CN101379065A

CN101379065A - Imidazopyridine derivatives inhibiting protein kinase activity, method for the preparation thereof and pharmaceutical composition containing same

Info

Publication number: CN101379065A
Application number: CNA2007800029050A
Authority: CN
Inventors: 李承哲; 崔珍硕; 吴政勋; 朴粉生; 金用恩; 李俊熙; 申束奎; 金哲玟; 玄英兰; 李哲淳; 曹重明; 卢成求
Original assignee: CrystalGenomics Inc; Yuyu Inc
Current assignee: CrystalGenomics Inc; Yuyu Inc
Priority date: 2006-01-23
Filing date: 2007-01-23
Publication date: 2009-03-04
Also published as: BRPI0707245A2

Abstract

The inventive imidazopyridine derivative can be used in a pharmaceutical composition for preventing or treating diseases such as diabetes, obesity, dementia, cancer, and inflammation, since it can efficiently inhibit the activities of several protein kinases including glycogen synthase kinase-3 (GSK-3), aurora kinase, extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and the likes, to control signal transductions thereof.

Description

Imidazopyridine derivatives inhibiting protein kinase activity, process for their preparation and pharmaceutical compositions containing them

Technical Field

The present invention relates to a novel compound inhibiting protein kinase activity, a process for preparing the same and a pharmaceutical composition comprising the same as an active ingredient.

Background

Protein kinases are enzymes that mediate intracellular signaling by phosphorylating a phosphoryl group derived from a Nucleoside Triphosphate (NTP) to a specific protein, phosphorylating them. A number of protein kinases have been reported to be involved in several signaling pathways that control cellular functions including cell proliferation, differentiation and death (schlessingert al, Neuron, 9, 383, 1992).

Thus, aberrant activation of protein kinases can cause a variety of diseases, such as central nervous system disorders, e.g., Alzheimer's disease (Mandelkow, E.M. et al, FEBS Lett., 314, 315, 1992; Senguta, A.et al, mol.cell.biochem., 167, 99, 1997), inflammatory diseases (Badger, J.pharm.Exp.Ther., 279, 1453, 1996), psoriasis (Dvir et al, J.cell biol., 113, 857, 1991), bone diseases, e.g., osteoporosis (Tanaka et al, Nature, 383, 528, 1996), Cancer (Hunter et al, Cell, 79, 573, 1994), arteriosclerosis (Hajjar et al, EB J, 6, 2933, 1992), thrombosis (FASari, FEBS, 263, 104, metabolic diseases, e.g., 1990, diabetes mellitus, vascular hypertension, 3556, rocky et al, 1996, rocky et al, rocker, 35284, rocker, 687, 1998), stent restenosis (buchdinger et al, proc.nat. acad.sci.usa, 92, 2258, 1991), autoimmune diseases, such as implant rejection (Bolen et al, ann.rev.immunol.immunol.15, 371, 1997), infectious diseases, such as fungal infections (international patent publication No. WO9805335), chronic kidney disease (Liu, i.et al, int.j.cardio, 69, 77-82, 1999) and chronic obstructive pulmonary disease (Nguyen, l.t.et al, Clinical nurr.18, 255-; solar, n.et al., eur.respir.j., 14, 1015-.

Aurora kinase is a Ser/Thr protein kinase involved in mitosis and has been demonstrated to be a recognized tumor protein that is overexpressed in several cancer cells of the breast, colon, pancreas and ovary (Carvajal RDet, clin. cancer res, 12(23), 6869-75, 2006), and it has recently been reported that Aurora protein kinases developed by vertex (usa) inhibit tumors in nude mice (Elizabeth a Harrington et al, nature, 10, 262 em 267, 2004).

The p38 mitogen-activated protein kinases (MAPKs) are proline-directed Ser/Thr kinases such as c-jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) which are known to be activated by bacterial lipopolysaccharide, physiochemical stress, proinflammatory cytokines including tumor necrosis factor (TNF- α) and interleukin-1 (IL-1) to mediate the signal pathways inducing the expression of inflammatory cytokines such as TNF- α, IL-8, IL-1 and cyclooxygenase-2.

Among such inflammatory cytokines expressed by p38 MAPK activation, TNF- α is known to be involved in viral infections, such as Human Immunodeficiency Virus (HIV), influenza and herpes virus infections, and inflammatory diseases, such as rheumatoid inflammation, multiple sclerosis and asthma (Newton R et al, Bio Drugs, 17(2), 113-129, 2003). Furthermore, IL-8 is expressed in nuclear cells, fibroblasts, endothelial cells and keratinocytes to be involved in inflammatory diseases, and IL-1 is expressed by activated monocytes and macrophages, partly in inflammation, fever and decreased bone resorption associated with rheumatoid arthritis (Bryan Coburn et al, British journal of Cancer, 95, 1568-.

It was demonstrated that C-iun-N-terminal kinase (JNK) is activated by extracellular stimuli such as Fas/FasL interaction, changes in the homeostasis and osmolarity of cytokines including IL-1 and TNF-. alpha., UV, and potassium to mediate signaling pathways inducing activation of AP1 transcription factors and participate in apoptosis and inflammatory diseases (Samadder, P.et al., J.Med.chem., 47(10), 2710-2713, 2004).

Extracellular signal-regulated kinases (ERKs) can activate other protein kinases such as Rsk90(Bjorbaek et al, j.biol. chem., 270, 18848, 1995) and MAPKAP2(Rouse et al, Cell, 78, 1027, 1994), as well as transcription factors such as ATF2 (raingeeud et al, mol.cell biol., 16, 1247, 1996), Elk-1 (raingeeud et al, mol.cell biol., 16(3), 1247-55, 1996), c-Fos (Chen et al, proc.natl.acad.sci.usa, 90, 10952, 1993) and c-Myc (Oliver et al, proc.soc.exp.biol.med., 210, 162, 1995) to mediate the expression of tumor proteins. Furthermore, ERK is reported to be overexpressed in Cancer cells of the human breast (Sivaraman et al, j.clin. invest, 99, 1478, 1997), regulate its negative growth (Frey et al, Cancer res, 57, 628, 1997), and it has also been reported to be involved in asthma (Whelchel et al, am.j.respir. cell mol. biol., 16, 589, 1997).

Cyclin-dependent kinases (CDKs) are known to play important roles in regulating cell growth during the cell cycle through G1/S migration and G2/M migration (Kim Nasmyth, Science, 274, 1643-1677, 1996). In particular, mutations in genes encoding CDKs or CDK regulatory genes in cancer cells in exponentially growing phages were found (Webster, exp. opin. invest. drugs, 7, 865-.

Kinase protein kinase B (PKB or AKT) (Kulik et al, mol.cell biol., 17, 1595. cndot. 1606, 1997; and Hemmings, b.a., Science, 275, 628. cndot. 630, 1997) is activated by activation of phosphatidylinositol 3(PI3K) induced by platelet-derived growth factor (PDGF), Nerve Growth Factor (NGF) or insulin-like growth factor-1 (IGF-1) to mediate metabolism of insulin (Calera, m.r.et al, j.biol.chem., 273, 7201. cndot. 7204, 1998), cell differentiation, and/or cell proliferation, as well as stress responses to protein synthesis (Alessi, d.r.et al, curr.opin.genet.dev., 8, 55-62, 1998).

Furthermore, AKT has been reported to be overexpressed in several cancers (Khwaja, A., Nature, 401, 33-34, 1999; Yuan, Z.Q.et al., Oncogene, 19, 2324-2330, 2000; and Namikawa, K., et al., J.Neurosci., 20, 2875-9286, 2000), especially in ovarian cancer cells (Cheng, J.Q.et al., Proc.Natl.Acad.Sci.USA, 89, 9267-9271, 1992) and pancreatic cancer (Cheng, J.Q.et al., Proc.Natl.Acad.Sci.USA, 93, 3636-3641, 1996).

Glycogen synthase kinase 3(GSK-3), one of the target proteins for the treatment of diabetes and dementia, is an enzyme that phosphorylates Glycogen Synthase (GS) to inhibit its activity. There are reports that GSK-3 activity in excessively hypertrophied diabetic mice is 2-fold as high as that of controls (H.Elder-Finkelman, Diabetes, 48, 1662-D1666, 1999), and that GSK-3 activity and expression are significantly higher than normal in type 2 diabetic patients (S.E.Nikoulina et al, Diabetes, 49, 263-D171, 2000).

Accordingly, the present inventors have made efforts to develop compounds effective in inhibiting the activity of several protein kinases and found that imidazopyridine derivatives can effectively inhibit the activity of protein kinases including glycogen synthase kinase-3 (GSK-3), aurora kinase, extracellular signal-regulated kinase (ERK), protein kinase b (akt), cyclin-dependent kinase (CDK), p38 (protein 38) mitogen-activated protein kinase (MAPK), kinase insert domain protein receptor (KDR) or vascular endothelial growth factor receptor-2 (VEGFR-2), c-Jun N-terminal group kinase (JNK) and Pyruvate Dehydrogenase Kinase (PDK).

Disclosure of Invention

Accordingly, it is an object of the present invention to provide a novel compound, a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, which effectively inhibits protein kinase activity.

It is another object of the present invention to provide a process for preparing such compounds.

It is a further object of the present invention to provide pharmaceutical compositions containing said compounds, pharmaceutically acceptable salts, hydrates, solvates and isomers thereof.

According to one aspect of the present invention, there is provided an imidazopyridine derivative of formula 1, and pharmaceutically acceptable salts, hydrates, solvates, and isomers thereof:

wherein,

R₁is hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, C_1-6Alkylsulfonyl, amides, optionally substituted by halogen, -CN, NO₂、C_1-6Alkyl radical, C_1-6Alkyl piperazinyl, C_1-6Alkylsulfinyl radical C_1-6Alkyl, piperidinyl, morpholinyl, pyrrolidinyl, morpholinyl C_1-6Alkylamino, pyrrolidinyl C_1-6Alkylamino, -OR ', -C (O) OR ', -OC (O) R ', -NR ' R ', -NHC (O) R ', -C (O) NR ' R ', -NHC (S) R ', -C (S) NR ' R ', -SR ', -S (O) R ', -SO₂R′、-NHSO₂R′、-SO₂NR′R＂、-OSO₂R′、-SO₂OR', aryl, heteroaryl, aryl-C_1-4Alkyl, formyl or trifluoromethyl substituted aryl or heteroaryl, each of R' or R "is independently hydrogen; or C_1-4Alkyl radical, C_3-7Cycloalkyl, optionally substituted by C_1-4Alkyl radical, C_1-4Alkoxy, CN, NO₂、NH₂、(C_1-4Alkyl) amino, OH, COOH, COO (C)_1-4Alkyl), -CONH₂Aryl or heteroaryl substituted with formyl or trifluoromethyl; aryl is phenyl, indanyl or naphthyl; and heteroaryl is an aryl group of 5-to 10-membered ring, or a mono-or bicyclic heterocycle containing one or more of nitrogen, sulfur or oxygen atoms in its ring structure;

R₂is hydrogen; unsubstituted or substituted C_1-8An alkyl group; or unsubstituted or substituted C containing nitrogen, sulfur or oxygen in its chain structure_1-7An alkyl group wherein the substituent of the alkyl group is a hydroxyl group,Halogen, C_1-6Alkoxy, alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl or amide; optionally is covered with C_1-4Alkyl, hydroxy, halogen, C_1-6Alkoxy, amino, C_1-6Alkylamino radical, amino radical C_1-6Alkyl, acetylamino, carboxyl, amide, dioxoindole, -CN, NO₂、-OR′、-C(O)OR′、-OC(O)R′、-NR′R＂、-NHC(O)R′、-NHC(O)OR′、-C(O)NR′R＂、-NHC(S)R′、-C(S)NR′R＂、-SR′、-S(O)R′、-SO₂R′、-NHSO₂R′、-SO₂NR′R＂、-OSO₂R′、-SO₂OR', aryl, heteroaryl, aryl-C_1-4Alkyl, formyl or trifluoromethyl substituted aryl or heteroaryl, each of R' or R "is independently hydrogen; or C_1-4Alkyl radical, C_3-7Cycloalkyl, optionally substituted by halogen, C_1-4Alkyl radical, C_1-4Alkoxy, CN, NO₂、NH₂、C_1-4Alkylamino radical, amino radical C_1-4Alkyl, OH, COOH, -COOC_1-4Alkyl, -CONH₂Formyl, C_1-6Alkyl piperazinyl, morpholinyl or trifluoromethyl substituted aryl or heteroaryl; wherein aryl is phenyl, indanyl or naphthyl; and heteroaryl is a 5-to 10-membered ring aryl, pyridone, or a monocyclic or bicyclic heterocycle containing 1-4 nitrogen, sulfur, or oxygen atoms in its ring structure; or

