C6H4 -leg- Ph (A) NH 2-FC6H4 MeNH 644 Me 4-MeS02C6H4 -NH -Ph. (A) NH 2-FC6H4. EtNH (A) 645 Me 4:-MeS02C6H4-NH- Ph (A) NH 2-FC6H4 EtNH (B) 646 Me 4 ~ M6S02C6H4 -NH- Ph (A) NH 2-FC6H4 EtNH (C) -75-200524880 647 Me 4-MeS02C6H4 ~ NH ~ Ph (A) NH 2-FC6H4 PhCH2CH2NH (A) 648 Me 4-MeS02C6H4-NH-Ph (A) NH 2-FC6H4 PhCH2CH2NH ⑻ 649 Me 4-MeNHS02C6H4 -NH- PhNH 2-FC6H4 H 650 Me 4-MeNHS02C6H4 -NH_ _ PhNH 2_FC6H4 1-Pyra 651 Me 4-MeNHS02C6H4 -Li-Phili 2-FC6H4 1-Imid 1 652 Me 4-MeNHS02C6H4 -NH-PhNH 2-FC6H4 1-Az t 653 Me 4- MeNHS02C6H4-NH-PhNH 2-FC6H4 Pyra (A) 654 Me 4-MeNHS02C6H4-NH-PhNH 2-FC6H4 nh2 655 Me 4-MeNHS02C6H4 -NH-PhNH 2-FC6H4 MeNH 656 Me 4-MeNHS02C6H4 -NH-PhNH 2- EtNH (A) 657 Me 4-MeNHS02C6H4 -NH-PhNH 2-FC6H4 EtNH (B) 658 Me 4-MeNHS02C6H4 -NH- PhNH 2-FC6H4 EtNH (C) 659 Me 4-MeNHS02C6H4-NH-PhNH 2-FC6H4 Ph. CH2CH2NH (A) 660 Me 4-MeNHS02C6H4 -NH-. PhNH 2-FC6H4 PhCH2CH2NH ⑻ 661 Me 4-MeNHS02C6H4 -NH- 3-Py. NH 2-FC6H4 H.   662 Me 4-MeNHS02C6H4-NH- 3-PyNH 2-FC6H4 1-Pyra 663 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-FC6H4 1-Imid 664 Me 4-MeNHS02C6H4 -NH-3-PyNH 2-FC6H4 l- Azt 665 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-FC6H4 Pyra (A) 666 Me 4-MeNHS02C6H4 -NH- 3-PyNH 2-FC6H4 nh2 667 Me 4-MeNHS02C6H4-NH- 3-PyNH 2-FC6H4 MeNH 668 Me 4-MeNHS02C6H4-Rei- 3-PyNH 2-fc6h4 EtNH (A) 669 Me 4-MeNHS02C6H4 -NH-3-Py Rei 2-FC6H4 EtNH (B) 670 Me 4-MeNHS02C6H4-NH-3-PyNH 2-FC6H4 EtNH (C) 671 Me. 4-MeNHS02C6H4-NH-3-PyNH 2-FC6H4 PhCH2CH2NH (A) 672 Me 4-Me Li S02C6H4 -NH- 3-PyNH 2-FC6H4 PhCH2CH2_) 673 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-FC6H4 H 674 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-FC6H4 1-Pyra 675 Me 4-MeNHS02C6H4 -NH- Ph (A) NH 2-FC6H4 1-Imid 676 Me 4-MeNHS02C6H4 -NH- Ph (A ) NH 2-FC6H4 1-Azt 200524880 677 Me 4-MeNHS02C6H; -NH- Ph (A) NH 2-FC6H4 Pyra (A) 678 Me 4-MeNHS02C6H4 -NH ~ Ph (A) NH 2-FC6H4 nh2 679 Me 4 -MeNHS02C6H4 -NH- Ph (A) NH 2-FC6H4 MeNH 680 Me 4-MeNHS02C6H4 _leg- Ph (A) NH 2-FC6H4 EtNH (A) 681 Me 4-MeNHS02C6H4-NH-Ph (A) NH 2-FC6H4 EtNH (B) 682 Me 4-MeNHS02C6H4 -NH-Ph (A) NH 2-FC6H4 EtNH (C) 683 Me 4-MeNHS02C6H4-NH-Ph (A) NH 2-FC6H4 PhCH2CH2NH (A) 684 Me 4-MeNHS02C6H4 Ph (A) NH 2-FC6H4 PhCH2CH2NH (B) 685 Me 4-Py -NH-3-Py 2-FC6H4 H 686 'Me 4-Py -NH-3-Py 2-FC6H4 1-Pyra 687 Me 4-Py- NH-3-Py 2-FC6H4 1-Imid 688 Me 4-Py -NH- 3-Py 2-FC6H4 1-Azt 689 Me 4-Py-NH-3-Py 2-FC6H4 Pyra (A) 690 Me 4- Py -NH-3-Py 2_FC6H4 nh2 691 Me 4-Py-NH-3-P y 2-FC6H4 MeNH 692 Me 4-Py -NH-3-Py 2-FC6H, EtNH (A) 693 Me 4-Py -NH-3-Py 2-FC6H4 EtNH ⑻ 694 Me 4-Py -NH- 3- Py 2-FC6H4 EtNH (C) 695 Me 4-Py -NH-3-Py 2-FC6H4 PhCH2CH2NH (A) 696 Me 4-Py -NH- 3-Py 2-FC6H4 PhCH2CH2NH (B) 697 Me 4-MeS02C6H4- NH-3-Py 2-FC6H4 H 698 Me 4-MeS02C6H4-NH-3-Py 2-FC6H4 l ~ Pyra 699 Me 4-MeS02C6H4-NH-3-Py 2-FC6H4 1-Imid 700. Me 4-MeS02C6H4 -NH-3-Py 2-FC6H4 1-Azt 701 Me 4-MeS02C6H4 -NH- 3-Py 2-FC6H4 Pyra (A) 702 Me 4-MeS02C6H4 -NH- 3-Py 2-FC6H4 nh2 703 Me 4-MeS02C6H4 -NH- 3-Py 2-FC6H4 MeNH 704 Me 4-MeS02C6H4 -NH- 3-Py 2-FC6H4. EtNH (A) 705 Me 4-MeS02C6H4 -NH- 3-Py 2-FC6H4 EtNH (B) 706 Me 4-MeS02C6H4 -NH- 3-Pv 2-FC6H4 EtNH (C) -77- 200524880 707 Me 4-MeS02C6H4- NH- 3-Py 2-FC6H4 PhCH2CH2NH (A) 708 Me 4 ~~ MeS02C6H4 -NH- 3-Py 2-FC6H4 · PhCH2CH2NH ⑻ 709 Me 4-MeNHS02C6H4 -NH- 3-Py 2-FC6H4 H 710 Me 4-MeNHS02C6H4 -Legs- 3-Py 2-FC6H4 1-Pyra 711 Me 4-MeNHS02C6H4 -Legs- 3-Py 2-FC6H4 1-Imid 712 Me 4-MeNHS02C6H4 -Question- 3-Py 2-FC6H4 1-Az t 713 Me 4 -Me Re S02C6H4 -NH- 3-Py 2-FC6H4 Pyra (A) 714 Me 4-MeNHS02C6H4 3-Py 2-FC6H4 nh2 715 Me 4-MeNHS02C6H4 -NH- 3-Py 2-FC6H4 MeNH 716 Me 4-MeNHS02C6H4- NH- 3-Py 2-FC6H4 EtNH (A) 717 Me 4-MeNHS02C6H4 -NH- 3-Py 2-FC6H4 EtNH (B) 718 Me 4-MeNHS02C6H4-NH-3-Py 2-FC6H4 EtNH (C) 719 Me 4-MeNHS02C6H4-NH-3-Py 2-FC6H4 PhCH2CH2NH (A) 720 Me 4-MeNHS02C6H4-NH- 3-Py.  2-FC6H4 PhCH2CH2NH ⑻ 721 Me 4-Py-NH-PhNH Ph⑻ H 722 Me 4-Py -NH-PhNH Ph⑻ 1-Pyra 723 Me 4-Py PhNH Ph (B) 1-Imid 724 Me 4-Py-NH- PhNE Ph⑻ 1-Az t 725 Me 4-Py -NH-PhNH Ph (B) Pyra (A) 726 Me 4-Py -Li- PhNH Ph (B) nh2 727 Me 4-Py -NH- PhNH Ph (B) MeNH 728 Me 4-Py -NH- PhNH Ph⑻ EtNH (A) 729 Me 4-Py -NH- PhNH Ph (B) EtNH (B) 730 Me 4-Py -NH- PhNH Ph⑻ EtNH (C) 731 Me 4- Py -NH- PhNH Ph (B) PhCH2CH2NH (A) 732 Me 4-Py -NH- PhNH Ph⑻ PhCH2CH2NH (B) 733 Me 4-Py -NH- 3-PyNH Ph⑻ H 734 Me 4-Py -NH- 3- PyNH Ph⑻ 1-Pyra 735 Me 4-Py -NH- 3-PyNH Ph⑻ 1-Imid 736 Me 4-Py -NH- 3-PyNH Ph (B) 1 -Az t -78- 200524880 737 Me 4-Py -NH -3-PyNH Ph (B) Pyra (A) 738 Me 4-Py -NH- 3-PyNH Ph (B) nh2 739 Me 4-Py -NH- 3-PyNH Ph (B) MeNH 740 M, e 4- Py -Li- 3-PyNH Ph (B) Et Li (A) 741 Me 4-Py -NH- 3-PyNH. Ph (B) EtNH ⑻ 742 Me 4-Py -NH-3-PyNH Ph (B) EtNH (C) 743 Me 4-Py • -NH- 3-PyNH Ph (B) PhCH2CH2NH (A) 744 Me 4-Py -NH-3-PyNH Ph (B) PhCH2CH2NH (B) 745 Me 4-Py -NH- Ph (A) NH Ph⑻ H 746 Me 4-Py -NH-Ph (A) NH Ph (B) 1-Pyra 747 Me 4-Py -NH-Ph (A) NH Ph (B) 1-Imid 748 Me 4-Py-NH-Ph (A) NH Ph (B) 1-Azt 749 Me 4-Py-NH- Ph (A ) NH Ph⑻ Pyra (A) 750 Me 4-Py -NH- Ph (A) NH Ph (B) nh2 751 Me 4-Py Ph (A) NH Ph (B) MeNH 752 Me 4-Py -NH- Ph ( A) NH Ph. (B) EtNH (A) 753 Me 4-Py -NH- Ph (A) NH Ph⑻ EtNH⑻ 754 Me 4-Py -NH-Ph (A) NH Ph (B) EtNH (C) 755 Me 4-Py-- Ph (A) NH Ph (B) PhCH2CH2NH (A) 756 Me 4-Py -NH-Ph (A) NH Ph (B) PhCH2CH2NH (B) 757 Me 4-MeS02C6H4 -NH- PhNH Ph (B) H 758 Me 4-MeS02C6H4 -NH-PhNH Ph (B) 1-Pyra 759 Me 4-MeS02C6H4-NH-PhNH Ph (B) 1-Imid 760 Me 4-MeS02C6H4 -NH-PhNH Ph (B) 1-Azt 761 Me 4- MeS02C6H4 '-NH-. PhNH Ph (B) Pyra (A) 762 Me 4-MeS02C6H4 -NH- PhNH Ph (B) nh2 763 Me 4-MeS02C6H4 -NH-PhNH Ph (B) MeNH 764 Me 4-MeS02C6H4-NH- • PhNH Ph (B ). EtNH (A) 765 Me 4-MeS02C6H4 -NH- PhNH Ph (B) EtNH (B) 766 Me 4-MeS02C6H4 -NH- PhNH Ph (B) EtNH (C) -79- 200524880 767 Me 4-MeS02C6H4-NH_ • PhNH Ph (B) PhCH2CH2NH (A) 768 Me 4-MeS02C6H4-Rei- PhNH Ph (B) PhCH2CH2NH (B) 769 Me 4-MeS02C6H4 -NH- 3-Py Rei Ph (B) H 770 Me 4_MeS02C6H4 -NH- 3 -PyNH Ph (B) 1-Pyra 771 Me 4_MeS02C6H4-NH- 3-PyNH Ph (B) 1-Imid 772 Me 4_MeS02C6H4 -NH- 3-PyNH Ph (B) 1-Azt 773 Me 4-MeS02C6H4 -NH- 3 -PyNH Ph⑻ Pyra (A) 774 Me 4-MeS02C6H4-NH- 3-PyNH Ph (B) nh2 775 Me 4-MeS02C6H4 -NH- 3-Py Ph (B) MeNH 776 Me 4-MeS02C6H4 -NH- 3- PyNH Ph (B) EtNH '(A) 777 Me 4-MeS02C6H4-NH- 3-PyNH Ph (B) EtNH ⑻ 778 Me 4-MeS02C6H4-NH- 3-PyNH Ph (B) EtNH (C) 779 Me 4- MeS02C6H4 -NH- 3-PyNH Ph⑻ PhCH2CH2NH (A) 780 Me 4-MeS02C6H4 _NH- 3-PyNH Ph (B) PhCH2GH2NH (B) 781 Me 4-MeS02C6H4 -NH- Ph (A) NH Ph (B) H 782 Me 4 a MeS02C6H4. -NH-.  Ph (A) NH Ph⑻ 1-Pyra 783 Me 4-MeS02C6H4-NH-Ph (A) NH Ph (B) 1-Imid 784 Me 4-MeS02C6H4 -NH- Ph (A) NH Ph (B) 1-Azt 785 Me 4-MeS02C6H4 -NH- Ph (A) NH Ph (B) Pyra (A) 786 Me 4-MeS02C6H4-NH- Ph (A) NH Ph (B) nh2 787 Me 4_MeS02C6H4 ~ NH ~ Ph (A) NH Ph (B) MeNH 788 Me 4-MeS02C6H4 -Li- Ph (A) NH Ph (B) EtNH (A) 789 Me 4-MeS02C6H4 -NH- Ph (A) NH Ph (B) EtNH ⑻ 790 Me 4-MeS02C6H4- NH- Ph (A) NH Ph (B) EtNH (C) 791 Me 4-MeS02C6H4 -NH- Ph (A) NH Ph⑻ PhCH2CH2NH (A) 792 Me 4-MeS02C6H4-NH- Ph (A) NH Ph (B) PhCH2CH2_) 793 Me 4-MeNHS02C6H4-. -PhNH Ph⑻ H 794 Me 4-MeNHS02C6H4 -NH- PhNH Ph (B). . 1-Pyra 795 Me 4-MeNHS02C6H4 -NH- PhNH Ph (B) 1-Imid 796 Me 4-MeNHS02C6H4 -NH- PhNH Ph (B) 1-Azt -80- 200524880 797 Me 4-MeNHS02C6H4 -NH- PhNH Ph ( B) Pyra (A) 798 Me 4-MeNHS02C6H4 -NH-PhNH Ph⑻ nh2 799 Me 4-MeNHS02C6H4 -NH-PhNH Ph⑻ MeNH 800 Me 4-MeNHS02C6H4 -NH- PhNH Ph (B) Et Li (A) 801 Me 4- MeNHS02C6H4 -NH- PhNH Ph (B) EtNH (B) 802 Me 4-MeNHS02C6H4-Rei- PhNH Ph⑻ Etmi (c) 803 Me 4-MeNHS02C6H4 -NH- PhNH Ph⑻ PhCH2CH2NH (A) 804 Me 4-MeNHS02C6H4-NH-PhNH Ph⑻ PhCH2CH2. (B) 805 Me 4-MeNHS02C6H4 -NH-3-PyNH Ph⑻ H 806 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph⑻ HPyra 807 Me 4-MeNHS02CfiH4 -NH- 3-PyNH Ph (B) 1-Imid 808 Me 4 -MeNHS02C6H4 -NH- 3-PyNH Ph (B) 1-Azt 809 Me 4-MeNHS02C6H4 -NH-3-PyNH Ph⑻ Pyra (A) 810 Me 4-MeNHS02C6H4-NH-3-PyNH Ph⑻ nh2 811 Me 4-MeNHS02C6H4- NH-3-PyNH Ph (B) MeNH 812 Me 4-MeNHS02C6H4-* NH- 3-PyNH Ph. ⑻ EtNH (A) 813 Me 4-MeNHS02C6H4 _NH_ 3-PyNH Ph (B) EtNH (B) 814 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph⑻ EtNH (C) 815 Me 4-MeNHS02C6H4 -NH- 3-PyNH Ph (B) PhCH2CH2NH (A) 816 Me 4-MeNHS02C6H4-NH_ 3-PyNH Ph (B) PhCH2CH2NH ⑻ 817 Me 4-MeNHS02C6H4-Rei- Ph (A) NH Ph⑻ H 818 Me 4-MeNHS02C6H4-NH-Ph (A) NH PMB) 1-Pyra 819 Me 4-MeNHS02C6H4 -NH-Ph (A) NH Ph⑻ 1-Imid 820 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph⑻ 1-Azt 821 Me 4-MeNHS02C6H4 -NH- Ph ( A) NH Ph⑻ Pyra (A) 822 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph⑻ nh2 823 Me 4-MeNHS02C6H4 -Li- Ph (A) NH Ph (B) • MeNH 824 Me 4-MeNHS02C6H4 -Book- Ph (A) NH Ph⑻. EtNH (A) 825 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph (B) EtNH (B) 826 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph (B) EtNH (C) -81-200524880 827 Me 4-MeNHS02C6H4 -NH- Ph (A) NH Ph (B) PhCH2CH2NH (A) 828 Me 4-MeNHS02C6H4 -NH_ Ph (A) NH Ph (B) PhCH2CH2_) 829 Me 4-Py -NH- 3-Py Ph (B) H 830 Me 4-Py -NH- 3-Py Ph (B).  1-Pyra 831 Me 4-Py -NH- 3-Py Ph (B) 1-Imid 832 Me 4-Py -NH- 3-Py Ph⑻ 1-Azt 833 Me 4-Py -NH- 3-Py Ph (B ) Pyra (A) 834 Me 4-Py -NH- 3-Py Ph (B) nh2 835 Me 4-Py -Li- 3-Py Ph (B) MeNH 836 Me 4-Py -NH- 3-Py Ph ( B) EtNH (A) 837 Me 4-Py-NH- 3-Py Ph (B) EtNH (B) 838 Me 4-Py -NH- 3-Py Ph (B) EtNH (C) 839 Me 4-Py- NH-3-Py. Ph (B) PhCH2CH2NH (A) 840 Me 4-Py-NH-3-Py Ph (B) PhCH2CH2NH (B) 841 Me 4-MeS02C6H4 -NH-3-Py Ph (B) H 842 Me.  4-MeS02C6H4 -NH-3-Py Ph (B) 1-Pyra 843 Me 4-MeS02C6H4-NH-3-Py Ph (B) 1-Im. id 844 Me 4-MeS02C6H4 -NH-3-Py Ph (B) l ~ Azt 845 Me 4-MeS02C6H4 -NH-. 3-Py Ph (B) Pyra (A) 846 Me 4-MeS02C6H4-NH-3-Py Ph (B) nh2 847 Me 4-MeS02C6H4 -NH- 3-Py Ph (B) MeNH 848 Me 4-MeS02C6H4 -NH -3-Py Ph (B) EtNH (A) 849 Me 4-MeS02C6H4 -Legs- 3-Py Ph (B) EtNH ⑻ 850 Me 4-MeS02C6H4-NH-.  3-Py Ph (B) EtNH (C) 851 Me 4-MeS02C6H4 -NH-3-Py Ph (B) PhCH2CH2NH (A) 852 Me 4-MeS02C6H4 -NH- 3-Py Ph (B) PhCH2CH2NH (B) 853 Me 4-MeNHS02C6H4 -NH- 3-Py Ph (B) H 854 Me 4-MeNHS02C6H4 -NH- 3-Py Ph (B). 1-Pyra 855 Me 4-MeNHS02C6H4 -NH- 3-Py Ph (B) 1-Imid 856 Me 4-MeNHS02C6H4 -NH- 3-Py Ph (B) 1-Azt -82-200524880 857 Me 4-MeNHS02C6H4 -NH -3-Py Ph (B) Pyra (A) 858 Me 4-MeNHS02C6H4 -NH- 3-Py Ph (B) nh2 859 Me 4-MeNHS02C6H4-Legs-3-Py Ph (B) MeNH 860 Me 4-MeNHS02C6H4- NH-3-Py Ph (B) EtNH (A) 861 Me 4-MeNHS02C6H4-NH-3-Py Ph (B) Et Lihua 862 Me 4-MeifflS02C6H4 -NH- 3-Py Ph (B) EtNH (C) 863 Me 4-MeNHS02C6H4 -NH- • 3-Py Ph (B) PhCH2CH2NH (A) 864 Me 4-MeNHS02C6H4 -NH-3-Py 'Ph (B) PhCH2CH2NH ⑻ 865 Me 4-MeNHS02C6H4-Li- PhNH Ph Pyra ( B) 866 Me 4-MeNHS02C6H4-NH-PhNH. H Pyra (B) 867 Me 4-Py -NH- PhNH Ph Pyra (B) 868 Me 4-Py -NH- PhNH H Pyra (B) 869 Me 4-MeNHS02C6H4 -NH- PhNH Ph 1-Pyrd 870 Me 4- MeNHS02C6H4 -NH-.  PhNH H 1-Pyrd 871 Me 4-Py -NH- PhNH Ph 1-Pyrd 872 Me 4-Py -NH- PhNH H 1-Pyrd 873 Me 4-MeS02C6H4 -NH-PhNH Ph 1-Pyrd 874 Me 4-MeS02C6H4- NH-PhNH H 1-Pyrd 875 Me 4-MeNHS02C. 6H4-NH-PhNH Ph NMe2 876 Me 4-MeNHS02C6H4-NH- PhNH H fiMe2 877 Me 4-Py -NH- PhNH Ph NMe2 878 Me 4-Py -NH- PhNH H ^ e2 879 Me 4-MeS02C6H4 -NH- PhNH Ph NMe2 880 Me 4-MeS02C6H4 -NH-PhNH H NMe2 881 Me 4-MeNHS02C6H4. -NH- PhNH Ph EtNH (D) 882 Me 4-MeNHS02C6H4 -NH- PhNH H EtNH (D) 883 Me 4-Py -NH- PhNH Ph EtNH (D) 884 Me 4-Py -NH- PhNH H. EtNH (D) 885 Me 4-MeS02C6H4 -NH- PhNH Ph EtNH⑼ 886 Me 4-MeS02C6H4 -NH-PhNH H EtNH (D) 200524880 887 Me 4-MeNHS02C6H4 -NH- PhNH 3-MeOC6H4 H 888 Me 4-MeNHS02C6H4 -NH -PhNH. 3-MeOC6H4 1-Pyra 889 Me 4-Py -NH- PhNH 3-MeOC6H4 H 890 Me 4-Py -NH- PhNH 3-MeOC6H4 1-Pyra 891 Me 4-MeNHS02C6H4 -NH- PhNH 1-Naph H • 892 Me 4-MeNHS02C6H4-NH-PhNH 1-Naph 1-Pyra 893 Me 4-Py -NH- PhNH 1-Naph H 894 Me 4-Py-NH- PhNH 1-Naph 1-Pyra 895 Me 4-MeNHS02C6H4 -NH- PhNH 3-PhC6H4 H 896. Me 4-MeNHS02C6H4 -NH-PhNH 3-PhC6H4. 1-Pyra 897 Me 4-Py '-NH- PhNH 3-PhC6H4 H 898 Me 4-Py -NH-PhNH 3-PhC6H4 1-Pyra 899 Me 4-MeNHS02C6H4 -NH ~ PhNH 4-MeC6H4 H 900 Me 4-MeNHS02C6H4 -NH-.  PhNH 4-MeC6H4 1-Pyra 901 Me 4-Py -NH- PhNH 4-MeC6H4 H 902 Me 4-Py -NH- PhNH 4-MeC6H4 1-Pyra 903 Me 4-MeNHS02C6H4 -NH- PhNH 3-FC6H4 H 904 Me 4-MeNHS02C6H4 'PhNH 3-FCeH4 1-Pyra 905 Me 4-Py-NH- PhNH 3-FC6H4 H 906 Me 4-Py-NH-PhNH 3-FC6H4 1-Pyra 907 Me 4-MeNHS02C6H4 -NH- PhNH 4- MeSC6H4 H 908 Me 4-MeNHS02C6H4 -NH- PhNH 4-MeSC6H4 1-Pyra 909 Me 4-Py-NH- PhNH 4-MeSC6H4 H 910 Me 4-Py-NH- PhNH 4-MeSC6H4 1-Pyra 911 Me 4-Me Rei S02C6H4 -NH- PhNH 2-ClC6H4 H 912 Me 4-MeNHS02C6H4 -NH- PhNH 2-ClC6H4 1-Pyra 913 Me 4-Py -NH- PhNH 2-C1C6H4 H 914 Me 4-Py -NH- PhNH 2-ClC6H4 1-Pyra 915 Me 4-MeNHS02C6H4 ~ NH_ PhNH Ph (C) H 916 Me 4-MeNHS02CfiH4-NH- PhNH Ph (C) 1-Pyra -84- 200524880

917 Me 4-Py -NH- PhNH Ph (C) H 918 Me 4-Py -NH- PhNH Ph (C) 1-Pyra 919 Me 4-MeNHS02C6H4 -NH- PhNH Ph (D) H 920 Me 4-MeNHS02C6H4- NH_ PhNH Ph⑼ 1-Pyra 921 Me 4-Py-NH- PhNH Ph (D) H 922 Me 4-Py-NH- PhNH Ph (D) 1-Pyra 923 Me 4-MeNHS02C6H4 -NH- PhNH • Ph (E) H 924 Me 4-MeNHS02C6H4 -NH- PhNH Ph (E) 1-Pyra 925 Me. 4-Py -NH- PhNH Ph (E) H 926 Me 4-Py -NH-PhNH Ph (E) 1-Pyra 927 Me 4-MeNHS02C6H4-NH- Hnd Ph H 928 Me 4-MeNHS02C6H4-NH-1-Ind Ph 1-Pyra 929 Me 4-MeNHS02C6H4 -NH- 1-Ind • HH 930 Me 4-MeNHS02C6H4 -NH- 1-Ind H 1 -Pyra 93.1. Me 4-Py-NH_ 1-Ind Ph H 932 Me 4-Py -NH-1-Ind .Ph 1-Pyra 933 Me 4-Py. -NH- 1-Ind H 'H 934 Me 4- Py -NH- 1-Ind H 1-Pyra 935 Me 4-MeNHS02C6H4 one leg_ 2-FC6H4NH Ph H 936 Me 4-MeNHS02C6H4 -NH-2-FC6H4NH Ph 1-Pyra 937 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH H .H 938 Me 4-MeMlS02C6H4 -NH-2-FC6H4NH H 1-Pyra 939 Me 4-Py -NH- 2-FC6H4NH Ph H 940 Me · 4-Py-NH-2-FC6H4NH Ph 1-Pyra 941 Me 4 -Py -NH-2-FC6H4NH HH 942 Me 4-Py -NH- 2-FG6 H4NH H 1-Pyra 943 Me Ph (F)-NH_ PhNH Ph H 944 Me Ph (F) -NH- PhNH Ph .1-Pyra 945 Me Ph (F) -NH- PhNH Ph 1-Imid 946 Me Ph (F )-NH- PhNH HH -85- 200524880 947 Me Ph (F) -NH- PhNH H 1-Pyra 948 Me .Ph (F) -NH- PhNH H 1-Imid 949 Me Ph (F) -NH-3- PyNH Ph H 950 Me Ph (F) -NH- · 3-PyNH Ph HPyra 951 Me Ph⑻ -NH- 3-PyNH Ph 1-Imid 952 Me Ph (F) -NH-3-PyNH HH 953 Me Ph (F) -NH- 3-PyNH H HPyra 954 Me Ph (F) -NH-3-PyNH H 1-Imid 955 Me 4-Py -NH- 2-Me0C6H4NH H 2-MeOC6H4NH 956 Me 4-MeS02C6H4-NH-2-Me0C6H4NH H 2-Me0C6H4NH 957 Me 4-Py-NH- PhNH H (3-Py) CH2CH2NH 958 Me 4-H2NS02C6H4 -NH- PhNH H PhCH2CH2NH (B) 959 Me 4-cPrNHS02C6H4-NH- PhNH H PhCH2CH2NH (B) 960 Me 4-EtNHS0, C6H4-NH- PhNH H EtNH ⑻ 961 Me 4-H2NS02C6H4 -NH- PhNH H EtNH⑻ 962 Me 4-cPrNHS02C6H4 -NH- PhNH H EtNH (B) 963 Me Pyrr (A)-NH-PhNH: H EtNH⑻ 964 Me 4-MeNHS02C6H4 -NH- PhNH H EtNH (E) 965 Me 4-MeS02C6H4-NH- PhNH H EtNH (E) 966 Me 4-Py-NH-PhNH H EtNH ⑻ 967 Me 4-MeNHS〇2C6H4 -NH- PhNH H 4-Me0C6H4CH2CH2NH 968 Me 4-MeS02C6H4 -NH-PhNH H 4-Me0C6H4CH2CH2NH 969 Me 4-Py -NH- PhNH H 4-Me0C6H4CH2CH2NH 970 Me 4-MeNHS02C6H4 -NH- PhNH H PhCH2CH2NH (C) 02 Me 4 -PhNH H PhCH2CH2NH (C) 972 Me 4-Py _NH-PhNH H PhCH2CH2NH (C) 973 Me 4-MeNHS02C6H4-NH- PhNH H 3-Me0C6H4CH2CH2NH 974 Me 4_MeS02C6H4 -NH- PhNH • H 3-MeOC6H4CH2CH2NH2 -NH- PhNH H 3-MeOC6H4CH2CH2NH 976 Me 4-MeNHS09CfiH4-NH-PhNH Ph Cl -86- 200524880 977 Me 4-MeS02C6H4-NH-PhNH Ph Cl 978 Me 4-Py -NH- PhNH Ph Cl 979 Me 4-MeNHS02C6H4 -NH- PhNH · 2-BrC6H4 H 980 Me 4-MeS02C6H4 PhNH 2-BrC6H4 H 981 Me 4-Py -NH-PhNH 2-BrC6H4 H 982 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeOC6H4 H 983 Me 4-MeS02C6H4 -NH-PhNH 2-MeOC6H4 H 984 Me 4-Py -NH- PhNH 2-MeOC6H4 H 985 Me 4-MeNHS02C6H4-NH- PhNH 4-FC6H4 H 986 Me 4-MeS02C6H4-NH-PhNH 4-FC6H4 H 987 Me 4 -Py -NH- PhNH 4-FC, H4 H. 988 Me · 4-MeNHS02C6H4 -NH- PhNH Ph cPrNH 989 Me 4-MeS02C6H4-NH_ PhNH Ph cPrNH 990 Me 4-Py -NH- PhNH Ph cPrNH 991 Me 4-MeNHS02C6H4 -NH- 'PhNH Ph EtNH (F) 992 Me 4-MeS02C6H4 -NH-PhNH Ph EtNH (F) 993 Me 4-Py-NH-PhNH Ph EtNH (F) 994 Me 4-MeNHS02C6H4-NH -PhNH Ph HOCH2CH2NH 995 Me 4-MeS02C6H4 -NH- PhNH Ph hoch2ch2nh • 996 Me 4-Py -Legs-PhNH Ph hoch2ch2nh 997 Me 4-MeNHS02C6H4 -NH- PhNH Ph Me2NCH2CH2NH2 Ph-NHN 999 Me 4_MeS02C6H4 Ph2 NH-NHN -Py -Legs- PhNH Ph Me2NCH2CH2NH 1000 Me 4-MeNHS02C6H4-NH- 4-FC6H4NH 4-FC6H4 1-Pyra 1001 Me 4-MeNHS02C6H4-NH-4-FC6H4NH 4-FC6H4 1-Imid 1002 Me 4-Me Li S02C6H4- NH- 4-FC6H4NH 4-FC6H4 Pyra (A) 1003 Me 4-MeNHS02C6H4 -NH- PhNH Ph 1-Tri (A) 1004 Me .4-MeS02C6H4 -NH- PhNH Ph .l-Tri (A) 1005 Me 4- Pv ~ NH ~ PhNH Ph 1-Tri (A) 1006 Me 4-MeNHS02C6H4 -NH- PhNH Ph 1-Tri (B) -87- 200524880 1007 Me 4-MeS02C6H4 -NH- PhNH Ph 'l-Tri (B) 1008 Me 4-Py-NH- PhNH Ph 1-Tri (B) 1009 Me 4-MeNHS02C6H4 -NH_ PhCH2CH2NH Ph H 1010 Me 4-MeS02C6H4 -NH- PhCH2CH2NH Ph H 1011 Me 4-Py -NH- PhCH2CH2NH Ph H 1012 Me 4 -MeNHS02C6H4-NH- PhNH 2,6-Cl2C6H 3 H 1013 Me 4-MeS02C6H4 -NH- PhNH 2,6-Cl2C6H3 H 1014 Me 4-Py -NH-PhNH 2,6-Cl2C6H3 H 1015 Me 4-MeNHS02C6H4 -NH_ PhNH 4-PhC6H4 H 1016 Me 4-MeS02C6H4- NH- PhNH 4-PhC6H4. H 1017 Me 4-Py -NH- PhNH 4-PhC6H4 H 1018 Me 4-MeNHS02C6H4-NH- PhNH Py (A) H 1019 • Me 4-MeS02C6H4 -NH- PhNH Py (A) H 1020 Me 4-Py -NH- PhNH Py (A) H 1021 Me. 4-MeNHS02C6H4 -NH-PhNH 3-MeC6H4 H 1022 Me 4-MeS02C6H4 -NH- PhNH 3-MeC6H4 H 1023 Me 4-Py -NH- PhNH 3-MeC6H4 H 1024 • Me 4-MeNHS02C6H4 -NH-PhNH 3-CF3C6H4 H 1025 Me • 4-MeS02C6H4-NH- PhNH 3-CF3C6H4 H 1026 Me 4-Py -leg- PhNH 3-CF3C6H4 H 1027 Me 4-MeNHS02C6H4 -NH- PhNH 2-CF3C6H4 H 1028 Me 4-MeS02C6H4 -NH- PhNH 2-CF3C6H4 H 1029 Me 4-Py-NH-PhNH 2-CF3C6H4 H 1030 Me 4-MeNHS02C6H4 -Li- PhNH Ph (G) Pyra (A ) 1031 Me 4-MeS02C6H4 -NH-. PhNH Ph (G) Pyra (A) 1032 Me 4-Py-NH-PhNH Ph (G) Pyra (A) 1033 Me 4-MeNHS02C6H4 -NH- PhNH Ph (G) 1 -Pyra 1034 Me 4-MeS02C6H4 -NH- PhNH Ph (G) Pyra 1035 Me 4-Py -NH- PhNH Ph (G) 1-Pyra 1036 Me 4- MeNHS02C5H4 -NH- PhNH Ph (H) Pyra (A) 200524880

1037 Me 4-MeS02C6H4 -NH-PhNH Ph⑻ Pyra (A) 1038 Me 4-Py -NH- PhNH Ph⑻ Pyra (A) 1039 Me 4-MeNHS02C6H4 -NH- H Ph H 1040 Me 4-MeS02C6H4-NH- · H Ph H 1041 Me 4-Py -NH- H Ph H 1042 Me 4-MeNHS02C6H4-NH- 2-MeOC6H4 Li Ph H 1043 Me 4-MeS02C6H4-NH- 2-MeOC6H4NH Ph H 1044 Me 4-Py -NH- 2-MeOC6H4NH Ph · H 1045 Me 4-MeNHS02C6H4-NH- Ph Ph H 1046 Me 4-MeS02C6H4 -NH- Ph Ph H 1047 Me 4-Py-NH- Ph Ph H 1048 Me 4-MeNHS02C6H4-NH- Me Ph H 1049 Me 4 -MeS02C6H4-NH- Me Ph H 1050 Me 4-Py -NH-Me Ph H 1051 Me 4-MeNHS02C6H4 -NH- 2-EtOC6H4NH Ph H 1052 Me 4-MeS02C6H4 -NH- 2-EtOC6H4NH Ph H 1053 Me 4-Py -NH- 2-EtOC6H4NH Ph H 1054 Me 4-MeNHS02C6H4 -NH- 2-MeC6H4NH Ph H 1055 Me 4-MeS02C6H4-NH-2-MeC6H4NH Ph H 1056 Me 4-Py-NH-2-MeC6H4NH Ph H 1057 Me 4 -MeNHS02C6H4 -NH- cHexNH Ph H 1058 Me 4-MeS02C6H4 -NH- cHexNH Ph H 1059 Me 4-Py -NH- cHexNH Ph H 1060 Me. 4-MeNHS02C6H4-NH-PhNH 2-Py H 1061 Me 4-MeS02C5H4- NH-PhNH 2-Py H 1062 Me 4-Py -NH- PhNH 2-Py H 1063 Me 4- MeNHS02C6H4 -NH- PhNH Ph⑴ H 1064 Me 4-MeS02C, 6H4 -NH- PhNH Ph (I) H 1065 Me 4-Py -NH- PhNH Ph⑴ H 1066 Me Ph (K) _NH-PhNH Ph H 200524880 1067 Me Ph ( K) -NH- PhNH Py (A) H 1068 Me 4-PrNHS02C6H4 -NH- PhNH Ph, H 1069 Me 4-Na0S02C6H4 -NH- PhNH Ph H 1070 Me 4-MeNHS02C6H4 -NH- PhNH Ph Pipe (A) .. 1071 Me 4-MeNHS02C6H4 -NH-PhNH Ph Pipe (B) 1072 Me .4-MeS02C6H4 -NH- PhNH Ph Pipe (C) 1073 Me 4-MeS02C6H4-NH- PhNH Ph Pipe (D) 1074 Me 4-MeNHS〇2C6H4 -NH- PhNH Ph 1-Tri (C) 1075 Me 4-MeS02C6H4-NH-PhNH Ph l-Tri (C > 1076 Me 4-Py -NH-PhNH Ph l-Tri (C) 1077 Me 4-MeNHS02C6H4 -NH -3-PyNH Me PhCH2CH2NH (A) 1078 Me 4-MeS02C6H4-NH-3-PyNH Me PhCH2CH2NH (A) 1079 Me 4-Py-NH- 3-PyNH Me PhCH2CH2NH (A). 1080 Me 4-MeNHS02C6H,-NH -Ph (A) NH Me 1-Pyra 1081 Me 4-MeS02C6H4 -NH-Ph (A) NH Me 1-Pyra 1082 Me 4-Py-NH-Ph (A) NH Me 1-Pyra 1083 Me 4-MeNHS02C6H4- NH-Ph (A) NH Me 1-Imid 1084 Me 4-MeS02C6H4-NH-Ph (A) NH Me 1-Imid1085 Me 4-Py-NH-Ph (A) NH Me 1-Imid 1086 Me 4-MeNHS02C6H4-NH-PhNH Ph (J) EtNH⑻ 1087 Me 4-MeS02C6H4-NH- PhNH Ph (J); EtNH (B) 1088 Me 4-Py-NH- Phray Ph (J) EtNH ⑻ 1089 Me 4- MeNHS02C6H4-NH- PhNH 4-FC6H4 EtNH⑻ 1090 Me 4-MeS02C6H4 -NH- PhNH 4-FC6H4 EtNH⑻ 1091 Me 4-Py -NH- PhNH 4-FC6H4 EtNH OB) 1092 Me 4-Py -NH- 4-FC6H4NH 4- FC6H4 4-PyCH2CH20 1093 Me 4-MeNHS02C6H4-Rei- PhNH PhCH2 PhCH2CH2NH (A) 1094 Me 4-MeS02C6H4 -NH- PhNH PhCH2 PhCH2CH2NH (A) 1095 Me 4-Py -NH- PhNH PhCH2 PhCH2CH2NH (A) 1096 Me 4- MeNHS02C6H4 -NH- PhNH PhCH2 PhCH2CH2NH (D) -90- 200524880 1097 Me 4-MeS〇2C6H4 -Li- PhNH PhCH2 PhCH2CH2NH (D) 1098 Me 4-Py-NH-PhNH PhCH2 PhCH2CH2NH (D) 1099 Me 4-MeNHS02C6H4 Lai-PhNH PhCH2 EtNH (A) 1100 Me 4-MeS02C6H4 -NH- PhNH PhCH2 EtNH (A) 1101 Me 4-Py-NH_ PhNH PhCH2 EtNH (A) 1102 Me 4-MeNHS02C6H4-Lai-PhNH PhCH2 cPrNH 1103 Me 4- MeS02C6H4 -NH- PhNH PhCH2 cPrNH 1104 Me 4-Py-NH- PhNH PhCH2 cPrNH 1105 Me 4-Py -NH- 4-FC6H4NH 4-FC6H4 Pyrr (B) 1106 Me 4-MeNHS02C6H4-NH- PhNH PhCH2 E Xinjiang 1107 Me 4-M.eS02C6H4-NH-PhNH PhCH2 EtNH⑻ 1108 Me 4-Py -NH- PhNH PhCH2 EtNH ⑻ 1109 Me 4-MeNHS0, C6H4-NH- PhNH PhCH2 NMe2 1110 Me 4-MeS02C6H4-NH- PhNH PhCH2 Lie2 1111 Me 4-Py .-NH- PhNH PhCH2 ^ e2 1112 Me Ph (K) -NH- PhNH PhCH2 Lie2 1113 Me 4-MeNHS02C6H4 • -NH- PhNH · PhCH2, EtNH⑻ 1114 Me 4-MeNHS02C6H4 -NH- PhNH PhCH2 cBuNH 1115 Me 4-MeNHS02C6H4 -NH-PhNH PhCH2 H0GH2CH2NH 1116 Me 4-MeS02C6H4 -NH- PhNH PhCH2 hoch2ch2nh 1117 Me 4-Py ~ NH ~ PhNH PhCH2 hoch2ch2nh 1118 Me Ph (K) -NH-PhNH. PhCH2 hoch2ch1n-1 MeNHS02C6H4 -NH- PhNH PhCH2 MeCH (OH) CH2NH 1120 Me 4-MeS02C6H4-NH-PhNH PhCH2 MeCH (OH) CH2NH 1121 Me 4-Py -NH- PhNH PhCH2 MeCH (OH) CH2NH 1122 Me 4-MeNHS02C6H4 -NH- PhNH PhCH2 (4-Py) CH (OH) CH2NH 1123 Me 4-MeS02C6H4 -NH- PhNH PhCH2 (4-Py) CH (0H) CH2NH 1124 Me 4-Py-NH- PhNH PhCH2 (4-Py) CH (OH) CH2NH 1125 Me 4-MeNHS02C6H4 -NH- PhNH H PhCH2CH, NH (D) 1126 Me 4-MeS02C6H4 -NH- PhNH H PhCH2CH2NlKD) 200524880 1127 Me 4-Py ~ NH ~ PhNH H PhCH2CH2NH (D) 1128 Me 4-MeNHS02C6H4 -NH- cPrNH H PhCH2CH2NH (A) 1129 Me 4_M6S02C6H4 -NH- cPrNH H .PhCH2CH2NH (A) 1130 Me 4-Py -NH- cPrNH H PhCH2CH2NH (A) 1131 Me 4-Py -NH- Py (B Rei H PhCH2CH2NH (A) 1132 Me 4-MeNHS02C6H4 -NH- Py (C) NH H 1-Pyra 1133 Me 4-M6NHS02C6H4 -NH-Py (C) NH H 1-Imid1134 Me 4-MeNHS02C6H4 -NH- 2-MeC6H4NH H 1-Pyra 1135 Me. 4-MeNHS02C6H4 -leg- 2-MeC6H4NH Ph 1-Imid 1136 Me 4-MeNHS02C6H4 _NH ~ PhNH H PhCH2NH (A) 1137 Me 4-MeS02C6H4 -NH-PhNH H PhCH2NH (A) 1138 Me 4-Py -NH-PhNH H PhCH2NH (A) 1139 Me 4-MeNHS02C6H4-NH- PhNH H 3,4- (OMe) 2C6H3NH 1140 Me 4-MeS02C6H4 -NH-PhNH H 3,4- (0Me) 2C6H3NH 1141 Me 4-Py .-NH- PhNH H 3,4- (0Me) 2C6H3NH 1142 Me 4-Me.NHS02C6H4 -NH- PhNH H PhCH2CH20 (A) 1143 Me 4-MeS02C6H4 -NH- PhNH H PhCH2CH20 (A) 1144 Me • 4-Py-NH-PhNH H PhCH2CH20 (A) 1145 Me 4-MeNHS02C6H4-ΝΉ-PhNH H Ph (B) CH2NH 1146 Me 4-MeS02C6H4 -NH- PhNH H Ph (B) CH2NH 1147 Me 4-Py- NH ~ PhNH H Ph (B) CH2NH 1148 Me 4-MeNHS02C6H4-NH- PhNH H PhCH2CH2NlKE) 1149 Me 4-MeS02C6H4 -NH -PhNH H PhCH2CH2NH (E) 1150 Me 4-Py -NH-PhNH H PhCH2CH2NH (E) 1151 Me 4-MeNHS02C6H4 -NH- PhNH H PhCH2CH2NH (F) 1152 Me 4-MeS02C6H4 -NH- PhNH H PhCH2CH2NH (F) 1153 Me 4-Py _-NH_ PhNH H PhCH2CH2NH (F) 1154 Me 4-MeNHS02C6H4 -NH- PhNH H PhCH2CH2NH (G) 1155 Me 4-MeS02C6H4 -NH- PhNH H PhCH2CH2NH (G) 1156 Me 4-Pv -NH- PhNH H PhCH2CH2NH (G) -92- 200524880

1157 Me 4-MeNHS02C6H4-NH- PhNH H 3-CF3C6H4CH2CH2NH 1158 Me 4-MeS02C6H4-NH-PhNH H 3-CF3C5H4CH2CH2NH 1159 Me 4-Py -NH- PhNH H 3-CF3C6H4CH2CH2NH 1160 Me 4-Py-NH_ PhNH ClC6H4CH2CH2NH 1161 Me 4-MeNHS02C6H4-NH- Phray Ph (4-Py) CH (OH) CH2NH 1162 Me 4-MeS02C6H4-NH_ Phray Ph (4-Py) CH (0H) CH2NH 1163 Me 4-Py -NH- PhNH .Ph (4-Py) CH (OH) CH2NH 1164 Me 4-MeNHS02C6H4-NH-PhNH H 4-FC6H4CH2CH2NH 1165 Me 4 ~ MeS02C5H4-Rei- PhNH H 4-FC6H4CH2CH2NH 1166 Me 4-Py-NH- PhNH H 4 -FC6H4CH2CH2NH 1167 Me 4-MeNHS02C6H4-NH- PhNH H 3-FC6H4CH2CH2NH 1168 Me 4_MeS02C6H4 -NH- PhNH H 3-FC6H4CH2CH2NH 1169 Me 4-Py -NH- PliNH H 3-FC6H4CH2CH2NH4CH-1170 Me 4-MeNH H 1-Imid 1171 Me 4-MeNHS02C6H4 .-NH- Ph (L) NH H 1-Imid 1172 Me 4-MeNHS02C6H4 -NH- 3-FC6H4NH H 1-Imid 1173 .Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH H 1-Imid 1174 Me 4-MeNHS02C6H4 -Li- Ph (C) NH H 1-Imid 1175 Me Ph (K)-NH- Ph (A) NH H 1-Imid 1176 Me Ph (K) -NH- Ph (A ) NH Ph 1-Pyra 1.177 Me Ph⑻ -NH- Ph (A) NH Ph 1-Imid 117 8 Me 4-MeS02C6H4 -NH-PhNH H 3,4-F2C6H3CH2NH 1179 Me 4-MeNHS02C6H4 -NH- PhNH H Et Li (I) 1180 Me 4-MeS02C6H4 -NH- PhNH H EtNH (I) 1181 Me 4-Py- NH- PhNH H .EtNH (I) 1182 Me 4-MeNHS02C6H4 -NH- PhNH Ph N (CH2CH2OH) 2 1183 Me 4 ~ M6S02C6H4 -NH- PhNH Ph N (CH2CH2OH) 2 1184 Me 4-Py -NH- PhNH Ph N (CH2CH20H) 2 1185 Me 4-MeS02C6H4 -NH- PhNH H (4-Py) CH2NH 1186 Me 4-MeS0, C6H4 -NH- .PhNH H (2-Th) CH2NH 93 200524880 1187 Me 4-MeS02C6H4 -NH- 4 -FC6H4NH 4-FC6H4 1-Pyra 1188 Me 4-MeNHS02C6H4 -NH- PhNH H EtNH (J) 1189 Me 4-MeS02C6H4 -leg- PhNH H EtNH (J) 1190 Me 4-Py .-NH- PhNH H EtNH ⑴ 1191 Me 4-MeNHS02C6H4 -NH- PhNH H H0CH2CH2NH 1192 Me 4-MeS02C6H4 -NH- PhNH H hoch2ch2nh 1193 Me 4-Py -NH-PhNH H hoch2ch2nh 1194 Me 4-Me Li S02C6H4 -NH- Ph (A) NH H PhCH2CH2NH ( D) 1195 Me 4-MeS02C6H4 -NH- Ph (A) NH H PhCH2CH2NH (D) 1196 Me 4-Py -NH- Ph (A) NH H PhCH2CH2NH (D) 1197 Me 4-MeNHS02C6H4 -NH- PhNH H (4 -Py) CH (0H) CH2NH 1198 Me 4-MeS02C6H4-NH- PhNH H (4-Py) CH (0H) CH2NH 1199 Me 4-Py-PhNH H (4-Py ) CH (OH) CH2NH 1200 Me 4-MeS02C6H4 -NH-4-FC6H4NH 4-FC6H4 1-Imid 1201 Me 4-MeS02C6H4 • -NH- 4-FC6H4NH 4-FC6H4 Pyra (A) 1202 Me 4-MeS02C6H4 -NH- 4-FC6H4NH .4-FC6H4 EtNH (B) 1203 Me 4-MeNHS02C6H4-NH- PhNH Ph MeCH (OH) CH2NH 1204 Me 4-MeS02C6H4 -NH- PhNH Ph MeCH (OH) CH2NH 1205 Me 4-Py-NH- PhNH Ph MeCH (OH) CH2NH 1206 Me 4_MeS02C6H4 -NH- PhNH. H MeCH (OH) CH2NH 1207 Me 4-MeNHS02C6H4-NH-PhNH Ph PhCH2CH2NH (D) 1208 Me 4-MeS02C6H4 -Band- PhNH Ph PhCH2CH2mi (D) 1209 Me 4-Py-NH- PhNH Ph PhCH2CH2NH (D) 1210 Me 4-MeS02C6H4-Rei- 4-FC6H4NH 4-FC6H4 PhCH2CH2NH (A) 1211 Me 4_MeS02C6H4 -NH-4-FC6H4NH 4-FC6H4 4-PyCH (0H) CH2NH 1212 Me 4-MeS02C6H4 -Li- 4-FC6H4NH 4-FC6H4 4-PyCH2fffl 1213 Me 4-MeS02C6H4 -NH- 4-FC6H4NH 4-FC6H4 4-PyCH2CH2CH2NH 1214 Me 4-MeS02C6H4 -NH- PhNH Ph .EtNH (K) 1215 Me 4-MeS0〇C6H4 -NH- PhNH Ph EtNH (L) 1216 Me 4-Py -NH- PhNH Ph EtNH (L) 94- 200524880

1217 Me 4-MeNHS02C6H4 -NH- PhNH Ph 4-PyCH2NH 1218 Me 4-MeS02C6H4 -NH- PhNH Ph 4-PyCH2NH 1219 Me 4-Py -NH- PhNH Ph 4-PyCH2NH 1220 Me 4-Py -NH- PhNH Ph iPrNH 1221 Me 4-MeNHS02C6H4 -NH- PhNH Ph PhCH2NH (A) 1222 Me 4-MeS02C6H4 -NH- PhNH Ph PhO ^ HOV) 1223 Me 4-Py * ~ NH_ PhNH Ph PhCH2NH (A) 1224 Me 4-MeNHS02C6H4-NH -4-FC6H4NH H EtNH (B) 1225 Me 4-MeS02C6H4 -NH- 4-FC6H4NH H EtNH (B) 1226 Me 4-Py -NH- 4-FC6H4NH H EtNH (B) 1227 Me 4-MeNHS02C6H4 -NH- 4 -C1C6H4NH H EtNH (B) 1228 Me 4-MeS02C6H4 • -NH-4-ClC6H4NH H Et_) 1229 Me 4-Py -NH- 4-ClC6H4NH H EtNH (B) 123.0 Me 4-MeNHS02C6H4 • -NH- 4-FC6H4NH Ph ； EtNH⑻ 1231 Me 4-MeS02C6H4 -NH- 4-FC6H4NH Ph EtNH⑻ 1232 Me 4-MeNHS02C6H4-NH-2-FC6H4NH Ph EtNH (B) 1233 Me 4-MeNHS02C6H4 -Li- PhNH Ph (4-Py) CH2CH2CH2NH 1234 Me 4-MeNHS02C6H4 ~ NH ~ PhNH H Pyrr (B) 1235 Me 4-MeS〇2C6H4 -NH- PhNH H Pyrr (B) 1236 Me 4-Py -NH- PhNH H Pyrr (B) 1237 Me 4-MeNHS02C6H4-NH- PhLi Ph Pyrr (B) 1238 Me 4-MeNHS02C6H4 -NH- PhNH Ph (4-Py) CH 2CH20 1239 Me 4-Py-NH- PhNH H. PhCH2NH (B) 1240 Me 4-MeS02C6H4 -NH- 4-FC6H4NH 4-FC6H4 4-PyCH2CH20 1241 Me Ph (M) '-NH- PhNH Ph H 1242 Me Ph ( N) -NH- PhNH Ph H 1243 Me 4-MeS02C6H4 _NH-4-FC6H4NH 4-FC6H4 Pyrr (B) 1244 Me 4-Py -NH- PhNH H PhCH2CH2NH (H) 1245 Me 4-Py -NH- PhNH H 4 -PyCH2NH 1246 Me 4-Py -ΝΉ- PhNH H 4-PvCH2CH2CH2NH -95- 200524880

1247 Me 4-Py -NH- PhNH H 4-PyCH2CH20 1248 Me 4-Py -NH- PhNH Ph 4-PyCH2CH2CH2NH 1249 Me 4-Py -NH- PhNH Ph 4-PyCH2CH20 1250 Me 4-Py -NH- PhNH. Ph Pyrr (B) 1251 • Me 4-Py -NH- PhNH 3-Th 4-PyCH (OH) CH2NH 1252 Me 4-Py-NH- PhNH 3-Th 4-PyCH2NH 1253 Me 4-Py -NH- PhNH 3- Th 4-PyCH2CH2CH2NH 1254 Me 4-Py -NH- PhNH, 3-Th 4-PyCH2CH20 1255 Me 4-Py -NH- PhNH 3-Th. Pyrr (B) 1256 Me 4-Py -NH-PhNH 2-MeC6H4 4 -PyCH (0H) CH2NH 1257 .Me 4-Py -NH- PhNH. 2-MeC6H4 4-PyCH2NH 1258 Me 4-Py, -NH- PhNH 2-MeC6H4 4-PyCH2CH2CH2NH 1259 Me 4-Py -NH- PhNH 2- MeC6H4 4-PyCH2CH20 1260 Me 4-Py-NH- PhNH 2-MeC6H4 Pyrr (B) 1261 Me 4-MeS02 (J6H4 _NH- PhNH H 4-PyCH2CH2CH2NH 1262 Me 4-MeS02C6H4-NH- PhNH H 4-PyCH2CH20 1263 Me 4 -MeS02C6H4-NH-PhNH Ph 4-PyCH2CH2CH2NH 1264 Me 4-MeS02C6H4-NH- PhNH Ph 4-PyCH2CH20 1265 Me 4-MeS02C6H4 -NH- PhNH Ph Pyrr (B) 1266 Me 4-MeS02C6H4 -NH-PhNH 3-Th 4 -PyCH (0H) CH2NH 1267 Me 4-MeS02C6H4-NH-PhNH 3-Th 4-PyCH2NH 1268 Me 4-MeS02C6H4 -NH- PhNH 3-Th 4-PyCH2 CH2CH2NH 1269 Me 4-MeS02C6H4-Legs-PhNH 3-Th 4-PyCH2CH20 1270 Me 4-MeS02C6H4 -NH- PhNH 3-Th Pyrr (B) 1271 Me 4-MeS02C6H4 -NH- PhNH .2-MeC6H4 4-PyCH (0H ) CH2NH 1272 Me 4-MeS02C6H4 -NH_ PhNH 2-MeC6H4 4-PyCH2NH 1273 Me 4-MeS02C6H4 .-NH- PhNH 2-MeC6H4 4-PyCH2CH2CH2NH 1274 Me 4-MeS02C6H4-NH- PhNH 2-MeC6H4 4-PyCH2CH20 -MeS02C6H4 -NH- PhNH 2-MeC6H4 Pyrr (B) 1276 Me 4-MeNHS02C6H4-NH-PhNH H 4-PyCH2NH -96- 200524880 1277 Me. 4-MeNHS02C6H4 -NH- PhNH H 4-PyCH2CH2CH2NH 1278 Me 4-MeNHS02C6H4 NH-. PhNH H. 4-PyCH2CH20 1279 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th 4-PyCH (0H) CH2NH 1280 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th 4-PyCH2NH 1281 Me 4-MeNHS02C6H4 -NH -PhNH 3-Th 4-PyCH2CH2CH2NH 1282 Me 4-MeNHS02C6H4 -NH- PhNH 3-Th 4-Py.CH2CH20 1283 Me 4-MeNHS02C6H4 -ΝΉ- PhNH .3-Th Pyrr (B) 1284 Me 4-MeNHS02C6H4-NH- PhNH 2-MeC6H4 4-PyCH (0H) CH2NH 1285 Me 4-MeNHS02C5H4 -NH- PhNH 2-MeC6H4 4-PyCH2fm 1286 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 4-PyCH2CH2CH2NH1287 Me 4-MeNHS02C6H4- NH- PhNH 2-MeC6H4 4-PyCH2CH20 1288 Me 4-MeNHS02C6H4 -NH- PhNH 2-MeC6H4 Pyrr OB) 1289 Me 4-Py .- NH- PhNH 2-FC6H4 4-Py CH (OH) CH2NH 1290 Me 4-Py -NH- PhNH 2-FC6H4 4-PyCH2NH 1291 Me 4-Py -NH- * PhNH .2-FC6H4 4-PyCH2CH2CH2NH 1292 Me 4-Py -NH- PhNH 2-FC6H4 4-PyCH2CH20 1293 Me 4-Py-NH- PhNH 2-FC6H4 Pyrr (B) 1294 Me 4-MeS02C6H4-NH- PhNH 2-FC6H4 4-PyCH (OH) CH2NH 1295 Me 4 ~ M6S02C6H4-NH- PhNH 2-FC6H4 4-PyCH2NH 1296 Me 4-MeS02C6H4-NH_ PhNH 2-FC6H4 4 ~ PyCH2CH2CH2NH 1297 Me 4-MeS02C6H4 -NH- PhNH 2-FC6H4 4-PyCH2CH20 1298 Me 4 ~ M6S02C6H4 -NH- PhNH 2-FC6H4 Pyrr ⑻ 1299 Me 4-MeNHS02C6H4-NH-PhNHP 2-FC6H4 ~ (OH) CH2NH 1300 Me 4-MeNHS02C6H4 _NH-PhNH 2-FC6H4 4-PyCH2NH 1301 Me 4-MeNHS02C6H4 -NH- PhNH 2-FC6H4 4-PyCH2CH2CH2NH 1302 Me 4-MeNHS02C6H4 -NH- PhNH 2-FC6H4 4-PyCH2CH20 130 4-MeNHS02C6H4-NH- PhNH 2-FC6H4 Pyrr (B) 1304 Me 4-Pv -NH- PhNH 4-FC6H4 .1-Pyra 1305 Me 4-Py -NH- PhNH 4-FC6H4 1-Imid 1306 Me 4-Py -NH- PhNH 4-FC6H4 Pyra (A) -97-200524880

