New aminopyridin derivative with inhibition activity in relation to syk

FIELD: chemistry.

SUBSTANCE: present invention refers to the aminopyridin compound of general formula (I) or its salt wherein X1, X2, X3, Z, Y1, Y2 are carbon or nitrogen atom, R, R1, R5, R6 are hydrogen atom, alkyl group, further see formula of the invention, and R7 is hydrogen or halogen atom, nitro or cyano group, -CpH2(p-1)(Ra1)(Ra2)-O-Ra3, -C(=O)-Rd1, 5-or 6-membered saturated heterocycle group, aromatic heterocycle group, -N(Rh1)(Rh2), further see formula of the invention. The invention refers also to the pharmaceutic composition thereof intended for treatment or prevention of allergic diseases, autoimmune diseases caused by malignant tumour, to the Syk inhibitor containing the compound of formula I and to the therapeutic and/or preventive agent.

EFFECT: compounds which not only possess high Syk inhibition activity but are selective Syk inhibitors are obtained and described.

24 cl, 24 ex, 2 tbl

 

The present invention relates to a new aminopyridine derivative having inhibitory activity against Syk (spleen tyrosine kinase), and a therapeutic agent for the treatment of allergic diseases containing this compound as an active ingredient.

1. What is an allergic disease such as asthma

It is known that allergic reaction of 1-St type (immediate type), which plays a Central role in allergic diseases such as bronchial asthma, allergic rhinitis, atopic dermatitis, triggered by the interaction of exogenous antigen, such as pollen or house dust, and immunoglobulin E (IgE)specific to him. Allergen, which enters the body, it seems helper T cells (Th cells) in the form of molecules HLA class II and the peptide fragment of the antigen presenting cells such as macrophages; Th-cells are activated due to antigenic stimulation through the T-cell receptors and produce cytokines, such as interleukin-4. Thus, the enhanced production of specific IgE antibodies to the allergen B-cells.

There are receptors that are associated with synthetic antibody IgE with high affinity on the surface of such cells, like mast cells, basophils, monocytes; they oboznachayut is as high-affinity IgE receptors (FcεRI). When IgE bound to FcεRI cross-linked with polyvalent antigen, it is activated and emits different types of mediators. In other words, it is assumed that the signal transmission from FcεRI in the cell triggers an allergic disease, such as bronchial asthma.

Among mediators, which releases fat cells, there are presentazione mediators, such as histamine, which is released from cells by degranulation, and mediators that are produced and released at an early stage of activation, such as metabolites of arachidonic acid. When they affect the bronchi, smooth muscles of the bronchi and reduced airway narrowing due to the swelling of the mucous, mucus secretion, etc. that causes asthma attack. When they affect the skin, there are inflammation, swelling and itching that leads to the development of urticaria. When they affect the mucous membrane of the nose, increased vascular permeability, is filling with blood and mucous membrane of the nose swells, which causes nasal congestion, which leads to allergic Renita, which marked the sneezing and the release of a large amount of mucus caused by nerve stimulation. When this reaction occurs in the digestive tract, reduced smooth muscles of the intestine and intestinal ILO is Rick (peristalsis) pathologically increased, which leads to gastrointestinal allergies such as abdominal pain, vomiting, and diarrhea.

Among mediators, which releases fat cells, there are also eosinophilic chemotactic factor and cytokines, which are accompanied by transcription and released due to protein synthesis with some delay. It is assumed that this is the cause of chronic inflammation (non-patent document 1; Enshou-to-Men eki (Inflammation and Immunity) vol.7, No. 2, 1999, RR-171). Activated eosinophil chemotactic factor and cytokines, isolated fat cells, eosinophil with powerful toxic chemicals, is sent in place of an allergic reaction and releases chemicals, causing tissue damage. If this reaction occurs in the bronchi, the epithelium of the mucous membrane clusives, facilitating the penetration of the antigen, and allergic reaction proceeds. In the asthma becomes refractory, thus increasing the Hyper-reactivity of the Airways, the Airways become narrower due to the swelling and mucus, breathing difficulty and other Pathological condition varies from manifestations of chronic cough and sputum serious condition with severe, fatal attacks. The number of such patients has been steadily increasing, up to the present time and it is expected that the Udet to grow in the future; highly desirable development of effective pharmaceutical products.

2. Existing asthma drugs

Currently widely used for the treatment of asthma inhaled steroid drugs as anti-inflammatory drugs, β-stimulants, such as procaterol, and xantinove derivatives, such as aminophylline and theophylline, as bronchodilatation. Inhaled steroids have broad anti-inflammatory effect, their use as a therapeutic agent for asthma is widespread, but there is a need to teach the correct way of inhalation, and the existence of asthma patients that are resistant to steroid drugs (non-patent document 2; GINA 13-1, 69-73 (2000), non-patent document 3; Naika (Internal medicine) 81, 485-490 (1998)). Bronchodilatory activate adenylate cyclase, the enzyme that synthesizes intracellular 3'5'-cyclic monophosphate (camp) or inhibit phosphodiesterase (PDE), the enzyme that breaks down cyclic amp in smooth muscle of the Airways, thereby increasing the level of camp in cells and relaxing the smooth muscle contraction of the respiratory tract (non-patent document 4; Naika (Internal medicine) 69, 207-214 (1992)). It is known that increased levels of intracellular camp causes curb cuts smooth muscular the market of the respiratory tract (non-patent document 5; Clin. Exp. Allergy, 22, 337-344 (1992), non-patent document 6; Drugs of the Future, 17, 799-807 (1992)) and is effective for improvement in asthma. However, it is known that xantinove derivatives have systemic side effects, such as lowering blood pressure and cardiotonic action (non-patent document 7; J. Cyclic Nucleotide and Protein Phosphorylation Res., 10, 551-564 (1985), non-patent document 8; J. Pharmacol. Exp. Ther., 257, 741-747 (1991)), and β-stimulants easily cause desensitization, while increasing their doses may cause side effects, such as tremor of the fingers and palpitations. Thus, the development of effective therapeutic agent for the treatment of asthma, devoid of such side effects is very desirable.

3. The definition of Syk

FcεRI is a basic structure that is shared with other immunoglobulin receptors (T-cell receptor, b-cell IgM receptor), and belongs to the superfamily, which is denoted mnogosektsionye receptors of immune recognition. FcεRI is heterotetramer structure (αβγ2consisting of one α-chains and one β-chains and two γ-chains connected ecovalence in the transmembrane region. the α-Chain of FcεRI has two domains that are homologous to the immunoglobulin (Ig), in the extracellular domain, and a domain homologous to the immunoglobulin (Ig) C-terminal region that binds IgE with high affinity (Nepal is entry document 9; E.J. Biol. Chem. 266, 1991, RR-2646). Its intracellular domain, however, is relatively short, and even if the intracellular domain of the C-Terminus of the α-chain to split, it will not cause changes in the signal transmission. On the other hand, the extracellular domain of the γ-chain is short, almost is located in the cell, forming glycosilated due to S-S bonds. Cleavage of the intracellular domain of γ-chains leads to the interrupt signal, thus γ-chain is involved in intracellular signal transmission. β-chain has a 4-transmembrane structure, and both end region, N-terminal and C-terminal are located in the cell. β-Chain has the effect of amplifying the transmission signal, while the intracellular signal transmission is considerably weakened, if β-chain to remove. β-Chain and γ-chain does not have the internal fermentative activity, respectively, there is a domain with a specific peptide sequence (immunoreceptor based on tyrosine activating fragment - ITAM or antigenicity activating fragment - ARAM), based on two tyrosine residues in the intracellular domain. When they are trainmasterryan they link the SH domain (domain homologous Srk) proteincontaining precepting type (proteinkinase - PTK) with high affinity.

When proteins TRAINFORTRADE by FcεRI aggregation PTK precepting type, such as Lyn, Syk and Btk, an adapter molecule, such as Shc and Grb2, PI3K, etc. are identified along with the β-chain of FcεRI γ-chain of FcεRI.

Syk is a molecule belonging to the subfamily, referred to as the Syk family, along with ZAP-70, which is PTK, important in signaling through the T-cell receptor. It is impermanent is associated with the γ-chain of FcεRI, but firmly associated with the ITAM sequence γ-chain, being tyrosinosolvens by Lyn after FcεRI aggregation through its SH2 domain. It is known that Syk undergoes autophosphorylation and phosphorylation by the enzyme Lyn when associating with him, then Syk causes further allosteric structural changes that enhance its activity (non-patent document 10; J. Biol. Chem. Vol.270. RR-10502, 1995). Activated Syk induces education adapter molecular complex and activation of the enzyme and transmits the signal over a common path, such as phospholipase γ (PLC-γ), MAP-kinase (MAPK), which is used by many receptors.

PLC γ TRAINFORTRADE through Syk and phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) is hydrolyzed to diacylglycerol (DAG) and Inositol-1,4,5-triphosphate (IP3). DAG induces the activation of protein kinase C (PKC)and PKC activation induces degranulation in combination with increased levels of intracellular calcium. In addition, Syk is associated with p is slishnimi adapter molecules, do not possess kinase activity and containing only the SH2 domain, and activates the MAPK superfamily, and arachidonic acid metabolism caused by phosphorylation PLA2. Activation of ERK, p38, JNK, etc. involved in the production of cytokines by mast cells through transcription factors such as AP1 (non-patent document 11; J. Biol. Chem. Vol.270, RR-16338, 1995).

It is reported that trainferrovie intracellular proteins and the reaction of phagocytosis, which are caused by stimulation of the receptor for immunoglobulin G (IgG) (FcγR), significantly limited in macrophages derived from Syk-deficient mice (non-patent document 12; Crowley, M. T. et al., J. Exp. Med. 186: 1027-1039 (1997)). Thus, Syk plays a critical role in the phagocytosis of macrophages mediated by FcγR, and demonstrated its involvement in tissue damage caused by antibody-dependent cellular cytotoxicity (ADCC). Moreover, Syk is involved in the activation of b-cells (for example, non-patent document 13; J. Biol. Chem., 1992, Vol.267, RR-8619 and non-patent document 14; EMBO J., 1994, Vol.13, RR-1349), survival of eosinophils induced by GM-CSF/IL-5 (for example, non-patent document 15; J. Exp. Med., 1996, Vol.183, R-1414), in platelet activation induced by stimulation of collagen (for example, non-patent document 16; EMBO J., 1997, Vol.16, RR-2341).

Accordingly, the Syk inhibitor is expected to be useful as t is repetitsionnogo treatment for such diseases, who came from the allergic reactions of immediate type and inflammatory reactions of the delayed type (for example, bronchial asthma, allergic rhinitis, contact dermatitis, urticaria, food Allergy, conjunctivitis, and the like), and diseases involving the activation of platelets. In particular, it is assumed that it is very useful if a specific Syk without inhibiting Zap-70, which belongs to the same family and is expressed only in T cells.

4. Existing Syk-inhibitors

(1) Reported a new compound used as a pharmaceutical component having inhibitory activity against proteincontaining, especially protein tyrosine kinase Syk, which refers to a derivative of imidazo[1,2-c]pyrimidine and represented by the following formula (patent document 1; Japanese Patent Laid-Open No. 2004-203748).

where R1and R2represent hydrogen, lower alkyl, phenyl which may be substituted, or heteroaryl, R3represents hydrogen, lower alkyl, cycloalkyl, phenyl which may be substituted, heteroaryl or aralkyl, and A represents hydrogen, lower alkyl, cycloalkyl, R4heteroaryl, OR5, SR5or NR6R7.

(2) Abignente E. et al. reveals imidazo[1,2-c]pyrimidines which e derivatives, it has anti-inflammatory effect, represented by the following General formula:

where RArepresents carboxy, etoxycarbonyl, carbarnoyl, or carboxymethyl; RBrepresents a methyl or methoxy; and RCrepresents methoxy and methyl or chlorine (for example, non-patent document 17; IL Farmaco, 1991, Vol.46, R-1110).

(3) in Addition, Yura T. et al. reveals imidazo[1,2-c]pyrimidine derivatives, useful as a Syk inhibitor represented by the following General formula:

where RDrepresents hydrogen, alkyl, carboxy, alkylsulphonyl or carbarnoyl; RErepresents-XA-RG, heterocyclyl, carbocyclic or condensed ring; XArepresents S, O or NH; RGrepresents aryl or heteroaryl; and RFrepresents aryl or heteroaryl (See, for example, patent document 2; WO01/83485).

(4) In connection with Syk inhibitory effect described 2-anilinopyrimidines derivatives represented by the following formula:

where Ar represents an aromatic ring group which may be substituted, and R2represents H, halogen or a group represented by-X1-R2arespectively (See, for example, p the patent document 3; WO98/18782).

In addition, it was reported Piceatannol (Piceatannol), which is a natural product, isolated from the plant (non-patent document 18; J. Biol. Chem. 269: 29697-29703(1994)).

(5) In connection with Syk inhibitory effect, presents a compound of the following formula (see patent document 4; WO02096905A1). The connection presented in the present description, however, demonstrates the inhibitory effect against multiple kinases and has inhibitory effect against GSK3 and Aurora2 on the same level as compared to Syk.

(6) also reported the compound represented by the following formula (patent document 5; WO2004016597A2).

(7) in Addition, it was also reported thiazole derivatives represented by the following formula (patent document 6; WO2004087698A2).

(8) in Addition, as a thiazole derivative also reported compound represented by the following formula (patent document 7; WO2004087699A2).

As stated above, to date, has been reported numerous Syk inhibitors, but these compounds are mainly pyrimidine skeleton and, in addition, demonstrate the inhibitory effect against numerous protein kinases and are not highly in the compared Syk specificity.

Each of the compounds listed above, with (1) through (8) inhibits not only Syk, but also ZAP-70 expressiona in T-cells on the same level, and has poor selectivity.

5. Relatively well-known aminopyridine connections

(1) Also reported the compound represented by the following formula (patent document 8; WO2004041810A1). However, the connection presented in the present description, demonstrating the inhibitory activity of many protein kinases, including Jak and selectivity for Syk, never has a satisfactory level.

(2) in Addition, reported diaminopyrimidines derived as PKC-theta inhibitor represented by the following formula (patent document 9; WO2004067516A1).

(3) in Addition, 2-substituted-4-heteroarylboronic derivatives, as shown below, known as inhibitors of cyclin-dependent kinases (CDK) (patent document 10; Japanese Patent Laid-Open No. 2003-528872).

In the formula X1represents CH, X2represents S; or one of X1and X2represents S, another X1and X2represent N; Z represents NH, NHCO, NHSO2, NHCH2CH2CH2CH2or CH=CH; R1, R2and R3independently provide the amount H, alkyl, aryl, aralkyl, heterocycle, halogen, NO2, CN, OH, alkoxy, aryloxy, NH2, NH-R', N(R')(R"), NH-COR', NH-aryl, N(aryl)2, COOH, COO-R', COO-aryl, CONH2, CONH-R', CON-(R')(R"), CONH-aryl,-CON - (aryl)2, SO3H, SO2NH2, CF3, CO-R' or CO-aryl, where the alkyl group, aryl group, kalkilya group, heterocyclic group and NH-aryl group may be substituted by one or more groups selected from halogen, NO2, CN, OH, O-methyl, NH2, COOH, CONH2and CF3; at least one of the groups R1and R2is not H when X1or X2represent S; R4, R5, R6, R7and R8independently of one another represent H, substituted or unsubstituted lower alkyl, halogen, NO2, CN, OH, substituted or unsubstituted alkoxy, NH2, NH-R', alkylaryl, alkylether, NH(C=NH)NH2N(R')3+N-(R')(R"), COOH, COO-R', CONH2, CONH-R', CON-(R')(R"), SO3H, SO2NH2, CF3or (CH2)nO(CH2)mNR'r R", (CH2)nCO2(CH2)mOR OR', where n is 0, 1, 2 or 3, m is 1, 2 or 3; and R', R" and R"' each independently represents an alkyl group, which may be the same or different.

[patent document 1] Japanese Patent Laid-Open No. 2004-203748

[patent document 2] WO01/83485

[patent document 3] WO98/18782

p> [patent document 4] WO02096905A1

[patent document 5] WO2004016597A2

[patent document 6] WO2004087698A2

[patent document 7] WO2004087699A2

[patent document 8] WO2004041810A1

[patent document 9] WO2004067516A1

[patent document 10] Japanese Patent Laid-Open No. 2003-528872

[non-patent document 1] Enshou-to-Men eki (Inflammation and Immunity) vol.7, No. 2, 1999, RR-171

[non-patent document 2] GINA 13-1, 69-73 (2000)

[non-patent document 3] Naika (Internal medicine) 81, 485-490 (1998)

[non-patent document 4] Naika (Internal medicine) 69, 207-214 (1992)

[non-patent document 5] Clin. Exp. Allergy, 22, 337-344 (1992)

[non-patent document 6] Drugs of the Future, 17, 799-807 (1992)

[non-patent document 7] J. Cyclic Nucleotide and Protein Phosphorylation Res., 10, 551-564 (1985)

[non-patent document 8] J. Pharmacol. Exp. Ther., 257, 741-747 (1991)

[non-patent document 9] E. J. Biol. Chem. 266, RR-2646, 1991

[non-patent document 10] J. Biol. Chem. Vol.270, RR-10502, 1995

[non-patent document 11] J. Biol. Chem. Vol.270, RR-16338, 1995

[non-patent document 12] Crowley, M.T. et al., J. Exp. Med. 186: 1027-1039 (1997)

[non-patent document 13] J. Biol. Chem., 1992, Vol.267, RR-8619

[non-patent document 14] EMBO J., 1994, Vol.13, p.1341-1349

[non-patent document 15] J. Exp. Med., 1996, Vol.183, R-1414

[non-patent document 16] EMBO J., 1997, Vol.16, RR-2341

[non-patent document 17] IL Farmaco, 1991, Vol.46, R-1110

[non-patent document 18] J. Biol. Chem. 269: 29697-29703 (1994)

The invention

The tasks solved by the inventions

Syk of inhibit the market, reported before, have low selectivity and demonstrate inhibitory effect against multiple protein kinases, and therefore, they can cause immune suppression activity in addition to controlling the inflammatory response. In this regard, it is necessary to develop pharmaceutical products with not only a high inhibitory effect against Syk, but also high selectivity for Syk.

Accordingly, an object of the present invention, which should be provided is a new connection that has a very high inhibitory activity against Syk.

Another object of the present invention, which should be provided is a pharmaceutical composition containing such a compound as an active ingredient, more specifically, a Syk inhibitor, a drug against allergic diseases, drug remedy for bronchial asthma, drug against allergic rhinitis drug against allergic dermatitis, drug against autoimmune diseases, drug against rheumatoid arthritis drug against systemic lupus erythematosus, a drug against multiple sclerosis, drug prot is in a malignant tumor, remedy against B-cell lymphoma, lymphocytic leukemia and their pharmaceutical composition, for use in combination with other therapeutic anti-allergic drugs.

Means for solving problems

Were conducted intensive studies of compounds that selectively inhibit Syk, and as a result found that the new aminopyridine derivative represented by the following General formula (I), has a specific and excellent inhibitory effect against Syk and applicable as a therapeutic or prophylactic agent for the treatment of diseases, such as allergies, which involved Syk. This conclusion led to the completion of the present invention.

Specifically, the present invention is as follows.

1. Aminopyridine the connection represented by the following General formula (I):

where X1represents a

(1) -C(R2)= or

(2) a nitrogen atom;

X2represents a

(1) -C(R2)= or

(2) a nitrogen atom;

X3represents a

(1) -C(R4)= or

(2) a nitrogen atom;

Z represents

(1) a nitrogen atom, or

(2) -C(R6')=;

Y1represents a

(1) -CH= or

(2) a nitrogen atom;

Y2represents a

(1) -CH= or

(2) a nitrogen atom;

R represents the oops

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) acyl group;

R1represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) a halogen atom;

R2represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) a halogen atom;

R3represents a

(1) a hydrogen atom,

(2) a halogen atom,

(3) -N(R31)(R32),

where R31and R32represent a hydrogen atom or a C1-6alkyl group,

(4) a hydroxyl group,

(5) C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup may be substituted by the Deputy, selected from the following group Aa:

[AA]

A. hydroxyl group,

b. C1-6alkoxygroup,

c. -N(R31)(R32),

where R31and R32have the meanings specified above,

d. -COOR33,

where R33represents a hydrogen atom or a C1-6alkyl group,

e. -CO-N(R31)(R32),

where R31and R32have the meanings specified above, and

f. halogen atom,

(6) urlcategory,

(7) acyl group,

(8) a saturated heterocyclic group or aromatic heterocyclic group, where the heterocyclic group may be substituted C1-6alkyl group, and a saturated heterocyclic g is the SCP may partially have a double bond,

(9) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ab:

[group Ab]

A. hydroxyl group,

b. -COOR33where R33has the meaning specified above,

c. -CO-N(R31)(R32), where R31and R32have the meanings specified above, and

d. halogen atom,

(10) -COOR33,

where R33has the meaning specified above,

(11) -CO-N(R31)(R32), where R31and R32have the meanings indicated above, or

(12) a cyano, or

R3together with R2can form a group-C=C-C=C-;

R4represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) a nitro-group;

R5represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,

(3) -COOR51,

where R51represents a hydrogen atom or a C1-6alkyl group, or

(4) a nitro-group;

R6and R6'may be the same or different and each represents

(1) a hydrogen atom,

(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,

(3) -COOR61,

where R61made the focus of an atom of hydrogen or C 1-6alkyl group,

(4) -N(R62)(R63),

where R62and R63may be the same or different and each represents a hydrogen atom, a C1-6alkyl group, a C1-6alkoxygroup or acyl group,

(5) -CO-N(R62)(R63),

where R62and R63have the meanings indicated above, or

(6) acyl group;

R7represents a hydrogen atom, a halogen atom, a nitro-group, a cyano or Ra, Rb, Rc, Rd, Re, Rf, Rgor Rh;

Rarepresents a CpH2(p-1)(Ra1)(Ra2)-O-Ra3,

where

(1) p is an integer from 1 to 6,

(2) Ra1represents a hydrogen atom or a C1-6alkyl group,

(3) Ra2represents a hydrogen atom, a C1-6alkyl group, aracelio group or aryl group, where C1-6alkyl group, kalkilya group and aryl group may be substituted by the Deputy, respectively, selected from the following group Ba:

[Group VA]

A. hydroxyl group,

b. carboxypropyl,

c. C1-6alkoxycarbonyl group,

d. amino group,

e. C1-6alkylamino,

f. di-C1-6alkylamino,

g. alloctype and

h. halogen atom.

(4) Ra3represents the atom bodoro is a, acyl group, -CON(Ra31)(Ra32or

C1-6alkyl group, where the alkyl group may be substituted C1-6alkoxycarbonyl group or-CON(Ra31)(Ra32),

where Ra31and Ra32may be the same or different and each represents

· a hydrogen atom,

· acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl,

· C1-6alkyl group (where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group, carbamoyl group, C1-6alkylcarboxylic group and di-C1-6alkylcarboxylic group,

· C1-6alkoxycarbonyl group or

· C1-6alkylsulfonyl group, or

Ra31and Ra32together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic group which has one or more nitrogen atoms, where the saturated heterocyclic group may be substituted by a hydroxyl group, exography, aralkylamines or allmineral;

Rbrepresents a CpH2(p-1)(Rb1)(Rb2)-N(Rb3)(Rb4),

where

(1) p is an integer from 1 to 6,

(2) Rb1represents a hydrogen atom or Csub> 1-6alkyl group,

(3) Rb2represents a

A. a hydrogen atom,

b. aracelio group, where kalkilya group may be substituted by a hydroxyl group, a C1-6alkoxygroup, which may be substituted by a hydroxyl group, aralkylamines or-N(Rb21)(Rb22),

where Rb21and Rb22may be the same or different and each represents a hydrogen atom, a C1-6alkyl group, acyl group, carbonyl group, a C1-6alkoxycarbonyl group or alcoxycarbenium group,

c. aryl group, where the aryl group may be substituted by a hydroxyl group, a C1-6alkoxygroup or urlcategory, or

d. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ca:

[Group Sa]

· a hydroxyl group,

· urlcategory,

· -COORb23,

where Rb23represents a hydrogen atom, a C1-6alkyl group or aracelio group,

· -N(Rb21)(Rb22), where Rb21and Rb22have the meanings specified above, and

· aryl group, where the aryl can be substituted by the Deputy selected from a hydroxyl group, a C1-6alkoxygroup, where C1-6alkoxygroup may be substituted by a hydroxyl group, urlcategory, -N(Rb21/sup> )(Rb22and alcoxycarboxylates,

where Rb21and Rb22have the meanings specified above, and

(4) Rb3and Rb4may be the same or different and each represents

A. a hydrogen atom,

b. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group, carbamoyl group, C1-6alkylcarboxylic group and di-C1-6alkylcarboxylic group,

c. -COORb41,

where Rb41represents a hydrogen atom, a C1-6alkyl group or aracelio group,

d. -CORb42,

where Rb42represents a

· C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from the

·· a hydroxyl group,

·· carboxypropyl,

·· C1-6alkoxycarbonyl group,

·· acyl group,

·· alloctype,

·· amino and

·· alluminare,

· C3-8cycloalkyl group, where C3-8cycloalkyl group may be substituted by a hydroxyl group,

· 5 - or 6-membered aromatic heterocyclic group having from 1 to 4 heteroatoms, where the heterocyclic group may be substituted C1-6alkyl group, or

· aryl group, where the aryl group may be substituted by a hydroxyl group,

e. -CO-N(Rb43)(Rb44), where Rb43and Rb44may be the same or different and each represents a hydrogen atom, a C1-6alkyl group or acyl group, or

f. -SO2-Rb45where Rb45represents a C1-6alkyl group;

Rcrepresents-C(=N-Rc1)-Rc2,

where

(1) Rc1represents a

A. hydroxyl group,

b. C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup may be substituted by a hydroxyl group or a C1-6alkoxygroup, or

c. alloctype, and

(2) Rc2represents a C1-6alkyl group, or amino group;

Rdrepresents-C(=O)-Rd1,

where Rd1represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or C1-6alkoxycarbonyl group,

(3) a hydroxyl group,

(4) C1-6alkoxygroup and

(5) -N(Rd11)(Rd12),

where Rd11and Rd12may be the same or different and each represents a Deputy selected from the following group Da:

[Group Da]

A. a hydrogen atom,

b. C1-6alkoxygroup,

c. C3-8cycloalkyl group, where cycloalkyl group mo is et to be substituted by a hydroxyl group, and

d. C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group or amino group, or

Rd11and Rd12together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic group which has one or more nitrogen atoms, where the saturated heterocyclic group may be substituted C1-6alkyl groups, where the alkyl group may be substituted by carboxypropyl, or carboxypropyl;

Rerepresents the following ring A:

where ring A is a

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,

· 5 - or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms,

· 9-12-membered condensed aromatic heterocyclic group having 1 or 2 heteroatoms, which may be partially saturated,

· C3-8cycloalkyl group or

· C7-11spiroheterocyclic group having 1 or 2 heteroatoms;

which may be substituted by the Deputy, respectively, selected from the following group Ea:

[Group EA]

A. -ORe1where Re1represents a

· a hydrogen atom,

· C1-6alkyl GRU is PU, where C1-6the alkyl group may be substituted by carboxypropyl or-CON(Re11)(Re12),

where Re11and Re12may be the same or different and each represents a hydrogen atom or a C1-6alkyl group,

· acyl group,

· karbamoilnuyu group or

· aracelio group,

b. -COORe2,

where Re2represents a hydrogen atom or a C1-6alkyl group,

c. -CO-N(Re41)(Re42),

where Re41and Re42may be the same or different and each represents

· a hydrogen atom,

· C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, a C1-6alkoxygroup, amino, C1-6alkylamino, di-C1-6alkylamino, halogen atom, carboxypropyl, carbamoyl group, C1-6alkylcarboxylic group, di-C1-6alkylcarboxylic group or 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatom,

· hydroxyl group,

· C1-6alkoxygroup,

· C5-6cycloalkyl group, where C5-6cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkyl group, where C1-6the alkyl group may be behind esena hydroxyl group, or

· C1-6alkylsulfonyl group,

d. -CORe3,

where Re3represents a

· a hydrogen atom,

·C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group and C1-6alkylsulfonyl group,

· 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatoms, where saturated heterocyclic group or aromatic heterocyclic group may be substituted by a hydroxyl group, exography, carboxypropyl, C1-6alkoxygroup, where C1-6alkoxygroup may be substituted carbamoyl group, carbamoyl group, where carnemolla group may be substituted by a hydroxyl group,acyl group, alloctype, amino group, allmineral where alluminare may be substituted by a hydroxyl group or carbamoyl group, C1-6alkylaminocarbonyl, di-C1-6alkylaminocarbonyl, C1-6alkylsulfonamides, 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group, and C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from hydroxyl the Oh group, C1-6alkoxygroup, where C1-6alkoxygroup may be substituted carbamoyl group, allmineral and carbamoyl group, or

· C5-6cycloalkyl group or aryl group, where C5-6cycloalkyl group or aryl group may be substituted by a hydroxyl group, exography, C1-6alkoxygroup, carbamoyl group, allmineral, oxymyoglobin or alloctype,

e. oxoprop,

f. -N(Re51)(Re52),

where Re51and Re52may be the same or different and each represents

· a hydrogen atom,

· C1-6alkylsulfonyl group,

· C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, a C1-6alkoxygroup and carbamoyl group,

· acyl group, where the acyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,

· -CON(Re11)(Re12)or, where Re11and Re12have the meanings specified above,

· -CORe511,

where Re511represents 5 - or 6-membered saturated heterocyclic group containing at least one nitrogen atom, C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C5-6cycloalkyl group, the de cycloalkyl group may be substituted by a hydroxyl group,

g. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Eb:

[Group Eb]

· a hydroxyl group,

· C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup, can be replaced by carboxypropyl or-CO-N(Re11)(Re12), where Re11and Re12have the meanings specified above,

· -COORe2,

where Re2has the meaning specified above,

· -N(Re51)(Re52),

where Re51and Re52have the meanings specified above,

· -CO-N(Re51)(Re52),

where Re51and Re52have the meanings specified above,

· halogen atom, and

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted by a hydroxyl group or a C1-6alkyl group,

h. -(CH2)n-N(Re61)-(CH2)m-CO(Re62),

where n and m represent an integer of 0 or from 1 to 4, and n+m have a value of from 1 to 6, Re61represents a hydrogen atom or a C1-6alkyl group, and Re62represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup, an amino group, a C1-6alkylaminocarbonyl or di-C1-6the alkyl what kinogruppoy,

i. hydroxyisopropyl,

j. C1-6alkylsulfonyl group,

k. cyano,

l. 5 - or 6-membered saturated heterocyclic group (which may be partially unsaturated, containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom, or a 5 - or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom and oxygen atom, where saturated heterocyclic group and aromatic heterocyclic group may be substituted by oxopropoxy or C1-6alkyl group,

m. aminosulfonyl group and

n. C1-6alkylidene group, where C1-6alkylidene group may be substituted by a halogen atom or carboxypropyl;

Rfrepresents a C1-6alkyl group or a C2-6alkenylphenol group where the specified C1-6alkyl group, and C2-6Alchemilla group may be substituted by the Deputy, selected from the following group Fa:

[Group F]

A. C1-6alkoxygroup, where C1-6the alkyl group in alkoxygroup, can be replaced by carboxypropyl, C1-6alkoxycarbonyl group or-CON(Rf21)(Rf22),

where Rf21and Rf22may be the same or different and each represents

· a hydrogen atom,

· acyl group, acyl group which may be substituted by a hydroxyl group or carboxypropyl,

· C1-6alkoxycarbonyl group,

· -O-COORf1,

where Rf1represents a hydrogen atom or a C1-6alkyl group,

· C1-6alkyl group,

where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group, carbamoyl group,

· C1-6alkylsulfonyl group or

· karbamoilnuyu group,

b. -COORf1,

where Rf1represents a hydrogen atom or a C1-6alkyl group,

c. -N(Rf21)(Rf22),

where Rf21and Rf22have the meanings specified above,

d. -CON(Rf21)(Rf22),

where Rf21and Rf22have the meanings specified above,

e. -N(Rf23)CON(Rf21)(Rf22),

where Rf23represents a hydrogen atom or a C1-6alkyl group, and Rf21and Rf22have the meanings specified above,

f. acyl group, and

g. halogen atom;

Rgis a Deputy with the ring B, represented by the following formula (II):

where A is a linker,selected from the following group Ga:

[Group GA]

· -(CH2)k-,

· -(CH2)k-NRg1-(CH2)j-,

· -(CH2)k-O-(CO)NRg1-(CH2)j-,

· -(CH2)k- NRg1(CO-(CH 2)j-,

· -(CH2)k-(CO)-(CH2)j-,

· -(CO)-,

· -(CH2)k-O-(CH2)j-,

· -(CH2)k-S-(CH2)j-,

· -(CH2)k-O-(CO)-(CH2)j-,

· -(CO)NRg1and

· -(CH2)k-O-(CH2)j(CO)-(CH2)g-,

where k, j and g may be the same or different and represent an integer from 0 to 4, but k and j or k and g cannot both be 0 at the same time,

Rg1represents a

·· the hydrogen atom,

·· a hydroxyl group,

·· C1-6alkoxygroup,

·· acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl,

·· C3-8cycloalkyl group, where cycloalkyl group may be substituted

C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl,

·· aracelio group or

·· C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group, -N(Rg41)(Rg42or-CON(Rg41)(Rg42),

where Rg41and Rg42may be the same or different and represent

··· the hydrogen atom,

··· acyl group, where the acyl group may be substituted by a hydroxyl group,

··· aracelio group,

··· C1-6alkylsulfonyl group or

··· C-6 alkyl group,

where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group, -N(Rg51)(Rg52or-CO-N(Rg51)(Rg52),

where Rg51and Rg52may be the same or different and represent

···· a hydrogen atom,

···· acyl group, where the acyl group may be substituted by a hydroxyl group,

···· C1-6alkyl group,

where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, allmineral, C1-6alkoxycarbonyl group or a halogen atom,

···· C1-6alkoxycarbonyl group,

···· C1-6alkylsulfonyl group or

···· C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup, or

Rg51and Rg52together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic group which has one or more nitrogen atoms, where the saturated heterocyclic group may be substituted by a hydroxyl group or a C1-6alkoxygroup,

ring B is a ring selected from the following group Ha:

[Group]

· aryl group,

· C3-8cycloalkyl group,

· 5-7 and a member of the Nai saturated heterocyclic group, having one or more nitrogen atoms,

· 5 - or 6-membered aromatic heterocyclic group having at least one heteroatom, and

· 8 to 11-membered condensed aromatic heterocyclic group having at least one heteroatom, and

ring B may be substituted by the Deputy, selected from the following group Ia:

[Group Ia]

A. -ORg2,

where Rg2represents a

· a hydrogen atom,

· C1-6alkyl group, or

· aracelio group,

b. -COORg3,

where Rg3represents a

· a hydrogen atom,

· C1-6alkyl group, or

· aracelio group, where the alkyl group may be substituted by a hydroxyl group,

c. -N(Rg41)(Rg42),

where Rg41and Rg42have the meanings specified above,

d. -CO-Rg53where Rg53represents a

· C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group, carboxypropyl or allmineral,

· C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup or exography,

· 5 - or 6-membered saturated heterocyclic group containing at least one heteroatom, where the saturated heterocyclic group may be substituted by hydroxylgroups, C1-6alkyl group or exography,

· aryl group, where the aryl may be substituted by a hydroxyl group,

· 5 - or 6-membered aromatic heterocyclic group containing at least one heteroatom,

· aracelio group or

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,

e. C1-6alkyl group, where C1-6alkyl group which may be substituted by a hydroxyl group, a C1-6alkoxygroup, urlcategory, carboxypropyl, C1-6alkoxycarbonyl group, -CO-Rg53where Rg53have the meanings specified above, -N(Rg51)(Rg52or-CO-N(Rg51)(Rg52),

where Rg51and Rg52have the meanings specified above,

f. -CO-N(Rg51)(Rg52),

where Rg51and Rg52have the values specified above.

g. C1-6alkylsulfonyl group,

h. oxoprop,

i. aryl group, where the aryl group may be substituted by a hydroxyl group,

j. kalkilya group and

k. halogen atom; and

Rhrepresents-N(Rh1)(Rh2),

where Rh1represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup, -N(Rg51)(Rg52), -CO-N(Rg51)(Rg52 ), where Rg51and Rg52have the meanings specified above, C1-6alkylsulfonyl group or a halogen atom,

(3) C2-6alkenylphenol group,

(4) C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup, or

(5) Uralkaliy group,

Rh2represents a

(1) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ja:

[Group J]

· a hydroxyl group,

· C1-6alkoxygroup,

· carboxypropyl,

· aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by a hydroxyl group, a C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, a halogen atom, a C1-6alkoxygroup, carboxypropyl, C1-6alkoxycarbonyl group, C2-6alkenylphenol group, where C2-6Alchemilla group may be substituted by carboxypropyl,

· C3-8cycloalkyl group, where cycloalkyl group may be substituted by carboxypropyl or urlcategory,

· 5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom, where the aromatic heterocyclic group may be substituted by carboxypropyl,

· 5-or 6-membered saturated heterocyclic group, containing 1 or 2 heteroatom,

· -N(Rg51)(Rg52),

where Rg51and Rg52have the meanings specified above,

· -CON(Rg51)(Rg52),

where Rg51and Rg52have the meanings specified above,

· -CORg53where Rg53has the values listed above, and

· -COORg3where Rg3has the meaning specified above,

(2) acyl group, where the acyl group may be substituted by a hydroxyl group,

(3) C1-6alkoxycarbonyl group,

(4) C2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl or a halogen atom,

(5) C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, -COORg3where Rg3has the meaning specified above, -CORg53where Rg53has the meaning specified above, -CONRg51Rg52where Rg51and Rg52each has the value specified above, or C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl,

(6) a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted-CORg53where Rg53has the meaning specified above, -COORg3where Rg3has the meaning specified above, -CONRg51Rg52where Rg51and Rg52, each is, has the meaning specified above, or C1-6alkylsulfonyl group, or

(7) an aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by carboxypropyl, C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl or C2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl,

or its pharmaceutically acceptable salt.

2. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 1, where Z represents a nitrogen atom.

3. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 2, where aminopyridine compound according to claim 1, represents aminopyridine the connection represented by the following General formula (Ia-1):

where

X1represents a

(1) -C(R2)=;

X2represents a

(1) -C(R3)= or

(2) a nitrogen atom;

X3represents a

(1) -C(R4)= or

(2) a nitrogen atom;

Y1represents a

(1) -CH= or

(2) a nitrogen atom;

R1represents a

(1) a hydrogen atom, or

(2) C1-6alkyl group;

R2represents a

(1) a hydrogen atom,

(2) a halogen atom, or

(3) C1-6alkyl group;

R3represents a

(1) a hydrogen atom,

(2) a halogen atom,

(3) C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup can be substituted by the Deputy, selected from the following group Aa-1:

[Group Aa-1]

A. hydroxyl group,

b. C1-6alkoxygroup,

c. -N(R31)(R32),

where R31and R32represent a hydrogen atom or a C1-6alkyl group,

d. halogen atom,

(4) urlcategory,

(5) acyl group,

(6) saturated heterocyclic group or aromatic heterocyclic group, where the heterocyclic group may be substituted C1-6alkyl group, and the saturated heterocyclic group may partially have a double bond,

(7) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ab-1:

[Group Ab-1]

A. hydroxyl group,

b. -COOR33where R33represents a hydrogen atom or a C1-6alkyl group,

c. -CO-N(R31)(R32), where R31and R32have the meanings specified above, and

d. halogen atom, or

(8) a cyano, or

R3together with R2can form a group-C=C-C=C-;

R4represents a

(1) a hydrogen atom, or

(2) C1-6alkyl group;

R6represents a

(1) a hydrogen atom,

(2) C1-6 alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,

(3) -COOR61,

where R61represents a hydrogen atom or a C1-6alkyl group,

(4) -N(R62)(R63),

where R62and R63may be the same or different and each represents a hydrogen atom, a C1-6alkyl group, a C1-6alkoxygroup or acyl group,

(5) -CO-N(R62)(R63), where R62and R63have the meanings indicated above, or

(6) acyl group; and

R7has the meaning as described above in item 1.

4. Aminopyridine compound or its pharmaceutically acceptable salt according to claims 1-3, where aminopyridine compound according to claims 1-3, is aminopyridine the connection represented by the following General formula (Ia-2):

where

X2represents a

(1) =C(R3)- or

(2) a nitrogen atom;

R2represents a

(1) a hydrogen atom, or

(2) a halogen atom;

R3represents a

(1) a hydrogen atom,

(2) a halogen atom,

(3) C1-6alkoxygroup,

where C1-6alkyl group, a C1-6alkoxygroup can be substituted by the Deputy, selected from the following group Aa-2:

[Group Aa-2]

A. hydroxyl group and

b. the halo atom is s,

(4) acyl group,

(5) a saturated heterocyclic group or aromatic heterocyclic group, where the heterocyclic group may be substituted C1-6alkyl group, and the saturated heterocyclic group may partially have a double bond,

(6) C1-6alkyl group which may be substituted by the Deputy, selected from the following group Ab-2:

[Group Ab-2]

A. hydroxyl group and

b. halogen atom, or

(7) a cyano, or

R3together with R2can form a group-C=C-C=C-;

R6represents a

(1) a hydrogen atom, or

(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup;

R7represents a hydrogen atom or Ra, Rb, Rc, Rd, Re, Rf, Rgor Rh;

Rarepresents a CpH2(p-1)(Ra1)(Ra2)-O-Ra3,

where

(1) p is an integer from 1 to 6,

(2) Ra1represents a hydrogen atom,

(3) Ra2represents a

· C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, alloctype, C1-6alkylaminocarbonyl or di-C1-6alkylaminocarbonyl,

· aralkyl the second group, where kalkilya group may be substituted by a hydroxyl group, carboxypropyl or alloctype, or

· aryl group,

(4) Ra3represents a hydrogen atom, acyl group, or -(CO)N(Ra31)(Ra32),

where Ra31and Ra32may be the same or different and represent a hydrogen atom or a C1-6alkyl group;

Rbrepresents a CpH2(p-1)(Rb1)(Rb2)-N(Rb3)(Rb4),

where

(1) p is an integer from 1 to 6,

(2) Rb1represents a hydrogen atom,

(3) Rb2represents a

A. aracelio group, where kalkilya group may be substituted by a hydroxyl group, a C1-6alkoxygroup, which may be substituted by a hydroxyl group, urlcategory or-N(Rb21)(Rb22),

where Rb21and Rb22represent a hydrogen atom, a C1-6alkyl group, acyl group or alcoxycarbenium group,

b. aryl group, where the aryl group may be substituted by a hydroxyl group or urlcategory, or

c. C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, urlcategory, alcoxycarbenium group, amino group, acyl group or aralkylamines group,

(4) Rb3/sup> represents a hydrogen atom or a C1-6alkyl group,

(5) Rb4represents a

A. a hydrogen atom,

b. C1-6alkyl group, where C1-6the alkyl group may be substituted by carboxypropyl or C1-6alkoxycarbonyl group,

c. -CORb32,

where Rb32represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, acyl group, carboxypropyl,

C1-6alkoxycarbonyl group or alloctype, or

d. -CON(Rb321)(Rb322),

where Rb321and Rb322represent a hydrogen atom or a C1-6alkyl group;

Rcrepresents-C(=N-Rc1)-Rc2,

where

(1) Rc1represents a

A. hydroxyl group,

b. C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup may be substituted by a hydroxyl group, or

c. alloctype,

(2) Rc2represents a C1-6alkyl group;

Rdrepresents-C(=O)-Rd1,

where Rd1represents a

(1) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or C1-6alkoxycarbonyl group,

(2) C1-6alkoxygroup,

(3) C3-8cycloalkyl is inuu group, where C3-8cycloalkyl group may be substituted by a hydroxyl group,

(4) -N(Rd11)(Rd12),

where Rd11and Rd12may be the same or different and each represents

· a hydrogen atom,

· C1-6alkoxygroup or

· C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or C1-6alkoxycarbonyl group;

Rerepresents a

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,

· 5 - or 6-membered aromatic heterocyclic group having from 1 to 4 heteroatoms,

· 9-12-membered condensed aromatic heterocyclic group which may be partially saturated, containing 1 or 2 heteroatom,

· C3-8cycloalkyl group or

· C7-11spiroheterocyclic group having 1 or 2 heteroatoms, and

each may be substituted by the Deputy, selected from the following group Ea-1:

[Group Ea-1]

A. -ORe1where Re1represents a

· a hydrogen atom,

· C1-6alkyl group, where C1-6the alkyl group may be substituted by carboxypropyl or-CON(Re11)(Re12),

where Re11and Re12may be the same or different and each represents a hydrogen atom is or C 1-6alkyl group,

· acyl group,

· karbamoilnuyu group or

· aracelio group,

b. -COORe2,

where Re2represents a hydrogen atom or a C1-6alkyl group,

c. -CO-N(Re41)(Re42),

where Re41and Re42may be the same or different and each represents

· a hydrogen atom,

· C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, a C1-6alkoxygroup, di-C1-6alkylamino, carboxypropyl, halogen atom, a C1-6alkylcarboxylic group and 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatom,

· hydroxyl group,

· C1-6alkoxygroup,

· acyl group, where the acyl group may be substituted by a hydroxyl group,

· C3-8cycloalkyl group, where C3-8cycloalkyl group may be substituted by a hydroxyl group, or

· C1-6alkylsulfonyl group,

d. -CORe3,

where Re3represents a hydrogen atom, a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxy-group, carboxypropyl or C1-6alkylsulfonyl group, 5 - or 6-membered saturated the heterocycle is ical group, having 1 or 2 heteroatoms, where the saturated heterocyclic group may be substituted by a hydroxyl group, carboxypropyl, C1-6alkyl group, acyl group, C1-6alkoxygroup, carbamoyl group, -N(Re41)(Re42), where Re41and Re42have the meanings specified above, allmineral or exography, C3-8cycloalkyl group, where C3-8cycloalkyl group may be substituted by a hydroxyl group, aromatic hydrocarbon group, aromatic hydrocarbon group may be substituted by a hydroxyl group or a 5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom,

e. oxoprop,

f. -N(Re51)(Re52),

where Re51and Re52may be the same or different and each represents

· a hydrogen atom,

· C1-6alkylsulfonyl group,

· C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group,

· acyl group, where the acyl group may be substituted by a hydroxyl group, or

· -CORe511,

where Re511represents 5 - or 6-membered saturated heterocyclic group containing at least one nitrogen atom, or C3-8cycloalkyl group, where C3-8cycloalkyl group may be the substituted hydroxyl group,

g. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Eb-1:

[Group Eb-1]

· a hydroxyl group,

· C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup can be replaced by carboxypropyl or-CO-N(Re11)(Re12), where Re11and Re12have the meanings specified above,

· -COORe2,

where Re2has the meaning specified above,

· -N(Re51)(Re52),

where Re51and Re52have the meanings specified above,

· -CO-N(Re51)(Re52),

where Re51and Re52have the meanings specified above,

· halogen atom, and

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,

h. hydroxyisopropyl,

i. C1-6alkylsulfonyl group,

j. cyano,

k. 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom (which may be partially unsaturated and may be substituted by oxopropoxy or C1-6alkyl group), or aromatic heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom and oxygen atom

l. aminosulfonyl group and

m. C1-6alkylidene group, where C1-6alkylidene group mo is et to be substituted by a halogen atom or carboxypropyl;

Rfrepresents a C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Fa-1:

[Group Fa-1]

A. C1-6alkoxygroup, where C1-6the alkyl group in alkoxygroup can be replaced by carboxypropyl, C1-6alkoxycarbonyl group or-CON(Rf21)(Rf22),

where Rf21and Rf22may be the same or different and each represents

· a hydrogen atom,

· acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl,

· C1-6alkoxycarbonyl group,

· -O-COORf1,

where Rf1represents a hydrogen atom or a C1-6alkyl group,

· C1-6alkyl group,

where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group or carbamoyl group,

· C1-6alkylsulfonyl group or

· karbamoilnuyu group,

b. -COORf1,

where Rf1has the meaning specified above,

c. -N(Rf21)(Rf22),

where Rf21and Rf22have the meanings specified above,

d. -CON(Rf21)(Rf22),

where Rf21and Rf22have the meanings specified above,

e. acyl group, and

f. halogen atom;

Rgdepict is to place a Deputy, with the ring B', represented by the following formula (IIA):

where A' represents a linker selected from the following group Ga-1:

[Group Ga-1]

· -(CH2)k-,

· -(CH2)k-NRg1-(CH2)j-,

· -(CH2)k-O-(CO) NRg1-(CH2)j-,

· -(CH2)k-NRg1(CO)-(CH2)j-,

· -(CH2)k-NRg1-(CH2)j-,

· -(CH2)k-(CO)-(CH2)j-,

· -(CO)-,

· -(CH2)k-O-(CH2)j-,

· -(CH2)k-S-(CH2)j-,

· -(CH2)k-O-(CO)-(CH2)jand

· -(CH2)k-O-(CH2)j(CO)-(CH2)g-,

where k, j and g may be the same or different and represent an integer from 0 to 4, but k and j or k and g cannot both be 0 at the same time,

Rg1represents a

·· the hydrogen atom,

·· acyl group, where the acyl group may be substituted by carboxypropyl or a hydroxyl group, or

·· C1-6alkyl group,

where the alkyl group may be substituted by carboxypropyl,

ring B' is a ring selected from the following group Ha-1:

[Group Ha-1]

· aryl group,

· C3-8cycloalkyl group,

· 5-7-membered saturated heterocyclic group with KRA is least one nitrogen atom, where the saturated heterocyclic ring may form a condensed ring with a phenyl group, and

· 5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom, and

ring B' can be substituted by the Deputy, selected from the following group Ia-1:

[Group Ia-1]

A. -ORg2,

where Rg2represents a

· a hydrogen atom,

· C1-6alkyl group, or

· aracelio group,

b. -COORg3,

where Rg3represents a

· a hydrogen atom or

· C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group,

c. -N(Rg41)(Rg42),

where Rg41and Rg42have the meanings specified above,

d. -CO-Rg53where Rg53represents a

· C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group, carboxypropyl or allmineral,

· C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup or exography,

· aryl group, where the aryl group may be substituted by a hydroxyl group,

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted hydroxyl the Oh group, C1-6alkyl group or exography,

· aracelio group or

· 5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom,

e. C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or-CO-Rg53where Rg53has the meaning specified above,

f. -CO-N(Rg51)(Rg52),

where Rg51and Rg52may be the same or different and represent

· a hydrogen atom,

· acyl group, where the acyl group may be substituted by a hydroxyl group,

· C1-6alkyl group,

where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, allmineral, C1-6alkoxycarbonyl group or a halogen atom,

· C1-6alkylsulfonyl group,

· C1-6alkoxycarbonyl group,

· karbamoilnuyu group or

· C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,

g. C1-6alkylsulfonyl group,

h. oxoprop and

i. halogen atom; and

Rhrepresents-N(Rh1)(Rh2),

where Rh1represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, where C1-6alkyl group mo is et to be substituted by a hydroxyl group, C1-6alkoxygroup, -N(Rg51)(Rg52), -CO-N(Rg51)(Rg52), C1-6alkylsulfonyl or a halogen atom,

where Rg51and Rg52have the meanings specified above,

(3) C2-6alkenylphenol group,

(4) C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup, or

(5) Uralkaliy group,

Rh2represents a

(1) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ja-1:

[Group Ja-1]

· a hydroxyl group,

· C1-6alkoxygroup,

· carboxypropyl,

· aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by a hydroxyl group, a C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, a halogen atom, a C1-6alkoxygroup, carboxypropyl, C1-6alkoxycarbonyl group, C2-6alkenylphenol group, where C2-6Alchemilla group may be substituted by carboxypropyl,

· C3-8cycloalkyl group, where cycloalkyl group may be substituted by carboxypropyl or urlcategory,

· 5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom, where the aromatic is heterocyclics group may be substituted by carboxypropyl,

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,

· -N(Rg51)(Rg52and

· -CON(Rg51)(Rg52),

where Rg51and Rg52have the meanings specified above,

(2) acyl group, where the acyl group may be substituted by a hydroxyl group,

(3) C2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl or a halogen atom,

(4) C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, -COORg3where Rg3has the meaning specified above, -CORg53where Rg53has the meaning specified above, -CONRg51Rg52where Rg51and Rg52everyone has the meaning specified above, or C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl,

(5) 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted-CORg53where Rg53has the meaning specified above, -COORg3where Rg3has the meaning specified above, -CONRg51Rg52where Rg51and Rg52each has the meaning specified above, or C1-6alkylsulfonyl group, or

(6) an aromatic carbocyclic group, an aromatic carbocyclic group may shall be replaced by carboxypropyl, C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl or C2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl.

5. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 4, where

R2represents a hydrogen atom,

R3represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a halogen atom,

R6represents a hydrogen atom, and

R7is an Re, Rgor Rh.

6. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 5, where

R7is an Reand

Rerepresents a

(1) a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group or-CO-N(Re41)(Re42), where Re41and R e42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group, or

(2) C3-8cycloalkyl group, where cycloalkyl group may be substituted C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group or-CO-N(Re41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group.

7. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 6), where

Rerepresents a

(1) a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, represented by the following ring L, where the saturated heterocyclic group may be substituted by 1 or 2 identical or different substituents selected from C1-6alkyl groups, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered ring is saturated heterocyclic group may be substituted by a hydroxyl group or-CO-N(R e41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group,

where the ring L represents a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatoms, or

(2) a 5 - or 6-membered cycloalkyl group, where cycloalkyl group may be substituted by 1 or 2 identical or different substituents selected from C1-6alkyl groups, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represent a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group or-CO-N(Re41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group.

8. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 5, where

Rhrepresents-N(Rh1)(Rh2and Rh1represents a C1-6alkyl group, Rh2represents a C3-8cycloalkyl group, where cycloalkyl group is a-COORg3where Rg3not only is em a hydrogen atom or a C 1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group.

9. Aminopyridine compound or its pharmaceutically acceptable salt according to the above claim 1, where aminopyridine compound selected from the following group of compounds.

(001) 1-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-2-it,

(002) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid,

(003) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(004) N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(005) N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(006) methyl ester of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid,

(007) TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,

(008) (4-hydroxypiperidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(009) N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)amine,

(010) N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(011) (S)-3-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-it,

(012) tert-butyl EPE is, (S)-2,2-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-3-carboxylic acid,

(013) (S)-2-amino-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol

(014) (S)-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-it,

(015) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(016) TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]cyclohexanecarbonyl acid,

(017) 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,

(018)-2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,

(019) N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}propionamide,

(020) N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetamide", she

(021) N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyrazin-2-yl]thiazol-2-yl}acetamide", she

(022) ethyl ester of (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetic acid,

(023) (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol

(024) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}Etalon,

(025) ethyl ester 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazole-2-carboxylic acid,

(026) the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanone,

(027) (S)-5-{5-[6-(4-IU is espiridion-2-ylamino)pyridine-2-yl]thiazol-2-yl}dihydrofuran-2-it,

(028) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}Etalon O-(2-hydroxyethyl)oxime,

(029) N-methoxy-N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-carboxamid,

(030) N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-carboxamid,

(031) N-methyl-N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(032) (S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-it,

(033) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentane acid,

(034) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentane-1-ol,

(035) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentanone,

(036) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanol,

(037) oxime 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanone,

(038) N-{6-[2-((S)-1-amino-ethyl)thiazol-5-yl]pyridine-2-yl}-N-([4,4']bipyridinyl-2-yl)amine,

(039) N-((S)-1-{5-[6-([4,4']bipyridinyl-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(040) N-((S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(041) (S)-2-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}propane-1-ol,

(042) N-((S)-1-{5-[6-(isoquinoline-3-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(043) (4-methylpyridin-2-yl)-[6-(2-piperidine-4-iltiazem-5-yl)pyridin-2-yl]amine,

(044) TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazo the-2-yl}cyclohexanecarboxylic,

(045) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentylamine,

(046) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}butane-1-ol,

(047) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenol,

(048) 2-hydroxy-N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(049) 3-({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazole-2-carbonyl}amino)propionic acid,

(050) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)benzoic acid,

(051) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-ol,

(052) 3,3-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}butane-1-ol,

(053) [4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]methanol,

(054) N-((R)-(4-hydroxyphenyl)-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}methyl)acetamide", she

(055) N-(2-hydroxyethyl)-4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)benzamide,

(056) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanone,

(057) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanol,

(058) ((3R,4S)-3,4-dihydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(059) (TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-(piperazine-1-yl)methanon,

(060) 4-{5-[6-(4-m is terpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-carboxamide,

(061) 2-hydroxy-1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-yl)Etalon,

(062) TRANS-4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,

(063) 3-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-yl)-3-oxopropionate acid,

(064) N-(4-methylpyridin-2-yl)-N-{6-[2-(piperazine-1-ylmethyl)thiazol-5-yl]pyridine-2-yl}amine,

(065) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-ylamine,

(066) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}methanesulfonamide,

(067) N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)acetamide", she

(068) TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,

(069) 2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol

(070) (TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanol,

(071) TRANS-4-{5-[6-(isoquinoline-3-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,

(072) TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylethylamine,

(073) ((3R,4S)-3,4-dihydroxypyrrolidine-1-yl)-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]metano,

(074) N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)ndimethylacetamide,

(075) N-(TRANS-4-{5-[6-(4-methylpyridin the-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)methanesulfonamide,

(076) 2-hydroxy-N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)ndimethylacetamide,

(077) 2-hydroxy-N-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]acetamide", she

(078) ((3R,4S)-3,4-dihydroxypyridine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(079) ((R)-3-hydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(080) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}phenyl)methanol,

(081) N-(4-methylpyridin-2-yl)-N-[6-(2-pyridin-3-ilmatieteen-5-yl)pyridin-2-yl]amine,

(082) N-(4-methylpyridin-2-yl)-N-{6-[2-(2-piperidine-4-retil)thiazol-5-yl]pyridine-2-yl}amine,

(083) N-(6-{2-[2-(1-methanesulfonamido-4-yl)ethyl]thiazol-5-yl}pyridine-2-yl)-N-(4-methylpyridin-2-yl)amine,

(084) 2-hydroxy-1-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)piperidine-1-yl]alanon,

(085) N-(2-hydroxyethyl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(086) N-(2-morpholine-4-retil)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(087) [3-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]methanol,

(088) (3-hydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(089) 4-(TRANS-4-{5-[6-(4-meth is pyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl)piperazine-2-it,

(090) ((R)-2-hydroxyethylpyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(091) (4-aminopiperidin-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(092) [4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)piperidine-1-yl]-(piperidine-4-yl)methanon,

(093) (TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-(4-hydroxypiperidine-1-yl)methanon,

(094) N-(4-hydroxypiperidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(095) N-[(R)-2-hydroxy-1-(3H-imidazol-4-ylmethyl)ethyl]-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(096) N-[(S)-2-hydroxy-1-(3H-imidazol-4-ylmethyl)ethyl]-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(097) N-(2-dimethylaminoethyl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(098) (3-aminopyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,

(099) N-[1-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl)pyrrolidin-3-yl]methanesulfonamide,

(100) (3R,4S)-1-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)pyrrolidine-3,4-diol,

(101) of TRANS-4-{5-[6-(4-metier the DIN-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonitrile,

(102) CIS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonitrile,

(103) (S)-5-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-it,

(104) (S)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol

(105) (S)-1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol

(106) (S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol

(107) (S)-5-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-it,

(108) 3-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-4H-[1,2,4]oxazol-5-he,

(109) N-(4-methylpyridin-2-yl)-N-(6-{2-[4-(1H-tetrazol-5-yl)cyclohexyl]thiazole-5-yl}pyridine-2-yl)amine,

(110) (S)-5-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-2-it,

(111) N-(1,1-dimethyl-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she

(112) (S)-1-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol

(113) N-methyl-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(114) N-(1,1-dimethyl-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)methanesulfonamide,

(115) TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(116) TRANS-4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,

(117) 4-{5-[6-(4-metier the DIN-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}cyclohexanol,

(118) (S)-1-(5-{6-[4-(2-hydroxyethoxy)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol

(119) ethyl ester of (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}dimethylcarbinol acid,

(120) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2-it,

(121) 4-(2-hydroxy-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenol,

(122) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}acetyl)piperazine-2-it,

(123) N-((R)-(4-hydroxyphenyl)-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}methyl)-N-methylacetamide,

(124) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2,6-dione,

(125) (S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-it,

(126) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2-it,

(127) N-(4-methylpyridin-2-yl)-N-[6-(2-morpholine-4-iltiazem-5-yl)pyridin-2-yl]amine,

(128) 1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,

(129) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-sulfonamide,

(130) N-(4-methoxypyridine-2-yl)-N-{6-[2-(morpholine-4-yl)thiazol-5-yl]pyridine-2-yl}amine,

(131) (3R,4S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3,4-diol,

(132) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetamide", she

(133) N-[6-(4-methyl-2-morpholine-4-iltiazem-5-yl)feast of the DIN-2-yl]-N-(4-methylpyridin-2-yl)amine,

(134) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,

(135) N-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxamide,

(136) 1-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(137) N-{6-[2-(4-methoxypiperidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,

(138) N-{6-[2-(4-methylpiperazin-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,

(139) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ol,

(140) N-methyl-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(141) 4-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carbaldehyde,

(142) methyl ester of 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-4-carboxylic acid,

(143) 2-hydroxy-1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,

(144) 1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)propane-1-he,

(145) N,N-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxamide,

(146) 1-(4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,

(147) 1-(4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,

(148) 4-(methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohex karbonova acid,

(149) 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic,

(150) 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)-4H-[1,2,4]oxadiazol-5-he,

(151) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-piperidine-4-ylamine,

(152) 4-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carbonyl)piperazine-2-it,

(153) N-(2,2-dimethoxymethyl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,

(154) 1-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,

(155) 2-hydroxy-1-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,

(156) N-methyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-

carboxamid,

(157) N-{2-[4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]-2-oxoethyl}ndimethylacetamide,

(158) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetic acid,

(159) 2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetamide", she

(160) N-methyl-2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetamide", she

(161) N-(2-hydroxyethyl)-2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetamide", she

(162) N-N-methylcarbamoylmethyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(163) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-tetrahydropyran-4-ylamine,

(164) 4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenol,

(165) N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetamide", she

(166) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ylamine,

(167) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,

(168) 2-hydroxy-N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetamide", she

(169) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,

(170) N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,

(171) N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,

(172) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol,

(173) of TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanol,

(174) N-{6-[2-(3-methoxypiperidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,

(175) 2-hydroxy-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she

(176) 2-hydroxy-N-methyl-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she

(177) N-(1-{5-[6-(4-methylpyridin-2-yl) - Rev. Mino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)methanesulfonamide,

(178) N-methyl-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)methanesulfonamide,

(179) 2-hydroxy-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ylmethyl)ndimethylacetamide,

(180) N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ylmethyl)ndimethylacetamide,

(181) N-methyl-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(182) N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)methanesulfonamide,

(183) N-{6-[2-((R)-3-ethoxypyrrolidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,

(184) N-methyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic,

(185) N-(2-hydroxyethyl)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic,

(186) N-(2-acetylamino)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic,

(187) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)

acetic acid,

(188) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)methanol,

(189) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)

the ndimethylacetamide,

(190) 4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

<> (191) N-methyl-4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(192) N-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)

the ndimethylacetamide,

(193) N-(2-hydroxyethyl)-4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(194) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she

(195) N-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she

(196) N-(2-hydroxyethyl)-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she

(197) N,N-diallyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,

(198) N-[2-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]acetamide", she

(199) 2-hydroxy-N-[2-(N'-methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]acetamide", she

(200) N-(4-methanesulfonamido-1-yl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,

(201) N,N-dimethyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-

carboxamid,

(202) (4-hydroxyphenyl)-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]

mechanon,

(203) 1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylamino}piperidine-1-yl)Etalon,

(204) 1-[4-(N-isopropyl-N-{5-[6-(4-shall ethylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,

(205) N-methyl-2-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yloxy)ndimethylacetamide,

(206) 1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(207) 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(208) 2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethanol,

(209) N-(2-methoxyethyl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,

(210) N-[2-(N'-(1-acetylpiperidine-4-yl)-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]methanesulfonamide,

(211) 1-[4-(N-(2-hydroxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,

(212) 1-[4-(N-(2-methoxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,

(213) (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(214) N-methyl-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(215) N-(2,2,2-triptorelin)-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(216) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,

(217) ((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)methanol,

(218) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ka is boxlid,

(219) 1-[4-(N-ethyl-N-{5-[6-(4-methylpyridin-2-ylamino)

(220) pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,

(221) 1-{4-[N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2,2,2-triptorelin)amino]piperidine-1-yl}Etalon,

(222) 1-[4-(N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-methylamino)piperidine-1-yl]alanon,

(223) 1-[4-(N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-methylamino)piperidine-1-yl]-2-hydroxyethane,

(224) (R)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol,

(225) (R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol,

(226) 4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid,

(227) (S)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(228) (S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(229) 1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,

(230) 2-(N-(2-hydroxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethanol,

(231) 2-[N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2-hydroxyethyl)amino]ethanol,

(232) (R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,

(233) 1-(5-{6-[4-(1-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-

carboxamid,

(23) (R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol,

(235) 1-(2-{6-[2-((R)-3-hydroxypyrrolidine-1-yl)thiazole-5-yl]pyridine-2-ylamino}pyridine-4-yl)Etalon,

(236) 4-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)-4-oxomalonate acid,

(237) N-hydroxy-(R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,

(238) 4-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]-4-oxomalonate acid,

(239) (R)-1-(5-{6-[4-(1-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol,

(240) 2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetamide", she

(241) (R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-3-carboxylic acid,

(242) (R)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,

(243) (S)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(244) (1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)methanol,

(245) 1-[(R)-3-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pyrrolidin-1-yl]

Etalon,

(246) (S)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxylic acid,

(247) (R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-3-

carboxamid,

(248) ((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]eazol-2-yl}piperidine-3-yl)acetic acid,

(249) (S)-3-methyl-2-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]butyric acid,

(250) 3-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]

propionic acid,

(251) [2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]acetic acid,

(252) [1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]

acetic acid,

(253) (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(254) 4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,

(255) ((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yloxy)acetic acid,

(256) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-carboxylic acid,

(257) (R)-1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol,

(258) 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)benzoic acid,

(259) (2S,4R)-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pyrrolidin-2-

carboxylic acid,

(260) {N-methyl-N-[2-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetyl]amino}acetic acid,

(261) 2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetr hydroisoquinoline-5-carboxylic acid,

(262) 3-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,

(263) {4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenyl}acetic acid,

(264) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetic acid,

(265) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)acetic acid,

(266) N-(4-methylpyridin-2-yl)-N-(6-{2-[(R)-3-(1H-tetrazol-5-yl)piperidine-1-yl]thiazol-5-yl}pyridine-2-yl)amine,

(267) CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,

(268) TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,

(269) 4-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid,

(270) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yloxy)acetic acid,

(271) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)acetic acid,

(272) 4-{[N-methyl-N-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)amino]methyl}

benzoic acid,

(273) 4-[(N-dimethylcarbamoyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,

(274) CIS-4-(N-carbamoylmethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]enous the l-2-yl}amino)cyclohexylcarbonyl acid,

(275) TRANS-4-[(N-carbamoylmethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid,

(276) 5-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]thiophene-2-

carboxylic acid,

(277) 3-chloro-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,

(278) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}benzoic acid,

(279) 3-methoxy-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,

(280) 2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid,

(281) 2-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]thiazol-4-

carboxylic acid,

(282) [TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid,

(283) [CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid,

(284) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanecarbonyl acid,

(285) (4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(286) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid,

(287) {5-[6-(4-shall ethylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}acetic acid,

(288) 4-[1-methyl-1-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid,

(289) [4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)phenyl]acetic acid,

(290) (1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(291) TRANS-4-[(N-benzyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid,

(292) [TRANS-4-(N-benzyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid,

(293) TRANS-4-[(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid,

(294) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroquinolin-5-carboxylic acid,

(295) fluoro-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ilidene)acetic acid,

(296) 5-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane acid,

(297) N-[2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetyl]

methanesulfonamide,

(298) 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)butyric acid,

(299) (1-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)

acetic acid,

(300) (1-{5-[6-(5-chloropyridin-2-ylamino)pyridin-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(301) (1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(302) of TRANS-4-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarbonyl acid,

(303) 3-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)phenyl]propionic acid,

(304) (E)-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,

(305) (2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-6-yl)acetic acid,

(306) 3-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-5-yl)propionic acid,

(307) 5-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane acid,

(308) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylamino}pentane acid,

(309) 6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)hexanoic acid,

(310) (Z)-2-fluoro-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,

(311) (8-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-8-azabicyclo[3.2.1]Oct-3-yl)acetic acid,

(312) (8-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-8-azabicyclo[3.2.1]Oct-3-yl)acetic acid,

(313) (1-{5-[6-(4-cyano-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ilocana acid,

(314) {4-[(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenyl}

acetic acid,

(315) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,

(316) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(317) 4-[1-methyl-1-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid,

(318) 3-methyl-6-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,

(319) 3-methyl-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,

(320) (E)-6-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,

(321) N-(2-hydroxyethyl)-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,

(322) 2-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetamide", she

(323) 3-methyl-2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)butyramide,

(324) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ethanol

(325) 5-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane-1-ol,

(326) (1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(327) [1-(5-{6-[4-(2-hydroxic the l)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]

acetic acid,

(328) fluoro-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(329) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-

carboxamid,

(330) (1-{5-[6-(4-ethylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(331) N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,

(332) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2-morpholine-4-retil)amine,

(333) 2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)acetamide", she

(334) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)butyric acid,

(335) of TRANS-4-[(N-methyl-N-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid,

(336) [1-(5-{6-[4-(2,2,2-triptoreline)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]

acetic acid,

(337)-2-methyl-1-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)propan-2-ol,

(338) 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)propionic acid,

(339) N-(2-hydroxyethyl)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-

carboxamid,

(340)-2-methyl-2-(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,

(341) 4-[(N-acetyl-N-{5-[6-(4-m is terpyridine-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)methyl]benzoic acid,

(342) (1-{5-[6-(4-tert-butylpyridinium-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(343) (1-{5-[6-(4-isopropylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(344) 2 ylamino)pyridine-2-yl]thiazol-2-yl}-6-azaspiro[2.5]octane-1-carboxylic acid,

(345) 2-[1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]-2-methylpropionate acid,

(346)-2-methyl-2-(1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,

(347) fluoro-(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(348) fluoro-(1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,

(349) [1-(5-{6-[4-(1-hydroxy-1-methylethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]acetic acid,

(350) 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,

(351) 5-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)pentane acid and

(352)-2-methyl-2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)propionamide.

10. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 9, where aminopyridine compound selected from the following group of compounds:

(01) (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-iltiazem-2-yl}pyrrolidin-2-carboxamid,

(02) CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}amino)cyclohexylcarbonyl acid,

(03) (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl)thiazol-2-yl}piperidine-4-yl)acetic acid and

(04) (4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid.

11. Aminopyridine compound or its pharmaceutically acceptable salt, in accordance with paragraph 10 above, where aminopyridine compound is an (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide.

12. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 10, where aminopyridine connection is a (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid.

13. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 10, where aminopyridine connection is a (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid.

14. Aminopyridine compound or its pharmaceutically acceptable salt according to the above claim 1, where aminopyridine compound is a CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}amino)cyclohexylcarbonyl acid.

15. And inoperative compound or its pharmaceutically acceptable salt according to the above-described item 1, where Z represents a carbon atom.

16. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 15, where aminopyridine connection in accordance with the above-described item 1 is aminopyridine the connection represented by the following General formula (Ib-1):

where

X1represents a

(1) -CH= or

(2) a nitrogen atom;

Y2represents a

(1) -CH= or

(2) a nitrogen atom;

R represents

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) acyl group;

R1represents a

(1) a hydrogen atom, or

(2) a halogen atom;

R3represents a

(1) a hydrogen atom,

(2) a halogen atom,

(3) -N(R31)(R32),

where R31and R32represent a hydrogen atom or a C1-6alkyl group,

(4) C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup can be substituted by the Deputy, selected from the following group Aa-3:

[Group Aa-3]

A. hydroxyl group and

b. -N(R31)(R32),

where R31and R32have the meanings specified above,

(5) acyl group,

(6) saturated heterocyclic group or aromatic heterocyclic group, where the heterocyclic group may be ameena C 1-6alkyl group, and the saturated heterocyclic group may partially have a double bond,

(7) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ab-3:

[group Ab-3]

A. hydroxyl group,

b. -COOR33where R33represents a hydrogen atom or a C1-6alkyl group, and

c. -CO-N(R31)(R32), where R31and R32have the meanings indicated above, or

(8) -COOR33where R33has the values listed above;

R5represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) -COOR51,

where R51represents a hydrogen atom or a C1-6alkyl group;

R6and R6'may be the same or different and each represents

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) acyl group; and

R7has the meaning as described above in item 1.

17. Aminopyridine compound or its pharmaceutically acceptable salt according to the above item 16, where aminopyridine connection is aminopyridine the connection represented by the following General formula (Ib-2):

where R3represents a

(1) a halogen atom,

(2) - N(R31)(R32),

<> where R31and R32represent a hydrogen atom or a C1-6alkyl groups,

(3) C1-6alkoxygroup,

where C1-6alkyl group, a C1-6alkoxygroup can be substituted by the Deputy, selected from the following group Aa-4:

[Group Aa-4]

A. hydroxyl group and

b. -N(R31)(R32),

where R31and R32have the meanings specified above,

(4) acyl group,

(5) a saturated heterocyclic group, where the heterocyclic group is partially has a double bond and may be substituted C1-6alkyl group,

(6) C1-6alkyl group which may be substituted by the Deputy, selected from the following group Ab-4:

[Group Ab-4]

A. hydroxyl group,

b. -COOR33where R33represents a hydrogen atom or a C1-6alkyl group, and

c. -CO-N(R31)(R32),

where R31and R32have the meanings indicated above, or

(7) -COOR33,

where R33has the meaning indicated above;

R5represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, or

(3) -COOR51,

where R51represents a hydrogen atom or a C1-6alkyl group;

R6and R6'may be the same or different and each represents

(1) a hydrogen atom,

(2) C1-6alkyl GRU is PU, which may be substituted by a hydroxyl group or a C1-6alkyl group which may be substituted C1-6alkoxygroup, or

(3) acyl group;

R7represents a hydrogen atom, a halogen atom, a nitro-group, a cyano or Ra, Rb, Rc, Rd, Re, Rf, Rgor Rh;

Rarepresents a CpH2(p-1)(Ra1)(Ra2)-O-Ra3,

where

(1) p is an integer from 1 to 6,

(2) Ra1represents a hydrogen atom,

(3) Ra2represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, a halogen atom, carboxypropyl, and

(4) Ra3represents a hydrogen atom or acyl group;

Rbrepresents a CpH2(p-1)(Rb1)(Rb2)-N(Rb3)(Rb4),

where

(1) p is an integer from 1 to 6,

(2) Rb1represents a hydrogen atom,

(3) Rb2represents a C1-6alkyl group,

(4) Rb3represents a hydrogen atom or a C1-6alkyl group, and

(5) Rb4represents a

A. a hydrogen atom or

b. -CO Rb42,

where Rb42represents a C1-6alkyl group;

Rcrepresents-C(=N-Rc1)-Rc2,

DG is

(1) Rc1represents a

A. hydroxyl group,

b. C1-6alkoxygroup, where C1-6alkyl group, a C1-6alkoxygroup may be substituted by a hydroxyl group or a C1-6alkoxygroup, or

c. alloctype, and

(2) Rc2represents a C1-6alkyl group, or amino group;

Rdrepresents-C(=O)-Rd1,

where Rd1represents a

(1) a hydrogen atom,

(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group,

(3) a hydroxyl group,

(4) C1-6alkoxygroup,

(5) -N(Rd11)(Rd12),

where Rd11and Rd12may be the same or different and represent

· a hydrogen atom or

· C1-6alkyl group, where C1-6the alkyl group may be substituted amino group, carboxypropyl or a hydroxyl group, or

Rd11and Rd12together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic ring, or

(6) C1-6alkoxygroup;

Rerepresents 5 - or 6-membered aromatic heterocyclic group having from 1 to 4 heteroatoms, where the aromatic heterocyclic group may be substituted C1-6alkyl group or oxopropoxy;

Rfnot only is em a C 1-6alkyl group or a C2-6alkenylphenol group where the specified C1-6alkyl group, and C2-6Alchemilla group may be substituted by the Deputy, selected from the following group Fa-2:

[Group Fa-2]

A. -COOH,

b. - N(Rf21)(Rf22),

where Rf21and Rf22may be the same or different and represent

· a hydrogen atom,

· acyl group, or

· C1-6alkyl group,

where C1-6the alkyl group may be substituted by carboxypropyl, and

c. halogen atom.

Rgis a Deputy with the ring B", represented by the following formula (IIb);

where A is a linker selected from the following group Ga-2:

[Group Ga-2]

· -(CH2)k-,

· -(CH2)k-NRg1(CO)-,

· -(CH2)k-NRg1-(CH2)j-,

· -(CH2)k-O-(CO)-,

· -(CH2)k-O-,

· -(CO)-NRg1-(CH2)j-,

· -(CO)- and

· -(CO)-NRg1-,

where k and j may be the same or different and represent an integer from 1 to 4

Rg1represents a

·· the hydrogen atom,

·· acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl, or

·· C1-6alkyl group, where the alkyl group can be for esena

-CON(Rg41)(Rg42).