Unsubstituted or substituted aryl; or an unsubstituted or substituted aryl group containing one or more of nitrogen, sulfur or oxygen within its ring structure; wherein the substituent for aryl is hydroxy; halogen; c_1-6An alkoxy group; c_1-6An alkyl group; an amino group; c_1-6An alkylamino group; a carboxyl group; a nitro group; a sulfonyl amide; c_1-6An alkylsulfonyl group; an amide; unsubstituted or substituted C_1-6An alkyl group; or a ring C containing one or more of nitrogen, sulfur or oxygen atoms in its ring structure_1-6An alkyl group, wherein the substituent of the alkyl group is a hydroxyl group; halogen; c_1-6An alkoxy group; c_1-6An alkyl group; an amino group; c_1-6An alkylamino group; a carboxyl group; a nitro group; sulfonyl radicalAn amide; c_1-6An alkylsulfonyl group; an amide; optionally substituted by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxy, nitro, amide or dioxoisoindolyl-substituted aryl; aryl by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, C_1-6Alkylsulfonyl-or amide-substituted sulfonylaminoaryl; aryl including one or more of nitrogen, sulphur or oxygen atoms within its ring structure, which represents pyrrole, pyrazole, imidazole, 1, 2, 3-triazole, 1, 2, 4-triazole, isoxazole, oxazole, isothiazole, thiazolidine, thiazole, 1, 2, 5-oxadiazole, 1, 2, 3-oxadiazole, 1, 2, 5-thiadiazole, 1, 2, 3-thiadiazole, 1, 3, 4-oxadiazole, 1, 3, 4-thiadiazole, pyridine, oxypyridine, pyrimidine or triazine, optionally substituted by hydroxyl, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, C_1-6Alkylsulfonyl or amide substitution; or optionally substituted by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro or amide substituted C_3-8A cycloalkyl group;

R₃is hydrogen; or optionally selected from halogen, C_1-4Alkyl radical, C_1-4Alkoxy, CN, NO₂、NH₂、(C_1-4Alkyl) -amino, amino- (C)_1-4Alkyl), OH, COOH, -COO (C)_1-4Alkyl) and-CONH₂C substituted with one or more substituents of (1)_1-4Alkyl or C_3-7Cycloalkyl groups, wherein each of them has a substituent selected from the group consisting of hydroxyl; halogen; an alkoxy group; an alkyl group; an amino group; an alkylamino group; a carboxyl group; a nitro group; a sulfonyl amide; an alkylsulfonyl group; or an optional substituent in an amide; or

R₂And R₃Fused together with the nitrogen to which they are attached to form a ring; and

R₄and R₅Each independently is hydrogen; or selected from halogen, C_1-4Alkyl radical, C_1-4Alkoxy, CN, NO₂、NH₂、C_1-4Alkylamino radical, amino radical C_1-4Alkyl, OH, COOH, COOC_1-4Alkyl and-CONH₂C optionally substituted with the substituent(s) of (1)_1-4Alkyl or C_3-7Cycloalkyl groups, wherein each of them has an optional substituent selected from the group consisting of hydroxy, halogen, alkoxy, alkyl, amino, alkylamino, carboxy, nitro, sulfonylamide, alkylsulfonyl, and amide.

Detailed Description

Among the compounds of formula 1, those are preferred, wherein:

R₁is phenyl, pyrrolidinylphenyl, dichlorophenyl, chlorophenyl, fluorophenyl, difluorophenyl, furyl, thiophene, cyclopropyl, C_1-2Alkyl piperazinyl phenyl, C_1-2Alkyl piperazinyl C_1-3Alkyl phenyl, C_1-2Alkyl piperazinyl C_1-3Alkylaminophenyl, methylsulfinylphenyl, di-C_1-2Alkylaminophenyl, morpholinylphenyl, piperidinylphenyl, morpholinyl C_1-3Alkylaminophenyl, pyrrolidinyl C_1-3Alkylamino phenyl, dimethylamino C_1-4Alkylamino phenyl, di-C_1-2Alkylaminoethylmethylaminophenyl, piperazinylaminophenyl, piperazino-C_1-2Alkylaminophenyl, thiomorpholinophenyl, piperidinylaminophenyl, piperidino C_1-2Alkylamino phenyl, methoxyphenyl, di-C_1-3An alkylamino pyrrolidinylphenyl or pyridyl group;

R₂is optionally sulfonylphenyl, C_1-2Alkyl pyridyl, di-C_1-2Alkyl, tri-C_1-2Alkyl, tetra C_1-2Alkyl, pyridyl, oxypyridyl, chloropyridyl, morpholinyl, amino C_1-2Alkyl pyridyl, acetyl amino phenyl, imidazole, dichloroimidazole, and,C_1-2Alkyl imidazole, di-C_1-2Alkylamino sulfonylaminophenyl, trifluoro C_1-2Alkylphenyl, benzyloxyoxapyridyl, hydroxyoxapyridyl, C_1-2Alkanesulfonylaminophenyl, di-C_1-2Alkylaminoacylaminophenyl, trifluoromethanesulfonylaminophenyl, fluoropyridyl, fluorohydroxyphenyl, C_1-2Alkylpiperazinyl acetylaminophenyl, chlorooxapyridyl, phenylthio, C_1-2Alkoxypyridyl, aminophenyl, hydroxyphenyl, C_1-2Alkyl piperazine carbonylaminophenyl, morpholinyl C_1-3Alkoxyphenyl, benzyl, hydroxy-di-C_1-2Alkyl or di-C_1-2Alkylamino radical C_1-2Alkyl substituted C_1-5An alkyl group; optionally substituted by tri C_1-2Alkyl, amino or hydroxy substituted ring C_3-7An alkyl group; optionally is covered with C_1-2Alkyl, di-C_1-2Alkyl, chloro C_1-2Alkoxy radical, C_1-2Alkylamino radical, amino radical C_1-2Alkyl radical, C_1-2Alkoxy radical, C_1-2Alkoxy radical C_1-2Alkyl radical, C_1-2Alkylsulfonyl, chloro C_1-2Alkyl, isobutoxy, cyclopropylmethoxy, di-C_1-2Alkylamino radical C_1-2Alkoxy, morpholinyl C_1-2Alkoxy, halogen, acetylamino or C_1-2Alkylsulfonyl radical C_1-2An alkyl-substituted pyridyl group; by benzoylamino, piperidinyl, hydroxy, C_1-2Alkoxy radical, C_1-2Alkyl, di-C_1-2Alkyl, diisopropyl, isopropyl, di-C_1-2Alkylamino acetylamino, fluoro C_1-2Alkyl, fluoro-hydroxy, trifluoro-C_1-2Alkoxy, di-C_1-2Alkoxy, acetylamino, cyano, benzyloxy, trifluoromethanesulfonylamino or C_1-2Alkylsulfonyl-substituted phenyl; benzothiazolyl, indazolyl, C_1-2Alkyl indolyl, naphthyl, quinolyl, C_1-2Alkylpyrazolyl, phenylthiazolyl, tolyl, benzodioxolyl, C_1-2Alkylphenyl acetamide, C_1-2Alkylphenoxyacetyl, ethylsulfonyl C_1-2Alkylphenylamides, C_1-2Alkylphenoxy acetic acid tert-butyl ester, C_1-2Alkylphenylmethanesulfonamide, C_1-2Alkyl piperazinyl, C_1-2Alkoxyphenylamide, piperidyl, benzylpiperidyl, C_1-2Alkylphenoxyacetyl, tri-C_1-2Alkyl bicycloheptyl, adamantyl, amino bicycloheptyl, azabicyclooctyl, bicycloheptyl, tert-butylamide or C_1-2Alkyl pyridyl radical C_1-2Alkyl carbamic acid tert-butyl ester; and

R₃is H, or R₂And R₃Fused together with the nitrogen to which they are attached to form a ring; r₄Is H or halogen; and R₅Is H.

Representative examples of compounds of the present invention are shown in table 1.

TABLE 1

The compound of formula 1 of the present invention may be in the form of a pharmaceutically acceptable salt derived from an inorganic or organic acid, or a base; and representative examples of pharmaceutically acceptable salts derived from inorganic or organic acids include salts obtained by adding an inorganic acid, such as, but not limited to, hydrochloric acid, hydrobromic acid, phosphoric acid or sulfonic acid, or an organic carboxylic acid, such as acetic acid, trifluoroacetic acid, citric acid, formic acid, oxalic acid, succinic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, ascorbic acid or malic acid, methanesulfonic acid or p-toluenesulfonic acid, to the compound of formula 1. Such acid salts can be prepared by conventional methods, and other acids which are not per se pharmaceutically acceptable, including oxalic acid, can be used in the preparation of the base.

Further, the compound of formula 1 may be in the form of a prodrug derivative, wherein the derivative or prodrug thereof may be a physiologically hydrolyzable ester or amide compound such as indanyl, 2-benzo [ c ] furanonyl (phthaladil), methoxymethyl, octanoyloxymethyl, glycyloxymethyl, phenylglycyloxymethyl and 5-methyl-2-oxo-1, 3-dioxolene-4-ylmethyl.

According to another aspect of the present invention, there is provided a method of preparing the compound of formula 1.

The compound of formula 1 may be prepared by a process comprising the steps of:

1) hydrogenating the compound of formula 2 in the presence of a catalyst to obtain a compound of formula 3;

2) refluxing a compound of formula 3 and R in the presence of an organic acid₁-(CO₂H) Or R₁A mixture of- (CHO), or heating the mixture in nitrobenzene by microwave radiation to obtain a compound of formula 4;

3) reacting the compound of formula 4 with an oxidizing agent in an alkaline hydroxide solution or an organic solvent, cooling the resulting mixture in an ice bath, adding SOCl thereto₂Or H₂SO₄And refluxing the resulting mixture to obtain a compound of formula 5;

4) refluxing a compound of formula 5 and LiOH H in a solvent₂O and adding an acid thereto to obtain a compound of formula 6; and

5) reacting a compound of formula 6 with a compound of formula R in the presence of a coupling agent in an organic solvent₂R₃Reacting the compound of NH to obtain a compound of formula 1:

wherein R is₁-R₅Have the same meaning as above.

The process of the present invention for preparing the compound of formula 1 is shown in scheme 1.

Reaction scheme 1

Wherein,

R₁、R₂、R₃、R₄and R₅Have the same meaning as above.

As shown in scheme 1, and in the hydrogenation reactor, first in a catalyst, e.g., 5% -10% Pd/C or PtO₂Hydrogenating the compound of formula 2 in an organic solvent in the presence of hydrogen, filtering the resulting mixture and concentrating under reduced pressure to obtain the compound of formula 3. The compounds of formula 2 useful as starting materials can be prepared by conventional methods (see, TANGA, M.J et al, J heterocyclic Chem 2003, 40(4), 569-573) or are commercially available. The organic solvent may be methanol, ethanol or dichloromethane, and the reaction is carried out at room temperature.

In step 2, the compound 3 is refluxed at 180-200 ℃ for 4-6 hours in the presence of an organic acid, or heated in nitrobenzene at 180-200 ℃ for 20-40 minutes by microwave radiation at a power of 200-300W, wherein R is based on the compound 3₁-(CO₂H) Or R₁The amount of- (CHO) is preferably in the range of 1 to 2 equivalents. The resulting mixture was neutralized with aqueous NaOH, extracted, filtered, the solvent was removed, and the resulting residue was subjected to flash column chromatography to obtain compound 4. The organic acid may be POCl₃Or phosphoric acid (PPA).

In step 3, compound 4 can be reacted with an oxidizing agent in an alkaline hydroxide solution or an organic solvent, the resulting mixture is cooled in an ice bath, and SOCl is added thereto₂Or H₂SO₄And reflux mixing in methanolCompound to obtain the compound of formula 5. The alkaline hydroxide can be NaOH or NaHCO₃Or Na₂CO₃And the organic solvent may be pyridine or tert-butanol. The oxidant may be KMnO₄、MnO₂Or SeO₂And is used in an amount ranging from 2 to 4 equivalents based on the compound of formula 4. SOCl can be used in an amount ranging from 0.1 to 4 equivalents based on compound 4₂Or H₂SO₄。

In step 4, compound 5 can be refluxed together with LiOH. H, based on compound 5, preferably in an amount ranging from 2 to 3 equivalents, in a mixture of water, MeOH, and THF at 80 deg.C₂O and treating the resulting mixture with HCl in a preferred amount ranging from 1 to 3 equivalents based on compound 5 to obtain the compound of formula 6. The weight ratio of water to MeOH to THF can range from 1:0.5 to 2:1 to 5, preferably about 1:1: 3.