1307 Me 4-Py -NH- PhNH 4-FC6H4 PhCH2CH2NH (A) 1308 Me 4-Py _NH_ PhNH 4-FC6H4 4-PyCH (0H) CH2NH 1309 Me 4-Py -NH- PhNH 4-FC6H4 4-PyCH2NH 1310 Me 4-Py _NH ~~ PhNH 4-FC6H4 4-PyCH2CH2CH2NH 1311 Me 4-Py _NH-PhNH 4-FCA 4-PyCH2CH20 1312 Me 4-Py -NH- PhNH 4-FC6H4 Pyrr (B) 1313 Me 4-MeS02C6H4-. -PhNH 4-FC6H4 1-Pyra 1314 Me 4-MeS02C6H4 -NH- PhNH 4-FC6H4 1-Imid 1315 Me 4-MeS02C6H4 _NH- PhNH 4-FC6H4 Pyra (A) 1316 Me 4-MeS02C6H4 -NH- PhNH 4-FC6H4 PhCH2CH2NH (A) 1317 Me 4-MeS02C6H4 -NH- PhNH 4-FC6H4 4 ~ PyCH (0H) CH2NH 1318 Me .4-MeS02C6H4 -NH- PhNH. 4-FC6H4 4-PyCH2NH 1319 Me 4-MeS02C6H4 PhNH 4-FC6H4 4 -PyCH2CH2CH2NH 1320 Me 4_M6S02C6H4 -NH- PhNH 4-FC6H4 4-PyCH2CH20 1321 Me 4-MeS02C6H4 -NH- PhNH 4-FC6H4 Pyrr (B) 1322 Me 4-MeNHS02C6H4-NH- PhNH 4-FC6H4 1-Py MeNHS02C6H4-NH- PhNH 4-FC6H4 1-Imid 1324 Me 4-MeNHS02C6H4-NH- PhNH 4-FC6H4 Pyra (A) 1325 Me 4-MeNHS02C6H4-NH-PhNH 4-FC6H4 PhCH2CH2NH (A) 1326 Me 4-MeNHS02C6 -PhNH 4-FC6H4 4-PyCH (0H) CH2NH 1327 Me 4-MeNHS02C6H4 -NH- PhNH 4-FC6H4 4-PyCH2NH 1328 Me 4-MeNHS02C6H4 -NH- PhNH 4-FC6H4 4-PyCH2CH2NH 2329 Me 4-Me Li S02C6H4 -NH-. PhNH 4-FC6H4 4-PyCH2CH20 1330 Me 4-MeNHS02C6H4 -NH- PhNH 4-FC6H4 Pyrr ⑻ 1331 Me 4-Py .-NH- 2-FC6H4NH H 1-Imid 1332 Me 4-Py-NH- 2-FC6H4NH H Pyra (A) 1333 Me 4-Py- NH-2-FC6H4NH .H EtNH (B) 1334 Me 4-Py -NH ~ 2-FC6H4NH H Ph.CH2CH2NH (A) 1335 Me 4-Py -NH- 2-FC6H4NH H-4-PyCH (0H) CH2NH 1336 Me • 4-Py -NH- 2-FC6H4NH H 4-PyCH2NH -98- 200524880 1337 Me 4-Py -NH- 2-FC6H4NH H 4-PyCH2CH2CH2NH 1338 Me 4-Py -NH- 2-FC6H4NH H 4-PyCH2CH20 1339 Me 4-Py -NH- 2-FC6H4NH H Pyrr (B) 1340 Me 4-MeS02C6H4-NH-2-FC6H4NH H 1-Pyra 1341 Me 4-MeS02C6H4 -NH- 2-FC6H4NH H 1-Imid 1342 Me 4-MeS02C6H4 -NH-2-FC6H4NH H Pyra (A) 1343 Me 4-MeS02C6H4-NH_ 2-FC6H4NH H EtNH ⑻ 1344 Me 4-MeS02C6H4-NH- 2-FC6H4NH H PhCH2CH2NH (A) 1345 Me 4-MeS02C6H4 -NH- 2- FC6H4NH H 4-PyCH (0H) CH2NH 1346 Me 4-MeS02C6H4-NH- 2-FC6H4NH H 4-PyCH2NH 1347 Me 4-MeS02 C6H4-NH-2-FC6H4NH H 4-PyCH2CH2CH2NH 1348 Me 4-M6S02C6H4 -NH- 2-FC6H4NH H 4-PyCH2CH20 1349 Me 4-MeS02C6H4-NH- 2-FC6H4NH H Pyrr ⑻ 1350 Me 4-MeNHS02C6H4 -NH FC6H4NH H Pyra (A) 1351 Me 4-MeNHS02C6H4 • -NH- 2-FC6H4NH H EtNH ⑻ 1352 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH H 4 ~ PyCH (0H) CH2NH 1353 Me 4-MeNHS02C6H4-NH- 2 ~ FC6H4NH H 4-PyCH2NH 1354 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH H .4-PyCH2CH2CH2NH 1355 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH H 4-PyCH2CH20 1356 Me 4-M.eNHS02C6H4 -NH H 2-FC6H4 Pyrr ⑻ 1357 Me 4-Py ~ NH_ 2-FC6H4NH Ph 1-Imid 1358 Me 4-Py -NH- 2-FC6H4NH Ph Pyra (A) 1359 Me 4-Py .- NH-2-FC6H4NH Ph EtNH (B). 1360 Me 4-Py -NH- 2-FC6H4NH Ph PhCH2CH2Iffl (A) 1361 Me 4-Py _NH_ 2-FC6H4NH Ph 4-PyCH (OH) CH2NH 1362 Me 4-Py -NH- 2-FC6H4NH Ph 4-PyCH2NH 1363 Me 4-Py-NH_ 2-FC6H4NH Ph 4-PyCH2CH2CH2NH 1364 Me 4-Py., -NH- 2-FC6H4NH Ph 4-PyCH2CH20 1365 Me 4-Py -NH- 2-FC6H4NH Ph Pyrr (B) 1366 Me 4-MeS02C6H4 -NH- 2-FC6H4NH Ph 1-Pyra -99- 200524880 1367 Me 4-MeS02C6H4 -NH- 2-FC6H4NH Ph 1-Imid 1368 Me. 4_MeS02C6H4 ~ NH- 2-FC6H4NH Ph Pyra (A) 1369 Me 4-MeS02C6H4 -Li- 2-FC6H4NH Ph EtNH (B) 1370 Me 4-MeS02C6H4 -NH- 2 -FC6H4NH Ph 'PhCH2CH2NH (A) 1371 Me 4_MeS02C6H4-NH-2-FC6H4 Li Ph 4-PyCH (0H) CH2NH 1372 Me 4-MeS02C6H4-NH-2-FC6H4NH Ph 4-PyCH2NH 1373. Me 4-MeS02C6H4-. 2-FC6H4NH Ph. 4-PyCH2CH2CH2NH 1374 Me 4-MeS02C6H4 -NH-2-FC6H4NH Ph 4-PyCH2CH20 1375 Me 4-MeS02C6H4 -NH- 2-FC6H4NH Ph Pyrr (B) 1376 Me 4-MeNHS02C6H4-NH-2-FC6H4 Ph 1-Imid 1377 Me 4-MeNHS02C6H4-NH- 2-FC6H4NH Ph Pyra (A) 1378 Me .4-MeNHS02C6H4 -NH-2-FC6H4NH Ph,, PhCH2CH2NH (A) 1379 Me 4-MeNHS02C6H4-NH- 2-FC6H4NH Ph 4-PyCH. (0H) CH2NH 1380 Me 4-MeNHS02C6H4-NH-2-FC6H4NH Ph 4-PyCH2NH 1381. Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH Ph 4-PyCH2CH2CH2NH 1382 Me 4-MeNHS02C6H4 -NH- 2- FC6H4NH Ph 4-PyCH2CH20 1383 Me 4-MeNHS02C6H4-NH- 2-FC6H4NH Ph Pyrr (B) 1384 • Me 4-Py -NH- 2-FC6H4NH 3-Th Pyra 1385 Me 4-Py-NH-2-FC6H4NH 3 -Th 1-Imid 1386 Me 4-Py -NH- 2-FC6H4NH 3-Th Pyra (A) 1387 Me 4-Py -NH- 2-FC6H4NH 3-Th EtNH (B) 1388 Me 4-Py -leg- 2-FC6H4NH 3-Th PhCH2CH2NH (A) 1389 Me 4-Py .-NH- 2-FC6H4NH 3-Th 4-PyCH (0H) CH2NH 1390 Me 4-Py -NH- 2-FC6H4NH 3-Th 4-PyCH2NH 1391 Me 4-Me Li S02C6H4 -NH- 4- FC6H4 Book 4-FC6H4 4-PyCH (0H) CH2NH 1392 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH 4-FC6H4 4-PyCH2NH 1393 Me 4-MeNHS02C6H4-NH-4-FC6H4NH 4-FC6H4 4-PyCH2CH2CH2NH 1394 Me 4- MeNHS02C6H4 -NH- 4-FC6H4NH 4-FC6H4. 4-PyCH2CH20 1395 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH 4-FC6H4 Pyrr (B) 1396 Me 4-MeS02C6H4 -NH- 4-FC6H4NH Ph Pyra (A) -100 -200524880 1397 Me 4-MeS02C6H4 -NH- 4_FC6H4NH Ph PhCH2CH2NH (A) 1398 Me '4-MeNHS02C6H4 -NH- 2-FC6H4NH 4-FC6H4 4-PyCH2CH2CH2NH 1399 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH 4-FC6 B) 1400 Me 4-MeNHS02C6H4-NH- 4-FC6H4NH 4-FC6H4 PhCH2CH2NH (A) 1401 Me 4-Py _NH ~ 2-FC6H4 Li 3-Th 4-PyCH2CH2CH2NH 1402 Me 4-Py-NH-2-FC6H4NH 3- Th 4-PyCH2CH20 1403 Me 4-Py-NH- 2-FC6H4NH 3-Th Pyrr ⑻ 1404 Me 4-MeS02C6H4 -leg- 2-F C6H4NH 3-Th 1-Pyra 1405 Me 4-MeS02C6H4 -NH-2-FC6H4NH • 3-Th 1-Imid 1406 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 3-Th Pyra (A) 1407 Me, 4-MeS02C6H4- NH-. 2-FC6H4NH 3-Th Et_) 1408 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 3-Th PhCH2CH2NH (A) 1409 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 3-Th 4-PyCH (0H) CH2NH 1410 Me 4-MeS02C6H4-NH- 2-FC6H4NH 3-Th 4-PyCHzNH 1411 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 3-Th 4-PyCH2CH2CH2NH 1412 Me 4-MeS02C6H4-NH- 2-FC6H4NH 3-Th 4- PyCH2CH20 1413 Me 4-MeS02C6H4-NH- 2-FC6H4NH 3-Th Pyrr (B) 1414 Me 4-MeNHS02C6H4 -NH-2-FC6H4NH 3-Th l ~ Pyra 1415 Me 4-MeNHS02C6H4 -leg- 2-FC6H4NH 3-Th 1-Imid 1416 Me 4-MeNHS02C6H4-NH-2-FC6H4NH 3-Th Pyra (A) 1417 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH 3-Th EtNH (B) 1418 Me 4-MeNHS02C6H4-NH-2-FC6H4NH 3-Th PhCH2CH2NH (A) 1419 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH 3-Th 4-PyCH (OH) CH2NH 1420 Me 4-MeNHS02C6H4-NH-2-FC6H4NH 3-Th 4-PyCH2NH 1421 Me 4-MeNHS02C6H4 -Li- 2-FC6H4NH 3-Th 4-PyCH2CH2CH2NH 1422 iMe 4-MeNHS02C6H4-NH- 2-FC6H4NH 3 -Th 4-PyCH2CH20 1423 Me 4-MeNHS02C6H4 -Li- 2-fc6h4nh 3-Th Pyrr (B) 1424 Me 4-Py -NH- 2-FC6H4NH 4-FC6H4 .1-Pyra 1425 Me 4-Py -NH- 2 -FC6H4NH 2-FC6H4 1-Imid 1426 Me 4_Py -ΝΉ- 2-FC6H4NH 2-FC6H4 Pyra (A) 200524880 1427 Me 4-Py -NH- 2-FC6H4NH 2-FC6H4 EtNH (B) 1428 Me. 4-Py- NH- 2-FC6H4NH 2-FC6H4 PhCH2CH2NH (A) 1429 Me 4-Py -NH- 2-FC6H4NH 2-FC6H4 4-PyCH (0H) CH2Iffl 1430 Me 4-Py -NH- 2-FC6H4NH 2-FC6H4 4-PyCH2NH 1431 Me 4-Py -NH-. 2-FC6H4NH 2-FC6H4 4-PyCH2CH2CH2NH 1432 Me 4-Py-NH-2-FC6H4 Li 2-FC6H4 4-PyCH2CH20 1433 Me 4-Py -NH- 2-FC6H4NH 2-FC6H4 Pyrr (B) 1434 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 2-FC6H4 1-Pyra 1435 Me 4-MeS02C6H4-NH_ 2-FC6H4NH 2-FC6H4 1-Imid 1436 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 2- FC6H4 Pyra (A) 1437 Me 4-MeS02C6H4-NH- 2-FC6H4NH 2-FC6H4 EtNH (B) 1438 Me 4-MeS02C6H4-NH- 2-FC6H4NH 2-FC6H4 PhCH2CH2NH (A) 1439 Me 4-MeS02C6H4-NH- 2-FC6H4NH 2-FC6H4 4-PyCH (0H) CH2NH 1440 Me 4-MeS02C6H4-NH_ 2-FC6H4NH 2-FC6H4 4-PyCH2NH 1441 Me 4-MeS02C6H4 -NH- 2-F C6H4NH 2-FC6H4 4-PyCH2CH2CH2NH 1442 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 2-FCA 4-PyCH2CH20 1443 Me 4-MeS02C6H4 -NH-2-FC6H4NH 2-FC6H4 Pyrr ⑻ 1444 Me 4-MeNHS02C6H4 -NH- FC6H4NH 2-FC6H4 1-Pyra 1445 Me 4-MeKHS02C6H4-NH_ 2-FC6H4 Li 2-FC6H4 1-Imid 1446 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH 2-FC6H4 Pyra (A) 1447 Me 4-MeNHS02C6H4 ~ NH- 2-FC6H4NH 2-FC6H4 EtNH ⑻ 1448 Me 4-MeNHS02C6H4-NH-2-FC6H4NH 2-FC6H4 PhCH2CH2NH (A) 1449 Me 4-MeNHS02C6H4 -NH- 2-FC6H4NH 2-FC6H4 4-PyCH (OH) CH2NH 1450 Me 4 -MemiS02C6H4 -NH- 2-FC6H4NH 2-FC6H4 4-PyCH2NH 1451 Me 4-MeNHS02C6H4 -Li- 2-FC6H4NH 2-FC6H4 4-PyCH2CH2CH2NH 1452 Me 4-MeNHS02C6H4-NH-2-FC6H4NH 2-FC6CH2 4-Py 4-Me Li S02C6H4 -NH- 2-FC6H4NH 2-FC6H4 Pyrr (B) 1454 Me 4-Py -NH- 2-FC6H4NH 4-FC6H4 1-Pyra 1455 Me '4-Py 2-FC6H4NH 4-FC6H4 1-Imid 1456 Me 4-Py -NH- 2-FC6H4NH 4-FC6H4 Pyra (A) -102-200524880 1457 Me. 4-Py-NH-2-FC6H4NH 4-FC6H4 EtNH⑻ 1458 Me 4-Py -NH- 2-FC6H4NH '' 4-FC6H4 PhCH2CH2NH (A) 1459 Me 4-Py ~ NH- 2-FC6H4 Li 4-FC6H4 4-PyCH (0H) CH2NH 1460 Me 4-Py -NH- 2-FC6H4NH 4-FC6H4 4-PyCH2Iffl 1461 Me 4-Py -NH- 2-FC6H4 Li 4-FC6H4 4- PyCH2CH2CH2NH 1462 Me 4-Py -NH- 2-FC6H4NH 4-FC6H4 4-PyCH2CH20 1463 Me 4-Py -NH- 2-FC6H4NH 4-FC6H4 Pyrr (B) 1464 Me 4-MeS02C6H4 ~ NH ~ 2-FC6H4NH 4-FC6H4 1-Pyra 1465 Me 4_M6S02C6H4 -NH- 2-FC6H4NH 4-FC6H4 1-Imid 1466 Me 4-MeS02C6H4-NH- 2-FC6H4NH 4-FC6H4 Pyra (A) 1467 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 4-FC6H4 EtNH⑻ 1468 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 4-FC6H4 PhCH2CH2NH (A) 1469 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 4-FC6H4 4-Py CH (OH) CH2NH 1470 Me 4-MeS02C6H4 -NH- 2 -FC6H4NH 4-FC6H4 4-PyCH2NH 1471 Me 4-MeS02C6H4-NH- 2-FC6H4NH 4-FC6H4 4-PyCH2CH2CH2NH 1472 Me 4-MeS02C6H4 -NH- 2-FC6H4NH 4-FC6H, 4-PyCH2CH20 1473 Me 4_MeS02 -FC6H4NH 4-FC6H4 Pyrr ⑻ 1474 Me 4-MeNHS02C6H4 -NH-2-FC6H4NH 4-FC6H4 1-Pyra 1475 Me 4-MeNHS02C6H4-NH- 2-FC6H4NH 4-FC6H4 1-Imid 1476 Me 4-MeNHS02C6H4-NH- -FC6H4NH 4-FC6H4 Pyra (A) 1477 Me 4-MeNHS0 2C6H4 -NH- 2-FC6H4NH 4-FC6H4 EtNH (B) 1478 Me 4-MeNHS02C6H4 -ΝΗ- 2-FC6H4NH. 4-FC6H4 PhCH2CH2NH (A) 1479 Me 4-MeNHS02C6H4 -ΝΗ-2-FC6H4NH 4-FC6H4 4-Py CH (OH) CH2NH 1480 Me 4-MeNHS02C6H4 -ΝΗ- 2-FC6H4 Li 4-FC6H4 4-PyCH2NH 1481 Me 4-MeNHS02C6H4 -ΝΗ- 2-FC6H4NH 4-FC6H4 4-PyCH2CH20 1482 Me 4-MeNHS02C6H4-ΝΗ- 2- FC6H4 Li 4-FC6H4 Pyrr ⑻ 1483 .Me 4-Py-ΝΗ-4-FC6H4 Li H 1-Pyra 1484 Me 4-Py -NH- 4-FC6H4NH H .1-Imid 1485 Me 4-Py-ΝΗ-4- FC6H4NH H Pyra (A) 1486 Me. 4-Py -NH- 4-FC6H4NH H PhCH2CH2NH (A) -103-200524880

1487 Me 4-Py -NH- 4-FC6H4 Li H 4-PyCH (0H) CH2NH 1488 Me 4-Py -NH- 4-FC6H4 Li H 4-PyCH2NH 1489 Me 4-Py -NH- 4-FC6H4NH H 4- PyCH2CH2CH2NH 1490 Me 4-Py -NH- 4-FC6H4NH H 4-PyCH2CH20 1491 Me 4-Py -NH- 4-FC6H4NH H Pyrr (B) 1492 Me 4-MeS02C6H4 -NH-. 4-FC6H4NH H 1-Pyra 1493 Me 4-MeS02C6H4 _NH-4-FC6H4NH H 1-Imid 1494 Me 4-MeS02C6H4 -NH- 4-FC6H4NH H Pyra (A) 1495 .Me 4-MeS02C6H4 -NH- 4-FC6H4NH H PhCH2CH2NH (A) 1496 Me 4-MeS02C6H4 -NH- 4-FC6H4NH H 4-PyCH (0H) CH2NH 1497 Me 4-MeS02C6H4-NH-4-FC6H; NH H 4-PyCH2NH 1498 Me 4-MeS02C6H4-NH-4-FC6H4NH H 4-PyCH2CH2CH2CH2NH1499 Me 4_MeS02C6H4- NH- 4-FC6H4NH H 4-PyCH2CH20 1500 Me 4-MeS02C6H4-NH- 4-FC6H4NH H Pyrr (B) 1501 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH H 1-Pyra 1502 Me 4-MeNHS02C6H4 -NH- 4- FC6H4NH H 1-Imid 1503 Me 4-MeNHS02C6H4 .-NH- 4-FC6H4NH H Pyra (A) 1504 Me 4-MeNHS02C6H4-NH- 4-FC6H4NH H PhCH2CH2NH (A) 1505 Me '4-MeNHS02C6H4-NH- 4-FC6H4 H 4-PyCH (0H) CH2NH 1506 Me 4-MeNHS02C6H4 -NH_ 4-FC6H4NH H 4-PyCH2NH 1507 Me 4-MeNHS02C6H4-NH- 4-FC6H4NH H 4-PyCH2CH2CH2NH 1508 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH H 4-PyCH2CH20 1509 Me 4-MeNHS02C6H4-NH- 4-FC6H4NH H Pyrr (B) 1510 Me Py-NH-4-FC6H4NH Ph 1-Pyra 1511 Me 4-Py-Legs-4-FC6H4 Li Ph 1-Imid 1512 Me 4-Py-Legs-4-FC6H4NH Ph Pyra (A) 1513 Me 4-Py -NH -4-FC6H4NH Ph PhCH2CH2NH (A) 1514 Me 4-Py-Album-4-FC6H4NH Ph 4-PyCH (0H) CH2NH 1515 Me 4-Py-NH- 4-FC6H4NH Ph 4-PyCH2NH 1516 Me 4-Py -NH -4-FC6H4NH Ph 4-PyCH2CH2CH2NH -104- 200524880 1517 Me 4-Py -NH- 4-FC6H4NH Ph 4-PyCH2CH20 1518 Me 4-Py -NH- 4-FC6H4NH Ph Pyrr (B) 1519 Me 4-MeS02C6H4-NH -4-FC6H4NH Ph 1-Pyra 1520 Me 4-MeS02C6H4 • -NH- 4-FC6H4NH Ph 1-Imid 1521 Me 4-MeS02C6H4-NH- 4-FC6H4NH Ph 4-PyCH (0H) CH2NH 15.22 Me 4-MeS02C6H4 -NH -4-FC6H4NH Ph 4-PyCH2NH 1523 Me 4-MeS02C6H4 -NH- 4-FC6H4NH Ph 4-PyCH2CH2CH2NH 1524 Me .4-MeS02C6H4 .- NH- 4-FC6H4NH Ph 4-PyCH2CH20 1525 Me 4-MeS02C6H4 -NH- 4- FC6H4NH Ph Pyrr (B) 1526 Me 4-MeNHS02C6H4 _NH ~ 4-FC6H4NH Ph 1-Pyra 1 527 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH Ph 1-Imid 1528 Me 4-MeNHS02C6H4-NH-4-FC6H4NH Ph Pyra (A) 1529 Me 4-Py-NH- 4-FC6H4NH 4-FC6H4 4-PyCH2CH2CH2NH 1530 Me 4-MeNHS02C6H4-NH-4-FC6H4NH Ph PhCH2CH2NH (A) 1531 Me 4-MeNHS02C5H4 • -NH- 4-FC6H4NH Ph 4-PyCH (0H) CH2NH 1532 Me 4-MeNHS02C6H4-NH- 4-FC6H4NH Ph 4-PyCH2NH 1533 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH Ph 4-PyCH2CH2CH2NH 1534 Me. 4-MeNHS02C6H4 '-NH-. 4-FC6H4NH Ph 4-PyCH2CH20 1535 Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH Ph Pyrr ⑻ 1536 Me 4- Py -NH- 4-FC6H4NH 3-Th 1-Pyra 1537 Me 4-Py -NH-4-FC6H4NH 3-Th 1-Imid 1538 Me 4-Py -NH- 4-FC6H4NH 3-Th Pyra (A) 1539 Me 4-Py -NH- 4-FC6H4NH 3-Th EtNH ⑻ 1540 Me 4-Py '-NH- 4-FC6H4NH 3-Th PhCH2CH2NH (A) 1541 Me 4-Py -NH- 4-FC6H4NH 3-Th 4-PyCH (0H) CH2NH 1542 Me 4-Py -NH- 4-FC6H4NH 3-Th 4-PyCH2NH 1543 Me 4-Py -NH-4-FC6H4 Leg 3-Th 4-PyCH2CH2CH2NH 1544 Me 4-Py -NH- 4-FC6H4NH 3-Th 4-PyCH2CH20 1545 Me 4-Py -NH- 4-FC6H4NH 3-Th Pyrr (B) 1546 Me 4-MeS02C6H4 -NH- 4-FC6H4NH 3-Th 1-Pyra -105-200524880 1547 Me 4-MeS02C6H4 -NH- 4-FC6H4NH 3-Th 1-Imid 154.8 Me · 4-MeS02C6H4 -NH- 4-FC6H4NH 3-Th Pyra (A) 1549 Me 4_MeS02C6H4 -leg- 4 -FC6H4 Lai 3-Th EtNH⑻ 1550 Me 4-MeS02C6H4. ~ NH_ 4-FC6H4NH. 3-Th PhCH2CH2NH (A). 1551 Me 4-MeS02C6H4 -cis- 4-FC6H4NH 3-Th 4-PyCH (0H) CH2NH 1552 Me 4-MeS02C6H4 -NH- 4-FC6H4NH 3-Th 4-PyCH2NH 1553 Me 4-MeS02C6H4 -M- 4-FC6H4NH 3-Th 4-PyCH2CH2CH2NH 1554 Me 4_MeS02C6H4-ΝΗ_ 4-FC6H4NH 3-Th 4-PyCH2CH20 1C 5555 Me 4Me ΝΗ_ 4-FC6H4NH 3-Th Pyrr (B) 1556 Me 4-MeNHS02C6H4 -leg- 4-FC6H4NH 3-Th 1-Pyra 1557 Me 4-MeNHS02C6H4 -ΝΗ- 4-FC6H4NH 3-Th 1-Iinid 1558 Me 4 ~ MeNHS02C6H4 -.- 4-FC6H4NH 3-Th Pyra (A) 1559 Me 4-MeNHS02C6H4-ΝΗ-4-FC6H4NH 3-Th EtNH ⑻. 1560 Me. 4-MeNHS02C6H4 -ΝΗ-4-FC6H4NH 3-Th PhCH2CH2NH (A) 1561 Me 4-MeNHS02C6H4 -ΝΗ- 4-FC6H4NH 3-Th 4-PyCH (0H) CH2NH 1562 Me 4-MeNHS02C6H4 -ΝΗ- 4-FC6H4NH 3-Th 4-PyCH2NH 1563 Me 4-MeNHS02C6H4 -ΝΗ- 4-FC6H4NH 3- Th 4-PyCH2CH2CH2NH 1564 Me 4-MeNHS02C6H4 -ΝΗ- 4-FC6H4NH 3-Th 4-PyCH2CH20 1565 Me 4-MeNHS02C6H4-ΝΗ-4-FC6H4NH 3-Th Pyrr (B) 1566 Me 4-Py-ΝΗ-4-FC6H4NH 2-FC6H4 1-Pyra 1567 Me 4 -Py-ΝΗ-4-FC6H4NH 2-FC6H4 1-Imid 1568 Me 4-Py-ΝΗ- 4-FC6H4NH 2-FC6H4 Pyra (A) 1569 Me 4-Py -Li- 4-FC6H4NH 2-FC6H4 EtNH (B) 1570 Me 4-Py-ΝΗ-4-FC6H4NH 2-FC6H4 PhCH2CH2NH (A) 1571 Me 4-Py -ΝΗ- 4-FC6H4NH 2-FC6H4 4-PyCH (0H) CH2NH 1572 Me 4-Py -ΝΗ- 4-FC6H4NH 2-FC6H4 4-PyCH2NH 1573 Me 4-Py.-ΝΗ- 4-FC6H4NH 2-FC6H4 4-PyCH2CH2CH2NH 1574 Me 4-Py -ΝΗ- 4-FC6H4NH 2-FC6H4; 4-PyCH2CH, 0 1575 Me 4-Py- ΝΗ- 4-FC6H4NH 2-FC6H4 Pyrr (B) 1576 Me 4-MeS02C6H4 -ΝΗ- 4-FC6H4NH 2-FC6H4 1-Pyra -106- 200524880 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1593 1594 1595 1596 1597 1598 1599 1600 1601 1602

Me 4-MeS02C6H4 -NH- 4-FC6H4NH 2-FC6H4 1-Imid Me 4-MeS02C6H4 -NH-4-FC6H4NH 2-FC6H4 Pyra (A) Me 4-MeS02C6H4 -NH- 4-FC6H4NH 2-FC6H4 E Sprinkle Me 4-MeS02C6H4-NH- 4-FC6H4NH 2-FC6H4 PhCH2CH2NH (A) Me 4-MeS02C6H4-NH- 4-FC6H4 Li 2-FC6H4 4-PyCH (0H) CH2NH Me 4-MeS02C6H4 -NH- 4-FC6H4NH 2-FC6H4 4-PyCH2NH Me 4-MeS02C6H4-NH- 4-FC6H4. 2-FC6H4 4-PyCH2CH2CH2NH Me 4-MeS02C6H4 -NH- 4-FC6H4NH 2-FC6H4 4-PyCH2CH20 Me 4-MeS02C6H4 -NH- 4-FC6H4NH 2-FC6H4 Py (B) Me 4-MeNHS02C6H4 -ra- 4-FC6H4NH 2-FC6H4 1-Pyra Me 4-MeNHS02C6H4-NH- 4-FC6H4NH 2-FC6H4 1-Imid Me 4-MeNHS02C6H4-NH- 4-FC6H4NH 2-FC6H4 Pyra ( A) Me. 4-MeNHS02C6H4 -NH- 4-FC6H4NH 2- FC6H4 Et_) Me 4-MeNHS02C6H4 -NH- 4-FC6H4NH * 2-FC6H4 PhCH2CH2NH (A) Me 4-MeNHS02C6H4-NH- 4-FC6H4NH 2-FC6H4 4 -PyCH (0H) CH2NH Me 4-MeNHS02C6H4-NH- 4-FC6H4NH 2-FCfiH4 4-PyCH2NH Me 4-MeNHS02C6H4-NH-4-FC6H4NH 2-FC6H4 4 ~ PyCH2CH2CH2NH Me 4-MeNHS02C6H4 -NH- 4-FC6H4 FC6H4 4-PyCH2CH20 Me 4-MeMlS02C6H4 -NH- 4-FC6H4NH 2-FC6H4 Pyrr (B) Me 4- Py-NH-4-FC6H4NH 4-FC6H4 1-Pyra Me 4-Py -NH- 4-FC6H4NH 4-FC6H4 1-Imid Me 4-Py-NH- 4-FC6H4NH 4-FC6H4 Pyra (A) Me 4-Py -Legs- 4-FC6H4NH 4-FC6H4 EtNH (B) Me 4-Py '-NH-4-FC6H4NH 4-FC6H4 PhCH2CH2NH (A) Me 4-Py -NH-4-FC6H4NH 4-FC6H4 4-PyCH (0H) CH2NH Me 4-Py -NH- 4-FC6H4NH 4-FC6H4 4-PyCH2NH 200524880 In Table 1, the preferred compounds are 9, 11, 13, 23, 149, 153, 157, 165, 293, 297, 299, 300, 30 1, 302, 303, 304, 305, 306, 307, 308, 309, 313, 317, 325, 329, 349, 541, 649, 6 5 3, 865, 866, 868, 895, 907, 920, 924 , 927, 93 5, 9 3 6, 943, 949, 1 089, 1090, 1106, 1127, 1161, 1197, 1217, 1224, 1230, 1231, 1232, 1233 > 1234 1237, 1238, 1322, 1323, 1324 , 1326 > 1327 1328, 1329, 1330, 1350, 1351, 1376, 1377, 1379 1380 138 1, 1382, 1383, 1503, 1526, 1527, 1528, 153 1 1532 \ 1533 '1 534 or 1 535 compounds, A further preferred compound is 1 1, 1 3, 23, 149, 153, 157, 165 293, 297, 301, 302, 303, 305, 309 > 313, 3 1 7, 329 349, 541, 653, 865, 866, 868, 936, 936, 1089, 1090 > 1106, 1127, 1161, 1197, 1217, 1224, 1230, 123 1 1232% 1233, 1234, 1237, 1238, 1322, 1323, 1324 1326 132 7, 1, 1328, 1329, 1330, 1350, 1351, 1329 1376, 1377 Λ 1379, 1380, 1381, 1382, 1383, 1503, 1526 1527 1528, 1531, 1532, 1533, 1534 or 1535, more preferably compounds 11, 13, 149, 153, 157, 165, 293, 297, 301, 302, 303, 305, 309, 313, 317, 329, 349, 653, 868, 936, 1089, 1090, 1106, 1127, 116 1, 1197, 12 17, 1 224, 1230, 123 1, 1232, 1233, 1 234, 1 23 7, 1, 2 3 8, 1, 3 22, 1323, 13 24, 1330, 1350, 135 1, 1 37 6, 1377, 1383, 1 526, 1 5 27 > 1 5 Compound No. 2 8 or 1 5 3 5 and -108- 200524880 particularly preferred compound N4- [2- (3,4-dimethoxyphenyl) -ethyl] -N2-phenyl-6- [N ^ (pyridin-4-yl-ethylene) -hydrazinopyrimidine-2 , 4-diamine (Compound No. 11), 5-phenyl-2-anilino- 4- [N '-(1-pyridin-4-yl-ethylene) -hydrazino] -pyrimidine (Compound No. 1 3), [4- {1 ^ '-[1- (4-Methanesulfonylphenyl) -ethylidene] -hydrazino 丨 -6- (4-pyridin-4-yl-pyrazol-1-yl ) -Pyrimidin-2-yl] -aniline (Compound No. 149), 6-methanesulfonylphenyl) -Ethylenesulfonyl N2-phenyl-N4- (2-pyridine-cardiyl-ethyl) -pyrimidine -2,4-diamine (compound number I53), # (4- {N '-[1- (4-methylsulfonylphenyl) -ethylene] -hydrazinob 5-phenylpyrimidin-2 -Yl) -aniline (Compound No. 157), [4- {N '[l- (4-Methanesulfonylphenyl) -ethylenehydrazinophenyl 5-phenyl-6- (2-pyridin-4-yl -Ethylamino) -pyrimidin-2-yl] -aniline (Compound No. 165), N-methyl-4- (1- {[2-phenylamino-6- (4-pyridin-4-yl-pyrazole) -1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (compound number 293), N-methyl-4- (1-{[2-phenylamino-6- (2 -Pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl)- Benzsulfonamide (compound number 297), ^ N-methyl-4- {l- [5-phenyl-2-anilinepyrimidin-4-yl] -hydrazinylethylethylbenzsulfonamide (compound number 3 0 1), N -methyl- 4- {1-[(5-phenyl-2-anilino-6-fluorenyl than D--1-yl-ranst-4-yl) -fluorenylene] • Ethyllbenzamide (Compound No. 3 0 2), 4-{1-[(6 -imidazolyl-phenyl-5 -phenyl-2 -anilinopyrimidinyl) -hydrazino] -ethylammonium N-toluenesulfonamide (compound number 3 0 3), N-methyl-4-(1-{[5-phenyl-2 -anilino-6-(4-pyridine-4 -yl-pyrazole- 1-yl-109- 200524880) -pyrimidin-4-yl; l · hydrazinylethyl) -benzenesulfonamide (compound number 305) N -methyl- 4- (l-{[5 -phenyl-2 -Anilino-6- (2-pyridin-4-yl-ethylamino) -uridine-4-yl; I-amidinophenylethyl) -benzenesulfonamide (compound number 309), N- Methyl-4- {l-[(2-anilino-5-thien-3-yl-pyrimidin-4-yl) -hydrazino] -ethylbenzsulfenimide (compound number 313), N- Methyl-4- (1-{[2-anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-thien-3-yl-pyrimidin-4-yl] -sub Hydrazine ethyl Amine (compound number 3 17), N-methyl-4- (1- {[2-anilino-6- (4-pyridin-4-yl-pyrazole_boxy) -5-o-tolylpyrimidine -4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 329), N-methyl-4- (1-{[5-phenyl-2- (pyridin-3-ylamino) -Pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 349), 4- (1- {[5- (2-fluorophenyl) -2-anilino-6- (4 -Pyridin-4-yl-pyrazole-pyridyl) -1¾, fluorenyl-4-yl] -pyridinyl} -ethyl) -N-methylbenzyl 5-methylbenzene (compound number 653) 'phenyl- [4- [N,-(1-pyridin-4-yl-ethylene) -hydrazino] -6- (3-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-2-yl Amine (Compound No. 86 8), 4- (1- {[5- (4-fluoro-phenyl) -2-aniline-6- (2-pyridin-4-yl-ethylamino) -pyrimidinyl] -Amidinoylethyl) -N-methyl-benzenesulfonamide (Compound No. 1 089), 5- (4-fluoro-phenyl) -6- {N '-[1- (4-methylsulfonyl -Phenyl) _ethylene] -hydrazinob N 2 -phenyl-N 4-(2 -pyridine-4 -yl-ethyl) -pyrimidine-2,4-diamine (Compound No.-110- 200524880 (Code 1090), 4-(1-((5 -Thyl-2 -anilino-6-(2- Pyridoxine-4 -yl-ethylamino) -methylpyridine_ 4 -yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (compound number 1 1 0 6), 1- ( 3,4-dimethoxy-phenyl) -2- (2-anilino-6- {N,-[l-pyridin-4-yl-ethylidene] -hydrazinopyrimidine-cardiylamino ) _Ethanol (Compound No. 1127), 4- (1- {[6- (2-hydroxy-2-pyridin-4-yl-ethylamino) -5-phenyl-2-anilino-pyrimidine-4- Phenyl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1161), 4-(1-{[6-(2 -Ethyl-2 -pyridine-4 -yl- Ethylamino) -2 -anilino-pyrimidin-4 -ylhydrazino} -ethyl) -N-methyl-benzenesulfonamide (Compound No. 1197), N-methyl-4- [l -({5-phenyl-2-anilino-6-[(D ratio of hydrazol-4-ylmethyl) -fec group] -Hydridine-4-yl} -hydrazinyl) -ethyl] -Benzyl fluorenamine (Compound No. 1 2 1 7) \ 4- (1-{[2- (4- Fluoro-aniline) -6- (2-pyridine hydrazine-4-yl-ethylamino) -¾, fluoren-4-4ylhazidinophenylethyl) -N-methyl-benzenesulfonamide (Compound No. 1224), 4- (1-{[2- (4-fluoro-aniline) -5 -Phenyl-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylbuya Phenylethyl) -N-methyl-benzenesulfonamide (Compound No. 1 230), N2- (4-aero-phenyl) -6- {N '-[1- (4-methylamidino-phenyl) ) -Ethylene hydrazinophenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine (Compound No. 1231), [2- (2-fluoro-aniline)- 5-phenyl-6- (2-pyridin-4-yl-ethylamino) _pyrimidine 1: 1 amidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (compound number 1232), -111-200524880 N_methyl_4- (l- {[5-phenyl-2-aniline-6- (3-pyridin-4-yl-propylamino) -pyrimidine-4- Phenyl] -hydrazinyl 丨 -ethyl) -benzylamine (Compound No. 1 2 3 3), N-methyl- 4- (1-{[2-aniline-6- (3-pyridine-4 -Yl-pyrrole-1-yl) -pyrimidin-4-yl] -hydrazinobiethyl) _benzenesulfonamide (compound number 1 234), N-methyl-4- (bu {[5-phenyl- 2-anilino-6- (3-pyridin-4-yl-pyrrole-butyl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (compound number 1237), or N-methyl -4- (1-{[5-phenyl-2-anilino-6- (2-pyridin-4-yl-ethoxy) -pyrimidin-4-ylpyrazinobethyl) -benzenesulfonamide (Compound No. 1 238), The preferred compounds are as follows: 1 ^ 4- [2- (3,4-dimethoxyphenyl) -ethyl]-> ^ 2-phenyl-6-[> ^ (oxpyridin-4-yl- Ethylene) -hydrazinol · pyrimidine-2,4 ** diamine (Compound No. 1 1), 5-phenyl-2-anilino-n--4-yl-ethylene) -fluorenyl]- Pyridine (Compound No. 1 3), 6- to,-[1- (4-methanesulfonylphenyl) -ethylenehydrazine, -phenyl'4- (2-1) -Yl-ethyl) -pyrimidine-2,4-diamine (compound number 1 5 3), (4- 丨) ^,-[1- (4-methanesulfonylphenyl) -ethylenehydrazine 5-Phenylpyrimidin-2-yl) -aniline (compound number 157), 1methyl-4- (1-{[2-phenylamino-6- (4-pyridin-4-yl-pyrazol- Pyridyl) -pyrimidin-4-ylpyridazinylethyl) _benzenesulfonamide (Compound No. 293), N-methyl-4- (l-{[2-phenylamino-6- (2-P ratio D-Ade-4-yl-ethenyl) -Yu-A-4-ylhydrazinylethyl) _benzenesulfonamide (compound number 297), N_methyl_4- {1- [5-phenyl -2-Anilinopyrimidin-4-yl] -hydrazinylethylethylbenzamine (Compound No. 3 01), -112- 200524880 N-methyl-4- {1-[(5-phenyl-2 -Anilino-6-pyrazol-1-yl-pyrimidine -4-yl) -hydrazinyl l-ethylsulfenylsulfonamide (Compound No. 3002), 4-{1-[(6 -imidazol-1 -yl-5-phenyl-2 -aniline pyrimidine -4 -yl) -hydrazinyl] -ethyl N-toluenesulfonamide (compound No. 303;), N-methyl_4- (1- {[5-phenyl-2-aniline -6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) _benzenesulfonamide (Compound No. 305) N-methyl-4 ( 1- {[5-phenyl-2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (compound number 309), N -methyl-4-(1-{[2 -anilino-6-(4-pyridine-4 -yl-pyrazole-1 -yl) -5 -thiophene-3 -yl-ran Hydrazine-4 -yl] -hydrazinyl} -ethyl) -benzenesulfonic acid amine (compound number 3 17), N-methyl-4-(1-{[2 -anilino-6-(4- Pyridine-4 -yl-pyrazol-butyl) -5 -o-tolylpyrimidine-4 -yl] -hydrazinylethyl) -benzenesulfonamide (compound number 329), N_methyl-4 -(1-{[5-phenyl-2-(pyridin-3-ylamino) -pyrimidin-4 -yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 349), 4-(1 -{[5-(2 -Fluorophenyl) -2 -anilino-6-(4-pyridine_4_yl-pyridine-1 -yl) _pyrimidin-4 -yl] -hydrazinylethyl) -N -Tosylsulfonamide (Compound No. 6 5 3) 'phenyl- [4-[N,-(1 -pyridin-4 -yl-ethylene) -hydrazino 6-(3 -pyridine-4 -yl- Orbizol-1 -yl) -pyrimidin-2 -ylpyramine (Compound No. 8 6 8), 4-(]-{[5-(4-fluoro-phenyl) -2 -anilino-6 -(2 -pyridinium-4-yl-ethylamino) -pyridin-4-yl] -hydrazinyl} -ethyl) -N-methyl-benzylidene (Compound No.-113-200524880 1089), 4- (1-{[6- (2-Hydroxy-2-pyridin-4-yl-ethylamino) -5-phenyl-2-anilino-pyrimidin-4-ylpyrazidinoethyl ) -N-methyl-benzenesulfonamide (compound number 1161), 4- (1- {[6- (2-hydroxy-2-pyridin-4-yl-ethylamino) -2-anilino-pyrimidine -4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1197), N-methyl-4- [l-({5-phenyl-2-phenylamino-6 -[(Pyridin-4-ylmethyl) -amino] -pyrimidin-4-ylpyridinyl) -ethyl] -benzenesulfonamide (Compound No. 1217), 4- (1-{[2- (4-fluoro-aniline) -6- (2-pyridin-4-yl-ethyl Group) -pyrimidin-4-yl l · hydrazinyl ethyl) -N-methyl-benzenesulfonamide (Compound No. 1 224), 4- (1-{[2- (4-fluoro-aniline)- 5-phenyl-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylhydrazinoylethyl) -N-methyl-benzenesulfonamide (Compound No. 1230), 4- (1- {[2- (2-fluoro-anilino) -5-phenyl-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl)- N-methyl-benzenesulfonamide (Compound No. 1232), N-methyl-4- (1- {[5-phenyl-2-aniline-6- (3-pyridin-4-yl-propylamino) ) -Pyrimidin-4-ylbuazidinylethyl) -benzenesulfonamide (Compound No. 1 23 3), N-methyl-4- (1-{[5-phenyl-2-phenylamino-6- (3-pyridin-4-yl-pyrrole-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 1237), or N-methyl-4- (1- {[5-phenyl-2-aniline-6- (2-pyridin-4-yl-ethoxy) _pyrimidin_4_yl] -amidinophenylethyl) -benzenesulfonamide (Compound No. 1 23 8 ). -114- 200524880 The compound of formula (I) of the present invention can be produced according to the following methods A to F. Method A Method A is a method for producing a compound of formula (IAA) and a compound of formula (IAB) in which R5 is hydrogen among compounds of formula (I).

RA method R3a R3a NH, 3a __ // A1 project N ^ N A2 project N person N Μ I 1 " Λ nh2 (II) R4a, A〇-r9 R5A person 〇H R4a R4a r5ajJ ( IV) (V) 11 (III) R3

N people N

CT Ί r R

3a R ° N person N

X 3a R Section A 3 Engineering 51a

HO d2a (VI)

NII

(V)

R5A, ya'X

R 3a Project A 4 R1a 、 N R dagger (VII) N R4a H2N ^ 2a

Ί r R R 3a R3 N person N Section A 5 Project > N ^ A6Xfg ^ N ^ 5A / j \ ^^ x H2N-NH2 meaning R5A ^^^ j ^ N, 『R;

R (V) 4a 4a FT (VIII) R2a R1a (IX) (IAb)

Y In the present invention, the definitions of R1, R2, R3, and R4 are as described above, and Rla, R2a, R3a, and R4a are R1, R2, R3, and R4. The substituent in the group includes an amine group, a hydroxyl group -115-200524880 and / or a carboxyl group. Protected amine, hydroxyl and / or carboxyl groups, and the same groups as defined in the R1, R2, R3 and R4 groups, X is a halogen atom, aromatic sulfonate group or alkanesulfonate group, R5A is hydrogen, R9, R1G and R1 1 is lower alkyl. In the above, the protective groups of "protectable amine group", "protectable hydroxyl group" and "protectable carboxyl group" in the definitions of Rla, R2a, R3a and R4a are available for hydrogenolysis, hydrolysis, electrolysis, and photolysis The protective group cleaved by isochemical methods may be a protective group generally used in organic synthetic chemistry (for example, see TW Greene 'Protective Groups in Organic Synthesis, 3rd Edition, John Wiley & Sons, Inc. (1999)). In the above, the "protecting group" of the "protectable hydroxyl group" in the definition of Rla, R2a, R3a and R4a is a hydroxyl protecting group used in organic synthetic chemistry, and is not particularly limited. For example, "a general protecting group for a hydroxyl ester", it is preferable Formyl, ethyl, propyl, propyl, butyl, isobutyl, pentyl, pentyl, pentyl, isopentyl, octyl, nonyl, decyl, 3-methyl Nonyl, 8-methylnonyl, 3-ethyloctyl, 3, 7-dimethyloctyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl Hexadecyl, 1-methylpentadecanyl, 14-methylpentadecanyl, 13, 13-dimethyltetradecanyl, heptadecanyl, 15-methylhexadecyl , Octadecyl, 1-methylheptadecyl, nonadecyl, eicosyl, icosyl, and other alkyl groups, chloroethenyl, dichloroethenyl, trichloroethenyl Haloalkylcarbonyl groups such as trifluoroethenyl, trifluoroethenyl, and alkoxycarbonyl such as methoxyethenyl, propenyl, propynyl, methacryl, butenyl, isobutenyl, (E) 2-methyl-2-butenyl "Substituted low-aliphatic fluorenyl groups" (such as C 2 to 6 low-aliphatic fluorenyl groups) and alkylcarbonyl groups; benzyl fluorenyl, α-naphthyl fluorenyl-116- 200524880, / 3-naphthyl, etc. Haloaryl groups such as arylcarbonyl, 2-bromobenzyl, and 4-chlorobenzyl, low-alkarylcarbonyls such as 2,4 '6-trimethylbenzyl, and tolyl, and 4-methoxymethyl Nitroaryl groups such as alkoxyarylcarbonyl, 4-nitrobenzylfluorenyl, 2-nitrobenzylfluorenyl, lower alkoxycarbonylated arylcarbonyl groups such as 2- (methoxycarbonyl) benzylfluorenyl, 4-phenylbenzylfluorenyl, etc. "Substituted aromatic fluorenyl groups" such as arylated arylcarbonyl: methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, second butoxycarbonyl, third butoxycarbonyl, isobutoxycarbonyl and other lower alkanes Halogens such as oxycarbonyl, 2,2,2_trichloroethoxymine group '2 -dimethylacetonyl ethoxyfluorenyl, or "alkoxycarbonyl" such as low alkoxycarbonyl substituted with trioxosulfuryl; tetrahydro Pyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, 4-methoxytetrahydropyran "Tetrahydropyranyl or tetrahydrothiopyranyl" such as ran-4-yl; tetrahydrofuran-2-yl, "Tetrahydrofuranyl or tetrahydrothiofuranyl" such as hydrothiofuran-2-yl; trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, tertiary butyldimethylsilyl, methyldiiso Trisalyl silane, methyltriterosuccinyl, triisopropylsilyl, triphenylsilyl, dibenzosilyl, diphenylbutylsilyl, diphenylisopropylsilyl, benzenediisopropyl Silanes, such as silanes, such as tri-lower silanes substituted with 1 to 2 aryl groups; methoxymethyl, 1,2-dimethyl-1-methoxymethyl, ethoxymethyl, and propoxymethyl Low alkoxymethyl such as isopropyloxymethyl, butoxymethyl, third butoxymethyl, low alkoxylated low alkoxymethyl such as 2-methoxyethoxymethyl, 2,2,2 -tri Chloroethoxymethyl, bis (2-chloroethoxy) methyl and other halogenated alkoxymethyl and other "homooxymethyl"; 1-ethoxyethyl, 1- (isopropoxy) ethyl and other low "Substituted ethyl" such as halogenated ethyl such as alkoxyethyl, 2,2,2-trichloroethyl, etc .; Thyl, α-naphthylmethyl, / 3-naphthylmethyl, diphenylmethyl, triphenylmethyl 1 to 3 aryl groups, such as naphthyl, naphthylbenzyl, 9-allyl-117- 200524880, etc. Alkyl group, a methylbenzyl 4_. ". One m _ τ Bu Chui, 2, 4, 6

Base, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxybenzyl, 2-nitrosyl, 4-nitro, 4-chlorofluorene, 4-bromofluorenyl, Substituents such as low alkyl groups, low alkoxy groups, low alkoxy groups, nitro groups, halogens, cyano groups, etc. 4 to aryl groups, etc. 丨 ~ 3 aryl groups to replace "aralkyl groups" such as lower alkyl groups; "Oxygen group" such as propoxy group; benzyl group, methoxybenzyl group, 34_dimethoxybenzyloxycarbonyl group, 2-nitrobenzyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, etc. 1 ~ 2 An aromatic ring such as a low-oxyl group or a nitro group may have a substituted "aralkoxycarbonyl group", which is preferably a low-aliphatic fluorenyl group, an aralkyl group, or a silane group. In the above, Rla, R2a, R3a and R4a are defined as "protective groups of carboxyl groups that can be protected" are carboxyl protective groups used in organic synthetic chemistry, and are not particularly limited. The above `` low alkyl ''

; Vinyl, polypropylene, 2-propenyl, 1-methpropenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl , 2-ethyl-2-propenyl, 丨 -butenyl, 2-butenyl, methyl-2-butenyl, ^ methyl-1-butenyl, 3-methyl-2-butene Ethyl, ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1 ~ Pentyl, 2-pentyl, 1-methyl-2-pentyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, cardiac pentenyl; 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, Lower alkenyl groups such as 3-hexenyl, 4-hexenyl, 5-hexenyl; ethynyl, 2-propynyl, i-methyl-2-propynyl, 2-methyl-2-propene Alkynyl, 2-ethyl-2-propynyl, 2-butynyl, 1-methyl-2 -butynyl, 2-methyl-2 -butynyl, 1-ethyl-2-but Alkynyl, 3-butynyl, 1-methyl-3-butynyl, 2-methyl-118- 200524880 group-3-butynyl, 1-ethyl-3-butynyl, 2-pentyne , 1-methyl-2-pentynyl, 2-methyl-2-pentynyl, 3-pentynyl, p-methyl-3-pentynyl, 2-methyl-3-pentynyl, 4-pentynyl, p-methyl-4-pentynyl, 2-methyl-4-pentynyl, Lower alkynyl groups such as 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl; the above-mentioned "halo-lower alkyl"; 2-hydroxyethyl, 2,3-dihydroxypropyl "Low-alkyl" such as hydroxy, 3-hydroxypropyl, 3,4-dihydroxybutyl, 4-hydroxybutyl, etc .; "low-aliphatic fluorenyl" such as acetomethyl;-"low-alkyl"; "Aralkyl": The aforementioned "silyl" is preferably a lower alkyl or aralkyl. In the above, the "protecting group" of the "protectable amine group" in the definitions of Rla, R2a, R3a and R4a is an amine group protecting group used in organic synthetic chemistry, and is not limited. For example, the above "General protection of hydroxy esters" "Aliphatic", "aromatic", "alkoxy", "alkoxycarbonyl", "aralkyloxycarbonyl", "silyl", or "aralkyl" group or N, N-dimethylamine methylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, thionylene, 5-chlorosulfinyl, diphenylmethylene, (5- Chlorohydroxyphenyl) phenylmethylene and other "substituted methylene groups that form Schiff's base" are preferably aliphatic, fragrant, or oxygen-based, most preferably oxygen-based . Lu A1 Project This project is a manufacturing process of a compound of formula (IV). A compound of formula (II) is reacted with a compound of formula (III) in an inert solvent in the presence of a base. The solvent used in this project is non-obstructive to the reaction, and there is no particular limitation on the solubility of starting materials to a certain extent, such as formamidine, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2_pyrrolidone, N_methylpyrrolidone, hexa-119-200524880 methylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethyl Ethers such as oxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, Alcohols such as cyclohexanol and 2-methoxyethanol; sub-maple such as dimethylarsine and cyclobutane; or halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chlorobenzene, preferably alcohols Type, and preferably ethanol. The base used in this project, such as alkali metal alkoxides, alkali metal carbonates or organic bases, is preferably an alkali metal alkoxide, and is also preferably sodium ethoxide or potassium third butoxide. The reaction temperature in this project may vary depending on the raw material compounds, the inert solvents used, etc., and is usually from room temperature to 120 ° C (preferably 80 ° c to 110 ° C). The reaction time in this project varies depending on the raw material compound, the inert solvent used, the reaction temperature, etc., and is usually 1 hour to 7 days (preferably 24 hours to 3 days). Project A2 This project is a manufacturing process of compounds of formula (V). (I) When X is halogen, in the presence or absence of an inert solvent (preferably in the presence of I ethers, aromatic hydrocarbons or halogenated hydrocarbons). ), Let the compound of formula (IV) and a halogenating agent (preferably phosphorus oxyhalides such as phosphorus oxychloride, phosphorus oxybromide, and phosphorus iodide, most preferably phosphorus oxychloride), at 20 ° C ~ 120 ° The reaction is performed at C (preferably 80 ° C to 100 ° C) for 30 minutes to 24 hours (preferably 4 hours to 8 hours), and the hydroxyl group and the halogen in the compound of the formula (IV) are changed. (ii) When X is an aromatic sulfonate or alkane sulfonate, in the presence or absence of an inert solvent (preferably in the presence of a halogenated hydrocarbon), make the compound of formula (IV) -120-200524880 and sulfonylated Agent (preferably tosylsulfonium chloride, 2,4,6-trimethylsulfonylsulfonium chloride, 2,4,6-tricumylsulfonylsulfonium chloride, methanesulfonyl chloride, trifluoromethanesulfonyl chloride and other sulfonyl chloride) 2. The most suitable is 2,4,6-tricumylsulfonylsulfonium chloride), and react at 0 ° C ~ 80 ° C (preferably room temperature ~ 40 ° C) for 30 minutes to 24 hours (preferably 4 hours to 8) Hours), and the hydroxyl group in the compound of the formula (IV) is converted with an aromatic sulfonate group or an alkanesulfonate group. Brother A 3 project This project is a manufacturing process of a compound of formula (IAA) where A is an oxygen atom in a compound of formula (I). In an inert solvent in the presence of a base, the compound of formula (V) and the compound of formula (VI) After the reaction, the desired amine, hydroxyl, and / or carboxyl protecting groups in Rla, R2a, R3a, and Rh are removed to proceed. The inert solvent used in this project is not specific as long as it does not affect the reaction and can dissolve the raw materials, such as formamidine, N, N-dimethyl.methylformamide, N, N-dimethylacetamide, N -Methyl-2-pyrrolidone, N-methylpyrididone, hexamethylphosphonium triamine, and other amines; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, Ethers such as diethylene glycol dimethyl ether; or halogenated hydrocarbons such as dichloromethane, i '2-dichloroethane, and chlorobenzene, preferably amines or ethers (most preferably N, N-dimethyl Methylformamide or N, N-dimethylacetamide). The tests used in this project are for example metal carbonates such as sodium carbonate, potassium carbonate, and lithium carbonate; alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate, and lithium bicarbonate; lithium hydride, sodium hydride, and hydrogenated Alkali metal hydrides such as potassium; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, palladium hydroxide, and lithium hydroxide; inorganic alkalis such as alkali metal fluorides such as sodium fluoride and potassium fluoride; Alkali metal alkoxides such as sodium oxide, sodium ethoxide, potassium methoxide, potassium ethoxide, tert-butane-121-200524880 Oxygen and lithium methoxide; alkane sulfide bases such as sodium methionine and sodium ethionate Metals; N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, methylpiperidine, pyridine, cardiac pyrrolidine and pyridine, picolin, 4- (N, N-dimethylamino) pyridine, 2,6-bis (third butyl) -4-formamidine ratio Dine, quinoline, n, N-dimethylaniline, N, N -Diethylaniline, 1,5-diazinebicyclo [4 · 3 · 0] non-5-ene (DBN), 1,4-diazinebicyclo [2.2.2] octane (DABCO), 1,8- Diazine bicyclo [5.4.0] -7- ~ f ——Carnes (DBU) and other organic amines, or organic metal bases such as butyllithium, lithium diisopropylamidide, lithium bis (trimethylsilyl) amine, and preferably alkali metal hydroxides or alkali alkoxides ( Most preferred is sodium hydroxide). The reaction temperature in this project varies depending on the raw material compound, the inert solvent used, the type of base, etc., and is usually 0 ° C ~ 110 ° C (preferably 60 ° C ~ 100t). The reaction time in this project may depend on the raw material compound and the used The inert solvent, the type of the base, the reaction temperature, etc. vary, but it is usually 30 minutes to 48 hours (preferably 15 hours to 24 hours). The removal of amine, hydroxyl, and / or carboxyl protective groups in this project varies depending on the type of _, and can be used according to the methods commonly used in organic synthetic chemistry, such as TW Green, (Protective Groups in Organic Synthesis), John Wiley & Sons : JFWMcOmis, (Protective Groups in 〇rganic C hemistry), P1 enu ni P i · ess record method to implement. Project A4 This project is a process for the production of compounds of formula (I B) in the compound of formula (I), where A is a -NH- group, in the presence or absence of an inert solvent (preferably in the presence of -122-200524880) After the compound of the formula (V) and the compound of the formula (VII) are reacted, the desired Ria, R2a, R3a, and R4a amino groups, hydroxyl groups, and / or carboxyl protecting groups are removed. The inert solvent used in this process is not specific as long as it does not affect the reaction, and it can dissolve the raw materials, such as those used in the above method A3A process. The reaction temperature in this project may vary depending on the raw material compound and the inert solvent used. Usually, it is 0 ° C ~ 150 ° C (preferably 6 (TC ~ 100 ° C). The reaction time in this project may depend on the raw material compound and use. The inert solvent, reaction temperature, etc. vary, usually 30 minutes to 48 hours (preferably 24 hours to 45 hours). The removal of the amine group, hydroxyl group and / or carboxyl protecting group in this project can be carried out according to the above method A, A3 project Let the desired method for removing the amine, hydroxyl and / or carboxyl protecting groups of Rla, R2a, R3a and R4a be implemented. A5th project This project is a manufacturing process of a compound of formula (V III), in the presence or absence of an inert solvent (It should be in the absence), the compound of formula (V) is reacted with hydrazine monohydrate or anhydrous hydrazine to carry out. The solvent used in this project is not to hinder the reaction, and there is no particular limitation on the solubility of starting materials to a certain degree, such as Formamides such as formamidine, N, N-dimethylformamide, N, N-dimethylacetamide; ether, diisopropyl ether, tetrahydrofuran, dioxin, dimethoxyethane, diamine Ethers such as ethylene glycol dimethyl ether; dichloromethane, 1 '2-dichloroethane, chlorine And other halogenated hydrocarbons; aromatic hydrocarbons such as benzene, toluene, xylene; or methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary -123- 200524880 butanol, isoamyl alcohol, ethanol and other alcohols Type, the reaction should be different in this project, usually the reaction temperature and other hours in the room project). Brother A 6 project This project is formula (Compound manufacturing compound and formula (IX: R3a and R4a amine group, the raw materials used in this project are not specific, such as acetylacetamide and other scorch, dimethoxyethane 2 ~ Dichloroethane, chlorine fume; methanol, ethanol; dimethylarsinol, ethyl acetate, or a mixed solvent of the above solvents (the most solvent). In this project, diethylene glycol, glycerin, octyl Alcohols, cyclohexanol, and 2-methoxy are alcohols (most preferably ethanol). The temperature depends on the raw material compound and the inert solvent used. Isotherm ~ 120 ° C (preferably 50 ° C ~ 1 10 ° C). Time depends on the raw material. The compound, the inert solvent used, is usually 30 minutes to 24 hours (preferably 1 hour to 3 I). Among the compounds, A is the formula (NHB) -based formula (IAB). In the presence of the inert solvent, let After the reaction of the compound of the formula (V III), the Rla, R2a, hydroxyl and / or carboxyl protecting groups can be removed as needed. The inert solvent used can dissolve, for example, formamidine, N, N as long as it does not affect the reaction. -Dimethylformamide, N, N-diamines; diethyl ether, diisopropyl ether, tetrahydrofuran, difluorene, diamine Ethers such as glycol dimethyl ether; halogenated hydrocarbons such as dichloromethane, benzene; aromatic alcohols such as benzene, toluene, xylene, n-propanol, isopropanol, diethylene glycol, glycerol, etc. Rhenium and other fluorene; nitriles such as acetonitrile; ester mixed solvents such as propyl formate, butyl acetate, diethyl carbonate, etc., preferably ethers, alcohols, or ethers and alcohols are dioxane, The mixing temperature of ethanol or dioxane and ethanol may vary depending on the raw material compound, the inert solvent used -124 '200524880, usually room temperature ~ 120t: (preferably 90 ° C ~ 100 ° C). The reaction time in this project is visible The raw material compound, the inert solvent used, the reaction temperature, etc. vary, usually 1 hour to 24 hours (preferably 15 hours to 22 hours). The removal of the amine group, hydroxyl group and / or carboxyl protecting group in this project can be based on the above In the A3 project of Method A, the method for removing the desired amine, hydroxyl, and / or carboxyl protecting groups of Rla, R2a, R3a, and R4a is implemented. After the reaction of each project in the above method A is completed, each target compound can be used in Prepared by a reaction mixture. For example, the reaction mixture is appropriately neutralized After filtering off when there are insoluble matters, add an immiscible organic solvent such as water and ethyl acetate to separate the organic layer containing the target compound, wash with water, etc., and then use anhydrous magnesium sulfate, anhydrous sodium sulfate, and anhydrous hydrogen carbonate. After drying the sodium, etc., it is obtained by distilling off the solvent. If necessary, the obtained target compound can be appropriately combined by conventional methods, such as recrystallization, re-sinking, and other organic compounds. The conventional methods are appropriately combined, and chromatography is used to dissolve and purify with an appropriate eluent. Method B Method B is a compound of formula (IBA) where r5 is a halogen atom and a method for producing a compound of formula (IB B) among compounds of formula (I). -125- 200524880 Method B

(X) (VII) _)

In the present invention, R1, R2, R3, R4, Rla, R2a, R3a & R4a are as defined above, and R5B is a halogen atom. Project B 1 This project is a manufacturing process of a compound of formula (IB A) in the compound of formula (0, A is an oxygen atom). In an inert solvent, in the presence of a base, the compound of formula (X) and the compound of formula (VI) After the reaction, the desired amine, hydroxyl, and / or carboxyl protecting groups in Rla, R2a, R3a, and R4a are removed to carry out, and this project can be carried out according to the method of the above method A3 project A. B2 project This project is of formula (I) In the production process of the compound of formula (1BB) in which 'A is a -NH- group in the compound, in the presence or absence of an inert solvent (preferably -126-200524880), let the compound of formula (X) and After the compound of formula (V II) is reacted, the desired amine, hydroxyl and / or carboxyl protecting groups in Rla, R2a, R3a and R4a are removed, and this process can be carried out according to the method of the above-mentioned A method A4 project. Section B 3 Project This project is a manufacturing process for a compound of formula (XI). The compound of formula (X) is reacted with hydrazine monohydrate or anhydrous hydrazine in the presence or absence of an inert solvent (preferably in the absence of it). The project can be carried out in accordance with the method of the above-mentioned A5 project A. _ Project B4 This project is a manufacturing process of a compound of formula (IBB) of formula (I), A is a compound of formula -NH-. After reacting a compound of formula (XI) with a compound of formula (IX) in the presence of an inert solvent, Let the desired amine, hydroxyl and / or carboxyl protective groups be removed in Rla, R2a, R3a and R4a, and this project can be carried out according to the method of the above method A and A6. After the reactions in the above methods B are completed, each The target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when insoluble matter is filtered off, an immiscible organic solvent such as water and ethyl acetate is added to separate the target compound containing the target compound. The organic layer is washed with water, dried over anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., and then obtained by distilling off the solvent. The obtained target compound is obtained by ordinary methods such as recrystallization, reprecipitation, etc., if necessary. The conventional methods for compound isolation and purification are appropriately combined, and applied with chromatography to dissociate and refine with an appropriate eluent. Method C-127- 200524880 Method C is the compound of formula (I), and R5 is the nitrogen atom bound to the pyrimidine ring. Production of compounds of the formula (ICA) and compounds of the formula (IC B) of heterocyclic groups substituted with 1 to 3 groups of the substituted group b of a nitrogen atom in a pyrimidine ring, -NR7R8 group or -OR7 group Method C Method R3a R3a N Human II I Project C 1 N ^ NJ 1 R5Ca—Η R4a (XXXXXV) R4a (χΠ) (XIII)

R3a

Project C 2 Project R1a HO \ p, N R2a (VI) Project C 3 Project R1a H2N, N ^ UR2a (VII) (XIII) R3a Project C4, R3a N 乂 II I Project C 5 Project R3 N 乂 " N Β50βΑΑχ H2N —NH2 R5Ca. R4a Λ ^ ν, η2 k η 0 r5C- R2a Human Rla R4 (XIII) (XIV) (IX) (ICb) In the present invention, 'R1, R2, R3, R4, Rla, R2a, R3i 1, R4a, and X are as defined above. R5e is a heterocyclic group having a pyrimidine ring bound to a nitrogen atom, a heterocyclic group substituted with 1 to 3 groups of a substituted group b of a pyrimidine ring bound to a nitrogen atom, -nW group, or- OR7 group, R5Ca is R5C group. Substituents include amine group, hydroxy group and / 200524880 or carboxyl group, amine group that can be protected, hydroxy group and / or carboxyl group, and the same group as defined in R5C group. Process C1 This process is a process for manufacturing a compound of formula (X III). The compound of formula (X II) is reacted with a compound of formula (X X X X X V) in an inert solvent. The solvent used in this project is non-obstructive to the reaction, and it is not limited to be able to dissolve the starting materials to a certain extent, such as formamidine, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2 -pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine, and other amines; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, Ethers such as diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, third butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, Alcohols such as 2-methoxyethanol; or halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chlorobenzene, preferably alcohols and ethanol. The reaction temperature in this project may vary depending on the raw material compounds, the inert solvents used, etc., and is usually room temperature to 100 ° C (preferably 40 ° C to 80 ° C). The reaction time in this project varies depending on the raw material compound, the inert solvent used, the reaction temperature, etc., and is usually 15 minutes to 24 hours (preferably 1 hour to 6 hours). This project can use alkali when necessary. At this time, the following manufacturing method conditions should be used. The solvent used in this project is non-obstructive to the reaction, and it is not limited to be able to dissolve the starting materials to a certain extent, such as formamidine, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidone, hexa-129- 200524880 methylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethyl Ethers such as oxyethane and diethylene glycol dimethyl ether; fluorenes such as dimethyl sulfene and cyclamidine; or halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chlorobenzene. It is amidamines or ethers, and also N, N-dimethylformamide or N, N-dimethylacetamide. The bases used in this project are, for example, alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides, third potassium butoxide, or organic bases, preferably alkali metal hydrides and also hydrogenated Sodium or potassium hydride. The reaction temperature in this project may vary depending on the raw material compound, the inert solvent used, etc., and is usually 0 ° C ~ 100 ° C (preferably room temperature ~ 80 ° C). The reaction time in this project varies depending on the raw material compound, the inert solvent used, the reaction temperature, etc., and is usually 1 hour to 48 hours (preferably 6 hours to 24 hours). Project C2 This project is a manufacturing process of compounds of formula (I A) in which the compound of formula (I) is A, and oxygen is an oxygen atom. In an inert solvent, in the presence of a base, compounds of formula (X III) and compounds of formula (VI) After the reaction, the desired amine, hydroxyl, and / or carboxyl protecting groups in Rla, R2a, R3a, R4a, and R5eA are removed to carry out. This process can be carried out according to the method of the A3 process of the above method A. Project C3 This project is a manufacturing process of a compound of formula (ICB) where A is a compound of formula (I). In the presence or absence of an inert solvent (preferably in the presence of), let formula (X III) The reaction of the compound with the compound of formula (V II) 200524880 or the removal of the carboxy protecting group is carried out. This project can be carried out in accordance with the method of the above-mentioned A method A4 project. Project C4 This project is a manufacturing process of a compound of formula (XIV). In the presence or absence of an inert solvent (preferably in the absence of), the compound of formula (X III) is reacted with hydrazine 1 hydrate or anhydrous hydrazine to Carry out, this project can be carried out according to the method of the above table A5 of the A method. Project C5 This project is a manufacturing process of a compound of formula (ICB) in which the compound of formula (I) is A, and A is a formula -NH-. After the compound of formula (XIV) is reacted with the compound of formula (IX) in the presence of an inert solvent Let the desired Rla, R2a, R3a, 114 & and R5eA be removed to remove the amine, hydroxyl and / or carboxyl protecting groups. This project can be carried out according to the method of the A6 project of the above method A. After the reaction of each process in the above method C is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when there is insoluble matter, it is filtered off, and an organic solvent containing water and ethyl acetate is added to separate the organic layer containing the target compound, and the organic layer containing the target compound is washed with water and then anhydrous magnesium sulfate. After drying, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent is distilled off. The obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, if necessary, by appropriate combination, and applying a layering method to dissolve and purify it with an appropriate eluent. D method D method is that in the compound of formula (I), r 5 is a low group, a ring group, a heterocyclic group bonded to a carbon atom or a substituted group of a pyrimidine ring bonded to a carbon atom b 200524880 1-3 Compound of formula (IDA) and method for producing compound of formula (IDB) of substituted heterocyclic group. Method D

R38

R3a

(XVII) (XV) R3a IN ^ N D3 project R5DaA ^ Ax R4a R1a η〇Ά (XVII) (VI) R3a IN ^ N D4 project || I R4a (XVII) R1a h2n, 2a N R2a ( VII) (XVI)

(XVII) Project D 5-^ H2N-NH2 R5Da R3a 丄 Project D 6 R3 1 N Eight N n ^ n II I ^ H 〇 y 2a p1a R4 (XVIII) (IX) (IDb)