Ring B is a ring selected from the following group Ha-2:

[Group Ha-2]

· aromatic hydrocarbon group,

· C3-8cycloalkyl group and

· 5-7-membered saturated heterocyclic group containing at least one nitrogen atom, where the saturated heterocyclic ring may form a condensed ring with a phenyl group, and

ring B may be substituted by the Deputy, selected from the following group Ia-2:

[Group Ia-2]

A. -ORg2,

(where Rg2represents a

· a hydrogen atom,

· C1-6alkyl group, or

· aracelio group, and

b. -COOORg3,

where Rg3represents a

· a hydrogen atom or

· C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group; and

Rhrepresents-N(Rh1)(Rh2),

where Rh1represents a hydrogen atom, and Rh2represents an acyl group, where the acyl group may be substituted by a hydroxyl group or a C1-6alkoxycarbonyl group.

18. Aminopyridine compound or its pharmaceutically acceptable salt according to the above claim 1, where aminopyridine compound selected from the following group of compounds:

(01) 1-{5-[6-(4-methylpyridin-2-ylamino)PI is one-2-yl]thiophene-2-yl}Etalon,

(02) 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carbaldehyde,

(03) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanol

(04) ethyl ester 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}acetic acid,

(05) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}acetamide", she

(06) N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamid,

(07) {5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}methanol,

(08) the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone,

(09) 1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,

(10) 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamid,

(11) 1-{5-[6-(6-isopropoxypyridine-4-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,

(12) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}acetamide", she

(13) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon O-(2-hydroxyethyl)oxime,

(14) N-(2-amino-ethyl)-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamid,

(15) the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}propane-1-it,

(16) ethyl ether {2-[6-(5-acetylthiophene-2-yl)pyridine-2-ylamino]pyridine-4-yl}acetic acid,

(17) methyl ester 2-[6-(5-acetylthiophene-2-yl)pyridine-2-ylamino]isonicotinic acid,

(18) 1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)ethanol

(19) N-hydroxy-5-[-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamidine,

(20) 1-(5-{6-[4-(2-hydroxyethoxy)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)Etalon,

(21) 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,

(22) the oxime of 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone,

(23) {5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}piperazine-1-ylmethanone,

(24) 1-(5-{6-[4-(4,4-dimethyl-4,5-dihydrooxazolo-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)

Etalon,

(25) 2.2-debtor-3-hydroxy-3-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}propionic acid,

(26) 4-[({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid,

(27) 4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid,

(28) TRANS-4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]

cyclohexanecarbonyl acid,

(29) 3-(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)propionic acid,

(30) 4-[(N-isobutyryl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid and

(31) 4-[(N-(2-hydroxyacyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid.

19. Pharmaceutical composition containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1,as an active ingredient.

20. Syk inhibitor containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

21. Therapeutic and/or prophylactic agent for the treatment of allergic diseases containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

22. Therapeutic and/or prophylactic agent for the treatment of asthma, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

23. Therapeutic and/or prophylactic agent for the treatment of allergic rhinitis, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

24. Therapeutic and/or prophylactic agent for treatment of allergic dermatitis, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

25. Therapeutic and/or prophylactic agent for the treatment of allergic conjunctivitis, containing aminopyridine compound or the pharmaceutically priemlemaya, in accordance with the above-described item 1, as an active ingredient.

26. Therapeutic and/or prophylactic agent for the treatment of autoimmune diseases, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

27. Therapeutic agent for the treatment of progressive deforming arthritis, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

28. Therapeutic agent for the treatment of systemic lupus erythematosus, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

29. Therapeutic agent for treatment of multiple sclerosis, containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

30. Therapeutic agent for treatment of a malignant tumor containing aminopyridine compound or its pharmaceutically acceptable salt, as described in the above item 1, as an active ingredient.

31. Therapeutic agent for the treatment of B-cell lymphoma and b-cell leukemia, containing aminopyridines the compound or its pharmaceutically acceptable salt, in accordance with the above-described item 1, as an active ingredient.

32. Therapeutic and/or prophylactic agent for the treatment of allergic diseases containing Syk inhibitor, in accordance with the above claim 20, in combination with other anti-allergic agent.

Advantages of the invention

The present invention relates to a new aminopyridinium the compound represented by the above General formula (I)or its pharmaceutically acceptable salt and medicinal product containing it as active ingredient.

These compounds according to the present invention is applicable as active ingredients of pharmaceutical preparations. As these compounds of the present invention have excellent inhibitory effect and the selectivity for Syk, they are useful as a therapeutic or prophylactic agent for the treatment of diseases that are associated with an allergic or inflammatory reaction and which involved Syk is the main etiological cause of asthma, rhinitis, atopic dermatitis, contact dermatitis, rash urticarnaya, food Allergy, conjunctivitis, elastic catarrhal inflammation etc) diseases, which, in turn, involved ADCC (autoimmune hemolytic anemia, asthenic is Albany paralysis and so on), a blood clot that has formed due to aggregation of platelets, etc.

The best way of carrying out the invention

Definitions used in the present description, are as follows. The value of the term is not explicitly defined, followed by the value usually used in this field.

The term "halogen atom" refers to fluorine atom, chlorine atom, bromine atom or iodine atom, and preferably it refers to fluorine atom, chlorine atom or bromine atom.

The term "C1-6alkyl group" refers to linear or branched alkyl group having from 1 to 6 carbon atoms and in particular includes methyl group, ethyl group, through the group, isopropyl group, boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group, pentelow group, isopentyl group, tert-pentelow group, hexoloy group, etc. are Preferably it refers to a linear or branched alkyl group having from 1 to 4 carbon atoms and in particular it refers to a methyl group, ethyl group, through the group, isopropyl group, butilkoi group, isobutylene group, sec-butilkoi group, tert-butilkoi group, etc.

The term "Allenova group" refers to alkalinous group that may be branched, having from 2 to 6 carbon atoms, and especially who engages methylene group, propylene group, isopropylene group, butylene group, 2-methylpropanoyl group, etc.

The term "C1-6alkoxygroup" refers to alkylacrylate, in which the alkyl part is C1-6alkyl group, as defined above, and in particular includes a methoxy group, ethoxypropan, propoxylate, isopropylacetate, butoxypropyl, isobutylacetate, tert-butylacrylate, pentyloxy, hexyloxy etc. Preferably it refers to "C1-4alkoxygroup".

The term "C1-6alkoxycarbonyl group" refers to alkoxycarbonyl group in which the alkyl part is C1-6alkoxygroup", as defined above, and in particular includes methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxyethanol group, sec-butoxycarbonyl group, tert-butoxycarbonyl group, ventilatsioonile group, isobutylacetophenone group, 2-metilbutanoilny group, neopentylglycol group, 1-ethylpropylamine group, hexyloxymethyl group, 4-methylbenzyloxycarbonyl group, 3-methylbenzyloxycarbonyl group, 2-methylbenzyloxycarbonyl group, 1-methyl is intracerebrally group, 3,3-dimethylbutylamino group, 2,2-dimethylbutylamino group, 1,1-dimethylbutylamino group, 1,2-dimethylbutylamino group, 1,3-dimethylbutylamino group, 2,3-dimethylbutylamino group or 2-metilbutanoilny group, etc. are Preferably it belongs to (C1-4alkoxy)carbonyl group, and more preferably it refers to methoxycarbonylamino group or ethoxycarbonyl group.

The term "C1-6alkylamino" refers to "C1-6alkyl group, as defined above, which is associated with the amino group and, for example, includes methylaminopropyl, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, intellimorph, isopentylamine, 2-methylbutylamine, neopentylene, 1-ethylpropylamine, hexylamino, isohexanol, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1-methylpentylamino, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino or 2-ethylbutylamine etc. Preferably it refers to C1-4alkylaminocarbonyl, such as metiram nogroup, atramentaria and propylamino.

The term "CI-C1-6alkylamino" refers to a group in which two "C1-6alkyl group, as defined above, linked to the amino group and includes, for example di-C1-6alkylamino, such as dimethylaminopropyl, diethylaminopropyl, N-ethyl-N-methylaminopropyl, dipropylamino, dibutylamino, dipetalonema or vexillaria and preferably it is di-C1-4alkylamine.

The term "C1-6alkylsulfonyl group" refers to a group in which "C1-6alkyl group, as defined above, associated with sulfonyloxy group and includes, for example methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylphenyl group, butylsulfonyl group, isobutylamino group, sec-butylsulfonyl group, tert-butylsulfonyl group, pentylaniline group, isopentenyladenine group, 2-methylbutyronitrile group, neopentylglycol group, 1-ethylpropylamine group, hexylaniline group, isohexanol group, 4-methylphenylsulfonyl group, 3-methylphenylsulfonyl group, 2-methylphenylsulfonyl group, 1-methylphenylsulfonyl group, 3,3-dimethylbutylamino group, 2,2-dimethylbutyl fanilow group, 1,1-dimethylbutylamino group, 1,2-dimethylbutylamino group, 1,3-dimethylbutylamino group, 2,3-dimethylbutylamino group or 2-ethylbutyraldehyde group, etc. are Preferably it refers to C1-4alkylsulfonyl group, such as methylsulfonyl group.

The term "carnemolla group" refers to carbamoyl group, C1-6alkylcarboxylic group or di-C1-6alkylcarboxylic group.

The term "C1-6acylcarnitine group" refers to a group in which one "C1-6alkyl group, as defined above, associated with carbamoyl group and includes, for example alkylcarboxylic group, such as methylcarbamoyl group, ethylcarbazole group, profilirovannaja group, isopropylcarbonate group, butylcarbamoyl group, isobutylbarbituric group, sec-butylcarbamoyl group, tert-butylcarbamoyl group, intercalatory group, isopentylamine group, 2-methylbutylamine group, neopentadactyla group, 1-ethylpropylamine group or paxilonline group, and preferably it refers to C1-4alkylcarboxylic group.

The term "CI-C1-6acylcarnitine group" refers to a group in which two

"C1-6alkyl group", as indicated the above, associated with carbamoyl group and includes, for example dialkylamino group, such as dimethylcarbamoyl group, diethylcarbamoyl group, N-ethyl-N-methylcarbamoyl group, dipropylamine group, dibutylaniline group, dependentAssembly group or dihexylfluorene group, and preferably it is di-C1-4alkylcarboxylic group.

The term "cycloaliphatic hydrocarbon" refers to a saturated or unsaturated C3-8cycloaliphatic hydrocarbon group, for example cycloalkyl group, cycloalkenyl group, cycloalkenyl group, etc.

The term "C3-8saturated hydrocarbon ring" and "C3-8cycloalkyl group" has the same meaning and refers to a saturated cycloalkyl group having from 3 to 8 carbon atoms, and includes, for example cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group, cyclooctyl group, bicyclo[2.2.1]heptylene group, bicyclo[2.2.2]octillo group, bicyclo[3.2.1]octillo group, etc. are Preferably it refers to a saturated 5-7 cycloalkyl group, and in particular it relates to cyclopentyloxy group, tsiklogeksilnogo group and cycloheptyl group.

The above-mentioned term "rich Ugledar is the initial ring may include a double bond in its side, and cycloalkenyl" etc. is also included in the term "saturated hydrocarbon ring".

The term "C3-8cycloalkenyl group" refers to cycloalkenyl group having from 3 to 8 carbon atoms and cycloalkenyl group containing at least one, preferably 1 or 2 double bonds. Particularly included are cyclopropylamino group, cyclobutenyl group, cyclopentenyl group, cyclopentadienyls group, cyclohexenyl group, 2,4-cyclohexadiene-1-ilen group, 2,5-cyclohexadiene-1-ilen group, cycloheptenyl group and cyclooctadiene group, etc. are Preferably it refers to 5-7 cycloalkenyl group.

The term "cycloalkyl C1-6alkyl group" refers to C1-6alkyl group, substituted C3-8cycloalkyl group"as described above, and preferred examples include cycloalkyl group having 4 to 13 carbon atoms, for example cyclopropylmethyl group, cyclopropylethyl group, cyclopentylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cyclohexylethyl group, etc.

The term "aryl group" refers to an aromatic hydrocarbon group or aromatic heterocyclic group, but represents an aromatic hydrocarbon group, when she relates the I to the specified simply as "aryl group". The aromatic hydrocarbon ring may be specified simply as an aromatic carbocyclic ring. The term "aromatic hydrocarbon group" refers to an aromatic hydrocarbon group having 6 to 14 carbon atoms, and in particular it includes phenyl group, naftalina group, biphenylene group, untilnow group, indenolol group, azulinebloo group, fluorenyl group, phenanthroline group, etc. are Preferably it refers to a phenyl group, naftilos group, biphenylenes group.

The terms "aromatic aliphatic hydrocarbon group" and "kalkilya group" have the same meaning and represent an aliphatic hydrocarbon group having from 7 to 14 carbon atoms, and particularly represents aracelio group, arylalkyl group, arylalkyl group, etc.

The term "kalkilya group" refers to C1-6alkyl group, substituted aryl group, as mentioned above, and preferred examples include

C7-10phenylalkyl group such as benzyl group, penicilina group, 1-phenylethylene group, 1-phenylpropionate group, 2-phenylpropionate group, 3-phenylpropionate group, phenylmethylene group; biphenylmethanol group;

C11-13naphthylethylene group, such as α-naphthylmethyl group is a, α-naphthylethylene group, β-naphthylmethyl group, β-naphthylethylene group. It may be C8-10fenilalanina group, such as sterelny group; naphthylethylene group, such as 2-(2-naphthylvinyl) group.

The term "urlcategory" refers to Alcochete in which it kalkilya part is aracelio group, as mentioned above, and includes, for example, C7-10fenilalanina, such as benzyloxy, penetratiegraad, 1-fenilatilamina, 1-phenylpropoxy, 2-phenylpropoxy, 3-phenylpropoxy, phenylbutyraldehyde; biphenylenediisocyanate; C11-13naphthalanotherapy, such as α-naphthalenyloxy, α-negotiationshave, β-naphthalenyloxy, β-negotiationshave.

The term "alcoxycarboxylates" refers to the amino group, substituted alcoxycarbenium group, and arakaki part alcoxycarbenium group is urlcategory, as mentioned above. For example, included are benzyloxycarbonylamino, ventilatsiooniinseneride etc.

The term "C2-6Alchemilla group" refers to alkenylphenol group having from 2 to 6 carbon atoms, and includes, for example, atenolol group, 1-propenyloxy group, 2-propenyloxy group, 1-butenyloxy group, 2-butenyloxy group, 3-b is tonilou group, 2-methyl-1-propenyloxy group, 1-pentanediol group, 2-pentanediol group, 3-pentanediol group, 4-pentanediol group, 3-methyl-2-butenyloxy group, 1-hexenyl group, 3-hexenyl group, 2,4-hexadienyl group and 5-hexenyl group. Among these C2-6alkenyl groups, for example, vinyl group or protanilla group is particularly preferred.

The term "acyl group" refers to an aliphatic acyl group, aromatic acyl group or a heterocyclic acyl group, in which the saturated or unsaturated hydrocarbon group or heterocyclic group is linked to a carbonyl group. In a narrow sense, it refers to an acyl group in which the hydrocarbon group alifaticheskii linked to a carbonyl group. In particular, C1-6acylcarnitine group (for example, acetyl group, propylaniline group, Butyrina group, isobutylene group, valerina group, isovaleryl group, pivellina group, hexanoyl group); C2-7alkenylamine group (for example, crotonylene group); C3-8cycloalkylcarbonyl group (for example, cyclobutanecarbonyl group, cyclopentanecarbonyl group, cyclohexanecarbonyl group, cyclohexylcarbonyl group); C3-8cycloalkylcarbonyl group (e.g. the, 2-cyclohexanecarbonyl group); C6-14arylcarbamoyl group (for example, arylcarbamoyl group, such as benzoline group, α-napolina group, β-napolina group, halogenated arylcarboxylic group, such as 2-bromobenzoyl group, 4-chlorbenzoyl group, alkilirovanny lower alkyl arylcarbamoyl group such as 2,4,6-trimethylbenzoyl group, 4-toluylene group, alkoxycarbonyl lower alkoxygroup arylcarbamoyl group, such as 4-ansorena group nitride arylcarbamoyl group, such as 4-nitrobenzoyl group, 2-nitrobenzoyl group, alkoxycarbonylmethyl arylcarbamoyl group, such as 2-(methoxycarbonyl)benzoline group, allrounda arylcarbamoyl group, such as 4-phenylbenzophenone group); C7-14analceleberty group (for example, benzylcarbamoyl group, ventilkappen phenylpropanolamine group, phenylmethylsulphonyl group); C8-13arylalkylamine group (for example, strykersville group); C8-13arylalkylamine group (for example, feniletinilpireny group); an aromatic heterocyclic carbonyl group (for example, nicotinoyl group, isonicotinoyl group, forelornly group, taylorsville group, pyrimidinecarbonitrile the group, benzofurazanyl group, 1H-indotricarbocyanine group, hinolincarbonova group); non-aromatic heterocyclic carbonyl group (for example, pyrrolidinylcarbonyl group, piperidinylcarbonyl group, morpholinosydnonimine group, tiomorfolina group, piperazinylcarbonyl group, diazolidinylurea group, hexamethylenediaminetetra group, tetrahydroxyphenylchlorin group), etc. can serve as an example.

The term "alloctype" refers to a group in which an oxygen atom is linked to the "acyl group"as mentioned above and, for example, includes benzoyloxy etc.

The term "alluminare" refers to a group in which the "acyl group"as mentioned above, is associated with an atom of the amino group, and, for example, it refers to linear or branched lower aliphatic alluminare having from 2 to 7 carbon atoms, such as acetylamino, Propionaldehyde, bucillamine, isobutylamino, valerianovna, isovaleraldehyde, pivaloylpyruvic, exonerating, aceleradora, methacryloylamido, crotonylene.

The term "heterocyclic group" or "heterocycle" refers to a saturated ring (which may have a double bond in its parts) or aromatically, having 1-4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom, other than a carbon atom as an atom constituting the ring, where the number of atoms forming the ring is 3-14. "Heterocyclic group" may be monocyclic or may form a condensed ring with cycloalkyl ring, such as tsiklogeksilnogo ring, an aromatic hydrocarbon ring such as benzene ring or another heterocyclic ring.

The term "5-7-membered saturated heterocyclic group" refers to the "heterocyclic group containing 5-7-membered, preferably 5 - or 6-membered saturated ring.

The term "heterocyclic group", which is a monocycle, includes, for example, pyridyloxy group, personilnya group, pyrimidinyl group, pyridazinyl group, 1,3,5-triazinyl group, pyrrolidino group, pyrazolidine group, imidazolidinyl group, 1,2,4-triazolyl group, tetrazolyl group, thienyl group, follow group, oxazolidinyl group, isoxazolyl group, thiazolidine group, isothiazolinone group, thiadiazolyl group, pyrrolidino group, pyrrolidinyl group, imidazolidinyl group, piperidino group, piperazinilnom group, morpholinyl group, thiomorpholine group, tetrahydropyranyl the ing group, etc.

"Heterocyclic group which is a monocycle"mentioned above, may be "aromatic heterocyclic group", or may be a saturated ring which may have double bond in its side). The term "saturated heterocyclic group", as used in the present description, is a so-called heterocyclic group that contains no double bond, as well as heterocyclic group having a double bond in its side. Examples of these "saturated heterocyclic group" include pyrrolidinyl group (for example, 2-pyrrolidinyl group, 3-pyrrolidinyl group), pyrrolidinyl group (for example, 2-pyrrolidin-3-yl), imidazolidinyl group (for example, 2-imidazolin-4-yl), piperidino group (for example, 2-piperideine group, 3-piperideine group), piperazinilnom group (for example, 2-piperazinilnom group), morpholinyl group (for example, 3-morpholinyl group), tetrahydrofuryl group, tetrahydrocannibinol group, pyrazolidine group, 1,3-DIOXOLANYL group, 1,3-oxathiolanes group, oxazolidinyl group, diazolidinyl group, tetrahydropyranyloxy group, tetrahydropyranyloxy group, dioxinlike group, morpholinyl group, thiomorpholine group, 2-oxopyrrolidin group, 2-oxopiperidine group-oxopiperidine group, 2,6-dioxopiperidin group, etc.

The term "aromatic heterocyclic group (heteroaryl group" refers to a 5-7-membered, preferably 5 - or 6-membered monocyclic aromatic heterocyclic group or a bicyclic or tricyclic aromatic heterocyclic group, in which such a monocycle is condensed with other rings, where the heterocyclic group contains, for example, from 1 to 5, preferably from 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom other than carbon atom, which forms a ring.

Preferred examples of such aromatic heterocyclic group (heteroaryl group) include follow group (for example, 2-furyl, 3-furyl), thienyl group (e.g., 2-thienyl, 3-thienyl), pyridyloxy group (for example, 2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl group (for example, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyridazinyl group (for example, 3-pyridazinyl, 4-pyridazinyl), personilnya group (for example, 2-pyrazinyl), pyrrolidinyl group (for example, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), imidazolidinyl group (for example, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), pyrazolidine group (for example, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), oxazolidinyl group (for example, 2-oxazolyl 4-oxazolyl, 5-oxazolyl), isoxazolyl group, thiazolino group (for example, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), isothiazoline group, oxadiazolyl group (for example, 1,2,4-oxadiazol-5-yl, 1,3,4 - oxadiazol-2-yl), thiadiazolyl group (for example, 1,3,4 - thiadiazole-2-yl), triazolyl group (for example, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-2-yl, 1,2,3-triazole-4-yl), tetrazolyl group (for example, tetrazol-1-yl, tetrazol-5-yl), pinolillo group (for example, 2-chinolin, 3-chinolin, 4-chinolin), chinadaily group (for example, 2-chinadoll, 4-chinadoll), khinoksalinona group (for example, 2-Minoxidil), benzofuran (for example, 2-benzofuran, 3-benzofuran), benzothiazoline group (for example, 2-benzothiazyl, 3-benzothiazol), benzoxazolyl group (for example, 2-benzoxazolyl), benzothiazolyl group (for example, 2-benzothiazolyl), benzimidazolyl group (for example, the benzimidazole-1-yl, benzimidazole-2-yl), indolenine group (e.g., indol-1-yl, indol-3-yl), 1H-indazolinone group (for example, 1H-indazol-3-yl), 1H-pyrrolo[2,3-b]personilnya group (for example, 1H-pyrrolo[2,3-b]pyrazin-2-yl), 1H-pyrrolopyridines group (for example, 1H-pyrrolo[2,3-b]pyridine-6-yl), 1H-imidazopyridine group (for example, 1H-imidazo[4,5-b]pyridine-2-yl, 1H-imidazo[4,5-c]pyridine-2-yl), 1H-imidazopyridine group (for example, 1H-imidazo[4,5-b]pyrazin-2-yl), triazinyl group, from inailo group, benzoxadiazole group, benzothiazolyl group, benzotriazolyl group, etc.

The term "5 - or 6-membered aromatic heterocyclic group or a saturated heterocyclic group" in particular includes pyridyloxy group, personilnya group, pyrimidinyl group, pyridazinyl group, 1,3,5-triazinyl group, pyrrolidino group, pyrazolidine group, imidazolidinyl group, 1,2,4-triazolyl group, tetrazolyl group, thienyl group, follow group, oxazolidinyl group, isoxazolyl group, thiazolidine group, isothiazolinone group, thiadiazolyl group, pyrrolidinyl group, piperidino group, piperazinilnom group, etc.

"Condensed heterocyclic group mentioned above may be partially saturated, and examples of partially saturated condensed heterocycle include isopropanolol group (for example, 3-Isopropenyl, etc), indolinyl group (for example, 2-indolinyl etc), isoindolyl group (for example, 1-isoindolyl etc), 1,2,3,4-tetrahydro-2-pinolillo group, 1,2,3,4-tetrahydro-3-izohinolinove group, etc.

Preferred examples of the condensed aromatic heterocyclic group or condensed heterocyclic group" include benzofuranyl group, isobenzofuranyl g is the SCP, benzo[b]thienyl group, indolenine group, isoindolyl group, 1H-indazolinone group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, 1H-benzotriazolyl group, pinolillo group, izohinolinove group, cinnoline group, chinadaily group, khinoksalinona group, talasila group, naphthyridinone group, parinello group, pteridinyl group, carbazolyl group, α-carbonello group, β-carbonello group, criminology group, phenoxazine group, phenothiazinyl group, pensininku group, phenoxathiin group, Centrenergo group, indolizinyl group, 5,6,7,8-tetrahydroquinoline group, pyrrolo[1,2-b]pyridazinyl group, a pyrazolo[1,5-a]pyridyloxy group, imidazo[1,2-a]pyridyloxy group, imidazo[1,5-a]pyridyloxy group, imidazo[1,2-b]pyridazinyl group, imidazo[1,2-a]pyrimidinyl group, 1,2,4-triazolo[4,3-a]pyridyloxy group, 1,2,4-triazolo[4,3-b]pyridazinyl group, etc.

The term "heterocytolysine group" is the same term as the term "saturated heterocyclic group".

The term "C7-11spirometrically group" refers to a group in which heterocytolysine group mentioned above, forms spirostane with C3-8cycloalkyl group mentioned above,or geteroseksualnoe group, mentioned above, and includes, for example, azaspiro[2.3]hexoloy group, azaspiro[2.4]heptylene group, azaspiro[3.4]octillo group, azaspiro[2.5]octillo group, azaspiro[3.5]nonalloy group, azaspiro[4.4]nonalloy group, azaspiro[4.5]deganello group, azaspiro[5.5]undecenyl group, etc.

The term "C1-6alkylidene group" refers to a group formed by removing two hydrogen atoms from one carbon atom alkane, and the free valence becomes part of a double bond, and includes, for example, metrodin, ethylidene, propylidene, butylidene, pentylidene, hexylidene etc.

The definition of each term is the fact, as stated above, and particularly preferred are the following. In addition, the substitution may be the same or different two or more substituents.

X1X2and X3preferably represent-CH=, =C(R3)- and-CH=, respectively.

For Y1and Y2either one of the Y1and Y2R preferably is a nitrogen atom, and more preferably both represent carbon atoms (-CH=) at the same time.

Preferably R represents a hydrogen atom.

R3preferably represents a halogen atom, a hydroxyl group or a C1-6alkyl group (where the alkyl group can be ameena alkoxycarbonyl group or a C 1-6alkoxygroup), especially preferably this applies to C1-6alkyl group (where the alkyl group may be substituted alkoxycarbonyl group or a C1-6alkoxygroup), and even more preferably it refers to a methyl group.

Preferably R5represents a hydrogen atom.

R6and R6' preferably represent hydrogen atoms or C1-6alkyl groups and particularly preferably represent hydrogen atoms.

R7particularly preferably represent Re, Rgor Rh.

"p" Raand Rbis an integer from 1 to 6 and preferably an integer from 1 to 4. Especially, when p is 1, Ra, Ra2preferably represents a Deputy, other than the hydrogen atom, and when p is 2 or more, the Deputy-O-Ra3preferably attached in position from the 2nd to the 6th group-CpH2(p-1)(Rb1)(Rb2)-.

Similarly, when p is 1, Rb, Rb2preferably represents a Deputy, other than the hydrogen atom, and when p is 2 or more Deputy-N(Rb3)(Rb4)3preferably attached in position from the 2nd to the 6th group

-CpH2(p-1)(Rb1)(Rb2)-.

In Rapreferably Ra1is an atom of water is kind and preferably R a2represents a C1-6alkyl group, aracelio group or aryl group (where the specified C1-6alkyl group, kalkilya group and aryl group may be substituted by the Deputy selected from a hydroxyl group or carboxypropyl), and preferably Ra3represents a hydrogen atom, acyl group, carbamoyl group presents-CON(Ra31)(Ra32or C1-6alkyl group (where the alkyl group may be substituted C1-6alkoxycarbonyl group or-CON(Ra31)(Ra32)).

As for Ra31and Ra32in particular 5 - or 6-membered saturated heterocyclic group together with the adjacent nitrogen atom and having one or more nitrogen atoms may serve as an example a saturated heterocyclic group, as shown below:

In Rbpreferably Rb1represents a hydrogen atom, and preferably

Rb2represents a phenyl group which may be substituted C1-6alkyl group which may be substituted by the Deputy selected from the group of Ca, or hydroxyl group, and preferably Rb3represents a hydrogen atom or a C1-6alkyl group, and preferably Rb4represents a hydrogen atom, acyl group, which mo is et to be substituted by a hydroxyl group or a C 1-6alkylsulfonyl group.

Rc1that is particularly preferred in Rcrepresents a hydroxyl group or a C1-6alkoxygroup (where C1-6alkoxygroup may be substituted by a hydroxyl group or a C1-6alkoxygroup).

Rd1, which is preferred in Rdrepresents a C1-6alkyl group, a C1-6alkoxygroup or-N(Rd11)(Rd12). In addition, Rd11and Rd12preferably in this description represent atoms of hydrogen, C1-6alkoxygroup or C1-6alkyl groups (where C1-6the alkyl group may be substituted by a hydroxyl group or carboxypropyl).

Preferably the ring A in Reis the following.

Particularly preferred examples for "5-6-membered saturated heterocyclic group having one to two heteroatoms in Reinclude saturated heterocyclic group

More specifically include the following groups

Of these groups, particularly preferred are saturated heterocyclic group, which are directly related to the thiazole ring or a thiophene ring compounds of the above General formula (I) via a nitrogen atom, formiruyusch the specified saturated heterocyclic ring

Preferred examples of the "5 - or 6-membered saturated heterocyclic group having from 1 to 4 heteroatoms" in Reinclude the following aromatic heterocyclic group

Preferred examples 9-12-membered condensed aromatic heterocyclic group having 1 or 2 heteroatoms, which may be partially saturated" in Reinclude condensed aromatic heterocyclic group

The following condensed ring is also included

Particularly preferred examples of "C3-8cycloalkyl group" in Reinclude the following cycloalkyl group.

Preferred examples of "C7-11spiroheterocyclic group having 1 or 2 heteroatoms in Reinclude the following spiroheterocyclic group

The substituents for ring A are as shown in the Ea group. Preferred substituents for ring A are as follows.

Preferred examples-ORe1include

· hydroxyl group,

· C1-6alkyl group, where C1-6the alkyl group may be zames is on carboxypropyl or-CON(R e11)(Re12) (where Re11and Re12may be the same or different and each represents a hydrogen atom or a C1-6alkyl group),

· alloctype,

· urlcategory or

· carbamoyloximes.

Preferred examples of-COORe2include

· carboxypropyl or

· C1-6alkoxycarbonyl group.

Preferred examples of-CO-N(Re41)(Re42include

-CO-NO(Re41)(Re42), where Re41and Re42may be the same or different and each represents

· a hydrogen atom,

· C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, a C1-6alkoxygroup, amino, C1-6alkylamino, di-C1-6alkylamino, halogen atom, carboxypropyl, carbamoyl group, C1-6alkylcarboxylic group, di-C1-6alkylcarboxylic group or 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatom,

· hydroxyl group,

· C1-6alkoxygroup,

· C5-6cycloalkyl group, where C5-6cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkyl group, where C1-6alkyl is Naya group may be substituted by a hydroxyl group; or

· C1-6alkylsulfonyl group.

Especially preferred is carnemolla group.

Preferred examples-CORe3include

-CORe3where Re3represents a

· C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group and C1-6alkylsulfonyl group,

· 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatoms, where saturated heterocyclic group and aromatic heterocyclic group may be substituted by the Deputy, selected from hydroxyl group, carbonyl group, carboxypropyl, C1-6alkoxygroup, where C1-6alkoxygroup may be substituted carbamoyl group, carbamoyl group, where carnemolla group may be substituted by a hydroxyl group, acyl group, alloctype, amino group, allmineral where alluminare may be substituted by a hydroxyl group or carbamoyl group, C1-6alkylaminocarbonyl, di-C1-6alkylaminocarbonyl, C1-6alkylsulfonamides, 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group is C 1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup, where C1-6alkoxygroup may be substituted carbamoyl group, allmineral and carbamoyl group, or

· C5-6cycloalkyl group or aryl group, where C5-6cycloalkyl group and aryl group may be substituted by a hydroxyl group, exography, C1-6alkoxygroup, carbamoyl group, allmineral, oxymyoglobin or alloctype.

In addition, preferable examples of the "5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatoms" in the above, Re3include the following heterocyclic group

In addition, preferable examples of the "5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatoms" in the above, Re3include heterocyclic aromatic group

In addition, preferred examples-CORe3in the above, Re3include the following

Preferred examples of-N(Re51)(Re52include

-N(Re51)(Re52), where Re51and Re52can be Odie is akovali or different and each represents

· a hydrogen atom,

· C1-6alkylsulfonyl group,

· C1-6alkalinuria, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, a C1-6alkoxygroup and carbamoyl group,

· -CON(Re11)(Re12),

where Re11and Re12have the meanings specified above,

· -CORe511,

where Re511represents 5 - or 6-membered saturated heterocyclic group containing at least one nitrogen atom, C1-6alkyl group (where

C1-6the alkyl group may be substituted by a hydroxyl group) or C5-6cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group.

Preferred examples for C1-6alkyl groups include

C1-6alkyl group which may be substituted

· a hydroxyl group,

· C1-6alkoxygroup, C1-6alkyl group, a C1-6alkoxygroup can be replaced by carboxypropyl or-CO-N(Re11)(Re12), and Re11and Re12have the values specified above;

· -COORe2,

where Re2has the meaning specified above,

· -N(Re51)(Re52),

where Re51and Re52have the meanings specified above,

· -CO-N(Re51)(Re52),

where Re51and Re52matter, is shown above,

· halogen atom, or

· 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted by a hydroxyl group or a C1-6alkyl group.

Especially preferred is C1-6alkyl group, substituted-COORe2for example carboxymethyl group or unsubstituted methyl group.

Preferred examples 5-6-membered saturated heterocyclic group (which may be partially saturated, containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom, or an aromatic heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom and oxygen atom, where saturated heterocyclic group and aromatic heterocyclic group may be substituted by oxopropoxy or C1-6alkyl group include

In addition, the preferred substituents for ring A are oxoprop, C1-6alkylsulfonyl group, and cyano.

k and l in the linker "A" group, Rgpreferably have a value of 1 or 2, and k+l has a value from 2 to 4.

In addition, preferably, the ring B in Rgis the following.

Preferred examples of the "aryl group" in Rginclude phenyl which ing group.

Preferred examples of "C3-8cycloalkyl group" in Rginclude C3-8cycloalkyl groups:

Preferred examples 5-7-membered saturated heterocyclic group having one or more nitrogen atoms in Rginclude saturated heterocyclic groups:

Preferred examples 5-6-membered aromatic heterocyclic group having at least one heteroatom in Rginclude aromatic heterocyclic groups:

Preferred examples 8 to 11-membered condensed aromatic heterocyclic group having at least one heteroatom in Rginclude condensed aromatic heterocyclic groups:

Rh1in Rhpreferably represents a hydrogen atom or a C1-6alkyl group.

In addition, preferred are aromatic carbocyclic ring group", "5-6-membered aromatic heterocyclic group containing 1 or 2 heteroatoms", "C3-8cycloalkyl group and 5-6-membered saturated heterocyclic group containing 1 or 2 heteroatom" is the SCP Ja for R h2. Especially preferred is C3-8cycloalkyl group".

Preferred examples of the "aromatic carbocyclic group" in the group Ja for Rh2include phenyl groups.

Preferred examples 5-6-membered aromatic heterocyclic group containing 1 or 2 heteroatoms in the Ja for Rh2include aromatic heterocyclic groups:

Preferred examples 5-6-membered saturated heterocyclic group containing 1 or 2 heteroatoms in the Ja for Rh2include saturated heterocyclic group

Preferred examples of "C3-8cycloalkyl group" in (5) for Rh2include tsiklogeksilnogo group. Especially preferred is tsiklogeksilnogo group, substituted carboxypropyl.

Preferred examples 5-6-membered saturated heterocyclic group containing 1 or 2 heteroatoms in (6) for Rh2include saturated heterocyclic groups:

The definition of each term is described above, but for each symbol X1X2X3, Z, Y1, Y2, R, R1, R5, R6, R7and various substituents are defined narrower concept in the General formula (I), is to "preferably X 1X2X3, Z, Y1, Y2, R, R1, R5, R6, R7and different substituents, which are described in the following specific examples (for example, methyl group, ethyl group, phenyl group, naftalina group"), and particularly preferred are values of X1X2X3, Z, Y1, Y2, R, R1, R5, R6, R7and different substituents derived from the groups of compounds that demonstrate among them are particularly high inhibitory activity

(more than ++).