In step 5, compound 6 can be reacted with formula R in an organic solvent in the presence of a coupling agent₂R₃Reacting the compound of NH to obtain the compound of formula 1. The organic solvent may be Dimethylformamide (DMF), Dimethylsulfoxide (DMSO), or dichloromethane (MC). The coupling agent may be 1-Hydroxybenzotriazole (HOBT)/1- (3-dimethylaminopropyl) -3-ethylcarbodiimide HCl salt (EDC)/triethylamine (Et)₃N) and pyBop ((benzotriazol-1-yl-oxy) trispyrrolidinylphosphonium hexafluorophosphate), HBTU (O-benzotriazol-N, N '-tetramethyluronium (uronium) hexafluorophosphate) or TBTU (O- (benzotriazol-1-yl) -N, N' -tetramethyluronium tetrafluoroborate). Furthermore, based on compound 5, a coupling agent and R₂R₃The amount of each NH used may range from 2 to 3 equivalents.

The compounds of formula 2 used as starting materials are commercially available.

According to a further aspect of the present invention, there is provided a composition for inhibiting protein kinase activity, which comprises the imidazopyridine derivative, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, as an active ingredient.

ProteinThe substance kinase may be selected from glycogen synthase kinase-3 (GSK-3), aurora kinase, extracellular signal-regulated kinase (ERK), protein kinase B (AKT), cyclin-dependent kinase (CDK), p38 (protein 38) mitogen-activated protein kinase (MAPK), kinase insert domain protein receptor (KDR) or vascular endothelial growth factor receptor-2 (VEGFR-2), c-Jun N-terminal group kinase (JNK) and Pyruvate Dehydrogenase Kinase (PDK). For the protein kinase, IC of the compound of the present invention₅₀Values ranged from 3nM to 50,000 nM.

In addition, the imidazopyridine derivative of formula 1, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, can be used as an active ingredient in a pharmaceutical composition for the prevention or treatment of a disease selected from the group consisting of diabetes, obesity, dementia, cancer, and inflammation, because it is effective in inhibiting the activity of several protein kinases, including aurora kinase, and controlling the signaling thereof. Accordingly, in the present invention, there is provided a pharmaceutical composition comprising the imidazopyridine derivative, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, as an active ingredient.

The salt, hydrate, solvate, or isomer of the compound of formula 1 may be prepared from the compound of formula 1 according to a conventional method.

The pharmaceutically acceptable compositions may be formulated for oral or parenteral administration. Compositions for oral administration may be in various forms, such as tablets, powders, hard or soft capsules, solutions, dispersions, emulsions, syrups and granules, and such formulations may include the active ingredient together with diluents (e.g., lactose, dextrose, sucrose, mannose, sorbitol, cellulose and/or glycerol), and lubricants (e.g., silica, talc, stearic acid, and magnesium or calcium salts thereof, and/or polyethylene glycols). In addition, these tablets may include binders such as magnesium aluminum silicate, starch pastes, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone, and may further include disintegrants such as starch, agarose, alginates or sodium salts thereof, or effervescent mixtures and/or absorption, coloration, flavoring, and sweetening agents.

In addition, when formulated for parenteral administration, the pharmaceutical composition of the present invention may preferably be in the form of an injection further comprising a saline solution or a suspension.

The pharmaceutical composition may be sterilized and/or it may further comprise preservatives, stabilizers, hydrating or emulsifying agents, salts for controlling osmotic pressure and/or supplemental agents, including buffers and other therapeutically available materials, and may be prepared by conventional mixing, granulating or coating methods.

The daily dose for administration of the compound of formula 1 as an active ingredient in the composition of the present invention to mammals, including humans, is set forth to be about 2.5mg/kg body weight to 100mg/kg body weight, more preferably about 5mg/kg body weight to 60mg/kg body weight. It will be understood that the daily dosage should be determined in view of various relevant factors, including the disease to be treated, the severity of the patient's symptoms, the route of administration, or the physiological form of the anticancer agent, and therefore the above-suggested dosage should not be construed as limiting the scope of the present invention in any way.

The following examples are intended to further illustrate the invention without limiting its scope.

Example 1: preparation of 2-phenyl-3H-imidazo [4, 5-b ] -pyridine-7-carboxylic acid [2- (4-acetamido-phenyl) -ethyl ] -amide

Step 1) preparation of 4-methylpyridine-2, 3-diamine

4-methyl-3-nitropyridin-2-amine (25g, 163.4mmol) was dissolved in 100ml MeOH and a catalytic amount of 5% Pd/C was added to it and the mixture was stirred for 2 h. The reaction solution was filtered through a celite pad, and the pad was thoroughly washed with MeOH, and the combined mixture was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the title compound (18.49g, 150.33 mmol; yield: 92%).

¹H-NMR(CDCl₃):2.17(s，3H)，3.27(br，2H)，4.14(br，2H)，6.54(d，2H)，7.55(d，2H)

M.W.:124

Step 2) preparation of 7-methyl-2-phenyl-3H-imidazo [4, 5-b ] pyridine

The compound obtained in step 1 (5g, 40.65mmol), benzoic acid (4.96g, 40.65mmol) and 20ml of POCl were mixed₃And the mixture was refluxed at 170-180 ℃ for 4 hours. The reaction mixture was concentrated under reduced pressure to remove POCl₃Neutralized with aqueous NaOH and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compound (5.09g, 24.39 mmol; yield: 60%).

¹H-NMR(CDCl₃):2.78(s，3H)，7.09(d，1H)，7.54(m，3H)，8.30(m，3H)

M.W.:210

Step 3) preparation of 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid methyl ester

The compound (200mg, 0.96mmol) obtained in step 2 and NaOH (76.80mg, 1.92mmol) were mixed, 20ml of water was added thereto, and the resulting mixture was heated to 60 ℃. Under heating, KMnO dissolved in water by heating₄The obtained aqueous KMnO₄(311mg, 1.92mmol) was added to the mixture, andthe mixture was stirred at 100 ℃ for 6 hours. The reaction mixture was filtered through a celite pad while keeping hot, the pad was thoroughly washed with hot water, and the combined aqueous solution was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 20ml MeOH and the mixture was cooled to 0 ℃ in an ice bath. Slowly adding 7-10 equivalents of SOCl thereto₂And the mixture was refluxed for 4 hours. The resulting mixture was neutralized with aqueous NaOH, concentrated under reduced pressure to remove the solvent, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compound (109mg, 0.43 mmol; yield: 45%).

¹H-NMR(MeOH-d₄):4.10(s，3H)，7.64(m，3H)，7.89(d，1H)，8.25(m，2H)，8.61(d，2H)

M.W.:254

Step 4) preparation of 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 3 (30mg, 0.12mmol) was dissolved in a mixture of 10ml of THF, 3ml of water and 3ml of MeOH, and LiOH. H.was added thereto₂O (14mg, 0.33mmol) and the mixture refluxed for 8 hours. After terminating the reaction by addition of 4M HCl (0.66mmol, 165 μ l) at room temperature, the reaction mixture was concentrated under reduced pressure and the solvent was removed. The resulting residue was dried in vacuum to obtain the title compound (25.8mg, 0.10 mmol; yield: 85%).

¹H-NMR(MeOH-d₄):7.79～7.67(m，3H)，8.14(d，1H)，8.28(m，2H)，8.78(d，1H)

M.W.:254

Step 5) preparation of 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [ (2- (4-acetylamino-phenyl) -ethyl) -amide

The compound obtained in step 4 was dissolved in 3ml of DMF, and 2 equivalents of each of EDC and HOBt were further dissolved in the solution while stirring. 4-acetylpentylamine was added to the mixture in an amount of 1.2 equivalents, and the mixture was stirred at room temperature for 12-24 hours. The reaction mixture was dried in vacuo, and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 60%).

Examples 2 to 31

The procedure of example 1 was repeated except for using each corresponding amine compound in place of 4-acetylpentylamine of step 5 to obtain each of the title compounds.

Examples 32 to 42

The procedure of example 1 was repeated, except that 2, 4-dichlorobenzoic acid (7.76g, 40.65mmol) and the corresponding amine compound were used in place of benzoic acid and 4-acetylpentylamine, respectively, in steps 2 and 5 to obtain the respective title compounds.

Example 43: preparation of 2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide

Step 1) preparation of 2- (4-chlorophenyl) -7-methyl-3H-imidazo [4, 5-b ] pyridine

The compound (0.75g, 6.14mmol) obtained in step 1 of example 1, 4-chlorobenzoic acid (1.153g, 7.37mmol) and PPA (10g) were mixed, and the mixture was stirred at 150 ℃ for 24 hours. The reaction mixture was cooled to room temperature and 20ml of water was slowly added thereto, followed by neutralization with water and saturated NaOH in an ice bath. The formed precipitate was filtered and dried in vacuo to obtain the crude title compound (1.24g, 5.10 mmol; yield: 83%).

¹H-NMR(CDCl₃):2.69(s，3H)，7.12(d，1H)，7.57(d，2H)，8.16(d，2H)，8.21(m，1H)

M.W.:244

Step 2) preparation of methyl 2- (4-chlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylate

The compound obtained in step 1 (0.138g, 0.67mmol) was dissolved in 3ml of t-BuOH and the mixture was stirred. To this was added in three portions aqueous and hot KMnO dissolved in 4ml of water under heating₄(450mg, 2.85mmol) and the mixture is stirred at 60-80 ℃ for 24 h. While maintaining the hot, the reaction mixture was filtered through celite, and the pad was thoroughly washed with hot water, and the combined mixture was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 5ml MeOH with stirring. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 1:1) to obtain the title compound (45mg, 0.16 mmol; yield: 23%).

¹H-NMR(CDCl₃):4.09(s，3H)，7.41(d，1H)，7.52(d，2H)，7.97(d，2H)，8.12(d，1H)，10.43(br，1H)

M.W.:289

Step 3) preparation of 2- (4-chlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (45mg, 0.16mmol) was dissolved in 2ml THF. To this was added LiOH. H dissolved in 1ml of water₂O (20mg, 0.48mmol), and the mixture was stirred at room temperature for 8 hours. Extracting the reaction mixture with ethyl acetate, and extracting with ethyl acetateThe aqueous layer was washed with ethyl acetate and adjusted to pH 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (45mg, 0.16 mmol; yield: 102%).

¹H-NMR(MeOH-d₄):7.32(d，2H)，7.56(d，1H)，7.90(d，2H)，8.39(d，1H)

M.W.:275

Step 4) preparation of 2- (4-chlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide

The compound obtained in step 3 was dissolved in DMF and 1.2 equivalents of benzotriazol-1-yl-oxytripyrrolidinylphosphonium (PyBOP), 3 equivalents of TEA and 1.2 equivalents of ethanesulfonic acid [4- (2-aminoethyl) -phenyl ] -amide were added thereto and the mixture was stirred at room temperature for 12 hours. The reaction mixture was dried in vacuo and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 65%).

Examples 44 to 61

The procedure of example 43 was repeated except that each corresponding amine compound was used in place of ethanesulfonic acid [4- (2-aminoethyl) -phenyl ] -amide in step 4 to obtain the title compounds.

Example 62: preparation of 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloro 3H-imidazol-1-yl) -propyl ] -amide

Step 1) preparation of 2-furan-2-yl-7-methyl-3H-imidazo [4, 5-b ] pyridine

The compound obtained in step 1 of example 1 (1g, 8.15mmol) and furan 2-aldehyde (783mg, 8.15mmol) were dissolved in 3ml of nitrobenzene and the mixture was held at 180 ℃ for 15 minutes at 300W power. The reaction solution was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 1:1) to obtain the title compound (730mg, 3.67 mmol; yield: 45%).

M.W.:200

Step 2) preparation of methyl 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylate

The compound obtained in step 1 (0.469g, 2.35mmol) was dissolved in 5ml of pyridine, and the mixture was stirred. Adding SeO thereto₂(1.303g, 11.75mmol) and the mixture was refluxed at 120 ℃ for 24 hours. While maintaining the hot, the reaction solution was filtered through celite, and the pad was thoroughly washed with hot water and MeOH, and the combined mixture was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 10ml MeOH with stirring. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered, and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 1:1) to obtain the title compound (188mg, 0.776 mmol; yield: 33%).

¹H-NMR(CDCl₃):4.08(s，3H)，6.74(d，1H)，7.52(d，1H)，7.78(d，1H)，7.87(d，1H)，8.51(d，1H)

M.W.:244

Step 3) preparation of 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (140mg, 0.58mmol) was dissolved in 2ml of THF, and the mixture was stirred. To this was added LiOH. H dissolved in 1ml of water₂O (73mg, 1.74mmol), and the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate, and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (109mg, 0.48 mmol; yield: 83%).

¹H-NMR(MeOH-d₄):6.71(d，1H)，7.40(d，1H)，7.67(d，1H)，7.83(d，1H)，8.39(d，1H)

M.W.:230

Step 4) preparation of 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloro 3H-imidazol-1-yl) -propyl ] -amide

The compound obtained in step 3 was dissolved in DMF, and 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of 3- (2, 4-dichloroimidazol-1-yl) propylamine were added thereto, and the mixture was stirred at room temperature for 12 hours. The reaction solution was dried in vacuo and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 45%).