In the present invention, Ri, R2, R3, R4, R] a, R2a, R3a, ruler, and parent are as defined above. R5D is a lower alkyl, cycloalkyl, pyrimidine ring heterocyclic group or pyrimidine ring combined with a carbon atom. Heterocyclic group substituted with 1 ~ 3 bases s of substituted group b of carbon atom, R5Da is R5D group. Substituent includes amine group, hydroxyl group and / or carboxyl group, amine group which can be protected, hydroxyl group and / or The carboxyl group and the same group in the definition of r5D group, R12 is a lower alkyl group. -132- 200524880 Project D1 This project is a manufacturing process for compounds of formula (XVI). In an inert solvent, in the presence of a base, compounds of formula (II) It is carried out by reacting with the compound of formula (XV). The solvent used in this project is not to hinder the reaction, and there is no particular limitation on the solubility of starting materials to a certain degree, such as formamidine, Ν, Ν-dimethylformamide, N , N-dimethylacetamidine, N-methyl-2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, Dioxane, dimethoxyethane, diethylene glycol dimethyl ether and other ethers; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol , Isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, 2-methoxyethanol and other alcohols; dimethylarsine, cyclobutane and other alcohols; or dichloromethane, 1,2- Halogenated hydrocarbons such as dichloroethane and chlorobenzene are preferably alcohols and ethanol. The bases used in this project are, for example, alkali metal alkoxides, alkali metal carbonates or organic bases. Alkali metal alkoxides, and preferably sodium ethoxide or potassium third butoxide. The reaction temperature in this project may vary depending on the raw material compounds and the inert solvents used, usually room temperature ~ 120 ° C (preferably 80 ° C) ~ 110 ° C). The reaction time in this project varies depending on the raw material compound, the inert solvent used, and the reaction temperature. It is usually 1 hour to 7 days (preferably 24 hours to 3 days). The D2 project of this project is The manufacturing process of the compound of formula (XV II) can be carried out according to the method of the above-mentioned A, A 2 project. -133-200524880 D3 project This project is the compound of formula (I), where A is an oxygen atom ( IDA) compound manufacturing process, in an inert solvent in the presence of a base, the compound of formula (XV Π) and After the compound of formula (VI) is reacted, the desired, amine, hydroxyl and / or carboxyl protecting groups in R3a, R4a and R5DA are removed to carry out 'this project can be carried out in accordance with the method of the above method A A3 project. D4 project This project is a compound of formula (I), where A is a compound of formula (NHB) -based formula (IDB), in the presence or absence of an inert solvent (preferably in the presence), let the compound of formula (XV II) After reacting with the compound of formula (V II), the desired amine, hydroxyl and / or carboxyl protecting groups in Rla, R2a, R3a, R4a and R5DA are removed, and this project can be carried out in accordance with the method of the above method A4 project A4 . Project D5: This project is a manufacturing process of compounds of formula (XV III). In the presence or absence of an inert solvent (preferably in the absence of), the compound of formula (XVII) is reacted with hydrazine monohydrate or anhydrous hydrazine to Carry out, this project can be carried out in accordance with the method of the above-mentioned A5th project of method A. Project D 6 This project is a manufacturing process of a compound of formula (IDB) where A is a compound of formula (I). In the presence of an inert solvent, the compound of formula (XV III) and the compound of formula (IX) After the reaction, the desired amine, hydroxyl, and / or carboxyl protecting groups in Rla, R2a, R3a, R4a, and R5DA are removed, and this process can be performed according to the method of the a6th process of the above method A. -134- 200524880 After the reaction of each process in the above D method is completed, each target compound can be prepared from the reaction mixture according to the usual method. For example, the reaction mixture is appropriately neutralized, and when insoluble matter is filtered off, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated, washed with water, and then dried with anhydrous magnesium sulfate. 'Dried after anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent was distilled off. The obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, if necessary, by appropriate combination, and applying a layering method to dissolve and purify it with an appropriate eluent. EA method E A method is a method for producing a compound of formula (IA) and a compound of formula (IEB) in which R5 is a 1-pyrazolyl group substituted at the 4-position with any group substituted in the substituent group b. -135- 200524880 E A

EA 1 project h2n-nh2 R3a

EA3 Project

(VI)

H2N, N_R2a EA4 project

R 1a J I (VII) (XXXXVIII)

EA5 Project->. h2n—nh2

In the present invention, R1, R2, R3, R4, Rla, R2a, R3a, ruler and 乂 are as defined above, R13 is an arbitrary group selected from the substituent group b, and R13a is an R13 group -136- 200524880. The substituent includes Amine group, hydroxy group and / or carboxyl group, the same group as defined in the definition of amine group, hydroxy group and / or carboxyl group, and R13 group. EA1 project This project is a manufacturing process of compound of formula (XIX), in the presence of an inert solvent In the absence or presence (preferably in the absence of presence), the compound of formula (XII) is reacted with hydrazine monohydrate or anhydrous hydrazine. This project can be carried out in accordance with the method of the above method A5 project A. EA2 project this project It is a manufacturing process of the compound of formula (XX). The compound of formula (XIX) is reacted with the compound of formula (XXXXV III) in an inert solvent. The solvent used in this project is not to hinder the reaction and can dissolve the starting materials to a certain degree. Not limited, such as formamidine, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidone , Amines such as hexamethylphosphonium triamine; ether, diisopropyl ether, tetrahydrofuran, Ethers such as pinane, dimethoxyethane, and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol, isoamyl alcohol, diethylene glycol, Glycerol, octanol, cyclohexanol, 2-methoxyethanol and other alcohols; dimethylarsine, cyclobutadiene and other fluorenes; or halogenated hydrocarbons such as dichloromethane, 1, 2-dichloroethane, and chlorobenzene It should be alcohol or ethanol. The reaction temperature in this project may vary depending on the raw material compounds and the inert solvents used. It is usually room temperature ~ 100 ° C (preferably 6 (TC ~ 90 ° C)). The intermediate reaction time may vary depending on the inert solvent and reaction temperature of the raw material compound, and is usually 3 hours to 24 hours (preferably 5 hours to -137- 200524880 1 5 hours). The EA3 project This project is of formula (I) Among the compounds, in the manufacturing process of the compound of the formula (IEA) in which A is an oxygen atom, the compound of the formula (XX) is reacted with the compound of the formula (VI) in an inert solvent in the presence of a base, and the desired Rla, R2a, R3a, R4a and R13A can be removed by removing the amine, hydroxyl and / or carboxyl protecting groups. The EA4 project is a process for the production of compounds of formula (IB) where A is a compound of formula -NH-, in the presence or absence of an inert solvent (preferably in the presence), After the compound of formula (XX) is reacted with the compound of formula (V II), the desired amine, hydroxyl and / or residue protecting groups in Rla, R2a, R3a, R4a and R13A are removed, and the project can be carried out according to the above method A It is carried out according to the method of the A4 project. The EA5 project is a manufacturing process of a compound of formula (XXI). The compound of the formula (XX) is hydrated with hydrazone 1 in the presence or absence of an inert solvent (preferably in the absence of). It can be carried out by reaction with anhydrous or anhydrous hydrazine. This project can be carried out according to the method of the A5th project of the above method A. Project EA6 This project is a manufacturing process of a compound of formula (IEB) where A is a compound of formula (I). In the presence of an inert solvent, a compound of formula (XXI) is reacted with a compound of formula (IX). , So that the desired R 1 a, R2 a, R3 a, R 4 a and R 1 3 a removal of amine, hydroxyl and / or carboxyl protecting groups to carry out, Method. After the reaction of each process in the above EA method is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when insolubles are filtered off, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated, washed with water, etc., and then dried with anhydrous magnesium sulfate. After drying, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent is distilled off. The obtained target compound is obtained by a conventional method, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, if necessary, by appropriate combination, applying chromatography, and dissolving and purifying with an appropriate eluent. EB method EB method is a compound of formula (I) in which R5 is a compound of formula (IEB) which has a 1-pyrazolyl group substituted at the 4-position with any group selected from the substituent group b. EB method R3a

Project EB1 h2n-nh2 (XII) h2n,

〇 〇 (XXXXVIII)

(XXII)

Χ p2a p1a (IX) In the present invention, the definitions of R1, R2, R3, R, R1 3a, and X are as described above. R3 EB 3 Project

Project EB 1-139- 200524880 This project is a manufacturing process for compounds of formula (χ χ II). In the presence or absence of an inert solvent (preferably in the absence of), the compound of formula (XII) and hydrazine 1 hydrate are made. Or anhydrous hydrazine reaction, this project can be carried out in accordance with the method of the above method A5 project A. Project EB2 This project is a manufacturing process of a compound of formula (XX III). The compound of formula (XX II) is reacted with a compound of formula (χ χ χ χ V III) in an inert solvent. This project can be performed according to the EA method described above. Method EA2. Project EB3 This project is a manufacturing process of a compound of formula (IEB) where A is a compound of formula (I). In the presence of an inert solvent, let the compound of formula (χ χ ΙΠ) and the compound of formula (IX) After the reaction, the desired amine, hydroxyl, and / or carboxyl protecting groups in Rla, R2a, R3a, Chin 43 and R13a are removed and the process can be performed according to the method of the A6 process of the above method A. After the reaction of each process in the above EB method is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when insolubles are filtered off, an immiscible organic solvent such as water and ethyl acetate is added to separate the organic layer containing the target compound, and the organic layer is washed with water and the like with anhydrous sulfuric acid. After magnesium, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc. are dried, the solvent is distilled off. The obtained target compound is obtained by a conventional method, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, if necessary, by appropriate combination, applying chromatography, and dissolving and purifying with an appropriate eluent. Method F-140-200524880 Method F is that of the compound of formula (I), R5 is -NHAr1 group (Ari is an aryl group substituted with 1 to 5 groups of aryl group, heterocyclic group or substituent group b), and R3 is _ NHAr2 group (where A r2 is a square group, a fluorene ring group, an aryl group substituted with 1 to 5 groups selected from the substituent group b or a heterocyclic group substituted with 1 to 3 groups selected from the substituent group b) Compound of formula (IFA) and compound of formula (IFB)

-141-200524880 F method

X

(XXIV) F1 Project Ar1a-NH2 (XXXXXVI)

F2 Project Ar2a-NH2 (XXXXXVII)

F3th project H〇, .Ar

R 1a r (VI)

R

F 5th project HgN — NH2 HN 2 2a

F 4th project

(XXVII) R2a person (IX) F6th project R1a

In the present invention, R1, R2, R4, Rla, R2a, R4a and X are defined as above, Ar1 is an aryl group substituted with 1 to 5 groups of aryl, heterocyclic group or substituent group b, and Ar2 is an aryl group , Heterocyclyl, aryl substituted with 1 to 5 groups selected from substituent group b or heterocyclic substituted with 1 to 3 groups selected from substituent group b -142- 200524880 group 'Ar is A r1 Substituents in the group include amine groups, via groups and / or residues, amine groups that can be protected, hydroxyl and / or carboxyl groups, the same groups as defined in the Ar1 group,

Ar2a is a substituent of Ar2 group including amine group, hydroxyl group and / or carboxyl group, amine group which can be protected, hydroxyl group and / or carboxyl group, and the same group as defined in Ar2 group. F1 project This project is a manufacturing process of a compound of formula (X X V). The compound of formula (XXIV) is reacted with a compound of formula (χχχχχνι) in an inert solvent to carry out. The solvent used in this project is non-obstructive to the reaction, and there is no particular limitation on the solubility of starting materials to a certain φ degree, such as formazan, N, N-dimethylformamide, N, N-dimethylacetamide , N-methyl-2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine, and other amines; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, and dimethoxyethyl Ethers such as alkane, diethylene glycol dimethyl ether; fluorene such as dimethylarsine, cyclobutane; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chlorobenzene; benzene, toluene, Aromatic hydrocarbons such as xylene; or ketones such as acetone, methyl ethyl ketone, cyclohexanone, etc., preferably ethers or ketones, but also tetrahydrofuran, dioxane or acetone. _ The reaction temperature in this project may vary depending on the raw material compound, the inert solvent used, etc., usually 0t: ~ 120 ° C (preferably room temperature ~ 80 ° C). The reaction time in this project varies depending on the raw material compound, the inert solvent used, the reaction temperature, etc., and is usually 30 minutes to 24 hours (preferably 1 hour to 15 hours). F2 Project This project is a manufacturing process of a compound of formula (X X. I). In an inert solvent -143-200524880, ‘the compound of formula (XXV) is reacted with the compound of formula (XXXXXVII). The solvent used in this project is non-obstructive to the reaction, and it is not limited to be able to dissolve the starting materials to a certain degree, such as formamidine, N, N-dimethylformamide, n, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, two slogans, dimethoxyethane, Ethers such as diethylene glycol dimethyl ether; Difluorenes such as dimethyl sulfene, cyclobutane; halogenated hydrocarbons such as dichloromethane, 1, 2-dichloroethane, and chlorobenzene; benzene, toluene, and xylene And other aromatic hydrocarbons; or ketones such as acetone, methyl ethyl ketone, cyclohexanone, and preferably tetrahydrofuran, dioxane or acetone. The reaction temperature in this project may vary depending on the raw material compound, the inert solvent used, etc., and it is usually room temperature to 120 ° C (preferably 60 to 10 CTC). The reaction time in this project may vary depending on the raw material compound, the inert solvent used, the reaction temperature, etc., usually 3 hours to 3 days (preferably 5 hours to 2 days) ° F3 project This project is represented by the formula The manufacturing process of a compound of formula (IFA) which is an oxygen atom 'After reacting a compound of formula (XXVI) with a compound of formula (VI) in an inert solvent in the presence of a base, let R1a, R2a, R4a, Arla and Ar2a The amine group, hydroxy group and / or carboxyl protecting group are removed to carry out, this project can be carried out according to the method of the above-mentioned A, A3 project. F4 project This project is a compound of formula (I), A is the formula _NH_ group In the manufacturing process of the compound of the formula (IFB) -144- 200524880, in the presence or absence of an inert solvent (preferably in the presence), after reacting the compound of the formula (XXVI) with the compound of the formula (VII), the desired Rla, R2a , R4a, Ba1 ^ and Ar2a to remove the amine group, hydroxyl group and / or carboxyl protecting group, this project can be carried out according to the method of the above method A4 project A. F5 project This project is a compound of formula (XXV II) Manufacturing process in the presence of inert solvents In the absence or presence (preferably in the absence of presence), the compound of formula (XXVI) is reacted with hydrazine monohydrate or anhydrous hydrazine. Process This process is the production process of a compound of formula (IFB) in which the compound of formula (I) is A, and A is a formula -NH-. After reacting the compound of formula (XXV II) with the compound of formula (IX) in the presence of an inert solvent, Let the desired r 1 a, r 2 a, R4a, Arla, and Ar2a be removed to remove the amine, hydroxyl, and / or carboxyl protecting groups. 'This process can be performed according to the method of the above method A and A6. Each of the above method F After the completion of the engineering reaction, each target compound can be prepared from the reaction mixture according to the usual method. For example, the reaction mixture is properly neutralized, and when there is insoluble matter, it is filtered off, and water and ethyl acetate, etc., are added as immiscible organic solvents. 'The organic layer containing the target compound is separated, washed with water, etc., dried over anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., and then obtained by distilling off the solvent. The obtained target compound may be obtained by a conventional method, for example, if necessary. Crystallization, reprecipitation, etc. The conventional methods for the separation and purification of substances are appropriately combined, and applied with chromatography to dissolve and purify with an appropriate eluent.-] 45-200524880 G method G method is a method for producing a compound of formula (III) of the above-mentioned raw material compound of method A. G Method 04a X (XXVIII) Project G1, R9-OH (XXIX).

R 丨 Project G2 R4a \ ^ x / R9 (XXX) Latch 5AJ ^

N. I · R 〇,, R10 (m) In the present invention, the definitions of R9, R1G, R11, ruler "and R5A are as above.

This project is a manufacturing process of a compound of formula (XXX). In the presence of an acid, a compound of formula (X X V III) is reacted with a compound of formula (X X IX). The acid used in this project is an inorganic acid such as sulfuric acid or hydrochloric acid; or an organic sulfonic acid such as p-toluenesulfonic acid, preferably sulfuric acid or hydrochloric acid. The compound of the formula (X X I X) used in this project is, for example, a lower alkanol, preferably methanol or ethanol. The reaction temperature in this project may vary depending on the raw material compounds, acid species, etc., and is usually room temperature to 120 ° c (preferably 80 ° c to 100 ° C). The reaction time in this project may vary depending on the raw material compound, the type of acid, and the reaction temperature, etc., usually 1 hour to 18 hours (preferably 3 hours to 8 hours). Project G2 This project is a manufacturing process for compounds of formula (III). A compound of the formula (XXX) is reacted with an N, N-dialkylformamide dioxane acetal derivative or a tetradecane methyldiamine derivative compound to proceed. -146-200524880 The N, N-dialkylformamide dioxane acetal derivative used in this project is, for example, N, N-dimethylformamide dimethyl acetal or N, N_di Methyl formase amine diethyl acetal is preferably N, N-dimethylformamide diethyl acetal. The tetradecanediamine derivative used in this project is, for example, c-methoxytetramethylmethyldiamine or C-tertiary butoxytetramethylmethyldiamine. The reaction temperature in this project may vary depending on the raw material compounds, etc., and is usually room temperature to 180 ° C (preferably 50 ° C to 150 ° C). The reaction time in this project may vary depending on the raw material compounds, reaction temperature, etc., and is usually 3 hours to 48 hours (preferably 10 hours to 30 hours). It is called that after the reaction of each project in the above G method is completed, each target compound can be prepared from the reaction mixture according to the usual method. For example, the reaction mixture is appropriately neutralized, and when insoluble matter is filtered off, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated, washed with water, and then dried with anhydrous magnesium sulfate. After drying, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent is distilled off. If necessary, the obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other methods for separating and refining organic compounds, which are usually used in an appropriate combination, and subjected to leaching to dissolve and purify them with an appropriate eluent. The reference method is a method for producing a compound of the formula (ν τ), which is a raw material compound of methods A to F above. (Method 1) Project 1 ------- 2N—〇 1 R1a U Rla p2a ho, A (IX) (VI) In the above formula, the definitions of 1 ^ 13 and R2a are as above in the first project -147-200524880 The process is a manufacturing process of a compound of formula (VI). In an inert solvent (preferably ethers or alcohols), the compound of formula (IX) and hydroxylamine are prepared at room temperature to 120 ° C (preferably 60 ° C to 100%). (:) The reaction is performed for 30 minutes to 24 hours (preferably 15 hours to 18 hours). After the completion of each engineering reaction in the above method, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when insoluble matter is filtered off, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated, washed with water, and then dried with anhydrous magnesium sulfate. After drying, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent can be obtained by distillation. The obtained target compound can be used in accordance with ordinary methods, such as recrystallization, reprecipitation, and other conventional methods to separate and purify organic compounds. It is obtained by dissolving and refining with appropriate dissolving agent. Method for producing compound of formula (X) as raw material compound of method B above

(XXXXXII) In the above formula, R3a, R4a and R5B are as defined above, and R14 is a lower alkyl group. The 11th project This project is a manufacturing process of a compound of formula (XX χ 1 v) 'in an inert solvent (preferably amidoamines, ethers, alcohols or halogenated hydrocarbons' most preferably alcohols) in the presence of a base (Alkali metal alkoxides, metal carbonate-148-200524880 or organic bases, most preferably alkali metal alkoxides), the compound of formula (II) and the compound of formula (XXX III), Room temperature to 120 ° C (preferably 80 ° C to 100 ° C). The reaction is performed for 1 hour to 48 hours (preferably 10 hours to 24 hours). The twelfth project This project is a manufacturing process of the compound of formula (X). This project can be carried out in accordance with the above-mentioned method A2 (i) of the A method. After the reaction of each project in the above method I is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when there is insoluble matter, filtered and removed, water and ethyl acetate and other immiscible organic solvents are added. After magnesium, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc. are dried, the solvent is distilled off. If necessary, the obtained target compound is subjected to ordinary methods such as recrystallization and reprecipitation.

t go to JL · ij [t C ydi, " ρ λ, 丄 method, EA method and method, and EB method raw material compound formula (χ π) Φ production method. J method

(XII) In the above formula, R3 and X are as defined above. The first] project -149-200524880 This project is a manufacturing process of the compound of formula (X II).

After the reaction of each project in the above method is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when there is insoluble matter, it is filtered off, and an organic solvent containing water and ethyl acetate is added to separate the organic layer containing the target compound, and the organic layer containing the target compound is washed with water and then anhydrous magnesium sulfate. After drying, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent is distilled off. If necessary, the obtained target compound can be obtained by appropriate combination according to a conventional method such as recrystallization, reprecipitation, and other conventional methods for separating and purifying organic compounds, and applying a layering method to dissolve and purify it with an appropriate eluent. Method K Method K is a method for producing a compound of formula (V) in which R3A is hydrogen among the compounds of formula (V) as the raw materials of method A above. Method K 〇 K 1

R nh2 (XXXV)

S ^ OH

K2 Project

(XXXVII) (XXXVI)

In the above formula, 1 ^ 4 £ 1 and the same are as defined above. Project K1 This project is a manufacturing process of a compound of formula (XXXVI) in an inert solvent (preferably formamidine, Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetamide, Ν_ Methylamines such as methyl-2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diamine Ethers such as ethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerin, -150- 200524880 afternoon alcohol, ring Alcohols such as hexanol and 2-methoxyethanol; fluorenes such as dimethylarsine and cyclobutane; or halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chlorobenzene, more preferably alcohols Class 'most preferably ethanol', alkali (preferably alkali metal alkoxides, alkali metal carbonates or organic bases, more preferably alkali metal alkoxides, most preferably sodium ethoxide or third butoxy Potassium), let the compound of formula (XXX V) and three coax, at room temperature ~; [1〇. 〇 (preferably 6crc ~ i〇 (rc) reaction is performed for 1 hour to 18 hours (preferably 3 hours to 8 hours). The K2 project is a manufacturing process for the compound of formula (XXXVII). It is carried out by the method of the A2 project of the A method. After the reaction of each project in the above K method is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and insoluble matter is filtered off Then, add water and ethyl acetate, which are immiscible organic solvents, to separate the organic layer containing the target compound, wash with water, etc., dry over anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., and then evaporate. It is obtained by removing the solvent. If necessary, the obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, and combining them appropriately, and applying chromatography to dissolve and purify with an appropriate eluent. In the compound of formula (XXXXX v), which is the raw material compound of the above-mentioned C method, R5eA is 1-pyrazolyl, 1.pyrrolyl, 1 having any group selected from (aryl, heterocyclic or haloaryl) substituted at the 4-position. -Pyrazolyl or selected from ( Aryl, heterocyclyl or haloaryl) A method for producing a compound of the formula (XXXXXV) with 1-pyrrolyl substituted at any position at the 3-position. ) The L3 project HO—B \ OH (XX> In the above formula, Ar3 is an aryl, heterocyclic or haloaryl group, R15 is an aromatic amine protecting group, M is a metal atom, U is N or CH. L1 Project This project is to introduce a protective group R15 (preferably an amine acetaldehyde or silane-based protective group) into the aromatic amine group of the compound of formula (XXXV III), more preferably methoxymethyl, ethoxymethyl, [2- ( Trimethylsilyl) ethoxy] methyl or benzyloxymethyl) 'to obtain compounds of formula (XXXIX) can be performed according to known methods (for example, "Protective Groups in Organic Synthesis" (Theodora W. Greene, Peter G. · M. Wuts, 1989, 1989, ^^ 16 乂 -Interscience Publication), etc.). L2 project This project is a manufacturing process for compounds of formula (XX χ XIX), in an inert solvent Medium (preferably ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, Ethers, such as ethylene glycol dimethyl ether, are more preferably diethyl ether or tetrahydrofuran) 'order (XXXXX) compounds and bases (preferably alkane alkali metals, and more preferably third butyl lithium, second butyl lithium, or n-butyl lithium) , At-loot ~ -401 (preferably · 8 0 C ~ -7 0 c) react for 5 minutes ~ 3 hours (preferably 10 minutes ~) hours 15

X (XXXIX) 15th L2 Project

U Μ (ΧΧΧΧΙΧ) R!, Ν 15 u f L4th project 15

, U Section L5 Project (XXXXI) Η Ν

U Ar (XXXXII) < X) -152- 200524880). Project L3 This project is a manufacturing process for compounds of formula (XXXX), in an inert solvent (preferably ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, diDfane, dimethoxyethane, diethylene glycol dimethyl ether, etc. Type, more preferably diethyl ether or tetrahydrofuran) 'Law compound (XXXXIX) and trialkyl borate (preferably trimethyl borate) compound, at -100 ° C ~ -40 ° C (preferably -80 ° C ~- 70 ° C) for 5 minutes to 3 hours (preferably 30 minutes to 1.5 hours). Project L4 calls this project to be a manufacturing process of compounds of formula (XXXXI) in an inert solvent (preferably formamidine, N, N-dimethylformamide, n, N-dimethylacetamide, N -Methyl-2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diamine Ethers such as ethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, 2 -Alcohols such as methoxyethanol; Difluorenes such as dimethylarsine, cyclobutadiene; Aromatic hydrocarbons such as benzene, toluene, xylene; and water or mixed solvents of the above solvents, more preferably aromatic hydrocarbons, A mixed solvent of alcohols and water, most preferably a mixed solvent of benzene, methanol and water), in the presence of a base (preferably an alkali metal alkoxide, an alkali metal carbonate or an organic base, more preferably an alkali metal Carbonates, most preferably sodium carbonate or potassium carbonate), palladium catalyst (preferably divalent palladium catalyst or zero-valent palladium catalyst, more preferably palladium-activated carbon, palladium (II) acetate, Palladium (II) fluoroacetate, palladium rhenium, palladium (Π), palladium (II) chloride, palladium iodide (Π), palladium cyanide (II), palladium nitrate (π), palladium oxide (-153- 200524880 II), palladium (II) sulfate, dichlorobis (acetonitrile) palladium (II), dichlorobis (benzonitrile) palladium (II), dichloro (1,5-cyclooctadienyl) palladium (Π) , Ethyl acetone palladium (II), palladium sulfide (Π), ginseng (dibenzylideneacetone) dialuminum (0), acetonitrile (palladium) (palladium) (π) tetrafluoroborate, chlorinated aryl absolute dimer, Palladium with phosphine or phosphite ligands (for example, dichloro [1,1 'bis (diphenylphosphine) ferrocene] palladium (II), triphenylphosphine) palladium (0), trans_di (_ Acetate) Bis [o- (di-o-tolylphosphine) benzyl] dipalladium (II) and palladium with phosphine or phosphite ligands (eg, cyclohexylphosphine, tri-tert-butyl) O-, 2- (dicyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2 '(N, N-di-methylamine ^ yl) biphenyl, 2,2, bis (diphenylphosphine)- 1,1 'binaphthyl, bis (2-diphenylphosphinophenyl) ether, 2- (di-tertiary butylphosphino) biphenyl, trifuran scale, ginseng (2, triphenyl-tertiary butylphenyl) phosphite Acid salt, tri-o-tolylphosphine, etc.)), most preferably (triphenylphosphine palladium), a compound of formula (XXXX) and an aryl halide, at room temperature ~ 120 ° C (preferably 80 ° C ~ llOt :) The reaction is performed for 5 hours to 48 hours (preferably 15 hours to 24 hours). Project L5 This project is a manufacturing process for a compound of formula (XXXX II). The deprotection of the protective group R15 of the compound of formula (χ · XXXI) can be performed according to Known methods (for example, "Protective Groups in Organic Synthesis" (Theodora W ·

Greene, Peter G. M. Wuts, 199, 9

(Interse knee Publication)). After the reaction of each process in the above L method is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, neutralize the reaction mixture appropriately. After filtering off any impurities, add an immiscible organic solvent such as water and ethyl acetate-154-200524880 to separate the organic layer containing the target compound and wash it with water. Then, it is obtained by drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., and then distilling off the solvent. The obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, if necessary, by appropriate combination, and applying a layering method to dissolve and purify it with an appropriate eluent. Method M is a compound of formula (XXXXX ν) of the above-mentioned method C raw material compound, R5 e A is an arbitrary group selected from 1-pyrazolyl, 1-pyrrolyl, (aryl, heterocyclic or haloaryl) Method for producing a compound of the formula (XXXXXV) substituted at the 5-position: 1-pyrazolyl or an arbitrary group selected from (aryl, heterocyclyl or haloaryl) substituted at the 2-position with 1-pyrrolyl. Μ 法 M 2nd project

(XXXXV)

M1th Project (ΧΧΧΧΙΙΙ) R16

I

Gu (XXXXIV) Λ β Project M 3

(XXXXVI) (XXXXVII) In the above formula, the meaning of U is as described above, and Ar is a square group, a fluorene ring group, or a tooth square group. R16 is an aromatic amine protecting group. Project M1 This project introduces a protective group R16 (preferably an amine-acetaldehyde or silane-based protective group) into the aromatic amine group of the compound of formula (XXXX ΙΠ), more preferably methoxymethyl, ethoxymethyl, [2 -(Trimethylsilyl) ethoxy] methyl or prooxymethyl) compounds of formula (XXXXIV) can be manufactured according to known methods -155- 200524880 (for example, "Protective Groups in Organic Synthesis" (Theodora W. Greene, Peter GMWuts, 1999, A Wiley-Interscience Publication)). Project M 2 This project is a manufacturing process of a compound of formula (xxxxv), so that the compound of formula (XXXXIV), according to a known method (for example, Qui Han, Chong-Hwan Chang, Renhu a Li, Yu Ru, Prabhakar K. Jadhav, and Patrick YS Lam J. Med. Chem. 1 998, 41, »20 1 9-2028, etc.). Project M 3 This project is a manufacturing process of a compound of formula (XXXXVI) in an inert solvent (preferably formamidine, Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetamide, Ν. -Methyl-2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diamine Ethers such as ethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol, 2 -Alcohols such as methoxyethanol; Dioxins such as dimethylarsine, cyclobutadiene; Aromatic hydrocarbons such as benzene, toluene, xylene; Water or a mixed solvent of the above solvents, more preferably aromatic hydrocarbons, alcohols And water mixed solvents,

Most preferably a mixed solvent of benzene, methanol and water), in the presence of a base (preferably alkali metal alkoxides, alkali metal carbonates or organic bases, more preferably alkali metal carbonates, most preferably carbonic acid Sodium or potassium carbonate), palladium catalyst (preferably divalent palladium catalyst or 0 valent palladium catalyst, more preferably palladium-activated carbon, palladium acetate (II -156-200524880), palladium trifluoroacetate (Π), Palladium rhenium, palladium (II) bromide, palladium (11), palladium (II) iodide, palladium (II) cyanide, palladium (II) nitrate, palladium (II) oxide, palladium (II) sulfate, two Chlorobis (acetonitrile) palladium (II), dichlorobis (benzonitrile) palladium (II), dichloro (1,5-cyclooctadienyl) palladium (Π), acetoacetonepalladium (Π), palladium sulfide (II) Ginseng (dibenzylideneacetone) dipalladium (0), acetonitrile, palladium (Π) tetrafluoroborate, chlorinated aryl palladium dimer, palladium with phosphine or phosphite ligands (For example, dichloro [1, factory-bis (diphenylphosphine) ferrocene] palladium (II), palladium (triphenylphosphine) palladium (0), trans-di (//-acetate) bis [o- (Di-o-o-tolylphosphine) benzyl] dipalladium (II) and palladium with phosphine or phosphite ligands For example, cyclohexylphosphine, tri-tertiary butylphosphine, 2- (dicyclohexylphosphine) biphenyl, 2-dicyclohexylphosphine-2 '(N, N-di-methylamino) biphenyl, 2,2 , Bis (diphenylphosphine) -1,1 ′ binaphthyl, bis (2-diphenylphosphinephenyl) acetic acid, 2_ (—-% dibutyltenyl) biphenyl, tri-2-pyran scale, ginseng ( 2,4-bis-tertiary-butylphenyl) phosphite, tri-o-tolylphosphine, etc.)), most of which are dibenzyl fG, compounds of formula (XXXXV) and aryl teeth, at room temperature ~ 120 ° C (preferably 80 ° C to 110 ° C) for 5 hours to 48 hours (preferably 15 hours to 24 hours). The M4 project is a manufacturing process of a compound of formula (XXXXV II). The deprotection of the protecting group R16 of the compound of formula (XXXXVI) can be carried out according to known methods (for example, "Protective Groups in Organic Synthesis" (Theodora W. Greene, Peter G. M. Wuts, 1999, August ^^ 16 -Interscience Publication) and other methods). After each engineering reaction in the above M method is completed, each target compound can be prepared from the reaction mixture according to the normal method -157-200524880. For example, the reaction is mixed The product is neutralized properly. After insoluble matter is filtered off, the organic layer containing the target compound is separated by adding an immiscible organic solvent such as water and ethyl acetate. After washing with water, the organic layer is dried with anhydrous magnesium sulfate and anhydrous sodium sulfate. After drying, anhydrous sodium bicarbonate, etc., it is obtained by distilling off the solvent. When necessary, the obtained target compound is appropriately combined according to a conventional method, for example, recrystallization, reprecipitation and other organic compounds are conventionally used for proper combination, and chromatography is used to appropriately elute Dissolved and refined. Method N Method N is the raw material of the above method A and D. Among the compounds of formula (Π), reference R3A is a formula of the formula -NHR6 (Production method of compound of formula χχχχχυ N method R6a

NH NH2 (XXXXXI) p6a I N1 project / NH-> Η (ΧΧΧΧΧ)

In the present invention, R6A is the same as the definition of R6 group except for the amino group, hydroxyl group and / or carboxyl group contained in R6 (the definition of R6 as above) as a substituent, and the amine group, hydroxyl group and / or carboxyl group that can be protected . Project N 1 This project is a manufacturing process of a compound of formula (XXXXXI) in an inert solvent (preferably formamidine, N, N-dimethylformamide, N, N-dimethylacetamide, N -Methyl-2 -pyrrolidone, N -methylpyrrolidone, hexamethylphosphonium triamine, and other amines; ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diamine Ethers such as ethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol-158- 200524880, octanol, cyclic Alcohols such as hexanol, 2-methoxyethanol; water or a mixture of the above solvents; cereals, and most of them are acid limbs or alcohols), so that the formula (χχχχχ) and the guanidine derivatives (for example, cyanide Hydrazine or i H -pyrimidine_ i _ residual formamidine or nitric acid 3,5-monomethylpyrazole _ 1 _ carboxyformamidine activated carboxamidine compounds, preferably cyanamide or hydrochloric acid 1 The pyrene-pyrazole-1 -carboxamidine) is reacted at room temperature to 120C (and 80C to 100 ° C) for 1 hour to 48 hours (preferably 10 hours to 24 hours.). After the reaction of each process in the above N method is completed, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when there is insoluble matter, it is filtered off, and an organic solvent containing water and ethyl acetate is added to separate the organic layer containing the target compound, and the organic layer containing the target compound is washed with water and then anhydrous magnesium sulfate. After drying, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., the solvent is distilled off. The obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other conventional methods for separating and refining organic compounds, if necessary, by appropriate combination, and applying a layering method to dissolve and purify it with an appropriate eluent. Method 0 is the raw material compound of method I. Among the compounds of formula (XXX III), R4A is an aryl group, a heterocyclic group, an aryl group substituted with 1 to 5 groups selected from the substituent group b, or a substituent selected from the group Method for producing a compound of formula (XXXXXIV) having a heterocyclic group substituted with 1 to 3 groups in group b.

(XXXXXIII) (XXXXXIV) In the present invention, R14 is as defined above, R17A is an aryl group, a heterocyclic group, an aryl group substituted with 1 to 5 groups of the -159- 200524880 group b, and a substituted group b 1-3 of the substituted heterocyclic groups or (i ~ 5 substituted aryl groups of the substituent group b or 1-3 substituted heterocyclic groups of the substituent group b) include amines Group, a hydroxyl group and / or a carboxyl group, a protected amino group, a hydroxyl group and / or a carboxyl group, and Z is a halogen atom. Project 01: This project is a manufacturing process for compounds of formula (XXXXXIV). It can be prepared in the manner described in Hennessy, EJ, Buchwald, SL Org. Lett. 4, 2, 2002, 269-272 in an inert solvent (preferably ether). Type, most preferably tetrahydrofuran or difane), copper (preferably copper (I) chloride, copper bromide (I), copper iodide (I), copper triflate (I) or monovalent copper Salt, most preferably copper (I) or copper triflate (I)), phenol (preferably 2-phenylphenol), base (preferably carbonic acid), the compound of formula (XXXXXII) and The compound of formula (XXXX XIII) is reacted at room temperature to 10 (TC (preferably 60 ° C to 80 ° C)) for 2 hours to 7 days (preferably 15 hours to 48 hours). The reaction of each process in the above method 0 ends After that, each target compound can be prepared from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and when there is insoluble matter, it is filtered off, and an immiscible organic solvent such as water and ethyl acetate is added to separate the target mixture. The organic layer of the compound is washed with water, etc., dried over anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium bicarbonate, etc., and then the solvent is distilled off. The obtained target compound is obtained by conventional methods, such as recrystallization, reprecipitation, and other conventional methods for separating and purifying organic compounds, if necessary, by appropriate combination, applying chromatography, and dissolving and purifying with an appropriate eluent. -160- 200524880 (Π), (VII), (IX), (χν), (X XIV) > (XX VIII) > (X XIX). (Χ χ χιπ) ~ (XXXV), (XXXV III), (XXXX In), (xxxx vm), (χχχχχ), (XXXXXiiu (XXXXX III)) are known compounds, or can be easily manufactured according to known methods or similar methods. In the present invention, the pyrimidine derivative of formula (I) or a pharmacologically acceptable salt thereof acts In the case of medical use, it can be mixed alone or with appropriate pharmaceutical acceptable excipients, diluents, etc., such as sharps, capsules, granules, powders, or sugars, etc. orally or non-monitored such as injections or suppositories. Oral administration. This formulation can be used with excipients (eg, sugar derivatives such as lactose, white sugar, glucose, mannose, sorbose, etc .; corn starch, potato starch, α-stimulus powder, dextrin # stimulus derivative; crystallization fiber And other cellulose derivatives; acacia gum; polydextrose; polytriglucose and other organic excipients; light silicic anhydride, synthetic aluminum silicate, calcium silicate, magnesium silicate and other silicate derivatives; hydrogen phosphate Phosphates such as calcium; carbonates such as calcium carbonate; inorganic excipients such as sulfate such as calcium sulfate; lubricants (eg, stearic acid, stearic acid15, magnesium stearate and other stearic acid metal salts) Talc; colloidal silica; propolis, wax and other waxes; boric acid; adipic acid; sodium sulfate and other sulfates; ethylene glycol; fumaric acid; sodium benzoate; DL leucine; fatty acid sodium salt; Dodecyl sulfates such as sodium dodecyl sulfate, magnesium dodecyl sulfate; silicic acids such as silicic anhydride, silicic acid hydrate; and the above starch derivatives), binding agents (for example, hydroxypropyl cellulose, hydroxypropyl Methylcellulose, polyvinylpyrrolidone, polyethylene glycol and the aforementioned excipients, etc.), disintegrating agents (for example, low-substituted hydroxypropyl cellulose-161-200524880, residual methyl cellulose, carboxymethyl Cellulose derivatives such as cellulose calcium and internal cross-linked sodium carboxymethyl cellulose; carboxymethyl starch Chemically modified starch celluloses such as sodium carboxymethyl starch, cross-linked polyethylene pyrrolidone, etc.), stabilizers (parabens such as methyl paraben, propyl paraben, etc .; chlorine Alcohols such as butanol, benzyl alcohol, phenethyl alcohol; benzyl ammonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; and sorbic acid), flavoring agents (for example, conventional sweeteners, sour ingredients, and Additives such as flavors and diluents are manufactured according to customary methods. The dosage varies depending on symptoms, age, etc. For example, when taken orally, the lower limit is 0.015 mg / kg body weight (preferably 0.008 mg / kg body weight), and the upper limit is 70 mg / kg body weight (preferably 7 mg) / Kg body weight), when administered intravenously to adults each time the lower limit of 0.00005mg / kg body weight (preferably 0.0008mg / kg body weight), the upper limit of 8.5mg / kg body weight (preferably 5mg / kg body weight) According to the symptoms, it can be administered 1 to 6 times a day. [Embodiment] Examples, reference examples, and test examples are described in detail below, but the present invention is not limited thereto. The measurement equipment for various analytical data and the measurement conditions for liquid chromatography are as follows: (Measurement Conditions for Liquid Chromatography and Mass Analysis) The measurement equipment for liquid chromatography mass fraction (LCMS) is HP-1100LC / MSD manufactured by HP. The column was an inverse layer, and CD-C18 manufactured by 1ntact was used. The analysis conditions were a column temperature of 40 ° C and acetonitrile and water (containing 0.01% trifluoroacetic acid) for the mobile layer. The flow rate is 1.5ml / min, and acetonitrile makes 8% ~-162- 200524880 99% linear gradient of 10%. The mass spectrometer uses an atmospheric pressure chemical ionization method (hereinafter referred to as APCI). (Measuring device for nuclear magnetic resonance spectrum (hereinafter referred to as 1H-NMR)) The iH-NMR data was measured using a JEOLJNM-GX 270FT-NMR or a Varian Mercury 400 or Varian Inova 500 measuring device. Tetramethylsilane is used as a reference substance, and chemical shifts are described as (5 ppm. The splitting pattern is described by the singlet line as s, the doublet line as d, the triplet line as t, and the quadruple line as q. DMF is dimethylformamide. Example 1 {4- [N '-(1-pyridin-4-yl-ethylene) -hydrazino] -pyrimidine-2,6-ylbibis- ( 2-methoxyphenyl) -amine (Compound No. 955) The 4-hydrazino-2,6-bis- (2-methoxyaniline) -pyrimidine (0.1 mmol) produced in Reference Example 1 in ethanol (1 ml) was dissolved, 4-acetamidine (0.66 ml, 0.3 mmol) was added, and the mixture was stirred for 18 hours. The precipitated solid was pulverized, and the target substance was obtained by filtration. MS (APCI, m / z): 456 (M + 1) + · HPLC (reverse phase): Rt. (Min) = 2.76. Example 2 Phenyl- [4- [N,-(1.pyridin-4-yl-ethylene) -hydrazino] -6 -(4-Pyridin-4-yl-pyridyl-1-yl) -annidine-2 -yl] -amine (compound number 5) was reacted and purified according to the method of Example 1 to obtain the target compound ( 6 1 mg, 6 9%) 〇! Η-NMK (270 MHz, DMSO-d6) ppm: 1 〇 · 5 3 (br s, 1 Η), 200524880 9.47 (s, 1H), 9.07 (s, 1H ), 8.68 (d, 2H, J = 5.9 Hz), 8.55 (s, 1H), 7.95 (d, 2H, J = 8.4 Hz), 7.79 (d, 2H, J = 5.9 Hz), 7.73 (d, 2H, J = 5.9 Hz), 7.35 (t, 2H, J = 7.6 Hz), 7.21 (s, 1H), 7.00 (t, 1H, J = 5.9 Hz), 2.41 (s, 3H). MS (APCI, m / z): 448 (M + l) +. HPLC (reverse Phase): Rt. (Min) = 3.09. Example 3 Phenyl- [4- [N '-(pyridin-4-yl-ethylene) -hydrazino] -6- (3-pyridine-4- -Pyrazol-1-yl) -pyrimidin-2-ylbamine (compound number 868) was reacted and purified according to the method of Example 1 to obtain the target compound (35 mg, 52%). 1H-NMR ( 270 MHz, DMSO-d6) 5 ppm: 9.49 (s, 1H), 8.72-8.65 (m, 5H), 7.95-7.93 (m, 4H), 7.83 (d, 2H? J = 5.9 Hz), 7.35 (d , 2H, J = 7.3 Hz), 7.31-7.29 (m, 2H), 7.24 (s, 1H), 7.00 (t, 1H, J = 7.6 Hz), 2.42 (s, 3H). MS (APCI, m / z): 448 (M + 1) +. HPLC (reverse phase): Rt. (min) = 3.47. Example 4 N2-phenyl-N4- (2-pyridin-4-yl-ethyl) -6- [N '-(1-pyridin-4-yl-ethylene) -hydrazino] -pyrimidine- 2,4-diamine (compound number 9) was reacted and purified according to the method of Example 1 to obtain the target compound (13 mg, 31%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 9.54 (brs, 1H), 8.60-8.58 (m, 3H), 8.48 (d, 2H, J = 5.7 Hz), 7.87-7.80 (m, 200524880 2H ), 7.73 (d, 2H, J = 5.7 Hz), 7.30 (d, 2H, J = 5.7 Hz), 7.22 (t, 2H, J = 7.3 Hz), 7.04 (brs, 1H), 6.87 (t , 1H, J = 7.0 Hz), 5.91 (s, 1H), 3.60-3.58 (m, 2H), 2.90 (t, 2H, J = 6.8 Hz), 2.30 (s? 3H). MS (APCI, m / z): 425 (M + l) +. HPLC (reverse phase): Rt. (min) = 2.52. Example 5 N2-phenyl-N4- (2-pyridin-3-yl-ethyl) -6- [N,-(l-pyridin-4-yl-ethylidene) -fluorenyl] -pyrimidine-2 4,4-diamine (compound number 957) was reacted and purified according to the method of Example 1 to obtain the target compound (36 mg, 81%). MS (APCI, m / z): 425 (M + 1) + . HPLC (reverse phase): Rt. (Min) = 2.58. Example 6 (4- {Nf- [1- (4-Methanesulfonylphenyl) -ethylidene] -hydrazinopyrimidine-2,6-yl) -bis- (2-methoxyphenyl)- Amine (Compound No. 95 6) The 4-hydrazino-2,6-bis- (2-methoxyaniline) -pyrimidine (0.1 mmol) produced in Reference Example 1 was dissolved in ethanol (1 ml), and 4- Methanesulfonylacetophenone (59 mg, 0.3 mmol) was stirred for 18 hours. The precipitated solid was pulverized, and the target substance was obtained by filtration. MS (APCI, m / z): 5 3 3 (Μ + 1) + · HPLC (reverse phase): Rt. (Min) = 4.16. Example 7 4- (2- {2-aniline-6- [ N '-(Pyridine-4-yl-ethylene) -hydrazino] -pyrimidine-4 200524880 Diylaminobethyl) -benzenesulfonamide (Compound No. 12) The reaction and purification were carried out according to the method of Example 1. To obtain the target substance (35 mg, 70%). MS (APCI, m / z): 503 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.09. Example 8 4- [2- (2-Anilino-6- { N '-[1- (4-Aminesulfenylphenyl) -ethylidene] -hydrazinopyrimidin-4-ylamino) -ethylbenzylsulfonamide (Compound No. 958) Reference Example 10 4- [2- (6-hydrazino-2-anilinopyrimidin-4-ylamino) -ethyl produced; l. Besysulfame (0.1 mmol) was dissolved in ethanol (1 ml), and 4-ethyl was added Toluenesulfonamide (60 mg, 0.3 mmol) was stirred for 18 hours. The precipitated solid was pulverized, and the target substance was obtained by filtration (43 mg, 74%). MS (APCI, m / z): 581 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.72. Example 9 4- [2- (2-Anilino-6- {N ' · [1- (4-Methylaminesulfonylphenyl) _Ethylene] -hydrazinobutyridin-4-ylamino) -ethyl] •• Benzsulfonamide (Compound No. 3 00) 4- [2- (6-hydrazinyl-2-phenylaminopyrimidin-4-ylamino) -ethyl] -benzidine (0.1 mmol) produced in Reference Example 10 in ethanol (1 mi) Dissolve, add 4-ethylammonium-N-toluenesulfonamide (64 mg, 0.3 mmol), and stir for 18 hours. The precipitated solid was pulverized and filtered to obtain the target compound (31 mg, 52%) ο 1 Η-NMR (2 7 0 Μ Η ζ, DMS 〇-d 6) (5 ppm: 9 · 3 9 (s , 1 Η), 8 · 5 9 (s, 1Η), 7.98 (d, 2H, J = 8.4 Hz), 7.86 (d, 2H, J = 7.6 Hz), 200524880 7.80-7.75 (m, 4H), 7.48 -7.44 (m, 3H), 7.28 (s, 2H)? 7.22 (t, 2H, J 7.8 Hz), 6.95 (brs, 1H), 6.87 (t, 1H, J = 7.6 Hz), 5.89 (s, 1H), 3.59-3.56 (m, 2H), 2.98-2.92 (m, 2H), 2.42 (d, 3H, J = 5.8 Hz), 2.34 (s, 3H). MS (APCI, m / z): 595 (M + 1) + · HPLC (reversed phase) · Rt. (Min) = 3.85. Example 1 0 4- [2- (2-Anilino-6- {N '-[1- (4-ring Propylaminesulfonylphenyl) -ethylidene] -hydrazinopyrimidinylamino) -ethyl] -benzenesulfonamide (Compound No. 959) φ 4- [2- (6- Hydrazine-2-aniline-pyrimidin-4-ylamino) -ethyl] -benzenesulfenilamide (0.1 mmol) was dissolved in ethanol (1 ml), and 4-ethylsulfanyl-N-cyclopropanesulfenylamine was added (72 mg, 0.3 mmol), stirred for 18 hours. The precipitated solid was pulverized, and the target substance (45 mg, 73%) was collected by filtration. MS (APCI, rn / z): 621 (M + 1) +. HPLC (Inverted): R t. (min) = 4.06. Example 1 1 _ 4- [2- (2-Anilino-6- {N '-[1- (4-methylsulfonylphenyl) -ethylidene] -hydrazino Pyrimidin-4-ylamino) -ethylbenzamide (Compound No. 156) was reacted and purified according to the method of Example 6 to obtain the target compound (47 mg, 81%). MS (APCI, m / z): 580 (M + 1) +. HPLC (reverse phase): Rt. (min) = 3.86. Example 1 2-167- 200524880 N-ethyl-4- (1- {[2- Aniline-6- (2-pyridin-4-yl-ethylamino) -pyrimidine-cardio] -hydrazinyl} -ethyl) -benzenesulfonamide (compound number 960) will be produced in Reference Example 8 4-Hydrazine-2-anilino-6- (2-pyridin-4-yl_ethylamino) -pyrimidine (0.1 mmol) was dissolved in ethanol (1 ml), and 4-acetic acid-N-ethyl was added Tolsulfame (68 mg, 0.3 mmol) was stirred for 18 hours. The precipitated solid was pulverized, and the target substance was obtained by filtration. MS (APCI, m / z): 531 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 3.24. Example 1 3 β 4- (1- {[2-aniline-6- (2-Pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinophenylethyl) -benzenesulfonamide (compound number 961) The reaction and purification were carried out according to the method of Example 8 to obtain the objective Thing. MS (APCI, m / z): 503 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 2.94. Example 14 N-methyl-4- (1-{[2-aniline -6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylhydrazinobethyl) -benzenesulfonamide (Compound No. 297) · The reaction and purification were carried out according to the method of Example 9, The object can be obtained. 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9.40 (s, 1H), 8.59 (s, 1H), 8.48 (dd, 2H, J = 1.6 Hz, 4.6 Hz), 7.98 (d, 2H, J = 8.6 Hz), 7.86 (d, 2H, J = 7.8 Hz), 7.78 (d, 2H, J = 8.6 Hz), 7.47 (dd, 1H, J = 4.6 Hz, 9.7 Hz), 7.29 (d, 2H, J = 5.9 Hz), 7.21 (t, 2H, J = 7.6 Hz), 6.96 (brs, 1H), 6.86 (t, 1H, J = 7.3 Hz), 5.88 (s, 1H), 3.60-3.55 (m, 2H), 2.92-2.87 (m, -168- 200524880 2H), 2.42 (d, 3H, J = 4.9 Hz), 2.34 (s? 3H). MS (APCI, m / z): 517 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.11. Example 1 5 N-cyclopropyl-4- (1- {[2-aniline-6- (2-pyridin-4-yl-ethyl) Amine) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 962) was reacted and purified according to the method of Example 10 to obtain the desired product. MS (APCI, m / z): 543 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 3.3. φ Example 1 6 6- (4-Methanesulfonylphenyl) -ethylene] -hydrazinob N2-phenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4 -Diamine (Compound No. 153) was reacted and purified according to the method of Example 6 to obtain the target substance. MS (APCI, m / z): 502 (M + l) +. HPLC (reversed phase): Rt. (Min) = 3.08. Example 17 6- {N '-[l- (l- (methylsulfonyl) -1H · pyrrole-3-yl) -ethylene] -hydrazinob N2-benzyl-N4- (2-pyridine-4-ethyl) -pyridine-2,4-diamine (compound number 963) 4-Amino-2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidine (0.1 mmol) produced in Reference Example 8 was dissolved in ethanol (1 ml), and 1 was added. -(1-Methanesulfonyl-1H-pyrrole-3-yl) -ethanone (56 mg, 0.3 mmol) 'Stir for 18 hours. The precipitated solid is pulverized, and the object is obtained by filtration. MS (APCI, m / z): 491 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.2. -169- 200524880 Example 1 8 N2-phenyl-6- [N,- (1-Pyridin-4-yl-ethylene) -hydrazino] -N4- (2-thiophen-2-yl-ethyl) -pyrimidine-2,4-diamine (Compound No. 966) according to Example 1 The method can be reacted and refined to obtain the target. MS (APCI, m / z): 430 (M + 1) 'HPLC (reversed phase) · · Rt. (Min) = 3.67 · Example 19 Methanesulfonylphenyl) -ethylenehydrazine Phenyl-N4- (2-thien-2-yl-ethyl) -pyrimidine-2,4-diamine (compound number 965) φ was reacted and purified according to the method of Example 6 to obtain the desired product. MS (APCI, m / z): 507 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.31. Example 20 N-methyl-4- (1-{[2-aniline -6- (2-thien-2-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 964) was reacted and purified according to the method of Example 9, The object can be obtained. MS (APCI, m / z): 522 (M + 1) +. # HPLC (reverse phase): Rt. (Min) = 4.52. Example 2 1 N4- [2- (4-methoxyphenyl) -ethyl] -N2-phenyl-6- [N '-(1-pyridyl-ethylene) -hydrazino] -pyrimidine- 2,4-diamine- [1- (4-methanesulfonylphenyl) ethylene] hydrazinob 4-pyrimidinyl) hydrazine (compound number 969) was reacted and purified according to the method of Example 1, but Get the object. MS (APCI, m / z): 454 (M + l) + .-170- 200524880 HPLC (reverse phase): Rt. (Min) = 3.66. Example 22 6- {N ^ [l- (4- 甲Sulfophenyl) -Ethylenetriazine N4- [2- (4-methoxyphenyl) -Ethylphenyl N2-phenylpyrimidinyl_2,4-diamine (Compound No. 968) according to Example 6 The method can be reacted and refined to obtain the target. MS (APCI, m / z): 531 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.46. Example 23 4- [1- ({6- [2- (4- 甲Oxyphenyl) -ethylamino] -2-anilino-pyridin-4-yldiazino) -ethyl] tosylsulfonamide (compound number 967) The reaction and purification were carried out according to the method of Example 9, but Get the object. MS (APCI, m / z): 546 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.45. Example 24 N4- [2- (3,4-dimethoxyphenyl) -Ethyl ethyl N2-phenyl-6- [N '-(l-pyridin-4-yl-ethylene) -hydrazino] -pyrimidine-2,4-diamine (Compound No. 11) according to Example 1 The method can be reacted and refined to obtain the target. 1H-NMR (270 MHz, DMSO-d6) ^ PPm: 9.50 (brs, 1H), 8.60 (s, 1H), 8.59 (d, 2H, J = 6.2 Hz), 7.87 (d, 2H, J = 7.6 Hz), 7.73 (d, 2H, J = 6.2 Hz), 7.22 (t, 2H, J = 7.6 Hz), 7.00-6.85 (m, 4H), 6.80 (t, 1H, J = 7.6 Hz), 5.93 (s, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 3.58-3.48 (m, 2H), 2.80 (t, 2H, J = 7.6 Hz), 2.30 (s, 3H). MS ( APCI, m / z): 484 (M + 1) +. 200524880 HPLC (reverse phase): Rt. (Min) = 3.4. Example 2 5 6- {1 ^,-[1- (4-methylsulfonium Phenyl) -ethylene] -hydrazino} -1 ^ 4- [2- (3,4-dimethoxyphenyl) -ethyl] -N2-phenylpyrimidin-2,4-diamine ( Compound No. l55) The reaction and purification were carried out according to the method of Example 6. MS (APCI, m / z): 561 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.2 . Example 2 6 4- [l-({6- [2- (3,4-Dimethoxyphenyl) -ethylamino] -2-anilino-pyridin-4-ylpyrazino) -ethyl Group: IN-toluenesulfonamide (compound number 299) was reacted and purified according to the method of Example 9 to obtain the target substance. 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9.39 (brs, 1H), 8.58 (brs, 1H), 8.00 (d, 2H, J = 8.1 Hz), 7.86 (d, 2H, J = 7.3 Hz), 7.79 (d, 2H, J = 8.1 Hz), 7.48 (q, 1H, J = 4.9 Hz), 7.22 (t, 2H, J = 7.3 Hz), 6.90-6.81 (m, 4H), 6.80 (t, 1H, J = 7.3 Hz), 5.89 (s, 1H), 3.73 (s, 6H), 3.5 8-3.43 (m, 2H), 2.80 (t, 2H, J = 7.3 Hz), 2.43 (d , 3H, J = 4 · 9 Hz), 2.34 (s, 3H) · MS (APCI, m / z): 576 (M + l) +. HPLC (reverse phase) ·· Rt. (Min) = : 4.28. Example 27 1 < 4- [2- (2,5-Dimethoxyphenyl) -ethyl]-> ^ 2-phenyl-6-[? ^-(1-pyridine-4- -Ethylene) -hydrazino] -pyrimidine-2, 'diamine (Compound No. 972) was reacted and purified according to the method of Example 1 to obtain the desired product. MS (APCI, m / z): 484 (M + 1) +. 200524880 HPLC (reverse phase): Rt. (Min) = 3.71 · Example 2 8 6- {1 ^-[1- (4- Methanesulfonylphenyl) -ethylene] -hydrazino} -1 ^ 4- [2- (2,5-dimethoxyphenyl) -ethyl: 1-N2-phenylpyrimidinyl-2,4 -Diamine (compound number 971) was reacted and purified according to the method of Example 6 to obtain the target substance. MS (APCI, m / z): 561 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.51. Example 29 4- [1-({6- [2- (2 (2 , 5-Dimethoxyphenyl) -ethylamino] -2-anilino-pyridin-4-yldiazino) -ethyl] tosylsulfonamide (compound number 970) was carried out according to the method of Example 9. Reaction and purification can get the target. MS (APCI, m / z): 576 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.53. Example 30 [4- {N,-[1- (4- 甲Sulfonylphenyl) -ethylenehydrazine 6- (4-pyridin-4-ylpyrazol-1-yl) -pyrimidinyl] -aniline (compound No. 149) was reacted and purified according to the method of Example 6, The target compound OM (APCI, m / z) can be obtained quantitatively: 525 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.8. Example 31 1 ^ -methyl-4- (1-{[2-anilino-6- (4-sleep-spin-4-yl-zibow-1-yl) -o / dense oxo- 4-yl ] -Hydrazynylethyl) -benzenesulfonamide (Compound No. 293) was reacted and purified according to the method of Example 9 to obtain the target compound (50-173-200524880 mg, 93%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 10.45 (s, 1H), 9.45 (s, 1H), 9.07 (s, 1H), 8.60 (d, 2H, J = 6.2 Hz) , 8.53 (s, 1H), 8.06 (d? 2H, J = 8.1 Hz), 7.94 (d, 2H, J = 8.4 Hz), 7.86 (d, 2H, J = 8.4 Hz), 7.74 (dd, 2H, J = 1.6 Hz, 4.6 Hz), 7.50 (dd, 1H, J = 4.6 Hz, 9.7 Hz), 7.35 (t, 2H, J = 7.6 Hz), 7.18 (s, 1H), 7.00 (t, 1H, J = 7.3 Hz), 2.46 (s, 3H), 2.45 (s, 3H). MS (APCI, m / z): 540 (M + l) + · HPLC (reversed phase): Rt. (Min) = 3.84. Example 3 2 N4- [2- (3-methoxyphenyl) -ethyl] -N2-phenyl-6- [N '-(l-pyridin-4-yl-ethylene) -hydrazino] -Pyrimidine-2,4-diamine (Compound No. 975) was reacted and purified according to the method of Example 1 to obtain the desired product. MS (APCI, m / z): 454 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 3.6. Example 3 3 6- {N '-[1- (3- 甲Sulfonylphenyl) -Ethylene] -hydrazinyl group N4- [2- (4-methoxyphenyl) -ethyl] -N2 -phenylsulfanyl-2,4 -a ^ fee (compound number 974) Perform the reaction and purification according to the method of Example 6 to obtain the target substance. MS (APCI, m / z): 531 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.38. Example 34 4- [l-({6- [2- (3- 甲Oxyphenyl) -ethylamino] -2-anilino-pyridin-4-ylbuya 200524880 hydrazino) -ethyl] -N-toluenesulfonamide (compound number 973) The reaction was carried out according to the method of Example 9. And refined, you can get the object. MS (APCI, m / z): 546 (Μ + 1) + · HPLC (reverse phase): Rt. (Min) = 4.43 · Example 3 5 4- {1-[(6-chloro-5- Phenyl-2-aniline pyrimidin-4-yl) -hydrazinyl] -ethylbenzene N-toluenesulfonamide (compound number 976) was reacted and purified according to the method of Example 9 to obtain the target compound (30 mg , 59%) MS (APCI, m / z): 507 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 5.95. Example 3 6 (4-chloro-6- {N '-[1- (4-methanesulfonylphenyl) -ethylene] -hydrazinob 5-phenylpyrimidin-2-yl) -aniline ( Compound No. 977) was reacted and purified according to the method of Example 6 to obtain the target compound (40 mg, 8 2%). MS (APCI, m / z): 492 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 5.96. Example 3 7 N-Methyl-4- {l- [5-phenyl-2-aniline pyrimidin-4-ylbazirazinylethyl benzsulfonamide (compound No. 30 1) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (32 mg, 68%). 〇1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9.46 (s, 1H), 9.31 200524880 (s, 1H), 8.10 (s, 1H), 8.04 (d, 2H, J = 8.1 Hz), 7.72-7.65 (m, 4H), 7.49-7.46 (m, 4H), 7.41-7.37 (m, 1H), 7.29 (t, 2H, J = 7.6 Hz), 6.96 (t, 1H, J = 7.0 Hz), 2.41 (d? 3H, J = 4.9 Hz), 2.24 (s, 3H). MS (APCI, m / z): 47 3 (M + 1) +. HPLC (reverse phase): Rt. (min) = 3.94. Example 38 (4- {Ν '-[1- (4-methylsulfonylphenyl)) -Ethylene] -hydrazino} -5-phenylpyrimidin-2-yl) -aniline (Compound No. 157) The reaction and purification were carried out according to the method of Example 6, which can be quantitatively obtained. 〇1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9 · 4 7 (s, 1 Η), 9 · 3 4 (s, 1H), 8.17 d, 1H, J = 8.9 Hz), 8.10 (d, 1H, J = 4.3 Hz), 8.04 (d, 2H, J = 8.9 Hz), 7.85 (d, 2H, J = 8.6 Hz), 7.70 (d, 2H, J = 8.4 Hz), 7.49 ( d, 2H? J = 4.3 Hz), 7.42-7.39 (m? 1H), 7.31 (t, 2H, J = 7.0 Hz), 6.96 (t, 1H, J = 7.3 Hz), 3.24 (s, 3H), 2.25 (s, 3H) MS (APCI, m / z): 45 8 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 4.01. Example 3 9 N-methyl-4 -{1-[(6-Methylamino-5-phenyl-2-phenylaminopyrimidin-4-yl) -hydrazino] -ethylsulfenylsulfonamide (Compound No. 307) According to the method of Example 9 After reaction and purification, the target substance (30 mg, 60%) can be obtained. 200524880 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 8.91 (s, 1H), 8 2 ((s, 1H), 8.03 (d, 2H, J = 8.1 Hz), 7.65 (d, 2H, J = 8.6 Hz) 7.58-7.50 (m, 4H), 7.45-7.40 (m, 2H), 7.34-7.22 (m, 4H) 6.89 (t, 1H, J = 7.3 Hz), 5.76-5.51 (m, 1H ), 2.83 (d, 3H, = 4.6 Hz), 2.00 (s, 3H). MS (APCI, m / z): 502 (M + l) + · HPLC (reverse phase): Rt. (Min) = 4.07 Example 40 (4- {N '-[1- (4-Methanesulfonylphenyl) -ethylene] -hydrazinob 6-methylaminophenyl. 2-aniline (Compound No. 163) The reaction and purification in the method of Example 6 can quantitatively obtain the target substance MS (APCI, m / z): 487 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.14. Example 4 1 4- {l- (6-Amino-5-phenyl-2-aniline, pyridine-4-yl) -amidinoylethyl} -N-toluenesulfonamide (compound number 306) · according to the examples Reaction and purification according to the method of 9 to obtain the target compound (23 mg, 47%). 〇1H-NMR (270 MHz, DMSO-d6) 5 ppm: 8.86 (s, 1H), 8.34 (s, 1H), 8.02 (d, 2H), 7.65 (d, 2H), 7.58-7.49 (m, 4H), 7.3 9-7.3 3 (m, 2H), 7.24 (t, 2H, J = 7.6 Hz), 6.89 (t, 1H , J = 7.6 Hz), 5.58 (brs, 2H), 5.24 (brs, 1H), 2.40 (d, 3H, J = 4.9 Hz), 2.03 (s, 3H). -177- 200524880 MS (APCI, m / z): 488 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.87. Example 4 2 6-Amino- (4- {1 ^ '-[1- (4-methylsulfonylphenyl) ) -Ethylene] -hydrazino} _5_phenyl-2-aniline (Compound No. 16 2) was reacted and purified according to the method of Example 6 to obtain the target compound (16 mg, 34%). MS (APCI, m / z): 473 (M + l) +. HPLC (reversed phase) · Rt. (Min) = 3.84 · φ Example 4 3 4- (1-{[5- (2 -Bromophenyl) -2-anilinepyrimidin-4-yl] -amidinophenylethyl) -N-toluenesulfonamide (compound number 979) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (35 mg, 64%). MS (APCI, m / z): 551 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.38. Example 44 · 4- (l- {[5- (2-methoxybenzene Group) -2-anilinopyrimidin-4-yl] -hydrazinobethyltoluenesulfonamide (compound number 982) was reacted and purified according to the method of Example 9 to obtain the target compound (13 mg, 5 2%). MS (APCI, m / z): 503 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.98. Example 45 -178- 200524880 4- (l-{[5- (4- Fluorophenyl) -2-aniline chemidin-4-yl] -hydrazinophenylethyl) _n-toluenesulfonamide (compound number 98 5) The reaction and purification were carried out according to the method of Example 9 to obtain the target product ( 4 mg, 4 1%). MS (APCI, m / z): 491 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.13. Example 46 N -methyl-4-U -[(5-Phenyl-2 -anilino-6 -pyrrolidin-1 -yl-pyrimidin-4-yl) -hydrazinyl] -ethylbenzasulfonamide (compound number 869) φ according to the example The method 9 was used for reaction and purification to obtain the target compound (40 mg, 74%). MS (APCI, m / z): 542 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.73. Example 47 4- {1-[(6-Acetidine-butyl-5-phenyl-2-phenylamino-pyrimidin-4-yl -Hydrazinylethyl ethyl N-toluidine (compound No. 304) The reaction and purification according to the method of Example 9 to obtain the target compound (3 1 · mg, 58%) 〇1H-NMR (270 MHz, DMSO-d6) δ ppm: 9.00 (s, 1H), 8.07-8.04 (m, 3H), 7.82 (d, 2H, J = 8.4 Hz), 7.73 (d, 2H, J = 8.4 Hz), 7.52-7.41 (m, 6H), 7.25 (t, 2H, J = 7.6 Hz), 6.90 (t, 1H, t, 1H, J = 7.3 Hz), 3.63-3.57 (m, 4H), 2.41 (d, 3H, J = 4.9 Hz), 2.06-2.00 (m, 2H), 1.94 (s, 3H). MS (APCI, m / z): 528 (M + l) +. -179- 200524880 HPLC (reverse phase): Rt. (min) = 4.58. Example 4 8 4- {1-[(6- {3- [1- [4- (methylaminosulfonylphenyl) -ethylene-hydrazine group] _Qiridinyl group 5-Phenyl-2-anilino-pyrimidin-4-yl) -hydrazino] -ethyl tosylsulfonamide (Compound No. 1071) was reacted and purified according to the method of Example 9 to obtain the target substance (42 mg, 52%). MS (APCI, m / z): 809 (M + 1) +. HPLC (reversed phase) Rt. (Min) = 4.25 Lu Example 49 4- {1-[(6- {4- [ 1- (4-methylaminesulfonylphenyl) -ethylene-hydrazinocarbonylpiperidine-1-ylbu 5-phenyl-2-aniline-pyrimidine-cardio) -hydrazinobuethylethyl- Tosulamide (Compound No. 1070) was reacted and purified according to the method of Example 9 to obtain the target compound (28 mg, 3 5%). MS (APCI, m / z): 809 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 4.23 φ Example 5 0 4- {1-[(6-dimethylamino-5 -Phenyl-2-phenylaminopyrimidin-4 · yl) -fluorenyl] -ethyl} -N-toluenesulfonamide (compound number 87 5) The reaction was carried out and purified according to the method of Example 9 to obtain the target substance. (6 mg, 12%) 〇1H-NMR (270 MHz, DMSO-d6) δ ppm: 9.03 (s, 1H), 8.08-7.97 (m, 5H), 7.79 (d, 2H, J = 8.6 Hz ), 7.58-7.2 (m, 6H), -180-200524880 7.26 (t, 2H, J = 7.6 Hz), 6.91 (t, 1H), 7.3 Hz), 2.72 (s, 6H), 2.42 (d, 3H )? 1.88 (s, 3H). MS (APCI, m / z): 5 16 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 4.45. Example 5 1 N-methyl-4-([5-phenyl-2-aniline-6- (2-pyridine · 4-yl-ethylamino) -ne, pyridin-4-yl] -hydrazine Benzyl ethyl) -benzenesulfonamide (Compound No. 309) was reacted and purified according to the method of Example 9 to obtain the target %% (28 mg, 48%). ! H-NMR (270 MHz, DMSO-d6) 5 ppm: 8.91 (s, 1H)? 8.49-8.44 (m, 3H), 8.26 (s, 1H), 7.98 (d, 2H, J = 8.1 Hz), 7.54-7.19 (m, 11H), 6.91 (t, 1H, J = 7.3 Hz), 5.45 (s, 1H, J = 5.4 Hz), 3.63-3.56 (m, 2H), 2.8 8-2.8 2 (m 9 2H), 2.40 (d, 3H, J = 5.1 Hz), 2.01 (s, 3H). MS (APCI, m / z): 593 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.32 Example 5 2 4- [l-({6- [2- (2-hydroxyethoxy) -ethylamino] -5-phenyl-2-phenylaminopyrimidin-4-ylbuzidino) -Ethyl] toluidine (Compound No. 308) was reacted and purified according to the method of Example 9 to obtain the target compound (42 mg, 73%). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 8.92 (s, 1H), 8.30 (s, 1H), 8.00 (d, 2H, J = 7.6 Hz), 7.65 (d, 2H, J = 8.6 Hz), 7.56-7.50 (m, 2H), 7.46-7.41 (m, 2H), 7.35-7.32 (m, 2H), 200524880 7.25 (t, 2H, J = 7.6 Hz), 6.89 (t, 1H, J = 7.3 Hz), 5.37 (s, 1H), 4.54 (t, 1H, J = 5.1 Hz), 3.51-3.37 (m, 8H), 2.40 (d, 3H, J = 5. 1 Hz ), 2.02 (s, 3H). MS (APCI, m / z): 576 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.79 Example 5 3 N_methyl_4_ { Phenyl-2-anilino-6-pyrazol-1-yl-pyrimidin-4-yl) -hydrazinyl] -ethylbenzamide (Compound No. 302) The reaction was carried out according to the method of Example 9 and Refined to obtain the target compound (13 mg, 24%). 〇1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9.77 (s, 1H), 8.44 (s, lH), 8.13-7.99 (m, 5H) ), 7.82 (d, 2H, J = 8.9Hz), 7.52-7.28 (m, 9H), 7.00 (t, 1H, J = 7.3 Hz), 6.37-6.36 (m, 1H), 2.43 (d, 3H, J = 5.1 Hz), 2.00 (s, 3H). MS (APCI, m / z): 53 9 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 5.55 Example 54 4- { 1-[(6-Cyclopropylamino-5-phenyl-2-phenylaminopyrimidin-4-yl) -hydrazino] -ethyl N_Tosulamide (Compound No. 988) was reacted and purified according to the method of Example 9 to obtain the target compound (8 mg, 53%). ^ -NMRiSOO MHz, DMSO-d6) (5 ppm: 8.15- 8.11 (m, 1H), 7.96-7.86 (m, 3H), 7.82-7.75 (m, 2H), 7.74-7.64 (m, 2H), 7.60-7.53 (m, 3H), 7.53-7.46 (m, 2H ), 7.42-7.30 (m, 4H), -182- 200524880 7.12-7.05 (m, 1H), 2.87-2.80 (m, 1H), 2.42 (d, 3H, J = 5.0 Hz), 2.12 (s, 3H ), 0.79-0.73 (m? 2H)? 0.62-0.56 (m, 2H). MS (APCI, m / z): 528 (M + l) + · HPLC (reverse phase): Rt. (Min) = 4.23 Example 5 5 4-Π-({6- [2- (3Η-imidazol-4-yl) -ethylaminophenyl-2-phenylaminopyrimidin-4-ylpyrazino) -ethyl] -N -Tosylate (Compound No. 991) was reacted and purified according to the method of Example 9 to obtain the target compound (15 mg, 26%). MS (APCI, m / z): 582 (M + 1) + · HPLC (reverse phase): Rt. (Min) = 3.14. Example 5 6 4- (1-{[6- (2-Hydroxyethylamino) -5-phenyl-2-phenylaminopyrimidin-4-yl] -hydrazino} -ethyl) -N-toluenesulfonate Amidine (compound number 994) was reacted and purified according to the method of Example 9 to obtain the target compound (35 mg, 6 6%). MS (APCI, m / z): 532 (M + 1) +. HPLC (Reverse phase): Rt. (Min) = 3.79 Example 5 7 4- (1-{[6- (2-dimethylamineethylamino) -5-phenyl-2-anilinepyridine-4- Group] -hydrazinylethyl) -N · toluenesulfonamide (compound number 997) was reacted and purified according to the method of Example 9 to obtain the target compound (13 mg, 23%). MS (APCI, m / z): 559 (M + l) +. 200524880 HPLC (reverse phase): Rt. (min) = 3.07 Example 5 8 4- (l-{[6- (2-methoxyethylamino) -5 -Phenyl-2-aniline pyrimidine-alkylideneethyl) -N-toluenesulfonamide (compound number 881) was reacted and purified according to the method of Example 9 to obtain the target substance ° MS (APCI, m / z) : 546 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.19 Example 5 9 (4- {N, Π- (4-Methanesulfonylphenyl) -ethylene] -hydrazine Benzyl 5-phenyl_6-pyrene ratio 11 D each · Benzyl-pyrimidin-2-yl) -aniline (compound number 873) The reaction and purification in the method of Example 6 can be performed to determine the target @% 〇1H-NMR (270 MHz, DMSO-d6) 5 ppm: 8 · 9 5 (s, 1 H), 8 · 1 8 (d, 2H, J = 8.6 Hz), 8.09-7.91 (m, 5H), 7.81 (s, 1H), 7.55_ y-7 2 7.41 (m, 4H), 7.27 (t, 2H, J = 7.7 Hz), 6.90 (t, 1H? / ¾ port, 1.72-