Preferred examples of the compounds of the present invention include the following compounds, where the number in parentheses represents the number of compounds mentioned in the examples:

1-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyridine-2-on (compound a-1),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (compound A-2),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-3)

N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-4),

N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-5),

methyl ester of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexane is arbonboy acid (compound A-6),

TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid (compound A-7),

(4-hydroxypiperidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-8),

N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)amine (compound A-9),

N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-10),

(S)-3-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-on (compound a-11),

tert-butyl ether (S)-2,2-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-3-carboxylic acid (compound A-12),

(S)-2-amino-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (compound A-13),

(S)-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-on (compound a-14),

the dihydrochloride (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-15),

TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid (compound A-16),

3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-17),

2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-18),

N-{4-IU the Il-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}propionamide (compound A-19),

N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ndimethylacetamide (compound A-20),

N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyrazin-2-yl]thiazol-2-yl}ndimethylacetamide (compound A-21),

ethyl ester of (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetic acid (compound A-25),

(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (compound A-26),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}Etalon (compound A-27),

ethyl ester 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazole-2-carboxylic acid (compound A-28),

the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanone (compound A-30),

(S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}dihydrofuran-2-on (compound a-33),

O-(2-hydroxyethyl)oxime 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanone (compound A-35),

N-methoxy-N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-carboxamide (compound A-46),

N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-carboxamide (compound A-47),

N-methyl-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-52),

(S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-on (compound a-55),

5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentane acid (compound A-69),

5-{5-[6-(4-methylpyridin-2-the laminitis)pyridine-2-yl]thiazol-2-yl}pentane-1-ol (compound A-70),

5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentanone (compound A-71),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanol (compound A-73),

the oxime of 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanone (compound A-74),

N-{6-[2-((S)-1-amino-ethyl)thiazol-5-yl]pyridine-2-yl}-N-([4,4']bipyridinyl-2-yl)amine (compound A-75),

N-((S)-1-{5-[6-([4,4']bipyridinyl-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-79),

N-((S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-81),

(S)-2-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}propane-1-ol (compound A-82),

N-((S)-1-{5-[6-(isoquinoline-3-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-91),

(4-methylpyridin-2-yl)-[6-(2-piperidine-4-iltiazem-5-yl)pyridin-2-yl]amine (compound A-92),

TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-111),

5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentylamine (compound A-128),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}butane-1-ol (compound A-132),

4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenol (compound A-135),

2-hydroxy-N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-147),

3-({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-Carbo is Il}amino)propionic acid (compound A-148),

4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)benzoic acid (compound A-151),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-ol (compound A-152),

3,3-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}butane-1-ol (compound A-158),

[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]methanol (compound A-159),

N-((R)-(4-hydroxyphenyl)-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}methyl)ndimethylacetamide (compound A-161),

N-(2-hydroxyethyl)-4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)benzamide (compound A-162),

4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanone (compound A-172),

4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanol (compound A-173),

((3R,4S)-3,4-dihydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-174),

(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-(piperazine-1-yl)

mechanon (compound A-176),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-carboxamide (compound A-182),

2-hydroxy-1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-yl)alanon (compound A-187),

TRANS-4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexan robonova acid (compound A-188),

hydrochloride 3-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-yl)-3-oxopropanoic acid (compound A-192),

N-(4-methylpyridin-2-yl)-N-{6-[2-(piperazine-1-ylmethyl)thiazol-5-yl]pyridine-2-yl}amine (compound A-194),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-ylamine (compound A-197),

N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}methanesulfonamide (compound A-200),

N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)ndimethylacetamide (compound A-202),

TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid (compound A-204),

2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (compound A-205),

(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanol (compound A-211),

TRANS-4-{5-[6-(isoquinoline-3-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid (compound A-215),

TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylethylamine (compound A-219),

((3R,4S)-3,4-dihydroxypyrrolidine-1-yl)-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]metano (compound A-223),

N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)ndimethylacetamide (compound A-228),

N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-illlogical)

methanesulfonamide (compound A-229),

2-hydroxy-N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)ndimethylacetamide (compound A-235),

2-hydroxy-N-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]ndimethylacetamide (compound A-237),

((3R,4S)-3,4-dihydroxypyridine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-239),

((R)-3-hydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-241),

(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}phenyl)methanol (compound A-243),

N-(4-methylpyridin-2-yl)-N-[6-(2-pyridin-3-ilmatieteen-5-yl)pyridin-2-yl]amine (compound A-248),

N-(4-methylpyridin-2-yl)-N-{6-[2-(2-piperidine-4-retil)thiazol-5-yl]pyridine-2-yl}amine (compound A-258),

N-(6-{2-[2-(1-methanesulfonamido-4-yl)ethyl]thiazol-5-yl}pyridine-2-yl)-N-(4-methylpyridin-2-yl)amine (compound A-260),

2-hydroxy-1-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)piperidine-1-yl]alanon (compound A-263),

N-(2-hydroxyethyl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-267),

N-(2-morpholine-4-retil)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-268),

[3-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridi the-2-yl]thiazol-2-yl}ethyl)phenyl]methanol (compound A-277),

(3-hydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-282),

4-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl)

piperazine-2-on (compound a-283),

((R)-2-hydroxyethylpyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-286),

(4-aminopiperidin-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon (compound A-290),

[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)piperidine-1-yl]-

(piperidine-4-yl)methanon (compound A-295),

(TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-(4-hydroxypiperidine-1-yl)methanon (compound A-297),

N-(4-hydroxypiperidine-1-yl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-298),

N-[(R)-2-hydroxy-1-(3H-imidazol-4-ylmethyl)ethyl]-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-303),

N-[(S)-2-hydroxy-1-(3H-imidazol-4-ylmethyl)ethyl]-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-304),

N-(2-dimethylaminoethyl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-309),

trihydrochloride 3-aminopyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanone (compound A-311),

N-[1-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl)

pyrrolidin-3-yl]methanesulfonamide (compound A-312),

(3R,4S)-1-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)pyrrolidine-3,4-diol (compound A-314),

TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonitrile (compound A-316),

CIS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonitrile (compound A-317),

(S)-5-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-on (compound a-319),

(S)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (compound A-320),

(S)-1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol (compound A-321),

(S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (compound A-322),

(S)-5-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-on (compound a-323),

3-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-4H-[1,2,4]oxazol-5-Oh (compound A-325),

N-(4-methylpyridin-2-yl)-N-(6-{2-[4-(1H-tetrazol-5-yl)cyclohexyl]thiazole-5-yl}pyridine-2-yl)amine (compound A-326),

(S)-5-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-2-on (compound a-330),

N-(1,1-dimethyl-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (link is A-334),

(S)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol (compound A-335),

N-methyl-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-336),

N-(1,1-dimethyl-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)methanesulfonamide (compound A-337),

TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-338),

TRANS-4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic (compound A-339),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}cyclohexanol (compound A-341),

(S)-1-(5-{6-[4-(2-hydroxyethoxy)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol (compound A-344),

ethyl ester of (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}dimethylcarbinol acid (compound A-345),

potassium carbonate 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2-she (compound A-351),

4-(2-hydroxy-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenol (compound A-362),

4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}acetyl)piperazine-2-on (compound a-370),

N-((R)-(4-hydroxyphenyl)-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}methyl)-N-methylacetamide (compound A-372),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ilma is Il}piperazine-2,6-dione (compound A-383),

(S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-on (compound a-409),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2-on (compound a-416),

N-(4-methylpyridin-2-yl)-N-[6-(2-morpholine-4-iltiazem-5-yl)pyridin-2-yl]amine (compound A-417),

1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)alanon (compound A-419),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-sulfonamide (compound A-421),

N-(4-methoxypyridine-2-yl)-N-{6-[2-(morpholine-4-yl)thiazol-5-yl]pyridine-2-yl}amine (compound A-422),

(3R,4S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3,4-diol (compound A-423),

N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ndimethylacetamide (compound A-424),

N-[6-(4-methyl-2-morpholine-4-iltiazem-5-yl)pyridin-2-yl]-N-(4-methylpyridin-2-yl)amine (compound A-425),

N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine (compound A-426),

N-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxamide (compound A-427),

1-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-429),

N-{6-[2-(4-methoxypiperidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine (compound A-431),

N-{6-[2-(4-methylpiperazin-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine (compound A-432,

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ol (compound A-433),

N-methyl-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-436),

4-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carbaldehyde (compound A-437),

methyl ester of 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxylic acid (compound A-438),

2-hydroxy-1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)alanon (compound A-439),

1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)propane-1-on (compound a-440),

N,N-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxamide (compound A-441),

1-(4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)alanon (compound A-442),

1-(4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)alanon (compound A-443),

4-(methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid (compound A-444),

4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic (compound A-446),

3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)-4H-[1,2,4]oxadiazol-5-Oh (compound A-450),

N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridi the-2-yl]thiazol-2-yl}-N-piperidine-4-ylamine (compound A-452),

4-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carbonyl)

piperazine-2-on (compound a-453),

N-(2,2-dimethoxymethyl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine (compound A-457),

1-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon (compound A-458),

2-hydroxy-1-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon (compound A-459),

N-methyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-

carboxamide (compound A-460),

N-{2-[4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]-2-oxoethyl}ndimethylacetamide (compound A-461),

the dihydrochloride (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetic acid (compound A-464),

2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)ndimethylacetamide (compound A-465),

N-methyl-2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)ndimethylacetamide (compound A-466),

N-(2-hydroxyethyl)-2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)ndimethylacetamide (compound A-468),

N-methyl-N-methylcarbamoylmethyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-469),

N-methyl-N-{5-[6-(4-metile the one-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-tetrahydropyran-4-ylamine (compound A-470),

4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenol (compound A-471),

N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)ndimethylacetamide (compound A-472),

(R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ylamine (compound A-473),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid (compound A-474),

2-hydroxy-N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)ndimethylacetamide (compound A-475),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide (compound A-476),

N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide (compound A-477),

N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide (compound A-478),

(R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol (compound A-479),

TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanol (compound A-480),

N-{6-[2-(3-methoxypiperidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine (compound A-481),

2-hydroxy-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ndimethylacetamide (compound A-482),

2-hydroxy-N-methyl-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}PIP is ridin-4-yl)ndimethylacetamide (compound A-483),

N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)

methanesulfonamide (compound A-484),

N-methyl-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)

methanesulfonamide (compound A-485),

2-hydroxy-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ylmethyl)ndimethylacetamide (compound A-486),

N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ylmethyl)ndimethylacetamide (compound A-487),

the dihydrochloride of N-methyl-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-488),

N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)

methanesulfonamide (compound A-489),

N-{6-[2-((R)-3-ethoxypyrrolidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine (compound A-490),

N-methyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic (compound A-492),

N-(2-hydroxyethyl)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic (compound A-493),

N-(2-acetylamino)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarboxylic (compound A-494),

the dihydrochloride (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)

acetic acid (compound A-47),

(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)methanol (compound A-498),

2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)

the ndimethylacetamide (compound A-499),

4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-500),

N-methyl-4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-501),

N-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)

the ndimethylacetamide (compound A-502),

N-(2-hydroxyethyl)-4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-503),

2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ndimethylacetamide (compound A-504),

N-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ndimethylacetamide (compound A-505),

N-(2-hydroxyethyl)-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ndimethylacetamide (compound A-506),

N,N-diallyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine (compound A-507),

N-[2-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]ndimethylacetamide (compound A-508),

2-hydroxy-N-[2-(N'-methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]ndimethylacetamide (compound A-509),

N-(4-methanesulfonanilide the-1-yl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine (compound A-510),

N,N-dimethyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-

carboxamide (compound A-511),

(4-hydroxyphenyl)-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]metano (compound A-513),

1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylamino}piperidine-1-yl)alanon (compound A-514),

1-[4-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon (compound A-515),

N-methyl-2-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yloxy)ndimethylacetamide (compound A-516),

1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-517),

1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-518),

2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethanol (compound A-519),

N-(2-methoxyethyl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine (compound A-520),

N-[2-(N'-(1-acetylpiperidine-4-yl)-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]methanesulfonamide (compound A-524),

1-[4-(N-(2-hydroxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon (compound A-525),

1-[4-(N-(2-methoxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperid the n-1-yl]alanon (compound A-526),

(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-528),

N-methyl-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-529),

N-(2,2,2-triptorelin)-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-530),

(R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid (compound A-531),

((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)methanol (compound A-532),

(R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide (compound A-533),

1-[4-(N-ethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon (compound A-534),

1-{4-[N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2,2,2-triptorelin)amino]piperidine-1-yl}Etalon (compound A-535),

1-[4-(N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-methylamino)piperidine-1-yl]alanon (compound A-536),

1-[4-(N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-methylamino)piperidine-1-yl]-2-hydroxyethane (compound A-537),

(R)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol (compound A-538),

(R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol (compound A-539),

4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)the feast of the DIN-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (compound A-540),

(S)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-541),

(S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-542),

1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-543),

2-(N-(2-hydroxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethanol (compound A-544),

2-[N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2-hydroxyethyl)amino]ethanol (compound A-545),

(R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid (compound A-546),

1-(5-{6-[4-(1-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-

carboxamide (compound A-547),

(R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol (compound A-548),

1-(2-{6-[2-((R)-3-hydroxypyrrolidine-1-yl)thiazole-5-yl]pyridine-2-ylamino}pyridine-4-yl)alanon (compound A-549),

4-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)-4-oxomalonate acid (compound A-551),

N-hydroxy-(R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide (compound A-552),

4-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]-4-oxomalonate acid (compound A-553),

(R)-1-(5-{6-[4-(1-hydroxyethyl)the feast of the DIN-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol (compound A-554),

2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ndimethylacetamide (compound A-556),

(R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-3-

carboxylic acid (compound A-558),

(R)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid (compound A-560),

(S)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-561),

(1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)methanol (compound A-562),

1-[(R)-3-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pyrrolidin-1-yl]alanon (compound A-563),

the dihydrochloride (S)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxylic acid (compound A-564),

(R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-3-

carboxamide (compound A-565),

((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)acetic acid (compound A-567),

the dihydrochloride (S)-3-methyl-2-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]butyric acid (compound A-568),

the dihydrochloride of 3-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]

propionic acid (compound A-570),

the dihydrochloride [2-(N-methyl-N-{5[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]acetic acid (compound A-571),

the dihydrochloride [1-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]

acetic acid (compound A-572),

the dihydrochloride (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-573),

the dihydrochloride of 4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid (compound A-574),

the dihydrochloride ((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yloxy)acetic acid (compound A-575),

the dihydrochloride of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-carboxylic acid (compound A-576),

the dihydrochloride of (R)-1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol (compound A-577),

4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)benzoic acid (compound A-578),

(2S,4R)-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pyrrolidin-2-

carboxylic acid (compound A-579),

the dihydrochloride {N-methyl-N-[2-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetyl]amino}acetic acid (compound A-580),

2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid (compound A-582),

the dihydrochloride of 3-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-the l]thiazol-2-yl}amino)methyl]benzoic acid (compound A-586),

the dihydrochloride {4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenyl}acetic acid (compound A-587),

(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetic acid (compound A-588),

the dihydrochloride (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)acetic acid (compound A-589),

N-(4-methylpyridin-2-yl)-N-(6-{2-[(R)-3-(1H-tetrazol-5-yl)piperidine-1-yl]thiazol-5-yl}pyridine-2-yl)amine (compound A-590),

CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid (compound A-591),

TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid (compound A-592),

the dihydrochloride of 4-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid (compound A-593),

the dihydrochloride (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yloxy)acetic acid (compound A-594),

hydrochloride (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)acetic acid (compound A-595),

4-{[N-methyl-N-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)amino]methyl}

benzoic acid (compound A-596),

the dihydrochloride of 4-[(N-dimethylcarbamoyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-the l}amino)methyl]benzoic acid (compound A-597),

CIS-4-(N-carbamoylmethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid (compound A-598),

TRANS-4-[(N-carbamoylmethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid (compound A-599),

5-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]thiophene-2-

carboxylic acid (compound A-603),

the dihydrochloride of 3-chloro-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid (compound A-604),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}benzoic acid (compound A-605),

the dihydrochloride of 3-methoxy-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid (compound A-606),

2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (compound A-607),

2-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]thiazol-4-

carboxylic acid (compound A-609),

[TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid (compound A-610),

[CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid (compound A-611),

4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-the l]thiazol-2-yl}ethyl)cyclohexanecarbonyl acid (compound A-612),

the dihydrochloride (4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-613),

4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (compound A-614),

hydrochloride {5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}acetic acid (compound A-615),

the dihydrochloride of 4-[1-methyl-1-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid (compound A-616),

the dihydrochloride [4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)phenyl]acetic acid (compound A-617),

the dihydrochloride (1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-620),

TRANS-4-[(N-benzyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid (compound A-622),

[TRANS-4-(N-benzyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid (compound A-624),

TRANS-4-[(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid (compound A-626),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroquinolin-5-carboxylic acid (compound A-627),

fluoro-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]TIA the ol-2-yl}piperidine-4-ilidene)acetic acid (compound A-631),

5-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane acid (compound A-632),

N-[2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetyl]

methanesulfonamide (compound A-633),

the dihydrochloride of 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)butyric acid (compound A-634),

the dihydrochloride (1-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)

acetic acid (compound A-635),

the dihydrochloride (1-{5-[6-(5-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-636),

the dihydrochloride (1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-637),

TRANS-4-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)

cyclohexanecarbonyl acid (compound A-638),

3-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)phenyl]propionic acid (compound A-639),

the dihydrochloride (E)-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ene acid (compound A-640),

(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-6-yl)acetic acid (compound A-641),

3-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-5-yl)about the IP acid (compound A-642),

5-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane acid (compound A-643),

5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylamino}pentane acid (compound A-644),

the dihydrochloride 6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)hexanoic acid (compound A-645),

the dihydrochloride of (Z)-2-fluoro-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ene acid (compound A-647),

(8-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-8-azabicyclo[3.2.1]Oct-3-yl)acetic acid (compound A-648),

(8-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-8-azabicyclo[3.2.1]Oct-3-yl)acetic acid (compound A-649),

the dihydrochloride (1-{5-[6-(4-cyano-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-650),

{4-[(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenyl}

acetic acid (compound A-651),

2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-652),

(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-653),

4-[1-methyl-1-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid (compound A-654),

the dihydrochloride of 3-m is Teal-6-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ene acid (compound A-655),

the dihydrochloride of 3-methyl-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ene acid (compound A-656),

the dihydrochloride (E)-6-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ene acid (compound A-657),

N-(2-hydroxyethyl)-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide (compound A-658),

2-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ndimethylacetamide (compound A-663),

3-methyl-2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)butyramide (compound A-668),

2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ethanol (compound A-677),

5-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane-1-ol (compound A-678),

(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-680),

the dihydrochloride [1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]

acetic acid (compound A-681),

fluoro-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-684),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-carboxamide (compound A-685),

the dihydrochloride (1-{5-[6-(4-ethylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-and the)acetic acid (compound A-692),

N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine (compound A-693),

N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2-morpholine-4-retil)amine (compound A-695),

2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)ndimethylacetamide (compound A-697),

2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)butyric acid (compound A-698),

the dihydrochloride, TRANS-4-[(N-methyl-N-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarboxylic acid (compound A-699),

the dihydrochloride [1-(5-{6-[4-(2,2,2-triptoreline)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]

acetic acid (compound A-700),

2-methyl-1-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)propan-2-ol (compound A-702),

3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)propionic acid (compound A-704),

N-(2-hydroxyethyl)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-

carboxamide (compound A-705),

the dihydrochloride of 2-methyl-2-(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-707),

4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)methyl]benzoic acid (compound A-709),

the dihydrochloride (1-{5-[6-(4-tert-butalbiral is n-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-710),

the dihydrochloride (1-{5-[6-(4-isopropylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-711),

6-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-6-azaspiro[2.5]octane-1-carboxylic acid (compound A-712),

2-[1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]-2-methylpropionate acid (compound A-713),

2-methyl-2-(1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-714),

the dihydrochloride fluoro-(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-715),

the dihydrochloride fluoro-(1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-716),

the dihydrochloride [1-(5-{6-[4-(1-hydroxy-1-methylethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-

yl]acetic acid (compound A-717),

the dihydrochloride of 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-718),

the dihydrochloride of 5-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)pentanol acid (compound A-719),

2-methyl-2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)propionamide (compound A-720),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon (compound B-1),

5-[6-(4-metier the DIN-2-ylamino)pyridine-2-yl]thiophene-2-carbaldehyde (compound B-2),

1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanol (compound B-3),

ethyl ester of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}acetic acid (compound B-4),

N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ndimethylacetamide (compound B-10),

N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamide (compound B-11),

{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}methanol (compound B-12),

the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone (compound B-15),

1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon (compound B-17),

5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamide (compound B-23),

1-{5-[6-(6-isopropoxypyridine-4-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon (compound B-30),

N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ndimethylacetamide (compound B-31),

O-(2-hydroxyethyl)oxime 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone (compound B-38),

N-(2-amino-ethyl)-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamide (compound B-43),

the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}propane-1-she (compound B-51),

ethyl ether {2-[6-(5-acetylthiophene-2-yl)pyridine-2-ylamino]pyridine-4-yl}acetic acid (compound B-52),

methyl ester 2-[6-(5-acetylthiophene-2-yl)pyridine-2-ylamino]isonicotinic is islote (compound B-53),

1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)ethanol (compound B-55),

N-hydroxy-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxyamide (compound B-60),

1-(5-{6-[4-(2-hydroxyethoxy)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)alanon (compound B-73),

1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon (compound B-74),

the oxime of 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone (compound B-75),

{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}piperazine-1-ylmethanone (compound B-84),

1-(5-{6-[4-(4,4-dimethyl-4,5-dihydrooxazolo-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)

Etalon (compound B-87),

2.2-debtor-3-hydroxy-3-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}propionic acid (compound B-109),

4-[({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid (compound B-116),

4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid (compound B-119),

TRANS-4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]

cyclohexanecarbonyl acid (compound B-120),

hydrochloride 3-(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)propional acid (compound B-124),

4-[(N-isobutyryl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-althofen-2-ylmethyl}amino)methyl]benzoic acid (compound B-127)

4-[(N-(2-hydroxyacyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid (compound B-128).

As for the salts of the compounds represented by formula (I), preferred are pharmaceutically acceptable salts, and examples include a salt with inorganic base, a salt with organic base, salt with inorganic acid, salt with organic acid, salt with basic or acidic amino acid, etc.

Preferred examples of the salt with inorganic base include, for example, a salt with an alkaline metal such as sodium, potassium, salts with alkaline earth metal such as calcium, magnesium, as well as salts with aluminum, ammonium, etc.

Preferred examples of the salt with organic base include, for example, salts with trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, N,N-dibenziletilendiaminom etc.

Preferred examples of the salt with inorganic acid include, for example, salts with hydrochloric acid, Hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.

Preferred examples of the salt with organic acid include, for example, salts with formic acid, acetic acid, triperoxonane acid, fumaric acid, is avaliou acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzosulfimide acid, p-toluensulfonate acid, etc.

Preferred examples of salts with basic amino acid include, for example, salts with arginine, lysine, ornithine, and preferred examples of salts with acidic amino acid include, for example, salts with aspartic acid, glutamic acid, etc.

The compound of the present invention has excellent Syk inhibitory effect and is useful as a therapeutic agent for the treatment of allergic diseases or therapeutic agent for autoimmune diseases.

When the compound of the present invention is used as a drug for the treatment of allergic diseases, especially medicines for the treatment of asthma, medications for the treatment of allergic rhinitis, drugs for treatment of allergic dermatitis and medicines for the treatment of allergic conjunctivitis or medicines for the treatment of autoimmune diseases, medicines for the treatment of progressive deforming arthritis medicines for the treatment of systemic lupus erythematosus, lekarstvennoj the tools for the treatment of multiple sclerosis, medicines for the treatment of malignant tumors, drugs for the treatment of B-cell lymphoma, b-cell leukemia; typically, it is introduced systemically or locally, oral or parenteral.

More preferably the compound (I) of the present invention or its salt can be combined with a pharmaceutically acceptable carrier and administered orally or parenterally in the form of a solid preparation such as tablet, capsule, granule and powder; or a liquid preparation such as syrup and injection.

The introduction can be carried out in any form for oral administration in the form of tablets, pills, capsules, granules, powder, liquid, etc. or through parenteral administration by injection, such as intravenous infusion, intramuscular injection, suppository or percutaneous drug. Parenteral administration includes intravenous, intramuscular, subcutaneous administration, introduction to tissue, intranasal, intradermal injection, drip infusion, intracerebrally, rectal, vaginal, intra-abdominal, intraperitoneal etc.

As solid compositions for oral administration in accordance with the present invention using a tablet, powder, granule, etc. In such a solid composition is mixed with one or more active substances, with at least one inert solvent, for example, lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, aluminometasilicate magnesium, etc. the Composition may include additives in addition to the inert solvent, for example a lubricant such as magnesium stearate, disintegrity agent, such as calcium carboxymethylcellulose, a stabilizer such as lactose, solubilizers agent such as glutamic acid or aspartic acid in accordance with the traditional way. Tablet or pill may be coated, as required, the shell of sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, phthalate of hydroxypropylmethylcellulose, macrocell, titanium dioxide, talc or glucocortoids or enteric film.

Liquid composition for oral administration includes pharmaceutically acceptable emulsions, liquid preparation, suspension, syrup and elixir and may include traditionally used inert solvent, such as purified water and ethanol. These compositions may include auxiliary agents such as solubilizers agent, moisturizer, suspendisse agent, a sweetener, a neutralizer, flavoring and preservative in addition to the inert solvent.

The injection for parenteral administration may bitopology by dissolving, the suspension or emulgirovanija predetermined amount of the active agent in aqueous solution (for example, distilled water for injection, saline solution, ringer's solution etc) or oil solvent (e.g., vegetable oil such as olive oil, sesame oil, cottonseed oil, corn oil, propylene glycol, etc. together with a dispersing agent (e.g., Polysorbate 80, polyoxyethylene hydrogenomonas castor oil 60, polyethylene glycol, carboxymethylcellulose, sodium alginate, etc.), a preservative (e.g. methylparaben, propylparaben, benzyl alcohol, chlorobutanol, phenol and so on), isotonic agent (for example, sodium chloride, glycerin, D-mannitol, D-sorbitol, glucose etc) and so on

This can be optionally used additives such as a solubilizer (e.g., sodium salicylate, sodium acetate, etc.), a stabilizer (e.g., human serum albumin, etc.) and emollient (e.g., benzyl alcohol etc).

In addition, if necessary, may include a preservative, antioxidant, colorant, flavor, sweetener, absorbent, hydrating agent and other additives.

As the pharmaceutically acceptable carrier can be mentioned various organic or inorganic excipients, is commonly used as pharmaceutical products. If necessary, in accordance with the traditional way can be used in the filler, lubricant, binder, disintegrity agent, which is respectively added to the solid mixture and the solvent, solubilizer, suspendisse agent, isotonic agent, buffer, soothing agent, which respectively add to the liquid drug. In addition, can be used pharmaceutical additives such as preservative, antioxidant, colorant, sweetener, absorbent, hydrating agent, etc.

Preferred examples of the filler include lactose, corn starch, sucrose, D-mannitol, D-sorbitol, starch, dextrin, crystalline cellulose, nitrosamino hydroxypropylcellulose, sodium carboxymethylcellulose, gum Arabic, glucose, silicon dioxide, etc.

Preferred examples of the antioxidant include, for example, sulfite salt, ascorbic acid, etc.

Preferred examples dezintegriruetsja agent include, for example, carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethyl-starch sodium, croscarmellose sodium, crosspovidone, nitrosamino hydroxypropylcellulose, hydroxypropylmethyl etc.

Preferred examples of the binders include, for example, hydroxypropylcellulose, hypromellose polyvinylpyrrolidone, crystalline cellulose, sucrose, powdered gum Arabic, etc. Preferred binder is hydroxypropylcellulose or polyvinylpyrrolidone. Polyvinylpyrrolidone is preferred, in particular, when the active ingredient used in the present invention, is Metformin hydrochloride.

Preferred examples of the lubricant include, for example, magnesium stearate, calcium stearate, talc, colloidal silica, etc.

Preferred examples of the isotonic agent include, for example, glucose, D-sorbitol, sodium chloride, glycerin, D-mannitol, etc.

Preferred examples of the pH regulating agent include, for example, citrate, phosphate, carbonate, tartrate, fumarate, acetate, salt, amino acids, etc.

Preferred examples of the solubilizer include, for example, polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, Tris-aminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, etc.

As a preferred example of the solvent, for example, may be used a solvent for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, olive oil, etc.

As a preferred example of a suspending agent such as surfactant, such as stearyl triethanolamine, sodium lauryl sulfate, l is arylaminopoly acid, commercial lecithin, benzalkonium chloride, chloride benzathine, glycerylmonostearate; hydrophilic macromolecule such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, for example, can serve as an example.

Preferred examples of mitigating measures include, for example, benzyl alcohol, etc.

Preferred examples of the buffer include buffers such as phosphate, acetate, carbonate, citrate, etc.

Preferred examples of the preservative include, for example, esters of p-oksibenzoynoy acid, chlorbutanol, benzyl alcohol, finitely alcohol, along with dehydroacetic acid, sorbic acid, etc.

The dose of a compound of the present invention varies depending on subject of administration, route of administration, disease, General condition etc, but when, for example, the specified dose refers to oral introduction to the adult patient allergies (about 60 kg), a single dose is generally from about 0.005-50 mg/kg body weight, preferably from 0.01 to 5 mg/kg body weight per dose, and more preferably the dose is from 0.025 to 2 mg/kg of body weight; preferably, this amount was administered once or several times a day.

In the case of oral introduction the usual suitable daily dose is from about 0.01 mg/kg to 10 g/kg of body weight, preferably from 0.1 mg/kg to 1 g/kg and the dose is administered once or separately 2-4 times a day. When the dose is injected intravenously, daily dose, respectively, ranges from about 0.01 mg/kg to 1 g/kg of body weight, and it is administered once or separately several times a day. Dose, respectively, determined in each case based on the status, age, sex etc

Pharmaceutical composition, a Syk inhibitor, a drug for treatment of allergic diseases, a drug for the treatment of bronchial asthma, drug for the treatment of allergic rhinitis, drug for treatment of allergic dermatitis, drug for treatment of allergic conjunctivitis, drug for the treatment of autoimmune diseases, a drug for the treatment of rheumatoid arthritis, the drug for the treatment of systemic lupus erythematosus, a drug for the treatment of multiple sclerosis, a drug for the treatment of malignant tumors, the drug for the treatment of B-cell lymphoma, b-cell leukemia containing the compound represented by the General formula (I) the present invention may be used in conjunction with other anti-allergic therapeutic and/or prophylactic agent.

In this case, in addition to the single tool of the present invention and another anti-allergic drug can be produced in the form of a combined preparation or separate pharmaceutical preparations respectively, containing a suitable quantity of each dose or, if necessary, can be set. When they are produced in the form of separate pharmaceutical drugs, each drug can be introduced at the same time or introduced with an interval of time.

As antiallergic drugs known inhibitor of the release of chemical mediators, the antagonist of histamine, an inhibitor of the synthesis of thromboxane, an inhibitor of TH2 cytokine, a leukotriene antagonist, etc. but antiallergic drug, which can be used in combination with a medicinal product according to the present invention is not limited to specific choices and can be used in appropriate combination. For example, as an inhibitor of the release of chemical mediators can be used cromoglycate sodium fumarate of emedastine, suplatast tosilate, hydrochloride of epinastine etc. as an antagonist of histamine can be used fumarate of clemastine, d-chlorpheniramine, hydrochloride ciprogeptadina, hydrochloride prometazina, hydrochloride homochlorcyclizine, mequitazine, diphenhydramine hydrochloride, Bastin, cetirizine hydrochloride, the hydrochloride of olopatadine, hydrochloride of Fexofenadine etc., as an inhibitor of the synthesis of thromboxane can be used hydrochlo the ID of ozagrel, etc., as a leukotriene antagonist may be used to hydrate pranlukast, zafirlukast, etc.

Further, in particular, describes a method of obtaining a compound represented by the General formula (I) according to the present invention. However, the present invention may not be limited in this way. Obtaining the compounds of the present invention can be appropriately executed in parts, which is easy to implement. In addition, when there is reaktsionnosposobnykh functional group, securing or removing protection can be suitably carried out at each stage, and accordingly can be used reagent other than illustrated reagents to promote the reaction.

Any connection that is received at each of the stages can be isolated and purified in the traditional way, but the connection may not necessarily be introduced into the reaction in the next stage without isolation and purification.

As the method of isolation and purification, when they are made the traditional way, such as distillation, crystallization, recrystallization, chromatography on a column of silica gel, thin layer chromatography, preparative HPLC, can be selected or implemented in combination.

When it is desired compound, in which R7represents nuclei the local Deputy, it can be obtained using the following method of obtaining.

The connection is obtained in example 1 (method presented in scheme 1)

(where X represents a leaving group such as halogen atom, and R7' represents a nucleophilic Deputy from among R7and each different symbol represents the value specified above).

Stage 1

The compound (3) obtained by the fact that the compound (2) is subjected to galogenirovannyie using a halogenation agent such as thionyl chloride, oxalicacid in a solvent such as dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, acetonitrile, toluene or subjected to reaction using cleavage of the leaving group with a reagent such as methanesulfonate, p-toluensulfonate, trifloromethyl the sulfonic acid anhydride in the presence of a base, such as triethylamine, N,N-diisopropylethylamine and pyridine.

Stage 2

The compound (5) obtained by conversion of the compound (4) thiourea, using 9-fluorenylmethoxycarbonyl, piperidine in a solvent such as ethanol, isopropanol, ethyl acetate, tetrahydrofuran, N,N-dimethylformamide, dimethylsulfoxide, chloroform, acetonitrile, dimethyl ether of ethylene glycol, 1,4-dioxane, followed by interaction with connect ().

Stage 3

Connection (6) receive, subjecting the reaction of the compound (5) in acetic anhydride as solvent, in the presence of formic acid or reaction, using dimethylacetal N,N-dimethylformamide, diethylacetal N,N-dimethylformamide, etc. in a solvent such as methanol, ethanol, isopropanol, tetrahydrofuran, acetonitrile, toluene in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine.

Stage 4

The connection represented by the General formula [I-2], obtained by interaction of the compound (6)obtained in stage 3, with the compound (8) in a solvent such as toluene, benzene, 1,4-dioxane, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, dimethyl ether of ethylene glycol, 1-methyl-2-pyrrolidinone, N,N-dimethylformamide, N,N-dimethylacetamide in the presence of a base, such as 2,2'-bis(diphenylphosphino)-1,1-binaphthyl, palladium acetate and cesium carbonate, potassium carbonate, potassium phosphate.

Getting connection example 2 (method presented in scheme 2)

(Each symbol in the diagram represents respectively the value specified above)

Stage 5

The compound (10) obtained by interaction of the acid chloride of nicotinic acid (8) and a derivative of malonic acid (9) in a solvent such as acetonitrile, is tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide in the presence of magnesium chloride and a base such as triethylamine, N,N-diisopropylethylamine, following the procedure described in Organic Letters, 5 (18), 3233-3236, (2003), and then by decarboxylation and removing the protecting tert-butoxycarbonyl group, using a combination of concentrated hydrochloric acid.

Stage 6

The compound (12) obtained by interaction of the compound (10) with compound (11) in a solvent such as acetonitrile, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride. In this reaction can be used bases, such as pyridine, triethylamine, N,N-diisopropylethylamine depending on methodology. When the compound (11) is a compound of carboxylic acid, the compound (12) can be obtained by conducting a reaction using a condensing agent, such as dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, diisopropylcarbodiimide, diphenylphosphoryl, 2-ethoxy-1-etoxycarbonyl-1,2-dihydroquinoline (EEDQ).

Stage 7

The compound (13) are obtained by reacting the compound (12)using the reagent of Lawesson (Lawesson) in a solvent such as tetrahydrofuran, 1,4-dioxane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride. The connection represented by the General formula [I], receive by executing then process according to methodology described above stage 4.

Getting connection example 3 (method presented in scheme 3)

Stage 8

The compound (15) can be obtained by reacting compound (7) and compound (14) in accordance with the method presented in stage 4.

Stage 9

The compound [I] can be obtained by reacting compound (15) with compound (16) in a solvent such as dimethoxyethane, diethyl ether, acetone, butanone, dioxane, tetrahydrofuran in the presence of tetrakis(triphenylphosphine)palladium and a base such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate.

When the compound [I]with "-CONH-bond in the substituent R7is desired, the desired compound [I]with "-CONH-relationship can be obtained by introducing a connection with "-COOH group, and compounds having the "-NH2group" in the amidation reaction.

In addition, when the compound [I]with "-N(-(substituted)C1-6alkyl)-" in the substituent R7is desirable, can be made known alkylation reaction using a compound having a group-NH-".

When the compound [I]having a group-CH(OH)-" in the substituent R7is desirable, may be to implement the well-known reaction of a Grignard reagent containing the group-CHO" connection.

When an acid additive salt or basic additive salt compounds represented by the General formula [I]is desirable, there may be used a well-known method. For example, the compound represented by the General formula [I], dissolved in water, methanol, ethanol, n-propanol, isopropanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, ethyl acetate, dichloromethane, 1,2-dichloroethane or chloroform or a mixed solvent, and then add the solvent mentioned above, which dissolves the desired acid or base, and loose precipitated crystal can be separated by filtration or concentration under reduced pressure.

When the compound represented by the General formula [I], or an intermediate compound is a racemate and required optically active substance, it can be divided well-known manner. As regards the manner of separation, the method may be appropriately selected or implemented in combination with the traditional way, such as separation by crystallization of salts using an optically active 1-phenethylamine, optically active alkaloid, optically active camphorsulfonic acid, optically active tartaric acid and their derivatives, recrystallization, chiral chromatography on a column, chiral preparative HLC.

The compound obtained according to the invention can be separated and purified, if necessary, by conventional means, such as recrystallization, re-planting or in the traditional way, usually used for separation and purification of organic compounds, for example, a method using a synthetic absorbent agent, such as adsorption chromatography on a column distribution chromatography on a column method using ion-exchange chromatography, the way in which respectively combine methods chromatography on a column using normal phase, reversed phase silica gel or alkilirovannami silica gel and elution is carried out using a suitable eluent.

The connection represented by the General formula [I] of the present invention, and the method of its production in more detail using the following examples. It is understood that the present invention is not limited to these examples.

Example 1

Obtain 1-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-2-she (compound A-1):

Stage 1. Obtain 2-bromo-6-chloromethylpyridine

2-Bromo-6-hydroxymethyluracil (of 5.00 g, 25.5 mmol) was dissolved in chloroform (30 ml) and added dropwise thionyl chloride (2.8 ml, to 38.3 mmol who), the mixture is then stirred at room temperature for 3 hours. After that, the reaction solution is concentrated and to the precipitate add saturated aqueous solution of sodium bicarbonate and the precipitate was separated by filtration. Then washed with water, carry out the drying in a vacuum and get listed in the title compound (5.20 g, 99%).

Stage 2. Getting amide 3-oxopiperidin-1-karbaminovoi acid

Piperazine-2-he (1,43 g of 14.3 mmol) dissolved in chloroform (30 ml) and add isothiocyanate 9-fluorenylmethoxycarbonyl (as 4.02 g of 14.3 mmol)and the mixture is then stirred at room temperature for 2 hours. After that, the reaction solution is concentrated and to the residue is added diethyl ether and the precipitate was separated by filtration. The precipitate is dissolved in N,N-dimethylformamide (10 ml), added piperidine (10 ml) and the mixture is stirred at room temperature for 6 hours. After this reaction solution was concentrated again to the residue add diethyl ether and the precipitate was separated by filtration and after drying in a vacuum get mentioned in the title compound (2,22 g, 98%).

Stage 3. Getting 6-bromopyridin-2-Eletropaulo ester 3-oxopiperidin-1-carboxamidine acid

2-Bromo-6-chloromethylpyridine (1.50 g, 7,26 mmol), polucen is th at stage 1, dissolved in ethanol (15 ml) and add amide 3-oxopiperidin-1-karbaminovoi acid (1,16 g, 7,29 mmol), obtained in stage 2, and the mixture is heated to boiling point for 2 hours. After that, the reaction solution is cooled to room temperature, the solution obtained by concentration in vacuo, neutralized with saturated aqueous sodium hydrogen carbonate solution and precipitated precipitated solid is separated by filtration, washed with water and get listed in the title compound (1,67 g, 70%).

Stage 4. Getting 4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperazine-2-it

Formic acid (5 ml) and acetic anhydride (10 ml) are added to 6-bromopyridin-2-ylmethylamino ether, 3-oxopiperidin-1-carboxamidine acid, obtained in stage 3 (1,67 g, 5.08 mmol), the mixture is stirred at room temperature for 12 hours. The crystals precipitated in the sediment at a concentration in vacuo of the reaction solution is separated by filtration, washed with water to give specified in the header of the connection (of 1.37 g, 80%).

1H-NMR (400 MHz, DMSO-d6) δ: by 8.22 (1H, usher.), 8,01 (1H, s), 7,83 (1H, d, J=7.8 Hz), 7,69 (1H, t, J=7.8 Hz), 7,38 (1H, d, J=7.8 Hz), Android 4.04 (2H, s), of 3.73-3,68 (2H, m), 3,38-to 3.34 (2H, m).