Examples 63 to 85

The procedure of example 62 was repeated, except that in step 4, each corresponding amine compound was used instead of 3- (2, 4-dichloroimidazolyl) propylamine, to obtain each of the title compounds.

Example 86: preparation of 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide

Step 1) preparation of 7-methyl-2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine

The compound obtained in step 1 of example 1 (1g, 8.15mmol) and thiophene-2-aldehyde (912mg, 8.15mmol) were dissolved in 3ml of nitrobenzene and held at 180 ℃ for 15 minutes at a power of 300W. The reaction solution was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 1:1) to obtain the title compound (877mg, 4.08 mmol; yield: 50%).

¹H-NMR(CDCl₃):2.17(s，3H)，7.36(t，1H)，8.00(m，2H)，8.48(d，1H)，8.82(d，1H)

M.W.:216

Step 2) preparation of 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid methyl ester

The compound obtained in step 1 (500mg, 2.33mmol) was dissolved in 5ml of pyridine, and the mixture was stirred. Adding SeO thereto₂(1.04g, 9.32mmol) and refluxing the mixture at 120 ℃ for 24 h. While maintaining the hot, the reaction solution was filtered through celite, the pad was thoroughly washed with hot water and MeOH, the combined mixture was concentrated under reduced pressure, the solvent was removed, and then dried under vacuum. The resulting residue was dissolved in 10ml MeOH with stirring. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compound (163mg, 0.63 mmol; yield: 27%).

¹H-NMR(CDCl₃):4.08(s，3H)，6.74(d，1H)，7.52(d，1H)，7.78(d，1H)，7.87(d，1H)，8.41(d，1H)

M.W.:260

Step 3) preparation of 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (163mg, 0.63mmol) was dissolved in 2ml of THF, and the mixture was stirred. Adding into itAdding LiOH. H dissolved in 1ml water₂O (126mg, 2.52mmol), and the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (103mg, 0.42 mmol; yield: 67%).

M.W.:246

Step 4) preparation of 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide

The compound prepared in step 3 was dissolved in DMF and 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of 4-ethanesulfonylaminophenylethylamine were added thereto, and the mixture was stirred at room temperature for 12 hours. The reaction solution was dried in vacuo, and the resulting residue was dissolved in a small amount of MeOH and filtered, and the filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 55%).

Examples 87 to 113

The procedure of example 86 was repeated except that each corresponding amine compound was used in place of 4-ethylsulfonylaminophenylethylamine in step 4 to obtain each title compound.

Example 114: preparation of 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide

Step 1) preparation of 2-furan-3-yl-7-methyl-3H-imidazo [4, 5-b ] pyridine

The compound (500g, 4.07mmol) obtained in step 1 of example 1 and furan 3-aldehyde (391mg, 4.07mmol) were dissolved in 3ml of nitrobenzene and the mixture was kept at 180 ℃ for 15 minutes under filtration of 300W. The reaction solution was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 1:1) to obtain the title compound (243mg, 1.22 mmol; yield: 30%).

¹H-NMR(CDCl₃):2.88(s，3H)，7.09(s，1H)，7.17(d，2H)，8.38(s，1H)，8.44(d，1H)

M.W.:200

Step 2) preparation of methyl 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylate

The compound obtained in step 1 (243mg, 1.22mmol) was dissolved in 5ml of pyridine, and the mixture was stirred. Adding SeO thereto₂(542mg, 4.88mmol) and refluxed at 120 ℃ for 24 hours. While maintaining the hot, the reaction solution was filtered through celite, the pad was thoroughly washed with hot water and MeOH, and the combined mixture was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 10ml MeOH with stirring. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting residue was washed with brine, over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compound (154mg, 0.63 mmol; yield: 52%).

¹H-NMR(CDCl₃):4.13(s，3H)，7.09(s，1H)，7.17(d，2H)，8.38(s，1H)，8.44(d，1H)

M.W.:244

Step 3) preparation of 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (154mg, 0.63mmol) was dissolved in 2ml of THF, and the mixture was stirred. To it is provided withTo which LiOH. H dissolved in 1ml of water was added₂O (106mg, 2.52 mmol). And the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate, and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (109mg, 0.48 mmol; yield: 76%).

M.W.:230

Step 4) preparation of 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide

The compound obtained in step 3 was dissolved in DMF, and 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of 4-methanesulfonylaminophenylethylamine were added thereto, and the mixture was stirred at room temperature for 12 hours. The reaction solution was dried in vacuo and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 45%).

Example 115-

The procedure of example 114 was repeated except for using each corresponding amine compound in place of 4-methanesulfonylaminophenylethylamine in the procedure to obtain the respective title compounds.

Example 142

Step 1) preparation of 2- (2, 4-difluorophenyl) -7-methyl-3H-imidazo [4, 5-b ] pyridine

The compound (0.75g, 6.14mmol) obtained in step 1 of example 1, 2, 4-difluorobenzoic acid (1.456g, 9.21mmol) and PPA (10g) were mixed, and the mixture was stirred at 150 ℃ and 160 ℃ for 24 hours. The reaction solution was cooled to room temperature, and 20ml of water was slowly added thereto, followed by neutralization with water and saturated NaOH in an ice bath. The formed precipitate was filtered and dried in vacuo to obtain the crude title compound (200mg, 0.816 mmol; yield: 13%).

¹H-NMR(CDCl₃):2.68(s，3H)，7.14(m，3H)，8.16(m，1H)，8.25(d，1H)

M.W.:246

Step 2) preparation of methyl 2- (4-difluorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylate

The compound obtained in step 1 (0.20g, 0.82mmol) was dissolved in 5ml of t-BuOH, and the mixture was stirred. To this was added in three portions aqueous and hot KMnO dissolved in 4ml water under heating₄(648mg, 4.1mmol) and stirred at 60-80 ℃ for 24 h. While keeping the heat, the reaction solution was filtered through a celite pad, the pad was thoroughly washed with hot water, and the combined mixture was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 5ml of MeOH simultaneously with the blocking. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting residue was washed with brine, over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compound (50mg, 0.17 mmol; yield: 21%).

¹H-NMR(CDCl₃):4.09(s，3H)，7.02(m，1H)，7.14(m，1H)，7.72(d，1H)，8.65(m，1H)，8.69(d，1H)，10.43(br，1H)

M.W.:290

Step 3) preparation of 2- (2, 4-difluorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

Obtained in step 2The compound (50mg, 0.17mmol) of (D) was dissolved in 2ml of THF. To this was added LiOH. H dissolved in 1ml of water₂O (21mg, 0.51mmol), and the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate, and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (70mg, 0.256 mmol; yield: 150%).

¹H-NMR(MeOH-d₄):7.23(d，2H)，7.79(d，1H)，8.38(m，2H)，8.48(d，1H)

M.W.:275

Step 4) preparation of 2- (2, 4-difluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide

The compound obtained in step 3 was dissolved in DMF and 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of methanesulfonyl aminophatic acid [4- (2-aminoethyl) -phenyl ] -amide were added thereto and the mixture was stirred at room temperature for 12 hours, the reaction solution was dried in vacuo, and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 45%).

Example 143-

The procedure of example 142 was repeated except that each corresponding amine compound was used in place of 4-methanesulfonylaminophenylethylamine in step 4 to obtain each title compound.

Example 145

Step 1) preparation of 2-cyclopropyl-7-methyl-3H-imidazo [4, 5-b ] pyridine

The compound obtained in step 1 of example 1 (500 mg) was mixed4.08mmol), cyclopropanecarboxylic acid (351mg, 4.08mmol) and 25ml of POCl₃And the mixture was refluxed at 170-180 ℃ for 4 hours. The reaction solution was concentrated under reduced pressure to remove POCl₃Neutralized with aqueous NaOH and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 2:1) to obtain the title compound (423mg, 2.45 mmol; yield: 60%).

¹H-NMR(CDCl₃):1.25(m，2H)，1.31(m，2H)，2.31(m，1H)，2.91(t，2H)，7.70(d，1H)，8.41(d，1H)

M.W.:174

Step 2) preparation of 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid methyl ester

The compound (423mg, 2.45mmol) obtained in step 1 and NaOH (196mg, 4.9mmol) were mixed, 20ml of water was added thereto, and the mixture was heated to 60 ℃. Aqueous KMnO to be dissolved in water (3ml) under heating₄(774mg, 4.9mmol) was added to the mixture, and the mixture was stirred at 100 ℃ for 6 hours. While keeping the heat, the reaction solution was filtered through a celite pad, the pad was thoroughly washed with hot water, and the combined mixture was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 20ml MeOH and the mixture was cooled to 0 ℃ in an ice bath. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was neutralized with aqueous NaOH, concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 2:1) to obtain the title compound (170mg, 0.78 mmol; yield: 32%).

¹H-NMR(CDCl₃):1.25(m，2H)，1.31(m，2H)，2.31(m，1H)，2.91(t，2H)，3.80(s，3H)，7.70(d，1H)，8.41(d，1H)

M.W.:218

Step 3) preparation of 2-chloropropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (170mg, 0.78mmol) was dissolved in 2ml THF. To this was added LiOH. H dissolved in 1ml of water₂O (66mg, 1.56mmol), and the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate, and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (140mg, 0.69 mmol; yield: 88%).

¹H-NMR(MeOH-d₄):1.25(m，2H)，1.31(m，2H)，2.31(m，1H)，7.70(d，1H)，8.41(d，1H)

M.W.:204

Step 4) preparation of 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide

The compound obtained in step 3 was dissolved in DMF, 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of 4-methanesulfonylaminophenylethylamine were added thereto, and the mixture was stirred at room temperature for 12 hours, the reaction solution was dried in vacuo, and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 65%).

Example 146-

The procedure of example 145 was repeated, except that each corresponding amine compound was used in place of 4-methanesulfonylaminophenylethylamine in step 4, to obtain each title compound.

Example 151

Step 1) preparation of 7-methyl-2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine

The compound obtained in step 1 of example 1 (500mg, 4.08mmol) and thiophene-2-aldehyde (456mg, 4.08mmol) were dissolved in 2ml of nitrobenzene and the mixture was held at 180 ℃ for 15 minutes at a power of 300W. The reaction solution was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate ═ 1:1) to obtain the title compound (526mg, 2.45 mmol; yield: 45%).

¹H-NMR(CDCl₃):2.66(s，3H)，7.11(t，1H)，7.64(d，1H)，7.86(d，1H)，8.19(s，1H)，8.29(d，1H)

M.W.:216

Step 2) preparation of 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid methyl ester

The compound obtained in step 1 (526mg, 2.45mmol) was dissolved in 5ml of pyridine, and the mixture was stirred. Adding SeO thereto₂(1.09mg, 9.80mmol) and the mixture was refluxed at 120 ℃ for 24 hours. While maintaining the hot, the reaction solution was filtered through a celite pad, and the pad was thoroughly washed with hot water and MeOH, and the combined mixture was concentrated under reduced pressure, the solvent was removed, followed by vacuum drying. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed at 80 ℃ for 4 hours, and the resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compound (260mg, 1.01 mmol; yield: 41%).

¹H-NMR(CDCl₃):4.18(s，3H)，7.11(t，1H)，7.64(d，1H)，7.86(d，1H)，8.19(s，1H)，8.29(d，1H)

M.W.:260

Step 3) preparation of 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (260mg, 1.01mmol) was dissolved in 2ml of THF, and the mixture was stirred. To this was added LiOH. H dissolved in 1ml of water₂O (196mg, 4.04mmol), and the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate, and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (200mg, 0.82 mmol; yield: 81%).

¹H-NMR(CDCl₃):7.13(t，1H)，7.68(d，1H)，7.86(d，1H)，8.19(s，1H)，8.29(d，1H)

M.W.:246

Step 4) preparation of 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide

The compound obtained in step 3 was dissolved in DMF, and 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of 2' -hydroxypentanamide were added thereto, and the mixture was stirred at room temperature for 12 hours. The reaction solution was dried in vacuo and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 35%).

Examples 152-

The procedure of example 151 was repeated except that each of the same amine compounds was used in place of 2-hydroxypentanamine in step 4 to prepare each title compound.

Example 179-

The procedure of example 151 was repeated, except for using the compound obtained in example 151 (89.65mg, 0.246mmol) and 2 equivalents of mCPBA (m-chloro-p-benzoic acid) (85mg), to prepare the title compounds.

Example 196

Step 1) preparation of 2- (2, 4-fluorophenyl) -7-methyl-3H-imidazo [4, 5-b ] pyridine

The compound (1.25g, 10.24mmol) obtained in step 1 of example 1, 4-fluorobenzoic acid (1.721g, 12.29mmol) and PPA (50g) were mixed, and the mixture was stirred at 150 ℃ and 160 ℃ for 24 hours. The reaction solution was cooled to room temperature, and 20ml of water was slowly added thereto, followed by neutralization with water and saturated NaOH in an ice bath. The formed precipitate was filtered and dried in vacuo to obtain the crude title compound (1.21g, 5.32 mmol; yield: 52%).

¹H-NMR(CDCl₃):2.67(s，3H)，7.11(d，1H)，7.28(t，2H)，8.21(m，3H)

M.W.:228

Step 2) preparation of methyl 2- (4-fluorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylate

The compound obtained in step 1 (0.1g, 0.44mmol) was dissolved in 3ml of t-butanol, and the mixture was stirred. To this was added in three portions aqueous and hot KMnO dissolved in 3ml water₄(139mg, 0.88mmol) and stirred at 60-80 ℃ for 24 hours. While keeping the heat, the reaction solution was filtered through a celite pad, the pad was thoroughly washed with hot water, and the combined mixture was concentrated under reduced pressure to remove the solvent, followed by vacuum drying. The resulting residue was dissolved in 6ml MeOH with stirring. Slowly adding 7-10 equivalents of SOCl₂And the mixture was refluxed for 4 hours. The resulting mixture was concentrated under reduced pressure, the solvent was removed, and extracted with ethyl acetate. The resulting extract was washed with brine over MgSO₄Dried, filtered and concentrated under reduced pressure to remove the solvent. The obtained residue was subjected to flash column chromatography (eluent: n-hexane/ethyl acetate 1:1) to obtain the title compoundCompound (50mg, 0.19 mmol; yield: 42%).

¹H-NMR(CDCl₃):4.09(s，3H)，7.23(m，2H)，7.67(d，1H)，8.20(m，2H)，8.66(d，2H)，10.43(br，1H)

M.W.:272

Step 3) preparation of 2- (4-fluorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid

The compound obtained in step 2 (30mg, 0.11mmol) was dissolved in 2ml THF. To this was added LiOH. H dissolved in 1ml of water₂O (13.86mg, 0.33mmol), and the mixture was stirred at room temperature for 8 hours. The reaction solution was extracted with ethyl acetate and the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 2 with 1N aqueous HCl. The resulting solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dried in vacuo to obtain the crude title compound (60mg, 0.12 mmol; yield: 106%).

¹H-NMR(MeOH-d₄):7.32(dd，2H)，7.68(d，1H)，8.30(dd，2H)，8.41(d，1H)

M.W.:258

Step 4) preparation of 2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide

The compound obtained in step 3 was dissolved in DMF, and 1.2 equivalents of PyBOP, 3 equivalents of TEA and 1.2 equivalents of 4-acetylpentylamine were added thereto, and the mixture was stirred at room temperature for 12 hours. The reaction solution was dried in vacuo and the resulting residue was dissolved in a small amount of MeOH and filtered. The filtrate thus obtained was subjected to preparative HPLC to obtain the title compound (yield: 50%).

Example 197-

The procedure of example 196 was repeated, except that each corresponding amine compound was used in place of 4-acetylpentylamine in step 4, to prepare each title compound.

Example 327

The compound obtained in example 196 (10mg, 0.03mmol) was dissolved in 2ml of a mixture of DMSO and N-methylpiperazine (1: 1). The resulting solution was kept at 150 ℃ for 1 hour at a power of 200W and 100psi, and subjected to preparative HPLC to obtain the title compound (3.72mg, 0.009 mmol; yield: 30%).

Example 328-

The procedure of example 327 was repeated, except that each corresponding compound was used instead of the compound obtained in example 196 and N-methylpiperazine, to obtain each title compound.

Test example 1: analysis of the inhibitory Capacity of protein kinases to enzymatic Activity

< glycogen synthase kinase-3 beta (GSK-3 beta) >

The compounds prepared in the examples were evaluated for their activity in inhibiting GSK-3 β enzyme by modification of U.S. Pat. No. 6153618(Shultz et al). GSK-3 beta is prepared by a gene recombination method.

First, a substrate of human GSK-3. beta. encoded by a polynucleotide corresponding to 5 '-terminus and 3' -terminus was designed and synthesized from the nucleotide sequence of human GSK-3. beta. (GenBank Reg. No. L33801). The substrate was then amplified by PCR (polymerase chain reaction) with the human DNA sequence used as template and treated with the restriction enzyme BamH 1/XhoI. The resulting gene fragment was inserted into the corresponding same restriction site of pGex vector (GE Healthcare Life Science) to prepare an expression vector transformed with E.coli (E.coli) BL21(DE3) strain (Invitrogen). The transformed E.coli strain was inoculated in LB medium (1% Bacto tryptone, 0.5% yeast extract, 1% sodium chloride) and cultured until the optical density of the bacterial cells was about 0.5 at 600nm and 37 ℃. Then, IPTG (isopropyl-. beta. -D-thiogalactoside) was added thereto to a final concentration of 0.5mM at 18 ℃.16 hours after IPTG addition, cells were centrifuged at 10,000 Xg for 10 minutes and cell pellet was collected. The cell pellet was suspended in buffer solution (30mM tris-HCl (pH7.5), 100mM NaCl, 5% glycerol, 2mM DTT) and the smahed cells were incubated in an ice bath using Sonic Dismembrator (Fisher, USA). The resulting solution was centrifuged at 16,000rpm for 30 minutes.

The supernatant obtained above was introduced into a pre-equilibrated GST column (Pharmacia, USA) and eluted with 5mM glutaminone. The eluate was subjected to SDS-PAGE and GSK-3. beta. protein was collected. The GST protein is cleaved using thrombin. The GSK-3. beta. protein thus obtained was diluted with a buffer solution (20mM HEPES (pH7.5), 5% glycerol, 2mM DTT) until the concentration of NaCl reached 50 mM. The diluted solution was introduced into a Mono S column (Pharmacia, USA) equilibrated with the above buffer solution, and eluted with aqueous NaCl while varying the concentration from 0-1M NaCl, and the GSK-3. beta. protein was collected by electrophoresis. The purified protein was used in the assay of enzymatic activity.

Meanwhile, each compound prepared in example was dissolved in dimethyl sulfoxide (DMSO) to a concentration of 12.5mM to prepare a test solution. In a buffer solution (50mM tris-HCl (pH7.5), 10mM MgCl₂1mM EGTA, 1mM EDTA and 1mM DTT). mu.M phosho-CREB peptide (NEB, USA), 100. mu.M ATP and 1. mu. Ci³²P-ATP is added as a substrate to the buffer solution. Then, 100nM recombinant GSK-3. beta. was added thereto, and the mixture was allowed to react at 30 ℃ for 1 hour. The reaction was terminated by adding 5. mu.l of 5% phosphoric acid solution to 25. mu.l of the reaction mixture. The resulting solution was centrifuged at 15,000 for 10 minutes, and 20. mu.l of the supernatant thus obtained was dropped onto a whatman p81 filter paper. The filter paper was washed in 0.5% phosphoric acid solution for 10 minutes. After repeated 3 washes, the filter paper was dried and analyzed for cpm (counts/min).

The above test solution prepared by dissolving the test compound in DMSO was added to the reaction solution in an amount of less than 5% based on the total reaction solution, and the ability of the enzyme inhibitory activity was analyzed. Relative to no storageCpm values at the test compound, obtained when the test compound was present, expressed as a percentage, and the concentration of test compound required to inhibit enzyme activity by 50% relative to the control solution, the IC was determined₅₀(μM)。

< Aurora kinase A >

Test solutions were prepared by dissolving one of the compounds of the examples in DMSO at a concentration of 12.5 mM. In the presence of 20mM of HEPES (pH7.5), 5mM MgCl₂0.5mM ethylene glycol bis (b-aminoethyl ether) tetraacetic acid (EGTA), 200mM KCl, 1mM DTT, and 0.05% triton X-100 in buffer solution. 100 μ M Kemptide peptide (Upstate) and 1 μ M ATP were added to the buffer solution as substrates. At a concentration of 10nM, recombinant aurora kinase (Upstate) was added to the resulting mixture, and the reaction was carried out at 30 ℃ for 1 hour. Mu.l of the resulting solution was mixed with 25. mu.l of the kinase glo (promega), thereby inducing a second reaction by luciferase. Residual ATP levels were measured by fusion a-FP (Packard, USA). The inhibitory ability of the test compound against the enzyme activity was analyzed according to the same method as the GSK-3. beta. assay, and the IC was calculated₅₀The value is obtained.

< extracellular Signal-regulated kinase-1 (ERK-1) >

Test compounds were prepared by dissolving the compounds prepared in example in dimethyl sulfoxide (DMSO) at a concentration of 12.5mM, and in a solution containing 50mM tris-HCl (pH7.5), 10mM MgCl₂1mM EGTA, 1mM EDTA and 1mM DTT. 0.33mg/ml MBP (Upstate), 100. mu.M ATP and 0.25. mu. Ci³²P-ATP is added as a substrate to the buffer solution. 5nM recombinant Erk-1(Upstate) was added to the resulting mixture and the mixture was allowed to react at 30 ℃ for 1 hour. The reaction was terminated by adding 5. mu.l of a 5% phosphoric acid solution to 25. mu.l of the reaction mixture. Mu.l of the resulting solution was dropped onto a whatmanp81 filter paper and then washed in 0.5% phosphoric acid solution for 10 minutes. After repeated 3 washes, the filter paper was dried and its cpm was measured by a liquid scintillation counter (Packard, usa). According to the same method as the GSK-3 beta analysisAnalyzing the inhibitory ability of the test compound on the enzyme activity, and calculating IC₅₀The value is obtained.

< cyclin-dependent kinase-2 (CDK-2) >

The procedure of the ERK-1 assay was repeated to assay for the inhibitory ability of test compounds against enzymatic activity, except that 2.5. mu.g of histone H1(Upstate) and 100nM of recombinant CDK-2/cyclin A (Upstate) were used.

< p38 mitogen-activated protein kinase (MAPK) >

The procedure of the ERK-1 assay was repeated to analyze the inhibitory ability of the test compounds against enzyme activity, except that 2.5. mu.g of histone H1(Upstate) and 5nM of recombinant p38a (Upstate) were used.

< c-jun N-terminal kinase-1 (JNK-1) >

The procedure of ERK-1 assay was repeated to analyze the inhibitory ability of the test compound against the enzymatic activity, except that 272nM GST-ATF2(Upstate) and 7nM recombinant JNK1(Upstate) were used.

< pyruvate dehydrogenase kinase-1 (PDK-1) >

The procedure of the aurora kinase A assay was repeated to analyze the inhibitory ability of the test compound on the enzyme activity, except that 50mM tris-HCl (pH7.5), 10mM MgCl₂1mM EGTA and 1mM DTA; mu.M PDKtide (peptide, Upstate) and 31.5nM recombinant PDK1 (Upstate).

< kinase insert Domain protein receptor (KDR) >

The compounds prepared in the examples were dissolved in dimethyl sulfoxide (DMSO) at a concentration of 12.5mM to prepare test solutions, and the solutions were mixed in a solution containing 50mM tris-HCl (pH7.5), 5mM MgCl₂、1mMMnCl₂0.01% tween-20 and 2mM DTT in buffer. 1nMBiotin-poly E4Y (Packard) and 0.1. mu. MATP were added as substrates to the buffer solution. Adding 2nM recombinant KDR (upstate) to the resulting mixture and heating at 30 deg.CThe reaction was carried out for 1 hour. Mu.l of a diluted solution prepared by diluting alphascreen phosphotyrosine (T-Tyr-100, Packard) beads with a solution containing 6.25mM HEPES (pH7.4), 250mM NaCl, 100mM EDTA and 0.25% BSA was added to 15. mu.l KDR reaction solution. After 1 hour of reaction at room temperature, the alphascreen signal was measured by fusion a-FP (packard). The inhibitory ability of the test compound against the enzyme activity was analyzed according to the same method as the GSK-3. beta. assay, and the IC was calculated₅₀The value is obtained.

The inhibitory ability of the test compounds on GSK-3 β is shown in Table 2 compared to the control compound 99021 derivative (Chiron) (Diabetes, 52, 588-595 (2003)).

TABLE 2

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	1	0.020
44	0.038	1	0.020
44	0.038	61	0.003
109	0.052	61	0.003
109	0.052	154	0.003
332	0.012	154	0.003
332	0.012	308	0.008
320	0.005	308	0.008
320	0.005	325	0.002
327	0.050	325	0.002
327	0.050	332	0.012
396	0.002	332	0.012
396	0.002	404	0.003
Comparison Compound (99021 derivative)	0.030	404	0.003

As can be seen from table 2, the compound of formula 1 in the examples of the present invention showed more excellent inhibitory ability against GSK-3 β than the comparative compound.

In addition, the inhibitory potency against aurora kinase A, ERK-1, CDK-2, JNK-1, PDK-1, KDR and p38 mitogen-activated protein kinase (MAPK) is shown in Table 3.

TABLE 3

Aurora kinase A

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	264	0.070
343	0.198	264	0.070
343	0.198	368	0.040
371	0.113	368	0.040
371	0.113	381	0.033
313	1.100	381	0.033
313	1.100	409	0.250
418	0.200	409	0.250
418	0.200	423	0.105
425	>6	423	0.105

TABLE 4

ERK-1

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	241	16.5
320	25.5	241	16.5
320	25.5	452	19.0

TABLE 5

CDK-2

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	198	2.4
246	0.225	198	2.4
246	0.225	340	0.4
343	0.3	340	0.4
343	0.3	287	0.12
308	0.95	287	0.12
308	0.95	320	0.17
451	0.36	320	0.17
451	0.36	452	0.35

TABLE 6

JNK-1

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	246	0.18
340	0.10	246	0.18
340	0.10	287	0.46
308	0.95	287	0.46
308	0.95	320	14.5
451	10.5	320	14.5

TABLE 7

PDK-1

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	343	3.1
241	28.5	343	3.1

TABLE 8

KDR

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	198	12.5
246	0.52	198	12.5
246	0.52	343	0.17
287	1.5	343	0.17
287	1.5	320	0.29
451	1.65	320	0.29

TABLE 9

p38 mitogen-activated protein kinase (MAPK)

Examples	IC₅₀(μM)
Examples	IC₅₀(μM)	308	50
320	50	308	50
320	50	451	3.25

As can be seen from tables 3 to 9, the compounds of formula 1 of the present invention showed inhibitory ability to various protein kinases.

While the invention has been described with reference to the above specific embodiments, it will be appreciated that various modifications and changes can be made to the invention by those skilled in the art which also fall within the scope of the invention as defined by the appended claims.

Claims

1. A compound of formula 1, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof:

wherein,

R₁is hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, C_1-6An alkylsulfonyl group,Amides, optionally substituted by halogen, -CN, NO₂、C_1-6Alkyl radical, C_1-6Alkyl piperazinyl, C_1-6Alkylsulfinyl radical C_1-6Alkyl, piperidinyl, morpholinyl, pyrrolidinyl, morpholinyl C_1-6Alkylamino, pyrrolidinyl C_1-6Alkylamino, -OR ', -C (O) OR ', -OC (O) R ', -NR ' R ', -NHC (O) R ', -C (O) NR ' R ', -NHC (S) R ', -C (S) NR ' R ', -SR ', -S (O) R ', -SO₂R′、-NHSO₂R′、-SO₂NR′R＂、-OSO₂R′、-SO₂OR', aryl, heteroaryl, aryl-C_1-4Alkyl, formyl or trifluoromethyl substituted aryl or heteroaryl, each of R' or R "is independently hydrogen; or C_1-4Alkyl radical, C_3-7Cycloalkyl, optionally substituted by C_1-4Alkyl radical, C_1-4Alkoxy, CN, NO₂、NH₂、(C_1-4Alkyl) amino, OH, COOH, COO (C)_1-4Alkyl), -CONH₂Aryl or heteroaryl substituted with formyl or trifluoromethyl; aryl is phenyl, indanyl or naphthyl; and heteroaryl is an aryl group of 5-to 10-membered ring, or a mono-or bicyclic heterocycle containing one or more of nitrogen, sulfur or oxygen atoms in its ring structure;

R₂is hydrogen; unsubstituted or substituted C_1-8An alkyl group; or unsubstituted or substituted C containing nitrogen, sulfur or oxygen in its chain structure_1-7Alkyl, wherein the substituents of the alkyl are hydroxy, halogen, C_1-6Alkoxy, alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl or amide; optionally is covered with C_1-4Alkyl, hydroxy, halogen, C_1-6Alkoxy, amino, C_1-6Alkylamino radical, amino radical C_1-6Alkyl, acetylamino, carboxyl, amide, dioxoindole, -CN, NO₂、-OR′、-C(O)OR′、-OC(O)R′、-NR′R＂、-NHC(O)R′、-NHC(O)OR′、-C(O)NR′R＂、-NHC(S)R′、-C(S)NR′R＂、-SR′、-S(O)R′、-SO₂R′、-NHSO₂R′、-SO₂NR′R＂、-OSO₂R′、-SO₂OR', aryl, heteroaryl, aryl-C_1-4Alkyl, formyl or trifluoromethyl substituted aryl or heteroaryl, each of R' or R "is independently hydrogen; or C_1-4Alkyl radical, C_3-7Cycloalkyl, optionally substituted by halogen, C_1-4Alkyl radical, C_1-4Alkoxy, CN, NO₂、NH₂、C_1-4Alkylamino radical, amino radical C_1-4Alkyl, OH, COOH, -COOC_1-4Alkyl, -CONH₂Formyl, C_1-6Alkyl piperazinyl, morpholinyl or trifluoromethyl substituted aryl or heteroaryl; wherein aryl is phenyl, indanyl or naphthyl; and heteroaryl is a 5-to 10-membered ring aryl, pyridone, or a monocyclic or bicyclic heterocycle containing 1-4 nitrogen, sulfur, or oxygen atoms in its ring structure; or unsubstituted or substituted aryl; or an unsubstituted or substituted aryl group containing one or more of nitrogen, sulfur or oxygen within its ring structure; wherein the substituent for aryl is hydroxy; halogen; c_1-6An alkoxy group; c_1-6An alkyl group; an amino group; c_1-6An alkylamino group; a carboxyl group; a nitro group; a sulfonyl amide; c_1-6An alkylsulfonyl group; an amide; unsubstituted or substituted C_1-6An alkyl group; or a ring C containing one or more of nitrogen, sulfur or oxygen atoms in its ring structure_1-6An alkyl group, wherein the substituent of the alkyl group is a hydroxyl group; halogen; c_1-6An alkoxy group; c_1-6An alkyl group; an amino group; c_1-6An alkylamino group; a carboxyl group; a nitro group; a sulfonyl amide; c_1-6An alkylsulfonyl group; an amide; optionally substituted by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxy, nitro, amide or dioxoisoindolyl-substituted aryl; aryl by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, C_1-6Alkylsulfonyl-or amide-substituted sulfonylaminoaryl; aryl including one or more of nitrogen, sulfur or oxygen atoms within its ring structure, which represents pyrrole, pyrazole, imidazole, 1, 2, 3-triazole, 1, 2, 4-triazole, isoxazole, oxazole, isothiazole, thiazolidine, thiazole, 1, 2, 5-oxadiazole, 1, 2, 3-oxadiazole, 1, 2, 5-oxadiazoleThiadiazole, 1, 2, 3-thiadiazole, 1, 3, 4-oxadiazole, 1, 3, 4-thiadiazole, pyridine, oxypyrideine, pyrimidine or triazine, optionally substituted by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro, sulfonylamide, C_1-6Alkylsulfonyl or amide substitution; or optionally substituted by hydroxy, halogen, C_1-6Alkoxy radical, C_1-6Alkyl, amino, C_1-6Alkylamino, carboxyl, nitro or amide substituted C_3-8A cycloalkyl group;

2. The compound of claim 1, wherein R₁Is phenyl, pyrrolidinylphenyl, dichlorophenyl, chlorophenyl, fluorophenyl, difluorophenyl, furyl, thiophene, cyclopropyl，C_1-2Alkyl piperazinyl phenyl, C_1-2Alkyl piperazinyl C_1-3Alkyl phenyl, C_1-2Alkyl piperazinyl C_1-3Alkylaminophenyl, methylsulfinylphenyl, di-C_1-2Alkylaminophenyl, morpholinylphenyl, piperidinylphenyl, morpholinyl C_1-3Alkylaminophenyl, pyrrolidinyl C_1-3Alkylamino phenyl, dimethylamino C_1-4Alkylamino phenyl, di-C_1-2Alkylaminoethylmethylaminophenyl, piperazinylaminophenyl, piperazino-C_1-2Alkylaminophenyl, thiomorpholinophenyl, piperidinylaminophenyl, piperidino C_1-2Alkylamino phenyl, methoxyphenyl, di-C_1-3An alkylamino pyrrolidinylphenyl or pyridyl group; r₂Is optionally sulfonylphenyl, C_1-2Alkyl pyridyl, di-C_1-2Alkyl radical, tri-C_1-2Alkyl, tetra C_1-2Alkyl, pyridyl, oxypyridyl, chloropyridyl, morpholinyl, amino C_1-2Alkyl pyridyl, acetylaminophenyl, imidazole, dichloroimidazole, C_1-2Alkyl imidazoles, di-C_1-2Alkylamino sulfonylaminophenyl, trifluoro C_1-2Alkylphenyl, benzyloxypyridyl, hydroxyxypyridyl, C_1-2Alkanesulfonylaminophenyl, di-C_1-2Alkylaminoacylaminophenyl, trifluoromethanesulfonylaminophenyl, fluoropyridyl, fluorohydroxyphenyl, C_1-2Alkylpiperazinyl acetylaminophenyl, chlorooxypyridinyl, phenylthio, C_1-2Alkoxypyridyl, aminophenyl, hydroxyphenyl, C_1-2Alkyl piperazine carbonylaminophenyl, morpholinyl C_1-3Alkoxyphenyl, benzyl, hydroxy-di-C_1-2Alkyl or di-C_1-2Alkylamino radical C_1-2Alkyl substituted C_1-5An alkyl group; optionally substituted by tri C_1-2Alkyl, amino or hydroxy substituted ring C_3-7An alkyl group; optionally is covered with C_1-2Alkyl, di-C_1-2Alkyl, chloro C_1-2Alkoxy radical, C_1-2Alkylamino radical, amino radical C_1-2Alkyl radical, C_1-2Alkoxy radical, C_1-2Alkoxy radical C_1-2Alkyl radical, C_1-2Alkylsulfonyl, chloro C_1-2Alkyl, isobutoxy, cyclopropylmethoxy, di-C_1-2Alkylamino radical C_1-2Alkoxy, morpholinyl C_1-2Alkoxy, halogen, acetylamino or C_1-2Alkylsulfonyl radical C_1-2An alkyl-substituted pyridyl group; by benzoylamino, piperidinyl, hydroxy, C_1-2Alkoxy radical, C_1-2Alkyl, di-C_1-2Alkyl, diisopropyl, isopropyl, di-C_1-2Alkylamino acetylamino, fluoro C_1-2Alkyl, fluorohydroxy, trifluoro C_1-2Alkoxy, di-C_1-2Alkoxy, acetylamino, cyano, benzyloxy, trifluoromethanesulfonylamino or C_1-2Alkylsulfonyl-substituted phenyl; benzothiazolyl, indazolyl, C_1-2Alkylindolyl, indolyl, naphthyl, quinolinyl, C_1-2Alkylpyrazolyl, phenylthiazolyl, tolyl, benzo-m-cyclopentenyl (dioxolyl), C_1-2Alkylphenyl acetamide, C_1-2Alkylphenoxyacetyl, ethylsulfonyl C_1-2Alkylphenylamides, C_1-2Alkylphenoxy acetic acid tert-butyl ester, C_1-2Alkylphenylmethanesulfonamide, C_1-2Alkyl piperazinyl, C_1-2Alkoxyphenylamide, piperidyl, benzylpiperidyl, C_1-2Alkylphenoxyacetyl, tri-C_1-2Alkyl-bicyclo (heptanyl), adamantyl, aminobicycloheptylcarboxyl, azabicyclo-octyl, bicyclo (heptanyl), tert-butylamide or C_1-2Alkyl pyridyl radical C_1-2Alkyl carbamic acid tert-butyl ester; and R₃Is H, or R₂And R₃Fused together with the nitrogen to which they are attached to form a ring; r₄Is H or halogen; and R₅Is H.

3. The compound of claim 1 selected from the group consisting of:

1) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide;

2) (4- {2- [ (2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carbonyl) -amino ] -ethyl } -phenoxy) -acetic acid;

3) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

4) (3- {2- [ (2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carbonyl) -amino ] -ethyl } -phenoxy) -acetic acid;

5) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

6) (3- {2- [ (2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carbonyl) -amino ] -ethyl } -phenoxy) -acetic acid tert-butyl ester;

7) (4- {2- [ (2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carbonyl) -amino ] -ethyl } -phenoxy) -acetic acid tert-butyl ester;

8) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-fluoro-3-hydroxy-phenyl) -ethyl ] -amide;

9) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

10) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloro-3H-imidazol-1-yl) -propyl ] -amide;

11) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

12) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-2-yl-ethyl) -amide;

13) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

14) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

15) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-morpholin-4-yl-propyl) -amide;

16) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-2-yl) -ethyl ] -amide;

17) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-3-yl) -ethyl ] -amide;

18) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-4-yl) -ethyl ] -amide;

19) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-3-yl) -ethyl ] -amide;

20) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

21) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-chloro-pyridin-3-yl) -ethyl ] -amide;

22) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

23) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-4-yl) -ethyl ] -amide;

24) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-benzoylamino-phenyl) -amide;

25) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-piperidin-1-yl-phenyl) -amide;

26) 6-bromo-2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-benzoylamino-phenyl) -amide;

27) 6-bromo-2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

28) 6-bromo-2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-thiophen-2-yl-ethyl) -amide;

29) 6-chloro-2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloroimidazol-1-yl) -propyl ] -amide;

30) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid phenylamide;

31) 2-phenyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

32)2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide;

33)2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

34)2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

35) [4- (2- { [2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carbonyl ] -amino } -ethyl) -phenoxy ] -acetic acid;

36) [3- (2- { [2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carbonyl ] -amino } -ethyl) -phenoxy ] -acetic acid;

37) [4- (2- { [2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carbonyl ] -amino } -ethyl) -phenoxy ] -acetic acid tert-butyl ester;

38) [3- (2- { [2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carbonyl ] -amino } -ethyl) -phenoxy ] -acetic acid tert-butyl ester;

39)2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (3H-imidazol-1-yl) -propyl ] -amide;

40)2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [4- (2-dimethylamino-acetylamino) -phenyl ] -ethyl } -amide;

41)2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-sulfonylphenyl) -ethyl ] -amide;

42) [2- (2- { [2- (2, 4-dichlorophenyl) -3H-imidazo [4, 5-b ] pyridine-7-carbonyl ] -amino } -ethyl) -phenoxy ] -acetic acid;

43)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

44)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide;

45)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

46)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [4- (2-dimethylamino-acetylamino) -phenyl ] -ethyl } -amide;

47)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-imidazol-1-yl-propyl) -amide;

48)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloroimidazol-1-yl) -propyl ] -amide;

49)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4-methyl-imidazol-1-yl) -propyl ] -amide;

50)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

51)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylaminosulfonylamino-phenyl) -ethyl ] -amide;

52)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

53)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-trifluoromethyl-phenyl) -ethyl ] -amide;

54)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4-benzyloxy-2-oxo-2H-pyridin-1-yl) -propyl ] -amide;

55)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-benzyloxy-2-oxo-2H-pyridin-1-yl) -ethyl ] -amide;

56)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-hydroxy-2-oxo-2H-pyridin-1-yl) -ethyl ] -amide;

57)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

58)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

59)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

60)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

61)2- (4-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

62) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloro-3H-imidazol-1-yl) -propyl ] -amide;

63) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

64) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

65) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

66) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [4- (2-dimethylamino-acetylamino) -phenyl ] -ethyl } -amide;

67) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4-methyl-imidazol-1-yl) -propyl ] -amide;

68) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

69) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylaminosulfonylamino-phenyl) -ethyl ] -amide;

70) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-2-yl-ethyl) -amide;

71) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

72) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

73) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-fluoro-3-hydroxy-phenyl) -ethyl ] -amide;

74) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-imidazol-1-yl-propyl) -amide;

75) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-2-yl) -ethyl ] -amide;

76) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-3-yl) -ethyl ] -amide;

77) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-4-yl) -ethyl ] -amide;

78) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

79) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-chloro-pyridin-3-yl) -ethyl ] -amide;

80) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

81) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-3-yl-propyl) -amide;

82) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-trifluoromethanesulfonylamino-phenyl) -ethyl ] -amide;

83) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-chloro-pyridin-3-yl) -propyl ] -amide;

84) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-4-yl-propyl) -amide;

85) 2-furan-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (2-fluoro-pyridin-3-yl) -propyl ] -amide;

86) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

87) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (5-methyl-3H-imidazol-1-yl) -propyl ] -amide;

88) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-2-yl-ethyl) -amide;

89) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

90) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

91) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

92) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

93) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [4- (2-dimethylamino-acetylamino) -phenyl ] -ethyl } -amide;

94) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylaminosulfonylamino-phenyl) -ethyl ] -amide;

95) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

96) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-fluoro-3-hydroxy-phenyl) -ethyl ] -amide;

97) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-imidazol-1-yl-propyl) -amide;

98) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-2-yl) -ethyl ] -amide;

99) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-3-yl) -ethyl ] -amide;

100) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-4-yl) -ethyl ] -amide;

101) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

102) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-chloro-pyridin-3-yl) -ethyl ] -amide;

103) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

104) (3- {2- [ (2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carbonyl) -amino ] -ethyl } -pyridin-2-ylmethyl) -carbamic acid tert-butyl ester;

105) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-4-yl) -ethyl ] -amide;

106) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-3-yl-propyl) -amide;

107) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-trifluoromethanesulfonylamino-phenyl) -ethyl ] -amide;

108) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-chloro-pyridin-3-yl) -propyl ] -amide;

109) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-4-yl-propyl) -amide;

110) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (2-fluoro-pyridin-3-yl) -propyl ] -amide;

111) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (2-chloro-pyridin-4-yl) -propyl ] -amide;

112) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-methyl-pyridin-3-yl) -ethyl ] -amide;

113) 2-thiophen-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-fluoro-pyridin-3-yl) -propyl ] -amide;

114) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

115) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

116) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylaminosulfonylamino-phenyl) -ethyl ] -amide;

117) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloro 3H-imidazol-1-yl) -propyl ] -amide;

118) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (5-methyl-3H-imidazol-1-yl) -propyl ] -amide;

119) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

120) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

121) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide;

122) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2- {4- [2- (4-ethyl-piperazin-1-yl) -acetylamino ] -phenyl } -ethyl) -amide;

123) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-2-yl-ethyl) -amide;

124) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

125) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

126) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-fluoro-3-hydroxy-phenyl) -ethyl ] -amide;

127) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-imidazol-1-yl-propyl) -amide;

128) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-2-yl) -ethyl ] -amide;

129) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-3-yl) -ethyl ] -amide;

130) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-4-yl) -ethyl ] -amide;

131) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-3-yl) -ethyl ] -amide;

132) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

133) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-chloro-pyridin-3-yl) -ethyl ] -amide;

134) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

135) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-4-yl) -ethyl ] -amide;

136) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-3-yl-propyl) -amide;

137) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-trifluoromethanesulfonylamino-phenyl) -ethyl ] -amide;

138) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-chloro-pyridin-3-yl) -propyl ] -amide;

139) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-4-yl-propyl) -amide;

140) 6-bromo-2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloroimidazol-1-yl) -propyl ] -amide;

141) 2-furan-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-benzoylamino-phenyl) -amide;

142)2- (2, 4-difluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

143)2- (2, 4-difluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

144)2- (2, 4-difluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloroimidazol-1-yl) -propyl ] -amide;

145) 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

146) 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

147) 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylaminosulfonylamino-phenyl) -ethyl ] -amide;

148) 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloro 3H-imidazol-1-yl) -propyl ] -amide;

149) 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (5-methyl-3H-imidazol-1-yl) -propyl ] -amide;

150) 2-cyclopropyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

151) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

152) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide;

153) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

154) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

155)2- (1-oxo-thiophen-3-yl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

156) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-2-yl-ethyl) -amide;

157) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

158) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

159) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

160) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylaminosulfonylamino-phenyl) -ethyl ] -amide;

161) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-fluoro-3-hydroxy-phenyl) -ethyl ] -amide;

162) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4-methyl-imidazol-1-yl) -propyl ] -amide;

163) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-imidazol-1-yl-propyl) -amide;

164) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-2-yl) -ethyl ] -amide;

165) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-3-yl) -ethyl ] -amide;

166) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-4-yl) -ethyl ] -amide;

167) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

168) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

169) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-chloro-1-oxy-pyridin-3-yl) -ethyl ] -amide;

170) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-fluoro-pyridin-4-yl) -ethyl ] -amide;

171) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-methylamino-pyridin-4-yl) -ethyl ] -amide;

172) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-3-yl-propyl) -amide;

173) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-trifluoromethanesulfonylamino-phenyl) -ethyl ] -amide;

174) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-chloro-pyridin-3-yl) -propyl ] -amide;

175) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-4-yl-propyl) -amide;

176) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (2-chloro-pyridin-4-yl) -propyl ] -amide;

177) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-methyl-pyridin-3-yl) -ethyl ] -amide;

178) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-fluoro-pyridin-3-yl) -propyl ] -amide;

179)2- (1-oxo-thiophen-3-yl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (1-oxo-pyridin-3-yl) -propyl ] -amide;

180)2- (1-oxo-1H-thiophen-3-yl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-3-yl-propyl) -amide;

181) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-yl-amide;

182) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-4-yl-amide;

183) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyloxy-pyridin-3-yl) -amide;

184) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-amino-phenyl) -ethyl ] -amide;

185) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

186) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cycloheptylamide;

187) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (5-methyl-2H-pyrazol-3-yl) -amide;

188) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methylamino-pyridin-3-yl) -amide;

189) 2-thiophen-3-yl-1H-pyrrolo [2, 3-b ] pyridine-4-carboxylic acid (4-benzoylamino-phenyl) -amide;

190) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-methanesulfonylamino-pyridin-3-yl) -propyl ] -amide;

191) 6-bromo-2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

192) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

193) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

194) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

195) 2-thiophen-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-6-methyl-pyridin-3-yl) -amide;

196)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-acetylamino-phenyl) -ethyl ] -amide;

197)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-hydroxy-phenyl) -ethyl ] -amide;

198)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

199)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (3H-imidazol-1-yl) -propyl ] -amide;

200)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [4- (2-dimethylamino-acetylamino) -phenyl ] -ethyl } -amide;

201)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-hydroxy-phenyl) -ethyl ] -amide;

202)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloroimidazol-1-yl) -propyl ] -amide;

203)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-chloro-phenyl) -ethyl ] -amide;

204)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2- {4- [ (4-methyl-piperazine-1-carbonyl) -amino ] -phenyl } -ethyl) -amide;

205)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4-methyl-imidazol-1-yl) -propyl ] -amide;

206)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-methanesulfonylamino-phenyl) -ethyl ] -amide;

207)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-dimethylamino-sulfonylamino-phenyl) -ethyl ] -amide;

208)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (3-trifluoromethyl-phenyl) -ethyl ] -amide;

209)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [3- (2-morpholin-4-yl-ethoxy) -phenyl ] -ethyl } -amide;

210)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [3- (3-morpholin-4-yl-propoxy) -phenyl ] -ethyl } -amide;

211)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid {2- [3- (2-dimethylamino-ethoxy) -phenyl ] -ethyl } -amide;

212)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-2-yl-ethyl) -amide;

213)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

214)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-4-yl-ethyl) -amide;

215)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-fluoro-3-hydroxy-phenyl) -ethyl ] -amide;

216)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (1-oxy-pyridin-4-yl) -ethyl ] -amide;

217)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-3-yl) -ethyl ] -amide;

218)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

219)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-chloro-pyridin-3-yl) -ethyl ] -amide;

220)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

221)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-aminomethyl-pyridin-4-yl) -ethyl ] -amide;

222)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (6-aminomethyl-pyridin-3-yl) -ethyl ] -amide;

223)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-fluoro-pyridin-4-yl) -ethyl ] -amide;

224)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-methylamino-pyridin-4-yl) -ethyl ] -amide;

225)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-trifluoromethanesulfonylamino-phenyl) -ethyl ] -amide;

226)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-3-yl-propyl) -amide;

227)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-pyridin-4-yl-propyl) -amide;

228)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (2-chloro-pyridin-4-yl) -propyl ] -amide;

229)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-methyl-pyridin-3-yl) -ethyl ] -amide;

230)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-fluoro-pyridin-3-yl) -propyl ] -amide;

231)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-2-ylamide;

232)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

233)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-4-ylamide;

234) [2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridin-7-yl ] -piperidin-1-yl-methanone;

235) [2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridin-7-yl ] - (4-methyl-piperazin-1-yl) -methanone;

236)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-amino-phenyl) -ethyl ] -amide;

237)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyloxy-pyridin-3-yl) -amide;

238)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (6-chloro-pyridin-3-yl) -propyl ] -amide;

239)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-methyloxy-pyridin-3-yl) -amide;

240)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cycloheptylamide;

241)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

242)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-chloro-pyridin-3-yl) -amide;

243)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (5-methyl-2H-pyrazol-3-yl) -amide;

244)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (5-methyl-pyridin-2-yl) -amide;

245)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-chloro-pyridin-3-yl) -amide;

246)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyloxy-pyridin-3-yl) -amide;

247)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-chloro-pyridin-3-yl) -amide;

248)2- (4-fluoro-phenyl) -3-methyl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (4-ethanesulfonylamino-phenyl) -ethyl ] -amide;

249)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-piperidin-1-ylphenyl) -amide;

250)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-morpholin-4-yl-phenyl) -amide;

251) 6-bromo-2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

252) 6-chloro-2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [2- (2-chloro-pyridin-4-yl) -ethyl ] -amide;

253)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid phenylamide;

254)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-hydroxy-cyclohexyl) -amide;

255)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-benzyl-piperidin-4-yl) -amide;

256)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid piperidin-4-ylamide;

257)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6-diethyl-phenyl) -amide;

258)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6-diisopropyl-phenyl) -amide;

259)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid benzyl-ethyl-amide;

260)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-benzyl-pyrrolidin-3-yl) -amide;

261)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid isopropyl-phenyl-amide;

262)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

263)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid adamantan-1-ylamide;

264)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid adamantan-2-ylamide

265)2- { [2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carbonyl ] -amino } -bicyclo [2.2.1] hepta-2-carboxylic acid;

266)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-azabicyclo [2.2.2] oct-3-yl) -amide;

267)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

268)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

269)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6, 6-trimethyl-bicyclo [3.1.1] hept-3-yl) -amide;

270)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6, 6-trimethyl-bicyclo [3.1.1] hept-3-yl) -amide;

271)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6-dimethyl-phenyl) -amide;

272)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-amino-cyclohexyl) -amide;

273)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclopentylamide;

274)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

275)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-hydroxy-1, 1-dimethyl-ethyl) -amide;

276)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

277)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid tert-butylamide;

278)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-dimethylamino-1-methyl-ethyl) -amide;

279)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-ethoxy-phenyl) -amide;

280)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-hydroxy-cyclopentyl) -amide;

281)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-hydroxymethyl-cyclopentyl) -amide;

282)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 1-dimethyl-propyl) -amide;

283)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3, 3, 5-trimethyl-cyclohexyl) -amide;

284)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid naphthalen-2-ylamide;

285)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid quinolin-6-ylamide;

286)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid quinolin-3-ylamide;

287)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

288)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-2-methyl-pyridin-3-yl) -amide;

289)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 3, 3-trimethyl-butyl) -amide;

290)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 4-dimethyl-pentyl) -amide;

291)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-ethyl-propyl) -amide;

292)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 1, 3, 3-tetramethyl-butyl) -amide;

293)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid benzothiazol-2-ylamide;

294)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1H-indazol-6-yl) -amide;

295)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-methyl-1H-indol-5-yl) -amide;

296)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1H-indol-5-yl) -amide;

297)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-trifluoromethoxy-phenyl) -amide;

298)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3, 5-dimethoxy-phenyl) -amide;

299)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-acetylamino-phenyl) -amide;

300)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-cyano-phenyl) -amide;

301)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-benzyloxy-phenyl) -amide;

302)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-phenylthiazol-2-yl) -amide;

303)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid p-tolylamide;

304)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid benzo [1, 3] dioxolan-5-ylamide;

305)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6-dimethyl-pyridin-3-yl) -amide;

306)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-chloro-6-methoxy-pyridin-3-yl) -amide;

307)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-5-methyl-pyridin-3-yl) -amide;

308)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

309)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-methanesulfonyl-phenyl) -amide;

310)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-chloro-4-methyl-pyridin-3-yl) -amide;

311)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-isobutoxy-pyridin-3-yl) -amide;

312)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-cyclopropylmethoxy-pyridin-3-yl) -amide;

313)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [4- (2-dimethylamino-ethoxy) -pyridin-3-yl ] -amide;

314)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [4- (2-morpholin-4-yl-ethoxy) -pyridin-3-yl ] -amide;

315)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-chloro-4-methyl-pyridin-3-yl) -amide;

316)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-chloro-5-methyl-pyridin-3-yl) -amide;

317)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-chloro-5-methyl-pyridin-3-yl) -amide;

318)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 5-dichloropyridin-3-yl) -amide;

319)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4, 6-dichloropyrimidin-5-yl) -amide;

320)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

321)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-dimethylamino-pyridin-3-yl) -amide;

322)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-acetylamino-pyridin-3-yl) -amide;

323)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [6- (2-morpholin-4-yl-ethoxy) -pyridin-3-yl ] -amide;

324)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4, 6-dimethyl-pyridin-3-yl) -amide;

325)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-6-methyl-pyridin-3-yl) -amide;

326)2- (4-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-6-methyl-pyridin-3-yl) -amide;

327)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

328)2- (4-methylsulfinylmethyl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

329)2- (4-diethylamino-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

330)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

331)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

332)2- (4-pyrrolidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

333)2- (4-pyrrolidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

334)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

335)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

336)2- (4-dimethylamino-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid pyridin-3-ylamide;

337)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

338)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

339)2- [4- (3-morpholin-4-yl-propylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

340)2- [4- (3-pyrrolidin-1-ylpropylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

341)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

342)2- [4- (3-dimethylamino-propylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

343)2- [4- (4-dimethylamino-butylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

344)2- {4- [ (2-diethylamino-ethyl) -methyl-amino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

345)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

346)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

347)2- [4- (piperidin-4-ylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

348)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid adamantan-2-ylamide;

349)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid adamantan-2-ylamide;

350)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cycloheptylamide;

351)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cycloheptylamide;

352)2- (4-thiomorpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cycloheptylamide;

353)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-aza-bicyclo [2.2.2] oct-3-yl) -amide;

354)2- [4- (piperidin-4-ylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

355)2- [4- (2-piperazin-1-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

356)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

357)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

358)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

359)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

360)2- {4- [ (2-diethylamino-ethyl) -methyl-amino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

361)2- [4- (4-ethyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid cyclohexylamide;

362)2- (4-morpholin-4-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-aza-bicyclo [2.2.2] oct-3-yl) -amide;

363)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6, 6-trimethyl-bicyclo [3.1.1] hept-3-yl) -amide;

364)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

365)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2, 6-dimethyl-phenyl) -amide;

366)2- [4- (2-piperidin-1-ylethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

367)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-hydroxy-cyclohexyl) -amide;

368)2- [4- (2-morpholin-4-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

369)2- [4- (2-piperazin-1-yl-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

370)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

371)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

372)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

373)2- [4- (2-piperidin-1-ylethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

374)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid bicyclo [2.2.1] hept-2-ylamide;

375)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-amino-cyclohexyl) -amide;

376)2- [4- (2-diethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

377)2- [4- (3-dimethylamino-propylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

378)2- [4- (2-pyrrolidin-1-ylethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

379)2- {4- [3- (4-methyl-piperazin-1-yl) -propylamino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

380)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-hydroxy-1, 1-dimethyl-ethyl) -amide;

381)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 1-dimethyl-propyl) -amide;

382)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3, 3, 5-trimethyl-cyclohexyl) -amide;

383)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid tert-butylamide;

384)2- [4- (3-diethylamino-pyrrolidin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

385)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-dimethylamino-1-methyl-ethyl) -amide;

386)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-ethoxy-phenyl) -amide;

387)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-hydroxy-cyclopentyl) -amide;

388)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-hydroxymethyl-cyclopentyl) -amide;

389)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (3-imidazol-1-yl-propyl) -amide;

390)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid [3- (4, 5-dichloroimidazol-1-yl) -propyl ] -amide;

391)2- [4- (3-pyrrolidin-1-ylpropylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-pyridin-3-yl-ethyl) -amide;

392)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 3, 3-trimethyl-butyl) -amide;

393)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 4-dimethyl-pentyl) -amide;

394)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1-ethyl-propyl) -amide;

395)2- [4- (2-dimethylamino-ethylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 1, 3, 3-tetramethyl-butyl) -amide;

396)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

397)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

398)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-pyridin-3-yl) -amide;

399)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

400)2- [4- (4-dimethylamino-butylamino) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

401)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

402)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

403)2- (4-pyrrolidin-1-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

404)2- (4-pyrrolidin-1-yl-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

405)2- (4-pyrrolidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

406)2- [4- (3-diethylamino-pyrrolidin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

407)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

408)2- (4-pyrrolidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

409)2- [4- (3-diethylamino-pyrrolidin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

410)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

411)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

412)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

413)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

414)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4, 6-dimethyl-pyridin-3-yl) -amide;

415)2- (4-pyrrolidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4, 6-dimethyl-pyridin-3-yl) -amide;

416)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4, 6-dimethyl-pyridin-3-yl) -amide;

417)2- (4-piperidin-1-ylphenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

418)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

419)2- {4- [ (2-dimethylamino-ethyl) -methyl-amino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4, 6-dimethyl-pyridin-3-yl) -amide;

420)2- {4- [ (2-dimethylamino-ethyl) -methyl-amino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

421)2- {4- [ (2-dimethylamino-ethyl) -methyl-amino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

422)2- {4- [ (2-dimethylamino-ethyl) -methyl-amino ] -phenyl } -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

423)2- [4- (4-methyl-piperazin-1-yl) -phenyl ] -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-6-methyl-pyridin-3-yl) -amide;

424)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

425)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

426)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-pyridin-3-yl) -amide;

427)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

428)2- (4-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

429) 6-bromo-2- (3-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

430)2- (3-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

431)2- (3-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-pyridin-3-yl) -amide;

432)2- (3-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

433)2- (3-methoxy-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

434) 2-pyridin-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

435) 2-pyridin-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

436) 2-pyridin-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-chloro-pyridin-3-yl) -amide;

437) 2-pyridin-2-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

438) 2-pyridin-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

439) 2-pyridin-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (2-chloro-pyridin-3-yl) -amide;

440) 2-pyridin-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-chloro-pyridin-3-yl) -amide;

441) 2-pyridin-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

442) 2-pyridin-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

443) 2-pyridin-3-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methoxy-4-methyl-pyridin-3-yl) -amide;

444) 2-pyridin-4-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

445) 2-pyridin-4-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

446) 2-pyridin-4-yl-3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

447)2- (3-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

448)2- (3-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

449)2- (3-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

450)2- (3-chloro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

451)2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

452) 6-bromo-2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-methyl-pyridin-3-yl) -amide;

453)2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (1, 7, 7-trimethyl-bicyclo [2.2.1] hept-2-yl) -amide;

454)2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (6-methyl-pyridin-3-yl) -amide;

455)2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-pyridin-3-yl) -amide;

456)2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethylsulfonyl-pyridin-3-yl) -amide;

457) 6-bromo-2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-6-methyl-pyridin-3-yl) -amide; and

458)2- (3-fluoro-phenyl) -3H-imidazo [4, 5-b ] pyridine-7-carboxylic acid (4-ethoxy-6-methyl-pyridin-3-yl) -amide.

4. A process for the preparation of a compound of claim 1, comprising the steps of:

wherein R is₁-R₅Have the same meaning as defined in claim 1.

5. The process of claim 4, wherein the catalyst used in step 1) is 5% to 10% Pd/C or PtO₂。

6. The process of claim 4, wherein the organic acid used in step 2) is POCl₃Or phosphoric acid (PPA).

7. The process of claim 4, wherein the alkaline hydroxide used in step 3) is NaOH, NaHCO₃Or Na₂CO₃。

8. The process of claim 4, wherein the organic solvent used in step 3) is pyridine or tert-butanol.

9. The method of claim 4, wherein the oxidizing agent used in step 3) is KMnO₄、MnO₂Or SeO₂。

10. The process of claim 4, wherein the solvent used in step 4) is a mixture of water, MeOH, and THF.

11. The process of claim 4, wherein the acid used in step 4) is HCl.

12. The process of claim 4, wherein the organic solvent used in step 5) is Dimethylformamide (DMF), Dimethylsulfoxide (DMSO) or dichloromethane (MC).

13. The process of claim 4, wherein the coupling agent used in step 5) is 1-Hydroxybenzotriazole (HOBT)/1- (3-dimethylaminopropyl) -3-ethylcarbodiimide HCl salt (EDC)/triethylamine (Et)₃N), and pyBop ((benzotriazol-1-yl-oxy) trispyrrolidinylphosphonium hexafluorophosphate), HBTU (O-benzotriazole-N, N '-tetramethyluronium hexafluorophosphate) or TBTU (O- (benzotriazole-1-yl) -N, N' -tetramethyluronium tetrafluoroborate).

14. A composition for inhibiting protein kinase activity, which comprises the compound of formula 1 of claim 1, or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof as an active ingredient.

15. The composition of claim 14, wherein the protein kinase is selected from glycogen synthase kinase-3 (GSK-3), aurora kinase, extracellular signal-regulated kinase (ERK), protein kinase b (akt), cyclin-dependent kinase (CDK), p38 (protein 38) mitogen-activated protein kinase (MAPK), kinase insert domain protein receptor (KDR) or vascular endothelial growth factor receptor-2 (VEGFR-2), c-Jun N-terminal kinase (JNK), and Pyruvate Dehydrogenase Kinase (PDK).

16. A pharmaceutical composition for preventing or treating diseases selected from diabetes, obesity, dementia, cancer and inflammation, comprising the compound of formula 1 of claim 1, or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof as an active ingredient.