Hz), 3. 24 (s, 3H), 3. 15-3. 05 (m, 4H), 1. 84 (s, # 1. 63 (m, 4H).  MS (APCI, m / z): 527 (M-fl) +.  HPLC (reverse phase): Rt. (min) = 4. 68 Example 60 (6-Acetidine-1-yl-4- {N, [1- (4-Methanesulfonylphenyl) -Ethylene Propylene Phosphate} phenyl-pyrimidin-2-yl)- Aniline (Compound No. 160) was reacted and purified according to the method of Example 6 to obtain mesh @% (mg, 65%). -184-200524880 MS (APCI? M / z): 513 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 50. Example 6 1 (6- {N,-[l- (4-Methanesulfonylphenyl) -ethylidene] -hydrazinob 5-phenylbenzylpyrimidin-4-yl) -piperidine-3 -Carboxylic acid [1- (4-methanesulfonylphenyl) _ethylene dimerase cake (Compound No. 1073) The reaction and purification were carried out according to the method of Example 6 to obtain @@ (34 mg, 44%) . MS (APCI, m / z): 779 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 20 Example 62 1- (4-Methanesulfonylphenyl) -ethylidene] -hydrazinob 5-phenylbenzylpyrimidin-4-yl) -piperidine-4-carboxylic acid [1- ( 4-Methanesulfonylphenyl) -Ethylenediamine (Compound No. 1072) was reacted and purified according to the method of Example 6 to obtain the target% (57 mg, 73%). MS (APCI, m / z): 779 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.20 Example 63 (6-Dimethylamino-4- {N, [l- (4-methylsulfonylphenyl) -ethylenesulfenyl} -5-phenyl-pyrimidine-2 -Yl) -aniline (compound number 879) was reacted and purified according to the method of Example 6 to obtain the target compound (24 mg, 48%). 〇1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 07 (s, 1H), 8 * 52 200524880 (s, lH), 8. 07-8. 02 (m, 4H), 7. 94 (d, 2H, J: = 8. 7Hz), 7. 61-7. 52 (m, 2H), 7. 48-7. 40 (m, 3H), 7. 28 (t, 2H, J = 7 · 8 HZ) ’6. 92 (t, 1H, J = 7. 3 Hz), 3. 25 (s, 3H), 2. 73 (s, 6H), l · 90 (S ’3H).  MS (APCI, m / z): 501 (M + l) + · HPLC (reverse phase): Rt. (min) = 4.42 Example 64 [4- {川 [1- (4-methylsulfonylphenyl) -ethylidene] -fluorenyl 5-phenyl-6- (2__ 了 _ 4- -Ethylamino) -pyrimidin-2-yl] -aniline (Compound No. 165) was reacted and purified according to the method of Example 6 to obtain the target compound (39 mg, 67%). MS (APCI, m / z): 578 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 3. 29 Example 65 2- [2- (6- {1 ^, [1- (4-Methanesulfonylphenyl) -ethylidene] -hydrazinob 5-phenyl-2-anilinopyrimidin-4-yl Amine) -ethoxy] -ethanol (compound No. 164) was reacted and purified according to the method of Example 6 to obtain the desired product. MS (APCI, m / z): 561 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 76 Example 6 6 4- {l-[(6-imidazol-1-yl-5-phenyl-2-phenylpyrimidinyl) -hydrazino] -ethylbenzene N-tosylsulfonamide (compound number 303 ) Perform the reaction and purification according to the method of Example 9 to obtain the target substance (37 mg, 69%). -186- 200524880 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 76 (s, 1H), 8. 58 (s, 1H), 8. 05 (d, 2H, J = 8. 1 Hz), 7. 95 (d, 2H, J = 8. 6 Hz), 7. 80 (d, 2H, J = 8. 4 Hz), 7. 61 (s, 1H), 7. 54-7. 48 (m, 4H), 7. 46-7. 39 (m, 2H), 7. 33 (t, 2H, J = 7. 6 Hz), 7. 04-6. 98 (m, 2H), 6. 86 (s, 1H), 2. 43 (d, 3H, J = 4. 3 Hz), 2. 05 (s, 3H).  MS (APCI, m / z): 539 (M + l) + · HPLC (reverse phase): Rt. (min) = 3. 94 Example 67 (6- [2- (3H-imidazol-4-yl) -ethylamino] -4- {N '[l- (4-methylsulfonylphenyl) -ethylene] -hydrazino The 5-phenyl-pyrimidin-2-yl) -aniline (compound No. 992) was reacted and purified according to the method of Example 6 to obtain the target substance. MS (APCI, m / z): 567 (M + 1) +.  HPLC (reverse phase) · Rt. (min) = 3.13 Example 6 8 2- (6- {N '-[1- (4-Methanesulfonylphenyl) -ethylene] -hydrazinob 5-phenyl-2-aniline pyrimidine 4-ylamino) -ethanol (compound number 995) was reacted and purified according to the method of Example 6 to obtain the target compound (45 mg, 8 7%). MS (APCI, m / z): 517 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 76 Example 6 9 (6- (2-Dimethylamineethylamino) -4- {N '[1- (4-methylsulfonylphenyl) -ethylene L · hydrazine 5-phenyl- Pyrimidin-2-yl) -aniline (Compound No. 998) was reacted and purified according to the method of Example 6 to obtain the desired product. 200524880 MS (APCI, m / z): 544 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 06 Example 7 0 (6- (2-methoxyethylamino) -4- {fT [l- (4-methylsulfonylphenyl) -ethylene L · hydrazine 5-phenyl-pyrimidine- 2-yl) -aniline (compound No. 885) was reacted and purified according to the method of Example 6 to obtain the target substance. ! Η-NMK (270 MHz, DMSO-d6) δ ppm: 8. 93 (s, 1H), 8. 33 (s, 1H), 8. 00 (d, 2H, J = 7.8 Hz), 7.80 (d, 2H, J = 8. 6 Hz), 7. 59-7. 42 (m, 5H), 7. 34-7. 23 (m, 4H), 6. 90 (t, IH, J = 7.4 Hz), 5. 35 (t, 1H, J = 5. 5 Hz), 3. 55-3. 35 (m, 4H), 3. 22 (s, 6H), 2. 03 (s, 3H) MS (APCI, m / z): 531 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 12. Example 7 1 2-Anilino-6- [l, 2,3] triazol-1-yl-pyrimidin-4-yl) -hydrazinylethylethylbenzsulfonamide, and N-methyl-4- {l-[(5-phenyl-2-aniline-6- [1,2,3] triazol-2-yl-pyrimidin-4-yl) -hydrazinyl ethyl ethyl benzylsulfonamide (compound number 1 006) The reaction and purification are performed according to the method of Example 9 to obtain a mixture of the target substance (5 mg, 9%) and regioisomers. MS (APCI, m / z): 540 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 74 Example 7 2 N -Methyl-4 · {1-[(5-phenyl-2-aniline-6- [l, 2,4] triazol-1-yl-pyrimidine- 200524880 cardio)- Hydrazinyl] -ethylbenzylsulfonamide (Compound No. 1003), and N-methyl-4- {l-[(5-phenyl-2-aniline-6- [1,2,4] Triazol-4-yl-pyrimidin-4-yl) -hydrazinyl] -ethylbenzamide (compound number 1074) was reacted and purified according to the method of Example 9 to obtain the target compound (27 mg, 50%) and a mixture of regioisomers. MS (APCI, m / z): 540 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.66 Example 7 3 N-methyl-4- {1-[(2-phenylethylamino-5-phenylpyrimidin-4-yl) -hydrazino] -ethylbenzene Besysulfame (Compound No. 1009) was reacted and purified according to the method of Example 9 to obtain the target compound (40 mg, 80%). MS (APCI, m / z): 501 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.83 Example 74 N-methyl-4- (1- {[5-phenyl-2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -Pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 305) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (21 mg, 68%) ° 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 83 (brs, 1H), 8. 78 (s, 1H), 8. 57 (brs, 1H), 8. 67 (d, 2H, J = 6. 2 Hz), 8. 11 (s, 1H), 8. 10 (d, 2H, J = 7. 6 Hz), 8. 00 (d, 2H, J = 8. 6 Hz), 7. 82 (d, 2H, J = 8. 6 Hz), 7. 58 (d, 2H, J = 6. 2 Hz), 7. 51-7. 27 (m, 8H), 7. 02 (t, 1H, J = 7. 6 Hz), 2. 44 (s, 3H), 2. 04 200524880 (s, 3H).  MS (APCI, m / z): 616 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3.83 Example 7 5 4- (l-{[5- (2-fluorophenyl) -2-anilinepentadine-4-ylburazinyl} -ethyl) -N- Tosulamide (Compound No. 649) was reacted and purified according to the method of Example 9 to obtain the target compound (15 mg, 30%). 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9. 80 (brs, 1H) 5 9. 48 (s, 1H), 8. 08 (s, 1H), 7. 94 (d, 2H, J = 7. 8 Hz), 7. 57 (d, 2H, J = 8. 6 Hz), 7. 55-7. 22 (m, 8H), 7. 16 (t, 1H, J = 8. 6 Hz), 6. 97 (t, 1H, J = 7. 6 Hz), 2. 39 (d, 3H, J = 4. 9 Hz), 2. 28 (s, 3H).  MS (APCI, m / z): 491 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.24. Example 7 6 4- (l-{[5- (3- (Methoxyphenyl) -2-anilinopyridin-4-yl] -hydrazinophenylethyl) -N-toluenesulfonamide (Compound No. 887 ) The reaction and purification were carried out according to the method of Example 9, and the target compound (34 mg, 68%) was obtained. 〇1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 49 (brs, 1H), 9. 32 (brs, 1H), 8. 12 (s, 1H), 8. 05 (d, 2H, J = 8. 1 Hz), 7. 82-7. 70 (m, 4H), 7. 49 (q, 1H, J = 4. 9 Hz), 7. 40 (t, 1H, J = 8. 1 Hz), 7. 30 (t, 2H, J = 8. 1 Hz), 7. 08 (d, 2H, J = 8. 1 Hz), 6. 97 (t, -190- 200524880 2H, J = 7. 3 Hz), 3. 79 (s, 3H), 2. 42 (d, 3H, J = 4. 9 Hz), 2. 25 (s, 3H) · MS (APCI, m / z): 503 (M + 1) 'HPLC (reverse phase) · Rt. (min): = 4. 1 Example 77 4- (l- {[5- (2,6-dichlorophenyl) -2-anilinepyrimidin-4-yl] -hydrazinylethyl)-N-toluenesulfonamide (compound number 1012 ) The reaction and purification were carried out according to the method of Example 9 to obtain the target substance (8 mg, 48%). ❿ MS (APCI, m / z): 541 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 74 Example 7 8 4- (l- {[5- (2-Tolyl) -2-anilinopyrimidin-4-yl] -hydrazinobethylbenzenesulfonamide (Compound No. 325) According to the method of Example 9 After reaction and purification, the target compound (15 mg, 31%) can be obtained. 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9 · 47 (brs, 1 Η), Bu (s, 1H), 7.96 (s, 1H), 7. 95 (d, 2H, J = 7. 8 Hz), 7.57 (d, 2ί ′ ’J = 8.4 Hz), 7.45 (q, 1H, J = 4. 9 Hz), 7. 38-7. 22 (m, 7ll) ’6. 96 (t, 1H, 7.3 Hz), 2.39 (d, 3H, J = 4. 9 Hz), 2. 21 (s, 3H) ’2. 09 (s, 3H).  MS (APCI, m / z): 487 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 4. 12 Example 7 9 -191-200524880 N-methyl-4- {l-[(5-naphthalen-1-yl-2-anilino-pyrimidin_4_yl) _hydrazinylethylsulfenylsulfonium The amine (compound number 891) was reacted and purified according to the method of Example 9 to obtain the target compound (33 mg, 59%). 1H-NMR (270 MHz, DMSO-d6) d ppm: 9. 47 (brs, lH), 9. 37 (brs, 1H), 8. 08 (s, 1H), 8. 05-7. 93 (m, 4H), 7. 67-7. 57 (m, 2H), 7. 5 Bu 7. 42 (m, 6H), 7. 31 (t, 2H, J = 7. 3 Hz), 7. 06-6. 93 (m, 2H), 6. 97 (t, 1H, J = 7. 3 Hz), 2. 36 (brs, 3H), 2. 01 (brs, 3H).  MS (APCI, m / z): 523 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.33 Example 80 4- {l-[(5-Biphenyl-4-yl-2-anilino-pyrimidin-4-yl) -hydrazinyl L · ethylbenzene N-toluene Sulfonamide (compound number 1015) was reacted and purified according to the method of Example 9 to obtain the target compound (45 mg, 72%). MS (APCI, m / z): 549 (M + 1) +.  Call HPLC (reverse phase): Rt. (min) = 4. 75. Example 8 1 4- {l-[(5-Benzo [1,3] bisomaro. Sulfonamide (compound number 793) was reacted and purified according to the method of Example 9 to obtain the target substance. MS (APCI, m / z): 517 (M + 1) 'HPLC (reverse phase): Rt. (min) = 3. 97 -192- 200524880 Example 8 2 4-{1-[(5 -Biphenyl-3 -yl-2 -anilino-pyrimidin-4 -yl) -hydrazinyl] -ethyl N- Tosulamide (Compound No. 8 9 5) was reacted and purified according to the method of Example 9 to obtain the target compound (27 mg, 49%). H-NMR (270 MHz, DMSO-d6) 5 ppm: 9 . 48 (s, 1H), 8. 21 (s, lH), 8. 04 (d, 2H, J = 7. 8Hz), 7. 71-7. 65 (m, 9H), 7. 59-7 · 27 (m, 8H), 6.96 (t, 1H, J = 7. 3 Hz), 2. 37 (d, 3H, J = 4.9 Hz), 2. 26 (s, 3H).  MS (APCI, m / z): 549 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 77 Example 8 3 N- (2-hydroxyethyl) -4- {1-[(5-phenyl-2-anilino-pyrimidin-4-yl) -hydrazino] -ethylbenzylsulfonium Amine (compound number 1066) The 4-hydrazino-5-phenyl-2-aniline pyrimidine (0.1 1 mmol) was dissolved in ethanol (1 ml), 4-ethylammonium-N- (2-hydroxyethyl) -benzenesulfonamide (73 mg, 0. 3 mmol) and stirred for 18 hours. The precipitated solid was pulverized and filtered to obtain the target substance (44 mg, 88%). MS (APCI, m / z): 503 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 3. 69 Example 84 4- {1-[(5-Phenyl-2-anilino-pyrimidin-4-yl) -hydrazino] -ethylbenzene N-propanesulfonamide (Compound No. 1068) The hydrazino-5-phenyl-2-aniline pyrimidine (0.1 1 200524880 mmol) was dissolved in ethanol (1 ml), and isethionyl-N-propanesulfonamide (72 mg, 0. 3 mmol) and stirred for 18 hours. The precipitated solid was pulverized and filtered to obtain the target substance (43 mg, 86%). MS (APCI, m / z): 501 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 41 Example 8 5 N-Methyl-4- (l-{[2-aniline-5- (5-phenylpyridin-3-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzene Sulfonamide (compound number 1018) was reacted and purified according to the method of Example 9 to obtain the target compound (36 φ mg, 65%). MS (APCI, m / z): 550 (M + 1) + · HPLC (reverse phase): Rt. (min) = 4. 19. Example δ Ν- (2-hydroxyethyl) -4- (Bu {[2-anilino-5- (5-phenylpyridin-3-ylpyrimidin_4-ylpyrazidinobuethyl) -benzenesulfon Amidine (compound number 1067) was reacted and purified according to the method of Example 83 to obtain the target compound (41 mg, 71%). MS (APCI, m / z): 580 (M + l) +.  Η PLC (reverse phase): R t · (mi η) = 3 · 8 6 Example 87 4- (l- {[5- (2-fluorophenyl) -2-anilino-6- (4-pyridine -4-yl-pyrazole-butyl) _pyrimidin-4-yl] -hydrazinophenylethyl) -N-tosylsulfonamide (compound number 653) The reaction and purification according to the method of Example 9 can be obtained (37 -194- 200524880 mg, 73%) H-NMR (270 MHz, DMSO-d6) 5 ppm: 9. 86 (s, 1H), 8. 95 (brs, 1H), 8. 93 (s, 1H), 8. 53 (d, 2H, J =: 4. 5 Hz), 8. 11 (s, 1H), 8. 08-8. 02 (m, 2H), 8. 87-8. 80 (m, 2H), 7. 77 (d, 2H, J = 8. 0 Hz), 7. 62 (d, 2H, J = 4. 5 Hz), 7. 55-7. 50 (m > 1H), 7. 47-7. 37 (m, 2H), 7. 32 (t, 2H, J = 8. 0 Hz), 7. 26 ^ 7. 18 (m, 2H), 7. 02 (t, 1H, J = 7. 0 Hz), 2. 43 (d, 3H, J = 4. 5 Hz), 2. 13 (s, 3H).  MS (APCI, m / z): 634 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 03 Example 8 8 N-Methyl-4- {l-[(2-aniline-5-m-methylbenzyl-D-A-4) -ylidene] -ethylbenzylsulfonamide (Compound No. 102 1) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (44 mg, 90%). MS (APCI, m / z): 487 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 4.37 Example 8 9 N-methyl-4- {1-[(2-anilino-5-p-tolylpyrimidin-4 · yl) -hydrazinyl ethyl ethyl benzylsulfonamide (Compound No. 899) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (44 mg, 90%). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 44 (brs, 1H), 9. 23 (brs, 1H), 8. 07 (s, 1H), 8. 05 (d, 2H, J = 7.3 Hz), 7. 73 (brs, 200524880 4H), 7. 49 (brs, 1H), 7. 38 (d, 2H, J = 8.1 Hz), 7. 29 (t, 2H, J = 7. 3 Hz), 7. 29 (d, 2H, J = 8. 1 Hz), 6. 96 (t, 1H, J = 7. 3 Hz), 2. 42 (s, 3H), 2. 37 (s, 3H), 2. 23 (s5 3H).  MS (APCI, m / z): 487 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 43 Example 90 4- (l- {[5- (3-Fluorophenyl) -2-anilinepyrimidin-4-yl] -hydrazinophenylethyl) -N-toluenesulfonamide (compound number 903) The method of Example 9 was reacted and purified to obtain the target compound (15 φ mg, 50%). W-NMR ^ O MHz, DMSO-d6) 5 ppm: 9. 50 (brs, 1H), 9. 50 (brs, 1H), 8. 12 (s, 1H), 8. 02 (d, 2H, J = 8. 1 Hz), 7. 73 -7. 60 (m, 4H), 7. 53-7. 45 (m, 2H), 7. 35-7. 7. 23 (m, 4H), 7. 22-7. 13 (m, 1H), 6. 96 (t, 1H, J = 7. 3Hz), 2. 41 (s, 3H), 2. 28 (s, 3H).  MS (APCI, m / z): 491 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. twenty three. Example 9 1 N-Methyl-4- (l-{[2-anilino-6- (4-pyridin-4-yl-pyrazol-1-ylfluoren-3-yl-pyrimidin-4- Glyphosazidinylethyl) -benzenesulfonamide (Compound No. ^ 3 17) was reacted and purified according to the method of Example 9 to obtain the target compound 1 (57 mg, 67%). ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 9 · 8 3 (s, 1 Η), 8 · -196- 200524880 (s, 1H), 8. 72 (s, 1H), 8. 52 (dd, 2H, J 2 1.6 Hz, 4. 5 Hz), 8. 18 (s? 1H)? 8. 11-8. 05 (m5 4H)? 7. 84 (d, 2H, J = 8. 7 Hz), 7. 66-7. 62 (m, 2H), 7. 59 (dd, 2H, J = 1. 6 Hz, 4. 5 Hz), 7. 55-7. 47 (m, 1H), 7. 33 (t, 2H, J 2 7. 9 Hz), 7. 02 (d, 1H, J = 7. 4 Hz), 6. 97 (dd, 1H, J = 1. 6 Hz, 4. 5 Hz), 2. 43 (d, 3H, J = 4. 3 Hz), 2. 12 (s, 3H).  MS (APCI, m / z): 622 (M + l) + · HPLC (reverse phase): Rt. (min) = 3. 82 Example 9 2 4- (l-{[5- [3- (4-fluorophenoxy) -phenyl] -2-anilino-6- (4-pyridin-4-yl-pyrazole-1 -Yl) -pyrimidin-4-ylbazirazinobethyl) -N-tosylsulfonamide (compound 5 tiger code 10 3 6) was reacted and purified according to the method of Example 9 to obtain the target compound (33 mg , 51%). MS (APCI, m / z): 726 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 40 Example 9 3 4- (l- {[2- (5-fluoro-2-tolylamino) -5-phenyl-6- (4-pyridin-4-yl-pyrazol-1-yl) -Pyrimidin-4-yl] -hydrazinylethyl) -N-tosylsulfonamide (compound number 401) was reacted and purified according to the method of Example 9 to obtain the target compound (45 mg, 60%). MS (APCI, m / z): 648 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 11 200524880 Example 94 4- (1-{[5_Benz [1,3] bisBfclocene-2-anilino-6- (4-pyridin-4-yl-pyrazole-butyl) -pyrimidine- 4-yl] -hydrazinylethyl) -N-toluenesulfonamide (compound number 797) was reacted and purified according to the method of Example 9 to obtain the target compound (15 mg, 41%). MS (APCI, m / z): 660 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3.84 Example 9 5 4- (1-{[5- (2,3-dihydrobenzo [1,4] disoying-6-yl) -2-anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -N-tosylsulfonamide (Compound No. 103) The method according to Example 9 After reaction and purification, the target substance (36 mg, 54%) was obtained. MS (APCI, m / z): 674 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.91. Example 96 N-Methyl-4- {1-[(2-aniline-6-pyrazol-1-yl-5-o-toluidine 棊 D 定 -4_yl) -fluorenylene] -ethyl Tolsulfenamide (compound number 326) was reacted and purified according to the method of Example 9 to obtain the target compound (16 mg, 47%). ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 8. 06-7. 8 3 (m, 8H), 7. 48-7. 32 (m, 8H), 7. 12-7. 06 (m, 1H), 6. 29-6. 27 (melon ’1H), 4. 35-4. 31 (m, 1H), 2. 67 (d, 3H, J = 5.4 Hz), 2.06 (s, 3H), -198- 200524880 1. 87 (s, 3H).  MS (APCI, m / z): 553 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 5. 65 Example 9 7 N-Methyl-4- (1-([2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-o-tolylpyrimidine-4 -Yl] -hydrazinylethyl) -benzenesulfonamide (compound number 329) was reacted and purified according to the method of Example 9 to obtain the target compound (7 mg, 19%). NMR (270 MHz, DMSO-d6) (5 ppm: 8 · 5 6 (brs, 3 Η), 7. 99-7. 81 (m, 8H), 7. 48-7. 26 (m, 9H), 7. 14-7. 12 (m, 1H), 4. 57 (m, 1H), 2. 67-2. 65 (m, 3H), 2. 11 (s, 3H)? 1. 88 (s, 3H).  MS (APCI, m / z): 630 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 4. 18 Example 98 N-methyl-4- (1- {[5- (4-Methanesulfonylphenyl) -2-anilinopyrimidin-4-yl] -hydrazinophenylethyl) -benzenesulfonamide 90.7) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (41 mg, 80%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 9. 49 (brs, 1H), 9. 40 (brs, 1H), 8. 08 (s, 1H), 8. 02 (d, 2H, J = 8. 1 Hz), 7. 75-7. 63 (m, 4H), 7. 49 (q, 1H, J = 4. 6 Hz), 7. 48-7. 25 (m, 5H), 6. 97 (t, 1H, J = 7. 3 Hz), 3. 33 (s, 3H), 2. 42 (d, 3H, J = 4. 6 Hz), 2. 27 (s, 3H).  200524880 MS (APCI, m / z): 519 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.25 Example 9 9 N-Methyl-4- (1-{[2-aniline group 3-trifluorotolyl) -pyrimidin-4-yl: 1-hydrazinyl ethyl -Benzamide (Compound No. 1024) was reacted and purified according to the method of Example 9 to obtain the target compound (49 mg, 90%). MS (APCI, m / z): 541 (M + 1) + · HPLC (reverse phase): Rt. (min) = 4. 64 Example 100 4- (l-{[5- (2-Chlorophenyl) -2-anilinepyrimidin-4-yl] -hydrazinylethyl) -N-toluenesulfonamide (compound number 9 1 1) The reaction and purification were performed according to the method of Example 9 to obtain the target substance (30 mg, 60%). ! Η-NMK (270 MHz, DMSO-d6) δ ppm: 9. 83 (brs, 1H), 9. 43 (s, 1H), 7. 93 (d, 2H, J = 7. 8 Hz), 7. 54-7. 27 (m, 9H), 7. 17-7. 14 (m, 2H), 6. 96 (t, 1H, J = 7. 2 Hz), 2. 39 (d, 3H, J = 4. 9 Hz), 2. 27 (s, 3H).  MS (APCI, m / z): 507 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 32. Example 1 〇1 N-methyl-4- (l-{[2-anilino-5- (2-trifluorophenyl) _pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 1027) The reaction was performed and purified according to the method of Example 9 to obtain the target compound (49 -200- 200524880 mg, 9 1%). MS (APCI, m / z): 541 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 4. 46 Example 102 N-methyl-4- {l-[(5-phenylpyrimidin-4-yl) -hydrazinyl] -ethylbenzasulfonamide (Compound No. 1039) According to Example 9 The method was reacted and refined to obtain the target substance (5 mg, 50%). MS (APCI, m / z): 382 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.37 Example 103 5-phenyl-2-anilino-4- [N '-(1-pyridin-4-yl-ethylene) -hydrazino; l · pyrimidine (Compound No. 13 ) The reaction and purification were carried out according to the method of Example 1 to obtain the target substance (916 mg, 93%). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 48 (s, 1H), 9. 37 (s, 1H), 8. 52 (d, 2H, J = 5. 9 Hz), 8. 04 (d, 2H, J = 8. 1 Hz), 7. 49-7. 27 (m, 9H), 6. 98-6. 93 (m, 1H), 2. 21 (s, 3H).  MS (APCI, m / z): 381 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 47 Example 104 4- (1- {[2- (5-Fluoro-2-tolylamino) -6-pyrazole-butyl-pyrimidin-4-yl] -hydrazinylethyl) -N-toluene Amidine (compound number 386) was reacted and purified according to the method of Example 9 to obtain the target compound (12 -201-200524880 mg, 12%). MS (APCI, m / z): 495 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5.39 Example 105 4- (1 [2- (2-methoxyanilino) -5-phenyl-pyrimidinyl; l.amidinolide ethyl) _N_tosylsulfonamide (compound number 1042) The reaction and purification were performed according to the method of Example 9 to obtain the target compound (63 mg, 84%). MS (APCI, m / z): 503 (M + 1) + · HPLC (reverse phase): Rt. (min) = 4. 10. Example 106 4- (1- {[2- (2,3-Dihydroindole-1 · yl) -5-phenyl-pyrimidin-4-yl] -hydrazinylethyl) -N-toluenesulfonium The amine (compound number 927) was reacted and purified according to the method of Example 9 to obtain the target compound (70 mg, 8 5%). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 36 (brs, 1H)? 8. 83 (d, 1H, J = 8. 2 Hz), 8. 17 (s, 1H), 7. 73 (s, 4H), 7. 54-7. 35 (m, 6H), 7. 26-7. 16 (m, 2H), 6. 94 (t, 1H, J = 7. 3 Hz), 4. 24 (t, 2H, J = 8. 9 Hz), 3. 19 (t, 2H, J = 8. 9 Hz), 2. 42 (s, 3H), 2. 26 (s, 3H).  MS (APCI, m / z): 499 (M + l) + · HPLC (reverse phase): Rt. (min) = 4. 64 Example 107 N_methyl_4_ {phenyl-2_pyridin-3_yl-pyrimidin-4-yl) _hydrazinylethyl-202- 200524880 glybensulfonamide (compound number 541) according to implementation The reaction of Example 9 was performed and purified to obtain the target compound (39 mg, 5 6%). ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 10. 11 (brs, 1H), 9. 59 (s, 1H), 8. 73-8. 71 (m, 2H), 8. 47 (s, 1H)? 7. 61-7. 45 (m, 8H), 7. 21 (d, 2H, J = 8. 6 Hz), 2. 38 (s, 3H), 2. 30 (s, 3H).  MS (APCI, m / z): 459 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 02 Example 108 4- {1-[(2,5-Diphenylpyrimidin-4-yl) -hydrazino] -ethylbenzene N-toluenesulfonamide (Compound No. 1045) According to the method of Example 9 After reaction and purification, the target compound (52 mg, 66%) was obtained. MS (APCI, m / z): 458 (M + 1) + · HPLC (reverse phase): Rt. (min) = 5. 00 Example 109 N-Methyl-4- {1-[(2-methyl-5-phenyl & pyridinyl-4-yl) -pienolidene] -ethyl} -benzenesulfonamide ( Compound No. 1048) It is reacted and purified according to the method of Example 9 to obtain the target substance. MS (APCI, m / z): 396 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 06 Example 1 1 〇4- (l- {[5- (2-fluoro-5-tolyl) -2-anilino-6-pyrazole-pyridyl-pyrimidin-4-ylpyridazinylethyl) -N-toluenesulfonamide (compound number 916) -203-200524880 The reaction and purification were performed according to the method of Example 9 to obtain the target compound (30 mg, 36%). ^ -NMR (270 MHz, DMSO-d6 ) (5 ppm: 9. 75 (s, 1H), 8. 68 (brs, 1H), 8. 30 (s, 1H), 8. 06-7. 78 (m, 7H), 7. 49-6. 98 (m, 7H), 6. 42-6. 41 (m, 1H), 2. 43 (s, 3H), 2. 30 (s, 3H), 2.08 (s, 3H), MS (APCI, m / z): 571 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5.82. Example 111 N-toluenesulfonamide (compound number 920) was reacted and purified according to the method of Example 9 to obtain the target compound (26 mg, 57%) ° 4-NMR (270 MHz, DMSO-d6) (5 ppm: 9. 74 (brs, 1H), 9. 17 (brs, 1H), 8. 34 (d, 1H, J = 2 · 6 Hz), 8. 01 (d, 2H, J = 8. 1 Hz), 7. 76 (s, 4H), 7. 58-7. 44 (m, 3H), 7. 36-7. 15 (m, 4H), 7. 04-6. 94 (m, 1H), 6. 42 (dd, 1H, J = 1. 7 Hz, 2. 5 Hz), 2. 43 (d, 3H, J = 4. 0 Hz), 2. 17 (s, 3H).  MS (APCI, m / z): 591 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5. 94 Example 1 1 2 4- (l- {[5- (2,3-Xylyl) -2-anilino-6-pyrazol-1-yl-pyrimidin-4-yl] -hydrazinylethyl ) -N-toluidine (Compound No. 924) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (30-204-200524880 mg, 39%). ] H-NMR (270 MHz, DMSO-d6) d p p m: 9 · 7 3 (b r s, 1 H), 8. 18-8. 13 (m, 2H), 8. 07 (d, 2H, J = 8. 1 Hz), 7. 96 (d, 2H, J = 8. 6 Hz), 7. 81 (d, 2H, J = 8. 6 Hz), 7. 54-7. 48 (m, 2H), 7. 33 (t, 2H, J = 8. 0 Hz), 7. 25-7. 13 (m, 2H), 7. 01 (q, 2H, J = 7. 3 Hz), 6. 38 (dd, 1H, J = 1. 7 Hz, 2. 5 Hz), 2. 43 (s, 3H), 2. 28 (s, 3H), 1. 94 (s, 3H), 1. 92 (s, 3H).  MS (APCI, m / z): 567 (M + l) + · HPLC (reverse phase): Rt. (min) = 6. 04 Example 1 -Pyrimidin-4-yl] -amidinophenylethyl) -N-toluenesulfonamide (compound No. 1 03 3) was reacted and purified according to the method of Example 9 to obtain the target compound (12 mg, 27%) . MS (APCI, m / z): 59 7 (Μ + 1) + · HPLC (reversed phase) · Rt. (min) = 5.25 Example 1 1 4 4- (1-{[2- (2-fluoroaniline) -5-phenylpyrimidin-4-yl] -hydrazinylethyl) -N-toluene Sulfonamide (compound number 935) was reacted and purified according to the method of Example 9 to obtain the target compound (10 mg, 31%). ^ -NMR (270 MHz, DMSO-d6) δ ppm: 9. 39 (brs, 1H), 8. 68 (brs, 1H), 8. 28 (t, 1H, J = 7. 9 Hz), 8. 06 (s, 1H), 7. 64 (d, 200524880 2H, J = 8. 6 Hz), 7. 53-7. 34 (m, 8H), 7. 29-7. 05 (m, 3H), 2. 40 (s, 3H), 2. 22 (s, 3H).  MS (APCI, m / z): 491 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.30 Example 1 1 5 4- (1-{[2- (2-ethoxyanilyl) -5-phenylpyrimidin-4-yl] -hydrazinylethyl) tosylsulfonium Amine (compound No. 1051) was reacted and purified according to the method of Example 9 to obtain the target substance. MS (APCI, m / z): 517 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 29. Example 11 Amine (compound number 3W) was reacted and purified according to the method of Example 9 to obtain the target compound (14 mg, 42%). ^ -NMR (270 MHz, DMSO-d6) S ppm: 9. 68 (brs, 1H), 9. 43 (brs, 1H), 9. 11 (d, 1H, J = 2. 3 Hz), 8. 55 (d, 1H, J = 8. 7 Hz), 8. 18 (dd, 1H, J = 1. 3 Hz, 4. 6 Hz), 8. 12 (s, 1H), 7. 69 (d, 2H, J = 8. 6 Hz), 7. 62 (d, 2H, J = 8. 6 Hz), 7. 48 (d, 4H, J = 4. 5 Hz), 7. 42-7. 28 (m, 3H), 2. 41 (s, 3H), 2. 25 (s, 3H) MS (APCI, m / z): 474 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.40 Example 1 1 7 N-methyl-4- {1-[(5-phenyl-2-o-toluidinepyrimidin-4-yl) -hydrazinyl] • ethane-206 -200524880 Gibendazole (Compound No. 1 054) was reacted and purified according to the method of Example 9. 1 The target substance (22 mg, 6 5%) was obtained. MS (APCI, m / z): 487 ( M + 1) +.  HPLC (reverse phase): Rt. (min) = 3. 83 Example 1 1 8 5_phenyl_4_ [NM bu bian_4_yl-ethylidene) _Pyrimidine (Compound No. 1041) According to the method of Example 1, the reaction and purification can be obtained. Target substance (12 mg, 41%). MS (APCI, m / z): 290 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.62 Example 1 1 9 (4- {1-[(5-Phenyl-2-anilino-pyridin-4-yl) -hydrazinyl] -ethylbenzylsulfonium Amine group) -acetic acid (Compound No. 943) The 4-hydrazino-5-phenyl-2-anilidine (0.01 1 mmol) was dissolved in ethanol (1 ml), (4-ethylamidinesulfonylamino) -acetic acid (77 mg, 0.3 mmol) was added, and stirred for 18 hours. The precipitated solid was pulverized and filtered to obtain the target substance (44 mg, 85%). h-NMR (270 MHz, DMSO-d ^) δ ppm: 9. 46 (s, 1H), 9. 29 (s, 1H), 8.10 (s, 1H), 8. 04 (d, 2H, J = 7. 8 Hz), 7.72 (d, 2H, J = 8 · 6 H z), 7 · 6 7 (d, 2 H, J = 8 · 6 H z), 7 · 5 0-7 · 2 7 ( m, 7 H), 7. 06-6. 93 (m, 2H), 3. 58 (s, 2H), 2. 23 (s, 3H) MS (APCI, m / z): 517 (M + l) +.  -207- 200524880 HPLC (reversed phase): Rt. (min) = 3.75 Example 120 [4- (1- {[5-phenyl-2- (pyridin-3-ylamino) -pyrimidin-4 · yl] -hydrazinylethyl) -benzenesulfonate Amido] -acetic acid (Compound No. 949) was reacted and purified according to the method of Example 11 to obtain the target compound (17 mg, 62%). ! H-NMR (270 MHz, DMSO-d6) δ ppm: 9. 66 (s, 1H), 9. 38 (s, 1H), 9. 08 (d, 1H, J = 2. 5 Hz), 8. 54 (d, 1H, J = 8. 6 Hz), 8. 16 (dd, 1H, J = 1. 3 Hz, 4. 6 Hz), 8. 10 (s, 1H), 7. 70 (d, 2H, J = 8. 7 Hz), 7. 59 (d, 2H, J = 8. 4 Hz), 7. 47 (d, 4H, J = 4. 3 Hz), 7. 43-7. 28 (m, 3H), 3. 56 (s, 2H), 2. 23 (s, 3H).  MS (APCI, m / z): 518 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 29. Example 1 2 1 4- {1-[(5-Phenyl-2-anilino-pyrimidin-4-yl) -sulfinyl] -ethylbenzenebenzenesulfonate (Compound No. 1 069) Reference Example 2 ′ produced 'hydrazino-5-phenyl-2-aniline pyrimidine (0. 1 mmol) was dissolved in Ν, Ν-dimethylformamide, water (1: 1) mixed solvent (i ml), and 4-acetamidine sulfonic acid sodium salt (67 mg, 0. 3 mmol) and stirred for 18 hours. The precipitated solid is pulverized, and the object is obtained by filtration. MS (APCI, m / z): 482 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.12 Example 122 N-methyl-4- {1-[(2-anilino-6-pyrazol-butyl-5-thien-3-yl-pyrimidine-4- -208- 200524880))-hydrazino] -ethylbenzamide (compound No. 314) was reacted and purified according to the method of Example 9 to obtain the target compound (28 mg, 26%). MS (APCI, m / z): 545 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 5. 22 Example 123 4- (1- {[2- (5-Fluoro-2-tolylamino) -5-phenyl-6-pyrazole-pyridyl-pyrimidin-4-yl] -hydrazinyl [Ethyl) -N-tosulamide (Compound No. 398) was reacted and purified according to the method of Example 9 to obtain the target compound (35 mg, 47%). MS (APCI, m / z): 571 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 5. 81 Example 124 4-{[[2-Cyclohexylamino-5-anilinepyrimidin-4-yl) -hydrazino] -Ethyl N-tosylsulfonamide (Compound No. 1057) According to Example 9 The method was used for reaction and purification to obtain the target substance (45 mg, 54%). MS (APCI, m / z) · · 479 (Μ + 1) + · HPLC (reversed phase): Rt. (min) = 3.86 Example 125 5-phenyl-2-aniline-4- [N, (1-pyridin-4-yl-ethylene) -hydrazino] -6- (4-pyridine The 4--4-yl-pyrazol-1-yl) -pyrimidine (compound number 17) was reacted and purified according to the method of Example 1 to obtain the target compound (48 mg, 92%). -209- 200524880 JH-NMR (270 MHz, DMSO-d6) 5 ppm: 9. 85 (s, 1H), 8. 78 (s, 1H), 8. 65 (d, 2H, J = 5. 9 Hz), 8. 60 (s, 1H), 8. 52 (d, 2H, 5. 9 Hz), 8. 11-8. 09 (m, 3H), 7. 74 (d, 2H? J = 5. 9 Hz), 7. 58 (d, 2H, J = 5. 9 Hz)? 7. 47-7. 32 (m, 7H), 7. 01 (t, 1H? J = 7. 0 Hz), 2. 00 (s, 3H).  MS (APCI, m / z): 524 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 15. Example 126 N-Methyl-4- {l-[(2-anilino-5-thien-3-yl-pyrimidin-4-yl) -hydrazinyl] -ethylbenzylsulfonamide (compound number 313) Perform the reaction and purification according to the method of Example 9 to obtain the target substance. ! H-NMR (270 MHz, DMSO-d6) 5 ppm: 9. 50 (s, 1H), 9. 25 (s, 1H), 8. 20 (s, 1H), 8. 07 (d, 2H, J = 8. 1 Hz), 7. 93 (d, 2H, J = 8. 1 Hz), 7. 81-7. 76 (m, 3H), 7. 72-7. 69 (m, 1H), 7. 51-7. 69 (m, 1H), 7. 52-7. 49 (m, 1H), 7. 36 (d, 1H, J = 4. 9 Hz), 7. 29 (t, 2H, J = 7. 8 Hz), 6. 96 (t, 1H, J = 7. 3 Hz), 2. 43 (d, 3H, J = 3. 5 Hz), 2. 30 (s, 3H).  MS (APCI, m / z): 479 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 98 Example 127 4- [N ·-[1- (4-Methanesulfonylphenyl) -ethylidene] -hydrazinob-2-anilino-5_thiophene-3-yl-pyrimidine (Compound No. 169) The reaction and purification were carried out according to the method of Example 6 to obtain the target substance. MS (APCI, m / z): 464 (M + 1) +.  -210- 200524880 HPLC (reversed phase): Rt. (min) = 4. 03 Example 1 2 8 2-Anilino-4- [N '-(pyridin-4-yl-ethylene) -hydrazino] -5-thien-3-yl-pyrimidine (Compound No. 25) The method of Example 1 was reacted and purified to obtain the target substance. MS (APCI, m / z): 3 87 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 43 Example 129 (4- {1-[(6-Imidazol-1-yl-5-phenyl-2-phenylpyrimidin-4-yl) -hydrazino] -ethylbenzylsulfonamido)- Acetic acid (Compound No. 945) · The reaction and purification were carried out according to the method of Example 119 to obtain the desired product. ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 9. 78 (s, 1H), 8. 56 (s, 1H), 8. 10-8. 04 (m, 3H), 7. 93 (d, 2H, J = 8. 1 Hz), 7. 82 (d, 2H, J = 8. 1 Hz), 7. 62 (s, 1H), 7. 56-7. 30 (m, 8H), 7. 04-6 · 98 (m, 3H), 6. 86 (s, 1H), 3. 61 (s, 2H), 2. 04 (s, 3H) MS (APCI, m / z): 583 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 61. Example 130 Sulfonamide (Compound No. 1060) was reacted and purified according to the method of Example 9 to obtain the target compound (20 mg, 59%). MS (APCI, m / z): 474 (M + 1) 'HPLC (reaction Phase): Rt. (min) = 4. 42. 200524880 Example 1 3 1 4- (1-{[5- (2-Chloro-6-fluorophenyl) -2-anilinepyrimidinylhydrazinobethyl) -N-toluidine (Compound No. 1) 63) The reaction and purification were carried out according to the method of Example 9 to obtain the target substance (18 mg, 56%). ^ -NMR (270 MHz, DMSO-d6) (5 ppm: 9. 95 (brs, 1H), 9. 47 (s, 1H), 8. 01 (s, 1H), 7. 92 (d, 2H, J = 7. 6 Hz), 7. 54 (d, 2H, J = 8. 4 Hz), 7. 43-7. 41 (m, 3H), 7. 33-7. 27 (m, 3H), 7. 14 (d, 2H, J = 7. 8 Hz), 6. 96 (t, 1H, J = 7. 3 Hz), 2. 39 (d, 3H, J = 4. 3 Hz), 2. 30 (s, 3H).  MS (APCI, m / z): 525 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 7 Example 132 N4- (2-Benzo [1,3] bisfluoren-5-yl-ethyl) -N2-phenyl-6- {N '-[l-pyridine-cardiyl-ethylidene ] -Amidinopyrimidine-2,4-diamine (Compound No. 10) was reacted and purified according to the method of Example 1 to obtain the desired product. MS (APCI, m / z): 468 (M + l) +.  Example 1 3 3 (4- (6,7-dimethoxy-3,4-dihydro-111-isoquinolin-2-yl) -6- {Chemized- [1-pyridin-4-yl- Ethylene] -hydrazino} -pyrimidin-2-yl) -phenyl-amine (compound No. 1 239) was reacted and purified according to the method of Example 1 to obtain the desired product. MS (APCI, m / z): 496 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 3. 82.  200524880 Example 134 N4- [2- (3,4-dimethoxy-phenyl) -ethylbenzene N, pyridin-3-yl-6- {N '-[1-pyridine_4-yl-ylidene Ethyl; l.hydrazinopyrimidine-2,4-diamine (compound number 59) was reacted and purified according to the method of Example 1 to obtain the target compound (4 mg, 80%). MS (APCI, m / z): 485 (M + 1) 'HPLC (reversed phase): Rt. (min) = 2. 81. Example 1 3 5 1 ^ 4- [2- (3,4-dimethoxy-phenyl) -ethyl] -5-methyl- > ^ 2-pyridin-3-yl-6- {Ν '-[Pyridine-4-yl-ethylene] -hydrazinopyrimidine-2,4-diamine (compound No. 1079) was reacted and purified according to the method of Example 1 to obtain the target compound (18 mg, 5 3%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 9. 04 (d, 1H, J = 2. 4 Hz), 8. 89 (s, 1H), 8.74 (s, 1H), 8. 61 (dd, 2H, J = 1. 6 Hz, 4. 6 Hz), 8. 55-8. 52 (m, 1H), 8. 07 (dd, 1H, J = 1. 6 Hz, 4. 6 Hz), 7. 7 8 (dd, 2H, J = 1. 6 Hz, 4. 6 Hz), 7. 24-7. 19 (m, 1H), 6. 90-6. 77 (m, 3H), 6. 51 (m, 1H), 3. 74 (d, 6H, J = 6. 2 Hz), 3. 60 (m, 2H), 2. 87-2. 81 (m, 2H), 2. 31 (s, 3H), 2. 03 (s, 3H).  MS (APCI, m / z): 499 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 83.  Example 1 3 6 N4- [2- (3,4-dimethoxy-phenyl) -ethylbenzene N2- (6-methoxy-pyridin-3-yl) -6- {N '-[ l-pyridyl-ethylenepyrazinylpyrimidine-2,4 · diamine (Chemical-213-200524880 Product No. 1 1 3 1) The reaction and purification were carried out according to the method of Example 1 to obtain the desired product. MS (APCI, m / z): 515 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 15.  Example 137 1- (3,4-dimethoxy-phenyl) -2- (2-anilino-6- {N '-[l-pyridin-4 · yl-ethylene] -hydrazinob Pyrimidin-4-ylamino) -ethanol (compound No. 1127) was reacted and purified according to the method of Example 1 to obtain the target compound (21 mg, 42%). ! H-NMR (500 MHz, DMSO-d6) δ ppm: 9. 51 (brs, 1Η), 8. 62-8. 57 (m, 3H), 7. 86 (d, 2H, J = 8. 5 Hz), 7. 74 (d, 2H, J = 4. 5 Hz), 7. 21 (t, 2H, J = 8. 5 Hz), 7. 00 (s, 1H), 6. 91 (s, 2H), 6. 86 (t, 1H, J = 8. 5 Hz), 6. 01 (brs, 1H), 5. 43 (brs, 1H), 4. 73-4. 67 (m, 1H), 3. 74 (s, 6H), 3. 72-3. 56 (m, 2H), 2. 30 (s, 3H).  MS (APCI, m / z): 500 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 94.  Example 138 4- [1-({6- [2- (3,4-Dimethoxy-phenyl) -2-hydroxyethylamino] -2-aniline-pyrimidin-4-ylbuya Hydrazine) -ethyl] -N-methyl-benzenesulfonamide (Compound No. 1125) was reacted and purified according to the method of Example 9 to obtain the target compound (45 mg, 7 6%). m / z): 592 (M + l) +.  -214- 200524880 HPLC (reversed phase): Rt. (min) = 3.71. Example 139 1- (3,4-monomethoxy-phenyl) -2- (6- {N '-[1- (4-methylfluorenyl-phenyl) -Ethylenehydrazineb 2-anilino-pyrimidinylamino) -ethanol (compound No. 1126) was reacted and purified according to the method of Example 6 to obtain the target compound (52 mg, 90%). MS (APCI, m / z): 577 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 71. φ Example 140 N2-Cyclopropyl " · N4- [2- (3,4 -monomethoxy-phenyl) -ethyl] -6- {Nf- [l-O-pyridin-4-yl -Ethylene] -hydrazinopyrimidine-2,4-diamine (Compound No. 1130) was reacted and purified according to the method of Example 1 to obtain the target compound (254 mg, 65%). MS (APCI, m / z): 448 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3.01.  Example 1 4 1 # Ν2-cyclopropyl-N4- [2- (3,4-dimethoxy-phenyl) -ethylmethanesulfonyl-phenyl) -ethylene] -hydrazine} -Pyrimidine-2,4-diamine (Compound No. 1 129) was reacted and purified according to the method of Example 6 to obtain the target compound (7 mg, 1%). MS (APCI, m / z): 525 (M + l) +.  HPLC (reverse phase): Rt. (min): = 3.77 · -215- 200524880 Example 142 4- [l-({2-Cyclopropylamino-6- [2- (3,4-dimethoxy-phenyl) -ethylamine [Methyl] -chryridin-4-ylbuazidinyl) -ethyl] -N-methyl-benzenesulfonamide (Compound No. 1128) was reacted and purified according to the method of Example 9 to obtain the target compound (46 mg, 8 5%) 〇MS (APCI, m / z): 540 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 82.  Example 143 4- (1-{[2- (5-Fluoro-2-methyl-anilino) -5-methyl-6-pyrazole-butyl-pyrimidin-4-yl] -hydrazinylethyl ) -N-methyl-benzenesulfonamide (Compound No. 1080) was reacted and purified according to the method of Example 9 to obtain the target compound (41 mg, 80%). MS (APCI, m / z): 509 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5. 48.  Example 144 N-Methyl-4- (l-{[5-phenyl-6-U than 1-sit-1-yl- than B-Ade-3-yl S female group) -pyridin-4-yl] -Hydrazinylethyl) -benzenesulfonamide (Compound No. 350) was reacted and purified according to the method of Example 9 to obtain the target compound (36 mg, 67%). O! -NMK (500 MHz, DMSO-d6 ) (5 ppm: 10. 01 (s, 1H), 9. 15 (s, 1H), 8. 62-8. 54 (m, 1H), 8.50 (brs, 1H), 8. 22 (d, 1H, J = 4. 5 Hz), 8. 11 (s, 1H), 7. 99 (d, 2H, J = 7. 5 Hz), 7. 82 (d, 2H, J = 8.0 Hz), 7. 55-7. 33 (m, 6H), 7. 30 (d, 2H, J = 8. 0 -216- 200524880 Ηζ), 6.37 (s, 1H), 2. 43 (d, 3H, J = 5 · 0 Ηζ), 2 · 01 (s, 3H) · MS (APCI, m / z): 540 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 75. Example 145 4- (l-{[2- (5-Fluoro-2-methyl-anilino) -6-imidazole-butyl-5-methyl-pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1 083) was reacted and purified according to the method of Example 9 to obtain the target compound (11 mg, 21%). MS (APCI, m / z): 509 (M + l) +.  # HPLC (reverse phase): Rt. (min) = 3. 58.  Example 146 4- (1-{[6-Imidazol-1-yl-5-phenyl-2- (pyridin-3-ylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N- Methyl benzsulfamide (Compound No. 351) was reacted and purified according to the method of Example 9 to obtain the target compound (28 mg, 52%). MS (APCI, m / z): 540 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 3.02. Example 147 4- {Bu [(6-imidazol-1-yl-2-o-tolylamino-pyrimidin-4-yl) -hydrazinyl] Ethyl Bu N _Methyl-toluenesulfonamide (compound number n35) was reacted and purified according to the method of Example 9 to obtain the target compound (34 mg, 71%). MS (APCI, m / z): 477 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.68-217-200524880 Example 148 N-methyl-4- {l-[(5-phenyl-6-pyrazol-1-yl-2-o-tolylamino-pyrimidine • 4-yl) -hydrazinoethylbenzamide (compound No. 1134) was reacted and purified according to the method of Example 9 to obtain the target compound (22 mg, 40%). ! Η-NMK (500 MHz, DMSO-d6) δ ppm: 8. 88 (s, 1H), B. 38 (brs, 1H), 8.02 (brs, 1H), 7. 84 (d, 2H, J = 8. 0 Hz), 7. 79 (d, 1H, J = 8. 0 Hz), 7. 74 (d, 2H, J = 8. 0 Hz), 7. 53-7. 48 (m, 1H), 7. 44-7. 38 (m, 3H), 7. 36 (t, 1H, J = 7. 5 Hz), 7. 28-7. 20 (m, 4H), 7. 09 (t, 1H, J = 7. 5 Hz), 6. 31 (s, 1H), 2. 41 (d, 3H, J = 4. 0 Hz), 2. 34 (s, 3H), 1. 95 (s, 3H).  MS (APCI, m / z): 553 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 5. 42.  Example 149 4- (l-{[2- (5-Fluoro-2-methyl-anilino) -6-imidazole-butyl-pyrimidinylpyrazino} -ethyl) methyl-benzenesulfonium The amine (compound number 3 87) was reacted and purified according to the method of Example 9 to obtain the target animal 1 (21 mg, 43%). MS (APCI, m / z): 495 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 86. Example 150 ^^ 4- (3,4-dimethoxybenzyl) * ^ 2-phenyl-6-{> ^ [1-pyridin-4-yl-methylene 2; yl] -hydrazinopyrimidine -2,4-Diamine (compound No. 1138) was reacted and purified according to the method of Example 1 to obtain the target compound (17 mg '-218- 200524880 3 6%). MS (APCI, m / z): 470 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 3. 41.  Example 1 5 1 N4- (3,4-Dimethoxyoctyl) -6- {N '-[l- (4-methylsulfonyl-phenyl) -ethylene] -hydrazine N2- Phenyl-pyrimidine-2,4-diamine (compound No. 1137) was reacted and purified according to the method of Example 6 to obtain the target compound (31 mg, 5 7%). MS (APCI, m / z): 547 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 4.07.  Example 152 4- (1- {[6- (3,4-Dimethoxybenzylamino) -2-anilino-pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfon Amidine (compound No. 1136) was reacted and purified according to the method of Example 9 to obtain the target compound (40 mg, 71%). MS (APCI, m / z): 562 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 03.  Example 1 5 3 N4- (3,4-dimethoxy-phenyl) -N2-phenyl-6- {N '-[l-pyridin-4-yl-ethylenepyrazinopyrimidine-2, 4-Diamine (compound No. 1141) was reacted and purified according to the method of Example 1 to obtain the target compound (20 mg, 44%). MS (APCI, m / z): 456 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 21 · 219-200524880 Example 154 N4- (3,4-dimethoxy-phenyl) -6- {N '-[1- (4, methanesulfonyl-phenyl) -ethylene] -Hydrazine N2-phenyl-pyrimidine-2,4-diamine (Compound No. 114) was reacted and purified according to the method of Example 6 to obtain the target compound (12 mg, 23%). MS (APCI, m / z): 53 3 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 14. Example 155 4- (l- {[6- (3,4-Dimethoxy-anilino) -2-anilino-pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzene Sulfonamide (compound number 1139) was reacted and purified according to the method of Example 9 to obtain the target compound (21 mg, 38%). MS (APCI, m / z): 548 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 4. 04.  Example 156 (4- [2- (3,4-Dimethoxy · phenyl) -ethoxy group 6. {N, _ [fluorene-pyridin-4-yl-ethylidene] -hydrazine group Pyrimidin-2-yl) -phenyl-amine (compound number 1144) was reacted and purified according to the method of Example 1 to obtain the target compound (21 mg, 43%) ° -NMRCSOO MHz, DMSO-d6) ( 5 ppm: 10. 03 (s, 1H), 9. 13 (s, 1H), 8. 60 (d, 2H, J = 4. 5 Hz), 7. 86 (d, 2H, J = 7. 5 Hz), 7. 76 (d, 2H, J = 4. 5 Hz), 7. 26 (t, 2H, J = 7. 5 Hz), 6. 95-6. 86 (m, 3H), 6. 82 (d, 1H, J = 8. 0 Hz), 6. 05 (s, 1H), 4. 49 (t, 2H, J = 7. 0 Hz), 3. 74 (s, 3H), 3. 72 (s, 3H), 2. 97 (t, 2H, • 220- 200524880 J = 7. 0 Hz), 2. 34 (s, 3H).  MS (APCI, m / z): 485 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 15.  Example 157 (4- [2- (3,4-Dimethoxy-phenyl) -ethoxy μ6- {N,-[1- (4-methylsulfonyl-phenyl) -ethylene ] -Hydrazinopyrimidinyl) -phenyl-amine (compound No. 1143) was reacted and purified according to the method of Example 6 to obtain the target compound (14 mg, 25%). # MS (APCI, m / z): 5 62 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5. 06.  Example 1 5 8 4- [l-({6- [2- (3,4-dimethoxy-phenyl) -ethoxy] -2-anilino-pyridine-4-ylbuya Hydrazine) -ethyl] -N-methyl-benzenesulfonamide (Compound No. 1142) was reacted and purified according to the method of Example 9 to obtain the target compound (33 mg, 57%). Lu MS (APCI, m / z): 577 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 5. 03.  Example 159 N4 -Benzo [1,3] disorocene-5-ylmethyl-6- {N '-[l- (4-methylsulfonyl-phenyl) _ethylene L · hydrazine N2-phenyl-pyrimidine-2,4-diamine (compound No. 1146) was reacted and purified according to the method of Example 6 to obtain the target compound (2 mg, -221-200524880 4%). MS (APCI, m / z): 531 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. twenty one. Example 160 4- [l-({6-[(In this case, [i, 3] monopentyl-5-ylmethylamino] aniline-pyrimidin-4-ylpyridinyl)- Ethyl] -N-methyl-benzenesulfonamide (Compound No. 1145) was reacted and purified in the same manner as in Example 9 to obtain the target compound (44 mg, 81%). MS (APCI, m / z): 546 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 4. 18.  Example 1 6 1 N4- [2- (4-ethoxy-3-methoxy-phenyl) · ethyl] · n2-phenylphenylene {N,-[Bubi ratio D fixed-4-yl -Ethylene] -hydrazinobupentine-2,4-diamine (Compound No. 115〇) The reaction and purification were carried out according to the method of Example 1 to obtain the target compound (19 mg, 38% MS (APCI, m / z): 498 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 46.  Example 162 N4- [2- (3-ethoxy-4-methoxy-phenyl) -ethylbenzene N2-phenyl-6- {N,-[1.pyridin-4-yl-ethylene Group] -hydrazinopyrimidine-2,4-diamine (Compound No. !! 53) was reacted and purified according to the method of Example 1 to obtain the target compound (2 5 mg, -222-200524880 50%). MS (APCI, m / z): 498 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3.39.  Example 163 N4- [2- (3,4-dichloro-phenyl) -ethyl] -N2-phenyl-6- {N '-[l-pyridine · 4-yl-ethylenehydrazine Pyrimidine-2,4 · diamine (Compound No. 1156) was reacted and purified according to the method of Example 1 to obtain the target compound (16 mg, 33%). MS (APCI, m / z): 492 (M + l) +.  · HPLC (reverse phase): Rt. (min) = 3.91. Example 164 N2-phenyl-6- {N '-[1-pyridin-4-yl-ethylidene] -hydrazinob N4- [2- (3-trifluorotoluene Group) -ethyl] -pyrimidine-2,4-diamine (compound No. 1159) was reacted and purified according to the method of Example 1 to obtain the target compound (10 mg, 20%). MS (APCI, m / z): 492 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.89. _ Example 165 N4- [2- (4-chloro-phenyl) -ethyl] -N2-phenyl-6- {N '-[1-pyridin-4-yl-ethylenepyrazinopyrimidine-2 , 4-Diamine (compound No. 1160) was reacted and purified according to the method of Example 1 to obtain the target compound (6 mg, 13%). MS (APCI, m / z): 458 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 69.  -223-200524880 Example 166 4- [l-({6- [2- (4--Ethoxy-3-methoxy-phenyl) -ethylamino] -2-anilino-pyrimidine-4- Group} -hydrazino) -ethyl: IN-methyl-benzenesulfonamide (compound No. 1148) was reacted and purified according to the method of Example 9 to obtain the target compound (23 mg, 39%). MS (APCI, m / z): 590 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.17.  Example 1674- [1-({6- [2- (3-ethoxy-4-methoxy-phenyl) -ethylamino] -2-anilino-pyrimidine-4_ylbuya Hydrazine) -ethyl: 1-N-methyl-benzenesulfonamide (Compound No. 115 1) was reacted and purified according to the method of Example 9 to obtain the target compound (25 mg, 42%). MS (APCI, m / z): 590 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 4.12. Example 1 6 8 # 4- [1-({6- [2- (3,4-dichloro-phenyl) -ethylamino] -2-aniline-pyrimidine- 4-Isopropylhydrazino) -ethyl] -N-methyl-benzenesulfonamide (Compound No. 1154) was reacted and purified according to the method of Example 9 to obtain the target compound (40 mg, 69%). ) MS (APCI, m / z): 584 (Μ + 1) + · HPLC (reverse phase) · Rt. (min) = 4 67 Example 1 6 9 -224- 200524880 N4- [2- (4-ethoxy-3-methoxy-phenyl) -ethyl] -6- {N '-[1- (4-Methanesulfonyl-phenyl) -ethylene] -hydrazinob N2-phenyl-pyrimidine-2,4-diamine (Compound No. 1149) The reaction and purification were carried out according to the method of Example 6, but The target substance (41 mg, 72%) was obtained. MS (APCI, m / z): 575 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.19. Example 170 Mono- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl] -6- {1 ^-[1- (4-methylsulfonyl-phenyl)- Ethylene] -hydrazinob N2-phenyl-pyrimidine-2,4-diamine (compound No. 1152) was reacted and purified according to the method of Example 6 to obtain the target compound (38 mg, 67%). MS (APCI, m / z): 575 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 11.  Example 1 7 1 6- {N '-[1- (4-methylsulfonyl-phenyl) -ethylidene] -hydrazinob N2-phenyl-N4- [2- (3-trifluorotoluene Group) -ethyl] -pyrimidine-2,4-diamine (compound No. 1158) was reacted and purified according to the method of Example 6 to obtain the target compound (36 mg, 63%). MS (APCI, m / z): 569 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 46.  Example 172 4- (1- {[2- (2,6-Dimethoxy-pyridin-3-ylamino) -6-pyrazol-1-yl-pyrimidine- -225-200524880 4-yl] -Amidinoylethyl) -N-methyl-benzenesulfonamide (Compound No. 1132) was reacted and purified according to the method of Example 9 to obtain the target compound (8 mg, 14%). MS (APCI, m / z): 524 (M + 1) 'HPLC (reverse phase) · Rt. (min) = 5.43.  Example 173 2- (5-Phenyl-2-phenylamino-6- {N '-[l-pyridin-4-yl-ethylidene] -hydrazinopyrimidin-4-ylamino) -1- Pyridine-4-yl-ethanol (Compound No. 1163) · The reaction was performed according to the method of Example 1 and purified to obtain the target compound (34 mg, 66%). MS (APCI, m / z): 517 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 71.  Example 174 2- (6- {N ^ [l- (4-Methanesulfonyl-phenyl) -ethylidene] -hydrazino-phenyl-2-aniline-pyrimidin-4-ylamino) -1-Pyridin-4-yl-ethanol (Compound No. 1162 • Reaction and purification were carried out according to the method of Example 6 to obtain the target compound (2 3 mg, 39%) 〇j-NMR OOO MHz, DMSO-d6) ^ ppm : 9. 02 (brs, 1H), 8. 68-8. 59 (m, 2H), 8. 19 (brs, 1H), 7. 90 (d, 2H, J = 7. 5 Hz), 7. 80-7. 66 (m, 2H), 7. 60 (t, 2H, J = 7. 5 Hz), 7. 56-7. 46 (m, 4H), 7.45-7 · 34 (m, 5H), 7. 18-7. 12 (m, 1H), 6.01 (brs, 1H), 4. 95-4. 89 (m, 1H), 3. 66-3. 50 (m, 2H), 3. 26 (s, 3H), 2. 50 (s, -226- 200524880 3H).  MS (APCI, m / z): 594 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 27. Example 1 7 5 4- (1-{[6- (2-Hydroxy-2-pyridin-4-yl-ethylamino ^ 5_phenyl_2_aniline 3 cyclo-4-ylhydrazinylethyl) -N-methyl-benzenesulfonamide (compound 1161) was reacted and purified according to the method of Example 9 to obtain the target substance mg, 3 5%) 〇iH-NMR OOO MHz, DMSO-d6) 5 ppm: 9 〇 7 (brs, 1H), (d, 2H, J = 4. 5 Hz), 8.22 (brs, 2H), 7. 80-7. 66 (m, 7. 64-7. 50 (m, 7H), 7. 46-7. 36 (m, 5H), 7. 20-7. 12 (m, 6. 05 (brs, 1H), 4. 97-4. 92 (m, 1H), 3. 66-3. 54 (m, 2H), (d, 3H, J = 5. 0 Hz), 2. 15 (s, 3H).  MS (APCI, m / z): 609 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 3. 30.  Example 176 N4- [2- (4-Fluorophenyl) -ethyl] -N2-phenyl-6- {N '-[1-pyridin-4-yl-yl] -hydrazinopyrimidine- 2,4-Diamine (compound No. 1166) was reacted and purified according to the method of Example 1 to obtain the target compound (34 77%). MS (APCI, m / z): 442 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.75.  Example 177 s-pyrimidine number (218. 66 4H), 1H), 2. 42 Ethylene mg, 200524880 4- [1- ({6- [2- (4- (Fluoro-phenyl) -ethylamino] -2-anilino-pyrimidin-4-ylpyrazino) -ethyl ] -N-methyl-benzenesulfonamide (Compound No. 1164) was reacted and purified according to the method of Example 9 to obtain the target compound (47 mg, 89%). MS (APCI, m / z): 534 (M + 1) 'HPLC (reverse phase): Rt. (min) = 4.25.  Example 178 Heart [1-({6- [2- (3-fluoro-phenyl) -ethylamino] -2-anilino-pyrimidin- [kilbrazinyl) -ethyl; IN-methyl -Benzamide (Compound No. 1167) was reacted and purified according to the method of Example 9 to obtain the target compound (44 mg, 83%). MS (APCI, m / z): 534 (M + 1) + .  HPLC (reverse phase): Rt. (min) = 4. 32.  Example 179 N4- [2- (4-Fluoro-phenyl) -ethyl] -6- {N,-[l- (4-methylsulfonyl-phenyl) -ethylidene] -hydrazine N2-phenyl-pyrimidine-2,4-diamine (compound No. 1165) was reacted and purified according to the method of Example 6 to obtain the target compound (39 mg, 7 5%). MS (APCI, m / z) : 519 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 32. Example 180 N4- [2- (3-Fluoro-phenyl) -ethyl] -6- {N '-[l- (4-methylsulfonyl-phenyl) -ethylene 1 · hydrazine N2-phenyl-pyrimidine-2,4-diamine (compound No. 1168) was reacted and purified according to the method of Example 6 to obtain the target compound (42 mg, -228-200524880 8 1%). MS (APCI, m / z): 519 (M + l) +.  HPLC (reverse phase Rt. (min) = 4. 29.  Example 18 1 4- {1-[(6-imidazol-1-yl-2-m-tolylamino-pyrimidin-4-yl) -amidinoylethylethylbenzene N-methyl-benzenesulfonamide (compound No. 1170) Perform the reaction and purification according to the method of Example 9 to obtain the target compound (38 mg, 79%). 〇! Η-NMK (500 MHz, DMSO-d6) δ ppm: 10. 40 (s, 1H), 9. 35 (brs, 1H), 8.63 (brs, 1H), 8. 18 (d, 2H, J = 8.0 Hz), 8.01 (s, 1H), 7. 82 (d, 2H, J = 7. 0 Hz), 7. 78-7. 72 (m, 1H), 7. 59 (brs, 1H), 7. 57-7. 52 (m, 1H), 7. 21 (t, 1H, J = 8. 0 Hz), 7. 17 (s, 1H), 6. 92 (brs, 1H), 6. 80 (d, 1H, J = 7.5 Hz), 2.46 ’2.41 (m, 6H), 2. 32 (s, 3H).  MS (APCI, m / z): 477 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 77.  Example 1 8 2 4- (l-{[6-imidazol-1-yl-2- (5-methoxy-2-methyl-anilino) -pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1171) was reacted and purified according to the method of Example 9 to obtain the target compound (38 mg, 75%). MS (APCI, m / z): 507 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 74.  Example 1 8 3 -229- 200524880 4- (l-{[2- (2,6-dimethoxy-pyridin-3-ylamino) -6-imidazol-1-yl-pyrimidin-4-yl ] -Hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1133) was reacted and purified according to the method of Example 9 to obtain the target compound (45 mg, 8 6%). MS (APCI, m / z): 524 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 85.  Example 184 4- (1-{[2- (2-Fluoro-aniline) -6-imidazol-1-yl-pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonium Amine (compound number 1173) was reacted and purified according to the method of Example 9 to obtain the target compound (42 mg, 8 7%). ^ H-NMR OOO MHz, DMSO-d6) 6 ppm: 10. 43 (s, 1H), 8. 79 (s, 1H), 8. 59 (s, 1H), 8. 17 (d, 2H, J = 8. 0 Hz), 7. 97 (brs, 2H), 7. 81 (d, 2H, J = 8. 0 Hz), 7. 56-7. 50 (m, 1H), 7.27 (t, 1H, J = 9. 5 Hz), 7. 22 (t, 1H, J = 7. 5 Hz), 7. 19-7. 12 (m, 2H), 6. 94 (s, 1H), 2. 44 (d, 3H, J = 5. 0 Hz), 2. 39 (s, 3H).  MS (APCI, m / z): 481 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 73. Example 1 8 5 4- (1-{[2- (3-fluoro · anilino) -6-imidazol-1-yl-pyrimidin-4-ylburazinyl} · ethyl) -N · methyl -Tosylate (Compound No. 1172) was reacted and purified according to the method of Example 9 to obtain the target compound (36 mg, 75%). -230- 200524880 ^ -NMRCSOO MHz, DMSO-d6) 5 ppm: 10. 54 (s5 1H), 9. 72 (brs, 1H), 8. 63 (brs, 1H), 8. 20 (d, 2H, J = 7. 5 Hz), 8. 05-7. 98 (m, 2H), 7. 82 (d, 2H, J = 7. 0 Hz), 7. 60-7. 51 (m, 2H), 7. 36-7. 28 (m, 1H), 7. 18 (s, 1H), 6. 95 (brs, 1H), 6. 78 (t, 1H, J = 8. 5 Hz), 2. 45-2. 42 (m, 6H).  MS (APCI, m / z): 481 (M + l) + · HPLC (reverse phase): Rt. (min) = 3. 78.  Example 1 8 6 4- (l-{[2- (2-fluoro-5-methyl-anilino) -6-imidazol-1-yl-pyrimidin-4-yl] -hydrazinylethyl) -N -Methyl-benzenesulfonamide (Compound No. 1174) was reacted and purified according to the method of Example 9 to obtain the target compound (35 mg, 71%). MW-NMR (OOO MHz, DMSO-d6) 5 ppm: 10 . 42 (s, 1H), 8. 75 (s, 1H), 8. 57 (s, 1H), 8. 16 (d, 2H, J = 8. 0 Hz), 7. 95 (s, 1H), 7. 81 (d, 2H, J = 8. 0 Hz), 7. 69-7. 62 (m, 1H), 7.56-7.51 (m, 1H), 7. 17-7. 10 (m, 2H), 6. 98-6. 88 (m, 2H), 2. 43 (d, 3H, J = 4. 5 Hz), 2. 39 (s, 3H), 2. 33 (s, 3H).  MS (APCI, m / z): 495 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.92.  Example 187 > 14- (3,4-difluorobenzyl) -6-{] ^ '-[1- (4-methanesulfonyl-phenyl) -ethylidenehydrazine N2-phenyl- Pyrimidine-2,4-diamine (compound No. 1178) was reacted and purified according to the method of Example 6 to obtain the target compound (41 mg, 79%). 231-200524880 MS (APCI, m / z): 523 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 4. 19.  Example 1 8 8 2- [2- (2-Anilino-6- {N '-[l-pyridin-4-yl-ethylidene] -hydrazinopyrimidin-4-ylamino) -ethoxy Group] -ethanol (compound number 8) was reacted and purified according to the method of Example 1 to obtain the target compound (8 mg, 20%). MS (APCI, m / z): 408 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 2.62. Example 189 (5-fluoro-2-methyl-phenyl)-(4-pyrazole-boxy-6- {N '-[l-pyridin-4-yl-ylidene Ethyl] -hydrazinopyrimidin-2-yl) -amine (Compound No. 98) was reacted and purified according to the method of Example 1 to obtain the target compound (18 mg, 45%). ! Η-NMK (500 MHz, DMSO-d6) δ ppm: 10. 50 (brs, 1H), 8. 64 (d, 2H, J = 4. 5 Hz), 8. 51 (s, 1H)? 8. 45 (s, 1H), 7. 90 (s, 1H), 7.76 (d, 2H, J = 4. 5 Hz), 7. 24 (t, 1H, J = 8. 0 Hz), 7. 17 (brs, 1H), 6. 87 (t, 1H, J = 8. 0 Hz), 6. 61 (s, 1H), 2. 36 (s, 3H), 2. 27 (s, 3H).  MS (APCI, m / z): 403 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 93. Example 190 (5-Fluoro-2-methyl-phenyl)-(4-imidazol-1-yl-6- {N '-[1 · pyridin-4-yl-ethylidene: 1 · hydrazinob Pyrimidin-2-yl) -amine (compound number 99) -232- 200524880 The reaction and purification were carried out according to the method of Example 1 to obtain the target compound (29 mg, 71%). ^ -NMRCSOO MHz, DMSO-d6) δ ppm: 10. 49 (s, 1H), 8. 64-8. 53 (m, 4H), 7. 98 (s, 1H), 7. 91 (d, 2H, J = 4. 5 Hz, 7. 70-7. 62 (m, 1H), 7.25 (t, 1H, J = 7. 5 Hz), 7. 15 (s, 1H), 6. 94 (brs, 1H), 6. 91-6. 85 (m, 1H), 2. 35 (s, 3H), 2. 26 (s, 3H).  MS (APCI, m / z): 403 (M + l) + · HPLC (reverse phase): Rt. (min) = 2. 97 · Example 191 (5-Fluoro-2-methyl-phenyl)-(5-methyl-4-pyrazole-boxy-6- {Nf- [1-pyridine-4-yl-ethylene Glypicrazinopyrimidin-2-yl) -amine (compound number 1 082) was reacted and purified according to the method of Example 1 to obtain the target compound (10 mg, 23%). MS (APCI, m / z): 417 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 91.  Example 192 (5-Fluoro-2-methyl-phenyl) · (4-imidazol-1 · yl-5-methyl-6- {N '-[l-pyridinyl-ethylene group: 1- Hydrazinopyrimidin-2-yl) -amine (compound No. 1085) was reacted and purified according to the method of Example 1 to obtain the target compound (41 mg, 98%). MS (APCI, m / z): 417 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.70.  Example 193 (5-Fluoro-2-methyl-phenyl)-(5-phenyl-4-pyrazol-1-yl-6- {N,-[l-_Didine-4- -233- 200524880 Amino-ethylene-1.hydrazinopyrimidin-2-yl) -amine (compound number 110) was reacted and purified according to the method of Example 1 to obtain the target compound (6 m§, 13%). MS (APCI, m / z): 479 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 4. 38.  Example 194 (5-Fluoro-2-methyl-phenyl)-(4-imidazol-1-yl-5-phenyl-6- {N '-[[pyridin-4-yl-ethylidene] pyridine Pyrimidin-2-yl) -amine (Compound No. 111) was reacted and purified according to the method of Example 1 to obtain the target compound (34 mg, · 70%). ^ -NMRCSOO MHz, DMSO-d6) δ ppm: 8. 86 (s, 1H), 8. 61 (brs, 1H), 8. 55 (d, 2H, J = 4. 5 Hz), 8. 09-8. 01 (m, 1H), 7. 64-7. 60 (m, 2H), 7. 58 (s, 1H), 7. 55-7. 46 (m, 3H), 7. 40 (d, 2H, J = 7. 0 Hz), 7. 25 (t, 1H, J = 7. 0 Hz), 7. 00 (s, 1H), 6. 89 (t, 1H, J = 8.5 Hz), 6. 84 (s, 1H), 2.32 (s, 3H), 1. 99 (s, 3H).  MS (APCI, m / z): 479 (M + l) +.  Lu HPLC (reverse phase): Rt. (min) = 3. 28. Example 1 9 5 4- (l-{[2- (5-Fluoro-2-methyl-aniline) -6-imidazol-1-yl-pyrimidin-4-yl] • hydrazinylethyl) -N -(2-Hydroxy-ethyl) -benzenesulfonamide (Compound No. 1175) was reacted and purified according to the method of Example 83 to obtain the target compound (25 mg, 48%). -234- 200524880 MS (APCI, m / z): 525 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 58 · Example 1 9 6 4- (1 · {[2- (5-fluoro-2-methyl-anilino) -5-phenyl-6-pyrazole-pyridyl-pyrimidin-4-yl]- Amidinoylethyl) -N- (2-hydroxy-ethyl) -benzenesulfonamide (Compound No. 1 176) was reacted and purified according to the method of Example 83 to obtain the target compound (24 mg, 4 1%) 〇MS (APCI, m / z): 601 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 5. twenty four.  Example 197 4- (l- {[2- (5-Fluoro-2-methyl-aniline) -6-imidazol-1-yl-5-phenyl-pyrimidin-4-yl] -hydrazinylethyl ) -N- (2-Hydroxy-ethylbenzenesulfonamide (Compound No. 1 177)) According to the method of Example 83, the reaction was refined and purified to obtain the target compound (27 mg, 4 6%). MS (APCI, m / z): 601 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 3. 77.  Example 198 4- (1-{[2- (5-Fluoro-2-methyl-aniline) -6-imidazol-1-yl-5-phenyl-pyrimidin-4-yl] -hydrazinylethyl ) -N-methyl-benzenesulfonamide (Compound No. 399) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (44 mg, 7 7%). 〇1H-NMR (500 MHz, DMSO-d6 ) 5 ppm: 8. 80 (s, 1H), 8. 56 200524880 (brs, 1H), 8. 17-8. 10 (m, 1H), 7. 91 (d, 2H, J = 7. 0 Ηζ), 7.73 (d, 2H, J = 8. 0 Hz), 7. 59 (s, 1H), 7. 56-7. 46 (m, 4H), 7. 40 (d, 2H, J = 7. 0 Hz), 7. 25 (t, 1H, J = 7. 0 Hz), 7. 01 (s, 1H), 6. 88 (t? 1H, J = 8. 0 Hz), 6. 84 (s, 1H), 2. 41 (d, 3H, J = 5. 0 Hz), 2. 33 (s, 3H) 5 2. 02 (s, 3H).  MS (APCI, m / z): 571 (M + l) +.  HPLC (Reversed Phase Rt. (min) = 4. 13.  Example 1 9 9 Phenyl- (4- {N '-[1-pyridin-4-yl-ethylidene] -hydrazinopyrimidin-2-yl) -amine (Compound No. 1) The reaction and purification were performed to obtain the target substance (14 mg, 46%). MS (APCI, m / z): 305 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 53. Example 200 6_ {Chem- [1- (4-methylsulfonyl-phenyl) -ethylenehydrazine 1 ^ 4- (2-morpholin-4-yl-ethyl) -N2-phenyl- Pyrimidine-2,4-diamine (Compound No. 1180) was reacted and purified according to the method of Example 6 to obtain the target compound (21 mg, 41%). MS (APCI, m / z): 510 (M + 1) + · HPLC (reverse phase): Rt. (min) = 2. 99.  Example 201 N-methyl- 4- (1- {[6- (2-morpholine · 4-yl-ethylamino) -2-anilino-pyrimidin-4-ylpyrazolylethyl) -benzene Sulfonamide (compound No. 1179) -236- 200524880 was reacted and purified according to the method of Example 9 to obtain the target compound (20 mg, 38%). MS (APCI, m / z): 525 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.04 Example 202 2-[(2-Cyto-ethyl)-(5-phenyl-2-anilino-6- {N '-[lD -Ethylene] -hydrazinopyrimidin-4-yl) -amino] -ethanol (compound number 1184) was reacted and purified according to the method of Example 1 to obtain the target compound (16 mg, 33%). MS (APCI, m / z): 484 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 94.  Example 203 2-[(2-hydroxy-ethyl)-(6- {N '-[1- (4-methylsulfonyl-phenyl) -ethylidene] -hydrazine 5-phenyl- 2-Anilino-pyrimidin-4-yl) -amino] -ethanol (compound No. 1183) was reacted and purified according to the method of Example 6 to obtain the target compound (30 mg, 54%). MS (APCI, m / z): 561 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.68.  Example 204 4- [1-({6- [Bis- (2-hydroxy-ethyl) -amino] -5-phenyl-2-anilino-pyrimidin-4-ylpyrazidinoethyl] -N-methyl-benzenesulfonamide (Compound No. 1182) was reacted and purified according to the method of Example 9 to obtain the target compound (30 mg, 5 2%). 200524880 MS (APCI, m / z): 576 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 71. Example 205 6- {N '-[l- (4-Methanesulfonyl-phenyl) -ethylidene] -hydrazinob N2-phenyl-N4-pyridin-4-ylmethyl-pyrimidine-2 , 4-Diamine (compound No. 1185) was reacted and purified according to the method of Example 6 to obtain the target compound (45 mg, 92%). MS (APCI, m / z): 488 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 2. 83.  φ Example 206 6- {N '-[1- (4-Methanesulfonyl-phenyl) -ethylidene] -hydrazinob N2-phenyl-N4-thien-2-ylmethyl-pyrimidine- 2,4-Diamine (Compound No. 1186) was reacted and purified according to the method of Example 6 to obtain the target compound (30 mg, 61% MS (APCI, m / z): 493 (M + 1) + .  HPLC (reverse phase): Rt. (min) = 3. 99.  Example 207 4- (1-{[6- (2 · [1,3] Difluorenyl-2-yl-ethylamino) -2-aniline-pyrimidin-4-yl] -fluorenylene Ethyl) -N-methyl-benzenesulfonamide (Compound No. 1188) was reacted and purified according to the method of Example 9 to obtain the target compound (51 mg, 100%). MS (APCI, m / z): 512 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 3.64. Example 208 -238-200524880 2- (6- {N,-[1- (4-methylsulfonyl-phenyl) -ethylene l · hydrazine} -2- Aniline-pyrimidin-4-ylamino) -ethanol (compound number 1192) was reacted and purified according to the method of Example 6 to obtain the target compound (37 mg, 84%). MS (APCI, m / z): 441 (M + 1) 'HPLC (reversed phase): Rt. (min) = 3. twenty four. Example 209 N4- (2- [l, 3] Difluorenane-2-yl-ethyl) -6- {N ·-[1- (4-methylsulfonyl-phenyl) -ethylene ] -HydrazinobN2-phenyl-pyrimidine-2,4-diamine (compound No. 1189) was reacted and purified according to the method of Example 6 to obtain the target compound (47 mg, 94% MS (APCI, m / z): 497 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.65.  Example 210 2- (2-Anilino-6- {N '-[1-pyridin-4-yl-ethylidene] -hydrazino} -pyrimidinylamino) -ethanol (compound number 1193) according to the example The reaction and purification were carried out according to the method 1 to obtain the target compound (29 mg, 81%). MS (APCI, m / z): 364 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 2. 51.  Example 2 1 1 4- (1-{[6- [2- (3,4-dimethoxy-phenyl) -ethylamino] -2- (5-fluoro-2-methyl-aniline ) -Pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Chemical-239-200524880 Compound No. 3 95) The reaction and purification were carried out according to the method of Example 9 to obtain the objective (17 mg, 29%) 〇MS (APCI, m / z): 608 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 13.  Example 2 1 2 4- (1- {[6- [2- (3,4-dimethoxy-phenyl) -2-hydroxyethylamino] _2- (5-fluoromethyl-aniline) -Pyrimidinyl] -aryleneidene) -N-methyl-benzenesulfonium (Compound No. 1 194) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (14 mg, 22%). MS (APCI, m / z): 624 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.76 · Example 2 1 3 4- [1-({2- (5-fluoro-2-methyl-aniline) -6- [2- (2-hydroxy-ethoxy) -Ethynyl] -5-phenyl-pyrimidin-4-yl} -hydrazinyl) -ethyl] methyl-benzenesulfonium (Compound No. 404) The reaction and purification were carried out according to the method of Example 9, but The target compound was obtained (15 mg, 24%). MS (APCI, m / z): 608 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 63. Example 2 1 4 1 ^ 4- [2- (3,4-dimethoxy-phenyl) -ethyl] -1 ^ 2- (5-fluoro-2-methyl-phenyl) -6- {N,-[1-Pyridin-4-yl-ethylidene] -hydrazinopyrimidine_2, diammonium diamine (Compound-240-200524880 No. 107) The reaction and purification were carried out according to the method of Example 1 to obtain Target (14 mg, 27%). MS (APCI, m / z): 516 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 46.  Example 2 1 5 1- (3,4-dimethoxy-phenyl) -2- (2- (5-fluoro-2-methyl-anilino) -6- {N '-[1-pyridine -4-yl-ethylidene] -hydrazinopyrimidin-4-ylamino) -ethanol (compound number 1196) was reacted and purified according to the method of Example 1 to obtain the target compound (11 mg, 20%) . MS (APCI, m / z): 5 3 2 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 05.  Example 2 1 6 2- [2- (2- (5- (Fluoro-2-methyl-anilino) -6- {N '-[1-pyridine-acyl group-ethylene group] hydrazinopyrimidine- 4-Aminoamino) -ethoxy] -ethanol (Compound No. 104) was reacted and purified according to the method of Example 1 to obtain the target compound jdQ mg, 22%). MS (APCI, m / z) : 440 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 2. 76.  Example 2 1 7 2- [2- (2- (5- (Fluoro-2-methyl-anilino) -5-phenyl-6- {Chemical- [1 ^ 比 | 1 定 -4-yl_ sub Ethyl] -hydrazino} -chrysidine-4 -ylamino) · ethoxy] «ethanol (compound No. Shima 116) -241-200524880 According to the method of Example 1, the reaction and purification can be obtained Target (19 mg, 3 6%). MS (APCI, m / z): 516 (M + l) +.  HPLC (reverse phase): Rt. (min) 2 3.14.  Example 218 2- (2-Anilino-6- {N,-[1-pyridin-4-yl-ethylene-1-hydrazinopyrimidin-4-ylamino) -1-pyridyl-ethanol ( Compound No. 1199) According to the method of Example 1, reaction and purification were carried out to obtain the target compound (23 m§, 52%). MS (APCI, m / z): 441 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.27. Example 219 4- (1-{[6- (2-Hydroxy-2-pyridin-4-yl-ethylamino) -2-anilino-pyrimidinylhydrazinoylethyl) -N-methyl-benzenesulfonate Amidine (Compound No. 1197) was reacted and purified according to the method of Example 9 to obtain the target compound (43 mg, 81%). 1H-NMR (500 MHz, DMSO-d6) ^ ppm: 9. 46 (brs, 1H), 8. 62 (s, 1H), 8.53 (d, 2H, J = 4. 5 Hz), 8. 01 (d, 2H, J = 8. 0 Hz), 7. 85 (d, 2H, J = 7. 5Hz), 7. 78 (d, 2H, J == 8-0Hz), 7.54-7. 48 (m, 1H), 7. 40 (d, 2H, J = 4. 5 Hz), 7. 22 (t, 2H, J = 7. 5 Hz), 7. 02 (brs, 1H), 6. 88 (t, 1H, J = 8.0 Hz), 5.98 (brs, 1H), 5. 78 (brs, 1H), 4.80 (brs, 1H), 3. 74-3. 62 (m, 1H), 3. 36-3. 28 (m, 2H), 2. 43 (d, 3H, J = 5. 0 Hz), 2. 34 (s, 3H).  -242- 200524880 MS (APCI, m / z): 533 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 2. 81.  Example 210 -Ethanol (Compound No. 1198) was reacted and purified according to the method of Example 6 to obtain the target compound (43 mg, 83%). ^ -NMRCSOO MHz, DMSO-d6) (5 ppm: 9. 49 (s, 1H), 8. 63 (s, 1H), 8. 53 (d, 2H, J = 4. 5 Hz), 8. 05 (d, 2H, J = 8. 0 Hz), 7. 94 (d, 2H, J = 8. 0 Hz), 7. 85 (d, 2H, J = 8. 0 Hz), 7. 40 (d, 2H, J = 4. 5 Hz), 7. 28 (t, 2H, J = 8. 0 Hz), 6. 88 (t? 1H, J = 8. 0 Hz), 5. 97 (brs, 1H), 5. 82-5. 74 (m, 1H), 4. 83-4. 77 (m, 1H), 3. 74-3. 60 (m, 1H), 3. 3 6-3. 28 (m, 1H), 3. 25 (s, 3H), 2. 35 (s, 3H).  MS (APCI, m / z): 518 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 79.  Example 221 5-Benzyl-N4- [2- (3,4-dimethoxy-phenyl) -ethyl] -N2-phenyl-6- {N ·-[1-pyridin-4-yl -Ethylpyrazine-pyrimidine-2,4-diamine (Compound No. 1095) was reacted and purified according to the method of Example 1 to obtain the target compound (43 mg, 7 5%). ^ -NMRCSOO MHz, DMSO-d6) ά ppm: 8. 76 (s, 1H), 8. 49 (d, 2H, J = 4. 5 Hz), 8. 47 (s, 1H), 8. 00 (d, 2H, J = 8. 0 Hz), 200524880 7. 55 (d, 2H, J = 4. 5 Hz), 7. 27 (t, 2H, J = 8. 0 Hz), 7. 25-7. 16 (m, 5H), 6. 89 ^ 6. 80 (m, 3H), 6. 73 (d, 1H, J = 8. 0 Hz), 6. 61 (brs, 1H), 4. 01 (s, 2H), 3. 72 (s, 3H), 3. 70 (s, 3H), 3.67 · 3.59 (m, 2H), 2. 82 (t, 2H, J: 7. 0 Hz), 2. 10 (s, 3H) MS (APCI, m / z): 574 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 09.  Example 222 4- [1-({5-Benzyl-6- [2- (3,4-dimethoxy-phenyl) -ethylamino] -2-aniline-pyrimidin-4-ylb Hydrazino) _ethyl] _N-methyl-benzenesulfonamide (Compound No. 1093) was reacted and purified according to the method of Example 9 to obtain the target compound (42 mg, 63%). / z): 666 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 4.63.  Example 223 2- (5-Benzyl-2-anilino-6- {N'-Π-pyridin-4-yl-ethylenehydrazinopyrimidin-4-ylamino) -1- (3,4 -Dimethoxy-phenyl) -ethanol (Compound No. 1 098) was reacted and purified according to the method of Example 1 to obtain the target compound (47 mg, 80%). ! Η-NMK (500 MHz, DMSO-d6) δ ppm: 8. 83 (brs, 1H), 8. 55 (brs, 1H), 8. 50 (d, 2H, J = 4. 5 Hz), 7. 98 (d, 2H, J = 6. 5 Hz), 7. 58-7. 52 (m, 2H), 7. 30-7. 15 (m, 7H), 6. 97 (s, 1H), 6. 91-6. 81 (m, 3H), 5. 43 (brs, 1H), 4. 82-4. 76 (m, 1H), 4. 03 -244- 200524880 (d, 1H, J = 17. 0 Hz), 3. 96 (d, 1H, J = 17. 0 Hz), 3. 74 (s, 3H), 3. 71 (s, 3H), 3. 76-3. 66 (m, 1H), 3. 50-3. 41 (m, 1H), 2. 12 (s, 3H) MS (APCI, m / z): 590 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 66. Example 224