Stage 5. Getting 4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]-1-methylpiperazin-2-it

4-[5-(6-Bromopyridin-yl)thiazol-2-yl]piperazine-2-it, obtained in stage 4 (200 mg, 0.59 mmol) dissolved in tetrahydrofuran (2 ml) and N,N-dimethylformamide (2 ml) and add sodium hydride (60% in oil, 26 mg, of 0.65 mmol), add methyliodide (39 μl, of 0.62 mmol) and the mixture is stirred over night at room temperature. To the reaction solution was added water and the residue obtained by concentration in vacuo, extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over sodium sulfate and concentrated in vacuo, get mentioned in the title compound (188 mg, 90%).

Stage 6. Obtain 1-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-2-it

4-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]-1-methylpiperazin-2-he received at stage 5 (188 mg, of 0.53 mmol), dissolved in toluene (5 ml) and then added 2-amino-4-methylpyridin (58 mg, of 0.53 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (66 mg, 0.11 mmol), palladium acetate (18 mg, 0.08 mmol) and cesium carbonate (260 mg, 0.80 mmol) and the mixture is stirred overnight at a temperature of 100°C. To the reaction solution was added water and extracted with ethyl acetate and the organic layer was washed with saturated saline solution. The organic layer is dried over sodium sulfate and, after concentration in vacuo the residue is washed with methanol, get mentioned in the title compound (77 mg, 38%.

1H-NMR (400 MHz, DMSO-d6) δ: of 8.09 (1H, d, J=4,8 Hz), 7,92 (1H, usher.), 7,89 (1H, s), 7,60 (1H, DD, J=8,4, a 7.6 Hz), 7,26 (1H, d, J=8,4 Hz), 7,26 (1H, d, J=7,6 Hz), to 6.75 (1H, userd, J=4,8 Hz), 4,07 (2H, s), 3,80-of 3.77 (2H, m), 3,52-3,50 (2H, m), of 2.92 (3H, s), of 2.34 (3H, s).

Example 2

Obtain 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (compound A-2):

(1) obtaining the ethyl ester of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid:

Stage 1. Obtaining the ethyl ester of 1-thiocarbamoylation-4-carboxylic acid

9-Fluorenylmethoxycarbonyl (5,90 g, 21,0 mmol) dissolved in chloroform (20 ml), then add a solution of ethyl ether piperidine-4-carboxylic acid (3,30 g, 21,0 mmol) in chloroform (10 ml) and the mixture is stirred at room temperature for 1 hour. The reaction solution was concentrated in vacuo and the residue obtained by adding diethyl ether, separated by filtration. The resulting substance was dissolved in N,N-dimethylformamide (20 ml) and added piperidine (20 ml) and the mixture is stirred at room temperature for 1 hour. After that, the reaction solution is washed with ethyl acetate and the organic layer was washed with saturated saline solution and dried over sodium sulfate, the residue obtained by concentration under vacuum, PTS who participate chromatography on silica gel (mixture of n-hexane:ethyl acetate) and get listed in the title compound (4,34 g, 100%).

Stage 2. Obtaining the ethyl ester of 1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-carboxylic acid

2-Bromo-6-chloromethylpyridine, obtained in stage 1 of example 1 (2,90 g, 14.0 mmol), dissolved in ethanol (30 ml) and add ethyl ester 1-thiocarbamoylation-4-carboxylic acid (3.00 g, a 13.9 mmol), obtained in stage 1, the mixture is heated to boiling point for 2 hours. The reaction solution is cooled to room temperature, add dimethylacetal of dimethylformamide (2.8 ml, 21.1 mmol) and triethylamine (5,9 ml of 42.3 mmol) and the mixture is again heated to the boiling temperature for 1 hour. After concentration, water is added and the reaction solution is extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over magnesium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 50:50 to 0:100) and receive specified in the header of the connection (of 3.60 g, 65%).

1H-NMR (400 MHz, DMSO-d6) δ: a 7.92 (1H, s), to 7.77 (1H, d, J=7.8 Hz), to 7.64 (1H, t, J=7.8 Hz), 7,32 (1H, d, J=7.8 Hz), of 4.05 (2H, q, J=7.2 Hz), 3,94-of 3.85 (2H, m), 3,22-of 3.12 (2H, m), 2,67-to 2.57 (2H, m), 1,94 is 1.86 (1H, m), 1,65-of 1.53 (2H, m)of 1.16 (3H, t, J=7.2 Hz).

Stage 3. Obtain ethyl 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylate

rac-2,2'-the IP(diphenylphosphino)-1,1'-binaphthyl (434 mg, 0.70 mmol) and palladium acetate (117 mg, 0.52 mmol) dissolved in toluene (15 ml), then successively added 2-amino-4-picoline (395 mg, 3.65 mmol) and a solution of ethyl 1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-carboxylate in toluene (15 ml), obtained in stage 2 (1,38 g of 3.48 mmol), then added cesium carbonate (1.70 g, with 5.22 mmol) and the mixture is stirred at a temperature of 100°C during the night. To the reaction solution was added water, extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over anhydrous sodium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:1 to 1:10) and get the specified header connection (817 mg, 55%).

1H-NMR (400 MHz, DMSO-d6) δ: at 9.53 (1H, s), 8,08 (1H, d, J=5,2 Hz), 7,92 (1H, s), 7,83 (1H, s), 7,58 (1H, DD, J=8.0 a, a 7.6 Hz), 7.23 percent (2H, DD, J=a 9.6 and 7.6 Hz), 6.75 in-6,74 (1H, m), 4.09 to (2H, q, J=6.9 Hz), 3,94-a 3.87 (2H, m), 3,24-3,164 (2H, m), 2,69-2,61 (1H, m), of 2.33 (3H, s), 1,99-of 1.93 (2H, m), 1,71 is 1.60 (2H, m)of 1.20 (3H, t, J=7.2 Hz).

(2) Obtain 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (compound A-2):

Ethyl 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylate obtained in above (1), (817 mg, of 1.93 mmol), dissolved in a mixed solvent of tetrahydrofuran (4 ml), methanol (4 ml) and the ode (2 ml), add the monohydrate of lithium hydroxide (202 mg, to 4.81 mmol) and the mixture is then stirred at 50°C for 5 hours. The concentrate obtained by concentration in vacuo, neutralized with 0,1N. hydrochloric acid, precipitated precipitated solid is separated by filtration, washed with water and get listed in the title compound (721 mg).

1H-NMR (400 MHz, DMSO-d6) δ: 12,34 (1H, users), at 9.53 (1H, s), 8,08 (1H, d, J=5,2 Hz), 7,92 (1H, s), 7,83 (1H, s), 7,58 (1H, DD, J=4,0, 8.0 Hz), 7.23 percent (2H, DD, J=11,6, 8.0 Hz), 6.75 in-of 6.73 (1H, m), 3,92-3,86 (2H, m), 3,23 is 3.15 (2H, m), 2,58-2,52 (1H, m), of 2.33 (3H, s), 1,99-1,90 (2H, m), 1,69 is 1.58 (2H, m).

MC: 396,2 (M++1).

Example 3

Obtain 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-3):

1-{5-[6-(4-Methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (100 mg, 0.25 mmol)obtained in example 2 was dissolved in N,N-dimethylformamide (2 ml) and add hexaphosphate benzothiazolylsulfenamide (263 mg, 0.50 mmol), diisopropylethylamine (of 0.18 ml of 1.03 mmol) and ammonium chloride (41 mg, 0.77 mmol), after which the mixture was stirred at room temperature for 1 hours. To the reaction solution was added saturated aqueous sodium hydrogen carbonate solution and precipitated precipitated solid is separated by filtration, washed with water, and get asanee the title compound (89 mg, 89%).

1H-NMR (400 MHz, DMSO-d6) δ: at 9.53 (1H, s), 8,08 (1H, d, J=5,2 Hz), to 7.93 (1H, s), 7,83 (1H, s), 7,58 (1H, t, J=8.0 Hz), 7,32 (1H, users), of 7.23 (2H, t, J=8.0 Hz), 6,83 (1H, users), 6,74 (1H, d, J=5,2 Hz), 3,99-to 3.92 (2H, m), 3,17-is 3.08 (2H,, m), 2,43-of 2.34 (1H, m), of 2.33 (3H, s), 1,86-of 1.78 (2H, m), 1,67-of 1.57 (2H, m).

MC: 395,2 (M++1).

Example 4

Obtaining N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)methyl-1-pyridin-2-yl]thiazol-2-yl}piperidine-4-

carboxamide (compound A-4):

1-{5-[6-(4-Methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (200 mg, 0.51 mmol)obtained in example 2 was dissolved in N,N-dimethylformamide (5 ml), added methylamine hydrochloride (68 mg, 1.00 mmol), hexaflurophosphate benzothiazolylsulfenamide (520 mg, 1.00 mmol) and triethylamine (0.28 in ml, a 2.01 mmol) and the mixture is stirred over night at room temperature. To the reaction solution was added water and the precipitated precipitated solid is separated by filtration, it is washed with water and get listed in the title compound (160 mg, 78%).

1H-NMR (400 MHz, DMSO-d6) δ: at 9.53 (1H, s), 8,08 (1H, d, J=5,1 Hz), to 7.93 (1H, s), 7,82 (1H, s), 7,79 (1H, q, J=4.5 Hz), 7,58 (1H, t, J=8.0 Hz), 7.23 percent (2H, t, J=8.0 Hz), 6,74 (1H, d, J=5,1 Hz), 4,01-to 3.92 (2H, m), 3,18-of 3.07 (2H, m,), to 2.57 (3H, d, J=4.5 Hz), 2,44 to 2.35 (1H, m), 2,32 (3H, s), 1,83 is 1.75 (2H, m), 1.70 to of 1.57 (2H, m).

MC: 409,2 (M++1).

Example 5

Obtaining N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)PI is one-2-yl]thiazol-2-yl}piperidine-4-carboxamide (compound A-5) :

Receive in accordance with methods analogous to the methods for obtaining compounds according to example 4, using 2-hydroxyethylamine (61 mg, 1.00 mmol) instead of methylamine hydrochloride, is indicated in the title compound (70 mg, 32%) was obtained from 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid (200 mg, 0.50 mmol)obtained in example 2.

1H-NMR (400 MHz, DMSO-d6) δ: at 9.53 (1H, s), 8,08 (1H, d, J=5,1 Hz), to 7.93 (1H, s), 7,82-7,86 (2H, m), 7,58 (1H, t, J=8.0 Hz), 7.23 percent (2H, t, J=8.0 Hz), 6,74 (1H, d, J=5,1 Hz), with 4.64 (1H, t, J=5.7 Hz), 4,01-to 3.92 (2H, m), 3.43 points-to 3.35 (2H,, m), 3,16-of 3.06 (4H, m), 2,47-of 2.38 (1H, m), of 2.33 (3H, s), 1,83 is 1.58 (4H, m).

MC: 439,2 (M++1).

Example 6

Obtain methyl ester of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid (compound A-6):

Stage 1. Obtain hydrochloride of 2-amino-1-(6-bromopyridin-2-yl)ethanone

Magnesium chloride (21,30 g, 224 mmol) and triethylamine (62 ml, 446 mmol) are successively added to the suspension in acetonitrile (300 ml) of monoethylene ether 2-tert-butoxycarbonylmethylene acid (50,30 g, 203 mmol) in an atmosphere of AG under ice cooling and the mixture is stirred for 1 hour. Then add dropwise a solution of 6-bromopyridin-2-carbonylchloride (37,40 g, 170 mmol) in acetonitrile (150 ml) at the same temperature for 3 hours and the mixture is PE is amerivault for 1 hour. After this reaction solution was concentrated, added ethyl acetate (300 ml) and the insolubles filtered off. The filtrate is washed with 10% aqueous citric acid solution, saturated saline solution and dried over magnesium sulfate and after concentration in vacuo get oily substance. Concentrated hydrochloric acid (200 ml) are added to a solution of the obtained oily substance in ethanol (200 ml) and heated to boiling point for 6 hours. Then concentrated to dryness under reduced pressure, the reaction solution was washed with a mixed solvent of ethanol-isopropyl ether (1:3), separated by filtration, dried in vacuum and get listed in the title compound (25,40 g, 50%).

1H-NMR (400 MHz, DMSO-d6) δ: 8,42-8,31 (3H, m), 8,16 (1H, t, J=7.8 Hz), 8,07 (1H, DD, J=7,8, 1.2 Hz), 7,92 (1H, DD, J=7,8, 1.2 Hz), 4,58 (2H, users).

Stage 2. Obtain methyl ester of TRANS-4-[2-(6-bromopyridin-2-yl)-2-oxoethylidene]cyclohexanecarbonyl acid

To a suspension of the hydrochloride of 2-amino-1-(6-bromopyridin-2-yl)ethanone (10,00 g, 39.8 mmol) in acetonitrile (200 ml), obtained in stage 1, is added dropwise under ice cooling methyl ester of TRANS-4-chlorocarbonylsulfenyl acid (9.00 g, to 44.0 mmol), a solution of triethylamine (of 13.9 ml, 100 mmol) in acetonitrile (60 ml) for 2 hours. P is after this reaction solution was concentrated, add water and extracted with ethyl acetate. The organic layer is successively washed with 10% citric acid solution, saturated aqueous sodium bicarbonate, saturated brine and dried over magnesium sulfate. After concentration the residue is purified flash chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:2) and get the specified header connection (7,38 g, 48%).

Stage 3. Obtain methyl ester of TRANS-4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]cyclohexanecarboxylic acid

A solution of methyl ester of TRANS-4-[2-(6-bromopyridin-2-yl)-2-oxoethylidene]cyclohexanecarbonyl acid (7,38 g, and 19.3 mmol) in tetrahydrofuran (120 ml), obtained in stage 2, and the reagent Lawesson (Lwson) (8,20 g, 20.3 mmol) is heated to boiling point for 2 hours in a stream of Ar. After that, the reaction solution concentrate add saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and dried over magnesium sulfate and after concentration the residue is purified flash chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:1) and receive specified in the header connection (6,1 g).

1H-NMR (400 MHz, DMSO-d6) δ: to 8.41 (1H, s), of 7.96 (1H, DD, J=7,6, 1.2 Hz), 7,92 (1H, t, J=7,6 Hz), the 7.43 (1H, DD, J=7,6, 1.2 G is), 3,62 (3H, s), 2,97 was 3.05 (1H, m), 2,45-is 2.37 (1H, m), 2,19-2,12 (2H, m), 2.05 is-to 1.98 (2H, m), 1,63 of 1.46 (4H, m).

Stage 4. Obtain methyl ester of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid

A suspension of methyl ester of TRANS-4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]cyclohexanecarboxylic acid (1.80 g, 4,72 mmol) in toluene (100 ml), obtained in stage 3, 2-amino-4-picoline (613 mg, to 5.66 mmol), palladium acetate (159 mg, 0.71 mmol), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (529 mg, 0.85 mmol), cesium carbonate (2.00 g, mmol 6,14) is heated and stirred at 90°C in a stream of Ar for 7 hours. To the reaction solution was added water and extracted with a mixed solvent: ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated saline and dried over magnesium sulfate; the residue obtained by concentration in vacuo, and purified flash chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:2) and then washed with a mixed solvent of n-hexane-ethyl acetate and get listed in the title compound (1.60 g, 83%).

1H-NMR (400 MHz, DMSO-d6) δ: 9,67 (1H, users), 8,30 (1H, s), 8,10 (1H, DD, J=5,2, 0.8 Hz), 7,92 (1H, usher.), to 7.68 (1H, DD, J=8.0 a, 7,6 Hz), 7,40 (1H, userd, J=8.0 Hz), 7,40 (1H, userd, J=7,6 Hz), 6,78-6,76 (1H, m), 3,62 (3H, s), 3,05-of 2.97 (1H, m), 2,45-of 2.38 (1H, m)to 2.35 (3H, s), 2.21 are of 2.15 (2H, m), 2.05 is of 1.99 (2H, m), 1,64 is 1.48 (4H, m).

Example 7

Getting t the ANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid (compound A-7) :

A solution of methyl ester of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid (1.50 g, to 3.67 mmol)obtained in the above example 6, the monohydrate of lithium hydroxide (770 mg, 18.4 mmol) in a mixture of methanol (40 ml), tetrahydrofuran (40 ml) and water (20 ml) was stirred at room temperature for 15 hours. After that, the reaction solution is concentrated and then neutralized with 2n. hydrochloric acid (to 9.2 ml, 18.4 mmol) and the precipitate filtered and washed with water and ethyl acetate. Then it is subjected to drying in a vacuum and get listed in the title compound (1,41 g, 97%).

1H-NMR (400 MHz, DMSO-d6) δ: 12,14 (1H, usher.), 9,67 (1H, users), 8,30 (1H, s), 8,10 (1H, d, J=4,8 Hz), to 7.93 (1H, usher.), to 7.68 (1H, t, J=8.0 Hz), 7,41 (1H, d, J=8.0 Hz), 7,39 (1H, d, J=8.0 Hz), 6,77 (1H, userd, J=4,8 Hz), 3.04 from-1,95 (1H, m)to 2.35 (3H, s), 2,33 was 2.25 (1H, m), 2.21 are of 2.15 (2H, m), 2.05 is of 1.99 (2H, m), 1,62-of 1.45 (4H, m).

Example 8

Obtaining (hydroxypiperidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}cyclohexyl)methanone (compound A-8):

To the suspension in dimethylformamide (4 ml) of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid (504 mg, 1.28 mmol)obtained in example 7 and 4-hydroxypiperidine (130 mg, 1,29 mmol) are successively added in to the room temperature, the triethylamine (4 ml, is 2.88 mmol), hexaflurophosphate benzothiazolylsulfenamide (731 mg, of 1.40 mmol) and the mixture is stirred for 1 hour. After that, the reaction solution is concentrated and add a saturated solution of sodium bicarbonate and water, the precipitate is filtered off and washed with water, it is subjected to drying in a vacuum and get listed in the title compound (585 mg, 96%).

1H-NMR (400 MHz, DMSO-d6) δ: 9,67 (1H, users), 8,30 (1H, s), 8,10 (1H, d, J=5,2 Hz), 7,92 (1H, usher.), of 7.69 (1H, DD, J=8,4, a 7.6 Hz), 7,41 (1H, d, J=8,4 Hz), 7,39 (1H, d, J=7,6 Hz), 6,77 (1H, userd, J=5,2 Hz), to 4.73 (1H, d, J=4.4 Hz), 3,98-are 3.90 (1H, m), 3,82-3,74 (1H, m), of 3.73-3,66 (1H, m), 3.25 to and 3.16 (1H, m), 3.04 from-of 1.94 (2H, m), 2,746-of 2.66 (1H, m)to 2.35 (3H, s), 2,20-to 2.13 (2H, m), 1,81-1,49 (8H, m), 1,39 is 1.16 (2H, m).

MC: 478,2 (M++1).

Example 9

Obtaining N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}ethyl)amine (compound A-9):

Stage 1. Obtain tert-butyl ester {(S)-1-[2-(6-bromopyridin-2-yl)-2-oxoethylidene]ethyl}carbamino acid

To a suspension of the hydrochloride of 2-amino-1-(6-bromopyridin-2-yl)ethanone (500 mg, 1,99 mmol) in acetonitrile (11 ml), obtained in stage 1 of example 6, is added dropwise under ice cooling for 15 minutes (S)-N-tert-butylcarbamoyl (376 mg, 1,99 mmol), hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (379 mg, 1,99 mmol), monohydrate, 1-hydroxybenzotriazole (305 mg, 1,99 mmol), the solution triethyl is mine (0.7 ml) in acetonitrile (4 ml). The mixture is then stirred at the same temperature for 1 hour, add water and extracted with ethyl acetate. The organic layer is washed with water, saturated salt solution, dried over magnesium sulfate, the residue obtained by concentration in vacuo, and purified flash chromatography on silica gel (mixture of n-hexane:ethyl acetate = 2:1) and get listed in the title compound (456 mg, 59%).

Stage 2. Obtain tert-butyl ester {(S)-1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]ethyl}carbamino acid

Specified in the title compound (282 mg, 71%) are obtained in accordance with methods analogous to the methods for obtaining compounds described in stage 3 of example 6, using tert-butyl ester {(S)-1-[2-(6-bromopyridin-2-yl)-2-oxoethylidene]ethyl}carbamino acid (400 mg, 1.04 mmol) and reagent Lawesson (419 mg, 1.04 mmol).

Stage 3. Obtain tert-butyl ester ((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}ethyl) - carbamino acid

Specified in the title compound (234 mg, 87%) are obtained in accordance with methods analogous to the methods for obtaining compounds described in stage 4 of example 7 using tert-butyl ester {(S)-1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]ethyl}carbamino acid (250 mg, of 0.65 mmol), obtained in stage 2, 2-amino-4-picoline (92 mg, 0.5 mmol), the palladium acetate (15 mg, 0.07 mmol), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (49 mg, 0.08 mmol) and cesium carbonate (276 mg, 0.85 mmol).

Stage 4. Getting amine N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}ethyl)

To a solution of tert-butyl methyl ether (S)-1-({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}ethyl) - carbamino acid (200 mg, 0.49 mmol) in chloroform (5 ml), obtained in stage 3, add triperoxonane acid (5 ml) and the mixture is stirred at room temperature for 2 hours. The reaction solution concentrate and add a saturated solution of sodium bicarbonate and extracted with a mixed solution of ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated saline and dried over magnesium sulfate. The obtained residue was washed with diisopropyl ether, dried in vacuum and get listed in the title compound (102 mg, 67%).

Example 10

Obtaining N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)ndimethylacetamide (compound A-10):

Acetic anhydride (0,02 ml, 0.24 mmol) are added to a solution of N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)amine (50 mg, 0.16 mmol) in pyridine (3 ml)obtained in example 9, and the mixture is stirred at room temperature for 2 hours. Rea the traditional solution is concentrated and extracted with a mixed solution of ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated saline and dried over magnesium sulfate. The obtained residue was washed with diisopropyl ether, dried in vacuum and get listed in the title compound (43 mg, 76%).

1H-NMR (400 MHz, DMSO-d6) δ: 9,68 (1H, s)8,71 (1H, d, J=7,6 Hz), 8,30 (1H, s), of 8.09 (1H, d, J=4,8 Hz), of 7.97 (1H, users), to 7.67 (1H, DD, J=8,4, a 7.6 Hz), 7,40 (1H, d, J=7,2 Hz), 7,34 (1H, d, J=8,4 Hz), 6,77 (1H, d, J=5,2 Hz), 5,19-5,12 (1H, m)to 2.35 (3H, s)of 1.92 (3H, s)and 1.51 (3H, d, J=7,2 Hz).

MC: 354,1 (M++1).

Example 11

Obtain (S)-3-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-she (compound A-11):

Stage 1. Obtain tert-butyl ether (S)-4-[2-(6-bromopyridin-2-yl)]-2-oxoethylidene-2,2-dimethyloxazolidine-3-carboxylic acid

To a suspension of 3-tert-butyl ester-4-lithium salt (S)-2,2-dimethyloxazolidine-3,4-dicarboxylic acid (12.00 g, while 47.7 mmol) in acetonitrile (150 ml) was added under ice cooling monohydrate, 1-hydroxybenzotriazole (7.30 g, while 47.7 mmol), hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (9,20 g of 47.7 mmol), hydrochloride of 2-amino-1-(6-bromopyridin-2-yl)ethanone (10,00 g, and 39.7 mmol)obtained in stage 1 of example 6, and the mixture is stirred for 3 hours. After this reaction solution was concentrated, water is added and extracted with ethyl acetate. The organic layer is successively washed with 10% in denim citric acid solution, saturated aqueous sodium hydrogen carbonate solution, saturated saline solution and dried over magnesium sulfate and then concentrated and dried in vacuum and get listed in the title compound (13,70 g, 78%).

Stage 2. Obtain tert-butyl ether (S)-4-[5-(6-bromopyridin-2-yl)-5-thiazol-2-yl]-2,2-dimethyloxazolidine-3-carboxylic acid

Specified in the header connection (10,50 g, 77%) are obtained in accordance with methods analogous to the methods for obtaining compounds described in stage 3 of example 6, using tert-butyl ether (S)-4-[2-(6-bromopyridin-2-yl)-2-oxoethylidene-2,2-dimethyloxazolidine-3-carboxylic acid (13,70 g, was 31.0 mmol), obtained in stage 1, the reagent Lawesson (12,50 g, was 31.0 mmol).

Stage 3. Getting dihydrochloride (S)-2-amino-2-[5-(6-bromopyridin-2-yl)thiazol-2-yl]ethanol

To a solution of tert-butyl methyl ether (S)-4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]-2,2-dimethyloxazolidine-3-carboxylic acid (5,00 g of 11.4 mmol) in tetrahydrofuran (30 ml), obtained in stage 2, type 4h. a solution of hydrogen chloride in ethyl acetate (30 ml) and heated to boiling point at the temperature of 90°C for 2 hours. After that, the reaction solution is cooled, then concentrated and washed with ethyl ether, dried, and get mentioned in the title compound (3.57 g).

1H-NMR (400 MHz, DMSO-d6) δ: 8,91-8,77 (2H, m), to 8.62 (1H, s), 8,07 (1H, d, J=8.0 Hz), 7,98 (1H, t, J=8.0 Hz), to 7.50 (1H, d, J=8.0 Hz), 6,12-to 5.85 (3H, m), 4,82-4,74 (1H, m), 3,90 (2H, d, J=5.6 Hz).

Stage 4. Obtain (S)-4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]oxazolidin-2-it

To a solution of dihydrochloride of (S)-2-amino-2-[5-(6-bromopyridin-2-yl)thiazol-2-yl]ethanol (1,00 g, 2.68 mmol) in chloroform (15 ml), obtained in stage 3, is added dropwise under cooling to a temperature of -78°C. triethylamine (3,7 ml, 2.68 mmol), a solution of triphosgene (278 mg, of 0.94 mmol) in chloroform (5 ml) and the mixture is stirred at the same temperature for 2 hours. The reaction solution is heated to room temperature and add water and then extracted with ethyl acetate. After washing with saturated salt solution and the organic layer is dried over magnesium sulfate. After concentration the residue is purified flash chromatography on silica gel (mixture of chloroform:methanol:ethyl acetate = 15:1:1) and get listed in the title compound (712 mg, 82%).

1H-NMR (400 MHz, DMSO-d6) δ: 8,66 (1H, users), 8,54 (1H, s), 8,03 (1H, DD, J=8.0 a, and 0.8 Hz), of 7.96 (1H, t, J=7.8 Hz), of 7.48 (1H, DD, J=8.0 a, and 0.8 Hz), 5,31 (1H, DDD, J=8,6, and 4.8, 1.2 Hz), 4,74 (1H, t, J=8.6 Hz), 4,36 (1H, DD, J=8,6, 4,8 Hz).

Stage 5. Obtain (S)-4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]-3-methyloxazolidine-2-it

(S)-4-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]oxazolidin-2-he (488 mg,1.50 mmol), obtained in stage 4, and sodium hydride (60% in oil, 72 mg, of 1.80 mmol) suspended in tetrahydrofuran (5 ml) and add dimethylformamide (5 ml) in the current Ar and methyliodide (0.1 ml, of 1.65 mmol) under ice cooling and the resulting solution was stirred at room temperature for 12 hours. After this reaction solution was concentrated, water is added and then extracted with ethyl acetate. Then the organic layer was washed with saturated saline and dried over magnesium sulfate, it is concentrated and the residue purified flash chromatography on silica gel (mixture of chloroform:methanol = 20:1) and get listed in the title compound (205 mg, 40%).

1H-NMR (400 MHz, DMSO-d6) δ: 8,59 (1H, s), with 8.05 (1H, d, J=7.8 Hz), of 7.97 (1H, t, J=7.8 Hz), 7,49 (1H, d, J=7.8 Hz), from 5.29 (1H, DD, J=9,0, 5.6 Hz), and 4.68 (1H, t, J=9.0 Hz), 4,32 (1H, DD, J=9,0, 5.6 Hz), was 2.76 (3H, s).

Stage 6. Obtain (S)-3-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-she (compound A-11)

Specified in the title compound (132 mg, 60%) are obtained in accordance with methods analogous to the methods for obtaining compounds described in stage 4 of example 7 using (S)-4-[5-(6-bromopyridin-2-yl)thiazol-2-yl]-3-methyloxazolidine-2-he (205 mg, of 0.60 mmol)obtained in stage 5, 2-amino-4-picoline (72 mg, 0.66 mmol), palladium acetate (20 mg, 0.09 mmol), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (75 mg, 0.12 and IMO the b) and cesium carbonate (295 mg, 0.90 mmol).

1H-NMR (400 MHz, DMSO-d6) δ: 9,71 (1H, users), of 8.47 (1H, s), 8,11 (1H, d, J=4,8 Hz), of 7.90 (1H, users), 7,73 (1H, t, J=8.0 Hz), of 7.48 (1H, d, J=8.0 Hz), 7,44 (1H, d, J=8.0 Hz), 6,78 (1H, d, J=4,8 Hz), 5,28 (1H, DD, J=8,8, 4,8 Hz), 4,69 (1H, t, J=8,8 Hz)to 4.33 (1H, DD, J=8,8, 4,8 Hz), and 2.79 (3H, s), of 2.34 (3H, s).

MC: 368,1 (M++1).

Example 12

Obtain tert-butyl ether (S)-2,2-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-3-carboxylic acid (compound A-12):

Specified in the header connection (1,91 g, 90%) are obtained in accordance with methods analogous to the methods for obtaining compounds described in stage 4 of example 6, using tert-butyl ether (S)-4-[5-(6-bromopyridin-2-yl)-5-thiazol-2-yl]-2,2-dimethyloxazolidine-3-carboxylic acid (2.00 g, of 4.54 mmol), obtained in stage 2 of example 11, 2-amino-4-picoline (540 mg, 5.00 mmol), acetate palladium (153 mg, of 0.68 mmol), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (565 mg, of 0.91 mmol) and cesium carbonate (2,22 g, to 6.80 mmol).

Example 13

Obtain (S)-2-amino-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (compound A-13):

To a solution of tert-butyl methyl ether (S)-2,2-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-3-carboxylic acid (1.90 g, 4,06 mmol) in tetrahydrofuran (10 ml)obtained in example 12, type 4h. the chloride is adored-ethyl acetate (10 ml) and stirred at 60°C for 5 hours under heating. After the reaction solution is concentrated, it is neutralized with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate, it is concentrated and the residue purified flash chromatography on silica gel (mixture of chloroform:methanol = 20:1) and get listed in the title compound (588 mg, 44%).

1H-NMR (400 MHz, DMSO-d6) δ: 9,65 (1H, users), 8,30 (1H, s), 8,10 (1H, d, J=4,8 Hz), 7,98 (1H, users), to 7.67 (1H, t, J=7.8 Hz), 7,39-7,37 (2H, m), 6,77 (1H, d, J=4,8 Hz), free 5.01 (1H, t, J=5.8 Hz), 4,16 (1H, DD, J=6,8, and 4.4 Hz), of 3.77-3.72 points 1H, m), 3,56-3,50 (1H, m)to 2.35 (3H, s).

MC: 328,1 (M++1).

Example 14

Obtain (S)-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-she (compound A-14):

To a solution of (S)-2-amino-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol (220 mg, 0.67 mmol) in chloroform (5 ml)obtained in example 13, add cooling to a temperature of -78°C. triethylamine (0,93 ml, 0.67 mmol), triphosgene (70 mg, 0.24 mmol) and the mixture is stirred at the same temperature for 3 hours. The reaction solution is heated to room temperature and add water and then extracted with ethyl acetate. After washing with saturated salt solution and the organic layer is dried over magnesium sulfate. After concentration the residue of the industry is with ethanol and receive specified in the title compound (41 mg, 17%).

1H-NMR (400 MHz, DMSO-d6) δ: 9,70 (1H, users), 8,66 (1H, usher.), 8,43 (1H, s), 8,11 (1H, d, J=5,2 Hz), 7,89 (1H, users), 7,72 (1H, t, J=8.0 Hz), 7,46 (1H, d, J=8.0 Hz), 7,44 (1H, d, J=8.0 Hz), 6,78 (1H, userd, J=5,2 Hz), 5,28 (1H, DDD, J=8,8, 4,4, 1.2 Hz), to 4.73 (1H, t, J=8,8 Hz), 4,35 (1H, DD, J=8,8, 4,4 Hz), was 2.34 (3H, s)

MC: 354,1 (M++1).

Example 15

Getting dihydrochloride (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid (compound A-15):

Stage 1. Obtain tert-butyl methyl ether (1-thiocarbamoylation-4-yl)acetic acid:

To a solution of tert-butyl methyl ether piperidine-4-luxusni acid (of 10.72 g, 50.0 mmol) in chloroform (100 ml) add a solution of 9-fluorenylmethoxycarbonyl (14,07 g, 50.0 mmol) in chloroform (100 ml) and the mixture is stirred at room temperature for 1 hour. Then added piperidine (80 ml) and the mixture is again stirred at room temperature for 30 minutes. Then the reaction solution is concentrated and water is added, extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over magnesium sulfate and the residue obtained by concentration under vacuum, washed with isopropyl ether and receive specified in the header connection (11,35 g, 98%).

Stage 2. Obtain tert-butyl ester 1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-yl}at ssnoi acid :

tert-Butyl methyl ether (1-thiocarbamoylation-4-yl)acetic acid (11,95 g, and 46.3 mmol), obtained in stage 1, are added to a solution of 2-bromo-6-chloromethylpyridine (of 9.55 g, 6.3 mmol) in ethanol (100 ml), obtained in stage 1 of example 1, and the mixture is heated to boiling point during the night. The temperature of the reaction solution is brought to room; add dimethylacetal of dimethylformamide (add to 9.3 ml, to 69.4 mmol) and triethylamine (19 ml, 139 mmol) and heated to boiling point for 2 hours. After this reaction solution was concentrated, water is added and then extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over magnesium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 50:50 to 0:100) and get the specified header connection (to 13.09 g, 65%).

1H-NMR (400 MHz, DMSO-d6) δ: of 7.95 (1H, s), 7,80 (1H, d, J=7.8 Hz), to 7.67 (1H, t, J=7.8 Hz), was 7.36 (1H, d, J=7.8 Hz), was 4.02-of 3.95 (2H, m), 3,14-is 3.08 (2H, m), 2,20 (2H, d, J=7,2 Hz), 2.00 in 1,89 (1H, m), 1,79-1,72 (2H, m)of 1.42 (9H, s), 1,34-to 1.21 (2H, m).

Stage 3. Obtain tert-butyl methyl ether (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid:

rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (1.85 g, of 2.97 mmol) and palladium acetate (500 mg ,22 mmol) suspended in toluene (30 ml), then successively added 2-amino-4-picoline (1.60 g, of 14.8 mmol) and tert-butyl methyl ether {1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-yl}acetic acid (6.50 g, of 14.8 mmol), obtained in stage 2, and then add cesium carbonate (7,25 g of 22.2 mmol) and the mixture is stirred overnight at a temperature of 100°C. To the reaction solution was added water, extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over anhydrous sodium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:1 to 1:10) and get the specified header connection (4,30 g, 62%).

Stage 4. Getting dihydrochloride (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}piperidine-4-yl)acetic acid:

Triperoxonane acid (20 ml) was added to a solution of tert-butyl methyl ether (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}piperidine-4-yl)acetic acid (4,30 g, 9,23 mmol) in chloroform (20 ml), obtained in stage 3, and stirred overnight at room temperature. Then 4h. the hydrochloric acid-ethyl acetate (20 ml) is added to the concentrate obtained by concentrating the reaction solution under vacuum, and precipitated precipitated solid is separated by filtration, washed with ethyl acetate (20 m is) and get the specified header connection (4,46 g, 100%).

1H-NMR (400 MHz, DMSO-d6) δ: 12,23 (1H, users), to 8.45 (1H, d, J=6.4 Hz), 8,07 (1H, s), 7,88 (1H, t, J=7.9 Hz), 7,56 (1H, d, J=7,7 Hz)to 7.50 (1H, users), 7,21 (1H, d, J=6.4 Hz), 7,10 (1H, d, J=8,2 Hz), 4,07-Android 4.04 (2H, m), 3.25 to a 3.15 (2H, m,), of 2.50 (3H, s), of 2.23 (2H, d, J=7,1 Hz), 2,05-of 1.92 (1H, m), 1,86-of 1.78 (2H, m), 1,37-1,24 (2H, m).

MC: 410,3(M++1).

Example 16

Obtain TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarboxylic acid (compound A-16):

Stage 1. Obtaining methyl ester hydrochloride, TRANS-4-aminomethylenemalonate acid:

Thionyl chloride (7 ml, 96 mmol) are added to a solution of TRANS-4-aminomethylenemalonate acid (5,00 g of 31.8 mmol) in methanol (50 ml) and the mixture is stirred at room temperature for 16 hours. The reaction solution is concentrated and the obtained solid is washed with diethyl ether (50 ml). The hydrochloride of the methyl ester of TRANS-4-aminomethylenemalonate acid (of 6.49 g, 98%) obtained by separation by filtration and drying in vacuum.

1H-NMR (400 MHz, DMSO-d6) δ: 8,11 for 7.78 (3H, m)and 3.59 (3H, s), 2,69 at 2.59 (2H, m), 2,31-2,19 (1H, m), 1,96-of 1.88 (2H, m), 1.85 to about 1.75 (2H, m), 1,59 to 1.47 (1H, m), 1,36-to 1.21 (2H, m), 1,05-of 0.90 (2H, m).

Stage 2. Obtain methyl ester of TRANS-4-theoreticmethodological acid:

Hydroc rbonate sodium (1.68 g, 20.0 mmol) are added to a solution of methyl ester hydrochloride, TRANS-4-aminomethylenemalonate acid (2,07 g, 10.0 mmol) in chloroform (40 ml), obtained in stage 1, 9-fluorenylmethoxycarbonyl isothiocyanate (of 2.81 g, 10.0 mmol) under cooling with ice. The reaction solution was stirred at room temperature for 16 hours, then added piperidine (5 ml, 50 mmol) and the mixture is stirred at room temperature for another 6 hours. Methyl ester of TRANS-4-theoreticmethodological acid (1.55 g, 67%) was obtained by concentration in vacuo of the reaction solution and purify the obtained solid by chromatography on a column of silica gel (ethyl acetate).

1H-NMR (400 MHz, DMSO-d6) δ: of 7.64-7,52 (1H, m), of 6.96-6,76 (2H, m)to 3.58 (1H, s), 3,26-and 3.16 (2H, m), 2,29-of 2.16 (1H, m), 1,95-of 1.84 (2H, m), 1,78 by 1.68 (2H, m)and 1.51-to 1.38 (1H, m), 1,34-1,19 (2H, m), 1,01-0,83 (2H, m).

Stage 3. Obtain methyl ester of TRANS-4-{[5-(6-bromopyridin-2-yl)thiazol-2-ylamino]methyl}cyclohexanecarboxylic acid:

A solution in ethanol (15 ml) of methyl ester of TRANS-4-theoreticmethodological acid (1.55 g, of 6.73 mmol), obtained in stage 2, 2-bromo-6-chloromethylpyridine (1,38 g of 6.73 mmol)obtained in stage 1 of example 1 is stirred while heating to boiling point for 4 hours. After that, the reaction solution is cooled to room is temperature, add N,N-dimethylacetal of dimethylformamide (0.9 ml, 10 mmol), triethylamine (1.8 ml, 20 mmol) and the mixture is stirred while heating to the boiling temperature under reflux for 1 hour. The reaction solution is cooled to room temperature and the solid obtained by concentration in vacuum, separated by filtration.