4- [l-({5-benzyl-6- [2- (3,4-dimethoxy-phenyl) -2-hydroxyethylamino] -2-aniline-pyrimidin-4-ylb Hydrazino) -ethyl] -N-methyl-benzenesulfonamide (Compound No. 1096) was reacted and purified according to the method of Example 9 to obtain the target compound (31 mg, 4 6%). MS ( APCI, m / z): 682 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.20. Example 225 2- [2- (5-benzyl-2-aniline- 6- {Chemized- [1-pyridin-4-yl-ethylidene] -fluorenylpyrimidin-4-ylamino) -ethoxy] -ethanol (Compound No. 1101) The reaction was carried out according to the method of Example 1. And purification, the target substance (49 mg, 98% Lu MS (APCI, m / z): 498 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.16. Example 226 4- [1-({5-Benzyl-6- [2- (2-hydroxy-ethoxy) -ethylamino] -2-anilino ^ pyrimidin_4-pyridylhydrazino)- Ethyl] -N-methyl-benzenesulfonamide (Compound No. 1 099) -245- 200524880 The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (44 mg, 7 5%). MS (APCI , m / z): 590 (M + 1) +. HPLC (reverse phase): Rt. (min) = 3.85. Example 227 5-Benzyl-N4-cyclopropyl-N2-phenyl-6 -{Ν '-[1- Pyridin-4-yl · ethylene] -hydrazinopyrimidine-2,4-diamine (Compound No. 1104) was reacted and purified according to the method of Example 1 to obtain the target compound (29 mg, 64%). MS (APCI, m / z): 450 (Μ + 1) + · HPLC (reverse phase): Rt. (Min) = 3.51. Example 228 4- {1-[(5-benzyl-6-cyclopropylamine) Phenyl-2-anilino-pyrimidin-4-yl) -hydrazine: yl] -ethylbenzene N-methyl-benzenesulfonamide (compound No. 1102) The reaction and purification were carried out according to the method of Example 9 to obtain Target (40 mg, 74%) 〇-NMROOO MHz, DMSO-d6) δ ppm: 8.81 (brs, 1H), 8.35 (brs, 1H), 8.08 (d, 2H, J = 8.0 Hz), 7.86 (d, 2H, J = 8.0 Hz), 7.70 (d, 2H, J = 8.0 Hz), 7.50-7.44 (m, 1H), 7.29 (t, 2H, J = 8.0 Hz), 7.26-7.16 (m, 5H), 6.89-6.82 (m, 1H), 6.67 (brs, 1H), 4.01 (s, 2H), 2.93-2.87 (m, 1H), 2.40 (d, 3H, J = 5.0 Hz), 2.10 (s , 3H), 0.76-0.70 (m, 2H), 0.55-0.50 (m, 2H). MS (APCI, m / z): 542 (M + l) + · -246- 200524880 HPLC (reverse phase): Rt . (min) = 4.16. Example 229 5-benzyl-N2 -phenyl-N4- (2-D) i 0-determined 4-yl-ethyl) -6- {N '-[l-batch 卩Amine-4_yl-ethylene] -fluorenyl Pyridine-2,4-diamine (compound number 1108) by reaction and purification methods of Example 1, the desired product can be obtained (4 1 mg, 80%). MS (APCI, m / z): 515 (M + l) +. HPLC (reverse phase): Rt. (Min) = 2.85. Example 2 3 0 4- (1-{[5-Benzyl-2-aniline-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1106) was reacted and purified according to the method of Example 9 to obtain the target compound (54 mg, 89%). 1H-NMR (500 MHz, DMSO-d6) δ ppm: 8.80 (brs, 1H), 8.45-8.40 (m, 3H), 7.99 (d, 2H, J = 7.0 Hz), 7.83 (d, 2H, J = 8.0 Hz), 7.68 (d, 2H, J = 8.0 Hz), 7.50-7.45 (m, 1H), 7.28 (t, 2H, 7.0 Hz), 7.25-7.14 (m, 6H), 6.88 (t, 1H, J = 7.0 HzMS (APCI, m / z): 607 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.48 · Example 2 3 1 5-Benzyl-? ^ 4, > ^ 4-Dimethyl-to-phenyl-6- {1 ^-[1-pyridin-4-yl-ethylidene] -hydrazinopyrimidine-2,4-diamine (compound number 1 1 1 1) The reaction and purification were carried out according to the method of Example 1 to obtain the target substance (61 mg, -247-200524880 70%). MS (APCI, m / z): 43 8 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.04. Example 232 4- {Bu [(5-benzyl-6-dimethylamino-2-anilino-pyrimidin-4-yl) -hydrazinyl Ethyl N-methyl-benzenesulfonamide (Compound No. 1109) was reacted and purified according to the method of Example 9 to obtain the target compound (88 mg, 84%). MS (APCI, m / z): 530 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.48. Example 233 4- {l-[(5-benzyl-6-dimethylamino-2-anilino-pyrimidine- 4 · yl) -arylene] -ethyl N- (2-hydroxy -Ethyl) -benzenesulfonamide (Compound No. 1112) was reacted and purified according to the method of Example 83 to obtain the target compound (89 mg, 80%). MS (APCI, m / z): 560 (M + l) +. HPLC (reverse phase): Rt. (min) = 4.27. Example 234 [1- ({5-Benzyl-2-aniline-6-[(tetrahydrofuran-2-ylmethyl)- Amine] -Pyrimidine_4-Bibazidino) -ethyl] methyl-benzenesulfonamide (compound No. Shima 1113) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (34 mg, 58%) MS (APCI, m / z): 5 86 (M + 1) +--248- 200524880 HPLC (reverse phase): Rt. (min) = 4.41. Example 235 4- {1-[(5-Benzyl-6-cyclobutylamino-2-anilino-pyrimidin-4-yl) -hydrazinyl] -ethylbenzene N-methyl-benzenesulfonium The amine (compound No. 1114) was reacted and purified according to the method of Example 9 to obtain the target compound (35 mg, 63%). MS (APCI, m / z): 556 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 4.80. Example 236 2- (5-benzyl-2-aniline-6- {N'-Π-pyridin-4-yl-ethylene group; 1-hydrazinopyrimidin-4-ylamino) -ethanol (compound number 1117) The reaction and purification were carried out according to the method of Example 1 to obtain the objective. (36 mg, 80%). MS (APCI, m / z): 454 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.16. Example 2 3 7 4- (1- {[5-benzyl- 6- (2-Hydroxy-ethylamino) -2-anilino-pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1115) According to the method of Example 9 After reaction and purification, the target substance (39 mg, 71%) was obtained. MS (APCI, m / z): 546 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.88. Example 238 4- (l- {[5-benzyl-6- (2-hydroxy-ethylamino) -2-aniline-pyrimidin-4-ylbuya-249- 200524880 hydrazinobuethyl) -N-(2-hydroxy-ethyl) -benzenesulfonamide (compound number 丨丨 i 8) The reaction and purification were carried out according to the method of Example 83 to obtain the target substance (47 mg, 81%). MS (APCI, m / z): 576 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 3.63 · Example 2 3 9 2- (5-Setyl-6- {N '-[1- (4-Methanesulfonyl-phenyl) -ethylidene] -hydrazinob-2-anilino-pyrimidin-4-ylamino) -ethanol (compound number 1116) The reaction was carried out and refined to obtain the target substance (38 mg, 72%). MS (APCI, m / z): 531 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.79. Example 240 N- (2-hydroxy-propyl) -4- {l-[(5-phenyl-2-anilino-pyrimidin-4-yl) -hydrazino] -ethylbenzsulfenylamine (Compound No. 1241) 4-hydrazino-5-phenyl-2-aniline (0.1 mmol) was dissolved in ethanol (1 ml), and 4-acetamyl-N- (2-hydroxy-propyl) was added ) -Benzamide (33 mg, 0.13 mmol), stir for 18 hours. The precipitated solid was pulverized and collected by filtration to obtain the target substance (39 mg, 75%). MS (APCI, m / z): 517 (Μ + 1) + · HPLC (reverse phase): Rt. (Min) = 3.73 · Example 241 1- (5-phenyl-2-anilino-6 -{Ν '-[1- 卩 比 卩 定 -4 -yl-ethylidene] -bakeryl} -compensation-250-200524880 pyridin-4-ylamino) -propan-2-ol (compound number 1 205 ) The reaction and purification were carried out according to the method of Example 1 to obtain the target substance (31 mg, 69%). MS (APCI, m / z): 454 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 3.05. Example 242 1- (6- {Ν ^ [1- (4-methylsulfonium Fluorenyl-phenyl) -ethylene] -hydrazinob 5-phenyl-2-aniline-pyrimidin-4-ylamino) -propan-2-ol (compound number 1204) After reaction and purification, the target substance (34 mg, 64%) was obtained. MS (APCI, m / z): 531 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.82. Example 243 4- (l-{[6- (2-hydroxy-propylamino) ) -5-phenyl-2-anilino-pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (compound number 1203) The reaction and purification were carried out according to the method of Example 9, The target compound was obtained (39 mg, 71%). MS (APCI, m / z): 546 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 3.78. Example 244 1- (6- {N '-[1- (4-methylsulfonyl-phenyl) -ethylene] -hydrazinob 2-anilino-pyrimidinylamino) -propan-2-ol (compound No. 1206) The reaction and purification were carried out according to the method of Example 6, and the target substance (30 mg, 66%) was obtained. 200504880 MS (APCI, m / z): 455 (M + 1) + · HPLC (reverse phase) : Rt. (Min) = 3.53. Example 245 1- (5-Methenyl-2-aniline-6- {N '-[1-pyridinium-4-yl-ethylidene] -pieyl} -n-pyridin-4-yl Amine) -propan-2-ol (compound number 1121) was reacted and purified according to the method of Example 1 to obtain the target compound (30 mg, 65%). MS (APCI, m / z): 468 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.29. Example 246 1- (5-benzyl-6- {N '-[1 -(4-methylsulfonyl-phenyl) -ethylidene] -hydrazinob-2-anilino-pyrimidin-4-ylamino) -propan-2-ol (Compound No. 1120) The reaction and purification were performed to obtain the target substance (39 mg, 71%). MS (APCI, m / z): 545 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.86. Example 247 4- (l- {[5-benzyl-6- (2 -Hydroxy-propylamino) -2-anilino-pyrimidin-4-yl: l · hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1119) The reaction and purification were carried out according to the method of Example 9. , The target substance can be obtained (41 mg, 74%). MS (APCI, m / z): 560 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 4.02. Example 248 -252- 200524880 2- (5 -fluorenyl-2- Anilinyl-6- {N '-[1-pyridinidine-4-yl-ethylidene] -pyridyl-pyridine-cardiylamino) -pyridyl-ethanol (compound number 1124) The method of Example 1 was reacted and purified to obtain the target compound (36 mg, 68%). MS (APCI, m / z): 531 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 2.76. Example 249 2- (5-benzyl-6-^ '-[1 -(4-methylsulfonyl-phenyl) -ethylidene] -hydrazinob-2-anilino-pyrimidin-4-ylamino) -1-pyridin-4-yl-ethanol (Compound No. 1123) The method of Example 6 was reacted and purified to obtain the target compound (44 mg, 72%). MS (APCI, m / z): 608 (M + 1) +. HPLC (reversed phase): Rt. (Min) = 3.26. Example 250 4- (1-{[5-Benzyl-6- (2-hydroxy-2-pyridin-4-yl-ethylamino) -2-anilino-pyrimidin-4-yl] -hydrazinyl Ethyl) -N-methyl-benzenesulfonamide (Compound No. 1122) was reacted and purified according to the method of Example 9 to obtain the target compound (49 mg, 78%). OH-NMR (OOO MHz, DMSO-d6) δ ppm: 8.79 (s, 1H), 8.49-8.45 (m, 3H), 7.98 (d, 2H, J = 8.5 Hz), 7.82 (d, 2H, J = 8.0 Hz), 7.68 (d, 2H, J = 8.0 Hz), 7.49-7.44 (m, 1H), 7.34-7.27 (m, 4H), 7.26-7.18 (m, 5H), 6.89 (t, 1H, J = 7.0 Hz), 6.51 200524880 (brs, 1H ), 5.74 (d, 1H, J = 4.0 Hz), 4.92-4.87 (m, 1H)? 4.04 (d5 1H, J = 18.0 Hz), 3.98 (d, 1H, J = 18.0 Hz), 3.72-3.65 ( m, 1H), 3.51-3.44 (m, 1H), 2.40 (d, 3H, J = 5.0 Hz), 2.15 (s, 3H). MS (APCI, m / z): 623 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.22. Example 251 (4- {N '-[l- [4- (morpholine-4-sulfonyl) -phenyl] -ethylene l · Hydrazine 5-phenyl-pyrimidin-2-yl) -phenyl-amine (Compound No. 1242) 4-Hydrazine-5-phenyl-2-aniline pyrimidine (0.250 mmol) was dissolved in ethanol (3 ml) , Add 1- [4- (morpholine-4-sulfonyl) -phenyl] -Ethyl ketone (67.3 mg, 0.250 mmol), stirred for 10 hours. The precipitated solid was pulverized, and the target substance was obtained by filtration (114 mg, 86%). j-NMROOO MHz, DMSO-d6) δ ppm: 9.48 (brs, 1H), 9.41 (brs, 1H), 8.11 (s, 1H), 8.03 (d, 2H, J = 7.6 Hz), 7.73-7.63 (m, 4H), 7.48 (s, 4H), 7.40-7.36 (m, 1H), 7.32-7.27 (m, 2H), 6.98-6.94 (m, 1H), 3.64 (brs, 4H), 2.87 (brs , 4H), 2.26 (s, 3H). MS (APCI, m / z): 529 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.40. Example 252 l- ( 3,4-dimethoxy-phenyl) -2- (5-phenyl-2-aniline-6- {N '-[l-pyridin-4-yl-ethylidene] -hydrazinopyrimidine 4-Aminoamino) -ethanol (Compound No. 1209) -254- 200524880 The reaction and purification were carried out according to the method of Example 1 to obtain the target substance (45 mg, 78%). 4-NMR (500 MHz, DMSO-d6) 5 ppm: 8.95 (s, 1H), 8.48-8.36 (m, 3H), 7.97 (d5 2H, J = 7.5 Hz), 7.50 (t, 2H, J = 7.5 Hz), 7.43 (t, 1H, J = 7.5 Hz), 7.30-7.14 (m, 6H), 6.92-6.83 (m, 3H), 6.81 (d, lH, J = 8.5Hz), 5.43-5.40 (m , LH), 5.18-5.12 (m, 1H), 4.68-4.62 (m, 1H), 3.74 (s, 3H), 3.71 (s, 3H), 3.71-3.63 (m, 2H), 2.00 (s, 3H ). MS (APCI, m / z): 576 (M + l) + · HPLC (reverse phase): Rt. (Min) = 3.53. Example 253 4- [l-({6- [2- (3 (3 , 4-Dimethoxy-phenyl) -2-hydroxyethylamino] -5-phenyl-2-aniline-pyrimidin-4-ylbazidino) -ethylb N-methyl-benzene Sulfonamide (compound No. 1207) was reacted and purified according to the method of Example 9 to obtain the target compound (47 mg, 70%). 〇iH-NMR OOO MHz, DMSO-d6) (5 ppm: 8.93 (s, 1H) , 8.41 (s, 1H), 7.98 (d, 2H, J = 8.0 Hz), 7.63 (d, 2H, J = 8.0 Hz), 7.54-7.39 (m, 6H), 7.33-7.18 (m, 3H), 6.93-6.84 (m, 3H), 6.81 (d, 1H, J = 8.5 Hz), 5.42 (d, 1H, J = 4.0 Hz), 5.16-5.09 (m, 1H), 4.68-4.62 (m, 1H) , 3.74 (s, 3H), 3.71 (s, 3H), 3.70-3.62 (m, 2H), 2.39 (d, 3H, J = 5.0 Hz), 2.04 ( s, 3H). MS (APCI, m / z): 668 (M + l) +. HPLC (reverse phase) Rt. (min) = 4.0 6. -255- 200524880 'Example 254 l- (3 , 4-dimethoxy-phenyl) -2- (6- {N '-[K (4-methylsulfonyl-phenylphenylene); I-hydrazinophenyl 5-phenyl-2-anilide -Pyrimidine, 4-ylamino) -ethanol (Compound No. 1208) was reacted and purified according to the method of Example 6 to obtain the target compound (58 mg, 89%). MS (APCI, m / z): 653 (M + 1) + · HPLC (reverse phase): Rt. (Min) = 4.05. Example 255 φ 6_ {N '-[1- (4-methylsulfonyl) -Phenyl) -ethylidene] -hydrazinob 5, ν2-diphenyl-N4- (2--ititridin-1-yl-ethyl) -ranoxidine-2,4-diamine (Compound No. 1214) The reaction and purification were carried out according to the method of Example 6 to obtain the target compound (43 mg, 7 5%). MS (APCI, m / z): 570 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.22. Example 256 · 5, N2-diphenyl-N4- (2-piperidine -1-yl-ethyl) -6- {N, [1.pyridin-4-yl-ethylenehydrazinopyrimidine-2,4-diamine (Compound No. 1216) The reaction was carried out according to the method of Example 1 and Refined to obtain the target substance (35 mg, 69%). MS (APCI, m / z): 507 (M + l) +. HPLC (reverse phase): Rt. (Min) = 2.86. Example 257 -256- 200524880 6 _ {! ^ '-[1- (4- Methanesulfonyl-phenyl) -ethylenehydrazine 5,1 ^ 2-diphenyl-N4- (2-piperidin-1-yl-ethyl) -pyrimidine-2,4-diamine (compound No. 1215) The reaction and purification were carried out according to the method of Example 6 to obtain the target substance (47 mg, 81%). MS (APCI, m / z): 584 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.48. Example 258 N4- [2- (3,4-dimethoxy-benzene (Yl) -ethyl] -5, N2-diphenyl-6- {N'-Π-pyridine-4 -yl-ethylene] -pyridyl-2,4-diamine ( Compound No. 23) The reaction and purification were carried out according to the method of Example 1. The target compound (48 mg, 8 6%) was obtained. 〇2Η-NMK (500 MHz, DMSO-d6) 5 ppm: 8.95 (s, 1H), 8.45 (d, 2H, J = 4.5 Hz), 8.35 (brs, 1H), 8.00 (d, 2H, J = 8.5

Hz), 7.48 (t, 2H, J = 8.0 Hz), 7.42 (d, 1H, J = 7.5 Hz), 7.28-7.20 (m, 6H), 6.92-6.87 (m, 1H), 6.85 (d, 1H , J = 8.5 Hz), 6.76 (s, 1H), 6.66 (d, 1H, J = 8.0 Hz), 5.34-5.29 (m, 1H), 3.72 (s, 3H), 3.70 (s, 3H), 3.59 -3.52 (m? 2H), 2.73 (t, 2H, J = 7.5 Hz), 1.97 (s, 3H). MS (APCI, m / z): 560 (M + l) +. HPLC (reverse phase Rt. (min) = 4.42. Example 259 4- [l-({6- [2- (3,4-dimethoxy-phenyl) -ethylamino] -5-phenylaniline-pyrimidine-4 -Gibbazidinyl) -ethyl] -N-methyl-benzenesulfonamide (Compound No. 200524880) The reaction and purification were carried out according to the method of Example 9 to obtain the target compound (43 mg, 6 6%). (APCI, m / z): 652 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.58. Example 260 N4- [2- (3,4-dimethoxy- Phenyl) -ethyl] -6- {N ·-[1- (4-methylsulfonyl-phenyl) -ethylidene] -pieyl} -5, N2 -monophenyl-hexidine- 2,4-Diamine (Compound No. 1 6 7) was reacted and purified according to the method of Example 6 to obtain the target compound (53 mg, 83%). MS (APCI, m / z): 637 (M + l) +. HPLC (reverse phase) · Rt. (min) = 4.43. Example 261 5,1 ^ 2-Diphenyl -6- {~-[1-pyridin-4-yl-ethylidene] -hydrazinyl 1 ^ 4-pyridin-4-ylmethyl-pyrimidine-2,4-diamine (compound number 1219) according to implementation The method of Example 1 was reacted and purified to obtain the target compound (47 mg, 96%). MS (APCI, m / z): 487 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 2.81. Example 262 N-Methyl-4- [1-({5-phenyl-2-phenylamino-6-[(pyridin-4-ylmethyl) -amino] -pyrimidin-4-yl Hydrazino) -ethyl] -benzenesulfonamide (Compound No. 1217) was reacted and purified according to the method of Example 9 to obtain the target compound (48 mg, 83%). 〇-258- 200524880 iH-NMROOO MHz , DMSO-d6) 5 PPm: 8.86 (s, 1H), 8.48 (d, 2H, J = 4.5 Hz), 8.27 (s, 1H), 7.79 to 7.71 (m, 2H), 7 66 (d, 2H, J = 8.5 Hz), 7.60-7.52 (m, 4H), 7.49-7.40 (m, 4H), 7.28 (d, 2H, J = 5.0 Hz), 7.14 (t, 2H , J = 8.0 Hz), 6.85 ((, 1H, J = 7.0 Hz), 6.32-6.2 6 (melon, 1H), 4.56 (d, 2H, J = 5.0

Hz), 2.40 (d, 3H, J = 5.0 Hz), 2.01 (s, 3H). MS (APCI, m / z): 579 (M + l) + · HPLC (reverse phase): Rt. ( min) = 3.26. Example 263 6-{> 1 '-[1- (4-methylsulfonyl-phenyl) -ethylene] -hydrazino} -5,1 ^ 2-diphenyl- N4-pyridin-4-ylmethyl-pyrimidine-2,4-diamine (compound No. 1218) was reacted and purified according to the method of Example 6 to obtain the target compound (53 mg, 95%). MS (APCI, m / z): 564 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3.27. Example 264 N4-isopropyl-5, N2 -monophenyl-6- {N ' -[1- 卩 比 D 定 -4-yl-ethylidene] _Pyridylpyrimidine-2,4-diamine (Compound No. 1220) was reacted and purified according to the method of Example 1 to obtain the target compound ( 26 mg, 59% MS (APCI, m / z): 438 (M + 1) +. HPLC (reverse phase) · · Rt. (Min) = 4.19. Example 265 1 ^ 4- (3 , 4-Dimethoxybenzyl) -5,1 ^ 2-diphenyl-6- {Hydroxy- [1-pyridin-4-yl_ethylene-259-200524880] -hydrazinopyrimidine-2, 4-Diamine (compound No. 1 223) was reacted and purified according to the method of Example 1 to obtain the target compound (28 mg, 51%). 1H-NMR (500 MHz, DMSO-d6) 5 ppm: 8 · 9 3 (s, 1 Η), 8 · 4 7 (d, 2H, J = 4.5 Hz), 8.33 (s, 1H), 7.90 (d, 2H, J = 8.0 Hz), 7.54 (t, 2H, J = 7.5 Hz), 7.44 (t, 1H, J = 8.0 Hz), 7.36 (d, 2H, J = 7.5 Hz), 7.33-7 · 26 (m, 2H), 7.21 (t, 2H, J = 8 · 0

Hz), 6.93 (s, 1H), 6.87 (t, 2H, J = 8.0 Hz), 6.81 (d, 1H, J = 8.0 Hz), 6.03-5.96 (m, 1H), 4.49 (d, 2H, J = 5.0 Hz), 3.69 (s, 3H), 3.67 (s, 3H), 1.97 (s, 3H). MS (APCI, m / z): 546 (M + l) +. HPLC (reverse phase): Rt . (min) = 3.89. Example 266: 4- (l- {[6- (3,4-Dimethoxybenzylamino) -5-phenyl-2-aniline-pyrimidin-4-ylbuya Amidinobuethyl) -N-methyl-benzenesulfonamide (Compound No. 1221) was reacted and purified according to the method of Example 9 to obtain the target compound (52 mg 5 8 1%). MS (APCI, m / z ): 638 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.47. Example 267 N4- (3,4-dimethoxybenzyl) -6- {N ^ [l- ( 4-methylsulfonyl-phenyl) -ethylidene] · fluorenyl 5,52-diphenyl-pyrimidine-2,4-diamine (Compound No. 1 222) The reaction was carried out according to the method of Example 6 and Refined to obtain the target substance (53 mg, 8 5%). -260- 200524880 MS (APCI, m / z): 623 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.42. Example 268 4- (l-{[5- (4- Ethyl-3,5-monomethyl-phenyl) -2-anilino-6- (2-1) pyridine-4_yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl ) -N-methyl-benzenesulfonamide (Compound No. 1086) was reacted and purified according to the method of Example 9 to obtain the target compound (45 mg, 63%). OH-NMR OOO MHz, DMSO-d6) ppm: 8.92 (s, 1H), 8.48-8.43 (m, 3H), 8.12 (s, 1H), 8.02 (d, 2H, J = 8.5 Hz), 7.78 (d, 2H, J = 8.0 Hz) , 7.73 (d, 2H, J = 7.5 Hz), 7.49-7.44 (m, 1H), 7.26-7.19 (m, 4H), 6.90 (t, 1H, J = 7.5 Hz), 6.80 (s, 2H), 5.48 (brs, 1H), 3.63-3.56 (m, 2H), 2.86 (t, 2H, J = 7.0 Hz), 2.42 (d, 3H, J = 4.5 Hz), 2.18 (s, 6H), 1.98 (s , 3H). MS (APCI, m / z): 637 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.19. Example 269 2,6-dimethyl-4- (2 -Anilino-4- (2-pyridin-4-yl-ethylamino) -6-{> 1 '-[1-pyridin-4-yl-ethylidene] -hydrazinopyrimidin-5-yl ) -Phenol (Compound No. 1088) The reaction and purification were carried out according to the method of Example 1. , Can be obtained the desired product (3 5 mg, 57%). MS (APCI, m / z): 545 (M + 1) +. HPLC (reverse phase) Rt. (Min) = 2.69. -261-200524880 Example 270 N2- (4-Fluoro-phenyl) -6- {N '-[1- (4-methylsulfonyl-phenyl) -ethylene] -hydrazinob N4- ( 2-Pyridine-4-yl-ethyl) -pyrimidine-2,4-diamine (compound No. 1225) was reacted and purified according to the method of Example 6 to obtain the target compound (38 mg, 73%). 1H-NMR (500 MHz, DMSO-d6) δ ppm: 9.48 (brs, 1H), 8.70 (s, 1H), 8.48 (d, 2H, J = 4.0 Hz), 8.03 (d, 2H, J = 7.0 Hz), 7.93 (d, 2H, J = 7.0 Hz), 7.90-7.84 (m, 2H), 7.30 (d, 2H, J = 4.0 Hz), 7.04 (t, 2H, J = 7.0 Hz) , 7.18-6.92 (m, 1H), 5.88 (s, 1H), 3.62-3.54 (m, 2H), 3.24 (s, 3H), 2.89 (t, 2H, J = 7.0 Hz), 2.34 (s, 3H ). MS (APCI, m / z): 520 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.06. Example 271 4- (1-{[2- (4-fluoro- Aniline) -6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylbuazidinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1224) according to Example 9 The method was used for reaction and purification to obtain the target substance (41 mg, 76%). 〇i-NMR OOO MHz, DMSO-d6) δ ppm: 9.45 (brs, 1H), 8.69 (s, 1H), 8.48 (d, 2H , J = 4.0 Hz), 7.99 (d, 2H, J = 9.0 Hz), 7.90-7.83 (m, 2H), 7.78 (d, 2H, J = 9.0 Hz), 7.53-7.48 (m, 1H), 7.30 (d, 2H, J = 4.0 Hz), 7.03 (t, 2H, J = 9.0 Hz), 6.98 (brs, 1H), 5.88 (brs, 1H), 3.61-3.54 (m, 2H), 2.89 ( t, -262- 200524880 2H, J = 7.0 Hz), 2.42 (d, 3H, J = 5.0 Ηζ), 2.33 (s, 3H) · MS (APCI, m / z): 53 5 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.09 · Example 272 1 ^ 4 -[2- (3,4-dimethoxy-phenyl)-[1,3] diphosphone-2-ylmethyl] -1 ^ 2-phenyl-6- {Ν '-[ Pyridin-4-yl-ethylene] -hydrazinopyrimidine-2,4 · diamine (compound No. 1244) was reacted and purified according to the method of Example 1 to obtain the target compound (276 mg, 94%) 〇MS (APCI, m / z): 542 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.31. Example 273 N2- (4-chloro-phenyl) -6- {N '-[l- (4-Methanesulfonyl-phenyl) -ethylene] -hydrazinob N4- (2-pyridin-4-yl-ethyl) · pyrimidine-2,4 · diamine (compound No. 1228) The reaction and purification were carried out according to the method of Example 6 to obtain the target substance (40 mg, 75%). MS (APCI, m / z): 536 (M + 1) +. HPLC (reaction): Rt. (Min) = 3.23. Example 274 4- (1- {[2- (4-Chloro-aniline) -6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl)- N-methyl-benzenesulfonamide (Compound No. 1227) was reacted and purified according to the method of Example 9 to obtain the target compound (40 mg, 73%). 2005024880 MS (APCI, m / z): 551 ( M + l) +. HPLC (reverse phase): Rt. (Min) = 3.28. Example 275 N-methyl-4- (l-{[5-phenyl-2-aniline-6- (2- Pyridin-4-yl-ethoxy) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 1 238) The reaction was carried out according to the method of Example 9 and purified. 16 1 mg, 90%) 〇1H-NMR (500 MHz, DMSO-d6) δ ppm: 9.36 (s, 1H), 8.82 (brs, 1H), 8.51 (d, 2H, J = 5.0 Hz), 8.00 (d, 2H, J = 7.0 Hz), 7.66 (d, 2H, J = 8.0 Hz), 7.59-7.52 (m, 2H), 7.50-7.45 (m, 1H), 7.42-7.25 (m, 7H) , 7.21 (d, 2H, J = 7.0 Hz), 6.97 (t, 1H, J = 7.0 Hz), 4.56 (t, 2H, J = 5.5 Hz), 3.04 (t, 2H, J = 5.5 Hz), 2.40 (d, 3H, J = 4.5 Hz), 2.10 (s, 3H). MS (APCI, m / z): 594 (M + l) + · HPLC (reverse phase): Rt. (min) = 3.91 Example 276 5- (4-Fluoro-phenyl)- 6- {N '-[1 · (4-Methylfluorenyl-phenyl) -ethylene] -fluorenyl} _N2-phenyl-N4- (2-U]: -Ethyl) pyridine-2,4-monoamine (compound number 1090) was reacted and purified according to the method of Example 6 to obtain the target compound (41 mg, 68%). ! Η-NMK (500 MHz, DMSO-d6) δ ppm: 8.93 (s, 1H), 8.46 (d, 2H, J: 4.5 Hz), 8.34 (s, 1H), 7.98 (d, 2H, J = 7 5 Hz), 7.81 (d, 2H, J = 8.0 Hz), 7.59 (d, 2H, J = 7.5 Hz), 7.34--264- 200524880 7.18 (m, 8H), 6.91 (t, 1H, J 2 7 · 5 Hz), 5.64-5.59 (m, 1H), 3.61-3.54 (m, 2H), 3.22 (s, 3H), 2.85 (t, 2H, J = 7.0 Hz), 2.06 (s, 3H). MS (APCI, m / z): 596 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.49 · Example 2 7 7 4- (l-{[5- (4- Fluoro-phenyl) -2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide ( Compound No. 1 089) was reacted and purified according to the method of Example 9 to obtain the target compound (40 mg, 6 5%) 〇 ^ -NMRCSOO MHz, DMSO-d6) δ ppm: 8.89 (s, 1H), 8.45 ( d, 2H, J = 5.9 Hz), 8.31 (s5 1H), 1.91 (d, 2H, J = 8.1 Hz), 7.66 (d, 2H, J = 8.8 Hz), 7.53 (d, 2H, J = 8.8 Hz ), 7.46 (brs5 1H), 7.32-7.19 (m, 8H), 6.90 (t, 1H, J = 7.3 Hz), 5.58 (t, 1H, J = 5.9 Hz), 3.58 (dt, 2H, J = 5.9 , 7.3 Hz), 2.84 (t, 2H, J = 7.3 Hz), 2.49 (d, 3H, J = 2.2 Hz ), 2.05 (s, 3H). MS (APCI, m / z): 611 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.52. Example 278 N-methyl-4- (1- {[2-Anilino-6- (3-pyridin-4-yl-pyrrolyl-butyl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide (Compound No. 1234) Reaction and purification were carried out according to the method of Example 9 to obtain the target compound (84.0 mg, 78%). 200524880 MS (APCI, m / z): 5 39 (M + 1) +. HPLC (reverse phase): Rt. ( min) = 4.06. Example 279 [4- {N '-[1- (4-Methanesulfonyl-phenyl) -ethylidene] -fluorenyl 6- (3-pyridin-4-yl-pyrrole-1-yl) -Pyrimidin-2-ylphenylphenyl-amine (Compound No. 1 235) was reacted and purified according to the method of Example 6 to obtain the target compound (86.9 mg, 83%). MS (APCI, m / z): 524 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.04. Example 280 N2- (4-fluoro-phenyl) -6- {Nf- [l- (4-methyl Sulfonyl-phenyl) -ethylenehydrazino} -5-phenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine (Compound No. 1231) according to the example The method 6 was used for the reaction and purification to obtain the target compound (42 mg, 70%). 1 Η-NMR (5 00 MH z, DM S Ο-D δ ppm: 9.00 (s, 1H), 8.45 (d, 2H, J = 4.5 Hz), 8.34 (s, 1H), 7.98 (brs, 2H), 7.80 (d, 2H, J = 7.0 Hz), 7.56-7.46 (m, 4H), 7.44 (t, 1H, J = 7 · 〇