Methyl ester of TRANS-4-{[5-(6-bromopyridin-2-yl)thiazol-2-ylamino]methyl}cyclohexanecarboxylic acid (2,02 g, 73%) is obtained by sequential washing with water (10 ml), diethyl ether (10 ml) and drying in vacuum.

1H-NMR (400 MHz, DMSO-d6) δ: 8,15 (1H, t, J=5.7 Hz), 7,83 (1H, s), 7,74 (1H, d, J=7.9 Hz), 7,63 (1H, t, J=7.9 Hz), 7,31 (1H, d, J=7.9 Hz), 3,15-of 3.06 (2H, m), 2,32-2,19 (1H, m), 1,97-to 1.87 (2H, m), 1.85 to to 1.76 (2H, m), 1,63-1,49 (1H, m), 1,37 is 1.23 (2H, m), 1.06 a-0,93 (2H, m).

Stage 4. Obtain methyl ester of TRANS-4-({[5-(6-bromopyridin-2-yl]thiazol-2-yl)methylamino}methyl)cyclohexanecarboxylic acid:

Sodium hydride (53,6 mg, 60% in oil, of 1.34 mmol) are added to a solution of methyl ester of TRANS-4-{[5-(6-bromopyridin-2-yl)thiazol-2-ylamino]methyl}cyclohexanecarboxylic acid (500 mg, 1,22 mmol) in N,N-dimethylformamide (5 ml), obtained in stage 3, and the mixture is stirred at room temperature for 15 minutes. To the reaction solution add methyliodide (84 μl, of 1.34 mmol), the mixture is stirred at room temperature for 2 h the owls and extracted by adding ethyl acetate (40 ml) and saturated aqueous solution of ammonia (20 ml). The organic layer was washed with saturated saline (20 ml × 2) and dried over magnesium sulfate. Methyl ester of TRANS-4-({[5-(6-bromopyridin-2-yl)thiazol-2-yl]methylamino}methyl)cyclohexanecarboxylic acid obtained as a crude substance by filtration and concentration in vacuum.

1H-NMR (400 MHz, DMSO-d6) δ: a 7.92 (1H, s), to 7.77 (1H, d, J=7.9 Hz), the 7.65 (1H, t, J=7.9 Hz), 7,32 (1H, d, J=7.9 Hz), to 3.58 (3H, s), 3,39-to 3.33 (2H, m), 3,10 (3H, s), 2,33-of 2.21 (1H, m), 1,97 is 1.86 (2H, m), 1,74-of 1.65 (2H, m), 1,57-1,47 (1H, m), 1,39-1,22 (2H, m), 1,11-0,97 (2H, m).

Stage 5. Obtain methyl ester of TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid:

To a solution of methyl ester of TRANS-4-({[5-(6-bromopyridin-2-yl)thiazol-2-yl]methylamino}methyl)cyclohexanecarboxylic acid in toluene (10 ml)obtained in stage 4, add to the atmosphere of AG 2-amino-4-picoline (132 mg, 1,22 mmol), palladium acetate (27 mg, 0.12 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (75 mg, 0.12 mmol), cesium carbonate (596 mg, to 1.83 mmol) and the mixture is stirred at a temperature of 100°C for 16 hours. After that, the reaction solution is cooled to room temperature, it is filtered, concentrated and the methyl ester of TRANS-4-[(methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino]methyl]

cyclohexanecarbonyl acid (217 mg, 39%) get put the m purification of the residue by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:1).

Stage 6. Obtain TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino]methyl]

cyclohexanecarbonyl acid:

A solution of methyl ester of TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid (217 mg, 0.48 mmol)obtained in stage 5, 1H. an aqueous solution of sodium hydroxide (2 ml, 2 mmol) in methanol (2 ml) and tetrahydrofuran (2 ml) was stirred at room temperature for 16 hours. It is neutralized using 1N. hydrochloric acid and extracted with chloroform (50 ml × 2). The organic layer was washed with saturated saline (20 ml) and dried over magnesium sulfate, filtered and concentrated in vacuo. The solid substance obtained by adding a mixture of chloroform-diethyl ether (1:1) (10 ml) to the residue is separated by filtration, dried under vacuum, thereby obtaining TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]

cyclohexanecarbonyl acid (190 mg, 90%).

1H-NMR (400 MHz, DMSO-d6) δ: 12,04 (1H, s), 9,54 (1H, s), 8,08 (1H, d, J=5,1 Hz), 8,03 (1H, s), 7,79 (1H, s), 7,56 (1H, t, J=7.9 Hz), 7,20 (1H, d, J=7.9 Hz), to 7.15 (1H, d, J=7.9 Hz), to 6.75 (1H, d, J=5,1 Hz), 3,38-3,29 (2H, m), the 3.11 (1H, s), 2,34 (1H, s), 2,19-of 2.08 (1H, m), 1,97-to 1.87 (2H, m), 1.77 in-of 1.66 (2H, m), 1,57 was 1.43 (1H, m), 1,36 is 1.20 (2H, m), 1,10-0,97 (2H, m).

MC: 438,2 (M+1).

Example 17

Paul is the significance of 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-17) :

Stage 1. Obtaining methyl ester 3-(1-thiocarbamoylation-4-yl)propionic acid:

To a solution of 9-fluorenylmethoxycarbonyl (4.26 deaths grams of 15.2 mmol) in chloroform (40 ml) add a solution of methyl ester hydrochloride (3-piperidine-4-yl)methylpropionic acid (2,62 g, 12.6 mol) in chloroform (10 ml) and sodium bicarbonate (6,40 g of 75.8 mmol) and the mixture is stirred over night at room temperature. After that, the reaction solution is filtered to remove insoluble impurities, add chloroform (20 ml) and piperidine (20 ml) and the mixture is stirred at room temperature for 1 hour. To the reaction solution was added water and extracted with ethyl acetate. The organic layer was washed with saturated saline solution and dried over sodium sulfate, the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate) and get listed in the title compound (2.10 g, 63%).

Stage 2. Obtaining methyl ester 3-{1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-yl}propionic acid:

To a solution of 2-bromo-6-chloromethylpyridine (1.88 g, 12 mmol) in ethanol (20 ml), obtained in stage 1 of example 1, add methyl ester 3-(1-thiocarbamoylation-4-yl)propionic acid (2.10 g, 9,12 mmol)obtained is in stage 1, and the mixture is heated to boiling point under reflux overnight. The temperature of the reaction solution is brought to room temperature, add dimethylacetal of dimethylformamide (1.8 ml, 14 mmol) and triethylamine (3.8 ml, 27 mmol) and the resulting solution is heated to boiling point under reflux for 1 hour. After this reaction solution was concentrated, water is added and then extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over magnesium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 50:50 to 0:100) and get listed in the title compound (748 mg, 20%).

1H-NMR (400 MHz, DMSO-d6) δ: of 7.95 (1H, s), 7,80 (1H, DD, J=7,9, 0.7 Hz), to 7.67 (1H, t, J=7.8 Hz), was 7.36 (1H, DD, J=7,7, 0.7 Hz), 4,00-of 3.97 (2H, m), 3,61 (3H, s), 3,11-to 3.02 (2H, m), is 2.37 (2H, t, J=7.4 Hz), 1,79-1,72 (2H, m), 1,57-1,49 (3H, m), 1,26-of 1.13 (2H, m).

Stage 3. Obtaining methyl ester 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid:

rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (91 mg, 0.15 mmol) and palladium acetate (25 mg, 0.11 mmol) suspended in toluene (7 ml), then successively added 2-amino-4-picoline (79 mg, 0.73 mmol) and methyl ester of 3-{1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-yl}propionic key is lots (300 mg, 0.73 mmol), obtained in stage 2, then add cesium carbonate (357 mg, 1.1 mmol) and the mixture is stirred overnight at a temperature of 100°C. To the reaction solution was added water, extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over anhydrous sodium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:1 to 1:10) and get listed in the title compound (250 mg, 55%).

1H-NMR (400 MHz, DMSO-d6) δ: of 9.55 (1H, users), of 8.09 (1H, d, J=5,1 Hz), of 7.96-to 7.93 (1H, m), 7,83 (1H, s), 7,58 (1H, t, J=8.0 Hz), 7.23 percent (2H, t, J=7,3 Hz), 6,77-6,74 (1H, m), 3,99-to 3.92 (2H, m), 3,61 (3H, s), 3,11-to 3.02 (2H, m), of 2.38 (2H, t, J=7,3 Hz), was 2.34 (3H, s), 1,81-of 1.74 (2H, m), 1,57-1,49 (3H, m), 1,29-of 1.15 (2H, m).

Stage 4. Obtaining 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid:

To a mixed solution of methyl ester of 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-)propionic acid (250 mg, or 0.57 mmol), obtained in stage 3, in tetrahydrofuran (5 ml) and methanol (5 ml) is added 4n. a solution of sodium hydroxide (1.5 ml, 6.0 mmol) and the mixture is stirred at room temperature for 12 hours. The concentrate obtained by concentration in vacuo of the reaction solution is neutralized 0,1N. solution of hydrochloric acid and precipitated in sieges is to the solid is separated by filtration, washed with water and get listed in the title compound (142 mg, 59%).

1H-NMR (400 MHz, DMSO-d6) δ: 12,07 (1H, users), 8,24 (1H, d, J=4.6 Hz), to $ 7.91 (1H, s), 7,76-7,66 (2H, m), 7,35 (1H, d, J=7,7 Hz), 7,16 (1H, d, J=8.1 Hz), of 6.96-6.90 to (1H, m)4,00 (2H, d, J=13,0 Hz), 3,13-3,03 (2H, m), is 2.41 (3H, s), 2,28 (2H, t, J=7,3 Hz), 1,82 is 1.75 (2H, m), 1.55V to 1.47 (3H, m), 1,29 is 1.16 (2H, m).

MC: 424,1 (M++1).

Example 18

Obtaining 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (compound A-18):

Stage 1. Obtaining the ethyl ester of 2-methyl-2-(1-thiocarbamoylation-4-yl)propionic acid:

To a solution of 9-fluorenylmethoxycarbonyl isothiocyanate (2,62 g to 9.32 mmol) in chloroform (20 ml) add a solution of the hydrochloride of the ethyl ester of 2-methyl-2-piperidine-4-ylpropionic acid (2,27 g, being 9.61 mmol) in chloroform (10 ml) and sodium bicarbonate (a 4.03 g, 48,0 mmol) and the mixture is stirred at room temperature. Then added piperidine (30 ml) and the mixture is stirred at room temperature for another 2 hours. The reaction solution was concentrated in vacuo and the solid is obtained by adding diethyl ether, separated by filtration. It is dissolved in N,N-dimethylformamide (20 ml) and added piperidine (20 ml) and the mixture is stirred at room temperature for 1 hour. To the reaction solution was added water, and ek is tracerout with ethyl acetate. The organic layer was washed with saturated saline solution and dried over sodium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate) and get listed in the title compound (2.4 g, 98%).

1H-NMR (400 MHz, DMSO-d6) δ: 7,30 (2H, users), 4,72-of 4.57 (2H, m), 4,08 (2H, q, J=7,1 Hz), 2,88-2,77 (2H, m), 1,83-1,72 (1H, m), 1,55 of 1.46 (2H, m), 1,20-of 1.09 (2H, m)to 1.19 (3H, t, J=7,1 Hz)of 1.06 (6H, s).

Stage 2. Obtaining the ethyl ester of 2-{1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-yl}-2-methylpropionic acid:

To a solution of 2-bromo-6-chloromethylpyridine (2.14 g, 10.4 mmol) in ethanol (30 ml), obtained in stage 1 of example 1, add ethyl ester of 2-methyl-2-(1-thiocarbamoylation-4-yl)propionic acid (2,44 g, 9.43 mmol), obtained in stage 1, and the mixture is heated to boiling point for 5 hours. The reaction solution is cooled to room temperature, add dimethylacetal of dimethylformamide (1.9 ml, 14 mmol) and triethylamine (3.9 ml, 28 mmol) and heated to boiling point under reflux for 1 hour. After this reaction solution was concentrated, water is added and then extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over magnesium sulfate and the residue obtained by concentration under vacuum, clean XP is matography on silica gel (mixture of n-hexane:ethyl acetate = 2:1 to 1:1) and receive specified in the header connection (2,48 g, 60%).

1H-NMR (400 MHz, DMSO-d6) δ: to 7.93 (1H, s), 7,78 (1H, d, J=7.8 Hz), 7,66 (1H, t, J=7.8 Hz), 7,34 (1H, d, J=7.8 Hz), 4,08-was 4.02 (2H, m), 4,08 (2H, q, J=7,1 Hz), is 3.08 are 2.98 (2H, m), 1,86 is 1.75 (1H, m), 1,66 is 1.58 (2H, m), 1,37-1,24 (2H, m)of 1.18 (3H, t, J=7,1 Hz), a 1.08 (6H, s).

Stage 3. Obtaining the ethyl ester of 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid:

rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (213 mg, 0.34 mmol) and palladium acetate (58 mg, 0.26 mmol) suspended in toluene (10 ml), then successively added 2-amino-4-picoline (203 mg, 1.88 mmol) and ethyl ester of 2-{1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-yl}-2-methylpropionic acid (748 mg, 1,71 mmol)obtained in stage 2, and then add cesium carbonate (1,11 g to 3.41 mmol) and the mixture is stirred overnight at a temperature of 100°C. To the reaction solution was added water, extracted with ethyl acetate and washed with saturated saline solution. The organic layer is dried over anhydrous sodium sulfate and the residue obtained by concentration in vacuo, purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate = 1:1 to 1:3) and get listed in the title compound (697 mg, 88%).

1H-NMR (400 MHz, DMSO-d6) δ: at 9.53 (1H, users), of 8.09 (1H, d, J=5,1 Hz), 7.95 is-a 7.92 (1H, m), 7,82 (1H, s), 7,58 (1H, t, J=8.0 Hz), 7,25 (1H, d, J=8,3 Hz), 7,22 (1H, d, J=7,4 Hz), to 6.75 (1H, d, J=5,1 Hz), 4.09 to (2H, q, J=7.0 Hz), 4,06-to 4.01 (2H, m),3,09-2,99 (2H, m)of 2.34 (3H, s), 1,86-to 1.77 (1H, m), 1,68 is 1.60 (2H, m), 1,41 of 1.28 (2H, m)to 1.19 (3H, t, J=7.0 Hz), 1,10 (6H, s).

Stage 4. Obtaining 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid:

To a mixed solution of ethyl ester of 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid (697 mg, 1.50 mmol), obtained in stage 3, in methanol (5 ml) and tetrahydrofuran (10 ml), add 4n. sodium hydroxide (to 3.7 ml, 15 mmol) and the mixture is stirred for 15 hours while heating up to the boiling temperature under reflux. After concentration of the reaction solution is neutralized 1H. hydrochloric acid (15 ml, 15 mmol) and precipitated precipitated solid is separated by filtration, washed with water, ethyl acetate, tetrahydrofuran. Then dried in vacuum and get listed in the title compound (438 mg, 67%).

1H-NMR (400 MHz, DMSO-d6) δ: at 9.53 (1H, users), of 8.09 (1H, d, J=5,1 Hz), 7.95 is-a 7.92 (1H, m), 7,82 (1H, s), 7,58 (1H, t, J=8.0 Hz), 7,25 (1H, d, J=8.0 Hz), 7,22 (1H, d, J=8.0 Hz), to 6.75 (1H, d, J=5,1 Hz), 4,07-4,00 (2H, m), 3,09-2,99 (2H,, m)of 2.34 (3H, s), 1.85 to about 1.75 (1H, m), 1,71-of 1.64 (2H, m), 1,42 of 1.28 (2H, m)of 1.06 (6H, s).

MC: 438,2 (M++1).

Below other aminopyridine compounds having a thiazole ring, get in accordance with a technique similar to the above-mentioned common procedures and/or mentioned in paragraph is imarah. The structure of these compounds was determined by NMR analysis.

These connections are presented in the following tables with the value of their inhibitory activity.

In the present description, the symbol "+++" IC50(·M) means less than 0.1 ·M, and the symbol "++" means not less than 0.1 M and less than 1.0 M, and the symbol "+" means not less than 1.0 ·M.

In addition, preferred compounds of the present invention also VK is ucaut the following connections:

In addition, obtaining the compounds of the present invention, containing thiophene, will be described in detail as examples.

Example 19

Obtain 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone (compound B-1)

Stage 1. Obtain (6-bromopyridin-2-yl)-(4-methylpyridin-2-yl)amine

Suspension in toluene (200 ml) 2,6-dibromopyridine (12.5 g), 2-amino-4-picoline (32,8 g, 139 mmol), palladium acetate (2,59 g, 11.6 mmol), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (8,64 g, a 13.9 mmol), tert-butoxide sodium (13.3 g, 139 mmol) are heated and stirred in a stream of Ar at a temperature of 80°C for 12 hours. To the reaction solution was added water and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, the residue obtained by concentration in vacuo, and purified flash chromatography on silica gel (mixture of n-hexane:ethyl acetate = 3:1) and then washed with isopropyl ether and receive specified in the header connection (15,4 g, 51%).

Stage 2. Obtain 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-and is}ethanone

Suspension in a solvent mixture of dimethoxyethane-water (12 ml) (6-bromopyridin-2-yl)-(4-methylpyridin-2-yl)amine (1,00 g, with 3.79 mmol), 5-acetylthiophene-2-Bronevoy acid (644 mg, with 3.79 mmol), tetrakis triphenylphosphine (440 mg, 0.38 mmol), sodium hydrogen carbonate (480 mg, of 5.68 mmol) are heated and stirred in a stream of Ar at a temperature of 130°C for 12 hours. To the reaction solution was added water and extracted with ethyl acetate. Then the organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, the residue obtained by concentration under vacuum, washed in a mixture of tetrahydrofuran-ethyl acetate (1:1) and get listed in the title compound (426 mg, 36%).

1H-NMR (300 MHz, DMSO-d6): 9,76 (users, 1H, users), to 8.12 (1H, d, J=4,8 Hz), 8,07 (1H, usher.), of 7.96 (1H, d, J=4, 2 Hz), 7,86 (1H, d, J=4, 2 Hz), 7,73 (1H, DD, J=8,1, 7.5 Hz), 7,52 (1H, d, J=7.5 Hz), the 7.43 (1H, d, J=8.1 Hz), to 6.80 (1H, userd, J=4,8 Hz), of 2.56 (3H, s), a 2.36 (3H, s).

Example 20

Getting 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxaldehyde (Compound B-2):

Specified in the title compound (293 mg, 26%) are obtained in accordance with methods analogous to the methods for obtaining compounds described for step 2 of example 14, using (6-bromopyridin-2-yl)-(4-methylpyridin-2-yl)amine (1,00 g, with 3.79 mmol), 5-formylthiophene-2-Bronevoy acid (1.30 grams, 8,33 mm is l), tetranitroaniline palladium (875 mg, from 0.76 mmol), sodium bicarbonate (954 mg, of 11.4 mmol).

1H-NMR (300 MHz, DMSO-d6): 9,95 (1H, s), 9,80 (1H, s), 8,13 (1H, d, J=5,2 Hz), 8,02-8,10 (2H, m), of 7.96 (1H, d, J=3.8 Hz), 7,76 (1H, t, J=7.9 Hz), EUR 7.57 (1H, d, J=7,2 Hz), 7,46 (1H, d, J=8,3 Hz), to 6.80 (1H, DD, J=5,2, 0.9 Hz), 2,37 (3H, s).

Example 21

Obtain 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanol (compound B-3):

The ether solution 3M-methylacrylamide (0,19 ml, or 0.57 mmol) is added to cooled with ice to a solution of 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carbaldehyde (70 mg, 0.24 mmol) in tetrahydrofuran (4 ml), then the mixture is stirred at room temperature for 3 hours in a stream of Ar. To the reaction solution was added water and extracted with ethyl acetate, the organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. Then the residue obtained by concentration under vacuum, washed with isopropyl ether and receive specified in the title compound (46 mg, 62%).

1H-NMR (300 MHz, CDCl3): 8,11 (1H, d, J=7,2 Hz), 7,89 (1H, s), EUR 7.57 (1H, t, J=10,6 Hz), 7,42 (1H, d, J=4,8 Hz), 7,33 (1H, usher.), 7,19 (1H, d, J=9,2 Hz), 7,12 (1H, d, J=11.2 Hz)and 6.9 (1H, DD, J=0,8, 1.2 Hz), was 6.73 (1H, d, J=7,2 Hz), 5,15 (1H, q, J=8,5 Hz)to 2.41 (3H, s), of 1.65 (3H, d, J=8,8 Hz).

Example 22

Obtaining an ethyl acetate ester 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl} acetic acid to the slots (compound B-4)

Acetic anhydride (0,02 ml to 0.19 mmol) are added to a solution of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanol (40 mg, 0.13 mmol) in pyridine (2 ml) and again heated and stirred at 60°C for 9 hours. To the reaction solution was added water and extracted with acetic acid. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, the residue obtained by concentration in vacuo, and purified flash chromatography on silica gel (mixture of n-hexane:ethyl acetate = 2:1) and get listed in the title compound (10 mg, 22%).

1H-NMR (400 MHz, DMSO-d6): for 9.64 (1H, s), to 7.61-8,11 (2H, m), of 7.36 (1H, d, J=10.0 Hz), 7,29 (1H, d, J=11,6 Hz), 7,14 (1H, d, J=4,8 Hz), 6,77 (1H, d, J=7,2 Hz), 6,05-6,11 (1H, m), a 2.36 (3H, s), is 2.05 (3H, s)to 1.61 (3H, d, J=8,4 Hz).

In the description below, other aminopyridine compounds having a thiophene ring, receive in accordance with the General methods and/or examples mentioned above. The structure of these compounds was determined by NMR analysis.

These connections are presented in the following tables with the value of their inhibitory activity.

In the present description, the symbol "+++" IC50(·M) means less than 0.1 ·M, and the symbol "++" means not less than 0.1 M and less than 1.0 ·M, and the symbol "+" means not less than 1.0 ·M.

Studied inhibitory activity against Syk-kinase compounds of the above example. The method of testing was the same as described below, the inhibitory activity, etc. presented in the above tables.

Example 23

Test of inhibition of Syk-kinase (HTRF method):

Once the connections serially diluted with dimethylsulfoxide (DMSO), 10 μl of 10-fold diluted with kinase buffer (20 mm HEPES pH 7.0, 10 mm MgCl 2, 50 mm NaCl, 1 mm 2-ME, of 0.05% BSA) is added to Opti-tablet HTRF-96 (Packard) (with the final concentration of DMSO 2%). Add 20 µl of substrate solution (kinase buffer mentioned above, containing Syk Specific-Peptide Substrate Biot-EDPDYEWPSA-NH2(Peptide Laboratory) 625 nm, 250 μm ATP (SIGMA)) (final substrate concentration of 250 nm, 100 μm ATP), then add 20 μl of an enzyme solution (mentioned above kinase buffer containing GST-Syk Full Protein (human) 16 nm) (final concentration of 6.4 nm); the mixture is immediately shaken on a plate shaker to start the enzymatic reaction. After reaching room temperature (20-25°C) for 30 min, the enzymatic reaction is stopped by adding 100 μl/well of buffer to stop and identify reaction (30 mm HEPES pH 7.0, 150 mm KF, and 0.15% BSA, 0,075% Tween-20, 75 mm EDTA)containing HTRF reagent (5 mg/ml XL665-Streptavidin (CIS bio), 170 ng/ml Eu(K)-anti-PhosphoTyrosin, PT-66 (CIS bio)) (at a final concentration of 20 mm HEPES pH 7.0, 100 mm KF, 0,1% BSA, 0.05% of Tween-20, 50 mm EDTA). After keeping the reaction mixture for 1 hour at room temperature the inhibitory effect of the compounds against Syk kinase enzymatic activity assessed by measurement of the ratio of fluorescence 665/620 to the light excitation at 337 nm using ARVO (Wallac).

Example 24

Test for inhibition of degranulation using a culture of fat cells

(1)Selection hematopoietically the stem cells

After 10-60 ml of umbilical blood collected with the addition of heparin, diluted with an equivalent amount of buffer (0,5% BSA, 2 mm EDTA/PBS), they combine to ficoll-Pak (Amersham Pharmacia Biotech) (ficoll/blood (1:2)) and the fraction of mononuclear leukocytes are selected by zentrifugenbau at 400×g (1350 rpm), 4°C within 30 minutes After centrifugal washing (1500 rpm, 5 min, 4°C × 3) buffer number of cells counted and 0.1 ml of CD34 Progenitor Cell Isolation Kit (Miltenyi Biotec), reagent A1 (Fc-blocking) add for every 1×108cells. After mixing add 0.1 ml of reagent A2 (CD34 antibody-hapten) (final volume 0.5 ml/1×108cells) and incubated at 9°C for an additional 15 minutes after mixing. After centrifugal washing (1500 rpm, 5 min, 4°C × 3) reaction resuspending buffer (0.4 ml) and add 0.1 ml of reagent b (anticapted antibody-beads), stir (final volume 0.5 ml/1×108cells) and incubated at 9°C for another 15 minutes. After centrifugal washing (1500 rpm, 5 min, 4°C × 2) reaction resuspending buffer (0.5 ml) and loaded into the column CS (Miltenyi Biotec), installed in MACS (MAgnetic Cell Sorting system; Miltenyi Biotec, Daiichi Pure Chemicals), then washed with 30 ml of buffer to remove the CD34-cells. The column is separated from MACS and elute with 30 ml of buffer, contacting column CD34+cells are harvested and used as population hematopoietically stem cells.

(2) Obtaining the fat cells of the human body through long-term cultivation of hematopoietic stem cells:

CD34+cells isolated as described in (1), resuspended in the environment Dulbecco modified Iscove's (IMDM, Gibco)containing human (rh)SCF (1 μg/ml, Peprotech), rhIL-6 (0.5 μg/ml, Peprotech), rhIL-3 (10 ng/ml, Peprotech), 1% Insulin-Transferrin (Gibco), 5×10-5M 2-ME (Gibco), 0.1% of BSA (Sigma) with a density of 1×106cells/ml and distributed in 24-hole cell tablet in an amount of 0.1 ml/well, add 0.9 ml of IMDM (Methocult SFBITStemCell technologies)containing 0.9% methylcellulose, and begin cultivation. Described culture medium (except methyl cellulose) is added through the week and then 100 μl/well of the indicated culture medium (excluding IL-3) is added with an interval of a week, so these cells are diluted to maintain the state of 105cells/ml/well and cultivated for more than 8 weeks and thus get the culture of the fat cells.

(3) Increased expression of FcεRI and test on the inhibition of cross-linking of IgE stimulating degranulation

rhIL-4 (at a final concentration of 1 ng/ml, R & D) and Homo sapiens(h) IgE (at a final concentration of 0.5 μg/ml, CHEMICON) add to get the culture of the fat cells and collect within 5 days to enhance the expression of FcεRI. After incubation, the cells are harvested and the Les of centrifugal washing (IMDM) distributed on 96-well culture plate in a 5 × 10 4cells/80 μl/well.

Add 10 ál of connection, 10-fold diluted with IMDM, after dilution in DMSO (the final concentration of DMSO 0.1%) and conducting the reaction for 10 minutes at 37°C. Then add 10 ál of anti-hIgE Ab (CHEMICON), increased to 100 μg/ml (final concentration 10 μg/ml), and cause degranulation by stimulation at 37°C for 30 minutes. After zentrifugenbau collect supernatant and 50 μl/well and stored at -40°C before the measured volume of degranulation. Volume measurement of degranulation perform, using as a measure the enzymatic activity of β-hexosaminidase contained in the granules. That is, an equivalent amount of p-nitrophenyl-N-acetyl-β-D-glucosaminide (1 mm) (containing 0.1% Triton X-100), which is the substrate of β-hexosaminidase add 50 ál of the filtrate of the culture and then incubated at 37°C for 2 hours, the reaction is stopped by application of 100 μl of carbonate buffer (0.1 M, pH 10). Measure the absorbance at a wavelength of 405 nm and the amount (ratio) of degranulation calculate relative level (Total), when cells are destroyed by water. The effect of test compounds on the degranulation reaction is studied using this enzyme activity as an indicator (IC50value (μm)).

Example 25

Test for inhibition of kinase Zap-70 (HTRF method)

Once the connections serially diluted DMSO, 10 µl of them, 10-fold diluted kinase buffer (20 mm HEPES pH 7.0, 10 mm MgCl2, 50 mm NaCl, 1 mm 2-ME, of 0.05% BSA)added to the Opti-tablet HTRF-96 (Packard) (final concentration of DMSO 2%).

Add 20 µl of substrate solution (kinase buffer mentioned above, containing Zap-70-specific peptide substrate Biot-EELQQDDYEMMEENLKKK-NH2(Peptide Laboratory) 625 nm, ATP (SIGMA), 25 μm) (final substrate concentration of 250 nm, 10 μm ATP) and then add 20 μl of an enzyme solution (above kinase buffer containing active Zap-70, UBI) 16 nm) (final concentration of 6.4 nm), the mixture is immediately shaken on a plate shaker to start the enzymatic reaction. After incubation at room temperature for 90 minutes, the enzymatic reaction is stopped by adding 100 μl/well of buffer to stop and determine the reaction (30 mm HEPES pH 7.0, 150 mm KF, and 0.15% BSA, 0,075% Tween-20, 75 mm EDTA)containing HTRF reagent (5 mg/ml XL665-Streptavidin (CIS bio), 170 ng/ml Eu(K)-anti-PhosphoTyrosin, PT-66 (CIS bio)) (final concentration of 20 mm HEPES pH 7.0, 100 mm KF, 0,1% BSA, 0.05% of Tween-20, 50 mm EDTA). After keeping the reaction mixture at room temperature for 1 hour the inhibitory effect of the compounds against Zap-70 kinase enzymatic activity assessed by measurement of the ratio of fluorescence 665/620 to the light excitation at 337 nm with p the power ARVO (Wallac).

Industrial applicability

The compound of the present invention is applicable as an active ingredient of a pharmaceutical product. Because it has inhibitory effect against Syk, the connection is particularly applicable as a preventive/therapeutic agent for diseases in which the allergic or inflammatory response, mediated Syk, is the main etiological cause of asthma, catarrhal rhinitis, atopic dermatitis, contact dermatitis, urticaria, food Allergy, conjunctivitis, spring catarrh, etc), diseases involving ADCC (autoimmune hemolytic anemia, malignant male and so on), and in the brain, involving the aggregation of platelets, etc.

1. Aminopyridine the connection represented by the following General formula (I)

where X1represents a
(1) -C(R2)= or
(2) a nitrogen atom;
X2represents a
(1) -C(R3)= or
(2) a nitrogen atom;
X3represents a
(1) -C(R4)= or
(2) a nitrogen atom;
Z represents a
(1) a nitrogen atom, or
(2) -C(R6')=;
Y1represents a
(1) -CH= or
Y2represents a
(1) -CH= or
(2) a nitrogen atom;
R represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) and the ilen group;
R1represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) a halogen atom;
R2represents a
(1) a hydrogen atom,
(2) C1-6alkyl group, or
(3) a halogen atom;
R3represents a
(1) a hydrogen atom,
(2) a halogen atom,
(3) -N(R31)(R32),
where R31and R32represent a hydrogen atom or a C1-6alkyl group,
(4) a hydroxyl group,
(5) C1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup may be substituted by the Deputy, selected from the following group AA:
[AA]
A. hydroxyl group,
C.-N(R31)(R32),
where R31and R32have the meanings specified above,
E.-CO-N(R31)(R32),
where R31and R32have the meanings specified above, and
f. halogen atom,
(6) urlcategory,
(7) acyl group,
(8) a saturated heterocyclic group, where the heterocyclic group may be substituted C1-6alkyl group, and the saturated heterocyclic group may partially have a double bond,
(9)1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group AB:
[group AB]
A. hydroxyl group,
b. -COOR33where R33has the meaning specified above,
C.-CO-N(R31)( 32), where R31and R32have the meanings specified above, and
d. halogen atom,
(10) -COOR33,
where R33has the meaning specified above,
(11) -CO-N(R31)(R32), where R31and R32have the meanings indicated above, or
(12) a cyano,
R3together with R2can form a group-C=C-C=C-;
R4represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) a nitro-group;
R5represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) -COOR51,
where R51represents a C1-6alkyl group,
R6and R6'may be the same or different, and each represents a
(1) a hydrogen atom,
(2)1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,
(3) -COOR61,
where R61represents a hydrogen atom or a C1-6alkyl group,
(4) -N(R62)(R63),
where R62and R63may be the same or different and each represents a hydrogen atom, a C1-6alkyl group, a C1-6alkoxygroup or acyl group,
(5) -CO-N(R62)(R63),
where R62and R63have the meanings indicated above, or
(6) acyl group;
R7represents a hydrogen atom, atom ha is ogena, the nitro-group, a cyano or Ra, Rb, Rc, Rd, Re, Rf, Rgor Rh;
Rarepresents a CpH2(p-1)(Ra1)(Ra2)-O-Ra3,
where (1) p is an integer from 1 to 6,
(2) Ra1represents a hydrogen atom or a C1-6alkyl group,
(3) Ra2represents a hydrogen atom, a C1-6alkyl group, aracelio group or aryl group, where C1-6alkyl group, kalkilya group and aryl group may be substituted by the Deputy, respectively, selected from the following group VA:
[Group VA]
A. hydroxyl group,
b. carboxypropyl,
S.1-6alkoxycarbonyl group,
d. amino group,
f. di-C1-6alkylamino,
g. alloctype,
(4) Ra3represents a hydrogen atom, acyl group, -CON(Ra31)(Ra32) or (C1-6alkyl group, where the alkyl group may be substituted C1-6alkoxycarbonyl group or-CON(Ra31)(Ra32),
where Ra31and Ra32may be the same or different and each represents a
a hydrogen atom,
With1-6alkyl group,
Ra31and Ra32together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic group which has one or more at the MOU nitrogen, where the saturated heterocyclic group may be substituted by a hydroxyl group, exography, aralkylamines or allmineral;
Rbrepresents-CpH2(p-1)(Rb1)(Rb2)-N(Rb3)(Rb4), where
(1) p is an integer from 1 to 6,
(2) Rb1represents a hydrogen atom or a C1-6alkyl group,
(3) Rb2represents a
A. a hydrogen atom,
b. aracelio group, where kalkilya group may be substituted by a hydroxyl group, With1-6alkoxygroup, which may be substituted by a hydroxyl group, aralkylamines or-N(Rb21)(Rb22),
where Rb21and Rb22may be the same or different, and each represents a hydrogen atom, a C1-6alkyl group, acyl group, carbonyl group, a C1-6alkoxycarbonyl group or alcoxycarbenium group,
C. aryl group, where the aryl group may be substituted by a hydroxyl group, With1-6alkoxygroup or urlcategory, or
d. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Sa:
[Group Sa]
hydroxyl group,
urlcategory,
-COORb23,
where Rb23represents a hydrogen atom, a C1-6alkyl group lierally group,
-N(Rb21)(Rb22), where Rb21and Rb22have the meanings specified above, and
(4) Rb3and Rb4may be the same or different and each represents a
A. a hydrogen atom,
b. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, carboxypropyl, C1-6alkoxycarbonyl group, carbamoyl group, C1-6alkylcarboxylic group and di-C1-6alkylcarboxylic group,
C.-COORb41,
where Rb41represents a hydrogen atom, a C1-6alkyl group or aracelio group,
d. -CORb42,
where Rb42represents a
With1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from
hydroxyl group,
carboxypropyl,
With1-6alkoxycarbonyl group,
acyl group,
alloctype,
the amino and
alluminare,
With3-8cycloalkyl group, where C3-8cycloalkyl group may be substituted by a hydroxyl group,
5 - or 6-membered aromatic heterocyclic group having from 1 to 4 heteroatoms, where the heterocyclic group may be substituted C1-6alkyl group, or
aryl group, where the aryl group may be substituted by a hydroxyl group,
E.-CO-N(R b43)(Rb44), where Rb43and Rb44may be the same or different and each represents a hydrogen atom, a C1-6alkyl group or acyl group, or
f. -SO2-Rb45where Rb45represents a C1-6alkyl group;
Rcrepresents-C(=N-Rc1)-Rc2,
where (1) Rc1represents a
A. hydroxyl group,
b. With1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup may be substituted by a hydroxyl group or a C1-6alkoxygroup, or
C. alloctype, and
(2) Rc2represents a C1-6alkyl group, or amino group;
Rdrepresents-C(=O)-Rd1,
where Rd1represents a
(1) a hydrogen atom,
(2)1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or1-6alkoxycarbonyl group,
(3) a hydroxyl group,
(4) C1-6alkoxygroup and
(5) -N(Rd11)(Rd12),
where Rd11and Rd12may be the same or different and each represents a Deputy selected from the following group Da:
[Group Da]
A. a hydrogen atom,
b. With1-6alkoxygroup,
S.3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group and
d. With1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl,1-6alkoxycarbonyl group or amino group, or
Rd11and Rd12together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic group which has one or more nitrogen atoms, where the saturated heterocyclic group may be substituted With1-6alkyl groups, where the alkyl group may be substituted by carboxypropyl, or carboxypropyl;
Rerepresents the following ring:

where ring a is a
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,
5 - or 6-membered aromatic heterocyclic group having from 1 to 4 heteroatoms,
9-12-membered condensed aromatic heterocyclic group having 1 or 2 heteroatoms, which may be partially saturated,
With3-8cycloalkyl group or
With7-11spiroheterocyclic group having 1 or 2 heteroatom; which can be substituted by the Deputy, respectively, selected from the following group EA:
[Group EA]
a. -ORe1where Re1represents a
a hydrogen atom,
With1-6alkyl group, a C1-6an alkyl group can is to be replaced by carboxypropyl or-CON(R e11)(Re12),
where Re11and Re12may be the same or different and each represents a hydrogen atom or a C1-6alkyl group,
acyl group,
karbamoilnuyu group or
aracelio group,
b. -COORE2,
where Re2represents a hydrogen atom or a C1-6alkyl group,
C.-CO-N(Re41)(Re42),
where Re41and Re42may be the same or different and each represents a
a hydrogen atom,
With1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy chosen from hydroxyl groups, With1-6alkoxygroup, amino, C1-6alkylamino, di-C1-6alkylamino, halogen atom, carboxypropyl, carbamoyl group1-6alkylcarboxylic group, di-C1-6alkylcarboxylic group or 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatom,
hydroxyl group,
With1-6alkoxygroup,
With5-6cycloalkyl group, where C5-6cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, or
With1-6alkylsulfonyl group,
d. -CORe3,
where R represents a
a hydrogen atom,
With1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy selected from a hydroxyl group, carboxypropyl, and C1-6alkylsulfonyl group,
5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatoms, where saturated heterocyclic group or aromatic heterocyclic group may be substituted by a hydroxyl group, exography, carboxypropyl,1-6alkoxygroup, acyl group, amino group, allmineral, di-C1-6alkylaminocarbonyl, and C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, or
With5-6cycloalkyl group or aryl group, where C5-6cycloalkyl group or aryl group may be substituted by a hydroxyl group,
E. oxoprop,
f. -N(Re51)(Re52),
where Re51and Re52may be the same or different, and each represents a
a hydrogen atom,
With1-6alkylsulfonyl group,
With1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy chosen from hydroxyl groups, With1-6alkoxygroup and carbamoyl group,
acyl group, acyl group which may be substituted by a hydroxyl group or a C 1-6alkoxygroup,
-CORe511,
where Re511represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C5-6cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group,
g. With1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group b:
[Group b]
hydroxyl group,
With1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup, can be replaced by carboxypropyl or-CO-N(Re11)(Re12), where Re11and Re12have the meanings specified above,
-COORe2,
where Re2has the meaning specified above,
-N(Re51)(Re52),
where Re51and Re52have the meanings specified above,
-CO-N(Re51)(Re52),
where Re51and Re52have the meanings specified above,
halogen atom, and
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted by a hydroxyl group,
h. -(CH2)n-N(Re61)-(CH2)m-CO(Re62),
where n and m represent an integer of 0 or from 1 to 4, and n+m have a value of from 1 to 6, Re61represents a hydrogen atom or a C1-6alkyl is the Rupp and R e62represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, With1-6alkoxygroup, amino group, With1-6alkylaminocarbonyl or di-C1-6alkylaminocarbonyl,
i. hydroxyisopropyl,
j. With1-6alkylsulfonyl group,
k. cyano,
l. 5 - or 6-membered saturated heterocyclic group (which may be partially unsaturated, containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom, or a 5 - or 6-membered aromatic heterocyclic group containing from 1 to 4 heteroatoms selected from nitrogen atom and oxygen atom, where saturated heterocyclic group and aromatic heterocyclic group may be substituted by oxopropoxy or1-6alkyl group,
m. aminosulfonyl group and
n. With1-6alkylidene group, where C1-6alkylidene group may be substituted by a halogen atom or carboxypropyl;
Rfrepresents a C1-6alkyl group or a C2-6alkenylphenol group specified With1-6alkyl group and C2-6Alchemilla group may be substituted by the Deputy, selected from the following group Fa:
[Group Fa]
A. With1-6alkoxygroup, where C1-6the alkyl group in alkoxygroup, can be replaced by carboxypropyl, 1-6alkoxycarbonyl group or-CON(Rf21)(Rf22),
where Rf21and Rf22may be the same or different and each represents a
a hydrogen atom,
acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl,
With1-6alkoxycarbonyl group,
-O-COORf1,
where Rf1represents a hydrogen atom or a C1-6alkyl group,
With1-6alkyl group,
where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl,1-6alkoxycarbonyl group, carbamoyl group,
With1-6alkylsulfonyl group or
karbamoilnuyu group,
b. -COORf1,
where Rf1represents a hydrogen atom or a C1-6alkyl group,
C.-N(Rf21)(Rf22),
where Rf21and Rf22have the meanings specified above,
d. -CON(Rf21)(Rf22),
where Rf21and Rf22have the meanings specified above,
that is,- N(Rf23)CON(Rf21)(Rf22),
where Rf23represents a hydrogen atom or a C1-6alkyl group, and Rf21and Rf22have the meanings specified above,
f. acyl group and
g. halogen atom;
Rgis a Deputy with the ring, represented by the following formula (II):

where And what predstavljaet a linker, selected from the following group Ga:
[Group Ga]
-(CH2)k-,
-(CH2)k-NRg1-(CH2)j-,
-(CH2)k-O-(CO)NRg1-(CH2)j-,
-(CH2)k-NRg1(CO)-(CH2)j-,
-(CH2)k-(CO)-(CH2)j-,
-(CO)-,
-(CH2)k-O-(CH2)j-,
-(CH2)k-S-(CH2)j-,
-(CH2)k-O-(CO)-(CH2)j-,
-(CO)NRg1and
-(CH2)k-O-(CH2)j(CO)-(CH2)g-,
where k, j and g may be the same or different and represent an integer from 0 to 4, but k and j, or k and g cannot both be 0 at the same time,
Rg1represents a
a hydrogen atom,
hydroxyl group,
With1-6alkoxygroup,
acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl,
With3-8cycloalkyl group, where cycloalkyl group may be substituted With1-6alkyl group, where the alkyl group may be substituted by carboxypropyl,
aracelio group or
With1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group, -N(Rg41)(Rg42or-CON(Rg41)(Rg42),
where Rg41and Rg42may be the same or different and represent
a hydrogen atom,
acyl group, where the acyl group may be substituted by a hydroxyl group,
aracelio group,
With1-6alkylsulfonyl group or
With1-6alkyl group,
where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl,1-6alkoxycarbonyl group, -N(Rg51)(Rg52or-CO-N(Rg51)(Rg52),
where Rg51and Rg52may be the same or different and represent
a hydrogen atom,
acyl group, where the acyl group may be substituted by a hydroxyl group,
With1-6alkyl group,
where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, allmineral,1-6alkoxycarbonyl group or a halogen atom,
With1-6alkoxycarbonyl group,
With1-6alkylsulfonyl group or
With3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup, or
Rg51and Rg52together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic group which has one or more nitrogen atoms, where the saturated heterocyclic group may be substituted by a hydroxyl group or a C1-6alkoxygroup,
the ring is a ring selected from the following group:
[Group]
aryl group,
With3-8cloacina group,
5-7-membered saturated heterocyclic group containing one or more nitrogen atoms,
5-6-membered aromatic heterocyclic group containing at least one heteroatom, and
the ring may be substituted by the Deputy, selected from the following group Ia:
[Group Ia]
a. -ORg2,
where Rg2represents a
a hydrogen atom,
With1-6alkyl group, or
aracelio group,
b. -COORg3,
where Rg3represents a
a hydrogen atom,
With1-6alkyl group, or
aracelio group, where the alkyl group may be substituted by a hydroxyl group,
C.-N(Rg41)(Rg42),
where Rg41and Rg42have the meanings specified above,
d. -CO-Rg53where Rg53represents a
With1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group, carboxypropyl or allmineral,
With3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, With1-6alkoxygroup or exography,
5 - or 6-membered saturated heterocyclic group containing at least one heteroatom, where the saturated heterocyclic group may be substituted by a hydroxyl group, With1-6alkyl group or exography,
aryl group, where the aryl may be substituted Hydra is Xylenol group,
5 - or 6-membered aromatic heterocyclic group containing at least one heteroatom, or
aracelio group;
that is, With1-6alkyl group, where C1-6alkyl group which may be substituted by a hydroxyl group, With1-6alkoxygroup, urlcategory, carboxypropyl,1-6alkoxycarbonyl group, -CO-Rg53where Rg53has the meaning specified above, -N(Rg51)(Rg52or-CO-N(Rg51)(Rg52),
where Rg51and Rg52have the meanings specified above,
f. -CO-N(Rg51)(Rg52),
where Rg51and Rg52have the meanings specified above,
g. With1-6alkylsulfonyl group,
h. oxoprop,
i. aryl group, where the aryl group may be substituted by a hydroxyl group,
j. kalkilya group and
k. halogen atom; and
Rhrepresents-N(Rh1)(Rh2),
where Rhlrepresents a
(1) a hydrogen atom,
(2)1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, With1-6alkoxygroup, -N(Rg51)(Rg52), -CO-N(Rg51)(Rg52), where Rg51and Rg52have the meanings stated above, With1-6alkylsulfonyl group or a halogen atom,
(3) (C2-6alkenylphenol group,
(4)3-8cycloalkyl group, where cycloalkyl group can bytesmessage a hydroxyl group or a C 1-6alkoxygroup, or
(5) Uralkaliy group,
Rh2represents a
(1) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ja:
[Group Ja]
hydroxyl group,
With1-6alkoxygroup,
carboxypropyl,
aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by a hydroxyl group, With1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, a halogen atom, a C1-6alkoxygroup, carboxypropyl,1-6alkoxycarbonyl group2-6alkenylphenol group, where C2-6Alchemilla group may be substituted by carboxypropyl,
With3-8cycloalkyl group, where cycloalkyl group may be substituted by carboxypropyl or urlcategory,
5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom, where the aromatic heterocyclic group may be substituted by carboxypropyl,
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,
-N(Rg51)(Rg52),
where Rg51and Rg52have the meanings specified above,
-CON(Rg51)(Rg52),
where Rg51and Rg52have the meanings specified above,
-CORg53where Rg53has, above, and
-COORg3where Rg3has the meaning specified above,
(2) acyl group, where the acyl group may be substituted by a hydroxyl group,
(3) (C1-6alkoxycarbonyl group,
(4)2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl or a halogen atom,
(5)3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, -COORg3where Rg3has the meaning specified above, -CORg53where Rg53has the meaning specified above, -CONRg51Rg52where Rg51and Rg52each has the meaning indicated above, or With1-6alkyl group, where the alkyl group may be substituted by carboxypropyl,
(6) a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted-CORg53where Rg53has the meaning specified above, -COORg3where Rg3has the meaning specified above, -CONRg51Rg52where Rg51and Rg52each has the meaning indicated above, or With1-6alkylsulfonyl group, or
(7) an aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by carboxypropyl,1-6alkyl group, where the alkyl group can be for esena carboxypropyl or 2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl, or its pharmaceutically acceptable salt.

2. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 1, where Z represents a nitrogen atom.

3. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 2, where aminopyridine compound according to claim 1 is aminopyridine the connection represented by the following General formula (Ia-1):

where X1represents a
(1) -C(R2)=;
X2represents a
(1) -C(R3)= or
(2) a nitrogen atom;
X3represents a
(1) -C(R4)= or
(2) a nitrogen atom;
Y1represents a
(1) -CH=;
R1represents a
(1) a hydrogen atom, or
(2)1-6alkyl group;
R2represents a
(1) a hydrogen atom,
(2) a halogen atom, or
(3) (C1-6alkyl group;
R3represents a
(1) a hydrogen atom,
(2) a halogen atom,
(3) (C1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup can be substituted by the Deputy, selected from the following group AA-1:
[AA-1]
A. hydroxyl group,
C.-N(R31)(R32),
where R31and R32represent a hydrogen atom or a C1-6alkyl groups is,
d. halogen atom,
(4) urlcategory,
(5) acyl group,
(6) saturated heterocyclic group, where the heterocyclic group may be substituted With1-6alkyl group, and the saturated heterocyclic group may partially have a double bond,
(7)1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group AB-1:
[Group AB-1]
A. hydroxyl group,
b. -COOR33where R33represents a hydrogen atom or a C1-6alkyl group,
C.-CO-N(R31)(R32), where R31and R32have the meanings specified above, and
d. halogen atom, or
(8) a cyano, or
R3together with R2can form a group-C=C-C=C-;
R4represents a
(1) a hydrogen atom, or
(2)1-6alkyl group;
R6represents a
(1) a hydrogen atom,
(2)1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,
(3) -COOR61,
where R61represents a hydrogen atom or a C1-6alkyl group,
(4) -N(R62)(R63),
where R62and R63may be the same or different and each represents a hydrogen atom, a C1-6alkyl group, a C1-6alkoxygroup or acyl group,
(5) -O-N(R 62)(R63), where R62and R63have the meanings indicated above, or
(6) acyl group; and
R7is the same as specified in claim 1.

4. Aminopyridine compound or its pharmaceutically acceptable salt according to claims 1-3, where aminopyridine compound according to claims 1-3 represents aminopyridine the connection represented by the following General formula (Ia-2):

where X2represents a
(1) =C(R3)- or
(2) a nitrogen atom;
R2represents a
(1) a hydrogen atom, or
(2) a halogen atom;
R3represents a
(1) a hydrogen atom,
(2) a halogen atom,
(3) (C1-6alkoxygroup,
where C1-6alkyl group With1-6alkoxygroup can be substituted by the Deputy, selected from the following group AA-2:
[Group AA-2]
A. hydroxyl group and
b. halogen atom,
(4) acyl group,
(5) a saturated heterocyclic group, where the heterocyclic group may be substituted With1-6alkyl group, and the saturated heterocyclic group may partially have a double bond,
(6)1-6alkyl group which may be substituted by the Deputy, selected from the following group AB-2:
[Group AB-2]
A. hydroxyl group and
b. halogen atom, or
(7) a cyano, or
R3together with R2can form a group is-C=C-C=C-;
R6represents a
(1) a hydrogen atom, or
(2)1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup;
R7represents a hydrogen atom or Ra, Rb, Rc, Rd, Re, Rf, Rgor Rh;
Rarepresents a CpH2(p-1)(Ral)(Ra2)-O-Ra3,
where (1) p is an integer from 1 to 6,
(2) Ra1represents a hydrogen atom,
(3) Ra2represents a
With1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, alloctype, or di-C1-6alkylaminocarbonyl,
aracelio group, where kalkilya group may be substituted by a hydroxyl group, carboxypropyl or alloctype, or
aryl group,
(4) Ra3represents a hydrogen atom, acyl group, or -(CO)N(Ra31)(Ra32),
where Ra31and Ra32may be the same or different and represent a hydrogen atom or a C1-6alkyl group;
Rbrepresents a CpH2(p-1)(Rbl)(Rb2)-N(Rb3)(Rb4), where
(1) p is an integer from 1 to 6,
(2) Rb1represents a hydrogen atom,
(3) Rb2is the Wallpaper
A. aracelio group, where kalkilya group may be substituted by a hydroxyl group, With1-6alkoxygroup, which may be substituted by a hydroxyl group, aralkylamines or-N(Rb21)(Rb22),
where Rb21and Rb22represent a hydrogen atom, a C1-6alkyl group, acyl group or alcoxycarbenium group,
b. aryl group, where the aryl group may be substituted by a hydroxyl group or urlcategory, or
S.1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, urlcategory, alcoxycarbenium group, amino group,
(4) Rb3represents a hydrogen atom or a C1-6alkyl group,
(5) Rb4represents a
A. a hydrogen atom,
b. C1-6alkyl group, where C1-6the alkyl group may be substituted by carboxypropyl or1-6alkoxycarbonyl group,
C.-CORb32,
where Rb32represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, acyl group, carboxypropyl,1-6alkoxycarbonyl group or alloctype,
or
d. -CON(Rb321)(Rb322),
where Rb321and Rb322represent a hydrogen atom or a C1-6alkyl g is the SCP;
Rcrepresents-C(=N-Rc1)-Rc2,
where (1) Rc1represents a
A. hydroxyl group,
b. With1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup may be substituted by a hydroxyl group, or
C. alloctype,
(2) Rc2represents a C1-6alkyl group
Rdrepresents-C(=O)-Rd1,
where Rd1represents a
(1) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or1-6alkoxycarbonyl group,
(2)1-6alkoxygroup,
(4) -N(Rd11)(Rd12),
where Rd11and Rd12may be the same or different and each represents a
a hydrogen atom,
With1-6alkoxygroup or
With1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl or1-6alkoxycarbonyl group;
Rerepresents a
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,
5 - or 6-membered aromatic heterocyclic group having from 1 to 4 heteroatoms,
9-12-membered condensed aromatic heterocyclic group which may be partially saturated, containing 1 or 2 heteroatom,
With3-8 With7-11spiroheterocyclic group having 1 or 2 heteroatoms, and each may be substituted by the Deputy, selected from the following group EA-1:
[Group EA-1]
a. -ORe1where Re1represents a
a hydrogen atom,
With1-6alkyl group, where C1-6the alkyl group may be substituted by carboxypropyl or SOP(Re11)(Re12),
where Re11and Re12may be the same or different and each represents a hydrogen atom or a C1-6alkyl group,
acyl group,
karbamoilnuyu group or
aracelio group,
b. -COORE2,
where RE2represents a hydrogen atom or a C1-6alkyl group,
C.-CO-N(Re41)(Re42),
where Re41and Re42may be the same or different and each represents a
a hydrogen atom,
With1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy chosen from hydroxyl groups, With1-6alkoxygroup, di-C1-6alkylamino, carboxypropyl, halogen atom, With1-6alkylcarboxylic group and 5 - or 6-membered saturated heterocyclic group or aromatic heterocyclic group having 1 or 2 heteroatom,
hydroxyl group,
With1-6alkoxygroup,
With5-6cycloalkyl group, where C5-6recloak is supplemented flax group may be substituted by a hydroxyl group, or,
With1-6alkylsulfonyl group,
d. -CORe3,
where Re3represents a hydrogen atom, a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxy-group, carboxypropyl or1-6alkylsulfonyl group, 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted by a hydroxyl group, carboxypropyl,1-6alkyl group, acyl group, With1-6alkoxygroup, amino group, alkylamino, dis1-6alkylaminocarbonyl, alkylsulfonamides, allmineral or exography, C5-6cycloalkyl group, where C5-6cycloalkyl group may be substituted by a hydroxyl group, aryl group, where the aryl group may be substituted by a hydroxyl group,
E. oxoprop,
f. -N(Re51)(Re52),
where Re51and Re52may be the same or different and each represents a
a hydrogen atom,
With1-6alkylsulfonyl group,
With1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group,
acyl group, where the acyl group may be substituted by a hydroxyl group, or
-CORe511,
where Re511represents a C5-6recloak the optimum group, where C5-6cycloalkyl group may be substituted by a hydroxyl group,
g. C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group b-1:
[Group b-1]
hydroxyl group,
With1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup can be replaced by carboxypropyl or-CO-N(Re11)(Re12), where Re11and Re12have the meanings specified above,
-COORe2,
where Re2has the meaning specified above,
-N(Re51)(Re52),
where Re51and Re52have the meanings specified above,
-CO-N(Re51)(Re52),
where Re51and Re52have the meanings specified above,
halogen atom, and
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,
h. hydroxyisopropyl,
i. With1-6alkylsulfonyl group,
j. cyano,
k. 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom (which may be partially unsaturated and may be substituted by oxopropoxy or C1-6alkyl group) or an aromatic heterocyclic group containing from 1 to 4 heteroatoms selected from nitrogen atom and oxygen atom,
l. aminosulfonyl group and
m. With1-6alkylidene the th group, where C1-6alkylidene group may be substituted by a halogen atom or carboxypropyl;
Rfrepresents a C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Fa-1:
[Group Fa-1]
A. C1-6alkoxygroup, where C1-6the alkyl group in alkoxygroup can be replaced by carboxypropyl,1-6alkoxycarbonyl group or-CON(Rf21)(Rf22),
where Rf21and Rf22may be the same or different and each represents a
a hydrogen atom,
acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl,
With1-6alkoxycarbonyl group,
-O-COORf1,
where Rf1represents a hydrogen atom or a C1-6alkyl group,
With1-6alkyl group,
where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl,1-6alkoxycarbonyl group or carbamoyl group,
With1-6alkylsulfonyl group or
karbamoilnuyu group,
b. -COORf1,
where Rf1has the meaning specified above,
C.-N(Rf21)(Rf22),
where Rf21and Rf22have the meanings specified above,
d. -CON(Rf21)(Rf22),
where Rf21and Rf22have the meanings specified above,
that is, Zilina group and
f. halogen atom;
Rgis a Deputy with the ring', represented by the following formula (IIA):

where a' represents a linker selected from the following group Ga-1:
[Group Ga-1]
-(CH2)k,
-(CH2)k-NRg1-(CH2)j-,
-(CH2)k-O-(CO)NRg1-(CH2)j-,
-(CH2)k-NRg1(CO)-(CH2)j-,
-(CH2)k-(CO)-(CH2)j-,
-(CO)-,
-(CH2)k-O-(CH2)j-,
-(CH2)k-S-(CH2)j-,
-(CH2)k-O-(CO)-(CH2)jand
-(CH2)k-O-(CH2)j(CO)-(CH2)g-,
where k, j and g may be the same or different and represent an integer from 0 to 4, but k and j, or k and g cannot both be 0 at the same time,
Rg1represents a
a hydrogen atom,
acyl group, where the acyl group may be substituted by carboxypropyl or a hydroxyl group, or
With1-6alkyl group,
ring a' is a ring selected from the following group 1:
[Group-1]
aryl group,
With3-8cycloalkyl group,
5-7-membered saturated heterocyclic group having at least one nitrogen atom, and
5 - or 6-membered aromatic heterocyclic group containing 1 or 2 gets is of rotoma, and
ring' may be replaced by Deputy, selected from the following group Ia-1:
[Group Ia-1]
a. -ORg2,
where Rg2represents a
a hydrogen atom,
C1-6alkyl group, or
aracelio group,
b. -COORg3,
where Rg3represents a
a hydrogen atom or
C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group,
c. -N(Rg41)(Rg42),
where Rg41and Rg42have the meanings specified above,
d. -CO-Rg53where Rg53represents a
C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group, carboxypropyl or allmineral,
C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup or exography,
aryl group, where the aryl group may be substituted by a hydroxyl group,
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted by a hydroxyl group, a C1-6alkyl group or exography,
aracelio group or
5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom,
e. C1-6alkyl group, where C1-6the alkyl group may be substituted by hydroximino group, carboxypropyl or-CO-Rg53where Rg53have the meanings specified above,
f. -CO-N(Rg51)(Rg52),
where Rg51and Rg52may be the same or different and represent
a hydrogen atom,
acyl group, where the acyl group may be substituted by a hydroxyl group,
C1-6alkyl group,
where C1-6the alkyl group may be substituted by a hydroxyl group, carboxypropyl, allmineral, C1-6alkoxycarbonyl group or a halogen atom,
C1-6alkylsulfonyl group,
C1-6alkoxycarbonyl group,
or
C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group or a C1-6alkoxygroup,
g. C1-6alkylsulfonyl group,
h. oxoprop and
i. halogen atom; and
Rhrepresents-N(Rh1)(Rh2),
where Rh1represents a
(1) a hydrogen atom,
(2) C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, a C1-6alkoxygroup, -N(Rg51)(Rg52), -CO-N(Rg51)(Rg52), C1-6alkylsulfonyl or a halogen atom,
where Rg51and Rg52have the meanings specified above,
(3) C2-6alkenylphenol group,
(4) C3-8cycloalkyl group, where cycloalkyl group can be Emesene a hydroxyl group or a C 1-6alkoxygroup, or
(5) Uralkaliy group,
Rh2represents a
(1) C1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group Ja-1:
[Group Ja-1]
hydroxyl group,
C1-6alkoxygroup,
carboxypropyl,
aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by a hydroxyl group, With1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, a halogen atom, a C1-6alkoxygroup, carboxypropyl,1-6alkoxycarbonyl group2-6alkenylphenol group, where C2-6Alchemilla group may be substituted by carboxypropyl,
With3-8cycloalkyl group, where cycloalkyl group may be substituted by carboxypropyl or urlcategory,
5 - or 6-membered aromatic heterocyclic group containing 1 or 2 heteroatom, where the aromatic heterocyclic group may be substituted by carboxypropyl,
5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom,
-N(Rg51)(Rg52and
-CON(Rg51)(Rg52),
where Rg51and Rg52have the meanings specified above,
(2) acyl group, where the acyl group may be substituted by a hydroxyl group,
(3) C 2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl or a halogen atom,
(4) C3-8cycloalkyl group, where cycloalkyl group may be substituted by a hydroxyl group, -COORg3where Rg3has the meaning specified above, -CORg53where Rg53has the meaning specified above, -CONRg51Rg52where Rg51and Rg52each has the value specified above, or C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl,
(5) 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted-CORg53where Rg53has the meaning specified above, -COORg3where Rg3has the meaning specified above, -CONRg51Rg52where Rg51and Rg52each has the value specified above, or C1-6alkylsulfonyl group, or
(6) an aromatic carbocyclic group, an aromatic carbocyclic group may be substituted by carboxypropyl, C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl or C2-6alkenylphenol group, where Alchemilla group may be substituted by carboxypropyl.

5. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 4, where
R2predstavljaet a hydrogen atom,
R3represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group or a halogen atom,
R6represents a hydrogen atom, and
R7is an Re, Rgor Rh.

6. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 5, where
R7is an Reand
Rerepresents a
(1) a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the saturated heterocyclic group may be substituted C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group or-CO-N(Re41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom, or a C1-6alkyl group, or
(2) C3-8cycloalkyl group, where cycloalkyl group may be substituted C1-6alkyl group, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclics the second group, having 1 or 2 heteroatoms, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group or-CO-N(Re41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group.

7. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 6, where
Rerepresents a
(1) a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, represented by the following ring L, where the saturated heterocyclic group may be substituted by 1 or 2 identical or different substituents selected from C1-6alkyl groups, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group, or-CO-N(Re41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group,

where the ring L represents a 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatoms, or (2) a 5 - or 6-membered cycloalkyl the ing group, where cycloalkyl group may be substituted by 1 or 2 identical or different substituents selected from C1-6alkyl groups, where the alkyl group may be substituted by carboxypropyl, -CORe3where Re3represents 5 - or 6-membered saturated heterocyclic group containing 1 or 2 heteroatom, where the 5 - or 6-membered saturated heterocyclic group may be substituted by a hydroxyl group, or-CO-N(Re41)(Re42), where Re41and Re42may be the same or different and each represents a hydrogen atom or a C1-6alkyl group.

8. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 5, where
Rhrepresents-N(Rh1)(Rh2and Rh1represents a C1-6alkyl group, Rh2represents a C3-8cycloalkyl group, where cycloalkyl group can be replaced by a-COORg3where Rg3represents a hydrogen atom or a C1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group.

9. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 1, where aminopyridine compound selected from the following group of compounds:
(001) 1-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-2-it,
(002) 1-{5-[6-(4-methylpyridin the-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid,
(003) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(004) N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(005) N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(006) methyl ester of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic acid,
(007) TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,
(008) (4-hydroxypiperidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(009) N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)amine,
(010) N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(011) (S)-3-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-it,
(012) tert-butyl ether (S)-2,2-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-3-carboxylic acid,
(013) (S)-2-amino-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol,
(014) (S)-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-it,
(015) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(016) TRANS-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl] thiazol-2-yl}amino)methyl]cyclohexanecarbonyl acid,
(017)3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,
(018)-2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,
(019) N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}propionamide,
(020) N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetamide", she
(021) N-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyrazin-2-yl]thiazol-2-yl}acetamide", she
(022) ethyl ester of (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetic acid,
(023) (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol,
(024) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}Etalon,
(025) ethyl ester 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazole-2-carboxylic acid,
(026) the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanone,
(027) (S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}dihydrofuran-2-it,
(028) O-(2-hydroxyethyl)oxime 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanone,
(029) N-methoxy-N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-carboxamid,
(030) N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-carboxamid,
(031) N-methyl-N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(032) (S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-it,
(033) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentane acid,
(034) 5-{5-[6-(4-methylpyridin-2-ylamino)is iridin-2-yl]thiazol-2-yl}pentane-1-ol,
(035) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentanone,
(036) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanol,
(037) oxime 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanone,
(038) N-{6-[2-((S)-1-amino-ethyl)thiazol-5-yl]pyridine-2-yl}-N-([4,4']bipyridinyl-2-yl)amine,
(039) N-((S)-1-{5-[6-([4,4']bipyridinyl-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(040) N-((S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(041) (S)-2-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}propane-1-ol,
(042) N-((S)-1-{5-[6-(isoquinoline-3-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(043) (4-methylpyridin-2-yl)-[6-(2-piperidine-4-iltiazem-5-yl)pyridin-2-yl]amine,
(044) TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(045) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pentylamine,
(046) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}butane-1-ol,
(047) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenol,
(048) 2-hydroxy-N-((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(049) 3-({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazole-2-carbonyl}amino)propionic acid;
(050) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)benzoic acid,
(051) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-ol, (052) 3,3-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}butane-1-ol,
(053) [4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]methanol,
(054) N-((R)-(4-hydroxyphenyl)-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}methyl)acetamide", she
(055) N-(2-hydroxyethyl)-4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)benzamide,
(056) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanone,
(057) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanol,
(058) ((3R,4S)-3,4-dihydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(059) (TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-(piperazine-1-yl)methanon,
(060) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-carboxamide,
(061) 2-hydroxy-1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-yl)Etalon,
(062) TRANS-4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,
(063) 3-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-1-yl)-3-oxopropionate acid,
(064) N-(4-methylpyridin-2-yl)-N-{6-[2-(piperazine-1-ylmethyl)thiazol-5-yl] pyridine-2-yl}amine,
(065) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-ylamine,
(066) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol--ylmethyl}methanesulfonamide,
(067) N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)acetamide", she
(068) TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,
(069) 2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol,
(070) (TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanol,
(071) TRANS-4-{5-[6-(isoquinoline-3-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl acid,
(072) TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylethylamine,
(073) ((3R,4S)-3,4-dihydroxypyrrolidine-1-yl)-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]metano,
(074) N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)ndimethylacetamide,
(075) N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)methanesulfonamide,
(076) 2-hydroxy-N-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)ndimethylacetamide,
(077) 2-hydroxy-N-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]acetamide", she
(078) ((3R,4S)-3,4-dihydroxypyridine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(079) ((R)-3-hydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(080) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-elmet the l}phenyl)methanol,
(081) N-(4-methylpyridin-2-yl)-N-[6-(2-pyridin-3-ilmatieteen-5-yl)pyridin-2-yl]amine,
(082) N-(4-methylpyridin-2-yl)-N-{6-[2-(2-piperidine-4-retil)thiazol-5-yl]pyridine-2-yl}amine,
(083) N-(6-{2-[2-(1-methanesulfonamido-4-yl)ethyl]thiazol-5-yl}pyridine-2-yl)-N-(4-methylpyridin-2-yl)amine,
(084) 2-hydroxy-1-[4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)piperidine-1-yl]alanon,
(085) N-(2-hydroxyethyl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(086) N-(2-morpholine-4-retil)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(087) [3-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenyl]methanol,
(088) (3-hydroxypyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(089) 4-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl)piperazine-2-it,
(090) ((R)-2-hydroxyethylpyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(091) (4-aminopiperidin-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(092) [4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)piperidine-1-yl]-(piperidine-4-yl)methanon,
(093) (TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)-(4-hydroxypiperidine-1-yl)methanon,
(094) N-(4-hydrox is piperidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(095) N-[(R)-2-hydroxy-1-(3H-imidazol-4-ylmethyl)ethyl]-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(096) N-[(S)-2-hydroxy-1-(3H-imidazol-4-ylmethyl)ethyl]-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(097) N-(2-dimethylaminoethyl)-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(098) (3-aminopyrrolidine-1-yl)-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)methanon,
(099) N-[1-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonyl)pyrrolidin-3-yl]methanesulfonamide,
(100) (3R,4S)-1-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexylmethyl)pyrrolidine-3,4-diol,
(101) of TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonitrile,
(102) CIS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarbonitrile,
(103) (S)-5-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-it,
(104) (S)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol,
(105) (S)-1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol,
(106) (S)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethanol,
(107) (S)-5-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-it,
(108) 3-(TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]enous the l-2-yl}cyclohexyl)-4H-[1,2,4]oxazol-5-he,
(109) N-(4-methylpyridin-2-yl)-N-(6-{2-[4-(1H-tetrazol-5-yl)cyclohexyl]thiazole-5-yl}pyridine-2-yl)amine,
(110) (S)-5-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-2-it,
(111) N-(1,1-dimethyl-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)acetamide", she
(112) (S)-1-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol,
(113) N-methyl-TRANS-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(114) N-(1,1-dimethyl-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)methanesulfonamide,
(115) TRANS-4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(116) TRANS-4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexanecarboxylic,
(117) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}cyclohexanol,
(118) (S)-1-(5-{6-[4-(2-hydroxyethoxy)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)ethanol,
(119) dimethylcarbinol acid (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl ester,
(120) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2-it,
(121) 4-(2-hydroxy-2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)phenol,
(122) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}acetyl)piperazine-2-it,
(123) N-((R)-(4-hydroxyphenyl)-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}methyl)-N-m is tileceramic,
(124) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2,6-dione,
(125) (S)-5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}oxazolidin-2-it,
(126) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperazine-2-it,
(127) N-(4-methylpyridin-2-yl)-N-[6-(2-morpholine-4-iltiazem-5-yl)pyridin-2-yl]amine,
(128) 1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,
(129) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-sulfonamide,
(130) N-(4-methoxypyridine-2-yl)-N-{6-[2-(morpholine-4-yl)thiazol-5-yl]pyridine-2-yl}amine,
(131) (3R,4S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3,4-diol,
(132) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}acetamide", she
(133) N-[6-(4-methyl-2-morpholine-4-iltiazem-5-yl)pyridin-2-yl]-N-(4-methylpyridin-2-yl)amine,
(134) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,
(135) N-methyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxamide,
(136) 1-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(137) N-{6-[2-(4-methoxypiperidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,
(138) N-{6-[2-(4-methylpiperazin-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,
(139) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ol,
(140) N-methyl-1-{5-[6-(4-methoxypyridine-2-eliminability-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(141) 4-{4-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carbaldehyde,
(142) methyl ester of 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-4-carboxylic acid,
(143) 2-hydroxy-1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,
(144) 1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)propane-1-he,
(145) N,N-dimethyl-4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-carboxamide,
(146) 1-(4-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,
(147) 1-(4-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)Etalon,
(148) 4-(methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,
(149) 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanecarboxylic,
(150) 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)-4H-[1,2,4]oxadiazol-5-he,
(151) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-piperidine-4-ylamine,
(152) 4-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carbonyl)piperazine-2-it,
(153) N-(2,2-dimethoxymethyl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,
(154) 1-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,
(155) 2-hydroxy-1-[4-(N-is ethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,
(156) N-methyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-carboxamide,
(157) N-{2-[4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]-2-oxoethyl}ndimethylacetamide,
(158) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetic acid,
(159) 2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetamide", she
(160) N-methyl-2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetamide", she
(161) N-(2-hydroxyethyl)-2-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-2-oxopiperidin-1-yl)acetamide", she
(162) N-methyl-N-methylcarbamoylmethyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(163) N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-tetrahydropyran-4-ylamine,
(164) 4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenol,
(165) N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetamide", she
(166) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ylamine,
(167) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,
(168) 2-hydroxy-N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetamide", she
(169) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}Pipa is one-3-carboxamide,
(170) N-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,
(171) N-(2-hydroxyethyl)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,
(172) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol,
(173) of TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanol,
(174) N-{6-[2-(3-methoxypiperidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,
(175) 2-hydroxy-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she
(176) 2-hydroxy-N-methyl-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she
(177) N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)methanesulfonamide,
(178) N-methyl-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)methanesulfonamide,
(179) 2-hydroxy-N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ylmethyl)ndimethylacetamide,
(180) N-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ylmethyl)ndimethylacetamide,
(181) N-methyl-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(182) N-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)methanesulfonamide,
(183) N-{6-[2-((R)-3-ethoxypyrrolidine-1-yl)thiazole-5-yl]pyridine-2-yl}-N-(4-methylpyridin-2-yl)amine,
(184) N-methyl-4-(N-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanecarboxylic,
(185) N-(2-hydroxyethyl)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanecarboxylic,
(186) N-(2-acetylamino)-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexanecarboxylic,
(187) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)acetic acid,
(188) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)methanol,
(189) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)ndimethylacetamide,
(190) 4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(191) N-methyl-4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(192) N-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-ylethoxy)ndimethylacetamide,
(193) N-(2-hydroxyethyl)-4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(194) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she
(195) N-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she
(196) N-(2-hydroxyethyl)-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetamide", she
(197) N,N-diallyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,
(198) N,N-[2-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-the l}amino)ethyl]acetamide", she
(199) 2-hydroxy-N-[2-(N'-methyl-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]acetamide", she
(200) N-(4-methanesulfonamido-1-yl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,
(201) N,N-dimethyl-4-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-carboxamide,
(202) (4-hydroxyphenyl)-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]metano,
(203) 1-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylamino}piperidine-1-yl)Etalon,
(204) 1-[4-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,
(205) N-methyl-2-((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yloxy)ndimethylacetamide,
(206) 1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(207) 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(208) 2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethanol,
(209) N-(2-methoxyethyl)-N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,
(210) N-[2-(N'-(1-acetylpiperidine-4-yl)-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]methanesulfonamide,
(211) 1-[4-(N-(2-hydroxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,
(212) 1-[4-(N-(2-methoxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamine is)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,
(213) (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(214) N-methyl-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(215) N-(2,2,2-triptorelin)-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(216) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,
(217) ((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)methanol,
(218) (R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,
(219) 1-[4-(N-ethyl-N-{5-[6-(4-methylpyridin-2-ylamino),
(220) pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]alanon,
(221) 1-{4-[N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2,2,2-triptorelin)amino]piperidine-1-yl}Etalon,
(222) 1-[4-(N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-methylamino)piperidine-1-yl]alanon,
(223) 1-[4-(N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-methylamino)piperidine-1-yl]-2-hydroxyethane,
(224) (R)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol,
(225) (R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-ol,
(226) 4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxylic acid,
(227) (S)-1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(228) (S)-1-{5-[6-(4-habiri the Jn-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(229) 1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-carboxamide,
(230) 2-(N-(2-hydroxyethyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethanol,
(231) 2-[N-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2-hydroxyethyl)amino]ethanol,
(232) (R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,
(233) 1-(5-{6-[4-(1-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-carboxamide,
(234) (R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol,
(235) 1-(2-{6-[2-((R)-3-hydroxypyrrolidine-1-yl)thiazole-5-yl]pyridine-2-ylamino}pyridine-4-yl)Etalon,
(236) 4-(4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)-4-oxomalonate acid,
(237) N-hydroxy-(R)-1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxamide,
(238) 4-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-yl]-4-oxomalonate acid,
(239) (R)-1-(5-{6-[4-(1-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol,
(240) 2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetamide", she
(241) (R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-3-carboxylic acid,
(242) (R)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-carboxylic acid,
(243) (S)--{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(244) (1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)methanol,
(245) 1-[(R)-3-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pyrrolidin-1-yl]alanon,
(246) (S)-1-{5-[6-(4-acetylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxylic acid,
(247) (R)-1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-3-carboxamide,
(248) ((S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)acetic acid,
(249) (S)-3-methyl-2-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]butyric acid,
(250) 3-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]propionic acid,
(251) [2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetylamino]acetic acid,
(252) [1-(5-{6-[4-(2-methyl-[1,3]dioxolane-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]acetic acid,
(253) (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(254) 4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,
(255) ((R)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yloxy)acetic acid,
(256) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-carboxylic acid,
(257) (R)-1-(5-{6-[4-(2-hydroxyethyl)Piri is in 2-ylamino]pyridine-2-yl}thiazol-2-yl)pyrrolidin-3-ol,
(258) 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)benzoic acid,
(259) (2S,4R)-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pyrrolidin-2-carboxylic acid,
(260) {N-methyl-N-[2-(N'-methyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetyl]amino}acetic acid,
(261) 2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid,
(262) 3-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,
(263) {4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenyl}acetic acid,
(264) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-3-yl)acetic acid,
(265) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperazine-1-yl)acetic acid,
(266) N-(4-methylpyridin-2-yl)-N-(6-{2-[(R)-3-(1H-tetrazol-5-yl)piperidine-1-yl]thiazol-5-yl}pyridine-2-yl)amine,
(267) CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,
(268) TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,
(269) 4-[2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid,
(270) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yloxy)acetic acid, (271) (4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}cyclohexyl)acetic acid,
(272) 4-{[N-methyl-N-(5-{6-[4-(2-methyl-[1,3]dioxolan-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)amino]methyl}benzoic acid,
(273) 4-[(N-dimethylcarbamoyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,
(274) CIS-4-(N-carbamoylmethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,
(275) TRANS-4-[(N-carbamoylmethyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]cyclohexanecarbonyl acid,
(276) 5-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]thiophene-2-carboxylic acid,
(277) 3-chloro-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,
(278) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}benzoic acid,
(279) 3-methoxy-4-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]benzoic acid,
(280) 2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid,
(281) 2-[(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]thiazole-4-carboxylic acid,
(282) [TRANS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid,
(283) [CIS-4-(N-METI is-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid,
(284) 4-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}ethyl)cyclohexanecarbonyl acid,
(285) (4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(286) 4-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid,
(287) {5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylethoxy}acetic acid,
(288) 4-[1-methyl-1-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid,
(289) [4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)phenyl]acetic acid,
(290) (1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(291) TRANS-4-[(N-benzyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]cyclohexanecarbonyl acid,
(292) [TRANS-4-(N-benzyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexyl]acetic acid,
(293) TRANS-4-[(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]cyclohexanecarbonyl acid,
(294) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroquinolin-5-carboxylic acid,
(295) fluoro-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-ilidene)acetic acid,
(296) 5-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentano the traveler acid,
(297) N-[2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetyl]methanesulfonamide,
(298) 4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)butyric acid,
(299) (1-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(300) (1-{5-[6-(5-chloropyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(301) (1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(302) of TRANS-4-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)cyclohexylcarbonyl acid,
(303) 3-[4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)phenyl]propionic acid,
(304) (E)-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,
(305) (2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-6-yl)acetic acid,
(306) 3-(2-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-1,2,3,4-tetrahydroisoquinoline-5-yl)propionic acid,
(307) 5-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane acid,
(308) 5-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-
ylamino}pentane acid,
(309) 6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)hexanoic acid,
(310) (Z)-2-fluoro-6-(N-methyl-N-{5-[6(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,
(311) (8-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-8-azabicyclo[3.2.1]Oct-3-yl)acetic acid,
(312) (8-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-8-azabicyclo[3.2.1]Oct-3-yl)acetic acid,
(313) (1-{5-[6-(4-cyano-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(314) {4-[(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl]phenyl}acetic acid,
(315) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,
(316) (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(317) 4-[1-methyl-1-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)ethyl]benzoic acid,
(318) 3-methyl-6-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,
(319) 3-methyl-6-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,
(320) (E)-6-(N-methyl-N-{5-[6-(4-triptorelin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)Gex-2-ANOVA acid,
(321) N-(2-hydroxyethyl)-(S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(322) 2-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)acetamide", she
(323) 3-methyl-2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)butyramide,
(324) 2-(-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)ethanol,
(325) 5-(N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)pentane-1-ol,
(326) (1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(327) [1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]acetic acid,
(328) fluoro-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(329) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}piperidine-4-carboxamide,
(330) (1-{5-[6-(4-ethylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(331) N-isopropyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amine,
(332) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}-N-(2-morpholine-4-retil)amine,
(333) 2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)acetamide", she
(334) 2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)butyric acid,
(335) of TRANS-4-[(N-methyl-N-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)methyl] cyclohexanecarbonyl acid,
(336) [1-(5-{6-[4-(2,2,2-triptoreline)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]acetic acid,
(337)-2-methyl-1-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)propan-2-ol,
(338) 3-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)propionic acid,
(339) N-(2-hydroxyethyl)-4-(N'-what ethyl-N'-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}amino)piperidine-1-carboxamide,
(340)-2-methyl-2-(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,
(341) 4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)methyl]benzoic acid,
(342) (1-{5-[6-(4-tert-butylpyridinium-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(343) (1-{5-[6-(4-isopropylpyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(344) 2 ylamino)pyridine-2-yl]thiazol-2-yl}-6-azaspiro[2.5]octane-1-carboxylic acid,
(345) 2-[1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]-2-methylpropionate acid,
(346)-2-methyl-2-(1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,
(347) fluoro-(1-{5-[6-(pyrazin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(348) fluoro-(1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid,
(349) [1-(5-{6-[4-(1-hydroxy-1-methylethyl)pyridine-2-ylamino]pyridine-2-yl}thiazol-2-yl)piperidine-4-yl]acetic acid,
(350) 2-methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)propionic acid,
(351) 5-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-3-yl)pentane acid and
(352)-2-methyl-2-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-ylmethyl}amino)propionamide.