Hz), 7.25 (d, 2H, J = 7.0 Hz), 7.19 (d, 2H, J = 4.5 Hz), 7.07 (t, 2H, J = 8.0 Hz), 5.46 (brs, 1H), 3.62-3.55 ( m, 2H), 3.22 (s, 3H), 2.84 (t, 2H, J = 7.0 Hz), 2.02 (s, 3H). MS (APCI, m / z): 596 (M + l) +. HPLC ( Reverse phase): Rt. (Min) = 3.34. Example 281 -266 · 200524880 4- (1-{[2- (4-fluoro-aniline) -5-phenyl-6- (2-pyridine-4 -Yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1 230) The reaction and purification were carried out according to the method of Example 9 to obtain the objective. (40 mg, 66%) 〇] Η-NMK (400 MHz, DMSO-d6) 5 ppm: 8.98 (s, 1H), 8.44 (d, 2H, J = 4.7 Hz), 8.27 (s, 1H) , 7.99-7.96 (m, 2H), 7.64 (d, 2H, J = 7.5 Hz), 7.49-7.39 (m, 6H), 7.24 (d5 2H, J = 8.2 Hz), 7.17 (d, 2H, J = 4.7 Hz), 7.04 (t, 2H, J = 8.2 Hz), 5.44 (t, 1H, J = 5.7 Hz), 3.57 (dd, 2H, J = 6.3, 12.9 Hz), 2.82 (t, 2H, J = 6.8 Hz), 2.39 (s, 3H), 2.00 (s, 3H). MS (APCI, m / z): 611 (M + l) +. HPLC (reversed phase): Rt. (Min) =. Example 282 4- (1-{[2- (2-fluoro-aniline) -5-phenyl-6- (2- Pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide (Compound No. 1 232) was reacted and purified according to the method of Example 9, Available target (32 mg, 53%) 〇! Η-NMK (400 MHz, DMSO-d6) δ ppm: 8.44-8.41 (m, 3H), 8.33 (t, 1H, J = 8.0 Hz), 8.03 (s, 1H), 7.60 (d, 2H, J = 7.8 Hz), 7.50-7.37 (m, 6H), 7.24-7.19 (m, 3H), 7.15-7.02 (m, 4H), 5.48 (t, 1H , J = 5.65 Hz), 3.49 (dd, 2H, J = 6.5, 13.5 Hz), 2.76 (t, 2H, J = 7.25 Hz), 2.38 (d, 3H, J = 5 Hz), 2.01 -267- 200524880 (s, 3H). MS (APCI, m / z): 611 (M + 1) + · HPLC (reverse phase): Rt. (min) = 3.10. Example 283 N2-phenyl-6- {N, -[[Pyridine-4-yl-ethylene]]-hydrazinopyrimidine_2,4-diamine (compound number 6) was reacted and purified according to the method of Example 1 to obtain the target compound (41 mg, 20 %). MS (APCI, m / z): 320 (M + l) +. HPLC (reverse phase): Rt. (Min) = 2.53. Example 284 N-Methyl- 4- (l-{[5-phenyl-2-aniline-6- (3-pyridin-4-yl-propylamino) -pyrimidin-4-yl] -hydrazinyl Ethyl) -sulfenamide (Compound No. 1 233) was reacted and purified according to the method of Example 9 to obtain the target compound (105 mg, 27%). ^ -NMRCSOO MHz, DMSO-d6) δ ppm: 9.02 (brs, 1H), 8.70 (d, 2H, J = 6.5 Hz), 8.37 (brs, 2H), 7.80-7.70 (m, 7H), 7.64-7.58 (m, 3H), 7.53 (t, 1H, J = 7.0 Hz), 7.44 (d, 2H, J = 8.0 Hz), 7.40 (t, 2H, J = 7.0 Hz), 7.28-7.22 (m, 1H) , 7.15 (t, 1H, J = 7.0 Hz), 3.50-3.20 (m, 2H), 2.83 (t, 2H, J = 7.0 Hz), 2.42 (d, 3H, J = 5.0 Hz), 2.14 (s, 3H), 1.98- 1.93 (m, 2H). MS (APCI, m / z): 607 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 3.40. -268- 200524880 Example 285 N-methyl-4- (l-{[5-phenyl-2-aniline-6- (3-p-pyridin-4-yl-pyrrol-1-yl) -pyrimidin-4-yl Benzaziridinylethyl) -benzenesulfonamide (Compound No. 1237) was reacted and purified according to the method of Example 9 to obtain the target compound (61 · 1 mg, 83%). 〇1H-NMR (500 MHz, DMSO -d6) 5 ppm: 9.75 (brs? iH), 8.52 (s, 1H), 8.43 (s, 2H), 8.12-7.97 (m, 2H), 7.82 (d, 2H, J = 7.8 Hz), 7.59- 7.30 (m, 13H), 7.01 (brs, IH), 6.83 (s, 1H), 6.62 (s, 1H), 2.44 (d, 3H, J = 4.4 Hz), 2.05 (s, 3H). MS (APCI , m / z): 615 (M + l) +. HPLC (reverse phase): Rt. (min) = 4.1 0. Reference Example 1 4-Amidino-2,6-bis- (2-methoxyaniline) -pyrimidine 2,4,6-trichloropyrimidine (3.67 g, 20 mmol) was dissolved in Ershuyuan, and 2- Methanilide, stirred for 3 days. After the reaction was completed, it was evaporated under reduced pressure, the residue was dissolved in ethyl acetate, and the organic layer was washed with water. After concentrating, purifying by silica gel column chromatography, a solution of hydrazine monohydrate-ethanol (2: 1, v / v, 30 ml) was added to the obtained residue, and the mixture was stirred at 95 ° C for 6 hours. The reaction solution was cooled at room temperature, and the solvent was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. After concentration, purification by silica gel column chromatography gave the target compound (1.6 6 mg, 24%). HPLC (reverse phase): Rt. (Min) = 3.54 MS (APCI, m / z): 353 (M + 1), Reference Example 2 -269- 200524880 4.6- Dihydroxy-2-aniline pyrimidine (0.456 ml , 5 mmol) was dissolved in ethanol (2 ml), 1H-pyrazole-carboxamidine hydrochloride (7 33 mg, 5 mmol) was added, and the mixture was heated under reflux for 15 hours. The solvent was evaporated under reduced pressure, dissolved in water, and the aqueous layer was washed three times with ether. The water layer was evaporated under reduced pressure and concentrated, and the residue was azeotropically dehydrated with dry ethanol three times. Dissolve in ethanol (20 ml) and add sodium ethoxide (21 wt%, 9.3 ml, 25 mmol). Diethyl malonate (2.3 ml, 15 mmol) was added to the reaction solution, and heated under reflux for 15 hours. Acetic acid was added to stop the reaction, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. After the organic layer was concentrated, diethyl ether was added to the residue, and the precipitated solid was pulverized and collected by filtration, and washed with diethyl ether to obtain the target compound (497 mg, 49%). ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 10.60 (brs, 2H), 8.85 (brs, 1H), 7.62 (d, 2H, J = 7.8 Hz), 7.34-7.27 (m, 2H), 7 〇3 (t, 1H, J = 7.0 Hz), 4.88 (s, 1H) HPLC (reverse phase): Rt. (Min) = 2.25 MS (APCI, m / z): 204 (M + 1) +. Reference Example 3 4.6-Dichloro-2-aniline pyrimidine To 2-phenylamino-4,6-dihydroxypyrimidine (10.1 g, .50 mmol) was added phosphorus oxychloride (15 ml). It was stirred at OO ° C for 6 hours. After completion of the reaction, the reaction solution was evaporated under reduced pressure, the residue was dissolved in ethyl acetate, and the organic layer was washed with a phosphate buffer solution (PH7 · 0) and water. It was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane) to obtain the target compound (10.3 g, 86%). 200524880 HPLC (reverse phase): Rt. (Min) = 5.83 MS (APCI, m / z): 240 (M + 1) +. Reference Example 4 4,6-Dihydrazino-2-aniline pyrimidine Add 2-aniline-4,6-dichloropyrimidine to a solution of hydrazone 1 hydrate-ethanol (2: 1, Wv, 15 ml) at 90 Stir at ° C for 2 hours. The reaction solution was cooled at room temperature, water was added to the reaction solution, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate and dried under reduced pressure to obtain the desired product. 1H-NMR (270 MHz, DMS 0-d6) 5 ppm: 8.47 (s, 1H), 7.79 (d, 2H, J = 7.8 Hz), 7.27 (s, 2H), 7.15 (t, 2H, J = 7.6 Hz), 6.79 (t, 1H, J = 5.4 Hz), 5.59 (s, 1H), 4.07 (brs, 4H) HPLC (reverse phase): Rt. (Min) = 2.35 MS (APCI, m / z): 232 (M + l) +. Reference Example 5 4-hydrazino-2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidine mg, 0.2 mmol) of ethanol (1.5 ml) was added to 2- (4-pyridyl) -malonate diacetaldehyde (33 mg, 0.22 mmol), and heat refluxed for 6 hours. After the reaction, the residue was concentrated and purified by silica gel column chromatography to obtain the target substance. HPLC (reverse phase): Rt. (Min) = 2.74 MS (APCI, m / z): 345 (M + 1) +. Reference Example 6 l- {[2- (trimethylsilyl) ethoxy] methyl 丨 pyrazol-5-yl-pyridine according to Han, Qi method (Han, Qi; Chang, Chong-H w an; Li,- 271-200524880

Renhua; Ru, Yu; Jadhav, Prabhakar K .; Lam, Patrick Y. s J. Med. Chem. 41, 1998, 2019-2028) Synthesis of l-{[2- (trimethylsitridyl) ethoxy) ] Methyl} pyrazolyl-5-boronic acid (1.52 g, 5 mmol) in benzene (100 ml), add methanol (20 ml), water (5 ml), and then add sodium carbonate (2.1 g, 20 mmol) ), 4-bromopyridine hydrochloride (1.94 g, 10 mmol), triphenylphosphine palladium (580 mg, 0.5 mmol), and heated to reflux under nitrogen for 18 hours. After the reaction, the mixture was extracted with ethyl acetate / saturated aqueous sodium hydrogen carbonate solution, and the organic layer was concentrated. The residue was purified by silica gel column chromatography to obtain ^ {[2- (trimethylsilyl) ethoxy] methyl} pyrazolyl- 5-pyridine (0.96 g, 44%). 1H-NMR (270 MHz, CDCL3) (5 ppm: 8.69 (dd, 2H, J = 1.6 Hz, 4.6 Hz), 7.61-7.59 (m, 3H), 6.55 (d, 1H, J = 1.9 Hz), 5.48 (s, 2H), 3.80-3.74 (m, 2H), 0.99-0.82 (m, 2H), 0.00 (s, 9H) MS (APCI, m / z): 276 (M + l) +. Reference Example 7 4-hydrazino-2-aniline-6- (3-pyridin-4-yl-pyrazol-1-yl) -pyrimidine on 1-{[2 · (trimethylsilyl) ethoxy] methyl} pyridine Add azole-5-yl-pyridine (55 1 mg, 2 mm ο 1) to 4 M hydrochloric acid / Ershuyuan solution, stir at room temperature for 1 hour, evaporate the solvent under reduced pressure, and azeotrope with toluene to obtain 4- ( 1Η-pyrazol-3-yl) -pyridine. In addition, sodium hydride (2 6 1 mg, 6 mm ο 1) in Ν, Ν -dimethylformamide (5 ml) at 0 ° C It was dissolved under reduced pressure, and the obtained 4- (1Η-pyrazol-3-yl) -pyridine was added. 4,6 · Dichloro-2-aniline (480 mg, 2 mmol) was added, and the mixture was stirred at room temperature for 3 hours. In the reaction solution An ammonium chloride aqueous solution was added to stop the reaction, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried, and concentrated. ) Solution, and stirred at 95 ° C for 2 hours. After cooling at room temperature, water was added to the reaction solution, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate and dried under reduced pressure to obtain the target substance. HPLC (reverse phase): Rt. (Min) = 3.25 MS (APCI, m / z): 345 (M + l) +. Reference Example 8 4-hydrazino-2-aniline-6- (2-pyridin-4-yl-ethylamino) -pyrimidine 4,6-Dichloro-2-aniline pyrimidine (240 mg, 1 mmol) was dissolved in ethanol (5 ml), and 2-pyridin-4-yl-ethylamine (0.142 ml, 1.2 mmol) and triethylamine (0.20) were added. 8 ml, 1.5 mmol) and heated to reflux for 1 hour. After the reaction, the mixture was extracted with ethyl acetate / water, and the organic layer was dried and concentrated. After concentration, hydrazine 1 hydrate-ethanol (2: 1, v / v, 3 ml) solution, stirred at 95 ° C for 2 hours. The reaction solution was cooled at room temperature, concentrated, and then ether was added. The precipitated solid was pulverized and filtered. The obtained solid was washed with water and ethyl acetate, and the pressure was reduced. Dry to obtain the target compound (235 mg, 73%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 8.9 (brs, 1H), 8.48-8.46 (m, 2H), 7.81-7.75 (m, 2H), 7.29-7.22 (m, 2H), 7.18-7.13 (m, 2H), 6.83-6.76 (m, 1H), 6.59 (brs, 1H), 5.59 (s, 1H), 5 .33 (s, 1H), 4.15 (brs, 2H), 3.51-3.48 (m, 2H), 2.89-2.84 (m, 2H) HPLC (reverse phase): Rt. (Min) = 2.42 MS (APCI , M / z): 322 (M + l) +. Reference Example 9 -273-200524880 4-hydrazino-2-aniline-6- (2-pyridin-3-yl-ethylamino) -pyrimidine 4,6_dichloro-2_aniline and 2_ (pyridine Group) -ethylamine, which can be reacted according to the method of Reference Example 8 to obtain the target substance. HPLC (reverse phase): Rt. (Min) = 2.49 MS (APCI, m / z): 322 (M + 1) +. Reference Example 1 0 4- [2- (6-Hydrazin-2-anilinopyrimidin-4-ylamino) -ethylbenzenesulfonamide was used 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) and 4, (2. Ethylamino) -benzenesulfonamide (240 mg, 1.2 mmol). The target compound can be obtained by reacting according to the method of Reference Example 8. ^ -NMR (270 MHz, DMS 0-d6) (5 ppm: 8.46 (s, 1H), 7.δκ 7.74 (m, 4H), 7.43 (d, 2H, J = 8.1Hz), 7.28 (s, lH ), 7.l9-7.13 (m, 3H), 6.81 (t, 1H, J = 7.3 Hz), 6.57 (brs, 1H), 5.33 (s, 1H), 4.08 (brs, 1H), 3.51-3.46 ( m, 2H), 2.91 (t, 2H, J = 7.8 Hz) yi HPLC (reverse phase): Rt. (min) = 3.19 MS (APCI, m / z): 400 (M + 1) +. Reference Example 11 4-hydrazino-2-aniline-6- (2-thien-2-yl-ethylamino) -pyrimidine by 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol), using 2- Thien-2-yl-ethylamine (0.35 ml, 3 mmol) was reacted according to the method of Reference Example 8 to obtain the target compound (254 mg, 78%). HPLC (reverse phase): Rt. (Min) = 3.67 MS ( APCI, m / z): 327 (M + l) +. -274- 200524880 Reference Example 12 4-Amino-6- [2- (4-methoxyphenyl factory ethylamino) -2-aniline 4,6-Dichloro-2-aniline memididine (240 mg, 1 mmol), using 2- (4-methoxyphenyl) -ethylamine (0.439 ml, 3 mmol), according to the method of Reference Example 8 The target compound was obtained (252 mg, 72%). HPLC (reverse phase): Rt. (Min) = 3.77 MS (APCI, m / z): 351 (M + l) +. Reference Example 1 3 4- [2- (3,4-Dimethoxy ) _Ethylamino-6-hydrazino-2_aniline pyrimidine was determined from 4,6-dichloro-2-aniline (240 mg, 1 mmol) using 2 (3,4-dimethoxyphenyl ) -Ethylamine (0.506 ml, 3 mmol). The target compound (3 31 mg, 87.7%) can be obtained according to the method of Reference Example 8.] H-NMR (270 MHz, DMSO-d6) (5ppm: 8 · 47 (s, 1H), 7.80 (d, 2H, J = 7.8 Hz), 7.19-7.12 (m, 3H), 6.90-6.74 (melon, 4H) '6.55-6.42 (m, 1H) , 5.33 (s, 1H), 4.12 (brs, 2H), 3 "(S '7 4 3H), 3.72 (s, 3H), 3.48-3.35 (m, 2H), 2.77 (t, 2H, J ^

Hz) HPLC (reverse phase): Rt. (Min) = 3.56 MS (APCI, m / z): 381 (M + l) +. Reference Example 14 4- [2- (2,5-Dimethoxyphenyl) -ethylamino] -6-hydrazino-2-aniline pyrimidine was prepared from 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol), using (2,5-dimethoxyphenyl) -ethylamine (0.499 ml, 3 mmol), according to the method of Reference Example 8 to obtain the target compound (266 mg, 70%). -275-200524880 HPLC (reverse phase): Rt. (Min) = 3.99 MS (APCI, m / z): 381 (M + l) + 〇 Reference Example 1 5 Hydrazine-6- [2_ (3_methoxy Phenyl) -ethylamino] aniline is composed of 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2- (3. Methoxyphenyl) -ethylamine (0.437 ml, 3 mmol ), According to the method of Reference Example 8 to obtain the target product (175 g, 49%). HPLC (reverse phase) Rt. (Min) = 3.91 MS (APCI, m / z): 351 (M + 1) + 〇Reference Example 16 4,6-Dihydroxy-5-phenyl-2-aniline Dissolve the aniline (0.456 ml, 5 mmol) in ethanol (2 ml), add 1Π-Πbile-1 · residue formamidine (733 mg, 5 mmol) and heat to reflux for 15 hours. After the reaction, ethanol (18 ml), sodium ethoxide (21 wt%, 9.3 ml, 25 mmol) and diethyl phenylmalonate (3.2 ml, 15 mmol) were added, and the mixture was heated under reflux for 15 hours. The reaction was stopped and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. After the organic layer was concentrated, diethyl ether was added to the residue, and the precipitated solid was pulverized and collected by filtration, and washed with diethyl ether to obtain the target substance (585 mg, 40%). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 10.67 (brs, 2H), 8.80 (s, 1H), 7.69 (d, 2H, J = 7.3 Hz), 7.46 (d, 2H, J = 7.6 Hz), 7.34 (t, 2H, J = 7.6 Hz), 7.28 (t, 2H, J = 7.3 Hz), 7.14 (t, 1H, J = 7.6 Hz), 7.06 (t, 1H, J = 7.3 Hz ) HPLC (reverse phase): Rt. (Min) = 3.42 200524880 MS (APCI, m / z): 280 (M + l) +. Reference Example 17 4,6-Dichloro-5-phenyl-2-aniline pyrimidine To 4,6-dihydroxy-5-phenyl-2-aniline pyrimidine (279 mg, 1 mmol) was added phosphorus oxychloride (1 ml) and stirred at 100 ° C for 6 hours. After the reaction was completed, it was evaporated under reduced pressure, the residue was dissolved in ethyl acetate, and the organic layer was washed with water. After concentration, purification by silica gel column chromatography gave the target compound (167 mg, 53%). 1H-NMR (270 MHz, DMS 0-d6) 5 ppm: 10.44 (brs, 1H), 7.70 (d, 2H, J = 7.6 Hz), 7.53-7.30 (m, 7H), 7.06 (t, 1H, J = 7.6

Hz) HPLC (reverse phase): Rt. (Min) = 6.32 MS (APCI, m / z): 316 (M + 1) + 〇 Reference Example 18 4-Chloro-6-hydrazino-5-phenyl-2 -Aniline. After dissolving 4,6-monoki-5-benzyl-2-aniline & meperidine (366 mg, 1.3 mmol) in ethanol (0.5 ml), add hydrazine monohydrate (1 ml). And stirred at room temperature for 3 hours. After the reaction was completed, the reaction mixture was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate 'and the organic layer was washed with water. After concentration, purification by silica gel column chromatography gave the title compound (229 mg, 57%). HPLC (reverse phase): Rt. (Min) = 4.18 MS (APCI, m / z): 312 (M + 1) +. Reference Example 19 Aniline (5.96 ml, 65 mmol) was dissolved in ethanol (2 ml) via 5--5-phenyl-2-aniline chelation, and -277- 200524880 hydrochloric acid 1 hydrazone-pyrazole-1-carboxymethyl was added. Rhenium (9.5 g, 65 mmol) was heated under reflux for 15 hours. The sodium ethoxide (21 wt%, 9.3 m1, 25 mmo1) of the solution after the reaction was mixed with ethyl acetate (4 ml, 100 mmol) and N, N-dimethylformamide diamine in another reaction container. Acetaldehyde (17 ml, 100 mmol) was heated and stirred at 140 ° C for 24 hours and then added. After heating and refluxing for 15 hours, acetic acid was added to stop the reaction, and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane and the organic layer was washed with water. The organic layer was concentrated and purified by column chromatography to obtain the target compound (4.4 g, 26%). ! H-NMR (270 MHz, DMS 0-d6) 5 ppm: 8.90 (brs, 1H), 8.00 (s, 1H), 7.67-7.62 (m, 4H), 7.39-7.27 (m, 6H), 7.06 ( t, 1H, J = 7.3 Hz) HPLC (reverse phase): Rt. (min) = 4.06 MS (APCI, m / z): 264 (M + l) + 0 Reference Example 20 4-hydrazino-5-benzene Phenyl-2-aniline is added to 4-hydroxy-5-phenyl-2-aniline pyrimidine (4.9 g, 18.6 mmol), and phosphorus oxychloride (1 ml) is added, followed by stirring at 100 ° C for 6 hours. After the reaction was completed, the reaction mixture was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate. The organic layer was washed with a phosphate buffer solution (pH 7.0) and water. After concentration, purification by silica gel column chromatography, a solution of hydrazine monohydrate-ethanol (2: 1, v / v, 3 ml) was added to the obtained residue, and the mixture was stirred at 95 ° C for 2 hours. The reaction solution was cooled at room temperature, water was added to the reaction solution, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the desired product (4.0 g, 78%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 9.18 (s, 1H)? 7.83 (dd, -278-200524880 2H? J = 1.1 Hz, 8.6 Hz), 7.75 (s, 1H), 7.60 (s , 1H), 7.46-7.22 (m, 7H), 6,89 (t, 1H, J = 7.3 Hz), 4.40 (brs, 2H) HPLC (reverse phase): Rt. (Min) = 2.85 MS (APCI, m / z): 27 8 (M + 1) +. Reference Example 21 4-Hydrazine-methylamino-5-phenyl-2-aniline pyrimidine was added to 4,6-dichloro-5-phenyl-2-aniline pyrimidine (250 mg, 0.79 mmol), and 2M was added. N-methylamine / methanol solution (4 ml, 8 mmol) and heated at reflux for 1 hour. After the reaction was completed, the solvent was distilled off under reduced pressure. The residue in ethanol (0.5 ml) was added with hydrazine monohydrate (1 ml) and stirred at 10 ° C for 24 hours. The reaction solution was cooled at room temperature and concentrated. Water was added, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the target substance. HPLC (reverse phase) Rt. (Min) = 3.63 MS (APCI , M / z): 307 (M + 1) +. Reference Example 22 6-Amino-4-hydrazino-5-phenyl-2-aniline pyrimidine 4,6-dichloro-5-phenyl-2 -Aniline (211 mg, 0.668 mmol) was sealed with 7M ammonia / methanol solution (5 ml), and stirred at 60 ° C for 7 days. Extracted with ethyl acetate / water, the organic layer was concentrated, and ether was added. The precipitated solid was pulverized and collected by filtration. The obtained solid was dissolved in ethanol (0.5 ml), hydrazine monohydrate (1 ml) was added, and the mixture was stirred at 100 ° C for 24 hours. The reaction solution was cooled at room temperature and concentrated. Water was added, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the target substance of -279- 200524880. 1H-NMR (270 MHz, DMS 0 > d 6 ) 5 pp m: 8.84 (s, 1H), 7.85 (d, 2H, J = 7.6 Hz), 7.46 (t, 2H, J = 7.3 Hz), 7.39-7.14 (m, 6H), 6.83 (t, 1H, J = 7.3 Hz), 6.08 (s, 1H), 5.24 (s, 2H), 4.16 (s, 2H) HPLC (reverse phase): Rt. (Min) = 3.29 MS (APCI, m / z): 29 3 (M + l) + Reference Example 23 5- (2-Bromophenyl) -4-hydroxy-2-aniline pyrimidine was reacted from ethyl 2-bromophenylacetate (10 mmol) according to the method of Reference Example 19 to obtain the objective. (23 8 mg, 14%). HPLC (reverse phase): Rt. (Min) = 4.31 MS (APCI, m / z): 342 (M + 1) + 〇 Reference Example 24 5- (2-Bromobenzene Amino) -4-hydrazino-2-aniline pyrimidine is obtained from 5- (2-bromophenyl) -4-hydroxy-2-aniline pyrimidine (171 mg, 0.5 mmol) according to the method of Reference Example 20 ( 4 lmg, 23%). HPLC (reverse phase): Rt. (Min) = 3. 18 MS (APCI, m / z): 35 6 (M + l) +. Reference Example 25 4-hydroxy-2-benzene Ethylamino-5-phenylpyrimidine can be obtained from 2-chloro-6-fluorophenyl ethyl acetate (15 mmol) according to the method of Reference Example 19. MS (APCI, m / z): 292 (M + l) +. -280- 200524880 Reference Example 2 6 4-Amino-2-phenylethylamino-5-phenylpyrimidine from 4-hydroxy-2-phenylethylamino-5-phenylpyrimidine (124 mg, 426 mmol), The reaction was carried out according to the method of Reference Example 20 (77 mg, 59%). HPLC (reverse phase): Rt. (Min) 3.07 MS (APCI, m / z): 306 (M + 1) + 〇Reference Example 2 7 4-hydroxy-5- (2-methoxyphenyl) -2 -Aniline is obtained from ethyl 2-methoxyphenylacetate (10 mmol) according to the method of Reference Example 19 (50 mg, 3%). HPLC (reverse phase): Rt. (Min) = 3.87 MS (APCI, m / z): 294 (M + 1) +. Reference example 2 8 4-Hydrazine-5- (2-methoxyphenyl) -2-aniline pyridine was determined by 4-amyl-5- (2-methoxyphenyl) -2-aniline (50 mg (0.7 mmol), which can be obtained by performing the reaction according to the method of Reference Example 20 (18 mg, 35%). HPLC (reverse phase): Rt. (Min) 3.07 MS (APCI, m / z): 308 (M + 1) +. Reference Example 29 5- (4-Fluorophenyl) -4-hydroxy-2-aniline pyrimidine was obtained from ethyl 4-fluorophenylacetate (10 mmol) according to the method of Reference Example 19 (155 mg, 11 1%). HPLC (reverse phase): Rt. (Min) = 4.20 MS (APCI, m / z): 282 (M + 1) + 〇200524880 Reference Example 30 5- (4-fluorophenyl)-[fluorenyl-2- Aniline can be obtained by reacting 5- (4-fluorophenyl) -4-hydroxy-2-aniline pyrimidine according to the method of Reference Example 20. HPLC (reverse phase): Rt. (Min) = 3.03 MS (APCI, m / z): 296 (M + 1) +. Reference Example 3 1 4-Hydrazyl-5-phenyl-2-anilino-6-pyrrolidin-1-yl-pyrimidine was prepared from 4,6-dichloro-5-phenyl-2-aniline mg, 0.5 mmol), using pyrrolidine (0.2 ml, 2.5 mmol), and reacting according to the method of Reference Example 8 to obtain the target compound (130 mg, 92%). HPLC (reverse phase): Rt. (Min) = 4.23 MS (APCI, m / z): 347 (M + 1) +. Reference Example 32 4-Azbutidin-1-yl-6-hydrazino-5-phenyl-2-aniline pyrimidine ), Using azetidine (.169 ml, 2.5 mmol) and reacting according to the method of Reference Example 8 to obtain the target compound (136 mg, 82%). 1 Η-NMR (2 7 Ο Μ H z, DMS Ο-d 6) (5 ppm: 8 · 8 3 (s, 1 Η), 7 · 8 5 (d, 2 Η, J = 7 · 6 Η z ), 7 · 4 3-7 · 1 7 (m, 7 Η), 6 · 8 4 (t, 1 Η, J = 2 · 4 Hz), 5.99 (s, 1H), 4.18 (brs, 2H), 3.52 (t, 4H, J = 7.3 Hz), 2.03- 1.92 (m, 2H) HPLC (reverse phase): Rt. (Min) = 4.07 MS (APCI, m / z): 33 3 (M + l) + -282- 200524880 Reference Example 3 3 1- (6-fluorenyl-5-phenyl-2-anilinopyrimidinyl) -piperidine-3-carboxyhydrazine from 4,6-dichloro-5-phenyl- 2-Aniflupyrimidine (158 mg, 0.5 mmol) was reacted with 3-Aminopyridine (320 mg, 2.5 mmol) according to the method of Reference Example 8 to obtain the target compound (196 mg, 94%). Phase): Rt. (Min) = 3.05 MS (APCI, m / z): 419 (M + 1) +. Reference Example 3 4 1-(6 -hydrazino-5 -phenyl-2 -aniline -4 -yl) -piperidine-4 -residone hydrazine was determined from 4,6-dichloro-5-phenyl-2-aniline pyridine (158 mg, 0.5 mmol) using 4-aminoformamidine Ondidine (320 mg, 2.5 mmol) was reacted according to the method of Reference Example 8 to obtain the target compound (172 mg, 82%). HPLC (reverse phase): Rt. (Min) = 2.93 MS (APCI, m / z ): 419 (M + l) + 〇Reference Example 3 5 4-N, N-dimethylamino-6-hydrazino-5-phenyl-2-aniline pyrimidine , 0.5 mmol), using dimethylamine hydrochloride (2.0 mg, 2.5 mmol) and triethylamine (0.184 ml, 2.5 mmol), and reacting according to the method of Reference Example 8 to obtain the target compound (丨 3 4 mg, 8 4%) HPLC (reverse phase): Rt. (Min) = 3.95 MS (APCI, m / z): 321 (M + 1) +. Reference Example 3 6 4-hydrazino-5-phenyl-2-aniline -6- (2-pyridin-4-yl-ethylamino) -pyrimidine-283-200524880 by 4,6-dichloro-5-phenyl-2-aniline pyridine (158 mg, 0.5 mmol ), Using 2-pyridin-4-yl-ethylamine (0.297 ml, 2.5 mmol) and reacting according to the method of Reference Example 8 to obtain the target compound (185 mg, 93%). 1H-NMR (270 MHz? DMS 0-d6) 5 ppm: 8.82 (s? 1H)? 8.49- 8.39 (m, 2H), 7.84 (d, 2H, J = 7.8 Hz), 7.45 (t, 2H, J = 8.6 Hz), 7.37-7.32 (m, 2H), 7.25-7.14 (m, 6H), 6.86 (t, 1H, J = 8.4 Hz), 5.94 (s, 1H), 5.20 (t, 1H, J = 5.7 Hz), 4.14 (brs, 2H), 3.55 (dd, 2H, J = 6.5 Hz, 13.8 Hz), 2.81 (t, 2H, J = 7.8 Hz) HPLC (reverse phase): Rt. (Min) = 2.78 MS (APCI, m / z): 3 98 (M + 1), Reference Example 37 2- [2- (6-hydrazino-5-phenyl-2-phenylaminopyrimidin-4-ylamino) -ethoxy Propyl] -ethanol was determined from 4,6-monochloro-5-phenyl-2-aniline hydrazone (158 mg, 0.5 mmol) 'using 2- (2-amineethoxy) ethanol (0.248 ml, 2.5 mm ο 1). The target compound (169 mg, 89%) can be obtained by reacting according to the method of Reference Example 8. ] Η-NMK (270 MHz, DMS 0-d6) 5 ppm: 8.81 (s, 1H), 7.84 (d, 1H, J = 7.8 Hz), 7.50-7.33 (m, 3H), 7.24-7.19 (m, 4H), 6.85 (t, 1H, J = 7.3 Hz), 5.99 (s, 1H), 4.53 (t, 1H, J = 5.1 Hz), 4.16 (brs, 2H), 3.48-3.36 (m, 8H) HPLC (Reverse phase): Rt. (Min) = 3.17 MS (APCI, m / z): 381 (M + l), Reference Example 3 8 Amidino-5-phenyl-2-anilino-6-fluorene Titanium-1-yl-pyrimidine D-284- 200524880 Put 4,6-dichloro-5-phenyl-2-aniline pyrimidine (3.16 g, 10 mmol) in N, N-dimethylformamide ( 50 ml), and sodium hydride (55% oil, 1 g, 24 mmol) was dissolved in N, N-dimethylformamide (20 ml), and 1H-pyrazole (1.5 g, 22 mmol) was added. After stirring at 0 ° C for 5 minutes, the solution was added dropwise at room temperature, and then stirred at room temperature for 15 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate. The organic layer was washed with water and concentrated to obtain the desired 4,6-bis (1H-pyrazolyl) -5-phenyl-2-aniline pyrimidine. Refined. Add a solution of hydrazine monohydrate-ethanol (2: 1, v / v, 15 ml) and stir at 95 ° C for 18 hours. The reaction solution was cooled at room temperature, concentrated, ethanol was added, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the desired product (1.99 g, 59%). 1H-NMR (270 MHz, DM S Ο-d6) δ ppm: 9.46 (s, 1H), 7.96-7.95 (m, 1H), 7.86-7.82 (m, 2H), 7.40-7.19 (m, 6H), 7.10- 6.90 (m, 4H), 6.28 (dd, 2H, J = 1.9 Hz, 2.7 Hz), 4.47 (brs, 2H) HPLC (reverse phase): Rt. (Min) = 3.75 MS (APCI , M / z): 344 (M + l) +. Reference Example 39 Cyclopropylamino-6-pentyl-5-phenyl-2-aniline Mouth: u determined by 4,6-dichloro-5-phenyl-2-aniline pyrimidine (158 mg, 0.5 mm 〇1), using cyclopropylamine (. 0 ml, 2.5 mmol), according to the method of Reference Example 8 to obtain the target product (157 g, 95%). HPLC (reverse phase): Rt. (Min) = 3.96 MS (APCI, m / z): 33 3 (M + 1) + 〇-285-200524880 Reference Example 4 〇 4_hydrazino-6- [2- ( 3Η-imidazolyl) · Ethylamine 5-phenyl-I aniline pyridine is determined by 4,6-monochloro-5-phenyl-2-propimidine II (158 mg, 0.5 mmol), using 2 -(3H-imidazo-4-yl) -ethylamine (278 mg, 2.5 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (180 g, 93%). HPLC (reverse phase): Rt. (Min) = 2.59 MS (APCI, m / z): 387 (M + 1) +. Reference Example 41 2- (6-hydrazino-5-phenyl-2-anilinepyrimidin-4-ylamino) -ethanol was determined from 4,6-dichloro-5-phenyl-2-aniline (158 mg, 0.5 mmol), using 2-amine ethanol (0.151 ml, 2.5 mmol), reacted according to the method of Reference Example 8 to obtain the target compound (135 g, 80%). HPLC (reverse phase): Rt. (Min) = 3. 17 MS (APCI, m / z): 3 37 (M + 1) +. Reference Example 4 2 N '-(6-hydrazino-5-phenyl-2-phenylaminopyrimidin-4-yl) -N, N-dimethylethane-1,2, diamine consisting of 4,6-di Chloro-5-phenyl-2-aniline pyrimidine (158 mg, 0.5 mmol) using N, N-dimethylethylenediamine (0.272 ml, 2.5 mmol) and reacting according to the method of Reference Example 8 to obtain the target substance (162 g, 90%). HPLC (reverse phase) Rt. (Min) = 2.44 MS (APCI, m / z): 364 (M + 1) +. Reference Example 43 4-Hydrazine-6- (2-methoxyethylamino) -5-phenyl-2-phenylaminopyrimidine-286- 200524880 By 4,6-dichloro-5-phenyl-2-aniline Fluoride (158 mg, 0.5 mmol), using 2-methoxyethylamine (0.217 ml, 2.5 mmol), and reacting according to the method of Reference Example 8 to obtain the target compound (142 g, 81%). HPLC (reversed phase): Rt. (Min) = 3.69 MS (APCI, m / z): 351 (M + 1) + 〇Reference Example 44 4-hydrazino-6-imidazole-butyl-5-phenyl- 2-aniline pyrimidine Dissolve 4,6-dichloro-5-phenyl-2-aniline pyrimidine (158 mg, 0.5 mmol) in N, N-dimethylformamide (2 ml), and sodium hydride (55% oil, 33 g, 0.75 mmol) was dissolved in N, N-dimethylformamide (1 ml), 1H-imidazole (41 mg, 0.6 mmol) was added, and the mixture was stirred at 0 ° C for 5 minutes. The solution was added dropwise at room temperature and stirred for 5 hours at room temperature. After the reaction, the solvent was distilled off under reduced pressure, the residue was dissolved in ethyl acetate, the organic layer was washed with water, and concentrated to obtain the desired (1H-imidazolyl) -6-chloro-5-phenyl-2-aniline. Steep refined product. Add a solution of hydrazine monohydrate-ethanol (2 ·· 1, ν / ν, 1.5 ml) and stir at 95 ° C for 18 hours. The reaction solution was cooled at room temperature, concentrated, and ethanol 'was added to pulverize the precipitated solid, followed by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the desired product. 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9.46 (s, 1H), 7.82 (d 2H, J = 7.8 Hz), 7.54-7.53 (m, 1H), 7.48-7.44 (m, 3H) , 7.42-7.18 (m, 5H), 6.96-6.91 (m, 2H), 6.80) t, 1H, J = ι · 4

Hz), 4.47 (brs, 2H) HPLC (reverse phase): Rt. (Min) = 2.87 MS (APCI, m / z): 344 (M + 1) + 〇-287 '200524880 Reference Example 45 4 -5-phenylanilino-6- [l, 2,3] triazol-1-yl-pyrimidine and 4-hydrazino-5-phenyl-2-anilino-6- [1,2,3] Triazol-2-yl-pyrimidine was treated with 4,6-dichloro-5-phenyl-2-aniline (158 mg, 0.5 mmol) 'using 1H- [1,2,3] triamidine (0.035 ml , 0.6 mmol), according to the method of Reference Example 44 to obtain a mixture of the title object. HPLC (reverse phase): Rt. (Min) = 3.59, 3.70 MS (APCI, m / z): 345 (M + 1), Reference Example 46 4-hydrazino-5-phenyl-2-aniline-6 -[l, 2,4] _triazol-1-yl-pyrimidine and hydrazino-5-phenyl-2-aniline-6- [1,2,4 , 6-Dichloro-5-phenyl-2-aniline pyrimidine (158 mg, 0.5 mmol) using 1H- [1,2,4] triazole (41 mg, 0.6 mmol), the reaction can be carried out according to the method of Reference Example 44 A mixture of the title objects was obtained. HPLC (reverse phase): Rt. (Min) = 3.37 MS (APCI, m / z): 345 (M + 1) + 〇 Reference Example 47 4,6-diazino-5-phenyl-2-aniline pyrimidine Add 4,6-dichloro-5-phenyl-2-aniline pyrimidine (3 15 mg, 1 mmol) to a solution of hydrazine monohydrate-ethanol (2: 1, v / v, 3 ml) at 95 ° Stir at C for 2 hours. The reaction solution was cooled at room temperature, water was added to the reaction solution, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the desired product (154 mg, 50%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 9.03 (s, 1H), 7.87 (d, 200524880 2H, J = 7.3 Hz), 7.79-7.18 (m, 7Η), 6.88 (t, 1H, J 7.3 Hz), 6.23 (s, 2H), 4.45 (brs, 4H) HPLC (reverse phase): Rt. (min) = 2.82 MS (APCI, m / z): 308 (M + l), Reference Example 4 8 4-hydrazino-5-phenyl-2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidine by 4,6-dichloro- 5-phenyl-2-aniline pyrimidine can be reacted according to the method of Reference Example 5 to obtain the target substance. 1H-NMR (270 MHz, DMS Ο-d6) (5 ppm: 9.51 (s, 1H), 8.62 (d, 1H, J = 0.8 Hz), 8.49 (dd, 2H, J = 1.7 Hz, 4.6 Hz), 8.03 (d, 1H, J = 0.8 Hz), 7.86 (dd, 2H, J = 1.0 Hz, 8.6 Hz), 7.53 (dd, 2H, J = 1.6 Hz, 4.6 Hz), 7.38-7.24 (m, 5H) , 7.20 (s, 1H), 7.15-7.10 (m, 2H), 6.94 (t, 1H, J = 7.3 Hz), 4.52 (brs, 2H) HPLC (reverse phase): Rt. (Min) = 2.92 MS ( APCI, m / z): 421 (M + l) +. Reference Example 49 5- (2-fluorophenyl X hydroxy-2-aniline pyrimidine from ethyl 2-fluorophenylacetate (10 mmol), according to the reference example The target compound (130 mg, 9%) can be obtained by the method of 19. 1 Η-NMR (2 70 MHZ, DMS 0, d 6) δ ppm: 1 1 · 0 8 (brs, 1 Η), 8 9 4 (brs, 1Η), 7.86 (s, 1Η), 7.63 (d, 2Η, J = 7.6 Ηζ), 7.47 (t 1H, J = 7.6 Hz), 7.40-7.30 (m, 3H), 7.22 (t, 2H, J = 7 6 Hz), 7.06 (t, 1H, J = 7.6 Hz) -289- 200524880 HPLC (reversed phase): Rt. (min) = 4.10 MS (APCI , m / z): 282 (M + 1) +. Reference Example 5 0 5- (2-fluorophenyl) -4-hydrazino-2-aniline pyrimidine by 5- (2-fluorophenyl) -4 · Hydroxy-2-aniline (116 mg, 0.413 mmol), by reference The reaction method of 20 can obtain the target compound (91 mg, 75%) ° 1H-NMR (270 MHz, DMS 0 ^ d6) 5 ppm: 9.22 (s, 1H), 7.83 (d, 2H, J = 7.6 Hz), 7.70 (brs, 1H), 7.70 (brs, 1H), 7.45-7.30 (m, 4H), 7.25 (t, 2H, J = 7.6 Hz), 6.90 (t, 1H, J = 7.6 Hz), 4.41 (brs , 2H) HPLC (reverse phase): Rt. (Min) = 2.83 MS (APCI, m / z): 296 (M + 1) + 〇 Reference Example 5 1 4-hydroxy-5- (3-methoxyphenyl ) -2-aniline pyrimidine was reacted from ethyl 3-methoxyphenylacetate (.10 mmol) according to the method of Reference Example 19 to obtain the target compound (145 mg, 10%). HPLC (reverse phase): Rt. (Min) = 4.09 MS (APCI, m / z): 294 (M + 1) +. Reference Example 52 4-Hydrazyl-5- (3-methoxyphenyl) -2-aniline pyrimidine was prepared from 4-amyl-5- (3-methoxybenzyl) -2-aniline (130 mg, 0.444 mmol), and reacted according to the method of Reference Example 20 to obtain the target compound (104 mg, 7 6%). -290- 200524880 1H-NMR (270 MHz, DMSO-d 6) 5 pp m: 9.20 (brs, 1H), 7.83 (d, 2H, J = 7.6 Hz), 7.77 (s, 1H), 7.65 (brs, 1H), 7.34 (t, 1H, J = 7.6 Hz), 7.25 (t, 2H, J = 7.6 Hz), 6.97-6.85 (m, 4H), 4.41 (brs, 2H), 3.79 (s, 3H ) HPLC (reverse phase): Rt. (Min) = 2.94 MS (APCI, m / z): 308 (M + 1) +. Reference Example 53 5- (2,5-dichlorophenyl) -4-hydroxy-2-aniline pyrimidine was prepared from ethyl 2,6-dichlorophenylacetate (10 mmol) according to the method of Reference Example 19. The target substance (170 mg, 11%) was obtained. HPLC (reverse phase): Rt. (Min) = 4.48 MS (APCI, m / z): 332 (M + 1) +. Reference Example 54 5- (2,6-dichlorophenyl) -4-hydrazino-2-aniline pyrimidine by 5- (2,5-dichlorophenyl) -4-hydroxy-2-aniline pyrimidine (130 mg , 0.392 mmol), and reacted according to the method of Reference Example 20 to obtain the target compound (10 mg, 7%). · HPLC (reversed phase) · Rt. (Min) = 3.25 MS (APCI, m / z): 346 (M + 1) +. Reference Example 5 5 4-Hydroxy-5- (2-tolyl) -2-anilidine was reacted with o-toluic acid ethyl acetate (10 mmol) according to the method of Reference Example 19 to obtain the target compound (97 mg, 7% ). 1H-NMR (270 MHz, DMSO-de) ^ ppm: 11.〇5 (brs, 1H), 8.88 -291-200524880 (brs, 1H), 7.69 (s, 1H), 7.64 (d, 2H, J = 7.6 Hz), 7.34 (t, 2H, J = 7.6 Hz), 7.25-7.11 (m, 4H), 7.05 (t, 1H, J = 7.6 Hz), 2.19 (s, 3H) HPLC (reverse phase): Rt . (min) = 4.17 MS (APCI, m / z): 278 (M + l) +. Reference Example 5 6 4-Hydrazyl-2-anilino-5-o-tolyl pyrimidine is determined by 4-Amino-5- (2-methylbenzyl) -2-aniline (85 mg, 0.307 mmol) According to the method of Reference Example 20, the target compound (46 mg, 52%) can be obtained. 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 9.15 (brs, 1H), 7.84 (d, 2H, J = 7.6 H), 7.59 (s, 1H), 7.30-7.18 (m, 3H), 7.24 (t, 2H, J = 7.6 Hz), 7.16-7.08 (m, 2H), 6.88 (t, 1H, J = 7.6 Hz), 4.41 (brs, 2H), 2.14 (s, 3H) HPLC (reverse phase ): Rt. (Min) = 2.95 MS (APCI, m / z): 292 (M + 1) + 〇 Reference Example 57 4-Hydroxy-5-naphthalene-1-yl-2-phenylpyrimidine by Cai-1- -Ethyl acetate (10 mmol), reacted according to the method of Reference Example 19 to obtain the target compound (297 mg, 19%). 1 Η-NMR (2 7 OM Hz, DMS 0-d 6) (5 ppm : 1 1 · 0 9 (brs, 1 Η), 8 · 9 8 (brs, 1H), 7.93 (t, 2H, J = 8.1 Hz), 7.75 (brs, 1H), 7.73 (d, 1H, J = 8.1 Hz), 7.68 (d, 2H, J = 8.1 Hz), 7.57-7.42 (m, 3H), 7.40 (d, 1H, J = 8.1 Hz), 7.36 (t, 2H, J = 8.1 Hz), 7.07 (t, 1H, J = 8.1 Hz) 200524880 HPLC (reverse phase): Rt. (min) = 4.50 MS (APCI, m / z): 314 (M + 1) + 〇 Reference Example 5 8 4- 胼Benzyl-5-naphthalen-1-yl-2-aniline pyrimidine was prepared from 4-hydroxy-5-naphthalen-1-yl-2-aniline pyrimidine (250 mg, 0.799 mm) according to the method of Reference Example 20. The target can be obtained by reaction (178mg, 68%) ° 1H -NMR (270 MHz, DMS 0-d6) 5 pPm: 9 * 24 (blS, 1H),? * 96 (t, 2H, J = 8.1Hz), 7.89 (d, 2H, J = 8,1 Hz) , 7.72 (S, 1H), 7.67-7.44 (m, 4H), 7.40 (d, 1H, J = 8.2 Hz), 7.26 (t, 2H, J = 8.2 Hz), 7.21 (brs , 1H), 6.90 ("1H, J = 8 · 2 Hz), 4 · 40 (brs, 2H) HPLC (reverse phase): Rt. (Min) = 3.23 MS (APCI, m / z): 328 (M + l) +. Reference Example 5 9 5-Biphenyl-4-yl-4-hydroxy-2-aniline pyrimidine The target compound was obtained by reacting biphenylyl-ethyl acetate (10 mmol) according to the method of Reference Example 19. HPLC (reverse phase): Rt. (Min) = 4.90 MS (APCI, m / z): 340 (M + 1) + 〇 Reference Example 6 0 5-biphenyl-4-yl-4-hydrazino-2 -Aniline is obtained from 5-biphenyl-4-yl-4-hydroxy-2-aniline pyrimidine (200 m§, 0.590 mmol) according to the method of Reference Example 20 to obtain the target compound (135 mg, 65%). ). -293- 200524880 HPLC (reversed phase): Rt. (Min) = 3.57 MS (APCI, m / z): 354 (M + 1) +. Reference Example 6 1 5-Benzo [1,3] difluorene §cene-5-yl-4-hydroxy-2-aniline pyrimidine (10 mmol), and reacted according to the method of Reference Example 19 to obtain the target compound (224 mg, 15%). HPLC (reverse phase): Rt. (Min) = 3.96 MS (APCI, m / z): 308 (M + 1) + 〇 Reference Example 6 2 φ 5-Benzo [1,3] difluorene-5- 4-Hydroxy-4-hydrazino-2-aniline pyrimidine consists of 5-benzo [1,3] difluoren-5-yl-4-hydroxy-2-aniline pyrimidine (100 mg, 0.3 26 mmol), according to reference The target compound (83 mg, 79%) was obtained by the method of Example 20. HPLC (reverse phase): Rt. (Min) = 2.91 MS (APCI, m / z): 322 (M + 1) +. Reference Example 6 3 5-Biphenyl-3-yl_4-hydroxyaniline pyrimidine 3 -bromophenylacetic acid (10 g, 46.9 mmol) was dissolved in ethanol (30 ml), and concentrated hydrochloric acid (0.2 ml) was added. Heat to reflux for 10 hours. After the reaction, the solvent was distilled off under reduced pressure, and the residue was washed with ethyl acetate / saturated aqueous sodium hydrogen carbonate solution, and the organic layer was concentrated to obtain a crude product of ethyl 3-bromophenylacetate (11.4G). Benzene (140 ml), methanol (28 ml), and water (7 ml) were added to the product 1.7G to dissolve, and sodium carbonate (1.78 g, 1 6.8 mmol) and phenylboronic acid (ι · 〇) were added in that order. 2 g, 8.4 mmol), triphenylphosphine palladium (406-294-200524880 mg, 0.35 mmol), and heated to reflux for 18 hours. After the reaction, the mixture was extracted with ethyl acetate / saturated aqueous sodium hydrogen carbonate solution, and the organic layer was concentrated. The residue was purified by silica gel column chromatography to obtain ethyl biphenyl-3-ylacetate (1.3 g, 78%). Using biphenyl-3-yl-ethyl acetate (5.4 mmol) and reacting according to the method of Reference Example 19, the target compound (156 mg, 17%) was obtained. 1H-NMR (270 MHz, DMS 0-d6) ^ ppm: 8.90 (brs, 1H), 8.14 (s, 1H), 7.96 (s, 1H), 7.7, 7.63 (m, 5H), 7.58-7.40 (m, 4H), 7.38-7.04 (m, 4H) HPLC (reverse phase): Rt. (min) = 5.17 MS (APCI, m / z): 340 (M + 1) +. Reference Example 64 5-Biphenyl-3-yl-4-hydrazino-2-aniline pyrimidine was prepared from 5-biphenyl-3-yl-4-hydroxy-2-aniline pyrimidine (152 mg, 0.45 mmol) According to the method of Reference Example 20, the target compound (117 g, 74%) can be obtained.] H-NMR (270 MHz, DMSO-d6) δ ppm: 9.22 (s, 1H), 7.86-7.83 (m, 4H) , 7.78-7.71 m, 2H), 7.63-7.60 (m, 2H), 7.55- 7.45 (m, 3H), 7.4 and 7.34 (m, 2H), 7.25 (t, 2H, J = 7.3 Hz), 6.89 (t, 1H, J = 7.3 Hz), 4.43 (brs, 2H) HPLC (reverse phase): Rt. (Min) = 3.72 MS (APCI, m / z): 354 (M + 1) +. Reference Example 65 4-Hydroxy-2-anilino-5- (5-phenylpyridin-3-yl) · pyrimidin (5-bromopyridin-3-yl) -acetic acid (5g, 23 mmol) in ethanol (30 ml -295-200524880) was dissolved, concentrated hydrochloric acid (0.2 ml) was added, and the mixture was heated under reflux for 10 hours. After the reaction, the solvent was distilled off under reduced pressure, and the residue was washed with ethyl acetate / saturated aqueous sodium hydrogen carbonate solution, and the organic layer was concentrated to obtain (5-bromopyridin-3-yl) -ethyl acetate as a crude product (4.66 g ). Benzene (140 ml), methanol (28 ml), and water (7 ml) were added to 1.7 g of this product to dissolve, sodium carbonate (1.78 g, 16.8 mmol), phenylboronic acid (1.02 g, 8.4 mmol), Triphenylphosphine palladium (406 mg, 0.35 mmol) was heated under reflux for 18 hours. After the reaction, the mixture was extracted with ethyl acetate / aqueous saturated sodium bicarbonate solution, and the organic layer was concentrated. The residue was purified by silica gel column chromatography to obtain quantitative ethyl biphenyl-3-ylacetate. Using biphenyl-3-yl-ethyl acetate (3.5 mmol) and reacting according to the method of Reference Example 19, the target compound (190 mg, 16.6%) was obtained. HPLC (reverse phase): Rt. (Min) = 3.56 MS (APCI, m / z): 341 (M + 1) +. Reference Example 6 6 4-Hydrazinyl-5- (5-phenylpyridin-3-yl) -2-anilidine D is determined by 4-hydroxy-2-anilino-5- (5-phenylpyridine- 3-yl) -pyrimidine (180 mg, 0.53 mmol) was reacted according to the method of Reference Example 20 to obtain the target compound (93 g, 49%). HPLC (reverse phase): Rt. (Min) = 3.04 MS (APCI, m / z): 35 5 (M + 1) +. Reference Example 67 Diethyl 2- (2-fluorophenyl) -malonate contains copper iodide (95 mg · 0.5 mmol), 2-phenylphenylhydrazone (170 mg, 1 mmol), and carbonic acid (4 · 89 g, 15 mmol) tetrahydrofuran solution (10 ml) -296- 200524880, add 1-fluoro-2-fluorene: benzene (1.8 ml, 16 mmol), diethyl malonate (3.04 ml, 20 mmol) ), And heated and stirred at 70 ° C. for 24 hours. After the reaction, it was filtered through celite, concentrated, and purified by silica gel column chromatography to obtain the target compound (2.50 g, 61%). 〇1H-NMR (270 MHz, CDCL3) 5 ppm: 7.50-7.44 (m, 1H), 7.36 -7.2 6 (m, 1 H), 7 · 1 9-7 · 0 5 (m, 2 H), 4 · 9 8 (s, 1 H), 4 · 3 3-4 · 1 6 (m, 4H ), 1.27 (t, 6H, J = 7.3 Hz) MS (APCI, m / z): 255 (M + 1), Reference Example 68 4,6-dihydroxy-5- (2-fluorophenyl) -2 -Anilino-pyrimidine was prepared from 2- (2-fluorophenyl) -malonic acid diethyl ester (7.9 mmol) according to the method of Reference Example 16 to obtain the target compound (805 mg, 54%). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 1 1.20 (br s, 2Η), 8.47 (brs, 1H), 7.67 (dd, 2H, J = 0.8 Hz, 7.6 Hz), 7.34-7.22 (m, 4H), 7.14-7.01 (m, 3H) HPLC (reverse phase): Rt. (min) = 3.25 MS (APCI, m / z): 298 (M + 1) +. Reference Example 69 4,6 · Dihydrazino-5-(. 2 · fluorophenyl) -2-anilino-pyrimidine by 4,6 · dihydroxy-5- (2-fluorophenyl) -2-anilino -Pyrimidine (595 mg, 2 mmol), which can be reacted according to the method of Reference Example 20 to obtain the target compound (526 mg, 79%). 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 8.92 (s, 1H), 7.87 (dd, 2H, J = 1.1 Hz, 8.4 Hz), 7.44-7.36 (m, 1H), 7.28-7.16 (m , 200524880 5H), 6.86 (t, 1H, J = 7.3 Hz), 6.31 (s, 2H), 4.17 HPLC (reverse phase): Rt. (Min) = 2.84 MS (APCI, m / z): 326 (M + l) +. Reference Example 70 5- (2-Phenylphenyl) -4-acetyl-2-benzylamino-6- (4-pyrene than D 疋 -4-ylpyrimidine by 4,6-diazino-5- ( 2-Fluorophenyl) -2-anilino-pyrimidine, the target compound can be obtained by the method of reaction. HPLC (reverse phase): Rt. (Min) = 3.01 MS (APCI, m / z) · 439 (M + l ) +. Reference Example 71 4-Hydroxy-2-anilino-5-m-tolylpyrimidine From m-toluylacetate (10 mmol), the target compound (2 1 0 mg, 1 5 %). HPLC (reverse phase): Rt. (Min) = 4.34 MS (APCI, m / z): 278 (M + 1) +. Reference Example 72 4-hydrazino-2-anilino-5-m- Toluylpyridine was prepared from 4-hydroxy-2-anilino-5-m-tolylpyrimidine (15 〖mmol) according to the method of Reference Example 2 to obtain the target compound () ° HPLC (reverse phase): Rt. (Min ) = 3.18 MS (APCI, m / z): 292 (M + l) +. Reference Example 73 (brs, 4H) -Pyrazol-1-yl h Inverse method according to Reference Example 5 1) mg, 0.542 8 5 mg, 54% -298- 200524880 4-hydroxy-2-anilino-5-p-tolylpyrimidine The target compound was obtained by reacting p-toluylacetate (10 mmol) according to the method of Reference Example 19 (1 39 mg, 10%). HPLC (reverse phase): Rt. (Min) = 4.35 MS (APCI, m / z): 246 (M + 1) +, Reference Example 74 4-hydrazino-2-aniline-5-p-tolylpyridine The target compound (130 mg, 62%) was obtained by reacting 4-hydroxy-2-anilino-5-p-tolylpyrimidine (200 mg, 0.722 mmol) according to the method of Reference Example 20. HPLC (reverse phase): Rt. (Min) = 3.14 MS (APCI, m / z): 292 (M + 1) + 〇 Reference Example 75 5- (3-fluorophenyl) -4-hydroxy-2-aniline The pyrimidine was reacted with ethyl 3-fluorophenylacetate (10 mmol) according to the method of Reference Example 19 to obtain the target compound (71 mg, 5%). HPLC (reverse phase): Rt. (Min) = 4.28 MS (APCI, m / z "282 (M + 1) +. Reference Example 7 6 5- (3-fluorophenyl) -4-hydrazino-2- Aniline is obtained from 5- (3-fluorophenyl) -4-hydroxy-2-aniline pyrimidine (50 mg, 0.178 mmol) according to the method of Reference Example 20 to obtain the target compound (18 mg, 34%). HPLC ( Reverse phase): Rt. (Min) = 3.13 MS (APCI, m / z): 296 (M + 1) +. -299- 200524880 Reference Example 77 2-Thien-3-yl-malonate 3-Iodothiophene (2.1 ml, 16 mmol) was reacted according to the method of Reference Example 67 to obtain the target compound (3.77 g, 94%). IH-NMRPTO MHz, CDCL3) < 5 ppm: 7.37-7.26 (m , 2H), 7.H 7.15 (m, 1H), 4.75 (s, 1H), 4.3 and 4.11 (m, 4H), 1.27 (t, 6H, J = 7.3 Hz) MS (APCI , M / z): 243 (M + 1), Reference Example 78 4.6-Dihydroxy-2-anilino-5-thien-3-yl-pyrimidine by 2-thien-3-yl-malonate diethyl ester (5.6 mmol), and reacted according to the method of Reference Example 16 to obtain the target compound (929 mg, 65%). 1 Η-NMR (27 0 MHZ, DMS 0-d 6) (5 ppm: 1 1 · 1 0 (brs, 2 Η), 8 · 8 1 (brs, 1H), 7.83 (dd, 1H, J = 1.1 Hz, 3.0 Hz), 7.74-7.65 (m, 3 H), 7.39-7.30 (m, 3H), 7.06 (t, 1H, J = 7.3 Hz) HPLC (reverse phase): Rt. (Min) = 3.51 MS (APCI, m / z): 286 (M + l ) +. Reference Example 7 9 4.6- Dichloro-2-anilino-5-thien-3-yl-pyrimidine (4,6-dihydroxy-2-anilino-5-thien-3-yl-pyrimidine (571 mg, 2 mmol), and reacted according to the method of Reference Example 17 (51 1 mg, 79%). HPLC (reverse phase): Rt. (min) = 6.36 MS (APCI, m / z): 322 (M + 1) + 〇-300- 200524880 Reference Example 80 4,6-Difluorenyl-2-anilino-5-thien-3-yl-pyrimidine by 4,6-dichloro-2-anilino-5 -Thien-3-yl-pyrimidine (511 mg, 1.58 mmol), and reacted according to the method of Reference Example 47 to obtain the target compound (43 6 mg, 88%). 1H-NMR (270 MHz, DMS 0-d6) 5 ppm: 8.92 (s, 1H), 7.86 (d, 2H, J = 7.8 Hz), 7.67 (dd, 1H, J = 3.0 Hz, 5.1 Hz), 7.40 (dd5 1H, J = 1.1 Hz, 3.0 Hz), 7.23 (t, 2H, J = 7.8 Hz), 6.99 (dd5 1H, J = 1.4 Hz, 5.1 Hz), 6.86 (t, 1H, J = 7.3 Hz) , 6.22 (s, 2H), 4.18 (s, 4H) HPLC (reverse phase): Rt. (Min) = 2.62 MS (APCI, m / z): 314 (M + 1) + 〇 Reference Example 8 1 4- Hydrazinyl-2-anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-thien-3-yl-pyrimidine by 4,6-diazino-2-anilino- 5-Thien-3-yl-pyrimidine can be reacted according to the method of Reference Example 5 to obtain the target compound. 1H-NMR (270 MHz, DMS 0-d6) (5 ppm: 9.52 (s, 1H), 8.57 (d, 1H, J = 0.5 Hz), 8.51 (dd, 2H, J = 1.7 Hz, 4.5 Hz), 8.12 (d, 1H, J = 0.7 Hz), 7.85 (dd, 2H, J = 1.0 Hz, 8.6 Hz), 7.56 (dd, 2H, J = 1.7 Hz, 4.6 Hz), 7.51 (dd, 1H, J = 2.8 Hz, 4.9 Hz), 7.38 (s, 1H), 7.36 (dd, 1H, J = 1.3 Hz, 3.0 Hz), 7.29 (t, 2H, J = 7.4 Hz), 6.94 (t, 1H, J = 7.4 Hz), 6.78 (dd, 1H, J = 1.3 Hz, 4.9 Hz), 4.54 (brs, 2H) -301-200524880 HPLC (reverse phase) · Rt. (Min) 2.87 MS (APCI, m / z) : 427 (M + l) +. Reference Example 8 2 2- [3- (4-fluorophenoxy) -phenyl] -malonic acid diethyl ester from 1- (4-fluorophenoxy) -3 -Iodobenzene (4.0 g, 13 mmol). The target compound (3.2 1 g, 72%) can be obtained by reaction according to the method of Reference Example 67. 1H-NMR (270 MHz, CDCL3) 5ppm: 7.33-7.24 (m, 1H) , 7.13-6.85 (m, 6H), 4.57 (s, 1H), 4.27-4.08 (m, 4H), 1.25 (t, 6H, J = 7.0 Hz) MS (APCI, m / z): 347 (M + l) +. Reference Example 8 3 4.6- Diacyl-5- [3- (4-fluorophenoxy) -phenyl] -2-anilino-ran |] is determined by 2- [3- (4- Fluorophenoxy) -phenyl) -diethyl malonate (5.5 mmol) can be reacted according to the method of Reference Example 16. The target substance (603 mg, 31%) was obtained. ^ -NMR (270 MHz, DMSO-d6) (5 ppm: 10.93 (brs, 2H), 8.84 (brs, 1H), 7.67 (dd, 2H, J = 1.1 Hz, 7.8 Hz), 7.36-7.16 (m, 7H), 7.10-7.02 (m, 3H), 6.77 (dt, 2H, J = 2.2 Hz, 7.0 Hz) HPLC (reverse phase): Rt. (Min) = 4.37 MS (APCI, m / z): 390 ( M + l) +. Reference Example 84 4.6- Dihydrazino-5- [3- (4-fluorophenoxy) -phenyl] -2-anilino-pyrimidine by 4,6-dihydroxy-5 · [ 3- (4 · fluorophenoxy) -phenyl] -2-anilino-pyrimidine (386 mg, 1 mmol) was reacted according to the method of Reference Example 20 to obtain the target compound (329 mg, 80%). -302 -200524880 1H-NMR (270 MHz, DMSO-d6) 5 ppm: 8.91 (s? 1H)? 7.86 (dd, 2H, J = 1.1 Hz, 8.6 Hz), 7.43 (t, 1H5 J = 7.8 Hz), 7.25 -7.16 (m, 6H), 6.99-6.77 (m, 4H), 6.35 (s, 2H), 4.17 (brs, 4H) HPLC (reverse phase): Rt. (Min) = 3.63 MS (APCI, m / z): 418 (M + 1) +. Reference Example 85 5- [3- (4-fluorophenoxy) -phenyl] -4-fluorenylaniline 4- (4-pyridin-4-yl- Pyrazole-pyridyl) -pyrimidine can be reacted from 4,6-diazino-5- [3- (4-fluorophenoxy) _phenyl] -2 ~ anilino-pyrimidine according to the method of Reference Example 5 Obtain the target ° HPLC (reverse phase): Rt. (Min) = 3.65 MS (APCI, m / z): 531 (M + l) +. Reference Example 8 ό 4,6-dihydroxy-2- (5-fluoro-2-tolylamino) -5-phenylpyrimidine 5-fluoro-2-toluidine (1.25 g, 10 mmol) was dissolved in ethanol (4 mi), 1H-pyrazole-1-carboxamidine hydrochloride (1.47 g, 10 mmol) was added, and the mixture was heated under reflux for 15 hours. After the reaction, ethanol (3 6 ml), sodium ethoxide (21wt%, 18.6 ml, 50 mmol), diethyl phenylmalonate (6.4 ml, 30 mmol), and heated under reflux for 15 hours, then acetic acid was added to stop the reaction, and the solvent was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. After the organic layer was concentrated, diethyl ether was added to the residue, the precipitated solid was pulverized and collected by filtration, and then washed with ether to obtain the target product (2.10 g, 34% ). 'H-NMR (270 MHz, DMSO-d6) (5 ppm: 10.95 (brs, 2H), 8.15-8.10 (m, 2H), 7.45 (d, 2H, J = 8.4 Hz), 7.30- 7.21 (m, 3H), -303-200524880 7.17-7.11 (m, 1H), 6.84 (dt5 1H, J = 2.4 Hz, 8.4 Hz), 2.24 (s, 3H) HPLC (reverse phase): Rt. (Min ) = 3.83 MS (APCI, m / z): 312 (M + l) +. Reference Example 87 4.6- Dichloro-2- (5-fluoro-2-tolylamino) -5-phenylpyrimidine 4,6-Dihydroxy-2- (5-fluoro-2-tolylamino) -5-phenyl-pyrimidine (360 mg, 1.16 mmol) was reacted according to the method of Reference Example 17 to obtain the target compound (306 mg, 76%). HPLC (reverse phase): Rt. (Min) = 6.86 MS (APCI, m / z): 348 (M + 1) +. Reference Example 8 8 4.6-Dihydrazino-2- (5 -Fluoro-2-tolylamino) -5 · phenyl-pyrimidine by 4,6-dichloro-2- (5-fluoro-2-tolylamino) -5-phenylpyrimidine (306 mg, 0.88 mmol) The target compound (185 mg, 62%) can be obtained by reaction according to the method of Reference Example 47. ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 8.05 (dd, 2H, J = 2.7 Hz, 12.2 Hz), 7.81 (s, 1H), 7.48-7.31 (m, 3H), 7.21-7.13 (m, 3H), 6.71 (dt, 1H, J = 2.7 Hz, 8.4 Hz), 6.11 (s, 2H), 4.15 (brs , 4H), 2.27 (s, 3H) HPLC (reverse phase): Rt. (Min) = 3. 01 MS (APCI, m / z): 340 (M + 1) +. Reference Example 8 9 (5-fluoro-2-tolyl) -4-hydrazino-5-phenyl-2-aniline-6- (4-Pyridin-4-yl- 200524880 pyrazol-1-yl) -pyrimidine was reacted from 4,6-dihydrazino-2- (5-fluorotolylamino-phenyl-pyrimidine) according to the method of Reference Example 5. HPLC (reverse phase): Rt. (Min) = 3.18 MS (APCI, m / z): 45 3 (M +1) + 0 Reference example 9 0 2-benzo [1,3] Pyrocene-5-yl-malonic acid diethyl ester was reacted with 5-iodo-benzo [1,3] dipyrocene (2.1 ml, 16 mmo1) according to the method of Reference Example 67 to obtain the target compound ( 2.63g, 59%) ° H-NMR (270 MHz, CDCL3) δ ppm: 6.95 (d, 1H, J = 1.5 Hz), 6.82 (dd, 1H, J = 1.5 Hz, 7.9 Hz), 6.77 (dd, 1H, J = 0.5 Hz, 7.9 Hz), 5.96 (s, 2H), 4.52 (s, 1H), 4.30-4.08 (m, 4H), 1.27 (t, 6H, J = 7.1 Hz) MS ( APCI, m / z): 281 (M + 1) +. Reference Example 91 5-Benzo [1,3] bisfluoren-5-yl-4,6-dihydroxy-2 —anilino-pyrimidine by 2-benzo [1,3] disulfo-5-yl -Diethyl malonate (4.3 mmol), which can be reacted according to the method of Reference Example 16 to obtain the target compound (231 mS, 14%). HPLC (reverse phase): Rt. (Min) = 3.29 MS (APCI, m / z): 324 (M + 1) +. Reference Example 92 5-Benzo [1,3] bisfluorenyl-4,6-diazino-2-anilino-pyrimidine 6-Once the compound is 2-anilino-ip-metidine (230 mg, 0.7 1 mmol) and reacted according to the method of Reference Example 20 to obtain the target compound -305-200524880 (66 mg, 26%). ^ -NMR ( 270 MHz, DMSO-d 6) (5 ppm: 8.89 (s, 1H), 7.86 (d, 2H, J = 7.8 Hz), 7.22 (t, 2H? J = 7.6 Hz), 6.97 (d, 1H, J = 7.8 Hz), 6.85 (t, 1H, J = 7.3 Hz), 6.68-6.61 (m? 2H), 6.21 (s, 2H), 6.04 (s, 2H), 4.23 (brs, 4H) HPLC (reverse phase ): Rt. (Min) = 2.90 MS (APCI, m / z): 3 52 (M + l) +. Reference Example 9 3 5-Benzo [1,3] bisarsino-5-yl- 4-hydrazino-2-anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidine by 5-benzo [1,3] difluoren-5-yl-4, 6-Dihydrazino-2-anilino-pyrimidine can be reacted according to the method of Reference Example 5. HPLC (reverse phase): Rt. (Min) = 2.98 MS (APCI, m / z): 465 (M + l) +。 Reference Example 94 2- (2,3-dihydrobenzo [1,4] disoying-6-yl) -malonic acid diethyl ester from 6-iodo-2,3-dihydro -Benzo [1,4] dioxin (4.19 g, 16 mmol), reacted according to the method of Reference Example 67 The target compound was obtained (3.90 g, 83%). 1H-NMR (270 MHz, CDCL3) 5 ppm: 6.94-6.93 (m, 1H), 6.84 (d, 2H, J = 1.5 Hz), 4.49 (s, 1H) , 4.32-4.12 (m, 8H), 1.34-1.21 (m, 6H) MS (APCI, m / z): 295 (M + 1) + 〇 Reference Example 9 5 5- (2,3-dihydrobenzo) [1,4] Dishuying-6-yl) -4,6-dihydroxy-2-aniline pyrimidine-306- 200524880 by 2- (2,3-dihydrobenzo [14] dishuying_6_ Group) _diethyl acetate malonate (5.5 mmol) 'The target compound was obtained according to the method of Reference Example 16. HPLC (reverse phase): Rt. (Min) = 3.32 MS (APCI, m / z): 3 3 8 (M + l) +. Reference Example 9 6 4.6-Dichloro-5- (2,3-dihydrobenzo [14] difluoren-6-yl) -2-aniline pyrimidine is derived from 5- (2,3-dihydrobenzo [14 ] Dishuying-6-yl) -4,6-dihydroxy-2-anilino-pyrimidine (82 mg, 0.243 mmol). The target compound (48 mg, 53%) was obtained by the reaction according to the method of Reference Example 17. HPLC (reverse phase): Rt. (Min) = 6.03 MS (APCI, m / z): 374 (M + 1) +. Reference Example 97 4.6-Dihydrazino-5- (2,3-dihydrobenzo [1,4] dissocin-6-yl) -2-anilino-pyrimidine by 4,6-dichloro-5- (2,3-dihydrobenzo [1,4] dioxin-6-yl) -2-aniline is reacted in the same manner as in Reference Example 47 to obtain the target compound. ^ -NMR (270 MHz, DMSO-d6) 5 ppm: 8.88 (s, 1H), 7.86 (d, 2H, J = 7.6 Hz), 7.22 (t, 2H, J = 7.6 Hz), 6.93-6.82 (m , 2H), 6.65-6.60 (m, 2H), 6.09 (s, 2H), 4.26 (s, 4H), 4.19 (brs, 4H) HPLC (reverse phase): Rt. (Min) = 2.99 MS (APCI, m / z): 366 (M + l) +. Reference Example 9 8 5- (2,3-Dihydrobenzo [1,4] difluoren-6-yl) -4-hydrazino-2-aniline-6- (4 ·-307- 200524880 pyridine- 4-yl-pyrazol-1-yl) -pyrimidine by 4,6-diazino- 5- (2,3-dihydrobenzo [I, 4] diDfin-6-yl) -2-aniline The base-pyrimidine can be reacted according to the method of Reference Example 5 to obtain the target substance. HPLC (reverse phase): Rt. (Min) = 2.96 MS (APCI, m / z): 479 (M + 1) +. Reference Example 9 9 Diethyl 2- (2-tolylmalonate) was reacted from 1-iodo-2-toluene (2.0 ml, 16 mmol) according to the method of Reference Example 67 to obtain the target compound (3.72 g, 93%). ). 1H-NMR (270 MHz, CDCL3) 5ppm: 7.42-7.36 (m, 1H), 7.26-7.16 (m, 3H), 4.87 (s, 1H), 4.31-4.15 (m, 4H), 2.34 (s , 3H), 1.27 (t, 6H? J = 7.0 Hz) MS (APCI, m / z): 251 (M + 1) +. Reference example 100 4,6-dihydroxy-5- (2-tolyl) The 2-aniline pyrimidine was obtained from 2- (2-tolyl) -malonic acid diethyl ester (8.3 mmol) according to the method of Reference Example 16 to obtain the target compound (1.03 g, 70%). HPLC (reverse phase) : Rt. (Min) = 3.47 MS (APCI, m / z): 294 (M + l) +. Reference Example 1 〇 1 4,6-dichloro-5- (2-tolyl) -2-aniline The target compound (8.39 g, 88%) can be obtained by reacting 4,6-dihydroxy-5- (2-tolyl) -2-anisidine (8.49 g, 28.9 mmol) according to the method of Reference Example 17- 308 200524880 ^ -NMR (270 MHz, DMS 0-d6) d ppm: 10.44 (s, 1H), 7.72-7.69 (m, 2H), 7.39-7.21 (m, 6H), 7.10-7.03 (m, 1H ), 2.12 (s, 3H) HPLC (reverse phase): Rt. (Min) = 6.89 MS (APCI, m / z): 330 (M + l) +. Reference Example 102 4,6-Dihydrazino-5 -( 2-Tolyl) -2-anilino-pyrimidine The desired compound can be obtained by reacting 4,6-dichloro-5- (2-tolyl) -2-anilinopyrimidine according to the method of Reference Example 47.! H-NMR (270 MHz, DMSO-d6) 5 ppm: 8.90 (s, 1H), 7.89 (dd, 2H, J = 1.1 Hz, 7.6 Hz), 7.34-7.19 (m, 6H), 6.85 (t, 1H, J = 7.6 Hz), 5.80 (s, 2H), 4.16 (brs, 4H), 2.07 (s, 3H) HPLC (reverse phase): Rt. (Min) = 2.76 MS (APCI, m / z): 322 (M + l) +. Reference Example 103 4-Hydrazyl-2-anilino-6-pyrazol-1-yl-5-o-tolylpyrimidine by 4,6-dichloro-5- (2-tolyl)- 2-Anilinopyrimidine was reacted according to the method of Reference Example 38 to obtain the target compound (22 mg, 48%). HPLC (reverse phase): Rt. (Min) = 3.96 MS (APCI, m / z): 3 5 8 (M + 1) +. Reference Example 1 0 4 4-Hydrazino-2-anilyl-6- (4-pyridin-4-yl-pyrazole-phenyl) -5-o-tolylpyrimidine is determined by 4,6-dihydrazyl -5- (2-Tolyl) -2-aniline, according to the method of 200524880 in Reference Example 5, to obtain the target compound. Η-NMR (270 MHz, DMS 0-d 6) $ ppm: 9 · 4 9 (s, 1 Η), 8.69 (s 1Η), 8.51-8 · 49 (m, 2Η) , 8.03 (s, 1Η), 7.88 (d, 2Η, J = 7.6 Hz), 7.5 5-7.53 (m, 2H), 7.33-6.92 (m, 8H), 4.50 (brs, 2H) , 2.04 (s, 3H) HPLC (reverse phase): Rt. (Min) = 3.06 MS (APCI, m / z): 435 (M + 1) + 〇 Reference Example 105 4-hydroxy-5- (4-form The sulfenyl phenyl) -2-aniline pyrimidine was reacted from ethyl 3-fluorophenylacetate (10 mmol) according to the method of Reference Example 19 to obtain the target compound (185 mg, 12%). 1 Η-NMR (2 7 OM H z, DMS 0-d 6) δ ppm: 9 · 0 0 (brs, 1 Η), 8 · 〇1 (s, 1 Η), 7 · 6 4 (d, 2 Η, J = 8 · 6 Η z), 7 · 6 2 (d, 2 Η, J = 7 · 6 Η z), 7.34 (t, 2H, J = 7.6 Hz), 7.26 (d, 2H, J = 8.6 Hz), 7.06 (t, 1H, 7.6 Hz), 2.50 (s, 3H) HPLC (reverse phase): Rt. (Min) = 4.25 MS (APCI, m / z): 310 (M + l) + . Reference Example 1 0 6 4-Hydroxy-5- (4-methylsulfenylphenyl) -2-aniline pyrimidine 100 mg, 0.324 mmol), and reacted according to the method of Reference Example 20 to obtain the target compound (42 mg, 40%). 0H-NMR (270 MHz, DMSO-d6) < 5 ppm: 9.19 (brs, 1H ), 7.83 (d, 2H, J = 7.6 Hz), 7.73 (s, 1H), 7.65 (brs, 1H), 7.32 (s, 200524880 4H), 7.25 (t, 2H, J = 7.6 Hz), 6.89 ( t, 1H, J = 7.6 Hz), 4.40 (brs, 2H), 2.51 (s, 3H) HPLC (reverse phase): Rt. (min) = 3.32 MS (APCI, m / z): 3 24 (M + l) +. Reference Example 1 0 7 4-Hydroxy-2-anilino-5- (3-trifluorophenyl) -pyrimidine was obtained by reacting 3-trifluoro / toluene ethyl acetate (10 mmol) according to the method of Reference Example 19. The target substance (182 mg, 11%). HPLC (reverse phase): Rt. (Min) = 4.64 MS (APCI, m / z): 3 32 (M + 1) +. Reference Example 108 4-Hydroxy-2-anilino-5- (3-trifluorotolyl) -pyrimidine by 4-hydroxy-2-anilino-5- (3-trifluorophenyl) -pyrimidine (100 mg , 0.324 mmol), and the target compound (53 mg, 51%) can be obtained by reaction according to the method of Reference Example 20. HPLC (reverse phase): Rt. (Min) = 3.55 MS (APCI, m / z): 346 (M + 1) + 〇 Reference Example 109 5- (2-chlorophenyl) -4-hydroxy-2-aniline The pyrimidine was reacted with ethyl 2-chlorophenylacetate (10 mmol) according to the method of Reference Example 19 to obtain the target compound (119 mg, 8%). HPLC (reverse phase): Rt. (Min) = 4.32 MS (APCI, m / z): 298 (M + 1) + 〇 Reference Example 1 1 〇 -311-200524880 5- (2-chlorophenyl) -4 -Hydrazine-2-aniline pyrimidine is prepared from 5- (2-chlorophenyl) -4-hydroxy-2-aniline pyrimidine (100 mg, 0.336 mmol) according to the method of Reference Example 20 to obtain the target compound (40 mg, 38%) ° HPLC (reverse phase): Rt. (Min) = 3.17 MS (APCI, m / z): 312 (M + 1) +. Reference Example 111 4-Hydroxy-2-anilino-5- (2-trifluorophenyl) -pyrimidine was reacted with ethyl 2-trifluorotoluene (10 mmol) according to the method of Reference Example 19 to obtain the target compound ( 116 mg, 7%). HPLC (reverse phase): Rt. (Min) = 4.46 MS (APCI, m / z): 332 (M + 1) +. Reference Example 1 2 Cardiohydrazino-2-anilino-5- (2-trifluorotolyl) -pyrimidine from 4-hydroxy-2-anilino-5- (2-trifluorophenyl) -pyrimidine (100 mg, 0.324 mmol), and reacted according to the method of Reference Example 20 to obtain the target compound (59 mg, 53%). HPLC (reverse phase): Rt. (min) = 3.24 MS (APCI, m / z "346 (M + l) +. Reference Example 1 1 3 4 · Hydroxy-5-phenyl-pyrimidine A 1,3,5-triple (1.62 g, 20 mmol), acetophenamine (2.70 g, 20 mmol) in ethanol ( 12 ml) solution, add sodium ethoxide (21 wt%, 7.47 ml, 20 mmol) and heat to reflux for 4 hours. After concentrating the reaction solution, dissolve the residue with a small amount of • 312- 200524880 water, and add 3 μM in an ice bath Hydrochloric acid. The precipitate was filtered and washed with dichloromethane to give the target compound (2.41 g, 70%). HPLC (reverse phase): Rt. (Min) = 2.69 MS (APCI, m / z): 173 (M + l ) +. Reference Example 1 1 4 4-hydrazino-5-phenylpyrimidine The target compound (37 mg) was obtained by reacting 4-hydroxy-5-phenylpyrimidine (172 mg, 1 mmol) according to the method of Reference Example 20. , 20%). HPLC (reverse phase): Rt. (Min) = 1.68 MS (APCI, m / z): 187 (M + l) +. Reference Example 115 4.6-dihydroxy-2- (5-fluoro- 2-toluidine ) -Pyrimidine is reacted with 5-fluoro-2-toluidine (5 mmol) according to the method of Reference Example 2 to obtain the target compound (228 mg, 19%).! H-NMR (270 MHz, DMSO-d6) (5 ppm: 7.99-7.93 (m, 1H), 7.30-7.15 (m, 1H), 6.87-6.80 (m, 1H), 4.86 (s, 1H), 2.22 (s, 3H) HPLC (reverse phase) · Rt . (niin) = 2.70 MS (APCI, m / z): 236 (M + l) +. Reference Example 1 1 6 4.6- Dichloro-2- (5-fluorotoluenyl) _pyrimidine is 4,6- The reaction of the two acyl-2- (5-chlorotoluamido) -anhydro 'according to the method of Case 3 can obtain the target compound. HPLC (reverse phase): Rt. (Min) = 6.08 -313- 200524880 MS (APCI, m / z): 272 (M + l) +. Reference Example 1 1 7 2- (5-fluoro-2-tolylamino) -4-hydrazino-6-pyrazol-1-yl -Pyrimidine is obtained from 4,6-chloro ^-(5-chloro-2-tolylaminyl) -pyridine (100 mg, 0.368 mmol) according to the method of Reference Example 38 to obtain the target compound. . HPLC (reverse phase): Rt. (Min) = 3.80 MS (APCI, m / z): 300 (M + 1) +. Reference Example 1 1 4-hydroxy-2- (2-methoxyaniline) -5-phenylpyrimidine Dissolve 2-methoxyaniline (0.56 ml, 5 mmol) in ethanol (2 ml), and add hydrochloric acid 1H- Pyrazole-carboxamidine (733 mg, 5 mmol) was heated under reflux for 15 hours. After the reaction, the solution was in sodium ethoxide (21 wt%, 9.3 ml, 25 mmol). In addition, ethyl phenylacetate (2.4 ml, 15 mmol) and N, N-dimethylformamide were added in other reaction vessels. Diacetal (2.6 ml, 15 mmol) was heated and stirred at 140 ° C for 24 hours, and the solution was added. The mixture was heated under reflux for 15 hours. The reaction was stopped with acetic acid and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane, and the organic layer was washed with water. The organic layer was concentrated and purified by column chromatography to obtain the target compound (184 mg, 13%). HPLC (reversed phase) Rt .. (niin) = 4.29 MS (APCI, m / z): 294 (M + 1) + 〇 Reference Example 1 1 9 4 -hydrazino- 2- (2-methoxyaniline Amino) -5-phenylanidine is determined from 4-Amino-2 · (2-methoxyaniline) -5-phenylanidine (177 mg, 0.603 mmol), which can be reacted according to the method of Reference Example 20. The target compound was obtained (80 mg, 43% -314- 200524880 HPLC (reversed phase): Rt. (Min) = 2.90 MS (APCI, m / z): 308 (M + 1) +. Reference Example 120 2_ (2, 3-Dihydroindole-1-yl) -4-hydroxy-5-phenylpyrimidine was reacted with 2,3-dihydroindole (5 mm ο 1) according to the method of Reference Example 18 to obtain the target compound ( 4 8 2 mg, 33%).! H-NMR (270 MHz, DMSO-d6) 5 ppm: 11.41 (brs, 1H), 8.40 (d, 1H, J = 7.6 Hz), 8.20 (brs, 1H), 7.66 (d, 2H, J = 7.4 Hz), 7.39 (t, 2H, J = 7.6 Hz), 7.31-7.16 (m? 3H), 6.96 (t, 1H, J = 7.4 Hz), 4.18 ( t, 2H, J = 8.5 Hz), 3.20 (t, 2H, J two 8.5 Hz) HPLC (reverse phase): Rt. (min) = 4.92 MS (APCI, m / z): 290 (M + l) + Reference Example 1 2 1 2- (2,3-Dihydroindole-1-yl) -4-hydrazino-5-phenylpyrimidine by 2- (2,3-dihydroindole-phenyl)- 4-hydroxy-5-phenylpyrimidine (462 mg, 1.60 m mol), and reacted according to the method of Reference Example 20 to obtain the target compound (240 mg, 50%) 〇] Η-NMK (270 MHz, D M S 〇-d 6) 5 p p m: 8.44 (d? 1H, J = 7.6