10. Aminopyridine compound or the pharmaceutical is Eski acceptable salt according to claim 9, where aminopyridine compound selected from the following group of compounds:
(01) (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamid,
(02) CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}amino)cyclohexylcarbonyl acid,
(03) (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl)thiazol-2-yl}piperidine-4-yl)acetic acid and
(04) (4-methyl-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid.

11. Aminopyridine compound or its pharmaceutically acceptable salt of claim 10, where aminopyridine compound is an (S)-1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}pyrrolidin-2-carboxamide.

12. Aminopyridine compound or its pharmaceutically acceptable salt of claim 10, where aminopyridine connection is a (1-{5-[6-(pyridine-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid.

13. Aminopyridine compound or its pharmaceutically acceptable salt of claim 10, where aminopyridine connection is a (1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiazol-2-yl}piperidine-4-yl)acetic acid.

14. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 1, where aminopyridine compound is a CIS-4-(N-methyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl)thiazol-2-yl}amino)the CEC is hexacarbonyl acid.

15. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 1, where Z represents a carbon atom.

16. Aminopyridine compound or its pharmaceutically acceptable salt according to clause 15, where aminopyridine compound according to claim 1 is aminopyridine the connection represented by the following General formula (Ib-1):

where X1represents a
(1) -CH= or
(2) a nitrogen atom;
Y2represents a
(1) -CH= or
(2) a nitrogen atom;
R represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) acyl group;
R1represents a
(1) a hydrogen atom, or
(2) a halogen atom;
R3represents a
(1) a hydrogen atom,
(2) a halogen atom,
(3) -N(R31)(R32),
where R31and R32represent a hydrogen atom or a C1-6alkyl group,
(4)1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup can be substituted by the Deputy, selected from the following group AA-3:
[Group AA-3]
A. hydroxyl group and
b. -N(R31)(R32),
where R31and R32have the meanings specified above,
(5) acyl group,
(6) saturated heterocyclic group, where the heterocyclic group may be substituted With1-6alkyl group, and saturated the heterocycle is ical group may partially have a double bond,
(7)1-6alkyl group, where C1-6the alkyl group may be substituted by the Deputy, selected from the following group AB-3:
[Group AB-3]
A. hydroxyl group,
b. -COOR33where R33represents a hydrogen atom or a C1-6alkyl group, and
C.-CO-N(R31)(R32), where R31and R32have the meanings indicated above, or
(8) -COOR33where R33has the values listed above;
R5represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) -COOR51,
where R51represents a C1-6alkyl group;
R6and R6' may be the same or different and each represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) acyl group; and
R7matter specified in claim 1.

17. Aminopyridine compound or its pharmaceutically acceptable salt according to clause 16, where aminopyridine connection is aminopyridine the connection represented by the following General formula (Ib-2):

where R3represents a
(1) a halogen atom,
(2) -N(R31)(R32),
where R31and R32represent a hydrogen atom or a C1-6alkyl group,
(3) (C1-6alkoxygroup,
where C1-6alkyl group With1-6alkoxygroup, can b shall be replaced by
Deputy selected from the following group AA-4:
[Group AA-4]
A. hydroxyl group and
b. -N(R31)(R32),
where R31and R32have the meanings specified above,
(4) acyl group,
(5) a saturated heterocyclic group, where the heterocyclic group is partially has a double bond and may be substituted With1-6alkyl group,
(6)1-6alkyl group which may be substituted by the Deputy, selected from the following group AB-4:
[Group AB-4]
A. hydroxyl group,
b. -COOR33where R33represents a hydrogen atom or a C1-6alkyl group, and
C.-CO-N(R31)(R32), where R31and R32have the meanings indicated above, or
(7) -COOR33,
where R33has the meaning indicated above;
R5represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) -COOR51,
where R51represents a C1-6alkyl group;
R6and R6'may be the same or different and each represents a
(1) a hydrogen atom,
(2)1-6alkyl group, or
(3) acyl group;
R7represents a hydrogen atom, a halogen atom, a nitro-group, a cyano or Ra, Rb, Rc, Rd, Re, Rf, Rgor Rh;
Rarepresents a CpH2(-1) (Ral)(Ra2)-O-Ra3where
(1) p is an integer from 1 to 6,
(2) RA1represents a hydrogen atom,
(3) RA2represents a C1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group, a halogen atom, carboxypropyl, and
(4) Ra3represents a hydrogen atom or acyl group;
Rbrepresents a CpH2(p-1)(Rb1)(Rb2)-N(Rb3)(Rb4), where
(1) p is an integer from 1 to 6,
(2) Rb1represents a hydrogen atom,
(3) Rb2represents a C1-6alkyl group,
(4) Rb3represents a hydrogen atom or a C1-6alkyl group and
(5) Rb4represents a
A. a hydrogen atom or
b. -Rb42,
where Rb42represents a C1-6alkyl group;
Rcrepresents-C(=N-Rc1)-Rc2,
where
(1) Rc1represents a
A. hydroxyl group,
b. With1-6alkoxygroup, where C1-6alkyl group With1-6alkoxygroup may be substituted by a hydroxyl group or a C1-6alkoxygroup, or
C. alloctype, and
(2) Rc2represents a C1-6alkyl group, or amino group;
Rdrepresents-C(=O)-Rd1,
where Rd1represents a
(1) the hydrogen atom is,
(2)1-6alkyl group, where C1-6the alkyl group may be substituted by a hydroxyl group,
(3) a hydroxyl group,
(4)1-6alkoxygroup,
(5) -N(Rd11)(Rd12),
where Rd11and Rd12may be the same or different and represent
a hydrogen atom or
With1-6alkyl group, where C1-6the alkyl group may be substituted
amino group, carboxypropyl or a hydroxyl group, or
Rd11and Rd12together with the adjacent nitrogen atom may form a 5 - or 6-membered saturated heterocyclic ring, or
(6)1-6alkoxygroup;
Rerepresents 5 - or 6-membered aromatic heterocyclic group having 1-4 heteroatoms, where the aromatic heterocyclic group may be substituted With1-6alkyl group or oxopropoxy;
Rfrepresents a C1-6alkyl group or a C2-6alkenylphenol group specified With1-6alkyl group and C2-6Alchemilla group may be substituted by the Deputy, selected from the following group Fa-2:
[Group Fa-2]
A. -COOH,
b. -N(Rf21)(Rf22),
where Rf21and Rf22may be the same or different and represent
a hydrogen atom,
acyl group, or
With1-6alkyl group,
where C1-6an alkyl group which may be substituted by carboxypropyl, and
C. halogen atom,
Rgis a Deputy with the ring"represented by
the following formula (IIb);

where a" refers to a linker selected from the following group Ga-2:
[Group Ga-2]
-(CH2)k-,
-(CH2)k-NRg1(CO)-,
-(CH2)k-NRg1-(CH2)j-,
-(CH2)k-O-(CO)-,
-(CH2)k-O-,
-(CO)- and
-(CO)-NRg1-,
where k and j may be the same or different and represent an integer from 1 to 4
Rg1represents a
a hydrogen atom,
acyl group, where the acyl group may be substituted by a hydroxyl group or carboxypropyl, or
- C1-6alkyl group, where the alkyl group can be substituted-CON(Rg41)(Rg42),
the ring" is a ring selected from the following group-2:
[Group-2]
aryl group,
With3-8cycloalkyl group and
5-7-membered saturated heterocyclic group containing at least one nitrogen atom, and
the ring may be substituted by the Deputy, selected from the following group Ia-2:
[Group Ia-2]
a. -ORg2,
where Rg2represents a
a hydrogen atom,
With1-6alkyl group, or
aracelio group, and
b. -COORg3,
where Rg3represents a
a hydrogen atom or
1-6alkyl group, where the alkyl group may be substituted by a hydroxyl group; and
Rhrepresents-N(Rh1)(Rh2),
where Rh1represents a hydrogen atom and Rh2represents an acyl group, where the acyl group may be substituted by a hydroxyl group or a C1-6alkoxycarbonyl group.

18. Aminopyridine compound or its pharmaceutically acceptable salt according to claim 1, where aminopyridine compound selected from the following group of compounds:
(01) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,
(02) 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carbaldehyde,
(03) 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanol,
(04) ethyl ester 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}acetic acid,
(05) N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}acetamide", she
(06) N-methyl-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamid,
(07) {5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}methanol,
(08) the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone,
(09) 1-{5-[6-(4-methoxypyridine-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,
(10) 5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamid,
(11) 1-{5-[6-(6-isopropoxypyridine-4-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,
(12) N-{5-[6-(4-methylpyridin-2-ylamino)p is ridin-2-yl]thiophene-2-yl}acetamide", she
(13) O-(2-hydroxyethyl)oxime 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone,
(14) N-(2-amino-ethyl)-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamid,
(15) the oxime of 1-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}propane-1-it,
(16) ethyl ether {2-[6-(5-acetylthiophene-2-yl)pyridine-2-ylamino]pyridine-4-yl}acetic acid,
(17) methyl ester 2-[6-(5-acetylthiophene-2-yl)pyridine-2-ylamino]isonicotinic acid,
(18) 1-(5-{6-[4-(2-hydroxyethyl)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)ethanol,
(19) N-hydroxy-5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-carboxamidine,
(20) 1-(5-{6-[4-(2-hydroxyethoxy)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)Etalon,
(21) 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}Etalon,
(22) the oxime of 1-{5-[6-(4-chloropyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}ethanone,
(23) {5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}piperazine-1-ylmethanone,
(24) 1-(5-{6-[4-(4,4-dimethyl-4,5-dihydrooxazolo-2-yl)pyridine-2-ylamino]pyridine-2-yl}thiophene-2-yl)Etalon,
(25) 2.2-debtor-3-hydroxy-3-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-yl}propionic acid,
(26) 4-[({5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid,
(27) 4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid,
(28) TRANS-4-[(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-yl]thiophene-2-ylmethyl}amino)methyl]cyclohexanecarbonyl acid,
(29) 3-(N-acetyl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)propionic acid;
(30) 4-[(N-isobutyryl-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid
(31) 4-[(N-(2-hydroxyacyl)-N-{5-[6-(4-methylpyridin-2-ylamino)pyridine-2-yl]thiophene-2-ylmethyl}amino)methyl]benzoic acid.

19. The pharmaceutical composition intended for the treatment or prevention of allergic diseases, autoimmune diseases or malignant tumors, containing as the active ingredient aminopyridine compound or its pharmaceutically acceptable salt according to claim 1.

20. Syk inhibitor containing as the active ingredient aminopyridine compound or its pharmaceutically acceptable salt according to claim 1.

21. Therapeutic and/or prophylactic agent for the treatment of allergic diseases, autoimmune diseases or malignant tumors, containing as the active ingredient aminopyridine compound or its pharmaceutically acceptable salt according to claim 1.

22. Therapeutic and/or prophylactic agent according to item 21, where the allergic disease is asthma, allergic rhinitis, allergic dermatitis or allergic conjunctivitis.

23. Therapeutic and/or prophylactic agent according to item 21, where autoimmune Soboleva who eat are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis.

24. Therapeutic or prophylactic agent according to item 21, where a malignant tumor is lymphoma or b-cell leukemia.



 

Same patents:

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry; medicine.

SUBSTANCE: compounds of claimed invention possess properties of positive allosteric modulator mGluR5. In general formula I , W represents 6-member heterocycloalkyl ring with 1-2 heteroatoms, selected from N, O; R1 and R2 independently represent hydrogen, C1-C6-alkyl; P and Q each independently is selected from: , R3, R4, R5, R6 and R7 independently represent hydrogen; halogen; -CN; nitro; C1-C6-alkyl; C3-C6-cycloalkyl; halogen-C1-C6-alkyl; 5-6-member heteroaryl with 1-2 atoms N as heteroatoms; 6-member heterocycle with 2 heteroatoms representing N, O; phenyl, optionally substituted with halogen; naphtyl; -OR8; where optionally two substituents together with located between them atoms form 9-10-member bicyclic aryl or heteroaryl ring with 1-2 heteroatoms, selected from N, S; R8 represents hydrogen, C1-C6-alkyl; D, E, F, G and H independently represent -C(R3)=, -O-, -N=, -N(R3)- or -S-; A represents ethinyl, -C(=O)NR8- or group of formula . B represents -C(=O)-C0-C2-alkyl-, -C(=O)-C2-C6-alkenyl-. Invention also relates to pharmaceutical composition based on invention compounds.

EFFECT: novel compounds possess useful biological proprties.

20 cl, 3 dwg, 75 ex

FIELD: chemistry.

SUBSTANCE: invention is related to compounds of formula (II) as inhibitor of leukotriene A4-hydrolase (LTA4H) and their enantiomers, racemic compounds and pharmaceutically acceptable salts, and also to treatment methods, method inhibition and pharmaceutical composition on their basis. In general formula (II) , X is selected from group that consists of O and S; Y is selected from group that consists of CH2 and O; R4 represents H; R6 represents H or F; and R2' is determined as R2, and R3' is determined as R3, as follows: R2 and R3, each, is independently selected from group that consists of A) H, C1-7alkyl, C3-7cycloalkyl, where each of substitutes of A) is independently substituted with 0 or 1 RQ, and each of mentioned RQ is substitute at carbon, which is distanced from nitrogen at least by one carbon atom; alternatively, R2 and R3, taken together with nitrogen, to which they are connected, create heterocyclic ring, which contains at least one heteroatom, which is specified nitrogen of connection, and specified heterocyclic ring is selected from group that consists of i) (4-7)-member heterocyclic ring HetRb, where specified (4-7)-member heterocyclic ring HetRb has single heteroatom, which is specified nitrogen of connection, and 0, 1 or 2 are substituted by substitutes at the same or different substituted atoms, at that specified substitutes are selected from group that consists of -RY, -C(O)RY, -C0-4alkylCO2RY, -C0-4alkylC(O)NRYRZ, -C0-4alkylNRYC(O)Rz, -C0-4alkylNRYC(O)CH2ORY, -C0-4alkylNRYCO2RY, -C0-4alkylNRYC(O)NRYRz, -C0-4alkylNRyC(S)NRyRz, -NRyC(O)CO2Ry, -C0-4alkylNRwSO2RY, tetrazol-5-yl, -C0-4alkylN(RY)(SO2)NRYRY, -C0-4alkylN(RY)(SO2)NRYCO2RY, ii) (5-7)-member heterocyclic ring HetRc, where specified (5-7)-member heterocyclic ring has single additional heteroatom distanced from specified nitrogen of connection at least by one carbon atom, thereat the specified additional heteroatom is selected from group that consists of O, S(=O)0-2 and >NRM, and where mentioned (5-7)-member heterocyclic ring HetRc has 0 or 1 carbonyl group; iv) one of 2,8-diazaspyro[4.5]decan-1-on-8-yl, 4-{[(2-tret- butoxycarbonylaminocyclobutancarbonyl)amino]methyl}-piperidine-1-yl, 4-{[(2-aminocyclobutancarbonyl)amino]methyl}piperidine-1-yl, tret-butyl ether of 3,9-diazaspyro [5.5]undecan-3-carbonic acid-9-yl; where RK is selected from group that consists of H, -C1-4alkyl, each not necessarily substituted by 1 substitute RN; RM is selected from group that consists of -SO2RY, -C(O)RY, -C(O)C1-4alkylORY, each not necessarily substituted by 1 substitute RN; RN is selected from group that consists of OH, NH2, CF3; RQ is selected from group that consists of -C0-4alkylRAr', -C0-4alkylCO2RY, -C0-4alkylNRYRz, -C0-4alkylNRYCORY, -C0-4alkylNRyCONRyRz; Rw is selected from group that consists of RY and -C3-7cycloalkyl; RY is selected from group that consists of H, -C1-4alkyl, -C0-4alkylRAr and -C0-4alkylRAr', each not necessarily substituted by 1 substitute RN; Rz is selected from group that consists of RY, -C1-2alkylCO2RY; RAr represents fragment connected via carbon atom, and specified fragment is selected from phenyl, pyridyl; RAr' represents (5-6)-member cyclic ring, having 1 or 2 heteroatoms selected from group that consists of O, N and >NRY, having 0 unsaturated connections, having 0 or 1 carbonyl group, where each atom, when allows for valency, in every of mentioned cyclic rings is independently substituted by 0 or 1 RK; provided that (a) specified R2' and R3', moreover, satisfy the following requirements: (e1): specified R2' and R3', both, are not H, when Y represents O and X represents S; (e3): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperazine group, when X represents O and Y is one of O and CH2; (e4): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperidine group, which is mono-substituted by 6-member cyclic group, when X represents O and Y is one of O and CH2; and (e5): specified R2' and R3', taken together with nitrogen, with which they are connected, create neither substituted piperidine group or substituted piperazine group, where specified substituted piperidine group or specified substituted piperazine group is substituted in position 4 by substitute XG, at that specified XG has structure , where n=0, 1, and when ne=1, then XL represents C1-6alkyl, OSG represents O or S, and XR1 and XR2, taken together with nitrogen, with which they are connected, create one of piperidine group, piperazine group, morpholine group, thiomorpholine group and pyrrolidine group, or each of XR1 and XR2, taken independently, represent one of H, C1-6alkyl, aryl, aralkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, heteroalkyl, heteroaryl-C1-6alkyl, heterocycloalkyl and heterocycloalkyl-C1-6alkyl; where aryl, aralkyl, cycloalkyl, heteroaryl or heterocycloalkyl may be not necessarily substituted by one or several substitutes, independently selected from halogen, hydroxy, C1-6alkyl, C1-6alkoxy, halogenated C1-6alkyl, halogenated C1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or heterocycloalkyl; and (b) further provided that when X represents S and Y represents O, then one of R2' and R3' is not XCG, while the other represents C1-6alkyl, where XCG represents group , where HC16 represents one of H, C1-6alkyl, halogenC1-6alkyl, allyl and C1-6alcoxymethyl, and GO represents group connected to carbon atom, which has substitute =0, creating amido group with nitrogen, with which all mentioned GO group is connected.

EFFECT: compounds may find application for treatment and prevention of diseases mediated by LTA4H, for instance, asthma, chronic obstructive lung disease, atherosclerosis, rheumatoid arthritis, disseminated sclerosis, inflammatory disease of bowels and psoriasis.

39 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of formula I: , their optical isomers or optical isomer mix, and pharmaceutically acceptable salts, where: R1 is independently selected out of group including: aryl, heteroaryl, arylcarboxyamido, heteroarylcarboxyamido, aryloxy, arylalcoxy or arylamino, and where indicated groups of aryl, aryalkyl or heteroaryl can be substituted by 0-3 substitutes R1a, where R1a is independently selected out of group including: halogen, alkyl, alkenyl, alcoxy, alcoxyalkyl, hydroxyalkyl, mono-, di- or trihalogenoalkyl, mono-, di- or trihalogenoalcoxy, mono- or disubstituted aminoalkyl, aminocarbonyl, mono- or disubstituted aminocarbonyl, cyclic aminocarbonyl, alkylsulfonyl, etherified carboxylic acid residue, arylcarbonylamino, carbamate, R1b-aryl or R1b-heteroaryl where R1b is H, halogen, OH, amino, mono- or disubstituted amino, mono-, di- or trihalogenoalkyl, alkcoxy, mono-, di- or trihalogenoalcoxy, hydroxyalkyl; R2 is independently selected out of group including: H, OH, cyano, halogen or aryl; optionally R1 and R2 can be linked to form spirocyclyl; R3, R4, R5 and R6 are H; optionally R1 and R3 can be cyclised to form carbocycle; optionally R3 and R4 or R5 and R6 are cyclised to form bicyclic bridge system including ethylene bridge; optionally R3 and R6 are cyclised to form bicyclic bridge system including methylene or ethylene group; R7 and R8 are independently selected out of group including hydrogen, OH, C1-C8alkyl, arylalcoxy, heteroarylalcoxy; optionally R7 and R9 can be cyclised to form spirocarbocycle or spiroheterocycle; and m=0-5; where "aryl" term denotes aromatic carbocyclic groups such as phenyl, biphenyl, indenyl, naphthyl, and aromatic groups condensed with heterocycles; where "heterocycle" term denotes aromatic and non-aromatic rings including 3 to 10 atoms in the ring, 1-4 of which are heteroatom selected out of oxygen, sulfur or nitrogen; where "alkyl" term, when used separately or as suffix, denotes branched or non-branched alkyl group including 1 to 8 carbon atoms in chain; where "alkenyl" term denotes non-saturated branched or non-branched alkyl group including 2 to 12 carbon atoms in chain.

EFFECT: compounds applicable as chemokine receptor activity modulators.

15 cl, 1 tbl, 372 ex

FIELD: chemistry.

SUBSTANCE: there are disclosed 1-(2-aminobenzol)piperazine derivatives of formula (I) and pharmaceutically acceptable acid-additive salts with radical values specified in patent claim. The compounds are characterised with inhibiting effect on glycine I carrier. There is also disclosed medical product based on the compounds of formula (I).

EFFECT: compound can be used for treatment of the diseases associated with glycine uptake inhibition.

12 cl, 5 tbl, 396 ex

FIELD: chemistry.

SUBSTANCE: described is novel compound of formula (I)

or its pharmaceutically acceptable salt, values of radicals are given in invention formula Compound has ability to inhibit receptor mGluR5, which intends it for prevention and/or treatment of receptor mGluR5- associated disturbances. Also described is pharmaceutical composition, method of inhibiting activation of receptors mGluR5, using compound of formula (I). Described is method of obtaining compound of formula 1a or 1b structure.

EFFECT: increasing output of suitable product.

18 cl, 825 ex

FIELD: chemistry.

SUBSTANCE: invention refers to benzothiazol derivatives of general formula (I) and to their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands and to based medicinal agent. In general formula (I) , R1 represents 1,4-dioxepanyl or tetrahydropyran-4-yl; R2 represents -N(R)-(CH2)n-5- or 6-merous nonaromatic heterocycle containing 1-2 nitrogen heteroatoms optionally substituted with one-two substitutes chosen from group, consisting of C1-C6alkyl or -NR2, or represents -(CH2)n-5- or 6-merous nonaromatic heterocycle containing 1-2 heteroatoms chosen of N, S or O, optionally substituted with group -(CH2)n-OH, C1-C6alkyl, C1-C6alkoxy, or represents -(CH2)n-5-or 6-merous aromatic heterocycle containing 1-2 nitrogen heteroatoms optionally substituted with the following group: C1-C6alkyl, C1-C6alkoxy, halogen, halogen-(C1-C6alkyl), -CH2N(R)(CH2)2OCH3, -N(R)(CH2)2OCH3, - CH2-morpholinyl or -CH2-pyrrolidinyl or represents (CH2)n-C3-C6cycloalkyl optionally substituted with group hydroxy, or represents -N(R)-C3-C6cycloalkyl optionally substituted with group hydroxy or C1-C6alkyl, or represents phenyl optionally substituted with group C1-C6alkoxy, halogen, halogen-(C1-C6alkyl), C1-C6alkyl, -CH2-pyrrolidine-1-yl, CH2N(R)(CH2)2OCH3 or -CH2-N(R)C(O)-(C1-C6alkyl), or represents 1,4-dioxa-8-azaspiro[4,5]decane, or 2-oxa-5-azabicyclo[2,2,1]heptane, or 1-oxa-8-azaspiro[4,5]decane, or -N(R)-7-oxabicyclo[2,2,1]hept-2-yl, or 2-azabicyclo[2,2,2]octane; R represents hydrogen or C1-C6alkyl; n stands for 0 or 1.

EFFECT: compounds can be applied for treatment and prevention of diseases mediated by adenosine A2A and A1 receptors, eg Alzheimer's disease, some depressions, toxicomania, Parkinson's disease.

8 cl, 3 dwg, 61 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: compounds of formula (I) as inhibitors of phosphotyrosine phosphotase 1B and their pharmaceutically acceptable salts, their application, based pharmaceutical composition and method of production. In general formula (I) , R1 indicates phenyl, naphthyl, thionaphthyl, pyridyl. Phenyl, naphthyl, thionaphthyl and pyridyl can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, CF3, OCF3, N(R9)(R10), piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, NO2, CN, O-(C1-C6)-alkyl, S(O)0-2-(C1-C6)-alkyl, SO2-N(R9)(R10), CO-(C1-C6)-alkyl, -COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkyleny-COO(C1-C6)-alkyl, (C3-C10)-cycloalkyl, phenyl. These piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, and phenyl rings can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, COOH, CN, NO2, O-(C1-C6)-alkyl, -NH-O-(C1-C6)-alkyl, -(CO)-NH-O-(C1-C6)-alkylene-N(R9)(R10), -(CO)-(C1-C6)-alkyl, -(C1-C6)-alkyl, CF3, OCF3, N(R9)(R10); R2 indicates H, (C1-C6)-alkyl, COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkylene-COO(C1-C6)-alkyl; R3 indicates H, (C1-C6)-alkyl, (C1-C6)-alkylenphenyl, -C(O)-phenyl, (C1-C6)-alkylenheterocycle, where heterocycle represents 5-6-merous heterocyclic ring containing 1-2 heteroatoms, chosen of nitrogen and oxygen, CO-(C1-C6)alkyl; R4, R5 indicate H; R6 indicates H, R9 indicates H, (C1-C4)-alkyl; R10 indicates H, (C1-C4)-alkyl.

EFFECT: applications for treating diseases mediated with phosphotyrosine phosphotase 1B activity, such as diabetes type II, lipidosis and carbohydrate metabolic imbalance, insulin resistivity, reduced sugar content in blood.

9 cl, 2 tbl, 1 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: new compounds of formula (I) and its pharmaceutically acceptable salts. Offered compounds possess properties of bacterial gyrase and Topo-IV activity inhibitor. In general formula (I) , W is chosen from CH or CF; X represents CH; Z represents O or NH; R1 represents phenyl or 5-6-merous heteroaryl ring containing 1-3 nitrogen atoms where R1 is substituted with 0-3 groups independently chosen from -(T)y-Ar, R', oxo, C(O)R', OR', N(R')2, SR', CN or C(O)N(R')2; R2 is chosen from C1-3alkyl and C3-7-cycloalkyl; and ring A represents 5-6-merous heteroaryl ring containing 1-3 heteroatoms, independently chosen of nitrogen, oxygen or sulphur provided the specified ring has hydrogen bond acceptor in position adjacent to that of joining to B ring where ring A is substituted with 0-3 groups independently chosen from R', oxo, CO2R', OR', N(R')2, halogen, CN, C(O)N(R')2, NR'C(O)R', or NR'SO2R', and where two substitutes in adjacent positions of ring A, together can form 6-merous saturated heterocyclic or heteroaryl ring containing 1-2 nitrogen atoms.

EFFECT: pharmaceutical compositions with properties of bacterial gyrase and Topo-IV activity inhibitor containing disclosed compound as active component, method of gyrase and/or Toro IV-activity inhibition, method of bacteria number reduction.

25 cl, 3 tbl, 4 dwg, 29 ex

FIELD: medicine.

SUBSTANCE: formula bond

or it pharmaceutically comprehensible salt where value of radicals are specified in the invention formula is described. The bonds are effective as inhibitors of protein kinases FLT-3 or KIT. A way of inhibition of activity kinases FLT-3 or KIT in the biological sample in vitro and application of bonds for manufacture of a medical product, suitable for treatment or simplification of gravity of disease or a condition, the chosen acute myelogenetic leukosis, acute progranulocytic leukemia or acute lymphocytic leukosis or cancer of ovaries are described also.

EFFECT: rising of efficiency of a composition and the method of treatment.

11 cl, 86 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry, medicine.

SUBSTANCE: invention refers to the triheterocylic compounds of formula (Ia) and their pharmaceutically acceptable salts used as growth inhibitors of the cancer or tumor cells, to the preparation method and pharmaceutical compositions thereof, to the treatment method used aforesaid compounds as well as to the intermediates of formula (II) the to the method of its preparation. In general formulas (Ia) and

, Q1 is -N(R1)-; Q2 is -C(R3)-; Q3 is -C(R5)-; Q4 is -C(R9)-; R1 is -Ym(Ra), where -Ra is -H, -OH, -C(O)R14, -O-C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OS(O)2ONa-; R2 is -H; R3, R4 and R5 independently are -Ym(Rb), where Rb is -H, halogen, -C1-C8 alkyl, -O-(C1-C8 alkyl) or -OR14, -at condition that if value m of radical Ym(Rb) is equal 0, then R5 is not H; R6 is -H; R7 is -Ym-(RC), where -RC is -O-(C1-C8 alkyl) or -NH(phenyl), R8 is -Ym(Rd), where - Rd is -H, -OH, R9, R10, R11, R12 and R13 independently are -Ym(Re), where Re is -H, halogen, 5-6-membered heterocycle containing 2 heteroatoms selected from N or O, -OR14, or -O-C(O)OR14; every R14 independently is -H, -C1-C8 alkyl, -phenyl, 5-6-membered heterocycle containing one heteroatom being S; every Y independently is -C1-C8 alkylene-; every m independently is equal 0 or 1.

EFFECT: claimed compounds can find application for treatment of different cancer species.

41 cl, 4 tbl, 4 dwg, 8 ex

FIELD: chemistry; medicine.

SUBSTANCE: compounds of claimed invention possess properties of positive allosteric modulator mGluR5. In general formula I , W represents 6-member heterocycloalkyl ring with 1-2 heteroatoms, selected from N, O; R1 and R2 independently represent hydrogen, C1-C6-alkyl; P and Q each independently is selected from: , R3, R4, R5, R6 and R7 independently represent hydrogen; halogen; -CN; nitro; C1-C6-alkyl; C3-C6-cycloalkyl; halogen-C1-C6-alkyl; 5-6-member heteroaryl with 1-2 atoms N as heteroatoms; 6-member heterocycle with 2 heteroatoms representing N, O; phenyl, optionally substituted with halogen; naphtyl; -OR8; where optionally two substituents together with located between them atoms form 9-10-member bicyclic aryl or heteroaryl ring with 1-2 heteroatoms, selected from N, S; R8 represents hydrogen, C1-C6-alkyl; D, E, F, G and H independently represent -C(R3)=, -O-, -N=, -N(R3)- or -S-; A represents ethinyl, -C(=O)NR8- or group of formula . B represents -C(=O)-C0-C2-alkyl-, -C(=O)-C2-C6-alkenyl-. Invention also relates to pharmaceutical composition based on invention compounds.

EFFECT: novel compounds possess useful biological proprties.

20 cl, 3 dwg, 75 ex

FIELD: chemistry.

SUBSTANCE: invention can be applied in medicine and concerns inhibitors of MaR-kinase p38 of formula where W represents N or O, when Y represents C, and W represents C, when Y represents N; U represents CH or N; V represents C-E or N; X represents O, S, SO, SO2, NH, C=O,-C=NOR1 or CHOR1; B represents H or NH2; R1, E and A stands for H or various alkyl, heteroalkyl, aromatic and heteroaromatic substitutes.

EFFECT: production of new biologically active compounds.

48 cl, 138 ex, 54 dwg

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: described is novel compound of formula (I)

or its pharmaceutically acceptable salt, values of radicals are given in invention formula Compound has ability to inhibit receptor mGluR5, which intends it for prevention and/or treatment of receptor mGluR5- associated disturbances. Also described is pharmaceutical composition, method of inhibiting activation of receptors mGluR5, using compound of formula (I). Described is method of obtaining compound of formula 1a or 1b structure.

EFFECT: increasing output of suitable product.

18 cl, 825 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: new compounds of formula (I) and its pharmaceutically acceptable salts. Offered compounds possess properties of bacterial gyrase and Topo-IV activity inhibitor. In general formula (I) , W is chosen from CH or CF; X represents CH; Z represents O or NH; R1 represents phenyl or 5-6-merous heteroaryl ring containing 1-3 nitrogen atoms where R1 is substituted with 0-3 groups independently chosen from -(T)y-Ar, R', oxo, C(O)R', OR', N(R')2, SR', CN or C(O)N(R')2; R2 is chosen from C1-3alkyl and C3-7-cycloalkyl; and ring A represents 5-6-merous heteroaryl ring containing 1-3 heteroatoms, independently chosen of nitrogen, oxygen or sulphur provided the specified ring has hydrogen bond acceptor in position adjacent to that of joining to B ring where ring A is substituted with 0-3 groups independently chosen from R', oxo, CO2R', OR', N(R')2, halogen, CN, C(O)N(R')2, NR'C(O)R', or NR'SO2R', and where two substitutes in adjacent positions of ring A, together can form 6-merous saturated heterocyclic or heteroaryl ring containing 1-2 nitrogen atoms.

EFFECT: pharmaceutical compositions with properties of bacterial gyrase and Topo-IV activity inhibitor containing disclosed compound as active component, method of gyrase and/or Toro IV-activity inhibition, method of bacteria number reduction.

25 cl, 3 tbl, 4 dwg, 29 ex

FIELD: medicine.

SUBSTANCE: formula bond

or it pharmaceutically comprehensible salt where value of radicals are specified in the invention formula is described. The bonds are effective as inhibitors of protein kinases FLT-3 or KIT. A way of inhibition of activity kinases FLT-3 or KIT in the biological sample in vitro and application of bonds for manufacture of a medical product, suitable for treatment or simplification of gravity of disease or a condition, the chosen acute myelogenetic leukosis, acute progranulocytic leukemia or acute lymphocytic leukosis or cancer of ovaries are described also.

EFFECT: rising of efficiency of a composition and the method of treatment.

11 cl, 86 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. Claimed compounds have antibacterial effect. In formula (I) , X is ; R1 is i) hydrogen, ii) (CH2)nNR5R6, iv) NRCO2R, v) (C1-6alkyl)CN, CN, (CH2)pOH; Y is NR*, O or S(O)p; is phenyl or 5-6-member heteroaryl with N or S as heteroatoms; R3 is NR(C=X2)R12, NR*R12, or -(O)n-5-6-member heteroaryl with 1-3 heteroatoms selected out of N, O, which can be linked over either carbon atom or heteroatom; the indicated 5-6-member heteroaryl can be optionally substituted by 1-3 groups of R7; R4, R4a, R4b and R4c are independently i) hydrogen, ii) halogen; other radicals are defined in the claim.

EFFECT: pharmaceutical composition containing effective volume of the claimed compound.

13 cl, 1 dwg, 194 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

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