Hz), 7. 84 (s, 1H), 7. 62 (s, 1H), 7. 48-7. 31 (m, 5H), 7. 22-7. 12 (m, 2H)? 6. 86 (dt, 1H, J = l. 〇 Hz, 7. 4 Hz), 4. 49 (brs, 2H), 4. 22 (t, 2H, J = 8. 6 Hz), 3. 14 (t) 2H, J = 8. 6 Hz) HPLC (reverse phase): Rt. (niin) = 3. 12 200524880 MS (APCI, m / z): 304 (M + l) +. Reference Example 1 2-Hydroxy-5-phenyl-2-pyridin-3-yl-pyrimidine 4 ml, 15 mmol) and N, N-dimethylformamide diethyl acetal (2. 6 ml, 15 mmol) at 140 ° C with stirring for 24 hours. To the reaction solution was added sodium ethoxide (21 wt%, 9. 3 ml, 25 mmol) and 3-formamidinepyridine hydrochloride (7.88 mg, 5 mmol) were heated under reflux for 15 hours, acetic acid was added to stop the reaction, and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane, and the organic layer was washed with water. The organic layer was concentrated and purified by column chromatography to obtain the target compound (344 mg, 28%). 1 Η-N M R (2 7 Ο Μ H z, D M S 0-d 6) (5 p p m: 1 3 · 0 3 (b r s, 1 Η), 9 · 2 9 (dd, 1Η, J = 0. 7 Hz, 2. 3 Hz), 8. 76 (dd, 1H, J = 1. 6 Hz, 4. 8 Hz), 8. 51-8. 46 (m, 1H), 8. 36 (s, 1H), 7. 80-7. 50 (m, 2H), 7. 62-7. 55 (m, 1H), 7. 49-7. 34 (m, 3H) HPLC (reverse phase): Rt. (min) = 3. 30 MS (APCI, m / z): 250 (M + l) +. Reference Example 1 2 3 4-Hydroxy-5-phenyl-2-pyridin-3-yl-pyrimidine by 4-hydroxy-5-phenyl-2-pyridin-3-yl-pyrimidine (3 3 3 mg, 1 . 33 mmol), and reacted according to the method of Reference Example 20 to obtain the target substance. 1H-NMR (270 MHz, D M S Ο-d 6) 5 p p m: 9. 60 (dd, 1H, J = 0. 8 Hz, 2. 1 Hz), 8. 77-8. 72 (m, 1H), 8. 68 (dd, 1H, J = 1. 6 Hz, 4. 8 Hz), 8. 09 (s, 1H), 8. 00 (brs, 1H), 7. 56-7. 38 (m, 6H), 4. 63 (brs, 2H) -316- 200524880 HPLC (reversed phase): Rt. (min) = 2.68 MS (APCI, m / z): 264 (M + l) + ο Reference Example 124 2,5-Diphenyl-4 -Hydroxypyrimidine from benzyl hydrochloride (5 mmol) The target compound (374 mg, 30%) can be obtained by reacting according to the method of Reference Example 1-22. HPLC (reverse phase): Rt. (min) = 4. 27 MS (APCI, m / z): 249 (M + l) +. Reference Example 125 2,5-Diphenylhydrazine Pyridazine (359 mg, 1. 45 mmol), according to the method of Reference Example 20 to obtain the target compound (214 mg, 56%). HPLC (reverse phase): Rt. (min) = 2. 84 MS (APCI, m / z): 263 (M + 1) +. Reference Example 126 4-Hydroxy-2-methyl-5-phenylpyrimidine The target compound (189 mg, 20%) was obtained by reacting acetamidine hydrochloride (5 mmol) according to the method of Reference Example 122. HPLC (reverse phase): Rt. (min) two 2. 76 MS (APCI, m / z): 187 (M + l) + 〇 Reference Example 1 2 7 Methylmethyl-5-phenylpyrimidine, |] determined by 4-hydroxy-2-methyl > 5- Phenylpyrimidine (170 mg, 0. 915 mmol), and reacted according to the method of Reference Example 20 to obtain the target substance. -317-200524880 HPLC (reversed phase): Rt. (min) = 1.53 MS (APCI, m / z): 201 (M + 1) +. Reference Example 1 2 8 2- (2-Fluoro-5-tolyl) -malonic acid diethyl ester 1-fluoro-2-iodo-4-toluene (2. 1 ml, 16 mmol), and the target compound (2. 6 9 g, 63%). 1H-NMR (270 MHz, CDCL3) (5 ppm: 7. 26-7. 22 (m, 1H), 7. 12-7. 06 (m, 1H), 6. 99-6. 92 (m, 1H), 4. 93 (s, 1H), 4. 33-4. 16 (m, 4H), 2. 32 (s, 3H), 1. 30- 1. 24 (m, 6H) Reference example 1 2 9 4. 6-Dihydroxy-5- (2-fluoro-5-tolyl) -2-aniline pyrimidine 5 mmol), according to the method of Reference Example 16, the target compound (813 mg, 52%) was obtained. 1H-NMR (270 MHz, DMS 0-d6) (5 ppm: 12. 00 (brs, 2H), 8. 85 (brs, 1H), 7. 67 (d, 2H, J = 8. 6 Hz), 7. 37-7. 31 (m, 2H), 7. 09-6. 96 (m? 4H), 2. 27 (s, 3H) HPLC (reverse phase): Rt. (min) = 3. 72 MS (APCI, m / z): 312 (M + l) +. Reference example 1 3 0 4. 6-Dichloro-5- (2-fluoro-5-tolyl) -2-aniline pyrimidine 60 mmol), and reacted according to the method of Reference Example 17 to obtain the target compound (453 mg, 50%). HPLC (reverse phase): Rt. (min) = 7. 03 MS (APCI, m / z): 348 (M + 1) +. 200524880 Reference Example 1 3 1 5- (2-Fluoro-5-tolyl) -4-hydrazinyl-2-anilino-6-pyrazol-1-yl-pyrimidine by 4,6-dichloro-5- ( 2-fluoro-5 -tolyl) -2-aniline (100 mg, 0. 287 mmol), and reacted according to the method of Reference Example 38 to obtain the target compound (62 mg, 57%). HPLC (reverse phase): Rt. (min) = 4. 20 MS (APCI, m / z): 376 (M + l) +. Reference Example 1 3 2 2- (3-Chloro-2-fluorophenyl) -diethyl malonate 10 g, 16 mmol) ′ according to the method of Reference Example 67 to obtain the target compound (2. 87 g, 62%). 1H-NMR (270 MHz, CDCL3) (5 ppm: 7. 4 2-7 · 3 5 (m, 2 Η), 7 · 1 1 (dt, 1H, J = 1. 0 Hz, 7. 8 Hz), 4. 98 (s, 1H), 4. 33-4. 17 (m, 4H), 1. 28 (t, 6H, J = 7. 0 Hz) Reference Example 1 3 3 5- (3-Chloro-2-fluorophenyl) -4,6-dihydroxy-2-aniline pyrimidine Diethyl acid (5. 5 mmol), according to the method of Reference Example 16 to obtain the target compound (6.88 mg, 41%). ! H-NMR (270 MHz, D M S Ο-d 6) (5 p p m: 12. 64 (brs, 2H), 7. 94 (brs, 1H), 7. 66 (d, 2H, J = 7. 8 Hz), 7. 50-7. 04 (m, 6H) HPLC (reverse phase): Rt. (min) = 3. 66 MS (APCI, m / z): 3 3 2 (M + l) +. Reference example 1 3 4 5- (3-Chloro-2-fluorophenyl) -4,6-dichloro-2-aniline pyrimidine-319- 200524880 By 5- (3-chloro-2-fluorophenyl) -4 , 6-Dioxo-2-aniline chelated Didine (452 mmol), and reacted according to the method of Reference Example 17 to obtain the target compound (53 mg, 32%). HPLC (reverse phase): Rt. (min) = 6. 90 MS (APCI, m / z): 368 (M + l) +. Reference Example 135 5- (3-Chloro-2-fluorophenyl) -4-hydrazino-2-anilino-6-pyrazol-1-yl-pyrimidine by 5- (3-chloro-2-fluorophenyl ) -4,6-dichloro-2-aniline (53 mg, 0. 144 mmol), according to the method of Reference Example 38 to obtain the target compound (36 mg, 63%). HPLC (reverse phase): Rt. (min) two 4. 39 MS (APCI, m / z): 396 (M + l) +. Reference Example 1 3 6 2- (2,3-Xylyl) -malonic acid diethyl ester from 1-iodo-2,3-xylene (2.3 ml, 16 mmol), according to the method of Reference Example 67 The target can be obtained by reaction (2. 63 g, 62%). 1H-NMR (270 MHz, CDCL3) (5ppm: 7. 21-7. 07 (m, 3H), 4. 92 (s, 1H), 4. 31-4. 15 (m, 4H), 2. 30 (s, 3H), 2. 22 (s, 3H), 1. 27 (t, 6H, J = 7. 0 Hz). Reference Example 137 4,6-Dihydroxy-5- (2,3-xylyl) -2-aniline pyrimidine From 2- (2,3-xylyl) -diethyl malonate (5. 8 mmol), according to the method of Reference Example 16, the target substance (1. 24 g, 81%). ^ -NMR (270 MHz, D M S Ο-d6) 5 p p m: 11. 40 (b r s, 2 H), 8. 79 (brs, 1H), 7.69 (d, 2H, J = 7. 6 Hz), 7. 36-7. 30 (m, 2H),-320-200524880 7. 07-6. 97 (m, 3H), 6. 93-6. 90 (m, lH), 2.18 (s, 3H), 2.00 (s, 3H) HPLC (reverse phase): Rt. (min) = 3. 70 MS (APCI, m / z): 3 08 (M + l) +. Reference Example 1 3 8 4,6-Dichloro-5- (2,3-xylyl) -2-anilidine 11 is determined by 4,6-dihydroxy-5- (2,3-xylylaniline 1 ^ '卩 (976 mm〇1), the reaction according to the method of Reference Example 17 to obtain the target compound (76 mg, 23%) ° HPLC (reverse phase): Rt. (min) = 6. 90 MS (APCI, m / z): 344 (M + l) +. Reference Example 1 3 9 5- (2,3-Xylyl) -4-hydrazinyl-2-anilino-6-pyrazol-1-yl-pyrimidine by 4,6-dichloro-5- (2, 3-xylyl) -2-aniline (76 mg, 0. 221 mmol), according to the method of Reference Example 38 to obtain the target compound (61 mg, 74%) ° HPLC (reverse phase): Rt. (min) = 4. 11 MS (APCI, m / z): 37 2 (M + 1) +. Reference Example 140 5-(2,3-Dihydrobenzo [1,4] difluoren-6-yl) -4 -hydrazino-2. -Anilino-6-pyrazole-1 · yl-pyrimidine by 4,6-dichloro-5- (2,3-dihydrobenzo [1,4] difluorenylaniline pyrimidine (48 mg, 0. 128 mmol), and reacted according to the method of Reference Example 38 to obtain the target substance (35 mg, 68%). HPLC (reverse phase): Rt. (min) = 3. 69 -321 ^ 200524880 MS (APCI, m / z): 402 (M + 1) +. Reference Example 1 4 1 2- (2-Fluoroaniline) -4-hydroxy-5-phenylpyrimidine was reacted from 2-fluoroaniline (5 mmol) according to the method of Reference Example 18 to obtain the target compound (4 3 mg, 3%). 1H-NMR (270 MHz, DMS〇-d6) 5 ppm: 11. 31 (brs, 1H), 8. 78 (brs, 1H), 8. 25 (t, 1H, J = 7. 9 Hz), 7. 99 (s, 1H), 7. 68-7. 63 (m, 2H), 7. 40-7. 09 (m, 6H) HPLC (reverse phase): Rt. (min) two 4. 32 MS (APCI, m / z): 282 (M + l) +. Reference Example 142 2- (2-Fluorophenylamino) -4-hydrazino-5-phenylpyrimidine By 2- (2-fluoroaniline) -4-hydroxy-5-phenylpyrimidine (40 mg, 0. 143 mmol), and reacted according to the method of Reference Example 20 to obtain the target compound (28 mg, 66%) ° 1 Η-NM R (2 7 0 MH z, DM S Ο-d6) 5 p p m: 8. 4 7 (s, 1H), 8. 11 (dt, lH, J = 1. 6Hz, 8. 4Hz), 7. 20 (s, lH), 7. 67 (brs, lH), 7. 46-7. 00 (m, 8H), 4. 55 (brs, 2H) HPLC (reverse phase): Rt. (min) = 2. 83 MS (APCI, m / z): 296 (M + 1) +. Reference Example 1 4 3 2- (2-Ethoxyanilide) -4-hydroxy-5-phenylpyrimidine The target compound was obtained by reacting 2-ethoxyaniline (5 mmol) according to the method of Reference Example 18. -322-200524880 HPLC (reversed phase): Rt. (min) = 4.71 MS (APCI, m / z): 3 08 (M + 1) +. Reference Example 144 2- (2-Ethoxyanilide) -4-hydrazino-5-phenylpyrimidine The reaction can be obtained by the method. HPLC (reverse phase) · Rt. (min) = 3. 10 MS (APCI, m / z): 3 22 (M + 1) +. Reference Example 145 4-Hydroxy-5-phenyl-2- (pyridin-3-ylamino) -pyrimidine The target compound was obtained by reacting 3-aminopyridine (5 mmol) by the method of Reference Example 18. HPLC (reverse phase) · Rt. (min) = 2. 70 MS (APCI, m / z): 265 (M + l) +. Reference Example 1 4 6 4-Hydrazyl-5-phenyl-2- (pyridin-3-ylamino) -pyrimidine by 4-hydroxy-5-phenyl-2- (pyridin-3-ylamino)- Pyrimidine can be reacted according to the method of Reference Example 20 to obtain the target substance. 1H-NMR (270 MHz, D M S 〇-d 6) 5 p p m: 9 · 4 2 (s, 1 Η), 8 · 9 1 (d, 1H, J 2 2.2 Hz), 8. 39-8. 34 (m, 1H), 8 · 10 (dd, 1H, J = 1. 4 Hz, 4. 6 Hz), 7. 77 (s, 1H), 7. 69 (brs, 1H), 7. 47-7. 34 (m, 5H), 7. 28 (dd, 1H, J = 4. 6 Hz, 8. 4 Hz), 4. 42 (brs, 2H) HPLC (reverse phase): Rt. (min) = 2. 20 MS (APCI, m / z): 279 (M + l) +. -323-200524880 Reference Example 147 4-Hydroxy-o-toluidine Pyrimidine The target compound (70 mg, 5%) was obtained by reacting o-methoxyaniline (5 mmol) according to the method of Reference Example 18. HPLC (reverse phase): Rt. (min) = 3. 90 MS (APCI, m / z): 278 (M + l) +. Reference Example 148 4-Hydrazyl-o-toluidine Pyrimidine 4-hydroxy-o-toluidine Pyrimidine (66 mg, 0. 239 mmol), and the target compound (36 mg, 52%) was obtained according to the method of Reference Example 20. HPLC (reverse phase): Rt. (min) = 2. 29 MS (APCI, m / z): 292 (M + 1) + 〇 Reference Example 149 4-hydrazino-2-anilino-6-pyrazol-1-yl-5-thien-3-yl-pyrimidine 4,6-dichloro-2-anilino-5-thien-3-yl-pyrimidine (186 mg, 0. 577 mmol), and reacted according to the method of Reference Example 38 to obtain the target compound (143 mg, 71%). HPLC (reverse phase): Rt. (min) = 3.65 MS (APCI, m / z): 350 (M + l) +. Reference Example 150 2- (5-Chloro-2-methylbenzylamino) -4-supranyl-5-phenyl-6-pyrazole-l-yl-pyrimidin is composed of 4,6-monochloro-2- (5-Fluoro-2-tolylamino) -5-phenylpyrimidine (mg, 0.287 mmol) can be reacted according to the method of Reference Example 38 to obtain the target compound (58 mg, 54%). 324 -200524880 HPLC (reversed phase): Rt. (min) = 4.14 MS (APCI, m / z): 376 (M + 1) + 〇 Reference Example 1 5 1 2-Cyclohexylamino-4-hydroxy-5-phenylpyrimidine from cyclohexylamine ( 5 mmol), according to the method of Reference Example 18 to obtain the target compound (410 mg, 30%). HPLC (reverse phase): Rt. (min) = 3. 79 MS (APCI, m / z): 270 (M + l) +. Reference Example 1 5 2 2-Cyclohexylamino-4-hydrazino-5-phenylpyrimidine is composed of 2-cyclohexylamino-4-hydroxy-5-phenylpyrimidine (341 m§, κ27 mmo1), according to reference The target compound (289 mg, 80%) was obtained by the reaction of the method of Example 20. HPLC (reverse phase): Rt. (min) = 2. 98 MS (APCI, m / z): 284 (M + 1) + 〇 Reference Example 153 4-Hydroxy-2-anilino-5-thien-3-yl-pyrimidine from ethyl thiophen-3-yl acetate (30 mmol) 'The reaction was carried out according to the method of Reference Example 19 to obtain the target compound (456 mg, 8%). ] H-NMR (270 MHz, DMS 0-d6) 5 ppm: 8 * 99 (brs? 1H), 8 * 29 (S, lH), 8. 05 (d, lH, J = 1. 9Hz), 7. 65: 7. 53 (m, 3H), 7. 37-7. 28 (m, 3H), 7. 08-7. 02 (m, 2H) HPLC (reverse phase): Rt. (min) 4. 12 MS (APCI, m / z): 270 (M + l) +. -325-200524880 Reference Example 1 5 4 4-Amino-2-anilino-5-thien-3-yl-pyrimidine by 4-hydroxy-2-anilino-5-thien-3-yl-pyrimidine, according to reference The target compound (101 g, 53%) was obtained by the method of Example 20. HPLC (reverse phase): Rt. (min) = 2. 82 MS (APCI, m / z): 284 (M + 1) + 〇 Reference Example 1 5 5 4-Hydroxy-2-anilino-5-pyridin-2-yl-pyrimidine from pyridin-2-ylacetate ethyl The ester (10 mmol) was reacted according to the method of Reference Example 19 to obtain the target compound (100 mg, 8%). HPLC (reverse phase): Rt. (min) = 2. 58 MS (APCI, m / z): 265 (M + l) +. Reference Example 1 5 6 4-Amino-2-anilino-5-pyridin-2-yl-pyrimidine By 4-hydroxy-2-anilino-5-pyridin-2-yl-pyrimidine (54 mg, 0. 205 mmol), and reacted according to the method of Reference Example 20 to obtain the target compound (30 mg, 53%) ° HPLC (reverse phase): Rt. (min) = 3. 04 MS (APCI, m / z): 279 (M + l) +. Reference Example 157 5- (2-Chloro-6-fluorophenyl) -4-hydroxy-2-aniline pyrimidine was reacted from ethyl 2-chloro-6-fluorophenylacetate (15 mmol) according to the method of Reference Example 19. Get the object. HPLC (reverse phase): Rt. (min) = 4. 43 -326-200524880 MS (APCI, m / z): 316 (M + l) +. Reference Example 1 5 8 5- (2-Chloro-6-fluorophenyl) -4-hydrazino-2-aniline pyrimidine by 5- (2-chloro-6-fluorophenyl) -4- mesityl-2- Aniline is determined by reaction according to the method of Reference Example 20 to obtain the target substance. HPLC (reverse phase): Rt. (min) = 3. 21 MS (APCI, m / z): 3 30 (M + l) +. Reference Example 1 5 9 4-Ethylsulfenyl-N-methyl-benzenesulfonylazine 2 mol, 43. 7 g) was dissolved in dioxane (200 ml), and triethylamine (0. 3 mol, 41. 8 ml), 40% methylamine_methanol solution (0 · 3 m m ο 1, 2 3 · 3 m 1), and stirred at room temperature for 2 hours. The reaction solvent was distilled off under reduced pressure, and then extracted with ethyl acetate-water, and the organic layer was concentrated. The obtained residue was recrystallized from ether to obtain the target compound (25. 6 G, 60%). HPLC (reverse phase) Rt. (min) = 3. 14 MS (APCI, m / z): 214 (M + 1) +. Reference Example 160 4-Ethyl benzsulfonamide The reaction product was purified according to the method of Reference Example 1 59 to obtain the target compound. HPLC (reverse phase): Rt. (min) = 2. 52 MS (APCI, m / z): 200 (M + l) +. Reference Example 161 Cardioethynyl-N-cyclopropyl-benzenesulfonamide The reaction product was purified according to the method of Reference Example 159 to obtain the target compound. -327-200524880 HPLC (reversed phase): Rt. (min) = 3. 69 MS (APCI, m / z): 240 (M + l) +. Reference Example 1 6 2 4-Ethyl-N-ethyl-benzenesulfonamide The reaction product was purified according to the method of Reference Example 159 to obtain the target compound. HPLC (reverse phase): Rt. (min) = 3. 58 MS (APCI, m / z): 228 (M + 1) +. Reference Example 1 6 3 1- (1-Methanesulfonyl-1H-pyrrole-3-yl) -ethanone Dissolve 3-ethylamidine B ratio (5 mmol, 546 mg) in DMF (30 ml) and add Potassium butyrate (5 mmol, 561 mg) and mesylate chloride (7.5 mmol, 580 ml) were stirred at 80 ° C for 18 hours. The reaction solvent was distilled off under reduced pressure, and then extracted with ethyl acetate-water, and the organic layer was concentrated. The target compound (285 mG, 31%) was obtained by silica gel column purification. HPLC (reverse phase) · Rt. (min) = 3. 01 MS (APCI, m / z): 188 (M + l) +. Reference Example 164 Acetylenyl-N- (2-hydroxyethyl) -benzenesulfonamide The reaction product was purified according to the method of Reference Example 159 to obtain the target compound. HPLC (reverse phase): Rt. (min) = 2. 79 MS (APCI, m / z): 244 (M + l) +. Reference Example 1 6 5 4-Ethylfluorenyl-N-n-propyl · benzenesulfonamide The reaction product was purified according to the method of Reference Example 159 to obtain the target compound. -328-200524880 HPLC (reversed phase): Rt. (min) = 3.96 MS (APCI, m / z): 242 (M + 1) +. Reference Example 1 6 6 (4-Ethylbenzenesulfonamido) -acetic acid 4-Ethylbenzenesulfenyl chloride (2 mmol, 43.7 mg) was dissolved in dioxane (20 ml), and triethylamine ( 4 mmol, 0.56 ml), tert-butyl glycine hydrochloride (2. 4 mmol, 402 mg), and stirred at room temperature for 2 hours. The reaction solvent was distilled off under reduced pressure, and then extracted with ethyl acetate-water, and the organic layer was concentrated. A trifluoroacetic acid-dichloromethane solution (1: 1, v / v, 10 ml) was added to the obtained residue, and the mixture was stirred at room temperature for 24 hours. After the reaction was completed, the residue was concentrated, and the residue was washed with ether to obtain a quantitative target substance. HPLC (reverse phase): Rt. (min) = 2.91 MS (APCI, m / z): 258 (M + 1) + 〇Reference Example 167 N4- (2-benzo [1,3] difluoren-5-yl-ethyl) -6-fluorenyl-N2-phenyl-pyrimidine-2,4-diamine by 4,6-dichloro-2-aniline pyrimidine (120 mg, 0. 5 mmol) using 2-benzo [1,3] difluorenylfmoc-5-yl-ethylamine (252 mg, 1. 25 mmol), according to the method of Reference Example 8 to obtain the target compound (100 mg, 55%). MS (APCI, m / z): 3 65 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 65.  Reference Example 1 6 8 [4- (6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl) -6-hydrazino-pyrimidin-2-ylphenylphenyl- Amine-329-200524880 was prepared from 4,6-dichloro-2-aniline (120 mg, 0.5 mmol) using 6,7-dimethoxy-1,2,3,4-tetrahydro- Isoquinoline (138 mg, 0. 6 mmol), and the target compound (90 mg, 46%) was obtained according to the method of Reference Example 8. MS (APCI, m / z): 3 93 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 68.  Reference Example 169 2- (pyridin-3-ylamino) -pyrimidine-4,6-diol. The reaction product was obtained from 3-aminopyridine (5 mmol) according to the method of Reference Example 2 to obtain the target compound (361 mg, 35% ). 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 8. 91 (s, 1H), 8. 22 (d, 1H, J = 8. 4 Hz), 8. 16 (d, 1H, J = 4. 6 Hz), 7. 32-7. 25 (m, 1H), 4. 87 (s, 1H) MS (APCI, m / z): 205 (M + l) +.  HPLC (reverse phase): Rt. (min) = 0. 87.  Reference example 1 7 0 (4,6-monogas-1¾ 卩 疋 -2 -yl) -fluorene ratio 卩 疋 -3 -yl-amine by 2- (pyridin-3-ylamino) -pyrimidine-4,6- The diol was reacted according to the method of Reference Example 3 to obtain the target compound (30 mg). MS (APCI, m / z): 241 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. twenty three. Reference Example 1 7 1 N4- [2- (3,4-dimethoxy-phenyl) -ethyl] -6-hydrazino-N2-pyridin-3-yl-pyrimidine-2,4-diamine was (4,6-dichloro-pyrimidin-2-yl) -pyridin-3-yl-amine (30 nig, 0.12-330-200524880 mmol) using 2- (3,4-dimethoxy-benzene Group) _ethylamine (0. 〇31111, 〇. 18 m m ο 1). The reaction was performed according to the method of Reference Example 8 to obtain the target compound (4 mg, 45%). MS (APCI, m / z): 3 82 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 2. 63.  Reference Example 172 5-methyl-2- (pyridin-3-ylamino) -pyrimidine-4,6-diol Dissolve 3-aminopyridine (940 mg, 10 mmol) in ethanol, and add 1 hydrazone-pyridine hydrochloride The azole-1 -carboxamidine (1.47 g, 10 mm ο 1) was heated under reflux for 15 hours. After the reaction, ethanol and sodium ethoxide (21 wt%, 1 1. 2 ml, 30 mmol), diethyl 2-methylmalonate (3.42 ml, 20 mmol), heated under reflux for 15 hours, the reaction was stopped with acetic acid, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. After the organic layer was concentrated, diethyl ether was added, and the precipitated solid was pulverized and collected by filtration, and washed with diethyl ether to obtain the target compound (0.5 51 g, 23%). MS (APCI, m / z): 219 (M + l) +.  HPLC (reverse phase): Rt. (min) = 1 · 5〇 · Reference Example 1 7 3 (4,6-Mono-5-methyl-pentadien-2-yl) -1] is more -2- (pyridin-3-ylamino) -pyrimidin-4,6-diol (510 mg, 2. 34 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (140 mg, 23%). MS (APCI, m / z): 255 (M + 1) +.  Η P L C (inverted): R t.  (mi η) = 3 · 4 6 · -331-200524880 Reference Example 1 7 4 N4- [2- (3,4-dimethoxy-phenyl) -ethyl] -6-fluorenyl-5-methyl Phenyl, 2-radidine, 3-yl-pyrimidin-2,4-diamine by (4,6-dichloro-5-methyl-pyrimidin-2-yl) -pyridin-3-yl-amine (77 mg, 0. 3 mmol), using 2- (3,4-dimethoxy-phenyl) · ethylamine (0.  〇 7 6 m], 0. 45 mmol), according to the method of Reference Example 8 to obtain the target compound (54 mg, 92%). MS (APCI, m / z): 396 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.68 · Reference Example 1 7 5 2- (6-methoxy-pyridin-3-ylamino) -pyrimidine-4,6-diol is determined by methoxy-fluorene ratio- 3-Amine (5 mmol) was reacted according to the method of Reference Example 2 to obtain the target compound (600 mg, 26%). MS (APCI, m / z): 23 5 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 13. Reference Example 1 7 6 (4,6-dichloro-pyrimidin-2-yl)-(6-methoxy-pyridin-3-yl) -lime 2- (6-methoxy-pyridin-3-yl) Amine) -pyrimidine-4,6-diol (150 mg, 0. 64 mmol), and reacted according to the method of Reference Example 3 to obtain the target substance. MS (APCI, m / z): 271 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.98 · Reference Example 1 7 7 N, [2- (3,4-dimethoxy-phenyl) -ethyl] -6-hydrazinomethoxy-radidine-3 -yl ) -Pyrimidine-2,4-diamine-332-200524880 by (4,6-dichloro-pyrimidin-2-yl M 6 -methoxy-pyridine-3 -yl) -amine (100 mg, 0 . 37 mmol) using 2- (3,4-dimethoxy-phenyl) -ethylamine (0.1  〇 9 4 m 1, 〇.  5 6 m m ο 1), the reaction was performed according to the method of Reference Example 8 to obtain the target product (47 m g 5 96%). MS (APCI, m / z): 412 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3.31.  Reference Example 1 7 8 1- (3,4-dimethoxy-phenyl) -2- (6-hydrazino-2-aniline-did-4-ylamino) -ethanol_ by 4, 6-Dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2-amino-1- (3,4-dimethoxy · phenyl) -ethanol (0. 35 g, 1. 5 mmol), according to the method of Reference Example 8 to obtain the target compound (190 mg, 70%). MS (APCI, m / z): 397 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 14.  Reference Example 1 7 9 (2,6-dichloro-pyrimidin-4-yl)-[2- (3,4-dimethoxy-phenyl) -ethyl] -amine will contain 2,4,6- Trichloro-pyrimidine (1.84 g, 10 mmol) and [2- (3,4-dimethoxyl-phenyl) -ethyl] -carbamic acid third butyl ester (2. 81 g, 10 mmol) of N, N-dimethylformamide (10 ml), sodium hydride (55 wt% oil, 524 mg, 12 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction, a mixed solution of diethyl ether and an aqueous ammonium chloride solution was added to stop the reaction, and the organic layer was washed with a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain (2,6-dichloro-pyrimidin-4-yl)-[2- (3, analdimethoxy-phenyl) _ethyl] _amine A crude product of third butyl formate. Add 10% trifluoroacetic acid-200524880 dichloromethane solution (20 ml) to the constituent organisms, and stir at room temperature for 1 hour. After the reaction, it was diluted with dichloromethane, and the organic layer was washed with an aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The organic layer was concentrated and purified by column chromatography to obtain the target compound (7 4 7 mg, 22%). MS (APCI, m / z): 328 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 72.  Reference Example 1 0 0 N2-Cyclopropyl-N4- [2- (3,4-dimethoxy-phenyl) -ethyl-butanyl 6-fluorenyl-pyrimidine-2,4-diamine , 6-dichloro-pyrimidin-4-yl)-[2- (3,4-dimethoxy-phenyl) _ethylbamine (305 mg, 0. (93 mmol) was added to cyclopropylamine (1 ml), and the tube was heated and stirred at 100 ° C for 30 minutes in a sealed tube. After cooling, dilute with dichloromethane to 1. 5 M hydrochloric acid, sodium bicarbonate aqueous solution, and saturated sodium chloride aqueous solution were washed. The methylene chloride solution was dried over anhydrous magnesium sulfate and concentrated to obtain 6-chloro-N2-cyclopropyl-^^ 4- [2- (3,4-dimethoxy-phenyl) -ethylpyrimidine _2,4-Diamine crude product. Add hydrazine monohydrate-ethanol (2: 1, v / v, 6 ml) to the crude product, and stir at 95 ° C for 1 hour. After the reaction was concentrated, water was added to the residue, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate to obtain the target compound (302 mg, 94%). MS (APCI, m / z): 345 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 82. Reference Example 1 8 1 2- (5-Fluoro-2-methyl-anilino) -5-methyl-pyrimidine-4,6-diol was prepared from 2-methylmalonic acid monoethyl acetate (5 · 1 m 1, 3 0 mm ο 1), according to the method of Reference Example -334-200524880 8 6 to obtain the target compound (4 8 1 mg, 19%). MS (APCI, m / z): 250 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 18.  Reference Example 182 (4,6-Dichloro-5-methyl-pyrimidin-2-yl)-(5-fluoro-2-methyl-phenyl) -amine consisting of 2- (5-fluoro-2-methyl -Anilino) · 5-methyl-pyrimidine-4,6-diol (481 mg, 1. 9 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (339 mg, 61%). MS (APCI, m / z): 286 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 6. 66.  Reference Example 1 8 3 (5-Fluoro-2-methyl-phenyl)-(4-hydrazino-5-methyl-6-pyrazol-1-yl-pyrimidin-2-yl) -amine is derived from (4 , 6-Dichloro-5-methyl-pyrimidin-2-yl)-(5-fluoro-2-methyl-phenyl) -amine can be reacted according to the method of Reference Example 38 to obtain the target compound. MS (APCI, m / z): 314 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 58.  Reference Example 1 8 4 5-phenyl-2- (pyridin-3-ylamino) -pyrimidine-4,6-diol was reacted from 3-aminopyridine (941 mg, 10 mmol) according to the method of Reference Example 16. The target substance was obtained (816 mg, 29%). MS (APCI, m / z): 281 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.41 · Reference Example 1 8 5-335-200524880 (4,6-mono--5-benzyl-¾, fluoren-2-yl) -fluorene ratio Π-decyl-3-yl- Amine consists of 5-phenyl-2- (pyridin-3-ylamino) -pyrimidine-4,6-diol (991 mg, 3. 5 mmol), and reacted according to the method of Reference Example 17 to obtain the target compound (7 15 mg, 64%). MS (APCI, m / z): 317 (M + l) +.  HPLC (reverse phase): Rt. (min) 2 4.16. Reference Example 1 8 6 (4-hydrazino-5-phenyl-6-pyrazol-1-yl-pyrimidin-2-yl) -pyridin-3-yl-amine consisting of (4,6-monogas-5-benzene The base compound (II 疋 -2-yl)-卩 JiD 疋 -3-yl-amine 'can be reacted according to the method of Reference Example 38 and 38 to obtain the target substance. MS (APCI, m / z): 345 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 57.  Reference Example 1 8 7 (5-¾-2-methyl-phenyl)-(4 -Cycyl-6-t-Doxy-1-yl-5-methyl-an-B--2-yl) -amine The target compound can be obtained by reacting (4,6-dichloro-5-methyl-pyrimidin-2-yl)-(5-fluoro-2-methyl-phenyl) -amine according to the method of Reference Example 44. MS (APCI, m / z): 314 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.67 · Reference Example 1 8 8 (4-hydrazino-6-imidazol-phenyl-5-phenyl-pyrimidin-2-yl) -pyridin-3-yl-amine consists of (4,6 -Dichloro-5-phenyl-pyrimidin-2-yl) -pyridin-3-yl-amine, which can be reacted according to the method of Reference Example 44 to obtain the target compound. MS (APCI, m / z): 345 (M + l) +.  -336-200524880 HPLC (reversed phase): RL (min) = 2. 00.  Reference Example 1 8 9 2-O-tolylamino-pyrimidine_4,6-diol From o-toluidine (5 mmol), the target compound was obtained according to the method of Reference Example 2. i-NMRpYO MHz, DMS0-d6) δ ppm: 7. 68 (d, 1H, J = 7. 8 Hz), 7. 03-7. 23 (m, 3H), 4. 74 (s, 1H), 2. 22 (s, 3H) · MS (APCI, m / z): 218 (M + 1) + · HPLC (reverse phase): Rt. (min) = 2. 27.  Reference Example 190 (4,6-dichloro-pyrimidin-2-yl) -o-toluene-amine From 2-o-tolylamino-pyrimidine'D-4,6-diol (351 mg, 1. 6 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (318 mg, 77%). MS (APCI, m / z): 254 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5.89. Reference Example 1 9 1 (4 -Chenyl-6-Miso Ran-1-yl-Chew-2 * 'yl) -O-formyl-Men-Yu Yuyou (4,6-dichloro-pyrimidine-2 -Yl) -o-toluene-amine (76 mg, 0. 3 mmol), according to the method of Reference Example 44 to obtain the target compound (7 mg, 8%). MS (APCI, m / z): 282 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 56.  Reference Example 1 9 2 5-phenyl-2-o-tolylamino-pyrimidine-4,6-diol was converted from o-toluidine (5 3 6 mg, 5 mm ο 1) according to the method of Reference Example 16 -337-200524880 The target substance should be obtained (3 27 mg, 22%). MS (APCI, m / z): 294 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 32.  Reference Example 1 9 3 (4,6-Dichloro-5-phenyl-pyrimidin-2-yl) -o-toluene-amine from 5-phenyl-2-o-tolylamino-pyrimidine-4,6- Diol (327 mg, 1. 1 mmol), according to the method of Reference Example 17, the target compound (177 mg, 48%) was obtained. MS (APCI, m / z): 3 30 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6. 61.  Reference Example 194 (4-hydrazino-5-phenyl-6-pyrazol-butyl-pyrimidin-2-yl) -o-toluene-amine 2-yl) -o-toluene-amine (99 mg, 0. 3 mmol), and reacted according to the method of Reference Example 38 to obtain the target compound (83 mg, 77%) ° MS (APCI, m / z): 35 8 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 3. 76.  Reference Example 1 9 5 (5-Fluoro-2-methyl-phenyl)-(4-hydrazino-6-imidazol-1-yl-pyrimidin-2-yl) -amine consisting of 4,6-dichloro-2 -(5-fluoro-2-tolylamino) -pyrimidine (82 mg, 0. 3 mmol), and the target compound (42 mg, 47%) was obtained according to the method of Reference Example 44. MS (APCI, m / z): 300 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 76. Reference Example 1 9 6-338-200524880 N4- (3,4-Dimethoxybenzyl) -6-hydrazino-N2 -phenyl-methanidine — 2,4 -diamine by 4,6-dichloro -2- Pyrimidine (554 mg, 2. 31 mmol), use 3. 4-dimethoxy-benzylamine (0.44 ml, 6. 93 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (148 mg, 18%). MS (APCI, m / z): 367 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 18.  Reference example 1 9 7 N4- (3,4-dimethoxy-phenyl) -6-hydrazino-N2-phenyl-pyrimidine_2,4-diamine is 4,6-monochloro-2-aniline II. Midine (480 mg, 2 mmol) in Luhuowu, etc. 5 ml) was dissolved ’, 3,4-mono * methoxybenzylamine (613 mg, 4 mmol) and carbonate (424 mg, 4 mmol) were added and heated under reflux for 4 8 hours. After the reaction, the organic layer was dried with ethyl acetate / water extraction 'and concentrated. After concentration, a solution of hydrazone-1 hydrate-ethanol (2: 1, v / v, 3 ml) was added to the residue, and the mixture was stirred at 95 ° C for 2 hours. After cooling at room temperature and concentrating, diethyl ether was added, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the target substance (441 mg, 63%). MS (APCI, m / z): 35 3 (M + 1) '· HPLC (reverse phase): Rt. (min) = 3.27 · Reference Example 1 9 8 {4-chloro-6- [2- (3,4-dimethoxy-phenyl) -ethoxy] -pyrimidine_2_ylphenyl _ Amine is a solution of 2- (3,4-dimethoxy-phenyl) -ethanol (1.09 g, 6 mm0) in tetrahydrofuran (15 m), and sodium hydride (55 wt% oil) 284 mg, 6. 5 mmol), heated to reflux for 30 minutes. The reaction solution was cooled at room temperature, and -339-200524880 4,6-dichloro-2-aniline (1. 2 g, 5 mmol), heated to reflux for 3 hours. After cooling, a mixed solution of diethyl ether and an ammonium chloride aqueous solution was added to the reaction solution to terminate the reaction, and the organic layer was washed with a saturated sodium chloride aqueous solution and dried over anhydrous magnesium sulfate. After concentration, purification by silica gel column chromatography gave the target compound (1.  1 1 g, 5 7%) 〇 MS (APCI, m / z): 3 86 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 6.44. Reference Example 1 9 9 {4- [2- (3,4-dimethoxy-phenyl) -ethoxy] -6-hydrazino-pyrimidin-2-ylbenzene -Amine in {4-chloro-6- [2- (3,4-dimethoxy-phenyl) -ethoxy] -pyrimidin-2-ylphenylphenyl-amine (3 85 mg, 1 mmol ) To the solution of hydrazone 1 hydrate-ethanol (2: 1, v / v, 3 ml) was added, and stirred at 95 ° C for 3 hours. After cooling and concentrating at room temperature, ethanol was added, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the target substance (307 mg, 81%). MS (APCI, m / z): 3 82 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 83.  Reference Example 200 N4 -Benzo [1,3] bisfluoren-5-ylmethyl-6-hydrazino-N2-. Phenyl-pyrimidine-2,4-diamine by 4,6-dichloro-2-aniline pyrimidine (427 mg, 1. 78 mmol) using benzo [1,3] difluoren-5-yl-methylamine (0.1 66 ml, 5. 34 mmol), and the target compound (140 mg, 22%) was obtained according to the method of Reference Example 8. MS (APCI, m / z): 351 (Μ + 1) +.  -340- 200524880 HPLC (reversed phase): Rt. (min) 2: 3.28. Reference Example 201 N4- [2- (4-ethoxy-3-methoxy-phenyl) -ethyl] -6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine consists of 4, 6-Dichloro-2-aniline chemodine (240 mg, 1 mmol) using 2- (4-ethoxy-3-methoxy-phenyl) -ethylamine (0. 28 ml, 1. 5 mmol), according to the method of Reference Example 8 to obtain the target compound (0. 3 1 g, 79%). MS (APCI, m / z): 3 95 (M + 1) 'HPLC (reverse phase): Rt. (min) = 3.78. Reference Example 202 N4- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl] -6-hydrazino-N2-phenyl-pyrimidine-2 4,4-diamine consists of 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2- (3-ethoxy-4-methoxy-phenyl) -ethylamine (0.5 28 ml, 1. 5 mmol), according to the method of Reference Example 8 to obtain the target compound (0. 32 g, 82%). MS (APCI, m / z): 3 95 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 66.  Reference Example 2 Ο 3 > ^ 4- [2- (3,4-dichloro-phenyl) -ethyl] -6-hydrazino-1 ^ 2-phenyl-pyrimidine-2,4-diamine 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2- (3,4-dichloro-phenyl) -ethylamine (0. 22 ml, 1. 5 mmol), according to the method of Reference Example 8 to obtain the target compound (0. 29 g, 74%). MS (APCI, m / z): 3 8 9 (M + l) +.  200524880 HPLC (reverse phase): Rt. (min) = 4.23. Reference Example 204 6-hydrazino-N2-phenyl-N4- [2- (3-trifluorotolyl) -ethyl] -pyrimidine-2,4-diamine by 4, 6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2- (3-trifluorotolyl) -ethylamine (0. 24 ml, 1. 5 mmol), and the reaction was carried out according to the method of Reference Example 8 to obtain the target compound (0.23 g, 59%). MS (APCI, m / z): 3 89 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 14.  Reference Example 205 N4- [2- (4-Chloro-phenyl) -ethylb-6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine by 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2- (4-chloro-phenyl) -ethylamine (0. 2 1 ml, 1. 5 mmol), and the target compound (0.19 g, 59%) was obtained according to the method of Reference Example 8. MS (APCI, rxi / z): 3 5 5 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4.10. Reference Example 2 Ο 6 2- (2,6-dimethoxy-pyridin-3-ylamino) -pyrimidin-4,6-diol by 2,6-dimethoxy-pyridin-3-ylamine (10 mmol), and reacted according to the method of Reference Example 2 to obtain the target compound (502 mg, 19%). MS (APCI, m / z): 265 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 60.  Reference Example 207 (4,6-dichloro-pyrimidin-2-yl)-(2,6-dimethoxy-pyridin-3-yl) -amine -3-ylamino) -pyrimidine-4,6-diol (502-342-200524880 mg, 1. 9 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (25 5 mg, 45%). MS (APCI, m / z): 301 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6. 49.  Reference Example 208 (2,6-dimethoxy-pyridin-3-yl)-(4-fluorenyl-6-pyrazol-1-yl-pyrimidin-2-yl) -amine Chloro-pyrimidin-2-yl)-(2,6-dimethoxy-pyridin-3-yl) -amine can be reacted according to the method of Reference Example 38 to obtain the target compound. MS (APCI, m / z): 329 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 57.  Reference Example 209 2- (6-hydrazino-5-phenyl-2-anilino-pyrimidin-4-ylamino) -1-pyridin-4-yl-ethanol composed of 4,6-dichloro-5-benzene 2-anilidine (3 16 mg, 1 mmol) using 2-amino-1-pyridin-4-yl-ethanol (207 mg, 1. 5 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (203 mg, 49%). MS (APCI, m / z): 414 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 2. 35.  Reference Example 2 1 0 Ν4- [2- (4-fluoro-phenyl) -ethyl] -6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine consists of 4,6-dichloro-2 -Aniline (240 mg, 1 mmol) using 2- (4-fluoro-phenyl) -ethylamine (0. 2 m 1, 1.5 m m 〇]), and the reaction was performed according to the method of Reference Example 8 to obtain the target product (0.29 g, 94%). 200524880 MS (APCI, m / z): 3 3 9 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 76. Reference Example 2 1 1 2-M-tolylamino-pyrimidine-4,6-diol was reacted from 3-toluidine (5 mmol) according to the method of Reference Example 2 to obtain the target compound (5 8 3 mg, 5 4 %). MS (APCI, m / z): 218 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 81.  Reference Example 2 1 2 (4,6-dichloro-pyrimidin-2-yl) -m-toluene-amine by 2-m-tolylamino-pyrimidine · 4,6-diol (460 mg, 2.1 mmol ), According to the method of Reference Example 3, the target compound (495 mg, 92%) ° MS (APCI, m / z): 254 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 6.08. Reference Example 2 1 3 2- (5-methoxy-2-methyl-anilino) -pyrimidine-4,6-diol by 2-methyl-5-methoxyaniline (5 mmol) and reacted according to the method of Reference Example 2 to obtain the target compound (3 57 mg, 29%). MS (APCI, m / z): 248 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 51 · Reference Example 2 1 4 (4,6-Dichloro-pyrimidin-2-yl)-(5-methoxy-2-methyl-phenyl) -amine by 2- (5-methoxy -2-methyl-aniline) -pyrimidine 6-diol (205 mg, 0. 83 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (130-344-200524880 mg, 55%). MS (APCI, m / z): 284 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 5. 65.  Reference Example 2 1 5 (4-hydrazino-6-imidazol-1-yl-pyrimidin-2-yl)-(5-methoxy-2-methyl-phenyl) -amine consists of (4,6-di Chloro-pyrimidin-2-yl M5-methoxy-2-methyl-phenyl) -amine (64 mg, 0. 23 mmol), and reacted according to the method of Reference Example 44 to obtain the target compound (38 mg, 54%). MS (APCI, m / z): 312 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.64. Reference example 2 1 6 (2,6-monomethoxy-pyridin-3-yl)-(4-benzyl-6-misothio-1-ylpyridin-2-yl) -amine By (4,6-dichloro-pyrimidin-2-yl)-(2,6-dimethoxy-pyridin-3-yl) -amine (90 mg, 0. 3 mmol), and reacted according to the method of Reference Example 44 to obtain the target compound (70 mg, 71%). MS (APCI, m / z): 3 29 (Μ + 1) + · HPLC (reverse phase) · Rt . (min) = 2. 68.  Reference Example 2 1 7 2- (2> fluoro-aniline) -pyrimidine-4,6-diol was reacted from 2-fluoroaniline (5 mmol) according to the method of Reference Example 2 to obtain the target compound (3 6 1 mg , 3 3%). 1 Η-N M R (2 70 MHz, DMS〇-d6) oppm: 8. 24 (s, 1H), 6. 97--345-200524880 7. 29 (m, 3H), 4. 81 (s, 1H).  MS (APCI, m / z): 222 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 46.  Reference Example 2 1 8 (4,6-Dichloro-pyrimidin-2-yl)-(2-fluoro-phenyl) -amine by 2- (2-fluoro-aniline) -pyrimidine-4,6-diol The target object can be obtained by reacting according to the method of Reference Example 3. MS (APCI, m / z): 258 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5.87.  Reference Example 2 1 9 (2-fluoro-phenyl)-(4-hydrazino-6-imidazol-1-yl-pyrimidin-2-yl) -amine consisting of (4,6-dichloro-pyrimidin-2-yl) )-(2-fluoro-phenyl) -amine (77 mg, 0.3 mmol), and reacted according to the method of Reference Example 44 to obtain the target compound (52 mg, 61%) ° MS (APCI, m / z): 286 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 49.  Reference Example 220 2- (3-Fluoro-aniline) -pyrimidine-4,6-diol By 3-fluoroaniline (5 m m ο 1). According to the method of Reference Example 2, the target substance can be obtained (7.18 mg, 65%). 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 10. 76 (brs, 2H), 9. 07 (brs, 1H), 7. 86 (dd, 1H, J = 2. 1 Hz, 14. 2 Hz), 7. 36-7. 20 (m, 2H), 6. 82 (dt, 1H, J = 2. 1 Hz, 8. 3 Hz), 4. 98 (s, 1H).  -346-200524880 MS (APCI, m / z): 222 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 74. Reference example 2 2 1 (4,6-dichloro-pyrimidin-2-yl)-(3-fluoro-phenyl) -amine derived from 2- (3-fluoro-aniline) · pyrimidine-4,6-diol (twenty two. 1 g, 100 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (17.5 g, 68%). MS (APCI, m / z): 258 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6. 17.  Reference Example 222 2- (2-fluoro-5-methyl-aniline) -pyrimidine-4,6-diol can be obtained by reacting 2-fluoro-5-toluidine (4 mmol) according to the method of Reference Example 2. The target (3 63 mg, 39%). 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 10. 67 (brs, 2H), 8. 59 (brs, 1H), 8. 11 (d, 1H, J = 8. 3 Hz), 7. 13 (dd, 1H, J 2 8. 3 Hz, 11. 2 Hz), 6. 89 (m, 1H), 4. 87 (s, 1H), 2. 30 (s, 3H).  MS (APCI, m / z): 23 6 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 04.  Reference Example 223 (4,6-Mono-methylid-2-yl)-(2-chloro-5-methyl-phenyl) -amine by 2- (2-fluoro-5-methyl-aniline) -Pyrimidine-4,6-diol (789 mg, 3. 4 mmol), according to the method of Reference Example 3 to obtain the target compound (486 mg, 53%) ° MS (APCI, m / z): 272 (M + l) +.  HPLC (reverse phase): Rt. (min) two 6. 27.  -347-200524880 Reference Example 224 (2-fluoro-5-methyl-phenyl)-(4-hydrazinoimidazol-1-yl-pyrimidin-2-yl) -amine consisting of (4,6-dichloro-pyrimidine) -2-yl)-(2-fluoro-5-methyl-phenyl) -amine (82 mg, 0. 3 mmol), and reacted according to the method of Reference Example 4 to obtain the target compound (66 mg, 73%). MS (APCI, m / z): 300 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 2. 80.  Reference Example 225 N4- (3,4-difluorobenzyl) -6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine consisting of 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 3,4-difluorobenzylamine (0. 18 ml, 1. 5 mmol), according to the method of Reference Example 8 to obtain the target object. MS (APCI, m / z): 343 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 70. Reference Example 2 2 6 2- [2- (6-Hyrazinyl-2-anilino-pyrimidin-4-ylamino) -ethoxy] -ethanol was derived from 4,6-dichloro-2-phenylpyrimidine (480 mg, 2 mmol), using 2- (2 amino-ethoxy) -ethanol (0.3 m 1, 3 mm ο 1), according to the method of Reference Example 8 to obtain the target product. MS (APCI, m / z): 305 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 66.  Reference Example 227 (5-fluoromethyl-phenyl)-(4-hydrazino-6-imidazol-1-yl-5-phenyl-pyrimidine,) -amine- 348-200524880 Chloro-2- (5-fluoro-2-tolylamino) -5-phenylpyrimidine (209 mg, 0. 6 mmol), according to the method of Reference Example 4 to obtain the target compound (186 mg, 83%). MS (APCI, m / z): 376 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 03.  Reference Example 2 2 8 2-Methylsulfanyl-pyrimidin-4-ol The 2-thiourea (12. 8 g, 100 mmol) of a 3M aqueous solution of sodium hydroxide (70 ml), methyl iodide (7 ml, 1.2 ml) was added, and the mixture was stirred at room temperature for 18 hours. After the reaction, acetic acid was added to acidify, and the crystals were collected by filtration. The target substance can be obtained by recrystallization from ethanol (14. 2 g, quant). MS (APCI, m / z): 143 (M + l) +.  HPLC (reverse phase): Rt. (min) = 1. 82.  Reference Example 2 2 2-Anilino-pyrimidin-4-ol The 2-methylsulfanyl-pyrimidin-4-ol (5. 0 g, 35 mmol) was dissolved in 2-methoxymethyl monoethyl ether (10 ml), and aniline (3. 85 ml, 42. 2 mmol) and heated to reflux for 1 hour. After the reaction solution was cooled, the obtained crystals were collected by filtration from ether, and from formazan? Recrystallization can obtain the target (3. 5 5 g, 54%). MS (APCI, m / z): 188 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 2. 41.  Reference Example 2 3 0 (4-Hydrazinyl-pyrimidin-2-yl) -phenyl-amine was determined from 2-anilino-πden |] -4-ol (5 6 1 mg, 3 mm ο 1), according to Reference Example -349-200524880 2 0 The reaction can be obtained by the method (27 7 mg, 34%). MS (APCI, m / z): 202 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 05. Reference Example 2 3 1 Monoamine 6-hydrazino-N4- (2-morpholin-4-yl-ethyl) -N2-phenyl-pyrimidine-2, Xinyiren n, using 4,6-dichloro -2- Pyrimidine (265 mg, 1. 1 mmo1; method was performed morpholin-4-yl-ethylamine (0.145 ml, 3. 3 mmol), and the target compound (233 mg, 65%) was obtained according to the 8-blade reaction of Reference Example. MS (APCI, m / z): 330 (M + 1) 'HPLC (reverse phase): Rt. (min) = 2. 14.  Reference Example 232 2-[(6-fluorenyl-5-phenyl-2-anilino-pyrimidinyl)-(2-hydroxy-ethylphenylamino] -ethanol made from 4,6-dichloro-5-benzene 2-aniline pyrimidine (63 2 mg, 2 mmol), using 2- (2-hydroxy-ethylamino) -ethanol (575 ml, 6 mmol), and reacting according to the method of Reference Example 8 to obtain the target compound (488 mg, 65%). MS (APCI, m / z): 381 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2.61. Reference Example 2 3 3 6-hydrazino-N2-phenyl-N4-pyridin-4-ylmethyl-pyrimidine-2,4-diamine by 4,6-dichloro-2 -Aniline (240 mg, 1 mmol), using pyridin-4-yl-methylamine (.  1 5 m 1, 1 · 5 m m ο I) ′ The reaction was carried out according to the method of Reference Example 8 to obtain the target substance. MS (APCI, m / z): 3 08 (M + l) +.  200524880 HPLC (reverse phase): Rt. (min) = 2. 12.  Reference Example 234 6-hydrazino-N2-phenyl-N4-thien-2-ylmethyl-pyrimidine-2,4-diamine by 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol) Using thiophen-2-yl-methylamine (0. 15 ml, 1. 5 mmol), followed by fT reaction according to the method of Reference Example 8 to obtain the target compound. MS (APCI, m / z): 313 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 50.  Reference Example 2 3 5 N4- (2- [l, 3] disorocene-2-yl-ethyl) -6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine consists of 4,6 -Dichloro-2-aniline pyrimidine (240 mg, 1 mmol) using 2- [1,3] difluorenyl-2-ethyl-ethylamine (0. 16 ml, 1. 5 mmol), according to the method of Reference Example 8 to obtain the target substance. MS (APCI, m / z): 317 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 04. Reference Example 2 3 6 2- (6-hydrazino-2-aniline-pyrimidin-4-ylamino) _ethanol was prepared from 4,6-dichloro-2-aniline pyridine (480 mg, 2 mmol), Use 2-amino-ethanol (0. 18 ml, 3 mmol), and the reaction was carried out according to the method of Reference Example 8 to obtain the target compound. MS (APCI, m / z): 261 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 50.  Reference example 237 200524880 N, [2- (3,4-dimethoxy-phenyl) -ethyl] -N2- (5-fluoro-2-methyl-phenylbenzene 6-hydrazino-pyrimidine-2 4,4-diamine consists of (4,6-dichloro-pyrimidin-2-yl)-(2-fluoro-5-methyl-phenyl) -amine (82 mg, O.  3 mmol) using 2- (3,4-dimethoxy-phenyl) -ethylamine (0.03  〇 5 9 m}, 0.35 mmol), according to the method of Reference Example 8 to obtain the target compound (86 mg, 70%). MS (APCI, m / z): 413 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 06.  Reference example 2 3 8 1- (3,4-dimethoxy-phenyl) -2- [2- (5-fluoro-2-methyl-anilino) -6_hydrazino_pyrimidin-4-yl Amine] -ethanol from (4,6-dichloro-pyrimidin-2-yl)-(2-fluoro-5-methyl-phenyl) -amine), using 2-amino-1- (3,4 -Monomethoxy-phenyl) -ethanol 'can be reacted according to the method of Reference Example 8 to obtain the target substance. MS (APCI, m / z): 429 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. twenty three.  Reference Example 2 3 9 2- {2- [2- (5-Truncated-2-methyl-benzylamino) -6-pieyl-5-benzyl-½ [, pyrene-4 -ylamino; 1-ethoxybutanol is composed of 4,6-dichloro-2- (5-fluoro-2-tolylamino) -5-phenylpyrimidine (174 mg, 0. 5 mmol), using 2- (2-amino-ethoxy) -ethanol (.  〇 6 m 1, 〇.  6 mmol), according to the method of Reference Example 8, the target compound (186 nig, 90%) can be obtained. MS (APCI, m / z): 413 (Μ + 1) +.  200524880 HPLC (reverse phase): Rt. (min) = 3. 22 · Reference Example 240 2- {2- [2- (5-Fluoro-2-methyl-anilino) · 6-Hydrazine-pyrimidinylamino] -ethoxybutanol is derived from (4,6-di Chloro-pyrimidin-2-yl)-(2-fluoro-5-methyl-phenyl) -amine (82 mg, 0. 3 mmol) using 2- (2-amino-ethoxy) -ethanol (0.035 ml, 〇.  35 mmol) ′ according to the method of Reference Example 8 to obtain the target compound (9i mg, 90%) MS (APCI, m / z): 337 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 2. 94. Reference Example 241 2- (6-hydrazino-2-anilyl-pyrimidinylamino) -1-pyridin-4-yl-ethanol was prepared from 4,6-dichloro-2-aniline (240 mg, 1 mmol), and the reaction was carried out in accordance with the method of Reference Example 8 by using 2-mercapto-4-pyridine hydrazine ethylamine (0.41 mg, 3 mm ο 1). MS (APCI, m / z): 3 3 8 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 15.  Reference Example 242 5-Benzyl-2-anilino-pyrimidine-4,6-diol was reacted with dibenzyl-malonate (100 mmol) according to the method of Reference Example 16 to obtain the target compound ( 8. 48 g, 58%). MS (APCI, m / z): 294 (M + 1) 'HPLC (reverse phase): Rt. (niin) = 3. 71.  Reference Example 2 6-diol (8. 48 g, 28. 9 mmol), and reacted according to the method of Reference Example 17 to obtain the target compound (8.36 g, 88%). MS (APCI, m / z): 330 (Μ + 1) + · HPLC (reversed phase) · Rt. (min) = 7.20. Reference Example 244 5-benzyl-N4- [2- (3,4-dimethoxy-phenyl) _ethyl] _6_hydrazinyl-phenyl-pyrimidine- 2,4-diamine consists of (5-benzyl-4,6-dichloro-pyrimidin-2-yl) -phenyl-amine (330 mg, 1 mmol) using 2- (3,4-dimethoxy -Phenyl) -ethylamine (0.51 ml, 3 mmol), the reaction was carried out according to the method of Reference Example 8 to obtain the target compound 31 g, 67%) MS (APCI, m / z): 471 (M + 1) + · HPLC (reverse phase): Rt. (min) = 4. 53.  Reference Example 2 4 5 2- (5-Benzyl-6-fluorenyl-2-aniline-pyrimidin-4-ylamino) -1- (3,4-dimethoxy-benzyl) -ethanol (5-Benzyl-4,6-dichloro-pyrimidin-2-yl) -phenyl-amine (330 mg, 1 mmol) using 2-amino-i_ (3,4-dimethoxy-benzene -)-Ethanol (0. 7 mg, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (0.  29 g, 81%) MS (APCI, m / z): 487 (Μ + 1) +.  HPLC (reverse phase): Rt. (min) = 3. 93. Reference Example 2 4 6-354-200524880 2- [2- (5-benzyl-6-hydrazinyl-2-anilino-pyrimidin-4-ylamino) -ethoxybutanol from (5-benzyl -4,6-dichloro-pyrimidin-2-yl) -phenyl-amine (330 mg, 1 mmol) using 2- (2-amino-ethoxy) -ethanol (0. 3 ml, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (298 mg, 76%). MS (APCI, m / z): 395 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 39.  Reference Example 247 5-Benzyl-N4-cyclopropyl-6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine ft from (5-benzyl-4,6-dichloro-pyrimidine-2 -Yl) -phenyl-amine (330 mg,! Mmol) using cyclopropylamine (0. 21 ml, 3 mmol), and the reaction was carried out according to the method of Reference Example 8 to obtain the target compound (315 mg, 91%). MS (APCI, m / z): 347 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 08.  Reference Example 248 5-Benzyl-6-hydrazino-N2-phenyl-N4- (2-pyridin-4-yl · ethyl) -pyrimidine-2,4-diamine · (5-benzyl-4 , 6-dichloro-pyrimidin-2-yl) -phenyl-amine (330 mg,! Mmol) using 2-pyridin-4-yl-ethylamine (0. 3 6 m 1, 3 mm ο 1), according to the method of Reference Example 8 to obtain the target compound (335 mg, 82%). MS (APCI, m / z): 412 (M + 1) 'HPLC (reversed phase) · Rt. (min) = 2. 82.  Reference Example 249 5-benzyl-6-hydrazino-N 4, N4 -dimethyl-N 2 -phenyl-pyrimidine-2,4-diamine-355 ^ 200524880 by (5-benzyl-4,6 -Dichloro-pyrimidin-2-yl) -phenyl-amine (33.0 mg, 1 mmol) using dimethylamine (0. 24 mg, 3 mmol), and the reaction was carried out according to the method of Reference Example 8 to obtain the target compound (269 mg, 84%). MS (APCI, m / z): 3 3 5 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 4 · 06 · Reference Example 2 5 5 5-Benzyl-6-hydrazino-N2-phenyl-N4- (tetrahydro-furan-2-ylmethyl) _pyrimidine-2,4 -Diamine consists of (5-benzyl-4,6-dichloro-pyrimidin-2-yl) -phenyl-amine (330 mg, 1 mmol) using (tetrahydro-furan-2-yl)- Methylamine (0.31 ml, 3 mmol) was reacted according to the method of Reference Example 8 to obtain the target compound (300 mg, 81%). MS (APCI, m / z): 391 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 97. Reference Example 2 5 1 5-Benzyl-N4-cyclobutyl-6-hydrazino-N2-phenyl-pyrimidine-2,4-diamine consists of (5-benzyl-4,6-dichloro-pyrimidine- 2-yl) -phenyl-amine (330 mg, 1 mmol) using cyclobutylamine (0.26 ml, 3 mmol) according to the method of Reference Example 8 to obtain the target compound (323 mg, 90%). MS (APCI, m / z): 361 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 29.  Reference Example 2 5 2 2- (5-Benzyl-6-hydrazinyl-2-anilino-pyrimidin-4-ylamino) -ethanol from (5-benzyl-4,6-dichloro-pyrimidine-2 -Yl) -phenyl-amine (330 mg, 1 mmol) using 2-amino-ethanol (0.  18 m 1, 3 mmο]), according to the method of Reference Example 8-356-200524880, the target compound (268 mg, 92%) can be obtained. MS (APCI, m / z): 351 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 28.  Reference Example 2 5 3 1_ (6_hydrazino-5_phenyl-2-anilino-pyrimidin-4-ylamino) -propan-2-ol from 4,6-dichloro-5-phenyl-2 -Aniline (500 mg, 1. 58 mmol) ’using 1-amino-propan-2-ol (238 mg, 3. 16 mmol), and the target compound (353 mg, 64%) was obtained according to the method of Reference Example 8. MS (APCI, m / z): 351 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 31.  Reference Example 2 5 4 1_ (6-hydrazino-2-anilino-pyrimidine-cardiylamino) -propan-2-ol consists of 4,6-dichloro-2-aniline pyrimidine (240 mg, 1 mmol), The target compound (192 mg, 70%) was obtained by reacting with aminopropyl-propan-2-ol (225 mg, 3 mmol) according to the method of Reference Example 8. MS (APCI, m / z): 275 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 80.  Reference Example 255 1- (5-benzyl-6-hydrazinyl-2-anilino-pyrimidinylaminopropan-2-ol by (5-benzyl-4,6-dichloro-pyrimidin-2-yl) -Phenylamine (330 mg, 1 mmol), using propylamino-propan-2-ol (225 mg, 3 mmol), according to the method of Reference Example 8 to obtain the target compound (269 mg, 74%) ° MS (APCI, m / z): 3 65 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 60. -357-200524880 Reference Example 2 5 6 2- (5-benzyl-6-hydrazino-2-anilino-pyrimidin-4-ylamino) -1-pyridin-4-yl-ethanol from (5-benzyl -4,6-dichloro-pyrimidin-2-yl) -phenyl-amine (330 mg, 1 mmol) using 2-amino-l- (3,4-dimethoxy-phenyl) -Ethanol (415 mg, 3 mmol). The reaction was performed according to the method of Reference Example 8 to obtain the target compound (290 mg, 68%). MS (APCI, m / z): 428 (M + 1) +.  HPLC (reverse phase): Rt. (min) = 2. 73.  Reference Example 2 5 7 1- (3,4-dimethoxy-phenyl) -2- (6-hydrazino-5-phenyl-2-anilino-pyrimidin-4-ylamino) -ethanol 4,6-dichloro-5-phenyl-2-aniline pyrimidine (320 mg, 1 mmol) using 2-amino-1- (3,4-dimethoxy-phenyl) -ethanol (0 · 7 g, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (0. 32 g, 94%). MS (APCI, m / z): 473 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 61.  Reference Example 2 5 8 6-hydrazino-5, N2-diphenyl-N4- (2-pyrrolidin-1-yl-ethyl) -pyrimidine-2,4-diamine by 4,6-dichloro- 5-phenyl-2-aniline pyrimidine (320 mg, 1 mmol) using 2-pyrrolidin-1-yl-ethylamine (0. 38 ml, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (0. 34 g, 92%). MS (APCI, m / z): 3 90 (M + l) +.  -358-200524880 HPLC (reversed phase): Rt. (min) = 2. 52.  Reference Example 2 5 9 6-hydrazino-5, N2-diphenyl-N4- (2-piperidin-1-yl-ethyl) -pyrimidine_2, cardiodiamine consisting of 4,6-dichloro-5 -Phenyl-2-aniline pyrimidine (3,201,1,0101) 'Using 2-piperidin-1-yl-ethylamine (0. 4 2 ml, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (0.36 g, 92%). MS (APCI, m / z): 404 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 2. 66.  Reference Example 260 · N4- [2- (3,4-dimethoxy-phenyl) -ethylbenzene 6-hydrazino-5, N2-diphenyl-pyrimidine-2,4-diamine consisting of 4, 6-Dichloro-5-phenyl-2-aniline pyrimidine (320 mg, 1 mmol) using 2- (3,4-dimethoxy-phenyl) -ethylamine (0. 51 ml, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (0.5 43 g, 93%). MS (APCI, m / z): 457 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 18. Reference Example 26 1- 6-hydrazino-5, N2-diphenyl- N4-pyridin-4-ylmethyl-pyrimidine-2,4-diamine consisting of 4,6-dichloro-5-phenyl-2 -Aniline (3 20 mg, 1 mmol), then pyridine-4-yl-methylamine (0.3 ml, 3 mmol) was reacted according to the method of Reference Example 8 to obtain the target compound (0. 22 g, 85%). MS (APCI, m / z): 3 84 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 63.  Reference example 2 6 2 -359-200524880 6 -Cretinyl-N4-isopropyl-5, N2-monobenzyl-leptadidin-2,4-one month female by 4,6-dichloro-5- Phenyl-2-aniline (320 mg, 1 mmol) using isopropylamine (0. 26 ml, 3 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (0.25 g, 89%). MS (APCI, m / z): 3 3 5 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 14.  Reference Example 2 6 3 2- (4-methoxy-3,5-dimethyl-phenyl) -diethyl malonate Sodium hydride (more than 55%, oily) (5. 59 g, 128 mmol) was dissolved in dry tetrahydrofuran (100 ml), and diethyl malonate (19. 4 ml, 128 mmol). After stirring for 20 minutes, 4-bromo-2,6-dimethylmethoxybenzene (25. 0g, 116 mmol), tributylphosphine (940 mg, 4. 65 mmol) and ginseng (dibenzylideneacetone) dipalladium (0) (2. 13 g, 2.32 mmol) and heated under reflux for 10 hours. Filter through a silica gel plate, concentrate the mother liquor under reduced pressure, and purify by silica gel column chromatography (hexane: dichloromethane = 1: 1) to obtain the target compound (16. 0 g, 42%). MS (APCI, m / z): 295 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 53.  Reference Example 264 5- (4-methoxy-3,5-dimethyl-phenyl) -2-anilino-pyrimidin-4,6-diol consists of 2- (4-methoxy-3,5 -Dimethyl-phenyl) -diethyl malonate (11. 9 g, 40. 6 mmol), and reacted according to the method of Reference Example 16 to obtain the target compound (1 1. 68 g, 8 5%). MS (APCI, m / z): 3 3 8 (M + 1) +.  200524880 HPLC (reverse phase): Rt. (min) = 3. 89.  Reference Example 2 6 5 [4,6-Dichloro-5- (4-methoxy-3,5-dimethyl-phenyl) -pyrimidine_2_yl] _aniline by 5- (4-methoxy -3,5-dimethyl-phenyl) -2-anilino-pyrimidine-4,6-diol (11. 7 g, 34. 6 mmol), and the target compound (3. 80 g, 29%). MS (APCI, m / z): 374 (M + l) +.  HPLC (reverse phase): Rt. (min) = 7.32. Reference Example 2 6 6 4- (4,6-Dichloro-2-aniline-pyrimidin-5-yl) -2,6-dimethylphenol Will be [4,6-dichloro-5- (4-methoxy -3,5-dimethyl-phenyl) -pyrimidin-2-ylphenylaniline (500 mg, 1. 34 mmol) was dissolved in dichloromethane (15 ml) and cooled under nitrogen at -78 ° C. Add Tribromoboron (1.0 mM dichloromethane solution) (8. (04 ml), and stirred for 1 hour. Remove the cooling bath and warm to room temperature. After cooling at -78 ° C, methanol (100 ml) was added and concentrated under reduced pressure. The residue was dissolved in dichloromethane, washed with water, a saturated sodium bicarbonate solution and a saturated saline solution, and then the organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography (dichloromethane) gave the target compound (252 mg, 52%). MS (APCI, m / z): 360 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6. 10.  Reference Example 2 6 7 4- [4-Hydrazino-2-anilino-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-5-yl] -2,6-dimethyl-phenol By 4- (4,6-dichloro-2-aniline-chrysidine-5-yl) -2,6-monomethyl-benzyl acid (200524880 252 mg, 0. 702 mmol) using 2-pyridin-4-yl-ethylamine (0.17 ml, 1. 40 mmol), and reacted according to the method of Reference Example 8 to obtain the target compound (148 mg, 48%). MS (APCI, m / z): 442 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 92.  Reference Example 268 2- (4-Fluoro-aniline) -pyrimidine-4,6-diol was obtained from 4-aniline (5 mm ο 1) by reaction according to the method of Reference Example 2 to obtain the target compound (760 mg, 69% ). 1H-NMR (270 MHz, DMSO-d6) δ ppm: 7. 70-7. 63 (m, 2H), 7. 20-7. 10 (m, 2H), 4.87 (s, 1H) · MS (APCI, m / z): 222 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 42.  Reference Example 269 (4,6-Dichloro-pyrimidin-2-yl)-(4-fluoro-phenyl) -amine from 2- (4-fluoro-aniline) -pyrimidine-4,6-diol (400 mg, 1. 8 mmol), and reacted according to the method of Reference Example 3 to obtain the target compound (400 mg, 86%). MS (APCI, m / z): 258 (M + l) +.  HPLC (reverse phase): Rt. (min) = 5. 76.  Reference Example 270 > ^ 2- (4-fluoro-phenyl) -6-hydrazinyl-1 ^ 4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine is derived from (4 , 6-dichloro-pyrimidin-2-yl)-(4-fluoro-phenyl) -amine (1 g, 3. 87 mmol) using 2-pyridin-4-yl-ethylamine (1 ml, 8. 5 1 mmol) ′ was reacted according to the method of Reference Example 8-362- 200524880 to obtain the target compound (650 mg, 50%). MS (APCI, m / z): 340 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 37. Reference Example 271 Ν4- [2- (3,4-dimethoxy-phenyl)-[1,3] bisphosphorane-2-ylmethyl] -6-hydrazino-N2-phenyl-pyrimidine -2,4-Diamine is determined by 4,6-dichloro-2-aniline (240 mg, 1. (00 mmol) using 2- (3,4-dimethoxy-phenyl)-[1,3] disorocene-2-yl-methylamine (263 ml, 1. 10 mmol), according to the method of Reference Example 8 to obtain the target compound (237 mg, 54%) MS (APCI, m / z): 439 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 47.  Reference Example 272 2- (4-Chloro-aniline) -pyrimidine-4,6-diol was reacted from 4-chloroaniline (5 mm ο 1) according to the method of Reference Example 2 to obtain the target compound (719 mg, 61 %). 1H-NMR (270 MHz, DMS0-d6) 5 ppm: 9. 00 (s, 1H), 7. 68 (dt5 2H, J = 2. 6 Hz, 9. 1 Hz), 7. 35 (dt, 2H, J = 2. 6 Hz, 9. 1 Hz), 4. 95 (s, 1H).  MS (APCI, m / z): 2 3 8 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 05.  Reference Example 273 (4-Chloro-phenyl)-(4,6-dichloro-pyrimidin-2-yl) -amine (6 4 2 mg, 2. .  7 m m ο 1)-363-200524880. The target compound (722 mg, 97%) was obtained by reacting according to the method of Reference Example 3. MS (APCI, m / z): 274 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6.31. Reference Example 274 Ν2- (4-chloro-phenyl) -6-fluorenyl- N4- (2-pyridyl-ethyl) · pyrimidine -Chloro-phenyl)-(4,6-dichloro-pyrimidin-2-yl) _amine (2.43 g, 8. 85 mmol), using 2-pyridine · 4-yl-ethylamine (2.1 ml, 17. 7 mmol), according to the method of Reference Example 8 to obtain the target (2. 2 g, 70%) MS (APCI, m / z): 356 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 67.  Reference Example 2 7 5 2- (6-hydrazino-2-anilino-pyrimidin-4-ylamino) -pyrrolidin-1-yl-ethanone consists of 4,6-dichloro-2-aniline pyrimidine ( 0. 48 mg, 2 mmol) using 2-amino-1-pyrrolidin-1-yl-ethanone (0. 49 mg, 3 mmol), according to the method of Reference Example 8 to obtain the target compound (0. 35 g, 85%). MS (APCI, m / z): 328 (M + 1) 'HPLC (reverse phase): Rt. (min) = 3. 05. Reference Example 2 7 6 [4-Chloro-5-phenyl-6- (2-pyridin-4-yl-ethoxy) -pyrimidin-2-ylphenylphenyl-amine -Hydroxy-ethanol (6 7 6 iB 1,6 m χη ο 1) in tetrahydrofuran (15 m 1) solution, sodium hydride (55 wt% oil, 2 8 4 mg, 6. 5 mmol), heated to reflux for 30 minutes. After the reaction solution was cooled at room temperature, 4,6-dichloro-5 -phenyl-2-anilidine was added (1. 5 8 g, 5 m m ο 1), heated under reflux for 4 hours. -364-200524880 After cooling, the reaction solution was added to a mixed solution of diethyl ether and ammonium chloride aqueous solution to stop the reaction. The organic layer was washed with a saturated sodium chloride aqueous solution and dried under anhydrous magnesium sulfate. After concentration, purification by silica gel column chromatography gave the target compound (1. 00 g, 50%) MS (APCI, m / z): 403 (M + l) +.  HPLC (reverse phase): Rt. (min) = 4. 16.  Reference Example 277 Diethyl 2- (4-fluorophenyl) -malonate From 1-chloro-4-iodo: benzene (1. 8 ml, 15 mmol), and the target compound (1. 45 g, 38%). 1H-NMR (270 MHz, DMSO-d6) (5 ppm: 7. 41-7. 36 (m, 2H), 7. 08-7. 02 (m, 2H), 4. 59 (s, 1H), 4. 28-4. 16 (m, 4H), 1. 26 (t, 6H ,: [2 7. 3 Hz).  MS (APCI, m / z): 25 5 (M + l) +.  Reference Example 278 5- (4-Fluoro-phenyl) -2-anilino-pyrimidine-4,6-diol From 2- (4-fluorophenyl) -malonic acid diethyl ester (3. 9 mmol), according to the method of Reference Example 16 to obtain the target compound (0. 3 g, 34%). 1H-NMR (500 MHz, DMSO-d6) δ ppm: 1 l. 〇〇 (brs, 1H), 10. 45 (brs, 1H), 8. 82 (brs, 1H), 7. 68 (d, 2H, J = 8. 5 Hz), 7. 49 (t, 2H, J = 6. 5 Hz), 7. 34 (t, 2H, J = 8. 5 Hz), 7. 13-7. 03 (m, 3H).  MS (APCI, m / z): 298 (M + l) +.  Η P L C (inverted): R t.  (min) = 3 · 6 3 ·-365-200524880 Reference Example 279 [4,6-Dichloro-5- (4-fluoro-phenyl) -pyrimidin-2-yl] -phenyl-amine by 5- ( 4-fluoro-phenyl) -2-anilino-pyrimidine-4,6-di | mmol), and reacted according to the method of Reference Example 17 to obtain 8%). MS (APCI, m / z): 334 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6. 55.  Reference Example 2 8 Ο 5- (4-Fluoro-phenyl) -6-hydrazino-1 ^ 2-phenyl-1 ^ 4- (2-pyridine-pyridine-2,4-diamine consists of (4,6 -Dichloro-5-phenyl-pyrimidin-2-yl) -aniline (lg, with 2-pyridine-Udin-4-yl-ethylamine (806 mg, 6. 6 mmol), and the target compound (561 mg, 45%) was obtained according to the law. MS (APCI, m / z): 416 (M + l) +.  HPLC (reverse phase) · Rt. (min) = 2.58. Reference Example 2 1 [4-chloro-6- (3-pyridin-4-yl-pyrrole-1-yl) -pyrimidin-2-yl] -sodium hydride (55% oil, 0. 209 g, 4. 80 mmol) of methylformamide (8 ml), and 4- (1Η-Η 定 (0 · 6 3 4 g, 4. 4 0 m m ο 1), stir for 15 minutes at room temperature. (4,6-dichloro-pyrimidin-2 -yl)-(6-methoxy-pyridine-3 -g, 4. 00 mmol), and stirred at room temperature for 18 hours. Reverse the water and filter out the solid to obtain the target substance (1. 45 g, quantitative white> MS (APCI, m / z): 348 (M + l) +.  (300 mg, 1 substance (270 mg, 4-yl-ethyl) -pyrimidine 3 mmol), so that the cubyl-amine of Reference Example 8 was dissolved in N, N-dimethylpyrrole-3-ylpyridine Add ice group) -amine (0.996 after termination of ice cooling, Likou 1). -366-200524880 HPLC (reversed phase): Rt. (min) = 3. 82.  Reference Example 2 8 2 [4-hydrazino-6- (3-pyridin-4-yl-pyrrole-butyl) -pyrimidin-2-yl] -phenyl-amine in [4-chloro-6- (3- Pyridin-4-yl-pyrrole-butyl) -pyrimidine-2_ylbutyl-amine (1. 00 g, 2. 88 mmol) was added to a solution of hydrazine 1 hydrate-ethanol (1: 2, v / v, 15 ml), and stirred at 95 ° C for 24 hours. After cooling at room temperature, water was added. The precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate, and dried under reduced pressure to obtain the target product (0. 896 g, 91%) ° MS (APCI, m / z): 344 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 82.  Reference Example 2 8 3 2- (4-Fluoro-aniline) -5-phenyl-pyrimidine-4,6-diol 4-fluoroaniline (3. 33 g, 30 mmol) was dissolved in ethanol (30 ml), and 1H-pyrazole-1-carboxamidine hydrochloride (4. 4 g, 30 mmol), and heat reflux for 15 hours. After the reaction, sodium ethoxide (2 1 wt%, 2 8 m 1,7 5 mm ο 1) and diethyl 2-phenylmalonate (7 ml, 33 mmol) were added, and the reaction mixture was heated under reflux for 15 hours to terminate the reaction with acetic acid. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. After the organic layer was concentrated, diethyl ether was added, and the precipitated solid was pulverized and collected by filtration. The target substance (5 J5 g, 60%) was obtained after washing with ether. : 8. 83 (brs, 1H), 7. 69 (dd, 2H, J = 5. 0, 7. 0 Hz), 7. 44 (d, 2H, J = 8. 0 Hz), 7. 27 (dd, J = 7. 0, 7. 0 Hz), 7. 19-7. 12 (m, 1H), 7. 16 (d, 2H, J = 8. 0 Hz).  367-200524880 MS (APCI, m / z): 29 8 (Μ + 1) + · HPLC (reverse phase): Rt. (min) = 3. 66.  Reference Example 284 (4,6-Dichloro-5-phenyl-pyrimidin-2-yl)-(4-fluoro-phenyl) -amine Luding -4,6 -diol mmol), according to the method of Reference Example 17, the reaction can be obtained 67%). -NMR (500 MHz, DMSO-d6) 5 ppm: 10. 48 7. 7. 68 (m, 2H), 7. 50-7. 45 (m, 3H), 7. 38 (d, Hz), 7. 21 (t, 2H, J = 7. 5 Hz).  MS (APCI, m / z): 334 (M + l) +.  HPLC (reverse phase): Rt. (min) = 6. 50.  Reference Example 2 5 5 N2- (4-fluoro-phenyl) -6-hydrazino-5-phenyl-N4- (2-pyridine-4pyridine-2,4-diamine consisting of (4,6-dichloro -5-phenyl-pyrimidin-2-yl)-(4-fluoro-phenylmmol), using 2-P to H--4-yl-ethylamine (806 mg, 6. 6 The reaction of the method of Examination Case 8 can obtain the target (61 1 mg, 49%) MS (APCI, m / z): 416 (M + l) +.  HPLC (reverse phase): Rt. (min) = 2. 89. Reference Example 2 8 6 2- (2-Fluoro-aniline) -5-phenyl-pyrimidine-4,6-diol The 2-fluoroaniline (14. 0 mL, 0.145 mo]) dissolved in ethyl acetate, and 1H-pyrazole-1-carboxamidine hydrochloride (21. 5 g, 丨 (5. 35 g, 18 things (4. 05 g, s, 1H), 7. 70-2H, J = 5. 0 • yl-ethyl) -pyran) -amine (1 g, 3 mmol), eshenol (67 ml) 1 ·] 4 7 m m ο 1)-368-200524880, heated under reflux for 12 hours. Add ethanol (290 ml), sodium ethoxide (21 wt%, 250 ml, 3. 19 mol), diethyl phenylmalonate (67 · 4 ml, 0. 3 19 mol), heated to reflux for 15 hours, the reaction was stopped with acetic acid, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with water. The organic layer was concentrated and purified by silica gel column chromatography to obtain the target compound (5. 87 g, 14%). ] Η-NMK (500 MHz, DMSO-d6) 5 ppm: 8 · 7 1 (brs, 1 Η), 8. 45 (t, 1H, 8. 5 Hz), 7. 45 (d, 2H, 8. 0 Hz), 7. 32-7. 26 (m, 3H), 7. 20 (t, 1H, J = 8. 0 Hz), 7. 17-7. 10 (m, 2H).  MS (APCI, m / z): 298 (M + l) +.  HPLC (reverse phase): Rt. (min) = 3. 54.  Reference Example 2 8 7 (4,6-dichloro-5-phenyl-pyrimidin-2-yl M2-fluoro-phenyl) -amine in 2- (2-fluoro-aniline) -5-phenyl-pyrimidine -4,6-diol (5.0 g, 2. 27 mmol) was added with phosphorus oxychloride (23 ml), and stirred at 100 ° C for 3 hours. After the reaction was completed, it was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate, and the organic layer was washed with water. After concentration, purification by silica gel column chromatography can obtain the target compound (2. 74 g, 49%). ! Η-ΝΜΚ (500 MHz, DMSO-d6) 5 ppm: 10. 09 (brs, 1H),

7.59 (t, 1H, J = 7.5 Hz), 7.52-7.42 (m, 2H), 7.4 7 (d, 2H, J = 7.0 Hz), 7.36 (d, 2H, J = 7.0 Hz), 7.33-7.21 (m, 2H). MS (APCI, m / z): 3 34 (M + 1) +. HPLC (reversed phase): Rt. (Min) 2 6.46 · Reference example 2 8 8-369 -200524880 N2- (4-fluoro-phenyl) -6-hydrazino-5-phenyl-N4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine consists of (4, 6-Dichloro-5-phenyl · pyrimidin-2-ylM2-fluoro-phenyl) -amine (1 g, 3 mmol) using 2-tl-tidin-4-yl-ethylamine (806 mg, 6.6 mmol), and the target compound (372 mg, 30%) was obtained by reaction according to the method of Reference Example 8. MS (APCI, m / z): 416 (M + l) +. HPLC (reverse phase): Rt. (Min) = 2.74 · Reference example 2 8 9 6 -hydrazino-N 2 -phenyl-pyrimidine -2,4-diamine Dissolve 4,6-dichloro-2-aniline pyrimidine (200 mg, 0.833 mmol) in ethanol (1.0 ml) and dioxane (1.0 ml), and add 28% -ammonia solution (0.5 ml), stir in a microwave oven at 150 ° C for 20 minutes. After the reaction, the organic layer was dried with dichloromethane / water extraction ', and then concentrated. After concentration, hydrazine monohydrate-ethanol (2: 1, v / v, 6.0 ml) was added, and the mixture was stirred at 95 ° C for 13 hours. After cooling at room temperature and concentrating, water was added thereto, followed by extraction with dichloromethane. The organic layer was dried and concentrated, and the solid obtained was washed with acetic acid and dried under reduced pressure to obtain the target compound (142 mg, 79%). MS (APCI, m / z): 217 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 2.36 · Reference Example 2 9 0 6-hydrazino-5, N2-diphenyl-N4 -(3-pyridin-4-yl-propyl) -pyrimidine — 2,4-diamine consisting of 4,6-dichloro-5-phenyl-2-aniline pyrimidine (893 mg, 2.83 mmol), using 3- Pyrimidin-4-yl-propylamine (3 4 9 mg, 2.5 7 mm ο 1) was reacted according to the method of Reference Example 8 to obtain the target compound (741 mg, 64%). 200524880 MS (APCI, m / z): 412 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 2.58. Reference Example 2 9 1 [4-chloro-5 -phenyl-6-(3 -pyridine-4 -yl-pyrrole-1 -yl) -pyrimidine-2 -ylphenylphenyl-amine sodium hydride (55% oil , 0.183 g, 4.20 mmol) was dissolved in N, N-dimethylformamide (8 ml), and 4- (1 fluorene-pyrrol-3-yl) -pyridine (0.5 62 g, 3.90 mmol) was added under ice cooling. ), And stirred at room temperature for 15 minutes. Under ice-cooling, 4,6-dichloro-5-phenyl-2-aniline acetidine (0.949 g, 3.00 mmol) was added, and the mixture was stirred at room temperature for 4 hours. After the reaction was completed, water was added to the reaction solution, and a solid was collected by filtration. The obtained solid was purified by silica gel column chromatography to obtain the target compound (70.0 mg, 6%). MS (APCI, m / z): 424 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 4.36. Reference Example 2 9 2 [4-hydrazino-5 -phenyl-6-( 3-pyridine-4 · -yl-pyrrole-1 -ylpyrimidine, pyridin-2-yl μphenyl-amine in [4-chloro-5 -phenyl-6-(3-pyridine-4 -yl -Pyrrole-1 _yl) _pyrimidin-2, yl] phenyl-amine (70.0 mg, 0.165 mmol) was added to hydrazine monohydrate-ethanol (4: 1, v / v, 2.5 ml), at 9 51: It was stirred for 5 hours. After cooling at room temperature, water was added. The precipitated solid was pulverized and filtered. The obtained solid was washed with water and ethyl acetate and dried under reduced pressure to obtain the target substance (5 2.4 mg, 76%). MS (APCI, m / z): 420 (M + l) +. Η PLC (j 又 相): R t. (Min) = 3. 1 3. 200524880 Reference Example 293 4-Ethyl-N- (2-Hydroxy-propyl) -benzenesulfonamide is reacted from 1-aminopropan-2-ol (1 mm ο 1) according to the method of Reference Example 159 to obtain the target compound (232 mg, 90%). MS (APCI, m / z): 258 (M + l) +. HPLC (reverse phase): Rt. (Inin) = 2.79. Reference Example 294 1- [4- (morpholine-4-sulfonyl) ) -Phenyl] -ethanone was obtained from morpholine (2.20 mmol) according to the method of Reference Example 1 59 to obtain the target compound (0.379 g, 70%) °! -NMK (500 MHz, DMSO-d6) 5 ppm: 8.20 (d, 2H, J = 8.1 Hz), 7.89 (d, 2H, J = 8.1 Hz), 3.64 (brs, 4H), 2.90 (brs, 4H), 2.66 (s, 3H). MS (APCI, m / z): 270 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.77. Reference example 2 9 5 N4- [2- (3-fluoro-phenyl) -ethyl] -6-fluorenyl-N2-phenyl-pyrimidine-2,4-diamine is determined by 4,6-dichloro-2-aniline (240 mg, 1 mmol), using 2- (3-fluoro-phenyl) -ethylamine (0.2 ml, 1.5 mmol), and reacting according to the method of Reference Example 8 to obtain the target compound (0.3 g, 91%). MS ( APCI, m / z): 3 3 9 (M + l) +. HPLC (reverse phase): Rt. (Min) = 3.76. Reference Example 296 (4-hydrazino-6-imidazol-1-yl-pyrimidin-2-yl) -m-toluene-amine- 372- 200524880 by (4,6-dichloro-pyrimidin-2-yl) -m -Toluene-amine (76 mg, 0.3 mmol). The target compound (77 mg, 92%) was obtained by the reaction according to the method of Reference Example 44. MS (APCI, m / z): 282 (M + l) +. HPLC (reverse phase): Rt. (Min) = 2.75. Reference Example 2 9 7 (3-Fluoro-phenyl)-(4-hydrazino -6-imidazol-1-yl-pyrimidin-2-yl) -amine by (4,6-dichloro-pyrimidin-2-yl)-(3-fluoro-phenyl) -amine (77 mg, 0.3 mmol) The target compound (47 mg, 55%) can be obtained by reacting according to the method of Reference Example 44. · W-NMROOO MHz, DMSO-d6) (5 ppm:. MS (APCI, m / z): 286 (M + 1) +. HPLC (reverse phase): Rt. (Min) = 2.62. Reference Example 2 9 8 N4- (3,4-dimethoxybenzyl) -6-hydrazino-5, N2-diphenyl-pyrimidine-2,4-diamine by 4,6-dichloro-5-phenyl-2 -Aniline (320 mg, 1 mmol) using 3,4-dimethoxy-benzylamine (0.45 ml, 3 mmol) and reacting according to the method of Reference Example 8 to obtain the target compound (0.44 mg, 100% ) 0 MS (APCI, m / z): 443 (M + l) +. HPLC (reverse phase): Rt. (Min) = 4.01. Reference Example 2 9 9 H-hydrazino-5-phenyl-6 -(2-pyridin-4-yl-ethoxy) -pyrimidin-2-ylphenylphenyl-amine in [4-chloro-5-phenyl-6- (2-pyridin-4-yl-ethoxy ) -Pyrimidin-2-yl] -phenyl-amine (220 mg, 0.55 mmo]) with hydrazone 1 hydrate-ethanol (2: 1,-373-200524880 v / v, 3 ml) at 95 ° c The mixture was stirred for 1 hour. After cooling and concentrating at room temperature, ethanol was added, and the precipitated solid was pulverized and collected by filtration. The obtained solid was washed with water and ethyl acetate and dried under reduced pressure to obtain the target product (141 mg, 65%). MS (APCI, m / z): 399 (M + 1) +. HPLC (reverse phase): Rt. (Min) 2: 2.83. Test Example 1 Measurement of MLR inhibition The test compound was dissolved in dimethylarsine to 10 mg / ml, and diluted to the desired concentration with the culture medium. Human peripheral hemolymph cells were peripheral blood provided by 2 healthy blood donors. Ficoll-Paque PLUS (Pharmacia (Manufactured), manufactured by Ficoll density gradient centrifugation. One of the two peripheral blood lymphocytes produced was irradiated with 6000 rad of X-rays so as not to proliferate and used as stimulating cells. Non-X-irradiated human peripherals Hemolymph and stimulating cells, each 130,000 cells, were mixed in 0.2 ml of RPMI culture medium (manufactured by Life Technologies) containing test compounds diluted in stages, 10% calf serum, 5mM 2-hydrothiothioethanol, Culture in a 96-well round-bottom plate (manufactured by Corning). After 120 hours, add [3H] thymidine (manufactured by Amersham) 25 // 1 / hole to make the final radioactivity of 82 kBq / ml, and incubate for another 16 hours. The radioactivity absorbed in the cells was measured by a plate (made by WALLAC). The 50% inhibitory concentration of each compound was calculated by semi-logarithmic calibration of the compound concentration and the% in the absence of the MLR reaction test compound. The results are shown in Table 2. -374-200524880 Table 2 Test compounds MLR inhibitory activity IC5G (ng / ml) Example 37 9.0 Example 66 3.5 Example 74 1.0

Based on the above results, the compounds of the present invention have significantly excellent MLR inhibitory effects. Formulation Example 1: Capsule Compound of Example 4 or 24 50 mg lactose 1 2 8 m g corn source powder 70 mg magnesium stearate 2 mg 2 50 m g

The above prescription powder was mixed, sieved through a 60 mesh, and 250 mg of the powder was poured into a No. 3 gelatin capsule to obtain a capsule. Formulation Example 2: Lozenge Compound of Example 4 or 24 50 mg Lactose 12 6 mg Corn source powder 23 mg Magnesium stearate 1 mg 2 0 mg The above prescription powder was mixed using corn starch paste to wet granulate, dry- 375-200524880 After drying, use a tableting machine to beat tablets to get 1 tablet of 200 mg. Lenses may be administered with sugar coating if necessary. Industrial Applicability The pyrimidine derivative of the formula (I) or a pharmacologically acceptable salt thereof according to the present invention has excellent MLR inhibitory effect and low cytotoxicity, and can be used as an inhibitor of rejection of transplanted tissues such as bone marrow transplantation and organ transplantation. Cancer cell inhibitors with selective cytocidal activity (eg, inhibitors of cancerous lymphocytes), or chronic rheumatoid arthritis as an inflammatory disease, organ-specific autoimmune diseases (eg, multiple sclerosis , Inflammatory bowel disease, diabetes, glomerulonephritis, primary biliary cirrhosis, chronic active hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis, 'myasthenia gravis, dry addiction, or Shekelian syndrome) , Organ non-specific autoimmune diseases (such as' systemic lupus erythematosus), preventive and / or therapeutic agents for allergic diseases (such as rhinitis, asthma or atopic dermatitis) (preferably bone marrow transplantation • organs Inhibitors of rejection of transplanted tissues such as transplantation or preventive and / or therapeutic agents for chronic rheumatoid arthritis). -376-

Claims (1)

200524880 10. Scope of patent application: 1. A pyrimidine derivative of the following formula or its pharmacologically acceptable salt: (I) [wherein R1 is a lower alkyl group, R2 is an aryl group, a heterocyclic group, an aryl group substituted with 1 to 5 groups selected from the substituent group a, or 1 to 1 selected from the substituent group & Heterocyclic group substituted by 3 groups, A is -NH- or oxygen atom, R3 is hydrogen /, low alkyl group, aryl group, .heterocyclic group or-NHR6 group (where R6 is low alkyl group, ring compound Base, low base substituted by ring base, ring base substituted with 1 to 3 groups selected from substituent group b, aryl group, heterocyclic group, aromatic base, and 1 selected from substituent group b ~ 5 group substituted aryl or heterocyclic group substituted with 1 ~ 3 groups selected from the substituent group b), R4 is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, cycloalkyl Substituted lower alkyl, aryl, heterocyclyl, aralkyl, aryl substituted with 1 to 5 groups selected from substituent group b or substituted with 1 to 3 groups selected from substituent group b Heterocyclyl (except when R3 is hydrogen and R4 is hydrogen), R5 is hydrogen, halogen atom, lower alkyl, cycloalkyl, heterocyclyl, 1 ~ 3 selected from substituent group b -Substituted heterocyclic group, -NR7R8 group or -OR7 group (R7 and R8 are the same or different, each is , Lower alkyl, cycloalkyl, lower alkyl, aryl, hetero200524880 ring group substituted with 1 ~ 5 groups selected from substituent group c or 5 ~ 5 groups substituted with optional substituent group b Aryl), except for the following {Wherein T is N or CH, Y is 0, S, SO, S02 or NZ (Z is an arbitrary group selected from the substituent group b)}, and the substituent group a is selected from the group consisting of a alkanesulfonyl group, Aminosulfonyl, mono-lower alkylamine sulfonyl, di-oligoalkylamine sulfonyl, mono-cycloalkylamine sulfonyl, mono- (hydroxylow alkyl) amine sulfonyl, mono- (carboxy low Alkyl) sulfamoyl group, nitrogen-containing saturated heterocyclic sulfonyl group and -S 03H group, and the substituent group b is selected from halogen atom, lower alkyl, halogen lower alkyl, lower alkoxy, and lower alkyl Thio, low alkylsulfonyl, low alkylsulfinyl, carboxyl, amine, mono-low alkylamino, di-low alkylamino, sulfamoyl, hydroxyl, aryl, aryloxy, Heterocyclyl, haloaryl, haloaryloxy, p- (4-methylaminesulfonylphenyl) -ethylene-hydrazinecarbonyl and p (4-methylsulfonylphenyl) -ethylene-hydrazinecarbonyl, Substituent group c is a mono-, which is selected from the group consisting of amine, mono-oligoalkylamino, di-oligoalkylamino, mono-fluorenylamino, and fluorenyl with 1 to 5 groups selected from substituent group b. Amido, hydroxyl, lower alkoxy, hydroxy lower alkoxy, carboxyl, guanidyl, aryl, aryloxy, heterocyclic, selected from An aryl group substituted with 1 to 5 groups of the substituent group b, an aryloxy group substituted with 1 to 5 groups selected from the substituent group b, and a hetero group substituted with 1 to 3 groups selected from the substituent group b Cyclic group] 〇2. The pyrimidine derivative or pharmacologically acceptable salt thereof according to item 1 of the scope of the application, wherein R1 is methyl, ethyl or n-propyl. -378-200524880 3 · If the pyrimidine derivative or pharmacologically acceptable salt thereof according to item 1 of the scope of patent application, wherein R1 is methyl. 4. The pyrimidine derivative or pharmacologically acceptable salt thereof according to any one of claims 1 to 3 in the scope of the patent application, wherein R2 is a heterocyclic group or an aromatic group substituted with 1 to 3 groups selected from the substituent group a base. 5. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 3 in the scope of patent application, wherein R2 is pyridyl or is selected from the group consisting of (lower alkylsulfonyl, sulfamoyl, mono- A lower alkylaminesulfonyl group, a mono-cycloalkylaminesulfonyl group and a mono ((lower alkyl) aminosulfonyl group) phenyl group substituted at the 4-position. 6. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 3 in the scope of patent application, wherein R2 is 4-pyridyl, 4-methanesulfonylphenyl, 4-ethylsulfonylphenyl , 4-Aminosulfenylphenyl, 4-Methylsulfenylsulfanyl, 4-Ethylaminesulfonylphenyl, 4-Cyclopropylaminesulfonylphenyl, or 4-Carboxamidinesulfonylphenyl. 7. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 3 in the scope of the patent application, wherein R2 is 4-pyridyl, 4-methanesulfonylphenyl, 4-aminesulfonylphenyl , 4-methylaminosulfonyl phenyl, 4-cyclopropylaminesulfonyl phenyl, or 4-carboxymethylaminesulfonyl phenyl. 8. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 3, wherein R2 is 4-pyridyl, 4-methanesulfenylphenyl, or 4-methylaminesulfonylbenzene base. 9. A pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of claims 1 to 8 in the scope of the patent application, wherein A is -NH-. 10. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 9 of the scope of the patent application, wherein R3 is an aryl group, a heterocyclic group, a mono-arylamino group, or The heterocyclic amino group or phenyl moiety has one or two substituted mono-aniline groups selected from the group consisting of (halogen atom, lower alkyl group, and lower alkoxy group). 1 1. The pyrimidine derivative or pharmacologically acceptable salt thereof according to any one of items 1 to 9 of the scope of the patent application, wherein R3 is 3-pyridyl, oxindolinyl, aniline, 3-pyridylamino Or the phenyl moiety has 1 or 2 substituted mono-aniline groups of any group selected from (fluorine, chlorine, methyl, and methoxy). 1 2. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 9 of the scope of patent application, wherein R3 is 3-pyridyl, oxindolinyl, aniline, 3-pyridylamine Group, 4-fluoroaniline group, 2-fluoroaniline group, 5-fluoro-2-toluidine group or 2-methoxyaniline group. 1 3 · The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 9 of the scope of the patent application, wherein R3 is aniline, 3-pyridylamino, 4-fluoroaniline or 2-fluoro Aniline. I4. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 13, wherein R4 is hydrogen, lower alkyl, aryl, heterocyclic, aralkyl, or selected from An aryl group substituted with 1 to 5 groups of the substituent group b. 1 5 · The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 3 in the scope of the patent application, wherein R4 is hydrogen, lower alkyl, phenyl, naphthyl, aromatic heterocyclic group, Fused bicyclic heteroaryl, benzyl or a radical having 1 or 2 substituents selected from the group consisting of (halogen atom, lower radical and lower radical). 16 · The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 13 in the scope of patent application, wherein R 4 is hydrogen, phenyl, phenyl, 3-thienyl, 1, 3- Benzo-Shumaoyuan-5-yl,]], 4-Benzodiphenyl, fluorenyl, or 1 or 2 substitutions of any group selected from (fluorine, chlorine, methyl, and methoxy)- 380-200524880 Phenyl. 17. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 13 of the scope of patent application, wherein R4 is hydrogen, phenyl, 3-thienyl, benzyl, 4-fluorophenyl , Fluorophenyl or 2-tolyl. 1 8 · The pyrimidine, π-Ding derivative or pharmacologically acceptable salt thereof according to any one of the items 1 to 13 of the scope of patent application, wherein R4 is hydrogen, phenyl, 3-thienyl, 4-fluorophenyl , 2-fluorophenyl or 2-tolyl. 1 9. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 18 in the scope of the patent application, wherein R5 is hydrogen, heterocyclic group, heterocyclic group substituted with 1 heterocyclic group, The amino group, mono-low alkylamino group, di-low alkylamino group or low alkyl moiety has any group selected from the group consisting of hydroxyl group, low alkoxy group, hydroxy low alkoxy group, heterocyclic group and substituent group b. Mono-lower alkylamino or lower alkoxy substituted with 1 to 5 groups of ~ 3 substituted aryl groups. 20. The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 18 in the scope of the application for a patent, wherein R5 is hydrogen, prazolyl, primizolyl, acridinyl, 1-pyrrolidine , 1- [4- (4-pyridyl)] pyrazolyl, M3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -pyrrolyl, (4-pyridyl) ) Methylamino, amine, methylamino, dimethylamino, 2-hydroxyethylamino, 2-methoxyethylamino, 2- (2-hydroxyethoxy) ethylamino, 2-([pyridine (Amino group) Ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 2- (1,3-benzobenzopyrene No. Maoyuan-5- Group) ethyl fee group, 3 ′ 4-monomethoxyphenethylamino group, 2- (3,4-dimethoxyphenyl) hydroxyethylamino group, sulfamophenethylamine group, or 2-(4-pyridine Group) ethoxy. 2 1 · As a sulfonium derivative or -381-200524880 of any of the items 1 to 18 in the scope of patent application, its pharmacologically acceptable salt, wherein R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl , 1-azetidinyl, 1- [4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -1-pyrrole (4-pyridyl) methylamino, amine, methylamino, 2- (2-hydroxyethoxy) ethylamino, 2- (4-pyridyl) ethylamino, 3- (4- Pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 2- (1,3-benzobisocorane-5-yl) ethylamino, 3,4-dimethyl Oxyphenylethylamino, 2- (3,4-dimethoxyphenyl) -2-hydroxyethylamino, 4-aminosulfonylphenylethylamino, or 2- (4-pyridyl) ethoxy. 2 2 · The chevalidine derivative or the pharmacologically acceptable salt thereof according to any one of items 1 to 18 in the scope of the patent application, wherein R5 is hydrogen, 1-pyrazolyl, 1-imidazolyl, 1- [ 4- (4-pyridyl)] pyrazolyl, 1- [3- (4-pyridyl)] pyrazolyl, 3- (4-pyridyl) -1-pyrrolyl, (4-pyridyl) formyl Amine, 2- (4-pyridyl) ethylamino, 3- (4-pyridyl) propylamino, 2- (4-pyridyl) -2-hydroxyethylamino, 3,4-dimethoxybenzene Ethylamino, 2- (3,4-dimethoxyphenyl) -2-hydroxyethylamino or 2- (4-pyridyl) ethoxy. 23. The pyrimidine derivative or pharmacologically acceptable salt thereof according to item 1 of the scope of patent application, which is? ^ 4- [2- (3,4-dimethoxyphenyl) -ethyl] -1 ^ 2-phenyl -6-[? ^-(1-pyridin-4-yl-ethylene) -hydrazinopyrimidine-2,4-diamine, 5-benzyl-2-benzylamino-4-[N'- (1- 卩 比 D 疋 -4-yl-ethylidene) -Pyridyl-Hpentine 6- {1 ^ '-[1- (4-Methanesulfonylphenyl) -Ethylpyridine 2-phenyl-1 ^ 4- (2-pyridin-4-yl-ethyl) -pyrimidine-2,4-diamine, (4-{? ^ '-[1- (4-methanesulfonylphenyl) ) -Ethylene] -hydrazinob 5-phenylpyrimidinyl_2--382-200524880 group)-this amine, N-methyl-4- (1- {[2-aniline-6- (4 -Pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-yl] -hydrazinophenylethyl) -benzenesulfonamide, N-methyl-4- (1- {[2-phenylamino- 6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinyl 丨 -ethyl) -benzenesulfonamide, N-methyl-4- {1- [5- Phenyl-2-phenylaminopyrimidin-4-yl] -hydrazinylethylethylbenzsulfenamine, N-methyl-4- {1-[(5-phenyl-2-phenylamino-6-pyrazole- 1-yl-pyrimidin-4-yl) -hydrazinyl] -ethylsulfenylsulfonamide, 4- {1-[(6-imidazol-1-yl-5-phenyl-2-phenylaminopyrimidin-4 -base)- Hydrazinyl] -ethyl} -N-toluenesulfonamide, N_methyl-4- (1-{[5-phenyl-2-aniline-6- (4-pyridin-4-yl-pyridine Azol-1-yl) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N_methyl_4- (1-{[5-phenyl-2-phenylamino-6- ( 2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl] -hydrazinophenylethyl) -benzenesulfonamide, N-methyl- 4- (1-{[2-phenylamino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-thiophene-3-yl-pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, 1methyl-4- ( 1-{[2-Anilino-6- (4-pyridin-4-yl-pyrazol-1-yl) -5-o-tolylpyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonyl Amine, N-methyl-4- (1-{[5-phenyl-2-((pyridin-3-ylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, 4 -(1-{[5- (2-fluorophenyl) -2-aniline-6- (4-pyridin-4-yl-pyrazol-1-yl) -pyrimidin-4-yl] -hydrazinyl Ethyl) -N-toluenesulfonylamine, Benzoyl- [4- [N '-(lD than fluoren-4-yl-ethylene) -cake group] -6- (3 -fluorene sulfonium-4 -Yl- -383-200524880 pyrazole-1 -yl) -pyrimidin-2 -yl] -amine, 4- (1-{[5- (4-chloro-phenyl) -2-benzylamino-6- (2-D than fluoren-4-yl-acetoyl -Pyridin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonylamine, 4- (1-{[6- (2- -Ethylamino) -5 -phenyl-2-benzyl-¾ & pyridin-4-yl] -hydrazinylethyl) -N-methyl-benzenesulfonamide, 4- (1-{[6 -(2-hydroxy-2-pyridin-4-yl-ethylamino) -2-anilino-pyrimidin-4-ylpyridinoylethyl) methyl-benzenesulfonylamine, N-methyl_4- Π-({5-phenyl-2-anilino-6-[(pyridin-4-ylmethyl) -aminol · pyrimidin-4-ylburazinyl) -ethyl] -benzenesulfonamide , 4- (1- {[2- (4-fluoro-aniline) -6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-ylpyridinoylethyl) methyl-benzene Sulfonamide, 4- (1- {[2- (4-fluoro-anilino) -5-phenyl-6- (2-pyridin-4-yl-ethylamino) -pyrimidin-4-yl]- Hydrazinylethyl) -N-methyl-benzenesulfonamide, 4- (1- {[2- (2-fluoro-aniline) -5-phenyl-6- (2-pyridin-4-yl- Ethylamino) -pyrimidin-4-yl] -pyridinyl} -ethyl) -N-methyl-benzamine, N-methyl-4_ (1- {[5-phenyl-2 -Anilino-6- (3-pyridin-4-yl-propylamino) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide, N-methyl-4- (1-{[5 -Phenyl-2-aniline -6- (3-pyridin-4-yl-pyrrole-1-yl) -pyrimidinylhydrazinobethyl) -benzenesulfonamide, or N-methyl-4- (1-{[5-phenyl 2-anilino-6- (2-pyridin-4-yl-ethoxy) -pyrimidin-4-yl] -hydrazinylethyl) -benzenesulfonamide. 24. A medicinal composition containing the pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of the scope of claims 1 to 23 of the patent application as an active ingredient. 25. —A pharmaceutical composition for inhibiting mixed lymphosphere culture reaction, containing the pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of the scope of the application -384-200524880 patent range 1 to 23 as an active ingredient . 2 6 · —Medicine that inhibits the rejection of transplanted tissues such as bone marrow transplantation and organ transplantation or prevents and / or treats inflammatory diseases, organ-specific autoimmune diseases, organ non-specific autoimmune diseases, or allergic diseases The composition contains, as an active ingredient, a pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 of the scope of patent application. 27 · — Prevention and / or treatment of chronic rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, diabetes, glomerulonephritis, primary biliary cirrhosis, chronic active hepatitis, malignant anemia, Hashimoto's thyroid Inflammation, atrophic gastritis, myasthenia gravis, psoriasis, Sjoegren's syndrome, systemic lupus erythematosus, rhinitis, asthma, or atopic dermatitis, a medicinal composition, including the items in the scope of patent applications from 1 to The pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of item 23 is an active ingredient. 28. A pharmaceutical composition for inhibiting cancer cells, containing the pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of the scope of claims 1 to 23 of the patent application as an active ingredient. 29. A pharmaceutical composition for inhibiting cancerous lymphocytes, containing the pyrimidine derivative or the pharmacologically acceptable salt thereof according to any one of claims 1 to 23 of the scope of patent application as an active ingredient. 30. —A pharmaceutical composition that inhibits the rejection of transplanted tissues such as bone marrow transplants and organ transplants, or prevents and / or treats chronic rheumatoid arthritis, and contains any of the items in the scope of patent applications 1 to 23 A pyrimidine derivative or a pharmacologically acceptable salt thereof is an active ingredient. -385-200524880 3 1. —The purpose of manufacturing a pharmaceutical composition is to use a pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 of the scope of patent application. 32. The use of item 31 in the scope of patent application, wherein the medicinal composition is a composition capable of inhibiting mixed lymphosphere culture reaction. 3 3 · If the application in the scope of patent application No. 31, the medicinal composition is capable of inhibiting the rejection of transplanted tissues such as bone marrow transplantation and organ transplantation or preventing and / or treating inflammatory diseases, organ-specific autoimmune diseases, Organ non-specific autoimmune disease or allergic disease. 3 4. The application according to item 31 of the scope of patent application, wherein the medicinal composition is capable of preventing and / or treating chronic rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, diabetes, glomerulonephritis, primary Biliary cirrhosis, chronic active hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis, myasthenia gravis, psoriasis, Shekelian syndrome, systemic lupus erythematosus, rhinitis, asthma or atopic dermatitis. 35. The use of item 3 丨 in the scope of patent application, wherein the pharmaceutical composition is a composition that can inhibit cancer cells. 36. If the application in the scope of patent application No. 31 is used, the medicinal composition is a composition capable of inhibiting cancerous lymphocytes. 37. The use of item 31 in the scope of patent application, wherein the medicinal composition is capable of inhibiting rejection of transplanted tissues such as bone marrow transplantation and organ transplantation, or preventing and / or treating chronic rheumatoid arthritis. 38. — A method for inhibiting the rejection of transplanted tissues such as bone marrow transplants and organ transplants, which is based on a pharmacologically effective amount of a pyrimidine derivative as described in any one of claims 1 to 23 or a pharmacological allowance Salt was administered to warm-blooded animals. -386-200524880 3 9 · A method for preventing and / or treating diseases, which is administered to a pharmacologically effective amount of a pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of claims 1 to 23 of the scope of patent application Warm-blooded animal. 40. The method of claim 39, wherein the disease is an inflammatory disease, an organ-specific autoimmune disease, an organ non-specific autoimmune disease, or an allergic disease. 4 1 · The method according to item 39 of the patent application, wherein the disease is chronic rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, diabetes, glomerulonephritis, primary biliary cirrhosis, chronic activity Hepatitis, malignant anemia, Hashimoto's thyroiditis, atrophic gastritis, myasthenia gravis, psoriasis, Shekelian syndrome, systemic lupus erythematosus, rhinitis, asthma or atopic dermatitis. 4 2. The method according to item 39 of the scope of patent application, wherein the disease is chronic rheumatoid arthritis. 43. A method for inhibiting cancer cells, which is administered to a warm-blooded animal with a pharmacologically effective amount of a pyrimidine derivative or a pharmacologically acceptable salt thereof according to any one of the scope of claims 1 to 23 of the patent application. 44. The method according to item 43 of the patent application, wherein the cancer cells are cancerous lymphocytes. 45. The method according to any one of item 38 to 44 of the patent application, wherein the warm-blooded animal is a human. -387-200524880 7. Designated Representative Map: (1) The designated representative map in this case is: None. (2) A brief description of the representative symbols of the components in this representative drawing: 8. If there is a chemical formula in this case, please disclose the chemical formula that can best show the characteristics of the invention: