Compound and pharmaceutical composition comprising same

Abstract

The present invention provides: a novel compound inhibiting the activity of bromodomain, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition comprising same, and is very useful for preventing and treating diseases and disorders responding to the inhibition of bromodomain-containing proteins.

Description

Compound and pharmaceutical composition containing same

[0001] The present invention relates to a novel compound that inhibits the activity of a bromodomain, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same.

[0002] Lysine acetylation of the N-terminus of histones plays a crucial role in various biological processes, including gene expression regulation, DNA damage repair, DNA replication, and chromosome integrity maintenance (Filippakopoulos et al. Nature Review of Drug Discovery. 2014, 13:337-356). Therefore, dysregulation of acetylation levels can cause various diseases. Bromodomains (BDs) are modules that can recognize and selectively bind to histone N-terminal acetylation. Human proteins, which contain a total of 61 known bromodomains, are divided into eight subfamilies based on amino acid sequence and structural similarity.

[0003] BRD4 (bromodomain-containing protein 4) belongs to the type II subfamily, which also includes bromodomain-containing protein 2 (BRD2), bromodomain-containing protein 3 (BRD3), and bromodomain testis-specific protein (BRDT) (Filippakopoulos et al. Cell. 2012, 149:214-231). Numbering from the N-terminal end of each bromodomain and extraterminal domain (BET) protein, the tandem bromodomains are typically labeled Bromo Domain 1 (BD1) and Bromo Domain 2 (BD2) (Chung et al., J Med. Chem. 2011, 54, 3827-3838).

[0004] BRD4 specifically recognizes and binds to histone acetylation, recruiting key transcription factors including RNA Pol II (RNA-polymerase II), transcription coactivators, and chromatin regulators to regulate transcriptional responses during gene expression. Therefore, inhibition of BRD4-histone lysine acetylation is emerging as a novel treatment option for various diseases caused by aberrant gene expression.

[0005] In numerous preclinical in vivo animal models, treatment with small molecule inhibitors has demonstrated anticancer, anti-inflammatory, and anti-fibrotic effects. Based on these animal experimental results, clinical trials are underway for various diseases, including cancer, inflammation, and neurological disorders.

[0006] Some of these clinical trials have shown dose-limiting on-target toxicities, including thrombocytopenia, anemia, neutropenia, gastrointestinal events, and fatigue, which have hindered their ultimate success. However, recent studies have shown that selective inhibition of BD2, located in the C-terminal domain of BRD4, reduces toxicity relative to efficacy (Omer Gilan et al. Science, 368(6489): 387-394, 2020; Emily J. Faivre et al. Nature, 578: 306-310, 2020).

[0007] Therefore, the development of inhibitors with enhanced bromodomain selectivity and their potential as novel therapeutics are receiving significant attention. While some bromodomain inhibitors are being studied in clinical and preclinical trials, there is a pressing need for new bromodomain inhibitors that can address the issues of disease recurrence and drug resistance while reducing side effects.

[0008] One aspect of the present invention provides a novel compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0009] Another aspect of the present invention provides a pharmaceutical composition for the prevention or treatment of diseases and disorders responsive to inhibition of a bromodomain-containing protein, comprising a novel compound of the present invention, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0010] Another aspect of the present invention provides a bromodomain inhibitor comprising a novel compound of the present invention, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0011] One aspect of the present invention provides a novel compound that inhibits the activity of a bromodomain, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein the novel compound of the present invention is represented by the following chemical formula 1.

[0012] [Chemical Formula 1]

[0013]

[0014] In the above chemical formula 1,

[0015] R is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, C3-C10 cycloalkylcarbonyl or C3-C10 cycloalkylsulfonyl;

[0016] Ar is or and;

[0017] R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb and;

[0018] R aa is hydrogen, C1-C10 alkylcarbonyl, C6-C12 arylcarbonyl, C3-C10 cycloalkylcarbonyl, C1-C10 alkylsulfonyl, C6-C12 arylsulfonyl or C3-C10 cycloalkylsulfonyl;

[0019] L aa is C1-C10 alkylene or C3-C10 cycloalkylene;

[0020] R bbis hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, -NR bb1 R bb2 , -NR bb1 -C(=O)R bb3 , -OR bb4 , -C(=O)-R bb5 , -C(=O)-NR bb1 R bb2 , -OC(=O)-NR bb1 R bb2 or -NR bb1 -C(=O)-NR bb1 R bb2 and;

[0021] R bb1 , R bb2 and R bb4 are each independently hydrogen, C1-C10 alkyl, C6-C12 aryl or C3-C10 cycloalkyl;

[0022] R bb3 and R bb5 are each independently C1-C10 alkyl, C6-C12 aryl, C3-C10 cycloalkyl C1-C10 alkoxy, C6-C12 aryloxy or C3-C10 cycloalkyloxy;

[0023] R c is hydrogen or C1-C10 alkyl or C3-C10 cycloalkyl;

[0024] X1 and X2 are each independently a single bond, NH, O or S, wherein one of X1 and X2 is a single bond and the other is NH, O or S;

[0025] R d and R e are each independently hydrogen, C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl, C1-C10 alkoxyC1-C10 alkyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl may be further substituted with C1-C10 alkyl;

[0026] R fis hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f Alkyl or cycloalkyl of may be further substituted by one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy;

[0027] R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, -C(=O)-R 1c , -NH-SO2-R 1d or -NH-C(=O)-R 1e and;

[0028] R 1c is C1-C10 alkyl, C3-C10 cycloalkyl or -NR 1f R 1g and;

[0029] R 1a , R 1b , R 1f and R 1g are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl;

[0030] R 1d and R 1e are each independently C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxy;

[0031] R 2 is C1-C10 alkyl, C3-C10 cycloalkyl, halogen, C1-C10 alkoxy, -NR 2a R 2b , -NR'-C(=O)-L 2a -R 2c , -C(=O)-NR 2aR 2b , -C(=O)-NR'-L 2a -R 2c , -C(=O)-NR'-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2b -C(=O)-R 2f , -NR'-S(=O)2-R 2g or -C(=O)-R 2h and;

[0032] R 2a and R 2b are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl;

[0033] R' is hydrogen or C1-C10 alkyl;

[0034] L 2a is a single bond, C1-C10 alkylene or C3-C10 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, halogen and haloC1-C10 alkyl;

[0035] R 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl, C6-C12 arylsulfonyl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2cAlkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 alkylcarbonyl, C3-C10 cycloalkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl and -L'-Ar';

[0036] L' is a single bond or C1-C10 alkylene;

[0037] Ar' is C1-C10 heteroaryl or C3-C10 cycloalkyl which is optionally substituted with C1-C10 alkyl;

[0038] R 2d is hydrogen or C1-C10 alkyl;

[0039] R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, -L''-R'', -C(=O)-R''' or -C(=O)-NR''''R'''';

[0040] L'' is C1-C10 alkylene or C3-C10 cycloalkylene;

[0041] R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl;

[0042] R''' is C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl or C1-C10 alkylaminoC1-C10 alkyl;

[0043] R'''' and R''''' are each independently hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxyC1-C10 alkyl;

[0044] L 2b is C1-C10 alkylene or C3-C10 cycloalkylene;

[0045] R 2f is amino or C3-C10 heterocycloalkyl;

[0046] R 2g is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and C6-C12 aryl;

[0047] R 2h is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy, C3-C10 cycloalkoxy or C6-C12 aryloxy;

[0048] R 3 is C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl, haloC1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkyl;

[0049] a is an integer from 0 to 4;

[0050] The above R 1 , R 2 , R 1d and R 1e Alkyl, cycloalkyl or alkoxy, R 1a , R 1b , R 1c , R 1f , R 1g , R 2a , and R 2bThe alkyl or cycloalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, C1-C10 alkoxy, hydroxy and haloC1-C10 alkoxy.

[0051] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating diseases and disorders responsive to inhibition of a bromodomain-containing protein, comprising a compound according to one aspect, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0052] Another aspect of the present invention provides a bromodomain inhibitor comprising a compound according to the above aspect, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0053] The compound according to the present invention can prevent or treat diseases selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory diseases, kidney diseases, and cancer through BRD4 inhibition. Furthermore, the compound according to the present invention can reduce toxicity without reducing efficacy by selectively inhibiting only the BD2 (bromodomain 2) of BRD4.

[0054] Therefore, a pharmaceutical composition comprising a compound according to the present invention is useful for preventing or treating diseases and disorders that respond to inhibition of bromodomain-containing proteins, particularly diabetes, metabolic syndrome, fibrosis, inflammatory diseases, kidney diseases, and cancer.

[0055] Hereinafter, the novel compounds of the present invention, their solvates, their hydrates, their prodrugs, their isomers, or their pharmaceutically acceptable salts will be described in detail. In this context, unless otherwise defined, the technical and scientific terms used herein have meanings commonly understood by those of ordinary skill in the art to which this invention pertains, and descriptions of known functions and structures that may unnecessarily obscure the gist of the present invention will be omitted.

[0056] The following terms used in this specification are defined as follows, but are for illustrative purposes only and are not intended to limit the invention, application, or use.

[0057] As used herein, the singular forms may be intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0058] Additionally, the numerical ranges used herein include lower and upper limits and all values ​​within that range, increments logically derived from the shape and width of the defined range, all doubly defined values, and all possible combinations of upper and lower limits of numerical ranges defined in different shapes. Unless otherwise specified herein, values ​​outside the defined numerical range that may arise due to experimental error or rounding of values ​​are also included in the defined numerical range.

[0059] The term "comprises" in this specification is an open-ended description equivalent to expressions such as "includes," "contains," "has," or "characterized by," and does not exclude additional elements, materials, or processes not listed herein.

[0060] The terms “substituent,” “radical,” “group,” “moiety,” and “fragment” in this specification are used interchangeably.

[0061] The term "C" in this specification A -C B " means "carbon number is A or more and B or less". That is, when it is written as "C1-C10", it means that the number of carbons is 1 to 10. For example, C1-C10 alkyl means alkyl having 1 to 10 carbons.

[0062] The term "alkyl" as used herein refers to a monovalent straight-chain or branched saturated hydrocarbon radical composed solely of carbon and hydrogen atoms. The alkyl may have 1 to 10 carbon atoms, 1 to 7 carbon atoms, 1 to 6 carbon atoms, 1 to 5 carbon atoms, or 1 to 4 carbon atoms. The alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, ethylhexyl, and the like.

[0063] The term "cycloalkyl" as used herein refers to a non-aromatic carbocyclic monovalent radical composed of one or more rings, which may include all saturated or partially unsaturated monocyclic, polycyclic or spirocyclic forms. Specific examples of the cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexyl, norbornyl, bicyclo[1.1.1]pentyl, bicyclo[3.1.0]hexyl, bicyclo[4.1.0]heptyl, bicyclo[2.2.1]heptyl, adamantly, and decalinyl.

[0064] The term "aryl" as used herein refers to a monovalent organic radical of an aromatic ring derived from an aromatic hydrocarbon by the removal of one hydrogen, including single or fused ring systems, each ring suitably containing 4 to 7, preferably 5 or 6, ring atoms, and even including a form in which multiple aryls are connected by single bonds. The ring atoms may have 6 to 20 carbon atoms, preferably 6 to 12 carbon atoms. Specific examples include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, indenyl, fluorenyl, and the like.

[0065] The term "heteroaryl" as used herein refers to a monovalent heteroaromatic ring radical which is an aryl group having at least one heteroatom selected from N, O and S as an aromatic ring skeletal atom, and the remaining aromatic ring skeletal atoms are carbon. The heteroaryl is a 5 to 8-membered monocyclic heteroaryl, a polycyclic heteroaryl in which two or more monocyclic heteroaryls are fused, and a polycyclic heteroaryl condensed with one or more benzene rings, and may be partially saturated. The heteroaryl also includes a form in which one or more heteroaryls are linked by a single bond. Specific examples thereof include, but are not limited to, monocyclic heteroaromatic rings such as furan, thiophene, pyrrole, imidazole, pyrazole, triazole, tetrazole, thiazole, isothiazole, isoxazole, oxazole, oxadiazole, thiadiazole, triazine, pyridine, pyrazine, pyrimidine, and pyridazine; polycyclic heteroaromatic rings such as benzofuran, benzothiophene, isobenzofuran, benzimidazole, benzothiazole, benzoisothiazole, benzoisoxazole, benzoxazole, isoindole, indole, indazole, tetrahydroindazole, benzo[d]oxazol-2(3H)-one, pyrazolopyrimidine, quinoline, isoquinoline, dibenzofuran, dibenzothiophene, carbazole, and benzocarbazole; and the like.

[0066] The term "alkylene" as used herein means a divalent straight-chain or branched saturated hydrocarbon divalent group composed solely of carbon and hydrogen atoms, specifically including, but not limited to, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, t-butylene, pentylene, hexylene, octylene, nonylene, and the like.

[0067] The term "cycloalkylene" as used herein refers to a divalent radical of cycloalkane, specifically including but not limited to cyclopropylene, cyclobutylene, cyclohexylene, and the like.

[0068] The term "halogen" as used herein refers to a halogen group element, including, for example, fluoro, chloro, bromo, and iodo.

[0069] The term "alkoxy" as used herein refers to an -O-alkyl radical, where 'alkyl' is as defined above. Specific examples include, but are not limited to, methoxy, ethoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, and the like.

[0070] The term "aryloxy" as used herein refers to an -O-aryl radical, where 'aryl' is as defined above. Specific examples include, but are not limited to, phenoxy.

[0071] The terms "haloalkyl," "haloalkoxy," or "halocycloalkyl," as used herein, mean an alkyl, alkoxy, or cycloalkyl group, respectively, in which one or more hydrogen atoms are replaced by a halogen atom. Here, alkyl, alkoxy, cycloalkyl, and halogen are as defined above.

[0072] The term "heterocycloalkyl" as used herein refers to a stable 3- to 18-membered saturated or partially unsaturated radical consisting of 2 to 20, preferably 2 to 15, preferably 2 to 10, preferably 2 to 6 carbon atoms and 1 to 6 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, for example 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 heteroatoms, or 1 to 2 heteroatoms. Exemplary heterocycloalkyls include, but are not limited to, a stable 3-15 membered saturated or partially unsaturated radical, a stable 3-12 membered saturated or partially unsaturated radical, a stable 3-9 membered saturated or partially unsaturated radical, a stable 8-membered saturated or partially unsaturated radical, a stable 7-membered saturated or partially unsaturated radical, a stable 6-membered saturated or partially unsaturated radical, or a stable 5-membered saturated or partially unsaturated radical. Heterocycloalkyl includes all saturated or partially unsaturated monocyclic, polycyclic or spirocyclic forms, and a nitrogen, carbon or sulfur atom in the heterocycloalkyl can be optionally oxidized; a nitrogen atom can be optionally quaternized; and the heterocycloalkyl can be partially or fully saturated. In addition, bonds can be made through heteroatoms or carbon atoms present in the heterocycloalkyl. Examples of such heterocycloalkyl radicals include oxetane, aziridine, pyrrolidine, azetidine, piperidine, tetrahydrofuran, tetrahydropyridine, tetrahydropyran, piperazine, morpholine, thiomorpholine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3-dihydrobenzo[c][1,2]oxaborole, imidazolidine-2,4-dione, thiazolidine-2,4-dione, pyrimidine-2,4(1H,3H)-dione, pyridazin-3(2H)-one, 3-azabicyclo[3.1.0]hexane, octahydropyrrolo[3,4-c]pyrrole, 2,7-diazaspiro[4.4]nonane, 2-azaspiro[4.4] It may contain a monovalent radical of a non-aromatic heterocycle such as nonane.

[0073] The term "alkylamino" as used herein includes mono-alkylamino and di-alkylamino, where "mono-alkylamino" means -NH(alkyl), including -NHCH3, -NHCH2CH3, -NH(CH2)2CH3, -NH(CH2)3CH3, -NH(CH2)4CH3, -NH(CH2)5CH3, and the like, and "di-alkylamino" means -N(alkyl)(alkyl), including -N(CH3)2, -N(CH2CH3)2, -N((CH2)2CH3)2, -N(CH3)(CH2CH3), and the like, wherein each alkyl is independently an alkyl as defined above.

[0074] The term "hydroxyalkyl" as used herein means alkyl having one or more hydrogen atoms replaced by hydroxy, including -CH2OH, -CH2CH2OH, -(CH2)2CH2OH, -(CH2)3CH2OH, -(CH2)4CH2OH, -(CH2)5CH2OH, -CH(OH)-CH3, -C(CH3)2OH, -CH2CH(OH)CH3, -C(CH3)(OH)2 and the like, wherein alkyl is as defined above.

[0075] The term "alkylsulfonyl" as used herein refers to a -SO2-alkyl radical, where "alkyl" is as defined above. Examples of such alkylsulfonyl radicals include, but are not limited to, methylsulfonyl, ethylsulfonyl, propylsulfonyl, and the like.

[0076] The term "alkylcarbonyl" as used herein means a -C(=O)alkyl radical, where 'alkyl' is as defined above. Examples of such alkylcarbonyl radicals include, but are not limited to, methylcarbonyl, ethylcarbonyl, isopropylcarbonyl, propylcarbonyl, butylcarbonyl, isobutylcarbonyl, t-butylcarbonyl, and the like.

[0077] The term "alkoxycarbonyl" as used herein means a -C(=O)-alkoxy radical, wherein 'alkoxy' is as defined above. Examples of such alkoxycarbonyl radicals include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, and the like.

[0078] The term "heterocycloalkylcarbonyl" as used herein means a -C(=O)-heterocycloalkyl radical, wherein 'heterocycloalkyl' is as defined above.

[0079] The term "alkylcarbonylamino" as used herein means a -NHC(=O)-alkyl radical, wherein 'alkyl' is as defined above. Examples of such alkylcarbonylamino radicals include, but are not limited to, methylcarbonylamino, ethylcarbonylamino, propylcarbonylamino, butylcarbonylamino, and the like.

[0080] The term "alkoxycarbonylamino" as used herein means a -NHC(=O)-alkoxy radical, wherein 'alkoxy' is as defined above. Examples of such alkoxycarbonylamino radicals include, but are not limited to, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, butoxycarbonylamino, and the like.

[0081] The term "alkylsulfonylamino" as used herein means an -NH-SO2-alkyl radical, wherein "alkyl" is as defined above. Examples of such alkylsulfonylamino radicals include, but are not limited to, methylsulfonylamino, ethylsulfonylamino, propylsulfonyl, and the like.

[0082] The term "alkylaminocarbonyloxy" as used herein means a -OC(=O)-NH(alkyl) or -OC(=O)-N(alkyl)(alkyl) radical, wherein 'alkyl' is as defined above. Examples of such alkylaminocarbonyloxy radicals include, but are not limited to, methylaminocarbonyloxy, dimethylaminocarbonyloxy, ethylaminocarbonyloxy, methylethylaminocarbonyloxy, and the like.

[0083] The term "alkylthio" as used herein means an -S-alkyl radical, where 'alkyl' is as defined above. Examples of such alkylthio radicals include, but are not limited to, methylthio, ethylthio, and the like.

[0084] As used herein, the term “amino” refers to the -NH2 radical, “hydroxy” refers to the -OH radical, “carboxylic acid” refers to the -COOH radical, and “nitro” refers to the -NO2 radical.

[0085] The term "heteroatom" as used herein means an atom other than carbon (C), and may specifically be a nitrogen (N), oxygen (O), or sulfur (S) atom. The above-mentioned heteroaryl and heterocycloalkyl may contain one or more heteroatoms, for example, 1, 1 to 2, 1 to 3, or 1 to 4 heteroatoms.

[0086] The term "pharmaceutically acceptable" as used herein means suitable for use in pharmaceutical preparations, generally considered safe for such use, and officially approved by a national regulatory agency for such use or listed in the Korean Pharmacopoeia or the United States Pharmacopoeia.

[0087] The term "pharmaceutically acceptable salt" as used herein means any and all organic or inorganic addition salts of the compounds of the present invention, which are relatively non-toxic and harmless to the subject and have an effective effect, and the side effects due to the salt do not diminish the beneficial effects of the compounds of the present invention themselves.

[0088] The term "prevention" as used herein means any act of inhibiting or delaying the occurrence, spread, and recurrence of a disease selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory disease, kidney disease, and cancer by administering the composition of the present invention.

[0089] The term "improvement" as used herein means any action that at least reduces a parameter associated with the condition being treated by administration of the composition of the present invention, for example, the severity of a symptom.

[0090] The term "treatment" as used herein means any action by which the symptoms of a disease selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory disease, kidney disease, and cancer are improved or beneficially changed by administration of the composition of the present invention.

[0091] The term "subject" as used herein refers to any animal, including humans, that has developed or is likely to develop a disease selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory diseases, kidney diseases, and cancer. The animal may be, but is not limited to, mammals such as cows, horses, sheep, pigs, goats, camels, antelopes, dogs, and cats that require treatment for similar symptoms, as well as humans.

[0092] The term "administration" in this specification means introducing the pharmaceutical composition of the present invention into a subject by any appropriate method, and the route of administration of the composition of the present invention may be administered through various routes, such as oral or parenteral, as long as it can reach the target tissue.

[0093] The term "therapeutically effective amount" or "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, and the effective dosage level can be readily determined by those skilled in the art based on factors including the patient's sex, age, weight, health condition, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration, and excretion rate, duration of treatment, drugs used in combination or simultaneously, and other factors well known in the medical field.

[0094] In the present invention, the bromodomain inhibitor may be a BET inhibitor (bromodomain and extraterminal inhibitor, BET inhibitor), and the BET inhibitor refers to a compound that functions to inhibit the binding of a BET family bromodomain to an acetylated lysine residue.

[0095] One aspect of the present invention provides a novel compound that inhibits the activity of a bromodomain, a hydrate thereof, a solvate thereof, an isomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof, which may be represented by the following chemical formula 1.

[0096] [Chemical Formula 1]

[0097]

[0098] In the above chemical formula 1,

[0099] R is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, C3-C10 cycloalkylcarbonyl or C3-C10 cycloalkylsulfonyl;

[0100] Ar is or and;

[0101] R a and R b are each independently C1-C10 alkyl, -NH-Raa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb and;

[0102] R aa is hydrogen, C1-C10 alkylcarbonyl, C6-C12 arylcarbonyl, C3-C10 cycloalkylcarbonyl, C1-C10 alkylsulfonyl, C6-C12 arylsulfonyl or C3-C10 cycloalkylsulfonyl;

[0103] L aa is C1-C10 alkylene or C3-C10 cycloalkylene;

[0104] R bb is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, -NR bb1 R bb2 , -NR bb1 -C(=O)R bb3 , -OR bb4 , -C(=O)-R bb5 , -C(=O)-NR bb1 R bb2 , -OC(=O)-NR bb1 R bb2 or -NR bb1 -C(=O)-NR bb1 R bb2 and;

[0105] R bb1 , R bb2 and R bb4 are each independently hydrogen, C1-C10 alkyl, C6-C12 aryl or C3-C10 cycloalkyl;

[0106] R bb3 and R bb5 are each independently C1-C10 alkyl, C6-C12 aryl, C3-C10 cycloalkyl, C1-C10 alkoxy, C6-C12 aryloxy or C3-C10 cycloalkyloxy;

[0107] R c is hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl;

[0108] X1 and X2 are each independently a single bond, NH, O or S, wherein one of X1 and X2 is a single bond and the other is NH, O or S;

[0109] R d and R e are each independently hydrogen, C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl, C1-C10 alkoxyC1-C10 alkyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl may be further substituted with C1-C10 alkyl;

[0110] R f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f Alkyl or cycloalkyl of may be further substituted by one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy;

[0111] R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, -C(=O)-R 1c , -NH-SO2-R 1d or -NH-C(=O)-R 1e and;

[0112] R 1c is C1-C10 alkyl, C3-C10 cycloalkyl or -NR 1f R 1g and;

[0113] R 1a , R 1b , R 1f and R1g are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl;

[0114] R 1d and R 1e are each independently C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxy;

[0115] R 2 is C1-C10 alkyl, C3-C10 cycloalkyl, halogen, C1-C10 alkoxy, -NR 2a R 2b , -NR'-C(=O)-L 2a -R 2c , -C(=O)-NR 2a R 2b , -C(=O)-NR'-L 2a -R 2c , -C(=O)-NR'-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2b -C(=O)-R 2f , -NR'-S(=O)2-R 2g or -C(=O)-R 2h and;

[0116] R 2a and R 2b are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl;

[0117] R' is hydrogen or C1-C10 alkyl;

[0118] L 2a is a single bond, C1-C10 alkylene or C3-C10 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, halogen and haloC1-C10 alkyl;

[0119] R 2cis C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl, C6-C12 arylsulfonyl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 alkylcarbonyl, C3-C10 cycloalkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl and -L'-Ar';

[0120] L' is a single bond or C1-C10 alkylene;

[0121] Ar' is C1-C10 heteroaryl or C3-C10 cycloalkyl which is optionally substituted with C1-C10 alkyl;

[0122] R 2d is hydrogen or C1-C10 alkyl;

[0123] R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, -L''-R'', -C(=O)-R''' or -C(=O)-NR''''R'''';

[0124] L'' is C1-C10 alkylene or C3-C10 cycloalkylene;

[0125] R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl;

[0126] R''' is C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl or C1-C10 alkylaminoC1-C10 alkyl;

[0127] R'''' and R''''' are each independently hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxyC1-C10 alkyl;

[0128] L 2b is C1-C10 alkylene or C3-C10 cycloalkylene;

[0129] R 2f is amino or C3-C10 heterocycloalkyl;

[0130] R 2g is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and C6-C12 aryl;

[0131] R 2h is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy, C3-C10 cycloalkoxy or C6-C12 aryloxy;

[0132] R 3 is C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl, haloC1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkyl;

[0133] a is an integer from 0 to 4;

[0134] The above R 1 , R 2 , R 1d and R 1e Alkyl, cycloalkyl or alkoxy, R 1a , R 1b , R 1c , R 1f , R 1g , R 2a , and R 2b Alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, C1-C10 alkoxy, hydroxy and haloC1-C10 alkoxy,

[0135] The above heteroaryl and heterocycloalkyl contain at least one heteroatom selected from the group consisting of N, O and S.

[0136] The compound according to the present invention can be usefully used for the prevention, improvement, or treatment of diseases selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory diseases, kidney diseases, and cancer through BRD4 inhibition. Furthermore, the compound according to the present invention selectively inhibits only the BD2 (bromodomain 2) of BRD4, thereby exhibiting low toxicity to normal cells without reducing efficacy.

[0137] In one embodiment, the compound of Chemical Formula 1 may be represented by Chemical Formula 2 or Chemical Formula 3 below.

[0138] [Chemical Formula 2]

[0139]

[0140] [Chemical Formula 3]

[0141]

[0142] In the above chemical formulas 2 and 3, Ar, R 1 and R 2 is the same as the definition in the above chemical formula 1;

[0143] R11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy.

[0144] In one embodiment, R is hydrogen, C1-C10 alkyl, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; and Ar is , , , , , or and; R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of R is C1-C10 alkyl; aa is hydrogen, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, amino or hydroxy; R c is hydrogen or C1-C10 alkyl; R d and R e are each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R fAlkyl or cycloalkyl of may be further substituted by one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy; R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e are each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy.

[0145] In one embodiment, the R 2 is C1-C10 alkyl, halogen or C1-C10 alkoxy, and R 2 The alkyl or alkoxy of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy.

[0146] In one embodiment, the R 2 is -C(=O)-NR 2a R 2b , -C(=O)-NH-L 2a -R2c , -C(=O)-NH-L 2a -NR 2d R 2e or -C(=O)-R 2h and; R 2a and R 2b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; L 2a is C1-C10 alkylene or C3-C10 cycloalkylene, and the above L 2a The alkylene or cycloalkylene of R may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, halogen and haloC1-C10 alkyl; 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl or C6-C12 arylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, or arylsulfonyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, and C1-C10 heteroaryl; R 2d is hydrogen or C1-C10 alkyl; R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl, C1-C10 alkoxyC1-C10 alkylcarbonyl, C1-C10 alkylaminoC1-C10 alkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl or C1-C10 alkoxyC1-C10 alkylaminocarbonyl; R 2hmay be C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy or C6-C12 aryloxy.

[0147] In one embodiment, the R 2 is -NR 2a R 2b , -NH-C(=O)-L 2a -R 2c , -NH-C(=O)-R 2cc , -NH-C(=O)-L 2a -NR 2d R 2e , -NH-C(=O)-NR 2dd R 2ee , -NH-C(=O)-L 2b -C(=O)-R 2f or -NH-S(=O)2-R 2g and; R 2a and R 2b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; L 2a is C1-C10 alkylene or C3-C10 cycloalkylene, and the above L 2a The alkylene or cycloalkylene of R may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, halogen and haloC1-C10 alkyl; 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl or C6-C12 arylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl or arylsulfonyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, and C1-C10 heteroaryl; R 2ccis C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2cc Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl of may be further substituted by one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 heteroaryl and -L'-Ar'; L' is C1-C10 alkylene; Ar' is C1-C10 heteroaryl which is optionally substituted with C1-C10 alkyl; R 2d is hydrogen or C1-C10 alkyl; R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl, C1-C10 alkoxyC1-C10 alkylcarbonyl, C1-C10 alkylaminoC1-C10 alkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl or C1-C10 alkoxyC1-C10 alkylaminocarbonyl; R 2dd is hydrogen or C1-C10 alkyl; R 2eeis hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, hydroxyC3-C10 cycloalkyl or -L''-R''; L'' is C1-C10 alkylene or C3-C10 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl; L 2b is C1-C10 alkylene or C3-C10 cycloalkylene; R 2f is amino or C3-C10 heterocycloalkyl; R 2g is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and C6-C12 aryl.

[0148] In one embodiment, the compound may be represented by any one of the following chemical formulae 4 to 9:

[0149] [Chemical Formula 4]

[0150]

[0151] [Chemical Formula 5]

[0152]

[0153] [Chemical Formula 6]

[0154]

[0155] [Chemical Formula 7]

[0156]

[0157] [Chemical Formula 8]

[0158]

[0159] [Chemical Formula 9]

[0160]

[0161] In the above chemical formulas 4 to 9,

[0162] R is hydrogen, C1-C6 alkyl, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl;

[0163] X1 and X2 are each independently NH, O or S;

[0164] R a and R b are each independently C1-C6 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of them is C1-C6 alkyl;

[0165] R aa is hydrogen, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl;

[0166] L aa is C1-C6 alkylene or C3-C8 cycloalkylene;

[0167] R bb is hydrogen, -NR bb1 R bb2 or -OR bb4 and;

[0168] R bb1 , R bb2 and R bb4 are each independently hydrogen, C1-C6 alkyl, C6-C12 aryl or C3-C8 cycloalkyl;

[0169] R c is hydrogen or C1-C6 alkyl;

[0170] R d and R eare each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl may be further substituted with C1-C6 alkyl;

[0171] R f is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f Alkyl or cycloalkyl of may be further substituted by one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl, amino, hydroxy, C1-C6 alkoxycarbonylamino, C1-C6 alkylaminocarbonylamino, C1-C6 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfonylamino and C1-C6 alkylaminocarbonyloxy;

[0172] R 1 is C1-C6 alkyl, C3-C8 cycloalkyl, -NH2, C1-C6 alkylamino, halogen, C1-C6 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and the alkyl or cycloalkyl of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl and hydroxy;

[0173] R 1d and R 1e are each independently C1-C6 alkyl, haloC1-C6 alkyl, C3-C8 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or C1-C6 alkoxyC1-C6 alkyl;

[0174] R 2 is C1-C6 alkyl, halogen, C1-C6 alkoxy, -NH2, -NH-C(=O)-L 2a -R 2c , -NH-C(=O)-R 2cc, -C(=O)NH2, -C(=O)NH-L 2a -R 2c , -C(=O)-NH-L 2a -NR 2d R 2e , -NH-C(=O)-L 2a -NR 2d R 2e , -NH-C(=O)-NR 2dd R 2ee , -NH-C(=O)-L 2b -C(=O)-R 2f or -NH-S(=O)2-R 2g and the above R 2 Alkyl or alkoxy of may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl and hydroxy;

[0175] L 2a is C1-C6 alkylene or C3-C8 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C6 alkyl, halogen and haloC1-C6 alkyl;

[0176] R 2c is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylthio, C3-C8 cycloalkylthio, C6-C12 arylthio, C1-C6 alkylsulfonyl, C3-C8 cycloalkylsulfonyl or C6-C12 arylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, or arylsulfonyl may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, C3-C8 cycloalkyl, and C1-C10 heteroaryl;

[0177] R 2ccis C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C8 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C6 alkyl, C6-C12 aryloxy, C1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy or C1-C6 alkoxyC1-C6 alkoxyC1-C6 alkyl, and the R 2cc Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkylamino, C1-C10 heteroaryl and -L'-Ar';

[0178] L' is C1-C6 alkylene;

[0179] Ar' is C1-C10 heteroaryl which is optionally substituted with C1-C6 alkyl;

[0180] R 2d is hydrogen or C1-C6 alkyl;

[0181] R 2e is hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C8 cycloalkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonyl, C1-C6 alkylaminoC1-C6 alkylcarbonyl, aminocarbonyl, C1-C6 alkylaminocarbonyl or C1-C6 alkoxyC1-C6 alkylaminocarbonyl;

[0182] R 2dd is hydrogen or C1-C6 alkyl;

[0183] R 2ee is hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, hydroxyC3-C8 cycloalkyl or -L''-R'';

[0184] L'' is C1-C6 alkylene or C3-C8 cycloalkylene;

[0185] R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylcarbonylamino, C1-C6 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C6 alkyl;

[0186] L 2b is C1-C6 alkylene or C3-C8 cycloalkylene;

[0187] R 2f is amino or C3-C10 heterocycloalkyl;

[0188] R 2g is C1-C6 alkyl, C3-C8 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl and C6-C12 aryl;

[0189] R 11 Inland R 13 are each independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy, haloC1-C6 alkyl or haloC1-C6 alkoxy.

[0190] In one embodiment, the compound may be represented by the following chemical formula 10:

[0191] [Chemical Formula 10]

[0192]

[0193] In the above chemical formula 10,

[0194] Y is or and;

[0195] R 2 is a halogen;

[0196] R 11 Inland R 13are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy;

[0197] R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e are each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy;

[0198] R c is hydrogen or C1-C10 alkyl;

[0199] R e is C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R fThe alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

[0200] In one embodiment, the compound may be represented by the following chemical formula 11 or 12:

[0201] [Chemical Formula 11]

[0202]

[0203] [Chemical Formula 12]

[0204]

[0205] In the above chemical formulas 11 and 12,

[0206] Y is or and;

[0207] R 2 is a halogen;

[0208] R 11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy;

[0209] R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1eare each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy;

[0210] R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of R is C1-C10 alkyl; aa is hydrogen, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, amino or hydroxy;

[0211] R c is hydrogen or C1-C10 alkyl;

[0212] R d is C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R fThe alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

[0213] In one embodiment, the compound may be represented by the following chemical formula 13:

[0214] [Chemical Formula 13]

[0215]

[0216] In the above chemical formula 13,

[0217] R is hydrogen, C1-C10 alkyl, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl;

[0218] Y is or and;

[0219] R 2 is C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 2a R 2b , -NR'-C(=O)-L 2a -R 2c , -C(=O)-NR 2a R 2b , -C(=O)-NR'-L 2a -R 2c , -C(=O)-NR'-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2b -C(=O)-R 2f , -NR'-S(=O)2-R 2g or -C(=O)-R 2h and the above R 2Alkyl, cycloalkyl or alkoxy of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy;

[0220] R 2a and R 2b are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl;

[0221] R' is hydrogen or C1-C10 alkyl;

[0222] L 2a is a single bond, C1-C10 alkylene or C3-C10 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, halogen and haloC1-C10 alkyl;

[0223] R 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl, C6-C12 arylsulfonyl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 alkylcarbonyl, C3-C10 cycloalkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl and -L'-Ar';

[0224] L' is a single bond or C1-C10 alkylene;

[0225] Ar' is C1-C10 heteroaryl or C3-C10 cycloalkyl which is optionally substituted with C1-C10 alkyl;

[0226] R 2d is hydrogen or C1-C10 alkyl;

[0227] R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, -L''-R'', -C(=O)-R''' or -C(=O)-NR''''R'''';

[0228] L'' is C1-C10 alkylene or C3-C10 cycloalkylene;

[0229] R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl;

[0230] R''' is C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl or C1-C10 alkylaminoC1-C10 alkyl;

[0231] R'''' and R''''' are each independently hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxyC1-C10 alkyl;

[0232] L 2b is C1-C10 alkylene or C3-C10 cycloalkylene;

[0233] R 2f is amino or C3-C10 heterocycloalkyl;

[0234] R 2gis C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and C6-C12 aryl;

[0235] R 2h is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy, C3-C10 cycloalkoxy or C6-C12 aryloxy;

[0236] R 11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy;

[0237] Ar 1 silver , or and;

[0238] R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e are each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy;

[0239] R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of R is C1-C10 alkyl; aa is hydrogen, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, amino or hydroxy;

[0240] R c is hydrogen or C1-C10 alkyl;

[0241] R d and R e are each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f The alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

[0242] In one specific example, the R 11 and R12 One of them is hydrogen, C1-C10 alkyl, and the other is C1-C10 alkyl; R 13 It can be C1-C10 alkyl.

[0243] In one specific example, R is hydrogen, C1-C6 alkyl, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; Ar is and; R a is C1-C6 alkyl; R b is C1-C6 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb and; R aa is hydrogen, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; L aa is C1-C6 alkylene or C3-C8 cycloalkylene; R bb can be hydrogen, amino or hydroxy.

[0244] In one specific example, R is hydrogen, C1-C6 alkyl, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; Ar is and; R a is C1-C6 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb and; R b is C1-C6 alkyl; R aa is hydrogen, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; L aa is C1-C6 alkylene or C3-C8 cycloalkylene; R bb can be hydrogen, amino or hydroxy.

[0245] In one specific example, the R a and R b One of them is C1-C6 alkyl, and the other is C1-C6 alkyl, -NH-Raa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb and; R aa is hydrogen, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; L aa is C3-C8cycloalkylene; R bb can be amino or hydroxy.

[0246] In one specific example, the R a and R b One of them is methyl and the other is amino, or can be selected from the following structures.

[0247]

[0248] In one specific example, R is hydrogen, C1-C6 alkyl, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; Ar is or and; R c is hydrogen or C1-C6 alkyl; R d and R e are each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R fThe alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

[0249] In one specific example, the R d and R e Each can be independently selected from the following structures.

[0250]

[0251] In one specific example, the R 1 Silver C1-C6 alkyl, C3-C8 cycloalkyl, -NH2, halogen, C1-C6 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and the alkyl or cycloalkyl of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl and hydroxy; R 1d and R 1e may each independently be C1-C6 alkyl, haloC1-C6 alkyl, C3-C8 cycloalkyl or C1-C6 alkoxyC1-C6 alkyl.

[0252] In one specific example, the R 1 is C1-C4 alkyl, C3-C7 cycloalkyl, hydroxyC3-C7 cycloalkyl, -NH2, halogen, C1-C4 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e , and the alkyl of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl and hydroxy; R 1d is C1-C4 alkyl, haloC1-C4 alkyl or C3-C7 cycloalkyl; R 1emay be C1-C4 alkyl, C3-C7 cycloalkyl or C1-C4 alkoxyC1-C4 alkyl.

[0253] In one specific example, the R 1 may be any one selected from the following structures:

[0254]

[0255] In one specific example, the R 2 may be C1-C4 alkyl or C1-C4 alkoxy.

[0256] In one specific example, the R 2 may be halogen.

[0257] In one specific example, the R 2 is -C(=O)-NR 2a R 2b , -C(=O)-NH-L 2a -R 2c , -C(=O)-NH-L 2a -NR 2d R 2e or -C(=O)-R 2h and; R 2a and R 2b are each independently hydrogen or C1-C6 alkyl; L 2a is C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with one or more selected from the group consisting of C1-C4 alkyl, halogen and haloC1-C4 alkyl; 2c is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylthio or C1-C6 alkylsulfonyl, and R 2c Aryl or heteroaryl of R may be further substituted with one or more selected from the group consisting of C1-C4 alkyl and C1-C10 heteroaryl; 2d is hydrogen or C1-C6 alkyl; R 2eis hydrogen, C1-C6 alkyl, C1-C10 heteroarylsulfonyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonyl, diC1-C6 alkylaminoC1-C6 alkylcarbonyl, aminocarbonyl, C1-C4 alkylaminocarbonyl or C1-C4 alkoxyC1-C10 alkylaminocarbonyl; R 2h may be C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C6 alkoxy or C6-C12 aryloxy.

[0258] In one specific example, the R 2 can be -NH2.

[0259] In one specific example, the R 2 is -NH-C(=O)-L 2a -R 2c or -NH-C(=O)-R 2cc and; L 2a is C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with one or more selected from the group consisting of C1-C4 alkyl, halogen and haloC1-C4 alkyl; 2c is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylthio or C1-C6 alkylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl of R may be further substituted with one or more selected from the group consisting of halogen, C1-C4 alkyl, C3-C10 cycloalkyl and C1-C10 heteroaryl; R 2cc is C1-C6 alkyl, haloC1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C6 alkyl, C6-C12 aryloxy, C1-C6 alkoxy, C1-C6 alkylaminoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl or C1-C6 alkoxyC1-C6 alkoxyC1-C6 alkyl, and R 2ccCycloalkyl, aryl, heterocycloalkyl or heteroaryl of may be further substituted by one or more selected from the group consisting of halogen, C1-C4 alkyl, C3-C10 cycloalkyl, C1-C10 heteroaryl and -L'-Ar'; L' is C1-C6 alkylene; Ar' may be C1-C10 heteroaryl which is optionally substituted with C1-C4 alkyl.

[0260] In one specific example, the R 2 is -NH-C(=O)-L 2a -NR 2d R 2e or -NH-C(=O)-NR 2dd R 2ee and; L 2a is C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with one or more selected from the group consisting of C1-C4 alkyl, halogen and haloC1-C4 alkyl; 2d is hydrogen or C1-C6 alkyl; R 2e is hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C8 cycloalkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonyl, C1-C6 alkylaminoC1-C6 alkylcarbonyl, aminocarbonyl, C1-C6 alkylaminocarbonyl or C1-C6 alkoxyC1-C6 alkylaminocarbonyl; R 2dd is hydrogen or C1-C6 alkyl; R 2eeis hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, hydroxyC3-C8 cycloalkyl or -L''-R''; L'' is C1-C4 alkylene or C3-C7 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylcarbonylamino, C1-C6 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C4 alkyl.

[0261] In one specific example, the R 2 is -NH-C(=O)-L 2b -C(=O)-R 2f and; L 2b is C1-C4 alkylene or C3-C7 cycloalkylene; R 2f may be amino or C3-C10 heterocycloalkyl.

[0262] In one specific example, the R 2 is -NH-S(=O)2-R 2g and; R 2g is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C4 alkyl and haloC1-C4 alkyl.

[0263] In one specific example, the R 2 is -C(=O)-NH2 or -C(=O)-NH-L 2a -NR 2d R 2e and; L 2a is C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with C1-C4 alkyl; 2d is hydrogen or C1-C6 alkyl; R 2e may be hydrogen or C1-C6 alkyl.

[0264] In one specific example, the R 2 is -NH-C(=O)-L 2a -R 2c or -NH-C(=O)-R 2cc and; L 2a is C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with C1-C4 alkyl; 2c is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylthio or C1-C6 alkylsulfonyl, and R 2c Aryl, heterocycloalkyl or heteroaryl of R may be further substituted with one or more selected from the group consisting of halogen, C1-C4 alkyl, C3-C10 cycloalkyl and C1-C10 heteroaryl; 2cc is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C6 alkyl, C6-C12 aryloxy, C1-C6 alkoxy, C1-C6 alkylaminoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl or C1-C6 alkoxyC1-C6 alkoxyC1-C6 alkyl, and the R 2cc Cycloalkyl, aryl, heterocycloalkyl or heteroaryl of may be further substituted by one or more selected from the group consisting of halogen, C1-C4 alkyl, C3-C10 cycloalkyl, C1-C10 heteroaryl and -L'-Ar'; L' is C1-C4 alkylene; Ar' may be C1-C10 heteroaryl which is optionally substituted with C1-C4 alkyl.

[0265] In one specific example, the R 2 is -NH-C(=O)-L 2a -NR 2d R 2e or -NH-C(=O)-NR 2dd R 2ee and; L 2ais C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with C1-C4 alkyl; 2d is hydrogen or C1-C6 alkyl; R 2e is hydrogen, C1-C6 alkyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C8 cycloalkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonyl, C1-C6 alkylaminoC1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl or C1-C6 alkoxyC1-C6 alkylaminocarbonyl; R 2dd is hydrogen or C1-C6 alkyl; R 2ee is hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, hydroxyC3-C8 cycloalkyl or -L''-R''; L'' is C1-C4 alkylene or C3-C7 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylcarbonylamino, C1-C6 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C4 alkyl.

[0266] In one specific example, the R 2 is -NH2, -NH-C(=O)-L 2a -R 2c , -NH-C(=O)-R 2cc , -NH-C(=O)-L 2a -NR 2d R 2e , -NH-C(=O)-NR 2dd R 2ee , -NH-C(=O)-L 2b -C(=O)-R 2f or -NH-S(=O)2-R 2g and; L 2a is C1-C4 alkylene or C3-C7 cycloalkylene, and L 2a The alkylene of R may be further substituted with C1-C4 alkyl; 2cis C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylthio or C1-C6 alkylsulfonyl, and R 2c Aryl, heterocycloalkyl or heteroaryl of R may be further substituted with one or more selected from the group consisting of halogen, C1-C4 alkyl, C3-C10 cycloalkyl and C1-C10 heteroaryl; 2cc is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C6 alkyl, C6-C12 aryloxy, C1-C6 alkoxy, C1-C6 alkylaminoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl or C1-C6 alkoxyC1-C6 alkoxyC1-C6 alkyl, and the R 2cc Cycloalkyl, aryl, heterocycloalkyl or heteroaryl of may be further substituted by one or more selected from the group consisting of halogen, C1-C4 alkyl, C3-C10 cycloalkyl, C1-C10 heteroaryl and -L'-Ar'; L' is C1-C4 alkylene; Ar' is C1-C10 heteroaryl optionally substituted with C1-C4 alkyl; R 2d is hydrogen or C1-C6 alkyl; R 2e is hydrogen, C1-C6 alkyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C8 cycloalkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonyl, C1-C6 alkylaminoC1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl or C1-C6 alkoxyC1-C6 alkylaminocarbonyl; R 2dd is hydrogen or C1-C6 alkyl; R 2eeis hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, hydroxyC3-C8 cycloalkyl or -L''-R''; L'' is C1-C4 alkylene or C3-C7 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylcarbonylamino, C1-C6 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C4 alkyl; L 2b is C1-C4 alkylene or C3-C7 cycloalkylene; R 2f is amino or C3-C10 heterocycloalkyl; R 2g is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C4 alkyl and haloC1-C4 alkyl.

[0267] In one specific example, the R 2 may be C1-C4 alkyl, halogen, C1-C4 alkoxy, C1-C4 alkylcarbonyl, C3-C8 cycloalkylcarbonyl or C6-C12 arylcarbonyl.

[0268] In one specific example, the R 2 is methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, fluoro, chloro, methylcarbonyl, ethylcarbonyl, butylcarbonyl, cyclopropylcarbonyl, cyclohexylcarbonyl, phenylcarbonyl or -NH2, or any one selected from the following structures:

[0269]

[0270]

[0271] In one embodiment, the compound may be any one selected from the group of compounds below, but is not limited thereto.

[0272] (1)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylphenyl)tetrahydrofuran-3-carboxamide,

[0273] (2)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylphenyl)-3-(piperidin-1-yl)propanamide,

[0274] (3) 1-(2-(dimethylamino)acetamido)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylphenyl)cyclobutanecarboxamide,

[0275] (4) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylphenyl)butanamide,

[0276] (5)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylphenyl)-3-(piperidin-1-yl)propanamide,

[0277] (6)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide,

[0278] (7) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)tetrahydrofuran-3-carboxamide,

[0279] (8)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-2-(2-methoxyethoxy)acetamide,

[0280] (9) 2-acetamido-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)acetamide,

[0281] (10)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-2-methoxyacetamide,

[0282] (11) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)acetamide,

[0283] (12)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)tetrahydro-2H-pyran-4-carboxamide,

[0284] (13) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)tetrahydrofuran-2-carboxamide,

[0285] (14)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide,

[0286] (15)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0287] (16)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide,

[0288] (17)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0289] (18) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)butanamide,

[0290] (19)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide,

[0291] (20)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-(2-methoxyethoxy)acetamide,

[0292] (21) 2-acetamido-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)acetamide,

[0293] (22)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-methoxyacetamide,

[0294] (23) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)acetamide,

[0295] (24) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)tetrahydrofuran-2-carboxamide,

[0296] (25)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide,

[0297] (26)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0298] (27)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide,

[0299] (28)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0300] (29) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)tetrahydrofuran-3-carboxamide,

[0301] (30) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)butanamide,

[0302] (31)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide

[0303] (32)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-hydroxyacetamide,

[0304] (33)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-(3,3-dimethylureido)acetamide,

[0305] (34) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-1-methylpyrrolidine-2-carboxamide,

[0306] (35)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide,

[0307] (36)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0308] (37)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0309] (38)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide,

[0310] (39)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide,

[0311] (40)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide,

[0312] (41)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide,

[0313] (42)N-(4-(3-acetamido-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0314] (43)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0315] (44)N-(4-(3-acetamido-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0316] (45)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0317] (46)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide,

[0318] (47)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide,

[0319] (48)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0320] (49)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide,

[0321] (50)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0322] (51)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0323] (52)N-(4-(3-(butylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0324] (53)N-(4-(3-(3-chloropropylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0325] (54)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-methylethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0326] (55)N-(4-(3-(cyclopropanesulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0327] (56) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)acetamide,

[0328] (57) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)acetamide,

[0329] (58) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)butanamide,

[0330] (59) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-methylethylsulfonamido)phenoxy)-3,5-dimethylphenyl)acetamide,

[0331] (60)N-(4-(3-(cyclopropanesulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide,

[0332] (61)N-(4-(3-(cyclopropanesulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide,

[0333] (62) 1-(2-(dimethylamino)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0334] (63) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-isopentylurea,

[0335] (64) 2-(dimethylamino)ethyl (4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate,

[0336] (65) Isopentyl (4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate,

[0337] (66) Phenyl(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate,

[0338] (67) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-((1r,4r)-4-hydroxycyclohexyl)urea,

[0339] (68) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0340] (69) Methyl (4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate,

[0341] (70) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-methylurea,

[0342] (71) 1-(2-aminoethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0343] (72) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-hydroxyethyl)urea,

[0344] (73) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-methoxyethyl)urea,

[0345] (74) 1-(2-(diethylamino)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0346] (75) 1-(2-aminoethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-1-methylurea,

[0347] (76) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(piperidin-1-yl)ethyl)urea,

[0348] (77) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-((tetrahydrofuran-2-yl)methyl)urea,

[0349] (78) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(4-methylpiperazin-1-yl)ethyl)urea,

[0350] (79)N-(2-(3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)ureido)ethyl)acetamide,

[0351] (80)N-(2-(3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)ureido)ethyl)methanesulfonamide,

[0352] (81) 1-(3-(dimethylamino)propyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0353] (82) 1-(2-(1H-imidazol-1-yl)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0354] (83) 1-(2-(1H-pyrrol-1-yl)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0355] (84) 1-(2-(1H-pyrazol-1-yl)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea,

[0356] (85) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(pyrrolidin-1-yl)ethyl)urea,

[0357] (86) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-morpholinoethyl)urea,

[0358] (87) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(methylamino)ethyl)urea,

[0359] (88) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-ethylurea,

[0360] (89)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)morpholine-4-carboxamide,

[0361] (90) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-isopropylurea,

[0362] (91) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-phenylurea,

[0363] (92) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-3,5-dimethylisoxazole,

[0364] (93) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(trifluoromethyl)phenoxy)-3,5-dimethylphenyl)butanamide,

[0365] (94)N-(4-(3-(difluoromethyl)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide,

[0366] (95)N-(4-(3-acetyl-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide,

[0367] (96) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-hydroxyethyl)phenoxy)-3,5-dimethylphenyl)butanamide,

[0368] (97) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-fluoroethyl)phenoxy)-3,5-dimethylphenyl)butanamide,

[0369] (98) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-hydroxypropan-2-yl)phenoxy)-3,5-dimethylphenyl)butanamide,

[0370] (99)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-2-(dimethylamino)acetamide,

[0371] (100) 2-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)acetamide,

[0372] (101)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide,

[0373] (102) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-2-methylphenyl)butanamide,

[0374] (103) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)butanamide,

[0375] (104)N-(5-(3-(butylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide,

[0376] (105) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-2-methylphenyl)butanamide,

[0377] (106) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-isobutyramidophenoxy)-2-methylphenyl)butanamide,

[0378] (107)N-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropanecarboxamide,

[0379] (108)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide,

[0380] (109)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide,

[0381] (110)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide,

[0382] (111)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-morpholinopropanamide,

[0383] (112)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-morpholinopropanamide,

[0384] (113)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0385] (114)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0386] (115)N-(5-(3-(butylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide,

[0387] (116)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-methoxypropanamide,

[0388] (117)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-2-methylphenyl)-3-methoxypropanamide,

[0389] (118)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-methoxypropanamide,

[0390] (119) 4-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0391] (120) 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0392] (121) 4-(3-(4-(4-(dimethylamino)butanamido)-2,6-dimethylmenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0393] (122) 4-(3-(4-(3-(1H-imidazol-1-yl)propanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0394] (123) 4-(3-(2,6-dimethyl-4-(3-(piperidin-1-yl)propanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0395] (124) 4-(3-(2,6-dimethyl-4-(3-(pyrrolidin-1-yl)propanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0396] (125) 4-(3-(2,6-dimethyl-4-(3-(4-methylpiperazin-1-yl)propanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0397] (126) 4-(3-(4-acetamido-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0398] (127)N-Ethyl-4-(3-(4-(2-methoxyacetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0399] (128) 4-(3-(2,6-dimethyl-4-(4-(piperidin-1-yl)butanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0400] (129) 4-(3-(4-(3-(dimethylamino)propanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0401] (130) 4-(3-(4-(4-(1H-imidazol-1-yl)butanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0402] (131) 4-(3-(2,6-dimethyl-4-(4-(pyrrolidin-1-yl)butanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0403] (132) 4-(3-(2,6-dimethyl-4-(2-(pyrrolidin-1-yl)acetamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0404] (133) tert-butyl(4-((4-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)amino)-4-oxobutyl)carbamate,

[0405] (134) tert-butyl(2-((4-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)amino)-2-oxoethyl)carbamate,

[0406] (135) 4-(3-(4-(4-aminobutanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide hydrochloride,

[0407] (136) 4-(3-(4-(2-aminoacetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide hydrochloride,

[0408] (137) 4-(3-(4-(2-(1H-imidazol-1-yl)acetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0409] (138) 4-(3-(2,6-dimethyl-4-(5-methylhexamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0410] (139) 4-(3-(4-(5-(dimethylamino)pentanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0411] (140) 4-(3-(2,6-dimethyl-4-(pyrrolidine-1-carboxamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0412] (141) 4-(3-amino-5-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0413] (142) 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-(methylsulfonamido)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0414] (143)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0415] (144) tert-butyl ((1r,4r)-4-(4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate,

[0416] (145) tert-butyl ((1r,4r)-4-(4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate,

[0417] (146) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0418] (147)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0419] (148)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0420] (149) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0421] (150) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0422] (151) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0423] (152) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0424] (153) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0425] (154) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0426] (155)N-Cyclopropyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0427] (156) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1s,4s)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0428] (157)N-(4,4-difluorocyclohexyl)-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0429] (158)N-((1r,4r)-4-acetamidocyclohexyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0430] (159) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-cyclohexyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0431] (160) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-cyclopropyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0432] (161) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-(3,3-dimethylureido)cyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0433] (162) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1s,4s)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0434] (163) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(4,4-difluorocyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0435] (164) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(1-(trifluoromethyl)cyclopropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0436] (165) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(1,1,1-trifluoro-2-methylpropan-2-yl)- 6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0437] (166) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(2,2,2-trifluoroethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0438] (167) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2-hydroxyethyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0439] (168) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(3-hydroxypropyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0440] (169) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2,2-difluoro-1-methylcyclopropyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0441] (170) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0442] (171)N-((1S,3S)-3-aminocyclohexyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0443] (172)N-((1S,3S)-3-aminocyclopentyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0444] (173)N-((1R,3R)-3-aminocyclopentyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0445] (174) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-N-((1S,3S)-3-(methylsulfonamido)cyclopentyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0446] (175) (1r,4r)-4-(4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid,

[0447] (176) (1r,4r)-4-(4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid,

[0448] (177) (1r,4r)-Methyl 4-(4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylate,

[0449] (178) (1r,4r)-Methyl 4-(4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylate,

[0450] (179) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1S,3S)-3-hydroxycyclopentyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0451] (180) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1S,3S)-3-hydroxycyclopentyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0452] (181) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one,

[0453] (182)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0454] (183) 4-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0455] (184)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(1-hydroxycyclopropyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0456] (185)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0457] (186) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0458] (187)N-Cyclopropyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0459] (188) 4-(3-amino-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0460] (189)N-Ethyl-6-methyl-4-(3-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)-5-(methylsulfonamido)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0461] (190)N-Ethyl-6-methyl-4-(3-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)-5-(ethylsulfonamido)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0462] (191) 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0463] (192) 4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0464] (193)N-Ethyl-6-methyl-4-(3-methyl-5-(4-methyl-3-(4-(piperidin-1-yl)butanamido)phenoxy)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0465] (194)N-Ethyl-6-methyl-4-(3-methyl-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0466] (195) 4-(3-(3-(3-(1H-imidazol-1-yl)propanamido)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0467] (196) 4-(3-(3-(2-(dimethylamino)acetamido)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0468] (197)N-Ethyl-4-(3-(3-(2-methoxyacetamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0469] (198) 4-(3-(3-acetamido-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0470] (199)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0471] (200)N-((1s,4s)-4-aminocyclohexyl)-4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0472] (201)N-(bicyclo[1.1.1]pentan-1-yl)-4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0473] (202) 4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0474] (203) 4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0475] (204) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide,

[0476] (205) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(4-methyl-1H-imidazol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide,

[0477] (206) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide,

[0478] (207) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-7-oxo-2-(1H-tetrazol-5-yl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide,

[0479] (208) 4-(3-(3-((3-(dimethylamino)propyl)carbamoyl)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0480] (209)N-Ethyl-4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0481] (210) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0482] (211) tert-butyl((1r,4r)-4-(4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate,

[0483] (212) tert-butyl((1r,4r)-4-(4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate,

[0484] (213)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0485] (214)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0486] (215) 4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0487] (216) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0488] (217) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-cyclopropyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0489] (218) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-((1s,4s)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0490] (219) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-(4,4-difluorocyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0491] (220) 4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0492] (221) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0493] (222) 4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0494] (223) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0495] (224) 4-(3-(3-chloro-4-methylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,

[0496] (225) 7-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0497] (226) 7-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0498] (227) 7-(3-(4-(3-(1H-imidazol-1-yl)propanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0499] (228)N-Ethyl-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0500] (229) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0501] (230) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0502] (231)N-((1r,4r)-4-aminocyclohexyl)-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0503] (232) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0504] (233) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2-hydroxyethyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0505] (234) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(3-hydroxypropyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0506] (235) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(3-hydroxypropyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0507] (236) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2-hydroxyethyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0508] (237) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-propyl-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0509] (238) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-propyl-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0510] (239) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,3r)-3-hydroxycyclobutyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0511] (240) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-(tetrahydro-2H-pyran-4-yl)-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0512] (241) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-((tetrahydro-2H-pyran-4-yl)methyl)-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0513] (242) (1r,4r)-4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid,

[0514] (243) (1r,4r)-4-(7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid,

[0515] (244) 4-(7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylate,

[0516] (245) (1r,4r)-Methyl 4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylate,

[0517] (246)N-Ethyl-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0518] (247) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0519] (248) 7-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0520] (249) 7-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0521] (250)N-Ethyl-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0522] (251) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N,5-dimethyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0523] (252) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0524] (253) (1r,4r)-4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid,

[0525] (254) (1r,4r)-Methyl 4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylate,

[0526] (255)N-Ethyl-7-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0527] (256) 7-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0528] (257) 7-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide,

[0529] (258)N-((1r,4r)-4-aminocyclohexyl)-7-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, and

[0530] (259) 7-(3-(3-Fluoro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide.

[0531] The compound of the above chemical formula 1 can be prepared by a variety of known methods depending on the type of substituent. It will be apparent to those skilled in the art that this can be accomplished using methods known in the art or by appropriate modifications. Details are described in the examples below.

[0532] The compound of the present invention can be prepared and used in the form of a prodrug, a hydrate, a solvate, and a pharmaceutically acceptable salt to promote absorption in the body or increase solubility, and therefore, not only the compound of the above chemical formula 1, but also its prodrug, hydrate, solvate, or pharmaceutically acceptable salt is included in the scope of the present invention.

[0533] The compound of the present invention can be used in the form of a pharmaceutically acceptable salt. The pharmaceutically acceptable salt is a salt prepared according to a method conventional in the art, and the preparation method thereof is well known to those skilled in the art. The pharmaceutically acceptable salt may be an acid addition salt formed with a pharmaceutically acceptable free acid.

[0534] The above-mentioned acid may be an inorganic acid or an organic acid. In this case, the inorganic acid may be hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, hydrobromic acid, etc., and the organic acid may be acetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, fumaric acid, trifluoroacetic acid, maleic acid, malonic acid, phthalic acid, succinic acid, propionic acid, citric acid, lactic acid, gluconic acid, tartaric acid, salicylic acid, malic acid, oxalic acid, benzoic acid, embonic acid, aspartic acid, glutamic acid, galacturonic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, etc. The above acid addition salt can be prepared by a conventional method, for example, by dissolving the compound of the above chemical formula 1 in a water-miscible organic solvent such as methanol, ethanol, acetone, dichloromethane, acetonitrile, etc., adding an organic acid or inorganic acid, filtering and drying the resulting precipitate, or by distilling the solvent and an excess acid under reduced pressure, drying, and crystallizing in the presence of an organic solvent.

[0535] The pharmaceutically acceptable salt may be an alkali metal salt (sodium salt, potassium salt, etc.) or an alkaline earth metal salt (calcium salt, etc.). The alkali metal salt or alkaline earth metal salt may be obtained, for example, by dissolving the compound of the above chemical formula 1 in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate.

[0536] The compound of the present invention may include a hydrate and a solvate of the compound of formula 1. The hydrate and solvate can be prepared using a known method, and are preferably non-toxic and water-soluble. Specifically, the hydrate refers to a compound of formula 1 or a pharmaceutically acceptable salt thereof, which contains a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. The solvate refers to a compound of formula 1 or a pharmaceutically acceptable salt thereof, which contains a stoichiometric or non-stoichiometric amount of an alcoholic solvent (particularly, ethanol, etc.) bound by non-covalent intermolecular forces.

[0537] The compound of the present invention may be administered in the form of a prodrug, which is broken down in the human or animal body to provide the compound of the present invention as an active ingredient. Prodrugs can be used to modify and / or improve the physical and / or pharmacokinetic profiles of the parent compound, and can be formed if the parent compound contains a suitable group or substituent that can be induced to form a prodrug.

[0538] Any compound (prodrug) that is cleaved in the body to produce a compound of the present invention or a salt thereof, such a compound, i.e. a prodrug, is also encompassed by the scope of the present invention. As used herein and unless otherwise indicated, the term "prodrug" means a compound of the present invention that can be hydrolyzed, oxidized, and otherwise reacted under biological conditions (in vitro or in vivo) to provide an active compound, particularly a compound of the present invention. Examples of prodrugs include, but are not limited to, compounds that contain a biohydrolyzable moiety (e.g., a biohydrolyzable amide, a biohydrolyzable ester, a biohydrolyzable carbamate, a biohydrolyzable carbonate, a biohydrolyzable ureide, or a biohydrolyzable phosphate analogue) that undergoes biohydrolysis to produce a compound of the present invention. Specifically, a prodrug of a compound having a carboxylic functional group may be a lower alkyl ester of a carboxylic acid. Carboxylic esters can be conventionally formed by esterifying the carboxylic acid moiety present in the molecule. Prodrugs can be readily prepared using well-known methods, such as those described in Burger's Medicinal Chemistry and Drug Discovery 6th ed. (Donald J. Abrahamed., 2001, Wiley) and Design and Application of Prodrugs (H. Bundgaarded., 1985, Harwood Academic Publishers Gmfh).

[0539] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating diseases and disorders responsive to inhibition of a bromodomain-containing protein, comprising a compound of the above chemical formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0540] Diseases and disorders responsive to inhibition of the above bromodomain-containing protein may be selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory diseases, renal diseases and cancer.

[0541] The compound of the above chemical formula 1 can selectively inhibit the activity of BRD4, a type of bromodomain. Specifically, the compound of the above chemical formula 1 can inhibit the binding of BRD4 to acetylated histones, thereby preventing or treating diseases selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory diseases, kidney diseases, and cancer.

[0542] In one embodiment, the compound of formula 1 may be more useful in preventing or treating cancer, inflammatory diseases, and fibrosis by regulating aberrant (pathogenic) proliferation, fibrotic and inflammatory gene expression through BRD4 inhibition.

[0543] According to one embodiment, the compound of the above chemical formula 1 can be expected to cause epigenetic reprogramming, which has limitations as an existing therapeutic agent, through BRD4 inhibition, thereby inducing de-differentiation of myofibroblasts and fibrotic macrophages, thereby leading to resolution of fibrotic regions.

[0544] According to one embodiment, the compound of formula 1 can selectively inhibit only BD2 of BRD4 while simultaneously inhibiting BRD4, thereby reducing toxicity without reducing efficacy.

[0545] The above inflammatory diseases include Addison's disease, acute gout, ankylosing spondylitis, asthma, atherosclerosis, Behcet's disease, bullous skin disease, chronic obstructive pulmonary disease, dermatitis, eczema, giant cell arteritis, glomerulonephritis, hepatitis, inflammatory bowel disease, Kawasaki disease, pancreatitis, pericarditis, polyarteritis nodosa, pneumonitis, primary biliary cirrhosis, psoriasis, and psoriatic arthritis. It may be selected from the group consisting of psoriatic arthritis, scleritis, sclerosing cholangitis, sepsis, Takayasu's arteritis, toxic shock, thyroiditis, type I diabetes, ulcerative colitis, uveitis, vitiligo, vasculitis, Wegener's granulomatosis, inflammatory skin disorders, respiratory diseases, gastrointestinal diseases, and eye diseases.

[0546] The above fibrotic disease may be selected from the group consisting of lung, liver, kidney, skin, heart, eye and systemic fibrosis.

[0547] The above kidney diseases include ischemia-reperfusion induced kidney disease, cardiac and major surgery induced kidney disease, percutaneous coronary intervention induced kidney disease, radio-contrast agent induced kidney disease, sepsis induced kidney disease, pneumonia induced kidney disease, drug toxicity induced kidney disease, diabetic nephropathy, hypertensive nephropathy, HIV-associated nephropathy, glomerulonephritis, lupus nephritis, IgA nephropathy, It may be selected from the group consisting of focal segmental glomerulosclerosis, membranous glomerulonephritis, polycystic kidney disease, and tubular interstitial nephritis.

[0548] The above cancers include acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, chronic myelogenous leukemia, colon cancer. cancer), cololectal cancer, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes, embryonal carcinoma, endometrial cancer, endothelial sarcoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma,Follicular lymphoma, germ cell testicular cancer, heavy chain disease, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphangioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, malignancies and hyperproliferative disorders of bladder, breast, colon, lung, ovaries, pancreas, prostate, skin, and uterus. prostate, skin, and uterus), lymphoma, medullary carcinoma, melanoma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, NUT midline carcinoma, non-small cell lung cancer, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma,Selected from the group consisting of pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, small cell lung cancer, solid tumor, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom's macroglobulinemia, testicular tumors, uterine cancer, and Wilms' tumor. can be,

[0549] The above pharmaceutical composition may be formulated as a conventional formulation in the pharmaceutical field, i.e., a formulation for oral administration or a formulation for parenteral administration, by additionally including a conventional non-toxic pharmaceutically acceptable carrier, excipient or diluent in addition to the above effective ingredient.

[0550] The pharmaceutically acceptable carriers, excipients or diluents include sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols such as propylene glycol; polyols such as glycerin, sorbitol, mannitol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffered solutions; and other commercially available non-toxic substances used in pharmaceutical preparations.

[0551] The above pharmaceutical composition can be formulated and used in various forms, such as oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, and injections of sterile injection solutions, according to conventional methods according to the intended use, and can be administered through oral administration (e.g., tablets, pills, powders, capsules, syrups, emulsions, etc.) or parenteral administration (e.g., intramuscular, intraperitoneal, intravenous, or subcutaneous injection).

[0552] The above pharmaceutical composition may additionally include fillers, anticoagulants, lubricants, humectants, fragrances, emulsifiers, preservatives, etc.

[0553] The above pharmaceutical composition may be formulated as a preparation for oral administration, and the additives used in this case may include cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, surfactants, suspending agents, emulsifiers, diluents, etc. Specifically, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations may be formulated by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc., into the composition. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may be used. In addition, liquid preparations for oral administration may include suspensions, solutions, emulsions, syrups, etc., and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.

[0554] In addition, examples of preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, etc. Non-aqueous solvents and suspending agents may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol, gelatin, etc. Meanwhile, injections may include conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives. In order to formulate an injection, the compound of the above chemical formula 1 or a pharmaceutically acceptable salt thereof is mixed with a stabilizer or buffer in water to prepare a solution or suspension, which may be prepared in a unit dosage form of an ampoule or vial.

[0555] The pharmaceutical composition may be sterilized or may further contain auxiliary agents such as preservatives, stabilizers, thickeners, wetting agents or emulsifying agents, salts for osmotic pressure control and / or buffers, and may further contain other therapeutically useful substances, and may be formulated by conventional methods such as dissolving, dispersing, mixing, granulating, gelling or coating.

[0556] The compound or pharmaceutical composition of the present invention may be administered to a subject in a therapeutically effective amount or a pharmaceutically effective amount.

[0557] Specifically, the effective amount of the compound in the pharmaceutical composition may vary depending on the patient's age, sex, and weight, and is generally about 0.01 to 1000 mg / kg / day, specifically 0.1 to 500 mg / kg / day, and more specifically 1 to 200 mg / kg / day, and may be administered daily or every other day, or administered once or several times a day in divided doses. However, since the dosage may increase or decrease depending on the administration route, severity of the disease, sex, body weight, age, etc., the dosage does not limit the scope of the present invention in any way.

[0558] The compound or pharmaceutical composition of the present invention can be administered as an individual therapeutic agent or in combination with another therapeutic agent, sequentially or simultaneously with conventional therapeutic agents, or in single or multiple doses. Taking all of the above factors into account, it is important to administer an amount that achieves maximum effect with the minimum amount possible without causing side effects, a determination readily made by those skilled in the art.

[0559] The present invention also provides a method for preventing or treating a disease or disorder responsive to inhibition of a bromodomain-containing protein, comprising administering the compound or pharmaceutical composition to a subject who has developed or is at risk of developing a disease or disorder responsive to inhibition of a bromodomain-containing protein.

[0560] The compound or pharmaceutical composition may be administered to a subject in a therapeutically effective amount or a pharmaceutically effective amount.

[0561] The route and method of administration for administering the compound or pharmaceutical composition are not particularly limited, and any route and method of administration may be followed as long as the compound or pharmaceutical composition can reach the target site. Specifically, the compound or composition may be administered through various routes, such as oral or parenteral, and non-limiting examples of the routes of administration include oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, intranasal, or inhalation.

[0562] Another aspect of the present invention provides a bromodomain inhibitor comprising a compound of the above formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0563] The compound of the above chemical formula 1 can selectively inhibit the activity of BRD4, a type of bromodomain. Specifically, the compound of the above chemical formula 1 can inhibit the binding of BRD4 to acetylated histones.

[0564] Hereinafter, specific examples and experimental examples will be described. However, the examples and experimental examples described below are only illustrative, and the technology described in this specification is not limited thereto.

[0565] [Examples 1 to 3]

[0566]

[0567] Step 1: Preparation of 1-(benzyloxy)-3-bromo-5-fluorobenzene

[0568] 3-Bromo-5-fluorophenol (5 g, 26.18 mmol, 1 eq) and benzyl bromide (3.74 mL, 31.41 mmol) were dissolved in N,N-dimethylformamide (90 mL), and potassium carbonate (5.4 g, 39.27 mmol, 1.5 eq) was added. The reaction mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 6.82 g (24.26 mmol, 93%) of the title compound.

[0569] Step 2: Preparation of 4-(3-(benzyloxy)-5-fluorophenyl)-3,5-dimethylisoxazole

[0570] 1-(Benzyloxy)-3-bromo-5-fluorobenzene (6.82 g, 24.26 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (3.42 g, 24.26 mmol, 1 eq), Pd(dppf)2Cl2 (1.78 g, 2.43 mmol, 0.1 eq), and cesium carbonate (11.86 g, 36.39 mmol, 1.5 eq) were mixed in dioxane (80 mL) and water (8 mL). The reaction mixture was heated to 90 °C, stirred under argon gas for 20 hours, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, and the layers were separated. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 6.81 g (22.93 mmol, 95%) of the title compound.

[0571] Step 3: Preparation of 3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenol

[0572] 4-(3-(Benzyloxy)-5-fluorophenyl)-3,5-dimethylisoxazole (6.81 g, 22.93 mmol) was dissolved in methanol (100 mL), 10% Pd / C (681 mg, 10% wt) was mixed, and the mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure to obtain 4.57 g (22.04 mmol, 96%) of the title compound without further purification.

[0573] Step 4: Preparation of 4-(3-fluoro-5-(2-methyl-4-nitrophenoxy)phenyl)-3,5-dimethylisoxazole

[0574] 3-(3,5-Dimethylisoxazol-4-yl)-5-fluorophenol (4.57 g, 22.04 mmol) and 1-fluoro-2-methyl-4-nitrobenzene (4.1 g, 26.45 mmol) were dissolved in N,N-dimethylformamide (75 mL), cesium carbonate (14.36 g, 44.08 mmol) was added, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 6.7 g (19.56 mmol, 89%) of the title compound.

[0575] Step 5: Preparation of 4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylaniline

[0576] 4-(3-Fluoro-5-(2-methyl-4-nitrophenoxy)phenyl)-3,5-dimethylisoxazole (6.7 g, 19.56 mmol), zinc powder (25.58 g, 391.2 mmol), and acetic acid (11.2 mL, 195.6 mmol) were mixed in tetrahydrofuran (100 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 5.6 g (92%) of the title compound without further purification.

[0577] Step 6: Amide coupling

[0578] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (hexafluorophosphate azabenzotriazole tetramethyl uronium) (1.5 eq), diisopropylethylamine (1.5 eq), and 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 1 below (yield: 60-90%).

[0579] [Table 1]

[0580]

[0581] [Examples 4 to 6]

[0582]

[0583] Step 1: Preparation of 1-(3-bromo-5-methylphenoxy)-2-methyl-4-nitrobenzene

[0584] 3-Bromo-5-methylphenol (5 g, 27.02 mmol) and 1-fluoro-2-methyl-4-nitrobenzene (5.03 g, 32.43 mmol) were dissolved in N,N-dimethylformamide (90 mL), cesium carbonate (17.61 g, 54.04 mmol) was added, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 7.85 g (24.38 mmol, 90%) of the title compound.

[0585] Step 2: Preparation of 3,5-dimethyl-4-(3-methyl-5-(2-methyl-4-nitrophenoxy)phenyl)isoxazole

[0586] 1-(3-Bromo-5-methylphenoxy)-2-methyl-4-nitrobenzene (1 g, 3.10 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (0.44 g, 3.10 mmol, 1 eq), Pd(dppf)2Cl2 (0.23 g, 0.31 mmol, 0.1 eq) and cesium carbonate (1.52 g, 4.65 mmol, 1.5 eq) were mixed and dissolved in dioxane (10 mL) and water (1 mL). The reaction mixture was heated to 90°C, stirred under argon gas for 20 hours and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 940 mg (2.78 mmol, 90%) of the title compound.

[0587] Step 3: Preparation of 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylaniline

[0588] 3,5-Dimethyl-4-(3-methyl-5-(2-methyl-4-nitrophenoxy)phenyl)isoxazole (940 mg, 2.78 mmol), zinc powder (3.64 g, 55.6 mmol), and acetic acid (1.59 mL, 27.8 mmol) were dissolved in tetrahydrofuran (30 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 697 mg (81%) of the title compound without further purification.

[0589] Step 4: Amide coupling

[0590] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 2 below (yield: 60-90%).

[0591] [Table 2]

[0592]

[0593] [Examples 7 to 19]

[0594]

[0595] Step 1: Preparation of 1-(benzyloxy)-3-bromo-5-fluorobenzene

[0596] 3-Bromo-5-fluorophenol (5 g, 26.18 mmol, 1 eq) and benzyl bromide (3.74 mL, 31.41 mmol) were dissolved in N,N-dimethylformamide (90 mL), potassium carbonate (5.4 g, 39.27 mmol, 1.5 eq) was added, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 6.82 g (24.26 mmol, 93%) of the title compound.

[0597] Step 2: Preparation of 4-(3-(benzyloxy)-5-fluorophenyl)-3,5-dimethylisoxazole

[0598] 1-(Benzyloxy)-3-bromo-5-fluorobenzene (6.82 g, 24.26 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (3.42 g, 24.26 mmol, 1 eq), Pd(dppf)2Cl2 (1.78 g, 2.43 mmol, 0.1 eq), and cesium carbonate (11.86 g, 36.39 mmol, 1.5 eq) were mixed in dioxane (80 mL) and water (8 mL), heated to 90 °C, stirred under argon gas for 20 hours, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 6.81 g (22.93 mmol, 95%) of the title compound.

[0599] Step 3: Preparation of 3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenol

[0600] 4-(3-(Benzyloxy)-5-fluorophenyl)-3,5-dimethylisoxazole (6.81 g, 22.93 mmol) was dissolved in methanol (100 mL), 10% Pd / C (681 mg, 10% wt) was mixed, and the mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure to obtain 4.57 g (22.04 mmol, 96%) of the title compound without further purification.

[0601] Step 4: Preparation of 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-fluorophenyl)-3,5-dimethylisoxazole

[0602] 3-(3,5-Dimethylisoxazol-4-yl)-5-fluorophenol (4.57 g, 22.04 mmol) and 2-fluoro-1,3-dimethyl-5-nitrobenzene (4.47 g, 26.45 mmol) were dissolved in N,N-dimethylformamide (75 mL), cesium carbonate (14.36 g, 44.08 mmol) was added, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 6.88 g (19.31 mmol, 88%) of the title compound.

[0603] Step 5: Preparation of 4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylaniline

[0604] 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-fluorophenyl)-3,5-dimethylisoxazole (6.88 g, 19.56 mmol), zinc powder (25.25 g, 386.2 mmol), and acetic acid (11.05 mL, 193.1 mmol) were mixed in tetrahydrofuran (100 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 5.64 g (89%) of the title compound without further purification.

[0605] Step 6: Amide coupling

[0606] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 3 below.

[0607] [Table 3]

[0608]

[0609]

[0610] [Examples 20 to 34]

[0611]

[0612] Step 1: Preparation of 2-(3-bromo-5-methylphenoxy)-1,3-dimethyl-5-nitrobenzene

[0613] 3-Bromo-5-methylphenol (1.84 g, 9.8 mmol) and 2-fluoro-1,3-dimethyl-5-nitrobenzene (1.83 g, 10.8 mmol) were dissolved in N,N-dimethylformamide (30 mL), cesium carbonate (4 g, 12.2 mmol) was added, and the mixture was stirred at room temperature overnight. Water (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 3 g (8.92 mmol, 91%) of the title compound.

[0614] Step 2: Preparation of 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-3,5-dimethylisoxazole

[0615] 2-(3-Bromo-5-methylphenoxy)-1,3-dimethyl-5-nitrobenzene (1 g, 2.97 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (0.42 g, 2.97 mmol, 1 eq), Pd(dppf)2Cl2 (0.22 g, 0.3 mmol, 0.1 eq), and cesium carbonate (1.45 g, 4.46 mmol, 1.5 eq) were mixed in dioxane (10 mL) and water (1 mL), heated to 90 °C, stirred under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 965 mg (2.74 mmol, 92%) of the title compound.

[0616] Step 3: Preparation of 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline

[0617] 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-3,5-dimethylisoxazole (2.85 g, 8 mmol), zinc powder (10.57 g, 160 mmol), and acetic acid (4.62 mL, 80 mmol) were mixed in tetrahydrofuran (100 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 2.2 g (84%) of the title compound without further purification.

[0618] Step 4: Amide coupling

[0619] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, mixed with HATU (1.5 eq), diisopropylethylamine (1.5 eq), and 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline (1 eq), and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 4 below.

[0620] [Table 4]

[0621]

[0622]

[0623] [Examples 35 to 39]

[0624]

[0625] Step 1: Preparation of 2-(benzyloxy)-1,3-dimethyl-5-nitrobenzene

[0626] 2,6-Dimethyl-4-nitrophenol (1 g, 5.99 mmol) and benzyl bromide (0.85 mL, 7.18 mmol) were dissolved in N,N-dimethylformamide (30 mL), potassium carbonate (1.24 g, 8.99 mmol, 1.5 eq) was added, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 1.49 g (5.81 mmol, 97%) of the title compound.

[0627] Step 2: Preparation of 4-(benzyloxy)-3,5-dimethylaniline

[0628] 2-(Benzyloxy)-1,3-dimethyl-5-nitrobenzene (1.49 g, 5.81 mmol, 1 eq), zinc powder (7.6 g, 116.2 mmol, 20 eq), and acetic acid (3.33 mL, 58.1 mmol, 10 eq) were mixed in tetrahydrofuran (20 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 1.19 g (5.23 mmol, 90%) of the title compound without any further purification.

[0629] Step 3: Amide coupling

[0630] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, mixed with HATU (1.5 eq), diisopropylethylamine (1.5 eq), and 4-(benzyloxy)-3,5-dimethylaniline (1 eq), and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the amide compound (yield: 60-90%).

[0631] Step 4: Deprotection of the benzyl group

[0632] The amide compound (1 eq) obtained in step 3 was dissolved in methanol, and 10% Pd / C (10% wt) was mixed, and the mixture was stirred at room temperature under hydrogen gas for 20 hours. The reaction mixture was filtered through Celite and washed with methanol. The solvent was distilled under reduced pressure to obtain a phenol compound without further purification (yield: 80–95%).

[0633] Step 5: Aromatic substitution

[0634] The phenol compound (1 eq) obtained in step 4 and 1-bromo-3-fluoro-5-nitrobenzene (1 eq to 1.2 eq) were dissolved in N,N-dimethylformamide, and cesium carbonate (1.5 eq) was mixed, followed by stirring at room temperature overnight. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain a bromonitrophenoxy compound (yield: 71-93%).

[0635] Step 6: Suzuki Cross Coupling

[0636] The bromonitrophenoxy compound (1 eq) obtained in step 5, (3,5-dimethylisoxazol-4-yl)boronic acid (1 eq), Pd(dppf)2Cl2 (0.1 eq), and cesium carbonate (1.5 eq) were mixed in dioxane and water, heated to 90°C, and stirred for 20 hours under argon gas. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain the nitrophenoxy compound (yield: 55-83%).

[0637] Step 7: Reduction of the nitro group

[0638] The nitrophenoxy compound (1 eq), zinc powder (20 eq), and acetic acid (10 eq) obtained in step 6 were mixed in tetrahydrofuran and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous solution of sodium bicarbonate were added to separate the layers, and the organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound in Table 5 below without further purification (yield: 75-96%).

[0639] [Table 5]

[0640]

[0641] [Examples 40 to 45]

[0642]

[0643] Step 1: Amide coupling

[0644] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and each aniline (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 6 below (yield: 70-90%).

[0645] [Table 6]

[0646]

[0647]

[0648] [Examples 46 to 61]

[0649]

[0650] Step 1: Sulfonamide coupling

[0651] Each aniline (1 eq) was dissolved in pyridine, and each sulfonyl chloride (1.2 eq) was added, followed by stirring at room temperature overnight. Water and ethyl acetate were added to the reaction mixture to separate the layers. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain the title compounds in Table 7 below (yield: 60-90%).

[0652] [Table 7]

[0653]

[0654]

[0655]

[0656] [Examples 62 to 91]

[0657]

[0658] Step 1: Preparation of 2-(3-bromo-5-methylphenoxy)-1,3-dimethyl-5-nitrobenzene

[0659] 3-Bromo-5-methylphenol (1.84 g, 9.8 mmol) and 2-fluoro-1,3-dimethyl-5-nitrobenzene (1.83 g, 10.8 mmol) were dissolved in N,N-dimethylformamide (30 mL), cesium carbonate (4 g, 12.2 mmol) was added, and the mixture was stirred at room temperature overnight. Water (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 3 g (8.92 mmol, 91%) of the title compound.

[0660] Step 2: Preparation of 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-3,5-dimethylisoxazole

[0661] 2-(3-Bromo-5-methylphenoxy)-1,3-dimethyl-5-nitrobenzene (1 g, 2.97 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (0.42 g, 2.97 mmol, 1 eq), Pd(dppf)Cl2 (0.22 g, 0.3 mmol, 0.1 eq), and cesium carbonate (1.45 g, 4.46 mmol, 1.5 eq) were mixed in dioxane (10 mL) and water (1 mL), heated to 90 °C, stirred under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 965 mg (2.74 mmol, 92%) of the title compound.

[0662] Step 3: Preparation of 4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline

[0663] 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-3,5-dimethylisoxazole (2.85 g, 8 mmol), zinc powder (10.57 g, 160 mmol), and acetic acid (4.62 mL, 80 mmol) were mixed in tetrahydrofuran (100 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 2.2 g (84%) of the title compound without further purification.

[0664] Step 4: Preparation of phenyl(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate

[0665] 4-(3-(3,5-Dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylaniline (1.29 g, 3.99 mmol, 1 eq) was dissolved in tetrahydrofuran, and phenyl chloroformate (0.54 mL, 4.39 mmol, 1.1 eq) and triethylamine (0.84 mL, 5.99 mmol, 1.5 eq) were mixed at 0°C, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.40 g (79.8%) of the phenyl carbamate compound.

[0666] Step 5: Urea Coupling

[0667] The phenyl carbamate compound (1 eq) obtained in step 4 was dissolved in tetrahydrofuran, and each amine or aniline (1.25 eq) and triethylamine (1.5 eq) were mixed, heated from room temperature to 50°C, and stirred for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 8 below (6.6% to 99% yield).

[0668] Step 6: Carbamate Coupling

[0669] The phenyl carbamate compound (1 eq) obtained in step 4 was dissolved in tetrahydrofuran, and each alcohol (1.25 eq) and triethylamine (1.5 eq) were mixed, heated from room temperature to 50°C, and stirred for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 8 below (23% to 91% yield).

[0670] [Table 8]

[0671]

[0672]

[0673]

[0674]

[0675]

[0676] [Example 92] Preparation of 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-3,5-dimethylisoxazole

[0677]

[0678] Step 1: Preparation of 2-(3-bromo-5-methylphenoxy)-5-fluoro-1,3-dimethylbenzene

[0679] 4-Fluoro-2,6-dimethylphenol (500 mg, 3.57 mmol, 1 eq) was dissolved in dichloromethane (10 mL), (3-bromo-5-methylphenyl)boronic acid (1.53 g, 7.13 mmol, 2 eq), copper acetate (648 mg, 3.57 mmol, 1 eq), and triethylamine (2.49 mL, 17.85 mmol, 5 eq) were mixed, and the mixture was stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Water (100 mL) and dichloromethane (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 261 mg (0.84 mmol, 24%) of the title compound.

[0680] Step 2: Preparation of 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-3,5-dimethylisoxazole

[0681] 2-(3-Bromo-5-methylphenoxy)-5-fluoro-1,3-dimethylbenzene (50 mg, 0.16 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (25 mg, 0.18 mmol, 1.1 eq), Pd(dppf)Cl2 (6 mg, 0.008 mmol, 0.05 eq), and cesium carbonate (78 mg, 0.24 mmol, 1.5 eq) were mixed in dioxane (10 mL) and water (1 mL), heated to 90 °C, stirred under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 11 mg (0.034 mmol, 21%) of the title compound.

[0682] 1 H NMR (400 MHz, CDCl3) δ 6.82 (s, 1H), 6.80 (s, 1H), 6.68 (s, 1H), 6.59 (s, 1H), 6.38 (s, 1H), 2.35 (s, 3H), 2.29 (s, 3H), 2.20 (s, 3H), 2.13 (s, 6H); LCMS: m / z 326 [M+H] +

[0683] [Example 93] Preparation of 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(trifluoromethyl)phenoxy)-3,5-dimethylphenyl)butanamide

[0684]

[0685] Step 1: Preparation of 2-(benzyloxy)-1,3-dimethyl-5-nitrobenzene

[0686] 2,6-Dimethyl-4-nitrophenol (5 g, 29.91 mmol, 1 eq) and benzyl bromide (4.26 mL, 35.89 mmol, 1.2 eq) were dissolved in N,N-dimethylformamide (90 mL), potassium carbonate (6.2 g, 44.87 mmol, 1.5 eq) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 6.63 g (25.77 mmol, 86%) of the title compound.

[0687] Step 2: Preparation of 4-(benzyloxy)-3,5-dimethylaniline

[0688] 2-(Benzyloxy)-1,3-dimethyl-5-nitrobenzene (6.63 g, 25.77 mmol), zinc powder (33.70 g, 515.4 mmol, 20 eq), and acetic acid (11.05 mL, 193.1 mmol) were mixed in tetrahydrofuran (100 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 5.75 g (95%) of the title compound without further purification.

[0689] Step 3: Preparation of N-(4-(benzyloxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide

[0690] 4-(Dimethylamino)butanoic acid (0.3 g, 2.29 mmol, 1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.31 g, 3.44 mmol, 1.5 eq), diisopropylethylamine (0.60 mL, 3.44 mmol, 1.5 eq), and 4-(benzyloxy)-3,5-dimethylaniline (0.52 g, 2.29 mmol, 1 eq) were mixed and stirred at room temperature for 18 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 0.58 g (1.70 mmol, 74%) of the title compound.

[0691] Step 4: Preparation of 4-(dimethylamino)-N-(4-hydroxy-3,5-dimethylphenyl)butanamide

[0692] N-(4-(Benzyloxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide (0.58 g, 1.70 mmol) was dissolved in methanol (10 mL), and 10% Pd / C (58 mg, 10% wt) was mixed, and the mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite, washed with methanol, and the filtrate was concentrated under reduced pressure to obtain 0.42 g (1.68 mmol, 99%) of the title compound without further purification.

[0693] Step 5: Preparation of 4-(3-fluoro-5-(trifluoromethyl)phenyl)-3,5-dimethylisoxazole

[0694] 1-Bromo-3-fluoro-5-(trifluoromethyl)benzene (1 g, 4.12 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (0.64 g, 4.53 mmol, 1.1 eq), Pd(dppf)Cl2 (0.15 g, 0.21 mmol, 0.05 eq), and cesium carbonate (2.01 g, 6.18 mmol, 1.5 eq) were mixed in dioxane (10 mL) and water (1 mL), heated to 90 °C, and stirred under argon gas for 20 h. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0% → 50%) to obtain 0.78 g (2.97 mmol, 72%) of the title compound.

[0695] Step 6: Preparation of 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(trifluoromethyl)phenoxy)-3,5-dimethylphenyl)butanamide

[0696] 4-(Dimethylamino)-N-(4-hydroxy-3,5-dimethylphenyl)butanamide (0.1 g, 0.4 mmol, 1 eq) and 4-(3-fluoro-5-(trifluoromethyl)phenyl)-3,5-dimethylisoxazole (0.1 g, 0.4 mmol, 1 eq) were dissolved in N,N-dimethylformamide (3 mL), and cesium carbonate (0.2 g, 0.6 mmol, 1.5 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 0.15 g (0.31 mmol, 78%) of the title compound.

[0697] 1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.43 (s, 2H), 7.39 (s, 1H), 7.01 (s, 2H), 2.38 (s, 3H), 2.30 (t, 2H,J= 7.48 Hz), 2.21 (t, 2H,J= 7.04 Hz), 2.18 (s, 3H), 2.13 (s, 6H), 2.05 (s, 6H), 1.70 (q, 2H,J= 7.24 Hz); LCMS: m / z 491 [M+H] +

[0698] [Example 94] Preparation of N-(4-(3-(difluoromethyl)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide

[0699]

[0700] Step 1: Preparation of 4-(3-(difluoromethyl)-5-fluorophenyl)-3,5-dimethylisoxazole

[0701] 1-Bromo-3-(difluoromethyl)-5-fluorobenzene (0.5 g, 2.22 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (0.34 g, 2.44 mmol, 1.1 eq), Pd(dppf)Cl2 (0.08 g, 0.11 mmol, 0.05 eq), and cesium carbonate (1.08 g, 3.33 mmol, 1.5 eq) were mixed in dioxane (5 mL) and water (0.5 mL), stirred at 90 °C under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0% → 50%) to obtain 0.36 g (1.49 mmol, 67%) of the title compound.

[0702] Step 2: Preparation of N-(4-(3-(difluoromethyl)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide

[0703] 4-(Dimethylamino)-N-(4-hydroxy-3,5-dimethylphenyl)butanamide (0.1 g, 0.4 mmol, 1 eq) and 4-(3-fluoro-5-(trifluoromethyl)phenyl)-3,5-dimethylisoxazole (0.1 g, 0.4 mmol, 1 eq) were dissolved in N,N-dimethylformamide (3 mL), and cesium carbonate (0.2 g, 0.6 mmol, 1.5 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 0.14 g (0.31 mmol, 74%) of the title compound.

[0704] 1 H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 7.42 (s, 2H), 7.22 (s, 1H), 7.02 (t, 1H,J= 55.72 Hz), 6.95 (s, 1H), 6.85 (s, 1H), 2.38 (s, 3H), 2.30 (t, 2H,J= 7.48 Hz), 2.21 (t, 2H,J= 7.08 Hz), 2.19 (s, 3H), 2.12 (s, 6H), 2.05 (s, 6H), 1.71 (q, 2H,J= 7.2 Hz); LCMS: m / z 473 [M+H] +

[0705] [Example 95] Preparation of N-(4-(3-acetyl-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide

[0706]

[0707] Step 1: Preparation of 4-(3-(difluoromethyl)-5-fluorophenyl)-3,5-dimethylisoxazole

[0708] 1-(3-Bromo-5-fluorophenyl)ethanone (0.5 g, 2.30 mmol, 1 eq), (3,5-dimethylisoxazol-4-yl)boronic acid (0.36 g, 2.53 mmol, 1.1 eq), Pd(dppf)Cl2 (0.08 g, 0.12 mmol, 0.05 eq), and cesium carbonate (1.12 g, 3.45 mmol, 1.5 eq) were mixed in dioxane (5 mL) and water (0.5 mL), heated to 90 °C, stirred under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 0.38 g (1.62 mmol, 71%) of the title compound.

[0709] Step 2: Preparation of N-(4-(3-(difluoromethyl)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide

[0710] 4-(Dimethylamino)-N-(4-hydroxy-3,5-dimethylphenyl)butanamide (0.1 g, 0.4 mmol, 1 eq) and 4-(3-(difluoromethyl)-5-fluorophenyl)-3,5-dimethylisoxazole (0.1 g, 0.4 mmol, 1 eq) were dissolved in N,N-dimethylformamide (3 mL), and cesium carbonate (0.2 g, 0.6 mmol, 1.5 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 0.11 g (0.24 mmol, 59%) of the title compound.

[0711] 1 H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 7.60 (s, 1H), 7.42 (s, 2H), 7.16 (s, 1H), 7.06 (s, 1H), 2.58 (s, 3H), 2.40 (s, 3H), 2.32 (t,J= 7.4 Hz, 2H), 2.25 - 2.19 (m, 5H), 2.13 (s, 6H), 2.05 (s, 6H), 1.76 - 1.66 (m, 2H); LCMS: m / z 465 [M+H] +

[0712] [Example 96] Preparation of 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-hydroxyethyl)phenoxy)-3,5-dimethylphenyl)butanamide

[0713]

[0714] N-(4-(3-Acetyl-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide (0.05 g, 0.11 mmol, 1 eq) was dissolved in methanol (1 mL), sodium borohydride (8 mg, 0.22 mmol, 2 eq) was added at 0°C, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 0.03 g (0.06 mmol, 59%) of the title compound.

[0715] 1 H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.39 (s, 2H), 6.94 (s, 1H), 6.74 (s, 1H), 6.55 (s, 1H), 4.69 (q, 1H,J= 6.36 Hz), 2.31 (s, 3H), 2.29 (t, 2H,J= 7.48 Hz), 2.21 (t, 2H,J= 7.16 Hz), 2.17 (s, 3H), 2.12 (s, 6H), 2.05 (s, 6H), 1.71 (q, 2H,J= 7.28 Hz), 1.29 (d, 3H,J=6.4 Hz); LCMS: m / z 467 [M+H] +

[0716] [Example 97] Preparation of 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-fluoroethyl)phenoxy)-3,5-dimethylphenyl)butanamide

[0717]

[0718] 4-(Dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-hydroxyethyl)phenoxy)-3,5-dimethylphenyl)butanamide (15 mg, 0.03 mmol, 1 eq) was dissolved in dichloromethane (1 mL), and diethylaminosulfur trifluoride (0.02 mL, 0.16 mmol, 5 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 7 mg (0.015 mmol, 50%) of the title compound.

[0719] 1 H NMR (400 MHz, DMSO-d6) δ 9.85 (s, 1H), 7.41 (s, 2H), 7.02 (s, 1H), 6.76 (s, 1H), 6.67 (s, 1H), 5.72 (dq, 1H,J1 = 47.6 Hz,J2 = 6.4 Hz), 2.31 (s, 3H), 2.30 (t, 2H,J= 7.48 Hz), 2.20 (t, 2H,J= 7.16 Hz), 2.17 (s, 3H), 2.13 (s, 6H), 2.05 (s, 6H), 1.70 (q, 2H,J= 7.32 Hz), 1.56 (dd, 2H,J1 = 24.32 Hz,J2 = 6.4 Hz); LCMS: m / z 469 [M+H] +

[0720] [Example 98] Preparation of 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-hydroxypropan-2-yl)phenoxy)-3,5-dimethylphenyl)butanamide

[0721]

[0722] N-(4-(3-Acetyl-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide (34.6 mg, 0.075 mmol, 1 eq) was dissolved in tetrahydrofuran (1 mL), and 3.0 M methylmagnesium bromide (ether solution) (0.05 mL, 0.15 mmol, 2 eq) was slowly added to the reaction mixture at 0 °C and stirred for 20 min. Since the starting material remained, 3.0 M methylmagnesium bromide (ether solution) (0.05 mL, 0.15 mmol, 2 eq) was added to the reaction mixture and stirred at 0 °C for 1 h. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 4 mg (0.008 mmol, 11%) of the title compound.

[0723] 1 H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.39 (s, 2H), 7.02 (2, 1H), 6.93 (s, 1H), 6.48 (s, 1H), 5.05 (s, 1H), 2.35 (s, 3H), 2.29 (t, 2H,J= 7.52 Hz), 2.20 (t, 2H,J= 7.2 Hz), 2.16 (s, 3H), 2.12 (s, 6H), 2.05 (s, 6H), 1.70 (q, 2H,J= 7.12 Hz), 1.40 (s, 6H); LCMS: m / z 481 [M+H] +

[0724] [Example 99] Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-2-(dimethylamino)acetamide

[0725]

[0726] Step 1: Preparation of 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole

[0727] 1-Bromo-3-fluoro-5-nitrobenzene (5 g, 22.7 mmol), 3,5-dimethylisoxazole-4-boronic acid (3.2 g, 22.7 mmol), Pd(dppf)2Cl2 (1.66 g, 2.27 mmol), and cesium carbonate (9.25 g, 28.4 mmol) were mixed in dioxane (50 mL) and water (5 mL), heated to 90°C, stirred under argon gas for 20 hours, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate 0%→15%) to obtain 4.5 g (84%) of the title compound.

[0728] Step 2: Preparation of 4-(benzyloxy)-1-methyl-2-nitrobenzene

[0729] 4-Methyl-3-nitrophenol (20 g, 130.6 mmol) and benzyl bromide (23.27 mL, 195.9 mmol) were dissolved in N,N-dimethylformamide (260 mL), potassium carbonate (36.1 g, 261.2 mmol) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate 0%→30%) to obtain 30.8 g (97%) of the title compound.

[0730] Step 3: Preparation of 5-(benzyloxy)-2-methylaniline

[0731] 4-(Benzyloxy)-1-methyl-2-nitrobenzene (17 g, 69.9 mmol), zinc powder (91.4 g, 1.40 mol), and acetic acid (40 mL, 698.8 mmol) were mixed in tetrahydrofuran (350 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 12.9 g (87%) of the title compound without further purification.

[0732] Step 4: Preparation of N-(5-(benzyloxy)-2-methylphenyl)-2-(dimethylamino)acetamide

[0733] 5-(Benzyloxy)-2-methylaniline (0.54 g, 2.53 mmol) was dissolved in N,N-dimethylformamide (5 mL), and HATU (1.44 g, 3.80 mmol), diisopropylethylamine (0.66 mL, 3.80 mmol), and 2-(dimethylamino)acetic acid (261 mg, 2.53 mmol) were mixed and stirred at room temperature for 3 hours. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.44 g (59%) of the title compound.

[0734] Step 5: Preparation of 2-(dimethylamino)-N-(5-hydroxy-2-methylphenyl)acetamide

[0735] N-(5-(Benzyloxy)-2-methylphenyl)-2-(dimethylamino)acetamide (0.44 g, 1.49 mmol) was dissolved in methanol (3 mL), 10% Pd / C (10% wt) was added, and the mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure to obtain 0.27 g (89%) of the title compound without further purification.

[0736] Step 6: Preparation of 2-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)acetamide

[0737] 2-(Dimethylamino)-N-(5-hydroxy-2-methylphenyl)acetamide (0.27 g, 1.33 mmol) and 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole (0.31 g, 1.33 mmol) were dissolved in N,N-dimethylformamide (4.4 mL), and cesium carbonate (0.86 g, 2.66 mmol) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.20 g (36%) of the title compound.

[0738] Step 7: Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-2-(dimethylamino)acetamide

[0739] 2-(Dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)acetamide (0.20 g, 0.48 mmol), zinc powder (0.62 g, 9.57 mol), and acetic acid (0.27 mL, 4.78 mmol) were mixed in tetrahydrofuran (2.4 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→3%) to obtain 0.12 g (67%) of the title compound.

[0740] 1 H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 7.54 (d,J= 2.5 Hz, 1H), 7.21 (d,J= 8.3 Hz, 1H), 6.75 (dd,J= 8.2, 2.6 Hz, 1H), 6.28 (d,J= 1.7 Hz, 1H), 6.13 (d,J= 2.1 Hz, 1H), 6.09 (t,J= 1.9 Hz, 1H), 5.33 (s, 2H), 3.06 (s, 2H), 2.36 (s, 3H), 2.32 (s, 6H), 2.19 (s, 3H), 2.18 (s, 3H); LCMS: m / z 395 [M+H] +

[0741] [Example 100] Preparation of 2-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)acetamide

[0742]

[0743] Step 1: Preparation of 2-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)acetamide

[0744] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-2-(dimethylamino)acetamide (0.068 g, 0.17 mmol) was dissolved in pyridine (1 mL), and ethanesulfonyl chloride (20 μL, 0.21 mmol) was added. The mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain 0.042 g (51%) of the title compound.

[0745] 1 H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 9.37 (s, 1H), 7.60 (d,J= 2.6 Hz, 1H), 7.25 (d,J= 8.3 Hz, 1H), 6.95 (t,J= 1.8 Hz, 1H), 6.84 (t,J= 2.1 Hz, 1H), 6.80 (dd,J= 8.3, 2.6 Hz, 1H), 6.70 (t,J= 1.8 Hz, 1H), 3.15 (q,J= 7.3 Hz, 2H), 3.06 (s, 2H), 2.39 (s, 3H), 2.31 (s, 6H), 2.21 (s, 3H), 2.20 (s, 3H), 1.19 (t,J= 7.3 Hz, 3H); LCMS: m / z 489 [M+H] +

[0746] [Example 101] Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide

[0747]

[0748] Step 1: Preparation of N-(5-(benzyloxy)-2-methylphenyl)-4-(dimethylamino)butanamide

[0749] 5-(Benzyloxy)-2-methylaniline (2.2 g, 10.3 mmol) was dissolved in N,N-dimethylformamide (21 mL), and HATU (5.88 g, 15.4 mmol), diisopropylethylamine (2.7 mL, 15.4 mmol), and 4-(dimethylamino)butanoic acid hydrochloride (1.73 g, 10.3 mmol) were mixed and stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. 8.9 g of the title compound was obtained without further purification.

[0750] Step 2: Preparation of 4-(dimethylamino)-N-(5-hydroxy-2-methylphenyl)butanamide

[0751] N-(5-(Benzyloxy)-2-methylphenyl)-4-(dimethylamino)butanamide (8.9 g) was dissolved in methanol (20 mL), and 10% Pd / C (10% wt) was mixed. The mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite, washed with methanol, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→16%) to give 0.95 g (39% in two steps) of the title compound.

[0752] Step 3: Preparation of 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)butanamide

[0753] 4-(Dimethylamino)-N-(5-hydroxy-2-methylphenyl)butanamide (0.95 g, 4.02 mmol) and 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole (0.95 g, 4.02 mmol) were dissolved in N,N-dimethylformamide (13.4 mL), and cesium carbonate (2.62 g, 8.04 mmol) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.58 g (32%) of the title compound.

[0754] Step 4: Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide

[0755] 4-(Dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)butanamide (0.58 g, 1.28 mmol), zinc powder (1.68 g, 25.74 mol), and acetic acid (0.73 mL, 12.87 mmol) were mixed in tetrahydrofuran (6.4 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→3%) to obtain 0.39 g (73%) of the title compound.

[0756] 1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.22 (s, 1H), 7.18 (d,J= 8.0 Hz, 1H), 6.76 (d,J= 8.0 Hz, 1H), 6.27 (s, 1H), 6.12 (s, 1H), 6.09 (s, 1H), 5.35 (s, 2H), 3.04 (s, 3H), 2.50 (s, 3H), 2.35 (m, 2H), 2.22 (m, 8H), 2.11 (s, 6H), 2.19 (s, 3H), 2.12 (s, 6H), 1.69 (p,J= 7.3 Hz, 2H); LCMS: m / z 424 [M+H] +

[0757] [Examples 102 to 104]

[0758]

[0759] Step 1: Sulfonamide coupling

[0760] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide (0.07 g, 0.16 mmol) was dissolved in pyridine (1 mL), and each sulfonyl chloride (1 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain the title compound in Table 9 below (yield: 27∼50%).

[0761] [Table 9]

[0762]

[0763] [Examples 105 to 107]

[0764]

[0765] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide (0.07 g, 0.16 mmol) was dissolved in N,N-dimethylformamide (1 mL), and HATU (0.094 g, 0.24 mmol), diisopropylethylamine (0.043 mL, 0.24 mmol), and each carboxylic acid (0.19 mmol) were mixed and stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain the title compound in Table 10 below.

[0766] [Table 10]

[0767]

[0768] [Example 108] Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0769]

[0770] Step 1: Preparation of N-(5-(benzyloxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0771] 5-(Benzyloxy)-2-methylaniline (2 g, 9.37 mmol) was dissolved in N,N-dimethylformamide (18.7 mL), and HATU (5.34 g, 14 mmol), diisopropylethylamine (2.4 mL, 14 mmol), and 3-(piperidin-1-yl)propanoic acid (1.47 g, 9.37 mmol) were mixed and stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 2.08 g (63%) of the title compound.

[0772] Step 2: Preparation of N-(5-hydroxy-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0773] N-(5-(Benzyloxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide (2.08 g, 5.90 mmol) was dissolved in methanol (11.8 mL), and 10% Pd / C (10% wt) was mixed. The mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→20%) to obtain 1.42 g (92%) of the title compound.

[0774] Step 3: Preparation of N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0775] N-(5-Hydroxy-2-methylphenyl)-3-(piperidin-1-yl)propanamide (1.42 g, 5.43 mmol) and 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole (1.28 g, 5.43 mmol) were dissolved in N,N-dimethylformamide (18.1 mL), and cesium carbonate (3.54 g, 10.8 mmol) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.98 g (38%) of the title compound.

[0776] Step 4: Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0777] N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide (0.98 g, 2.06 mmol), zinc powder (2.70 g, 41.30 mol), and acetic acid (1.18 mL, 20.65 mmol) were mixed in tetrahydrofuran (10.3 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→3%) to obtain 0.75 g (81%) of the title compound.

[0778] 1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.50 (d,J= 2.6 Hz, 1H), 7.18 (d,J= 8.3 Hz, 1H), 6.73 (dd,J= 8.2, 2.6 Hz, 1H), 6.27 (t,J= 1.7 Hz, 1H), 6.16 - 6.04 (m, 2H), 5.33 (s, 2H), 2.57 (t,J= 6.4 Hz, 2H), 2.44 - 2.38 (m, 6H), 2.36 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 1.59 - 1.30 (m, 6H); LCMS m / z 450 [M+H] +

[0779] [Examples 109 to 110]

[0780]

[0781] Step 1: Sulfonamide coupling

[0782] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide (0.07 g, 0.15 mmol) was dissolved in pyridine (1 mL), and each sulfonyl chloride (1 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain the title compound in Table 11 below (yield: 37∼70%).

[0783] [Table 11]

[0784]

[0785] [Example 111] Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-morpholinopropanamide

[0786]

[0787] Step 1: Preparation of N-(5-(benzyloxy)-2-methylphenyl)-3-morpholinopropanamide

[0788] 5-(Benzyloxy)-2-methylaniline (1 g, 4.68 mmol) was dissolved in N,N-dimethylformamide (9.3 mL), and HATU (2.67 g, 7.03 mmol), diisopropylethylamine (1.2 mL, 7.03 mmol), and 3-morpholinopropanoic acid (0.74 g, 4.68 mmol) were mixed and stirred at room temperature for 3 hours. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 1.19 g (72%) of the title compound.

[0789] Step 2: Preparation of N-(5-hydroxy-2-methylphenyl)-3-morpholinopropanamide

[0790] N-(5-(Benzyloxy)-2-methylphenyl)-3-morpholinopropanamide (1.19 g, 3.37 mmol) was dissolved in methanol (6.7 mL), and 10% Pd / C (10% wt) was mixed. The mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→20%) to obtain 0.73 g (82%) of the title compound.

[0791] Step 3: Preparation of N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-morpholinopropanamide

[0792] N-(5-Hydroxy-2-methylphenyl)-3-morpholinopropanamide (0.73 g, 2.76 mmol) and 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole (0.65 g, 2.76 mmol) were dissolved in N,N-dimethylformamide (9.2 mL), and cesium carbonate (1.80 g, 5.53 mmol) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.43 g (33%) of the title compound.

[0793] Step 4: Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-morpholinopropanamide

[0794] N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-morpholinopropanamide (0.43 g, 0.91 mmol), zinc powder (1.19 g, 18.27 mol), and acetic acid (0.52 mL, 9.13 mmol) were mixed in tetrahydrofuran (4.5 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→5%) to obtain 0.34 g (83%) of the title compound.

[0795] 1H NMR (400 MHz, DMSO-d6) δ 9.54 (s, 1H), 7.42 (d,J= 2.6 Hz, 1H), 7.19 (d,J= 8.3 Hz, 1H), 6.74 (dd,J= 8.3, 2.6 Hz, 1H), 6.27 (t,J= 1.7 Hz, 1H), 6.16 - 6.04 (m, 2H), 5.34 (s, 2H), 3.59 (t,J= 4.7 Hz, 4H), 2.61 (t,J= 6.5 Hz, 2H), 2.56 - 2.47 (m, 2H), 2.47 - 2.40 (m, 4H), 2.36 (s, 3H), 2.21 (s, 3H), 2.18 (s, 3H); LCMS m / z 450 [M+H] +

[0796] [Example 112] Preparation of N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-morpholinopropanamide

[0797]

[0798] Step 1: Preparation of N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-morpholinopropanamide

[0799] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-morpholinopropanamide (0.070 g, 0.15 mmol) was dissolved in pyridine (1 mL), and ethanesulfonyl chloride (20 μL, 0.21 mmol) was added. The mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain 0.035 g (45%) of the title compound.

[0800] 1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 9.57 (s, 1H), 7.50 (d,J= 2.6 Hz, 1H), 7.23 (d,J= 8.3 Hz, 1H), 6.94 (d,J= 1.8 Hz, 1H), 6.83 (t,J= 2.1 Hz, 1H), 6.79 (dd,J= 8.2, 2.6 Hz, 1H), 6.70 (t,J= 1.9 Hz, 1H), 3.59 (t,J= 4.7 Hz, 4H), 3.15 (q,J= 7.3 Hz, 2H), 2.61 (t,J= 6.6 Hz, 2H), 2.56 - 2.46 (m, 2H), 2.46 - 2.41 (m, 4H), 2.39 (s, 3H), 2.24 (s, 3H), 2.20 (s, 3H), 1.19 (t,J= 7.3 Hz, 3H); LCMS m / z 545 [M+H] +

[0801] [Example 113] Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide

[0802]

[0803] Step 1: N-(5-(benzyloxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide

[0804] 5-(Benzyloxy)-2-methylaniline (1 g, 4.68 mmol) was dissolved in N,N-dimethylformamide (9.3 mL), and HATU (2.67 g, 7.03 mmol), diisopropylethylamine (1.2 mL, 7.03 mmol), and 3-(1H-imidazol-1-yl)propanoic acid (0.65 g, 4.68 mmol) were mixed and stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 1.39 g (89%) of the title compound.

[0805] Step 2: N-(5-hydroxy-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide

[0806] N-(5-(Benzyloxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide (1.39 g, 4.17 mmol) was dissolved in methanol (8.3 mL), and 10% Pd / C (10% wt) was mixed. The mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→20%) to obtain 0.92 g (90%) of the title compound.

[0807] Step 3: N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide

[0808] N-(5-Hydroxy-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide (0.92 g, 3.75 mmol) and 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole (0.88 g, 3.75 mmol) were dissolved in N,N-dimethylformamide (12.5 mL), and cesium carbonate (2.44 g, 7.51 mmol) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.60 g (35%) of the title compound.

[0809] Step 4: N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide

[0810] N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide (0.60 g, 1.31 mmol), zinc powder (1.71 g, 26.28 mol), and acetic acid (0.75 mL, 13.14 mmol) were mixed in tetrahydrofuran (6.5 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→3%) to obtain 0.49 g (87%) of the title compound.

[0811] 1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 7.59 (d,J= 1.2 Hz, 1H), 7.23 - 7.05 (m, 3H), 6.86 (t,J= 1.1 Hz, 1H), 6.77 (dd,J= 8.3, 2.6 Hz, 1H), 6.29 (t,J= 1.7 Hz, 1H), 6.17 - 6.04 (m, 2H), 5.35 (s, 2H), 4.25 (t,J= 6.6 Hz, 2H), 2.83 (t,J= 6.7 Hz, 2H), 2.37 (s, 3H), 2.19 (s, 3H), 2.09 (s, 3H); LCMS m / z 432 [M+H] +

[0812] [Examples 114 to 115]

[0813]

[0814] Step 1: Sulfonamide coupling

[0815] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide (0.07 g, 0.16 mmol) was dissolved in pyridine (1 mL), and each sulfonyl chloride (1 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain the title compound in Table 12 below (yield: 32∼69%).

[0816] [Table 12]

[0817]

[0818] [Example 116] Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-methoxypropanamide

[0819]

[0820] Step 1: Preparation of N-(5-(benzyloxy)-2-methylphenyl)-3-methoxypropanamide

[0821] 5-(Benzyloxy)-2-methylaniline (1 g, 4.68 mmol) was dissolved in N,N-dimethylformamide (9.3 mL), and HATU (2.67 g, 7.03 mmol), diisopropylethylamine (1.2 mL, 7.03 mmol), and 3-methoxypropanoic acid (0.44 mL, 4.68 mmol) were mixed and stirred at room temperature for 3 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 1.22 g (87%) of the title compound.

[0822] Step 2: Preparation of N-(5-hydroxy-2-methylphenyl)-3-methoxypropanamide

[0823] N-(5-(Benzyloxy)-2-methylphenyl)-3-methoxypropanamide (1.22 g, 4.07 mmol) was dissolved in methanol (8.1 mL), and 10% Pd / C (10% wt) was mixed. The mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→20%) to obtain 0.64 g (76%) of the title compound.

[0824] Step 3: Preparation of N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-methoxypropanamide

[0825] N-(5-Hydroxy-2-methylphenyl)-3-methoxypropanamide (0.64 g, 3.10 mmol) and 4-(3-fluoro-5-nitrophenyl)-3,5-dimethylisoxazole (0.73 g, 3.10 mmol) were dissolved in N,N-dimethylformamide (10.3 mL), and cesium carbonate (2.02 g, 6.20 mmol) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→10%) to obtain 0.50 g (38%) of the title compound.

[0826] Step 4: Preparation of N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-methoxypropanamide

[0827] N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-nitrophenoxy)-2-methylphenyl)-3-methoxypropanamide (0.50 g, 1.17 mmol), zinc powder (1.54 g, 23.56 mol), and acetic acid (0.67 mL, 11.78 mmol) were mixed in tetrahydrofuran (5.8 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→3%) to obtain 0.38 g (82%) of the title compound.

[0828] 1H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 7.26 (d,J= 2.6 Hz, 1H), 7.19 (d,J= 8.3 Hz, 1H), 6.76 (dd,J= 8.2, 2.6 Hz, 1H), 6.27 (t,J= 1.7 Hz, 1H), 6.17 - 6.05 (m, 2H), 5.34 (s, 2H), 3.60 (t,J= 6.2 Hz, 2H), 3.25 (s, 3H), 2.57 (t,J= 6.2 Hz, 2H), 2.36 (s, 3H), 2.18 (s, 6H); LCMS m / z 396 [M+H] +

[0829] [Examples 117 to 118]

[0830]

[0831] Step 1: Sulfonamide coupling

[0832] N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-methoxypropanamide (0.07 g, 0.17 mmol) was dissolved in pyridine (1 mL), and each sulfonyl chloride (1 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain the title compound in Table 13 below. (yield: 45∼51%).

[0833] [Table 13]

[0834]

[0835] [Example 119] Preparation of 4-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0836]

[0837] Step 1: Preparation of ethyl 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

[0838] 4-Bromo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (50 g, 131 mmol, 1 eq) was dissolved in tetrahydrofuran (2.4 L) and cooled to -65°C. Lithium diisopropylamide tetrahydrofuran solution (2 M, 98.4 mL, 1.5 eq) was slowly added to the reaction mixture at -65°C and stirred for 1 h 30 min. Ethyl carbonochloridate (20.9 g, 193 mmol, 18.4 mL, 1.47 eq) was dissolved in tetrahydrofuran (100 mL), slowly added to the reaction mixture at -65°C and stirred for 2 h. LCMS revealed that 4-bromo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (RT = 1.305 mins) remained, and the mass value of the title compound (RT = 1.448 mins) was confirmed. Saturated aqueous ammonium chloride solution (2.5 L) was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (2 L × 2). The organic layer was washed with water (3 L) and saturated aqueous sodium chloride solution (3 L), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Phenomenex luna c18 250 mm x 100 mm x 10 μm; mobile phase: [water(FA)-ACN]; gradient: 45%-75% B over 24 mins) and concentrated under reduced pressure to remove acetonitrile. The residual aqueous solution was lyophilized to obtain the title compound (50 g, 108 mmol, 33.6% yield, 97.5% purity) as an off-white solid.

[0839] Step 2: Preparation of 4-bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[0840] Ethyl 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (1 g, 2.13 mmol, 1 eq) was dissolved in tetrahydrofuran, and lithium hydroxide (128 mg, 5.33 mmol, 2.5 eq) was mixed and stirred at 40°C for 18 hours. The reaction mixture was cooled to room temperature, water was added, and then extracted with ethyl acetate to remove byproducts. After acidification, the reaction mixture was extracted with ethyl acetate and concentrated under reduced pressure to obtain the title compound (450 mg, 1.57 mmol, 77% yield).

[0841] Step 3: Preparation of 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0842] 4-Bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (450 mg, 1.57 mmol, 1 eq) was dissolved in N,N-dimethylformamide, and HATU (894 mg, 2.35 mmol, 1.5 eq), diisopropylethylamine (0.41 mL, 2.35 mmol, 1.5 eq), and ethylamine (0.10 mL, 1.57 mmol, 1 eq) were mixed and stirred at room temperature for 18 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (480 mg, 1.53 mmol, 97% yield).

[0843] Step 4: Preparation of 2-(3-bromo-5-methylphenoxy)-1,3-dimethyl-5-nitrobenzene

[0844] 3-Bromo-5-methylphenol (1.84 g, 9.8 mmol) and 2-fluoro-1,3-dimethyl-5-nitrobenzene (1.83 g, 10.8 mmol) were dissolved in N,N-dimethylformamide (30 mL), cesium carbonate (4 g, 12.2 mmol) was added, and the mixture was stirred at room temperature overnight. Water (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 3 g (8.92 mmol, 91%) of the title compound.

[0845] Step 5: Preparation of 2-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0846] 2-(3-Bromo-5-methylphenoxy)-1,3-dimethyl-5-nitrobenzene (0.35 g, 1.04 mmol, 1 eq), bis(pinacolato)diborane (0.25 g, 1.04 mmol), potassium acetate (0.12 g, 1.25 mmol), Pd2(dba)3 (0.095 g, 0.104 mmol), and x-Phos (2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl) (0.05 g, 0.104 mmol) were mixed in dioxane (5 mL), heated to 90°C, stirred under argon gas for 20 h, and then cooled to room temperature. Water (10 mL) and ethyl acetate (20 mL) were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 0.36 g (0.94 mmol, 90%) of the title compound.

[0847] Step 6: Preparation of 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0848] 2-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.3 g, 0.78 mmol, 1 eq), 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (0.246 g, 0.78 mmol, 1 eq), Pd(dppf)2Cl2 (0.057 g, 0.078 mmol, 0.1 eq), and cesium carbonate (0.38 g, 1.17 mmol) were mixed in dioxane (5 mL) and water (0.5 mL), heated to 90°C, stirred under argon gas for 20 h, and then cooled to room temperature. Water (10 mL) and ethyl acetate (10 mL) were added to the reaction mixture, the layers were separated, the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 0.05 g (0.11 mmol, 14%) of the title compound.

[0849] Step 7: Preparation of 4-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0850] 4-(3-(2,6-dimethyl-4-nitrophenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (50 mg, 0.11 mmol, 1 eq), zinc powder (144 mg, 2.2 mmol, 20 eq), and acetic acid (0.06 mL, 1.1 mmol, 10 eq) were mixed in tetrahydrofuran (3 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 44 mg (0.1 mmol, 91%) of the title compound.

[0851] LCMS: m / z 446 [M+H] +

[0852] [Examples 120 to 139]

[0853]

[0854] Step 1: Amide coupling

[0855] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), 4-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 14 below (yield: 60-90%).

[0856] [Table 14]

[0857]

[0858]

[0859]

[0860] [Example 140] Preparation of 4-(3-(2,6-dimethyl-4-(pyrrolidine-1-carboxamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0861]

[0862] Step 1: Preparation of phenyl(4-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate

[0863] 4-(3-(4-Amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (100 mg, 0.22 mmol, 1 eq) was dissolved in tetrahydrofuran, and phenyl chloroformate (0.03 mL, 0.25 mmol, 1.1 eq) and triethylamine (0.05 mL, 0.33 mmol, 1.5 eq) were mixed at 0°C, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 99 mg (80%) of the title compound.

[0864] Step 2: Preparation of 4-(3-(2,6-dimethyl-4-(pyrrolidine-1-carboxamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0865] Phenyl(4-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate (99 mg, 0.18 mmol, 1 eq) was dissolved in tetrahydrofuran, and pyrrolidine (0.02 mL, 0.23 mmol, 1.25 eq) and triethylamine (0.04 mL, 0.27 mmol, 1.5 eq) were mixed and stirred at 50°C for 18 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 51 mg (52%) of the title compound.

[0866] 1 H NMR (400 MHz, CD3OD) δ 7.25 (s, 1H), 7.19 (s, 2H), 7.08 (s, 1H), 7.06 (s, 1H), 6.85 (s, 1H), 6.51 (s, 1H), 3.68 (s, 3H), 3.48 - 3.39 (m, 6H), 2.34 (s, 3H), 2.12 (s, 6H), 1.98 (t,J= 6.6 Hz, 4H), 1.23 (t,J= 7.3 Hz, 3H); LCMS: m / z 543 [M+H] +

[0867] [Example 141] Preparation of 4-(3-amino-5-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0868]

[0869] Step 1: Preparation of 2-(benzyloxy)-1,3-dimethyl-5-nitrobenzene

[0870] 2,6-Dimethyl-4-nitrophenol (1 g, 5.99 mmol) and benzyl bromide (0.85 mL, 7.18 mmol) were dissolved in N,N-dimethylformamide (30 mL), and calcium carbonate (1.24 g, 8.99 mmol, 1.5 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 1.49 g (5.81 mmol, 97%) of the title compound.

[0871] Step 2: Preparation of 4-(benzyloxy)-3,5-dimethylaniline

[0872] 2-(Benzyloxy)-1,3-dimethyl-5-nitrobenzene (1.49 g, 5.81 mmol, 1 eq), zinc powder (7.6 g, 116.2 mmol, 20 eq), and acetic acid (3.33 mL, 58.1 mmol, 10 eq) were mixed in tetrahydrofuran (20 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 1.19 g (5.23 mmol, 90%) of the title compound without any further purification.

[0873] Step 3: Preparation of N-(4-(benzyloxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide

[0874] 4-(Benzyloxy)-3,5-dimethylaniline (1.19 g, 5.23 mmol, 1 eq) was dissolved in N,N-dimethylformamide, and HATU (2.98 g, 7.85 mmol, 1.5 eq), diisopropylethylamine (1.37 mL, 7.85 mmol, 1.5 eq), and 2-(dimethylamino)acetic acid (529 mg, 5.23 mmol, 1 eq) were mixed and stirred at room temperature for 18 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (1.32 g, 4.23 mmol, 81% yield).

[0875] Step 4: Preparation of 2-(dimethylamino)-N-(4-hydroxy-3,5-dimethylphenyl)acetamide

[0876] N-(4-(Benzyloxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide (1.32 g, 4.23 mmol) was dissolved in methanol (20 mL), and 10% Pd / C (132 mg, 10% wt) was mixed, and the mixture was stirred at room temperature under hydrogen gas for 20 hours. The reaction mixture was filtered through Celite and washed with methanol, and the filtrate was concentrated under reduced pressure to obtain 893 mg (4.02 mmol, 95%) of the title compound without further purification.

[0877] Step 5: Preparation of N-(4-(3-bromo-5-nitrophenoxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide

[0878] 2-(Dimethylamino)-N-(4-hydroxy-3,5-dimethylphenyl)acetamide (893 mg, 4.02 mmol, 1 eq) and 1-bromo-3-fluoro-5-nitrobenzene (973 mg, 4.42 mmol) were dissolved in N,N-dimethylformamide (14 mL), and cesium carbonate (1.96 g, 6.03 mmol, 1.5 eq) was mixed, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 1.55 g (3.68 mmol, 91%) of the title compound.

[0879] Step 6: Preparation of N-(3,5-dimethyl-4-(3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)phenyl)-2-(dimethylamino)acetamide

[0880] N-(4-(3-Bromo-5-nitrophenoxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide (1.55 g, 3.68 mmol, 1 eq), bis(pinacolato)diborane (0.93 g, 3.68 mmol), potassium acetate (0.43 g, 3.68 mmol), Pd2(dba)3 (0.34 g, 0.37 mmol), and x-Phos (0.18 g, 0.37 mmol) were mixed in dioxane (15 mL), heated to 90 °C, stirred under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.43 g (3.05 mmol, 83%) of the title compound.

[0881] Step 7: Preparation of 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-nitrophenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0882] N-(3,5-dimethyl-4-(3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)phenyl)-2-(dimethylamino)acetamide (1.43 g, 3.05 mmol, 1 eq), 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (0.96 g, 3.05 mmol, 1 eq), Pd(dppf)2Cl2 (0.23 g, 0.31 mmol, 0.1 eq) and cesium carbonate (1.49 g, 4.58 mmol) were mixed in dioxane (10 mL) and water (1 mL), heated to 90°C and stirred for 20 h under argon gas. Cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 0.88 g (1.57 mmol, 51%) of the title compound.

[0883] Step 8: Preparation of 4-(3-amino-5-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0884] 4-(3-(4-(2-(Dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-nitrophenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (500 mg, 0.89 mmol, 1 eq), zinc powder (1.17 g, 17.84 mmol, 20 eq), and acetic acid (0.51 mL, 8.9 mmol, 10 eq) were mixed in tetrahydrofuran (10 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous solution of sodium bicarbonate were added to separate the layers, and the organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 414 mg (0.78 mmol, 88%) of the title compound without further purification.

[0885] 1 H NMR (400 MHz, DMSO-d6) δ 12.31 (s, 1H), 10.48 (s, 1H), 8.39 (t,J= 5.3 Hz, 1H), 7.37 (s, 2H), 7.33 (s, 1H), 6.98 (d,J= 2.2 Hz, 1H), 6.57 (s, 1H), 6.33 (s, 1H), 5.97 (s, 1H), 4.11 (s, 2H), 3.56 (s, 3H), 3.36 - 3.22 (m, 2H), 2.88 (s, 6H), 2.12 (s, 6H), 1.14 (t,J=7.2 Hz, 3H); LCMS: m / z 532 [M+H] +

[0886] [Example 142] Preparation of 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-(methylsulfonamido)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0887]

[0888] Step 1: Preparation of 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-(methylsulfonamido)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0889] 4-(3-Amino-5-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (0.05 g, 0.09 mmol) was dissolved in pyridine (1 mL), 1-methanesulfonyl chloride (8 μL, 0.11 mmol) was added, and the mixture was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain 0.03 g (56%) of the title compound.

[0890] 1 H NMR (400 MHz, DMSO-d6) δ 12.37 (s, 1H), 9.85 (s, 1H), 9.64 (s, 1H), 8.37 (t,J= 5.3 Hz, 1H), 7.48 (s, 2H), 7.41 (s, 1H), 7.09 (t,J= 1.7 Hz, 1H), 6.97 (s, 1H), 6.77 (t,J= 1.9 Hz, 1H), 6.55 (t,J= 2.2 Hz, 1H), 3.57 (s, 3H), 3.31 - 3.21 (m, 2H), 3.05 (s, 2H), 3.00 (s, 3H), 2.28 (s, 6H), 2.09 (s, 6H), 1.14 (t,J= 7.2 Hz, 3H); LCMS: m / z 610 [M+H] +

[0891] [Examples 143 to 180]

[0892]

[0893] Step 1: Preparation of 4-bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[0894] Methyl 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (1 g, 2.20 mmol, 1 eq) was dissolved in tetrahydrofuran and water, and sodium hydroxide (264 mg, 3.19 mmol, 3 eq) was mixed, heated to 50°C, and stirred for 3 hours. The mass of the title compound was confirmed by LCMS. The pH of the reaction mixture was adjusted to 3 with 1 N hydrochloric acid, water (10 mL) was added, and ethyl acetate (10 mL x 3) was extracted. The organic layer was washed with a saturated aqueous sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 550 mg (87%) of the title compound.

[0895] Step 2: Amide coupling

[0896] 4-Bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and each amine (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the carboxamide compound (yield: 60-90%).

[0897] Step 3: Chan-Lam reaction for dimethyl ether synthesis

[0898] 4-Fluoro(or chloro)-2,6-dimethylphenol (1 eq) was dissolved in dichloromethane (10 mL), and (3-bromo-5-methylphenyl)boronic acid (2 eq), copper acetate (1 eq), and triethylamine (5 eq) were mixed and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Water (100 mL) and dichloromethane (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain a bromophenoxy compound (yield: 3-25%).

[0899] Step 4: Synthesis of pinacol borane

[0900] The bromophenoxy compound (1 eq) obtained in step 3, bis(pinacolato)diborane (2 eq), potassium acetate (2 eq), Pd2(dba)3 (0.05 eq), and x-Phos (0.05 eq) were mixed in dioxane, heated to 90°C, stirred under argon gas for 20 hours, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (yield: 53-75%).

[0901] Step 5: Suzuki Cross Coupling

[0902] Each of the 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamides obtained in Step 2 (1 eq), 2-(3-(4-X-2,6-dimethylphenoxy)-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1 eq), Pd(dppf)2Cl2 (0.1 eq) and cesium carbonate (1.5 eq) obtained in Step 4 were mixed in dioxane and water, heated to 90°C, stirred under argon gas for 20 hours and cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain the title compound in Table 15 below (yield: 55-83%).

[0903] [Table 15]

[0904]

[0905]

[0906]

[0907]

[0908]

[0909]

[0910]

[0911] [Example 181] Preparation of 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[0912]

[0913] Step 1: Preparation of N'-acetyl-4-bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbohydrazide

[0914] 4-Bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (200 mg, 0.70 mmol, 1 eq) was dissolved in N,N-dimethylformamide, and HATU (397 mg, 1.04 mmol, 1.5 eq), diisopropylethylamine (0.18 mL, 1.04 mmol, 1.5 eq), and acetohydrazide (52 mg, 0.70 mmol, 1 eq) were mixed and stirred at room temperature for 18 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 110 mg (45%) of the title compound.

[0915] Step 2: Preparation of 4-bromo-6-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[0916] N'-Acetyl-4-bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbohydrazide (100 mg) was dissolved in acetonitrile, phosphoryl chloride was added, heated to 50°C, and stirred for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 35 mg (37%) of the title compound.

[0917] Step 3: Preparation of 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[0918] 2-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxyborolane (40 mg, 0.11 mmol, 1 eq), 4-bromo-6-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (35 mg, 0.11 mmol, 1 eq), Pd(dppf)2Cl2 (8 mg, 0.011 mmol, 0.1 eq) and cesium carbonate (54 mg, 0.17 mmol, 1.5 eq) were mixed in dioxane and water, stirred at 90°C under argon gas for 20 hours and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 25 mg (54%) of the title compound.

[0919] 1 H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 7.48 (s, 1H), 7.28 (s, 2H), 7.09 (s, 1H), 6.83 (s, 1H), 6.75 (s, 1H), 6.59 (s, 1H), 3.58 (s, 3H), 2.61 (s, 3H), 2.34 (s, 3H), 2.12 (s, 6H); LCMS: m / z 476 [M+H] +

[0920] [Example 182] Preparation of N-ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0921]

[0922] Step 1: Preparation of 2-(3-bromo-5-(trifluoromethyl)phenoxy)-5-fluoro-1,3-dimethylbenzene

[0923] 4-Fluoro-2,6-dimethylphenol (317 mg, 2.26 mmol, 1 eq) and 1-bromo-3-fluoro-5-(trifluoromethyl)benzene (660 mg, 2.71 mmol, 1.2 eq) were dissolved in N,N-dimethylformamide (7.5 mL), and cesium carbonate (1.47 g, 4.52 mmol, 2 eq) was mixed, and the mixture was stirred at room temperature overnight. Water (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 597 mg (87%) of the title compound.

[0924] Step 2: Preparation of 2-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0925] 2-(3-Bromo-5-(trifluoromethyl)phenoxy)-5-fluoro-1,3-dimethylbenzene (310 mg, 2.98 mmol, 1 eq), Pd(dppf)Cl2.CH2Cl2 (70 mg, 0.085 mmol, 0.1 eq), potassium acetate (250 mg, 2.55 mmol, 3 eq) and bis(pinacolato)diborane (432 mg, 1.70 mmol, 2 eq) were dissolved in dioxane, and the gas in the reaction mixture was removed three times using nitrogen gas, and then heated to 95°C and stirred for 16 h under nitrogen gas. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1, R1 R f = 0.5, P1 R f= 0.4) was confirmed that reactant 1 (2-(3-bromo-5-(trifluoromethyl)phenoxy)-5-fluoro-1,3-dimethylbenzene) was completely consumed and a new spot was generated. According to thin layer chromatography, the reaction proceeded cleanly. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 100: 1, petroleum ether: ethyl acetate = 20: 1, P1: R f = 0.4) was purified to obtain 244 mg (64%) of the title compound.

[0926] Step 3: Preparation of N-ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0927] 2-(3-(4-Fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (30 mg, 0.073 mmol, 1 eq), 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (23 mg, 0.073 mmol, 1 eq), Pd(dppf)2Cl2 (5.3 mg, 0.0073 mmol, 0.1 eq) and cesium carbonate (36 mg, 0.11 mmol, 1.5 eq) were mixed in dioxane and water, heated to 90°C, stirred under argon gas for 20 hours and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 15 mg (39%) of the title compound.

[0928] 1H NMR (400 MHz, CD3OD) δ 7.56 (m, 1H), 7.40 (s, 1H), 7.35 (m, 1H), 7.04 (s, 1H), 6.97 (d,J= 8.9 Hz, 2H), 6.89 (m, 1H), 3.71 (s, 3H), 3.49 - 3.40 (m, 2H), 2.19 (s, 6H), 1.25 (m, 3H); LCMS: m / z 502 [M+H] +

[0929] [Example 183] Preparation of 4-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0930]

[0931] Step 1: Preparation of 2-(3,5-dibromophenoxy)-5-fluoro-1,3-dimethylbenzene

[0932] 4-Fluoro-2,6-dimethylphenol (849 mg, 6.06 mmol, 2 eq) and 1,3-dibromo-5-fluorobenzene (769 mg, 3.03 mmol, 1 eq) were dissolved in N,N-dimethylformamide (20 mL), and cesium carbonate (1.97 g, 6.06 mmol, 2 eq) was mixed and stirred at room temperature overnight. Water (100 mL) and ethyl acetate (100 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 1057 mg (93%) of the title compound.

[0933] Step 2: Preparation of 2-(3-bromo-5-cyclopropylphenoxy)-5-fluoro-1,3-dimethylbenzene

[0934] 2-(3,5-Dibromophenoxy)-5-fluoro-1,3-dimethylbenzene (62 mg, 0.17 mmol, 1 eq), cyclopropylboronic acid (14 mg, 0.17 mmol, 1 eq), Pd(dppf)Cl2 (12 mg, 0.017 mmol, 0.1 eq), and cesium carbonate (83 mg, 0.26 mmol, 1.5 eq) were mixed in dioxane and water, heated to 90°C, stirred under argon gas for 20 hours, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 15 mg (28%) of the title compound.

[0935] Step 3: Preparation of 2-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0936] 2-(3-Bromo-5-cyclopropylphenoxy)-5-fluoro-1,3-dimethylbenzene (105 mg, 0.31 mmol, 1 eq), Pd(dppf)Cl2.CH2Cl2 (25 mg, 0.031 mmol, 0.1 eq), potassium acetate (91 mg, 0.93 mmol, 3 eq) and bis(pinacolato)diborane (159 mg, 0.63 mmol, 2 eq) were dissolved in dioxane, and the gas in the reaction mixture was removed three times using nitrogen gas, heated to 95°C and stirred for 16 h under nitrogen gas. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1, R1 R f = 0.5, P1 R f= 0.4) was confirmed that the reactant (2-(3-bromo-5-cyclopropylphenoxy)-5-fluoro-1,3-dimethylbenzene) was completely consumed and a new spot was generated. According to thin layer chromatography, the reaction proceeded cleanly. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 100: 1, petroleum ether: ethyl acetate = 20: 1, P1: R f = 0.4) was purified to obtain 53 mg (44%) of the title compound.

[0937] Step 4: Preparation of 4-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0938] 2-(3-Cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (11.6 mg, 0.03 mmol, 1 eq), 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (9.5 mg, 0.03 mmol, 1 eq), Pd(dppf)2Cl2 (2.2 mg, 0.003 mmol, 0.1 eq) and cesium carbonate (14.7 mg, 0.045 mmol, 1.5 eq) were mixed in dioxane and water, heated to 90°C, stirred under argon gas for 20 hours and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 2.1 mg (13%) of the title compound.

[0939] 1H NMR (400 MHz, CD3OD) δ 7.13 (s, 1H), 6.92 (s, 1H), 6.87 (m, 1H), 6.79 (d,J= 8.9 Hz, 2H), 6.72 - 6.66 (m, 1H), 6.29 - 6.26 (m, 1H), 3.58 (s, 3H), 3.32 (q,J= 7.3 Hz, 2H), 2.05 (s, 6H), 1.85 - 1.79 (m, 1H), 1.14 (m, 3H), 0.87 (m, 2H), 0.60 - 0.53 (m, 2H); LCMS: m / z 475 [M+H] +

[0940] [Example 184] Preparation of N-ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(1-hydroxycyclopropyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0941]

[0942] Step 1: Preparation of 1-(3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)cyclopropanol

[0943] Methyl 3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)benzoate (1 g, 2.83 mmol, 1 eq) and Ti(Oi-Pr)4 (1.45 g, 5.1 mmol, 1.5 mL, 1.8 eq) were dissolved in tetrahydrofuran (20 mL). Bromo(ethyl)magnesium (3 M, 3 mL, 3.18 eq) was added at 0°C, and the mixture was heated to 20°C and stirred for 12 h under nitrogen gas. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1) gave methyl 3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)benzoate (R f = 0.54, 254 nm) and one new spot that is more polar (R f= 0.12, 254 nm and I2) was generated. The reaction mixture was quenched by adding saturated ammonium chloride aqueous solution (20 mL) and filtered. The filtrate was extracted with ethyl acetate (15 mL × 3), and the organic layer was washed with water and saturated sodium chloride aqueous solution (15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (column chromatography (silica gel, petroleum ether / ethyl acetate = 20 / 1, R f = 0.12, 200:1-100:1-10:1)) was purified to obtain the title compound (530 mg, 1.51 mmol, 53.30% yield) as a transparent, sticky substance.

[0944] Step 2: Preparation of (1-(3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)cyclopropoxy)(tert-butyl)dimethylsilane

[0945] 1-(3-Bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)cyclopropanol (530 mg, 1.51 mmol, 1 eq) was dissolved in dichloromethane (10 mL), cooled to 0°C, imidazole (205 mg, 3.02 mmol, 2 eq) was added, and TBSCl (269.50 mg, 1.79 mmol, 220 μL, 1.18 eq) was added, and stirred at 20°C for 2 h. Thin layer chromatography (petroleum ether: ethyl acetate = 10:1) gave 1-(3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)cyclopropanol (R f = 0.36) were all exhausted, and one main spot (R f= 0.64) was generated. To terminate the reaction, water (20 mL) was added and extracted with dichloromethane (10 mL×3). The organic layer was washed with a saturated aqueous solution of sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (586 mg, 1.26 mmol, 83.43% yield) as a bright yellow sticky substance.

[0946] Step 3: Preparation of tert-butyl(1-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropoxy)dimethylsilane

[0947] (1-(3-Bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)cyclopropoxy)(tert-butyl)dimethylsilane (586 mg, 1.26 mmol, 1 eq), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (645 mg, 2.54 mmol, 2.02 eq), potassium acetate (369 mg, 3.77 mmol, 2.99 eq), Pd(dppf)Cl2·CH2Cl2 (110 mg, 134.70 μmol, 1.07 e -1 eq) was dissolved in dioxane (15 mL), heated to 85°C, and stirred for 12 h under nitrogen gas. LCMS (EC25246-45-P1A1) showed that (1-(3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)cyclopropoxy)(tert-butyl)dimethylsilane was consumed, and the mass of the title compound (Rt = 0.692 min, m / z = 513) was confirmed. After cooling to room temperature, water (20 mL) was added to the reaction mixture, and extracted with ethyl acetate (15 mL × 3). The reaction mixture was washed with a saturated aqueous solution of sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (petroleum ether: ethyl acetate = 10:1, Rf = 0.42) was purified to obtain the title compound (250 mg, 487.77 μmol, 38.74% yield) having a yellow sticky appearance.

[0948] Step 4: Preparation of 4-(3-(1-((tert-butyldimethylsilyl)oxy)cyclopropyl)-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0949] tert-Butyl(1-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropoxy)dimethylsilane (250 mg, 487.77 μmol, 1 eq) and 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (170 mg, 570.21 μmol, 1.17 eq) were dissolved in dioxane (5 mL) and water (1 mL), and sodium carbonate (157.48 mg, 1.49 mmol, 3.05 eq) and Pd(dppf)Cl2 (35.69 mg, 48.78 μmol, 0.1 eq) were mixed under nitrogen gas at 20°C. The reaction mixture was heated to 100°C under nitrogen gas and stirred for 12 hours. LCMS (EC25246-46-P1A1) showed that tert-butyl(1-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropoxy)dimethylsilane was consumed, and the title compound mass (Rt = 0.595 min, m / z = 604) was confirmed. To terminate the reaction, water (20 mL) was added to the reaction mixture, and the mixture was extracted with dichloromethane (10 mL×3). The organic layer was washed with a saturated aqueous solution of sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (586 mg, 1.26 mmol, 83.43% yield) as a bright yellow sticky substance.

[0950] Step 5: Preparation of N-ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(1-hydroxycyclopropyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0951] 4-(3-(1-((tert-butyldimethylsilyl)oxo)cyclopropyl)-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (167 mg, 276.58 μmol, 1 eq) was dissolved in dichloromethane (20 mL), and TBAF (1 M, 3 mL, 10.85 eq) was mixed and stirred at 20 °C for 5 h. Starting material was consumed by LCMS (EC25246-47-P1A33), and the title compound mass (R t = 0.452 min, m / z = 490) was confirmed. The reaction mixture was purified by prep-TLC (petroleum ether: ethyl acetate = 0:1, and 5% EtOH, R f = 0.24) was performed to obtain the title compound (66.80 mg, 130.45 μmol, 47.17% yield, 95.6% purity) as a white solid.

[0952] 1 H NMR (400 MHz, DMSO-d6) δ 12.27 (s, 1H), 8.35 (t,J= 5.3 Hz, 1H), 7.37 (s, 1H), 7.03 (d,J= 9.1 Hz, 2H), 6.90 (s, 1H), 6.86 (s, 1H), 6.74 (dd,J= 9.4, 1.4 Hz, 2H), 5.93 (s, 1H), 3.57 (s, 3H), 3.28 - 3.25 (m, 2H), 2.13 (s, 6H), 1.14 (dd,J= 9.4, 4.9 Hz, 3H), 1.12 - 1.09 (m, 2H), 0.98 (dd,J= 7.3, 4.9 Hz, 2H); LCMS: m / z 491 [M+H]+

[0953] [Examples 185 to 187]

[0954]

[0955] Step 1: Preparation of methyl 3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)benzoate

[0956] 4-Fluoro-2,6-dimethylphenol (594 mg, 4.24 mmol, 1 eq) and (3-bromo-5-methoxycarbonyl-phenyl)boronic acid (1.54 g, 5.93 mmol, 1.4 eq) were dissolved in dichloromethane (12 mL), and copper acetate (770 mg, 4.24 mmol, 1 eq), 4A MS (600 mg, 4.24 mmol, 1 eq), and triethylamine (2.14 g, 21.19 mmol, 2.95 mL, 5 eq) were mixed, and stirred at 25°C under oxygen gas (15 psi) for 12 h. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1) gave 4-Fluoro-2,6-dimethylphenol (R f = 0.43) was exhausted and two new spots (R f = 0.39, P: R f = 0.60) was generated. After the reaction was completed, the reaction mixture was filtered, water (20 mL) was added to the filtrate, and extracted with dichloromethane (5 mL × 3). The organic layer was washed with a saturated aqueous solution of sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 20:1, R f = 0.60) and purified by reverse phase-HPLC (FA) to obtain 180 mg (509.65 μmol, 12.03% yield) of the yellow title compound as a sticky substance.

[0957] Step 2: Preparation of 2-(3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)propan-2-ol

[0958] Methyl 3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)benzoate (180 mg, 509.65 μmol, 1 eq) was dissolved in tetrahydrofuran (5 mL) and cooled to 0°C under nitrogen gas. Methylmagnesium bromide (3 M, 450 μL, 2.65 eq) dissolved in diethyl ether was slowly added and stirred at 20°C for 4 h. Thin layer chromatography (petroleum ether: ethyl acetate = 30:1) gave methyl 3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)benzoate (R f = 0.70) was exhausted, and one main spot (R f = 0.20) was generated. After the reaction was completed, saturated ammonium chloride aqueous solution (20 mL) was added to neutralize. The reaction mixture was extracted with dichloromethane (10 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (160 mg, 452.97 μmol, 88.88% yield) as a sticky yellow substance.

[0959] Step 3: Preparation of 2-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol

[0960] 2-(3-Bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)propan-2-ol (160 mg, 452.97 μmol, 1 eq) and bis(pinacolato)diborane (230 mg, 905.73 μmol, 2 eq), Pd(dppf)Cl2·CH2Cl2 (36.99 mg, 45.30 μmol, 0.1 eq), and potassium acetate (134 mg, 1.37 mmol, 3.01 eq) were mixed in dioxane (4 mL), heated to 80 °C, and stirred under nitrogen gas for 12 h. LCMS showed that 2-(3-bromo-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)propan-2-ol was consumed, and the mass (R) of the title compound t= 0.521 min, m / z-18 = 383) was confirmed. After cooling to room temperature, the reaction mixture was filtered, water (20 mL) was added to the filtrate, and extracted with ethyl acetate (5 mL × 3). The organic layer was washed with saturated aqueous sodium chloride solution (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (petroleum ether: ethyl acetate = 3:1, R f = 0.30) was purified to obtain 58 mg (144.89 μmol, 31.99% yield) of the title compound as a transparent, sticky substance.

[0961] Step 4: Suzuki Cross Coupling

[0962] Each 4-bromo-N-Rf-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1 eq), 2-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol (1 eq), Pd(dppf)2Cl2 (0.1 eq) and cesium carbonate (1.5 eq) were mixed in dioxane and water, stirred at 90°C under argon gas for 20 hours and cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain the title compound in Table 16 below (yield: 67-95%).

[0963] [Table 16]

[0964]

[0965] [Example 188] Preparation of 4-(3-amino-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0966]

[0967] Step 1: Preparation of 4-(benzyloxy)-1-methyl-2-nitrobenzene

[0968] 4-Methyl-3-nitrophenol (20 g, 130.6 mmol) and benzyl bromide (17.09 mL, 143.7 mmol) were dissolved in N,N-dimethylformamide (200 mL), potassium carbonate (27.07 g, 196 mmol) was mixed, and the mixture was stirred at room temperature overnight. Water (400 mL) and ethyl acetate (400 mL) were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain 31 g (97%) of the title compound.

[0969] Step 2: Preparation of 5-(benzyloxy)-2-methylaniline

[0970] 4-(Benzyloxy)-1-methyl-2-nitrobenzene (17 g, 69.9 mmol), zinc powder (91.3 g, 1.4 mol), and acetic acid (40 mL, 699 mmol) were mixed in tetrahydrofuran (300 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous sodium bicarbonate solution were added to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 12.9 g (87%) of the title compound without further purification.

[0971] Step 3: Preparation of N-(5-(benzyloxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0972] 5-(Benzyloxy)-2-methylaniline (1.5 g, 7.03 mmol, 1 eq) was dissolved in N,N-dimethylformamide, and HATU (4.01 g, 10.55 mmol, 1.5 eq), diisopropylethylamine (1.84 mL, 10.55 mmol, 1.5 eq), and 3-(piperidin-1-yl)propanoic acid (1.11 g, 7.03 mmol, 1 eq) were mixed and stirred at room temperature for 18 h. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 2.3 g (6.52 mmol, 93% yield) of the title compound.

[0973] Step 4: Preparation of N-(5-hydroxy-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0974] N-(5-(Benzyloxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide (2.3 g, 6.52 mmol) was dissolved in methanol (20 mL), and 10% Pd / C (10% wt) was mixed. The mixture was stirred at room temperature under hydrogen gas for 20 h. The reaction mixture was filtered through Celite and washed with methanol. The solvent was distilled under reduced pressure to obtain 1.65 g (96%) of the title compound without further purification.

[0975] Step 5: Preparation of N-(5-(3-bromo-5-nitrophenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide

[0976] N-(5-Hydroxy-2-methylphenyl)-3-(piperidin-1-yl)propanamide (1.65 g, 6.29 mmol) and 1-bromo-3-fluoro-5-nitrobenzene (1.66 g, 7.55 mmol) were dissolved in N,N-dimethylformamide (21 mL), and cesium carbonate (4.10 g, 12.58 mmol) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain 2.52 g (87%) of the title compound.

[0977] Step 6: Preparation of N-(2-methyl-5-(3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)phenyl)-3-(piperidin-1-yl)propanamide

[0978] N-(5-(3-Bromo-5-nitrophenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide (2.52 g, 5.46 mmol, 1 eq), bis(pinacol)diborane (1.37 g, 5.46 mmol), potassium acetate (0.64 g, 6.55 mmol), Pd2(dba)3 (0.50 g, 0.55 mmol), and x-Phos (0.26 g, 0.55 mmol) were mixed in dioxane (18 mL), heated to 90°C, stirred under argon gas for 20 h, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 2.14 g (4.21 mmol, 77%) of the title compound.

[0979] Step 7: Preparation of N-ethyl-6-methyl-4-(3-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)-5-nitrophenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0980] N-(2-methyl-5-(3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)phenyl)-3-(piperidin-1-yl)propanamide (2.14 g, 4.21 mmol, 1 eq), 4-bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1.32 g, 4.21 mmol, 1 eq), Pd(dppf)2Cl2 (0.31 g, 0.42 mmol, 0.1 eq) and cesium carbonate (2.06 g, 6.32 mmol) were mixed in dioxane (15 mL) and water (1.5 mL), heated to 90°C and stirred under argon gas for 20 h. After stirring for a while, it was cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain 1.30 g (2.17 mmol, 51%) of the title compound.

[0981] Step 8: Preparation of 4-(3-amino-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0982] N-Ethyl-6-methyl-4-(3-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)-5-nitrophenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (500 mg, 0.83 mmol, 1 eq), zinc powder (1.09 g, 16.6 mmol, 20 eq), and acetic acid (0.47 mL, 8.3 mmol, 10 eq) were mixed in tetrahydrofuran (10 mL) and stirred at room temperature overnight. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. Dichloromethane and a saturated aqueous solution of sodium bicarbonate were added to separate the layers, and the organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 342 mg (0.60 mmol, 72%) of the title compound.

[0983] 1 H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 9.77 (s, 1H), 8.41 (t,J= 5.2 Hz, 1H), 7.49 (s, 1H), 7.36 (s, 1H), 7.19 (d,J= 8.3 Hz, 1H), 7.04 (s, 1H), 6.76 (dd,J= 8.2, 2.1 Hz, 1H), 6.56 (s, 1H), 6.34 (s, 1H), 6.14 (s, 1H), 5.35 (s, 2H), 3.56 (s, 3H), 3.40 - 3.22 (m, 4H), 2.68 - 2.53 (m, 2H), 2.42 (s, 4H), 2.21 (s, 3H), 1.61 - 1.45 (m, 4H), 1.45 - 1.31 (m, 2H), 1.31 - 1.17 (m,J= 14.1 Hz, 3H), 1.13 (t,J= 7.2 Hz, 3H), 0.86 (t,J=6.6 Hz, 2H); LCMS: m / z 572 [M+H] +

[0984] [Examples 189 to 190]

[0985]

[0986] Step 1: Sulfonamide

[0987] 4-(3-amino-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1 eq) was dissolved in pyridine, and each sulfonyl chloride (1.2 eq) was mixed and stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→30%) to obtain the title compound in Table 17 below (50%∼75%).

[0988] [Table 17]

[0989]

[0990] [Example 191] Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0991]

[0992] Step 1: Preparation of 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[0993] 4-Bromo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (12 g, 31.4 mmol, 1 eq) was dissolved in tetrahydrofuran (360 mL), and LDA (2 M, 23.6 mL, 1.5 eq) was slowly added, and the mixture was stirred at -75 °C for 1 h under nitrogen gas. The reaction mixture was stirred at -75 °C under carbon dioxide (1.39 g, 31.4 mmol, 1 eq) and 15 psi for 1 h. The mass of the title compound was confirmed by LCMS. To terminate the reaction, saturated aqueous ammonium chloride solution was added to the reaction mixture at 0 °C, and extracted with ethyl acetate (100 mL x 2). The organic layer was discarded, and the aqueous layer was adjusted to pH 3-4 by adding 1N hydrochloric acid, and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with a saturated aqueous solution of sodium chloride (100 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with tert-butyl methyl ether (50 mL) at 25°C for 30 minutes to obtain 5 g (10.3 mmol, 32.8% yield, 88% purity) of the title compound as a brown solid.

[0994] Step 2: Preparation of 4-bromo-N-ethyl-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0995] 4-Bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (5 g, 11.7 mmol, 1 eq) and ethylamine (1.92 g, 23.5 mmol, 2.78 mL, 2 eq, HCl) were dissolved in N,N-dimethylformamide (50 mL), and HATU (5.36 g, 14.11 mmol, 1.2 eq) and diisopropylethylamine (7.60 g, 58.8 mmol, 10.24 mL, 5 eq) were mixed and stirred at 25 °C for 2 h. The mass value of the title compound was confirmed by LCMS. Water (100 mL) was added to the reaction mixture and extracted with ethyl acetate (100 mL x 2). The organic layer was washed with a saturated aqueous solution of sodium chloride (100 mL x 4), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with tert-butyl methyl ether (50 mL) at 20°C for 10 minutes to obtain 4.60 g (10.1 mmol, 86.4% yield) of the title compound as a brown solid.

[0996] Step 3: Preparation of 4-(3-bromo-5-methylphenoxy)-1-methyl-2-nitrobenzene

[0997] 4-Methyl-3-nitrophenol (10 g, 65.3 mmol, 1 eq) and (3-bromo-5-methylphenyl)boronic acid (28.1 g, 130 mmol, 2 eq) were dissolved in dichloromethane (200 mL), and copper acetate (11.8 g, 65.3 mmol, 1 eq), 4Å molecular sieve (4Å molecular sieve, hereinafter referred to as '4A MS') (65.3 mmol, 1 eq), and triethylamine (33 g, 326 mmol, 45.4 mL, 5 eq) were mixed and stirred at 25°C for 12 hours. Thin layer chromatography (petroleum ether: ethyl acetate = 10:1) gave 4-methyl-3-nitrophenol (R1,R f = 0.10) was exhausted, and one new spot (P1,R f= 0.55) was produced. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 100: 1, thin layer chromatography: petroleum ether: ethyl acetate = 10: 1, P1 R f = 0.55) to obtain the title compound (10 g, 31 mmol, 47.5% yield) having a colorless oily state.

[0998] Step 4: Preparation of 5-(3-bromo-5-methylphenoxy)-2-methylaniline

[0999] 4-(3-Bromo-5-methylphenoxy)-1-methyl-2-nitrobenzene (10 g, 31 mmol, 1 eq) was dissolved in ethanol (110 mL) and water (22 mL), and ammonium chloride (3.32 g, 62 mmol, 2 eq) and iron (6.93 g, 124 mmol, 4 eq) were mixed at 50°C, and stirred at 80°C for 1 hour. The mass of the title compound was confirmed by MS. After completion of the reaction, the reaction mixture was filtered through Celite, concentrated under reduced pressure, dissolved in ethyl acetate (200 mL), washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (9 g, 30.8 mmol, 99.2% yield) as a yellow oil.

[1000] Step 5: Preparation of 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)aniline

[1001] 5-(3-Bromo-5-methylphenoxy)-2-methylaniline (7 g, 23.9 mmol, 1 eq) was dissolved in dioxane (70 mL), potassium acetate (7.05 g, 71.8 mmol, 3 eq), bis(pinacolato)diborane (12.2 g, 47.9 mmol, 2 eq), and Pd(dppf)Cl2.CH2Cl2 (1.96 g, 2.40 mmol, 0.1 eq) were mixed, heated to 90°C, and stirred under nitrogen gas for 12 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 100: 1 to 30: 1, thin layer chromatography: petroleum ether: ethyl acetate = 10: 1, P1, R f = 0.50) was purified to obtain the title compound (11 g, crude) as a yellow solid.

[1002] Step 6: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1003] 4-Bromo-N-ethyl-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (3.37 g, 7.47 mmol, 1 eq) and 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (3.82 g, 11.2 mmol, 1.5 eq) were dissolved in dioxane (48 mL), and cataCXium A Pd G3 (547 mg, 751 μmol, 0.1 eq) and tripotassium phosphate (1.50 M, 25.1 mL, 5 eq) were mixed. The mixture was stirred at 90°C for 2 hours, and the mass value of the title compound was confirmed by LCMS. To terminate the reaction, water (50 mL) was added to the reaction mixture, and extracted with ethyl acetate (100 mL x 3). The organic layer was washed with a saturated aqueous sodium chloride solution (70 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (5 g, crude) as a yellow oil.

[1004] Step 7: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1005] 4-(3-(3-Amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (4 g, 6.84 mmol, 1 eq) was dissolved in methanol (50 mL), and sodium hydroxide (3 M, 22.8 mL, 10 eq) was mixed and stirred at 25°C for 2 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 10: 1 to 0: 1, thin layer chromatography: petroleum ether: ethyl acetate = 0: 1, P1, Rf = 0.30) to obtain the title compound (2.40 g, 5.57 mmol, 81.5% yield) as a yellow solid. 100 mg of the obtained compound was subjected to prep-HPLC (column: CD04-Welch Ultimate C18 150*25*7um; mobile phase: [water(FA)-ACN]; gradient: 36%-66% B over 15 min) to obtain the title compound (36.9 mg, 47.1 μmol, 36.9% yield, 99.4% purity) as a white solid.

[1006] 1 H NMR (400 MHz, DMSO-d6) δ 12.30 (s, 1H), 8.49-8.30 (m, 1H), 7.41 (s, 1H), 7.11 (s, 1H), 6.99 (s, 2H), 6.90 (d,J= 8.0 Hz, 1H), 6.73 (s, 1H), 6.32 (d,J= 2.4 Hz, 1H), 6.17 (dd,J= 2.4, 8.0 Hz, 1H), 4.98 (s, 2H), 3.57 (s, 3H), 3.29 (dd,J= 5.8, 7.4 Hz, 2H), 2.34 (s, 3H), 2.01 (s, 3H), 1.14 (t,J=7.2 Hz, 3H); LCMS: m / z 432 [M+H] +

[1007] [Examples 192 to 198]

[1008]

[1009] Step 1: Amide coupling

[1010] Each carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 18 below (yield: 11-21%).

[1011] [Table 18]

[1012]

[1013]

[1014] [Examples 199 to 203]

[1015]

[1016] Step 1: Amide coupling

[1017] 4-Bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and each amine (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (yield: 58-70%).

[1018] Step 2: Suzuki Cross Coupling

[1019] 4-Bromo-N-Rf-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1 eq) and 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)aniline (1.5 eq) obtained in step 1 were dissolved in dioxane, and cataCXium A Pd G3 (0.1 eq) and tripotassium phosphate (5 eq) were mixed and stirred at 90°C for 2 hours. The mass value of the title compound was confirmed by LCMS. To terminate the reaction, water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (yield: 38-92%).

[1020] Step 3: Amide coupling

[1021] 4-(Dimethylamino)butanoic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and each aniline obtained in step 2 (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound in Table 19 below (yield: 17-78%).

[1022] [Table 19]

[1023]

[1024] [Example 204]

[1025]

[1026] Step 1: Preparation of 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole

[1027] 2-Methyl-1H-pyrrole (1.10 g, 13.5 mmol, 1 eq), bis(pinacolato)diborane (1.72 g, 6.78 mmol, 0.5 eq), 4,4'-di-tert-butyl-2,2'-bipyridine (145 mg, 542 μmol, 0.04 eq), and [Ir(OMe)(1,5-cod)]2 (179 mg, 270 μmol, 0.02 eq) were dissolved in hexane (66 mL). The reaction mixture was purged three times with nitrogen gas, and then heated to 30°C under nitrogen gas and stirred for 2 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 10: 1, thin layer chromatography: petroleum ether: ethyl acetate = 10: 1, P1: R f = 0.83) was purified to obtain the title compound (1.60 g, 7.73 mmol, 28.49% yield) as a white solid.

[1028] Step 2: Preparation of 4-bromo-2-iodo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1029] 4-Bromo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (2 g, 5.25 mmol, 1 eq) was dissolved in tetrahydrofuran (80 mL), and freshly prepared LDA (2 M, 3.93 mL, 1.5 eq) was added from a cold solution (-78°C, dry ice / acetone bath) and stirred at -78°C for 2 h. Iodine (3.06 g, 12 mmol, 2.43 mL, 2.3 eq) was dissolved in tetrahydrofuran (6 mL), added at -78°C, and stirred at 0°C for 2 h. The mass value of the title compound was confirmed by LCMS. To terminate the reaction, 1 M hydrochloric acid was added to the reaction mixture at 0℃ to adjust the pH to <6, and after filtration, water (50 mL) was added and extracted with ethyl acetate (100 mL x 3). The organic layer was washed with a saturated aqueous solution of sodium chloride (30 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 10: 1 to 1: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1, P1, R f = 0.30) was purified to obtain 1.10 g (2.17 mmol, 41.3% yield) of the title compound as a white solid.

[1030] Step 3: Preparation of 4-bromo-6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1031] 4-Bromo-2-iodo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (630 mg, 1.24 mmol, 1 eq), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (514 mg, 2.48 mmol, 2 eq), Pd(PPh3)4 (143 mg, 124 μmol, 0.1 eq), and potassium carbonate (342 mg, 2.48 mmol, 2 eq) were dissolved in dioxane (7 mL). After degassing the reaction mixture three times using nitrogen gas, the mixture was heated to 40°C under nitrogen gas and stirred for 1 h. The mass value of the title compound was confirmed by LCMS. To terminate the reaction, water (50 mL) was added to the reaction mixture and extracted with ethyl acetate (100 mL×2). The organic layer was washed with saturated aqueous sodium chloride solution (70 mL×2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 10: 1 to 1: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1, P1 R f = 0.30) was purified to obtain 450 mg (977 μmol, 78.6% yield) of the title compound as a brown solid.

[1032] Step 4: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1033] 4-Bromo-6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (380 mg, 825 μmol, 1 eq) and 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)aniline (364 mg, 1.07 mmol, 1.3 eq) were dissolved in dioxane (8 mL), and cataCXium A Pd G3 (60.1 mg, 82.5 μmol, 0.1 eq) and tripotassium phosphate (1.5 M, 2.75 mL, 5 eq) were mixed and stirred at 90 °C for 2 h. The mass value of the title compound was confirmed by LCMS. To terminate the reaction, water (30 mL) was added to the reaction mixture and extracted with ethyl acetate (50 mL×3). The organic layer was washed with saturated aqueous sodium chloride solution (30 mL×2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 10: 1 to 0: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1, P1, R f = 0.11) was purified to obtain 380 mg (641 μmol, 77.6% yield) of the title compound as a yellow solid.

[1034] Step 5: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1035] 4-(3-(3-Amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (200 mg, 337 μmol, 1 eq) was dissolved in methanol (2 mL), and sodium hydroxide (3 M, 1.12 mL, 10 eq) was mixed and stirred at 25°C for 12 h. The mass value of the title compound was confirmed by LCMS. The reaction solution was filtered to obtain the title compound (70 mg, 159 μmol, 47.3% yield) as a yellow solid.

[1036] Step 6: Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1037] 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (60 mg, 136 μmol, 1 eq) and 4-(dimethylamino)butanoic acid (60 mg, 457 μmol, 3.34 eq) were dissolved in N,N-dimethylformamide (1.5 mL), and EDCI (209 mg, 1.09 mmol, 8 eq), HOBt (147 mg, 1.09 mmol, 8 eq), DMAP (66.8 mg, 547 μmol, 4 eq), and diisopropylethylamine (141 mg, 1.09 mmol, 190 μL, 8 eq) were mixed at 25°C. The mixture was stirred for 2 hours. The mass value of the title compound was confirmed by LCMS. To terminate the reaction, water (30 mL) was added to the reaction mixture and extracted with ethyl acetate (40 mL x 3). The organic layer was washed with a saturated aqueous sodium chloride solution (30 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-HPLC (hydrochloric acid condition) to obtain 28 mg (50.2 μmol, 36.7% yield, 99% purity, HCl) of the title compound as a brown solid.

[1038] 1H NMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H), 10.97 (s, 1H), 9.82 (dd,J= 8.4, 3.4 Hz, 1H), 9.40 (s, 1H), 7.39 (s, 1H), 7.21-7.30 (m, 2H), 7.19 (s, 1H), 7.01 (s, 1H), 6.84 (dd,J= 8.2, 2.4 Hz, 1H), 6.78 (s, 1H), 6.64 (t,J= 2.8 Hz, 1H), 6.58 (d,J= 2.2 Hz, 1H), 5.78 (s, 1H), 3.56 (s, 3H), 3.00-3.08 (m, 2H), 2.74 (d,J= 4.8 Hz, 6H), 2.45 (t,J= 7.2 Hz, 2H), 2.37 (s, 3H), 2.21 (d,J= 12.0 Hz, 6H), 1.87-1.95 (m, 2H); LCMS: m / z 553 [M+H] +

[1039] [Example 205] Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(4-methyl-1H-imidazol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1040]

[1041] Step 1: Preparation of 4-bromo-2-(hydroxymethyl)-6-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1042] Methyl 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (2 g, 4.82 mmol, 1 eq) and DIBAL-H (1 M, 19.2 mL, 4 eq) were dissolved in tetrahydrofuran (40 mL), and the reaction mixture was purged with nitrogen gas three times, then stirred under nitrogen gas at 0 °C for 1 h. The mass of the title compound was confirmed by LCMS. The reaction mixture was adjusted to pH<6 with 1 M hydrochloric acid at 0 °C, filtered, water was added, and extracted with ethyl acetate (30 mL × 3). The organic layer was washed with 60 mL of saturated sodium chloride aqueous solution (30 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 5: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1 P1: R f = 0.3) was purified to obtain 900 mg (2.32 mmol, 48.2% yield) of the title compound as a yellow solid.

[1043] Step 2: Preparation of 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde

[1044] 4-Bromo-2-(hydroxymethyl)-6-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (900 mg, 2.32 mmol, 1 eq) was dissolved in dichloromethane (27 mL) and N,N-dimethylformamide (3 mL), manganese dioxide (4.04 g, 46.47 mmol, 20 eq) was mixed, and the mixture was stirred at 20°C for 12 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was filtered and concentrated under reduced pressure, and the mixture was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 10: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1, P1: R f = 0.44) was purified to obtain the title compound (580 mg, 1.51 mmol, 64.7% yield) as a gray solid.

[1045] Step 3: Preparation of 4-bromo-6-methyl-2-(4-methyl-1H-imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1046] 4-Bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde (530 mg, 1.38 mmol, 1 eq) was dissolved in methanol (10 mL), and ammonium acetate (1.59 g, 20.6 mmol, 15 eq) was mixed under nitrogen gas, and the mixture was stirred at 20 °C for 30 min. 2-Oxopropanal (693 mg, 9.63 mmol, 583 μL, 7 eq) was added to the reaction mixture, and the mixture was stirred at 50 °C for 2 h. The mass value of the title compound was confirmed by LCMS. Water (20 mL) was added to the reaction mixture, and ethyl acetate (10 mL × 3) was extracted. The organic layer was washed with saturated sodium chloride aqueous solution (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 0: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1 P1: R f = 0.25) was purified to obtain 405 mg (925 μmol, 67.32% yield) of the title compound having a yellow liquid phase.

[1047] Step 4: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(4-methyl-1H-imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1048] 4-Bromo-6-methyl-2-(4-methyl-1H-imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (400 mg, 914 μmol, 1 eq), 2-methyl-5-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]aniline (465 mg, 1.37 mmol, 1.5 eq), tripotassium phosphate (1.5 M, 3.05 mL, 5 eq), cataCXium A Pd G3 (66.6 mg, 91.4 μmol, 0.1 eq) were mixed in dioxane (8 mL), and the gas in the reaction mixture was removed three times using nitrogen gas. After heating to 90℃, it was stirred for 2 hours under nitrogen gas. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 5: 1 to 0: 1, thin layer chromatography: petroleum ether: ethyl acetate = 1: 1, P1 R f = 0.15) was purified to obtain 345 mg (605 μmol, 66.2% yield) of the title compound as a brown solid.

[1049] Step 5: Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(4-methyl-1H-imidazol-2-yl)-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1050] 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(4-methyl-1H-imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (345 mg, 605 μmol, 1 eq) and 4-(dimethylamino)butanoic acid (345 mg, 2.63 mmol, 4.34 eq) were dissolved in N,N-dimethylformamide (7 mL), and EDCI (928 mg, 4.84 mmol, 8 eq), HOBt (654 mg, 4.84 mmol, 8 eq), DMAP (295 mg, 2.42 mmol, 4 eq) and diisopropylethylamine (626 mg, 4.84 mmol, 843 μL, 8 eq) were mixed and stirred at 40°C for 3 hours. The mass value of the title compound was confirmed by LCMS. 10 mL of water was added to the reaction mixture, and the mixture was filtered to obtain 310 mg (352 μmol, 58.1% yield, 77.6% purity) of the title compound as a brown solid.

[1051] Step 6: Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(4-methyl-1H-imidazol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1052] 4-(Dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(4-methyl-1H-imidazol-2-yl)-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide (310 mg, 453 μmol, 1 eq) was dissolved in dichloromethane (6 mL), and trifluoroacetic acid (4.76 g, 41.7 mmol, 3.10 mL, 91.9 eq) was added. The mixture was stirred at 20°C for 2 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure to remove dichloromethane (6 mL) and trifluoroacetic acid (4.76 g, 41.7 mmol, 3.10 mL, 91.9 eq). Methanol (5 mL) and ammonia water (1 mL) were added to the reaction mixture, stirred at 20°C for 1 h, and then concentrated under reduced pressure. The residue was purified by prep-HPLC (column: CD01-Phenomenex luna C18 150*25*10um; mobile phase: [water(FA)-ACN]; gradient: 4%-34% B over 10 min) to obtain 111 mg (182 μmol, 40.1% yield, 98.3% purity, HCOOH) of the title compound as a white solid.

[1053] 1H NMR (400 MHz, DMSO-d6) δ 12.11 (s, 1H), 9.49 (s, 1H), 8.20 (s, 1H), 7.47 (s, 1H), 7.26-7.20 (m, 2H), 7.19 (s, 1H), 7.00 (s, 1H), 6.88 (s, 1H), 6.84 (dd,J= 2.4, 8.3 Hz, 1H), 6.81 (s, 1H), 6.76 (s, 1H), 3.61-3.53 (m, 3H), 2.37 (s, 4H), 2.34 ( dd,J= 2.4, 7.0 Hz, 4H), 2.22 (s, 3H), 2.19 (s, 8H), 1.72 (quin,J= 7.2 Hz, 2H); LCMS: m / z 554 [M+H] +

[1054] [Example 206] Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1055]

[1056] Step 1: Preparation of methyl ethaneimidothioate hydroiodide

[1057] Ethanimidothioamide (5 g, 66.5 mmol, 1 eq) was dissolved in acetone (20 mL), and iodomethane (14.2 g, 99.8 mmol, 6.21 mL, 1.5 eq) was added at 0°C, and the mixture was stirred at 20°C for 12 hours. The reaction mixture formed a large amount of solid precipitate, which was filtered to obtain the title compound (14 g, 64.5 mmol, 96.9% yield, HI) as a white solid.

[1058] Step 2: Preparation of 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbohydrazide

[1059] Methyl 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (1 g, 2.41 mmol, 1 eq) was dissolved in ethanol (10 mL), and hydrazine hydrate (4.54 g, 77.1 mmol, 4.40 mL, 85% purity, 32 eq) was mixed and stirred at 80°C for 6 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 5:1 to 1:1, thin layer chromatography: petroleum ether: ethyl acetate = 0:1, P1 R f = 0.4) was purified to obtain the title compound (880 mg, 2.12 mmol, 88% yield) as a gray-white solid.

[1060] Step 3: Preparation of 4-bromo-6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1061] 4-Bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbohydrazide (440 mg, 1.06 mmol, 1 eq), methyl ethaneimidothioate hydroiodide (345 mg, 1.59 mmol, 1.5 eq, HI) and silica gel (880 mg, 14.6 mmol, 13.8 eq) were dissolved in N,N-dimethylformamide (4 mL), triethylamine (536 mg, 5.30 mmol, 737 μL, 5 eq) and ammonium acetate (980 mg, 12.7 mmol, 12 eq) were mixed and microwaved at 120°C for 1 h. The mixture was stirred. The mass value of the title compound was confirmed by LCMS. The reaction mixture was filtered and extracted with water (20 mL) and ethyl acetate (20 mL × 2) to obtain 780 mg (1.51 mmol, 71.3% yield, 85% purity) of the title compound as a light yellow solid.

[1062] Step 4: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1063] 4-Bromo-6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (770 mg, 1.76 mmol, 1 eq), 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)aniline (893 mg, 2.63 mmol, 1.5 eq), cataCXium A Pd G3 (128 mg, 175 μmol, 0.1 eq), tripotassium phosphate (1.5 M, 5.85 mL, 5 eq) were dissolved in dioxane (18 mL), and the gas in the reaction mixture was removed using nitrogen gas. After repeating this three times, it was heated to 90℃ and stirred for 12 hours under nitrogen gas. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 10:1 to 0:1, thin layer chromatography: petroleum ether: ethyl acetate = 1:1, P1 R f = 0.15) was purified to obtain 780 mg (1.37 mmol, 77.8% yield) of the title compound as a yellow solid.

[1064] Step 5: Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1065] 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (350 mg, 613 μmol, 1 eq) and 4-(dimethylamino)butanoic acid (350 mg, 2.67 mmol, 4.35 eq) were dissolved in N,N-dimethylformamide (8 mL), and EDCI (235 mg, 1.23 mmol, 2 eq), HOBt (165 mg, 1.23 mmol, 2 eq), diisopropylethylamine (634 mg, 4.91 mmol, 854 μL, 8 eq) and DMAP (74.9 mg, 613 μmol, 1 eq) was mixed and stirred at 40°C for 12 hours. The mass value of the title compound was confirmed by LCMS. 30 mL of water was added to the reaction mixture, and the mixture was filtered to obtain 350 mg (440 μmol, 71.7% yield, 86% purity) of the title compound as a brown solid.

[1066] Step 6: Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1067] 4-(Dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide (300 mg, 438 μmol, 1 eq) was dissolved in dichloromethane (3 mL), trifluoroacetic acid (4.60 g, 40.4 mmol, 3 mL, 92 eq) was added, and the mixture was stirred at 20°C for 1 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure to remove dichloromethane (3 mL) and trifluoroacetic acid (4.60 g, 40.4 mmol, 3 mL, 92 eq). 5 mL of methanol and 1 mL of ammonia water were added to the reaction mixture, stirred at 20°C for 1 h, and then titrated to pH 3 with 1 N hydrochloric acid, followed by filtration to obtain a yellow solid. The obtained solid was purified by prep-HPLC (column: CD02-Waters Xbidge BEH C18 150*25*10um; mobile phase: [water(NH3H2O)-ACN]; gradient: 24%-44% B over 10 min) to obtain 50.1 mg (88.6 μmol, 20.2% yield, 98% purity) of the title compound as a light yellow solid.

[1068] 1H NMR (400 MHz, DMSO-d6) δ 13.97-13.58 (m, 1H), 12.53-12.22 (m, 1H), 9.28 (s, 1H), 7.48 (s, 1H), 7.30-7.15 (m, 3H), 7.01 (s, 1H), 6.86-6.76 (m, 3H), 3.57 (s, 3H), 2.40 (s, 3H), 2.37 (s, 3H), 2.36-2.31 (m, 2H), 2.23-2.19 (m, 2H), 2.18 (s, 3H), 2.08 (s, 6H), 1.68 (quin,J= 7.2 Hz, 2H); LCMS: m / z 555 [M+H] +

[1069] [Example 207] Preparation of 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-7-oxo-2-(1H-tetrazol-5-yl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide

[1070]

[1071] Step 1: Preparation of 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[1072] Methyl 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (2 g, 4.82 mmol, 1 eq) was dissolved in methanol (15 mL), tetrahydrofuran (5 mL), and water (5 mL), and sodium hydroxide (385 mg, 9.63 mmol, 2 eq) was mixed and stirred at 20 °C for 1 h. The mass value of the title compound was confirmed by LCMS. To terminate the reaction, water (20 mL) was added at 20 °C, and the mixture was titrated to pH 3 with 1 N hydrochloric acid and extracted with ethyl acetate (50 mL × 2). The organic layer was washed with a saturated aqueous sodium chloride solution (50 mL×2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 1.51 g (3.76 mmol, 78.1% yield) of the title compound as a yellow solid.

[1073] Step 2: Preparation of 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1074] 4-Bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1.51 g, 3.76 mmol, 1 eq) and ammonium chloride (3.02 g, 56.4 mmol, 15 eq) were dissolved in N,N-dimethylformamide (15 mL), and HATU (1.72 g, 4.52 mmol, 1.2 eq) and diisopropylethylamine (1.46 g, 11.3 mmol, 1.97 mL, 3 eq) were mixed and stirred at 20 °C for 2 h. The mass value of the title compound was confirmed by LCMS. 20 mL of water was added to the reaction mixture, and ethyl acetate (20 mL × 2) was extracted. The organic layer was washed with a saturated aqueous solution of sodium chloride (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 1.36 g (3.40 mmol, 90.2% yield) of the title compound as a yellow solid.

[1075] Step 3: Preparation of 4-bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbonitrile

[1076] 4-Bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (1.36 g, 3.40 mmol, 1 eq) was dissolved in dichloromethane (18 mL), and trifluoroacetic anhydride (1.43 g, 6.79 mmol, 944 μL, 2 eq) and triethylamine (687 mg, 6.79 mmol, 945 μL, 2 eq) were mixed. The mixture was stirred at 0°C for 1 h. The mass value of the title compound was confirmed by LCMS. 20 mL of water was added to the reaction mixture, and extracted with dichloromethane (20 mL × 2). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 20: 1 to 5: 1, thin layer chromatography: petroleum ether: ethyl acetate = 3: 1, P1 R f = 0.4) was purified to obtain 1.11 g (2.90 mmol, 85.4% yield) of the title compound as a white solid.

[1077] Step 4: Preparation of 4-bromo-6-methyl-2-(1H-tetrazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1078] 4-Bromo-6-methyl-7-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbonitrile (800 mg, 2.09 mmol, 1 eq) was dissolved in N,N-dimethylformamide (16 mL), and sodium azide (272 mg, 4.18 mmol, 2 eq) and ammonium chloride (223 mg, 4.18 mmol, 2 eq) were mixed and stirred at 100°C for 16 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was titrated to pH=12 with 0.2 M sodium hydroxide, and sodium hypochlorite (0.5 mL) was added and stirred at 25°C for 0.2 h. The reaction mixture was titrated to pH = 3 with 1N hydrochloric acid and extracted with ethyl acetate (30 mL x 2). The organic layer was washed with saturated aqueous sodium chloride solution (30 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 780 mg (1.51 mmol, 71.3% yield, 85% purity) of the title compound as a light yellow solid.

[1079] Step 5: Preparation of 4-bromo-6-methyl-2-(1H-tetrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1080] 4-Bromo-6-methyl-2-(1H-tetrazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (790 mg, 1.86 mmol, 1 eq) was dissolved in dichloromethane (8 mL), and trifluoroacetic acid (6.14 g, 53.8 mmol, 4 mL, 28.9 eq) was added. The mixture was stirred at 20°C for 1 h. The mass value of the title compound was confirmed by LCMS. The reaction mixture was concentrated under reduced pressure to remove dichloromethane (8 mL) and trifluoroacetic acid (6.14 g, 53.8 mmol, 4 mL, 28.9 eq). Methanol (8 mL) and ammonia water (2 mL) were added to the residue, stirred at 20°C for 1 hour, and the mixture was titrated to pH 3 with 1 N hydrochloric acid, filtered, and 600 mg (1.85 mmol, 99.6% yield, 91% purity) of the title compound as a yellow solid were obtained.

[1081] Step 6: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(1H-tetrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1082] 4-Bromo-6-methyl-2-(1H-tetrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (350 mg, 1.19 mmol, 1 eq), 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)aniline (603 mg, 1.78 mmol, 1.5 eq), cataCXium A Pd G3 (86.3 mg, 118 μmol, 0.1 eq), tripotassium phosphate (1.50 M, 3.95 mL, 5 eq) and sodium carbonate (628 mg, 5.93 mmol, 5 eq) were dissolved in dioxane (16 mL), and the gas in the reaction mixture was removed three times using nitrogen gas. The mixture was heated to 90°C and stirred under nitrogen gas for 12 hours. The mass value of the title compound was confirmed by LCMS. The reaction mixture was cooled to 20°C, water (10 mL) was added, and extracted with ethyl acetate (30 mL × 1). The aqueous layer was adjusted to pH = 4-5 with 1 N hydrochloric acid and filtered to obtain 247 mg (560 μmol, 47.2% yield, 97% purity) of the title compound as a brown solid.

[1083] Step 7: Preparation of 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(1H-tetrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

[1084] 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-6-methyl-2-(1H-tetrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (230 mg, 538 μmol, 1 eq) and 4-(dimethylamino)butanoic acid (230 mg, 1.75 mmol, 3.26 eq) were dissolved in N,N-dimethylformamide (6 mL), and DMAP (263 mg, 2.15 mmol, 4 eq), diisopropylethylamine (556 mg, 4.30 mmol, 750 μL, 8 eq), HOBt (581 mg, 4.30 mmol, 8 eq) and EDCI (825 mg, 4.30 mmol, 8 eq) were mixed and heated to 40°C. The mixture was stirred for 12 hours. The mass value of the title compound was confirmed by LCMS. Ethyl acetate (80 mL) was added to the reaction mixture, and the brown solid was filtered. The residue was purified by prep-HPLC (column: CD04-Welch Ultimate C18 150*25*7um; mobile phase: [water(FA)-ACN]; gradient: 12%-42% B over 15 min) to obtain 60 mg (110 μmol, 20.5% yield, 99.5% purity, HCOOH) of the title compound as a light brown solid.

[1085] 1 H NMR (400 MHz, DMSO-d6) δ 11.99 (s, 1H), 10.64 (s, 1H), 8.14 (s, 1H), 7.44 (s, 1H), 7.25 (d,J= 8.4 Hz, 1H), 7.21 (d,J= 2.4 Hz, 1H), 7.13 (s, 1H), 6.96-6.89 (m, 2H), 6.84 (s, 1H), 6.56 (s, 1H), 3.55 (s, 3H), 3.04-2.94 (m, 2H), 2.70 (s, 6H), 2.53 (s, 2H), 2.39 (s, 3H), 2.17 (s, 3H), 1.92 (quin,J= 7.4 Hz, 2H); LCMS: m / z 542 [M+H] +

[1086] [Example 208] Preparation of 4-(3-(3-((3-(dimethylamino)propyl)carbamoyl)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1087]

[1088] Step 1: Preparation of methyl 5-(3-bromo-5-methylphenoxy)-2-methylbenzoate

[1089] Methyl 5-hydroxy-2-methylbenzoate (500 mg, 3.01 mmol, 1 eq) and (3-bromo-5-methylphenyl)boronic acid (1.29 g, 6.02 mmol, 2 eq) were dissolved in dichloromethane (20 mL), and copper acetate (546 mg, 3.01 mmol, 1 eq), 4A MS (3.01 mmol, 1 eq), and triethylamine (1.52 g, 15 mmol, 2.09 mL, 5 eq) were mixed and stirred at 20°C for 16 h. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1, R1 R f = 0.7, P1 R f = 0.5), reactant 1 was completely consumed, and one new spot was generated. According to thin layer chromatography, the reaction proceeded cleanly. The reaction mixture was filtered, concentrated under reduced pressure, and purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 1: 0 to 30: 1, petroleum ether: ethyl acetate = 20: 1, P1: R f = 0.5) was purified to obtain 1 g (2.98 mmol, 99.1% yield) of the title compound having a colorless oily state.

[1090] Step 2: Preparation of methyl 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)benzoate

[1091] Methyl 5-(3-bromo-5-methylphenoxy)-2-methylbenzoate (1 g, 2.98 mmol, 1 eq), Pd(dppf)Cl2·CH2Cl2 (243 mg, 298 μmol, 0.1 eq), potassium acetate (878 mg, 8.95 mmol, 3 eq), and bis(pinacolato)diborane (1.52 g, 5.97 mmol, 2 eq) were dissolved in dioxane (10 mL), and the reaction mixture was degassed three times using nitrogen gas, heated to 95°C, and stirred for 16 h under nitrogen gas. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1, R1 R f = 0.5, P1 R f = 0.4) methyl 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)benzoate was completely consumed, and one new spot was generated. According to thin layer chromatography, the reaction proceeded cleanly. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (SiO2, petroleum ether: ethyl acetate = 1: 0 to 100: 1, petroleum ether: ethyl acetate = 20: 1, P1: R f = 0.4) was purified to obtain 1 g (2.62 mmol, 87.6% yield) of the title compound having the properties of a yellow oil.

[1092] Step 3: Preparation of methyl 5-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-2-methylbenzoate

[1093] 4-Bromo-N-ethyl-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (300 mg, 663 μmol, 1 eq), methyl 2-methyl-5-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)benzoate (507 mg, 1.33 mmol, 2 eq), cataCXium A Pd G3 (48.30 mg, 66.32 μmol, 0.1 eq), and tripotassium phosphate (1.5 M, 2.21 mL, 5 eq) were dissolved in dioxane (6 mL), and the gas removal in the reaction mixture was repeated three times, heated to 90°C, and stirred under nitrogen gas for 2 h. The mass value of the title compound was confirmed by LCMS. Water (20 mL) was added to the reaction mixture and extracted with ethyl acetate (20 mL × 2). The organic layer was washed with a saturated aqueous sodium chloride solution (20 mL × 1), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (600 mg, crude) as a brown oil.

[1094] Step 4: Preparation of 5-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-2-methylbenzoic acid

[1095] Methyl 5-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-2-methylbenzoate (600 mg, 955 μmol, 1 eq) was dissolved in methanol (6 mL), mixed with sodium hydroxide (3 M, 3.19 mL, 10 eq), and stirred at 20°C for 3 hours. The mass value of the title compound was confirmed by LCMS. The reaction mixture was titrated to pH = 3 using 1 N hydrochloric acid, water (10 mL) was added, and extracted with ethyl acetate (10 mL × 3). The organic layer was washed with a saturated aqueous solution of sodium chloride (10 mL×2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (450 mg, crude) having a brown, sticky appearance.

[1096] Step 5: Preparation of 4-(3-(3-((3-(dimethylamino)propyl)carbamoyl)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1097] 5-(3-(2-(Ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-2-methylbenzoic acid (400 mg, 870 μmol, 1 eq) and N',N'-dimethylpropane-1,3-diamine (97.8 mg, 957 μmol, 119 μL, 1.1 eq) were dissolved in N,N-dimethylformamide (8 mL), and HATU (364 mg, 957 μmol, 1.1 eq) and diisopropylethylamine (337 mg, 2.61 mmol, 454 μL, 3 eq) were mixed and stirred at 20°C for 2 h. The mass value of the title compound was confirmed by LCMS. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (10 mL x 3). The organic layer was washed with saturated aqueous sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: CD04-Welch Ultimate C18 150*25*7um; mobile phase: [water(FA)-ACN]; gradient: 13%-43% B over 15 min) to obtain 29 mg (50.7 μmol, 5.83% yield, 95.2% purity, HCOOH) of the title compound as a white solid.

[1098] 1H NMR (400 MHz, DMSO-d6) δ 12.33 (d,J= 1.0 Hz, 1H), 8.41 (t,J= 5.4 Hz, 1H), 8.29 (t,J= 5.6 Hz, 1H), 8.20-8.16 (m, 1H), 7.45 (s, 1H), 7.26 (d,J= 8.4 Hz, 1H), 7.19 (s, 1H), 7.07-7.00 (m, 2H), 6.99-6.94 (m, 2H), 6.80 (s, 1H), 3.57 (s, 3H), 3.30-3.27 (m, 2H), 3.21 (d,J= 5.8 Hz, 2H), 2.39-2.35 (m, 3H), 2.33-2.28 (m, 5H), 2.15 (s, 6H), 1.62 (quin,J= 7.0 Hz, 2H), 1.14 (t,J= 7.2 Hz, 3H); LCMS: m / z 545 [M+H] +

[1099] [Examples 209 to 223]

[1100]

[1101] Step 1: Preparation of 4-bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[1102] Methyl 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (1 g, 2.20 mmol, 1 eq) was dissolved in tetrahydrofuran and water, and sodium hydroxide (264 mg, 3.19 mmol, 3 eq) was mixed, heated to 50°C, and stirred for 3 hours. The mass value of the title compound was confirmed by LCMS. The reaction mixture was titrated to pH = 3 with 1 N hydrochloric acid, water (10 mL) was added, and ethyl acetate (10 mL x 3) was extracted. The organic layer was washed with a saturated aqueous sodium chloride solution (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (550 mg, 87%).

[1103] Step 2: Amide coupling

[1104] 4-Bromo-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1 eq) was dissolved in N,N-dimethylformamide, and HATU (1.5 eq), diisopropylethylamine (1.5 eq), and each amine (1 eq) were mixed and stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the carboxamide compound (yield: 60-90%).

[1105] Step 3: Chan-Lam reaction for dimethyl ether synthesis

[1106] 3-Fluoro(or chloro)-4-methylphenol (1 eq) was dissolved in dichloromethane (10 mL), and (3-bromo-5-methylphenyl)boronic acid (2 eq), copper acetate (1 eq), and triethylamine (5 eq) were mixed and stirred at room temperature overnight. The reaction mixture was filtered through Celite, the filtrate was concentrated under reduced pressure, and water and dichloromethane were added to separate the layers. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane) to obtain a bromophenoxy compound (yield: 15-25%).

[1107] Step 4: Synthesis of pinacol borane

[1108] The bromophenoxy compound (1 eq) obtained in step 3, bis(pinacolato)diborane (2 eq), potassium acetate (2 eq), Pd2(dba)3 (0.05 eq), and x-Phos (0.05 eq) were mixed in dioxane, heated to 90°C, stirred under argon gas for 20 hours, and then cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, the layers were separated, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (58-86%).

[1109] Step 5: Suzuki Cross Coupling

[1110] Each of the 4-bromo-N-Rf-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamides (1 eq) obtained in Step 2, 2-(3-(3-X-4-methylphenoxy)-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1 eq) obtained in Step 4, and Pd(dppf)2Cl2 (0.1 eq) were mixed with cesium carbonate (1.5 eq) dioxane and water, heated to 90°C, stirred under argon gas for 20 hours, and cooled to room temperature. Water and ethyl acetate were added to the reaction mixture to separate the layers, and the organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol 0%→50%) to obtain the title compound in Table 20 below (yield: 28-83%).

[1111] [Table 20]

[1112]

[1113]

[1114]

[1115]

[1116] [Example 224] Preparation of 4-(3-(3-chloro-4-methylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1117]

[1118] Step 1: Preparation of methyl 3-bromo-5-(3-chloro-4-methylphenoxy)benzoate

[1119] (3-Bromo-5-(methoxycarbonyl)phenyl)boronic acid (1 g, 7.01 mmol, 1 eq) and 3-chloro-4-methylphenol (2 g, 7.73 mmol, 1.1 eq) were dissolved in dichloromethane (10 mL), and copper acetate (1.28 g, 7.05 mmol, 1 eq), 4A MS (1 g), and triethylamine (5.82 g, 57.48 mmol, 8 mL, 8.2 eq) were mixed under oxygen gas (15 psi), and stirred at 25 °C for 12 h. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1, R1: R f = 0.16, P1: R f = 0.80) the starting material was exhausted and one new spot was generated. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 20:1, R f = 0.80) was performed, and reverse phase HPLC (FA) was performed to obtain the title compound (470 mg, 1.32 mmol, 18.84% yield) as a light yellow liquid.

[1120] Step 2: Preparation of 2-(3-bromo-5-(3-chloro-4-methylphenoxy)phenyl)propan-2-ol

[1121] Methyl 3-bromo-5-(3-chloro-4-methylphenoxy)benzoate (470 mg, 1.32 mmol, 1 eq) was dissolved in tetrahydrofuran (5 mL) and cooled to 0°C under nitrogen gas. Methylmagnesium bromide (3 M, 1.10 mL, 2.5 eq) dissolved in diethyl ether was slowly added and stirred at 20°C for 12 h. Thin layer chromatography (petroleum ether: ethyl acetate = 20:1) gave the starting material (R f = 0.78) was exhausted, and the mass of the title compound (R f = 0.42) was confirmed. After the reaction was completed, saturated ammonium chloride aqueous solution (20 mL) was added to neutralize. The reaction mixture was extracted with dichloromethane (10 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (460 mg, 1.29 mmol, 97.86% yield) as a sticky, bright yellow substance.

[1122] Step 3: Preparation of 2-(3-(3-chloro-4-methylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol

[1123] 2-(3-Bromo-5-(3-chloro-4-methylphenoxy)phenyl)propan-2-ol (590 mg, 2.32 mmol, 2.02 eq), 2-[3-bromo-5-(3-chloro-4-methyl-phenoxy)phenyl]propan-2-ol (410 mg, 1.15 mmol, 1 eq), Pd(dppf)Cl2·CH2Cl2 (98.4 mg, 120.49 μmol, 0.105 eq), potassium acetate (339 mg, 3.46 mmol, 3 eq) were dissolved in dioxane (8 mL), and the reaction mixture was purged with nitrogen gas three times, heated to 90°C, and stirred for 6 hours under nitrogen gas. Starting material was depleted by LCMS (EC25246-8-P1A1) and the mass of the title compound (R t= 0.551 min, m / z - 18 = 385) was confirmed. After cooling the reaction mixture to room temperature, it was filtered, and water (20 mL) was added to the filtrate, and extracted with ethyl acetate (5 mL × 3). The organic layer was washed with saturated aqueous sodium chloride solution (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (petroleum ether: ethyl acetate = 2:1, R f = 0.48) was purified to obtain the title compound (376 mg, 933.66 μmol, 80.99% yield) as a colorless, sticky substance.

[1124] Step 4: Preparation of 4-(3-(3-chloro-4-methylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[1125] 4-Bromo-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (130 mg, 436.04 μmol, 1 eq), 2-(3-(3-chloro-4-methylphenoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol (200 mg, 496.63 μmol, 1.14 eq), Pd(dppf)Cl2 (34.67 mg, 47.38 μmol, 0.109 eq), sodium carbonate (143 mg, 1.35 mmol, 3.09 eq) was dissolved in dioxane (2 mL) and H2O (0.4 mL), and the gas in the reaction mixture was removed three times using nitrogen gas, then heated to 100°C and stirred for 16 h under nitrogen gas. LCMS (EC25246-13-P1A1) showed that the starting material was consumed, and the mass (R) of the title compound t= 0.455 min, m / z = 494) was confirmed. After cooling the reaction mixture to room temperature, it was filtered, and water (20 mL) was added to the filtrate, and extracted with ethyl acetate (15 mL × 3). The organic layer was washed with saturated aqueous sodium chloride solution (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (petroleum ether: ethyl acetate = 0:1...

Claims

1. A compound represented by the following chemical formula 1, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, R is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, C3-C10 cycloalkylcarbonyl or C3-C10 cycloalkylsulfonyl; Ar is or and; R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb and; R aa is hydrogen, C1-C10 alkylcarbonyl, C6-C12 arylcarbonyl, C3-C10 cycloalkylcarbonyl, C1-C10 alkylsulfonyl, C6-C12 arylsulfonyl or C3-C10 cycloalkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, -NR bb1 R bb2 , -NR bb1 -C(=O)R bb3 , -OR bb4 , -C(=O)-R bb5 , -C(=O)-NR bb1 R bb2 , -OC(=O)-NR bb1 R bb2 or -NR bb1 -C(=O)-NR bb1 R bb2 and; R bb1 , R bb2 and R bb4 are each independently hydrogen, C1-C10 alkyl, C6-C12 aryl or C3-C10 cycloalkyl; R bb3 and R bb5 are each independently C1-C10 alkyl, C6-C12 aryl or C3-C10 cycloalkyl C1-C10 alkoxy, C6-C12 aryloxy or C3-C10 cycloalkyloxy; R c is hydrogen or C1-C10 alkyl or C3-C10 cycloalkyl; X1 and X2 are each independently a single bond, NH, O or S, wherein one of X1 and X2 is a single bond and the other is NH, O or S; R d and R e are each independently hydrogen, C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl, C1-C10 alkoxyC1-C10 alkyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl may be further substituted with C1-C10 alkyl; R f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f Alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy; R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, -C(=O)-R 1c , -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1c is C1-C10 alkyl, C3-C10 cycloalkyl or -NR 1f R 1g and; R 1a , R 1b , R 1f and R 1g are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl; R 1d and R 1e are each independently C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or C1-C10 alkoxy; R 2 is C1-C10 alkyl, C3-C10 cycloalkyl, halogen, C1-C10 alkoxy, -NR 2a R 2b , -NR'-C(=O)-L 2a -R 2c , -C(=O)-NR 2a R 2b , -C(=O)-NR'-L 2a -R 2c , -C(=O)-NR'-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2b -C(=O)-R 2f , -NR'-S(=O)2-R 2g or -C(=O)-R 2h and; R 2a and R 2b are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl; R' is hydrogen or C1-C10 alkyl; L 2a is a single bond, C1-C10 alkylene or C3-C10 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, halogen and haloC1-C10 alkyl; R 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl, C6-C12 arylsulfonyl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 alkylcarbonyl, C3-C10 cycloalkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl and -L'-Ar'; L' is a single bond or C1-C10 alkylene; Ar' is C1-C10 heteroaryl or C3-C10 cycloalkyl which is optionally substituted with C1-C10 alkyl; R 2d is hydrogen or C1-C10 alkyl; R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, -L''-R'', -C(=O)-R''' or -C(=O)-NR''''R''''; L'' is C1-C10 alkylene or C3-C10 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl; R''' is C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl or C1-C10 alkylaminoC1-C10 alkyl; R'''' and R''''' are each independently hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxyC1-C10 alkyl; L 2b is C1-C10 alkylene or C3-C10 cycloalkylene; R 2f is amino or C3-C10 heterocycloalkyl; R 2g is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and C6-C12 aryl; R 2h is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy, C3-C10 cycloalkoxy or C6-C12 aryloxy; R 3 is C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl, haloC1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkyl; a is an integer from 0 to 4; The above R 1 , R 2 , R 1d and R 1e Alkyl, cycloalkyl or alkoxy, R 1a , R 1b , R 1c , R 1f , R 1g , R 2a , and R 2b The alkyl or cycloalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, C1-C10 alkoxy, hydroxy and haloC1-C10 alkoxy.

2. In paragraph 1, The compound is a compound represented by the following chemical formula 2 or chemical formula 3, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 2] [Chemical Formula 3] In the above chemical formulas 2 and 3, Ar, R 1 and R 2 is the same as the definition in chemical formula 1 of claim 1; R 11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy.

3. In paragraph 1, wherein R is hydrogen, C1-C10 alkyl, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; Ar is , , , , , or and; R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of R is C1-C10 alkyl; aa is hydrogen, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, amino or hydroxy; R c is hydrogen or C1-C10 alkyl; R d and R e are each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f Alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy; R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e A compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein each independently represents C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl, or haloC1-C10 alkoxyC1-C10 alkyl; wherein the alkyl, cycloalkyl, and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, and hydroxy.

4. In paragraph 2, The above R 2 is C1-C10 alkyl, halogen or C1-C10 alkoxy, and R 2 A compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein the alkyl or alkoxy of the compound may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, and hydroxy.

5. In paragraph 2, The above R 2 is -C(=O)-NR 2a R 2b , -C(=O)-NH-L 2a -R 2c , -C(=O)-NH-L 2a -NR 2d R 2e or -C(=O)-R 2h and; R 2a and R 2b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; L 2a is C1-C10 alkylene or C3-C10 cycloalkylene, and the above L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, halogen and haloC1-C10 alkyl; R 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl or C6-C12 arylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, or arylsulfonyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, and C1-C10 heteroaryl; R 2d is hydrogen or C1-C10 alkyl; R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl, C1-C10 alkoxyC1-C10 alkylcarbonyl, C1-C10 alkylaminoC1-C10 alkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl or C1-C10 alkoxyC1-C10 alkylaminocarbonyl; R 2h is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy or C6-C12 aryloxy, a compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof or a pharmaceutically acceptable salt thereof.

6. In paragraph 2, The above R 2 is -NR 2a R 2b , -NH-C(=O)-L 2a -R 2c , -NH-C(=O)-R 2cc , -NH-C(=O)-L 2a -NR 2d R 2e , -NH-C(=O)-NR 2dd R 2ee , -NH-C(=O)-L 2b -C(=O)-R 2f or -NH-S(=O)2-R 2g and; R 2a and R 2b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; L 2a is C1-C10 alkylene or C3-C10 cycloalkylene, and the above L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, halogen and haloC1-C10 alkyl; R 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl or C6-C12 arylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl or arylsulfonyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, and C1-C10 heteroaryl; R 2cc is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2cc wherein alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 heteroaryl and -L'-Ar'; L' is C1-C10 alkylene; Ar' is C1-C10 heteroaryl which is optionally substituted with C1-C10 alkyl; R 2d is hydrogen or C1-C10 alkyl; R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl, C1-C10 alkoxyC1-C10 alkylcarbonyl, C1-C10 alkylaminoC1-C10 alkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl or C1-C10 alkoxyC1-C10 alkylaminocarbonyl; R 2dd is hydrogen or C1-C10 alkyl; R 2ee is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, hydroxyC3-C10 cycloalkyl or -L''-R''; L'' is C1-C10 alkylene or C3-C10 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl; L 2b is C1-C10 alkylene or C3-C10 cycloalkylene; R 2f is amino or C3-C10 heterocycloalkyl; R 2g is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g A compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein the alkyl, cycloalkyl, aryl, or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, and C6-C12 aryl.

7. In paragraph 2, The compound is a compound represented by any one of the following chemical formulae 4 to 9, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] [Chemical Formula 9] In the above chemical formulas 4 to 9, R is hydrogen, C1-C6 alkyl, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; X1 and X2 are each independently NH, O or S; R a and R b are each independently C1-C6 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of them is C1-C6 alkyl; R aa is hydrogen, C1-C6 alkylcarbonyl or C1-C6 alkylsulfonyl; L aa is C1-C6 alkylene or C3-C8 cycloalkylene; R bb is hydrogen, -NR bb1 R bb2 or -OR bb4 and; R bb1 , R bb2 and R bb4 are each independently hydrogen, C1-C6 alkyl, C6-C12 aryl or C3-C8 cycloalkyl; R c is hydrogen or C1-C6 alkyl; R d and R e are each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl may be further substituted with C1-C6 alkyl; R f is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f Alkyl or cycloalkyl of may be further substituted by one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl, amino, hydroxy, C1-C6 alkoxycarbonylamino, C1-C6 alkylaminocarbonylamino, C1-C6 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfonylamino and C1-C6 alkylaminocarbonyloxy; R 1 is C1-C6 alkyl, C3-C8 cycloalkyl, -NH2, C1-C6 alkylamino, halogen, C1-C6 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and the alkyl or cycloalkyl of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl and hydroxy; R 1d and R 1e are each independently C1-C6 alkyl, haloC1-C6 alkyl, C3-C8 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or C1-C6 alkoxyC1-C6 alkyl; R 2 is C1-C6 alkyl, halogen, C1-C6 alkoxy, -NH2, -NH-C(=O)-L 2a -R 2c , -NH-C(=O)-R 2cc , -C(=O)NH2, -C(=O)NH-L 2a -R 2c , -C(=O)-NH-L 2a -NR 2d R 2e , -NH-C(=O)-L 2a -NR 2d R 2e , -NH-C(=O)-NR 2dd R 2ee , -NH-C(=O)-L 2b -C(=O)-R 2f or -NH-S(=O)2-R 2g and the above R 2 Alkyl or alkoxy of may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl and hydroxy; L 2a is C1-C6 alkylene or C3-C8 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C6 alkyl, halogen and haloC1-C6 alkyl; R 2c is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylthio, C3-C8 cycloalkylthio, C6-C12 arylthio, C1-C6 alkylsulfonyl, C3-C8 cycloalkylsulfonyl or C6-C12 arylsulfonyl, and R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, or arylsulfonyl may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, C3-C8 cycloalkyl, and C1-C10 heteroaryl; R 2cc is C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C8 heterocycloalkyl, C1-C10 heteroaryl, hydroxyC1-C6 alkyl, C6-C12 aryloxy, C1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy or C1-C6 alkoxyC1-C6 alkoxyC1-C6 alkyl, and the R 2cc Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkylamino, C1-C10 heteroaryl and -L'-Ar'; L' is C1-C6 alkylene; Ar' is C1-C10 heteroaryl which is optionally substituted with C1-C6 alkyl; R 2d is hydrogen or C1-C6 alkyl; R 2e is hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C8 cycloalkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonyl, C1-C6 alkylaminoC1-C6 alkylcarbonyl, aminocarbonyl, C1-C6 alkylaminocarbonyl or C1-C6 alkoxyC1-C6 alkylaminocarbonyl; R 2dd is hydrogen or C1-C6 alkyl; R 2ee is hydrogen, C1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C6-C12 aryl, aminoC1-C6 alkyl, C1-C6 alkylaminoC1-C6 alkyl, hydroxyC3-C8 cycloalkyl or -L''-R''; L'' is C1-C6 alkylene or C3-C8 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C6 alkylcarbonylamino, C1-C6 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C6 alkyl; L 2b is C1-C6 alkylene or C3-C8 cycloalkylene; R 2f is amino or C3-C10 heterocycloalkyl; R 2g is C1-C6 alkyl, C3-C8 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C6 alkyl, haloC1-C6 alkyl and C6-C12 aryl; R 11 Inland R 13 are each independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy, haloC1-C6 alkyl or haloC1-C6 alkoxy.

8. In paragraph 1, The compound is a compound represented by the following chemical formula 10, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 10] In the above chemical formula 10, Y is or and; R 2 is a halogen; R 11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy; R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e are each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy; R c is hydrogen or C1-C10 alkyl; R e is C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f The alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

9. In paragraph 1, The compound is a compound represented by the following chemical formula 11 or 12, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 11] [Chemical Formula 12] In the above chemical formulas 11 and 12, Y is or and; R 2 is a halogen; R 11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy; R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e are each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy; R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of R is C1-C10 alkyl; aa is hydrogen, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, amino or hydroxy; R c is hydrogen or C1-C10 alkyl; R d is C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f The alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

10. In paragraph 1, The compound is a compound represented by the following chemical formula 13, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 13] In the above chemical formula 13, R is hydrogen, C1-C10 alkyl, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; Y is or and; R 2 is C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 2a R 2b , -NR'-C(=O)-L 2a -R 2c , -C(=O)-NR 2a R 2b , -C(=O)-NR'-L 2a -R 2c , -C(=O)-NR'-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2a -NR 2d R 2e , -NR'-C(=O)-L 2b -C(=O)-R 2f , -NR'-S(=O)2-R 2g or -C(=O)-R 2h and the above R 2 Alkyl, cycloalkyl or alkoxy of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy; R 2a and R 2b are each independently hydrogen, C1-C10 alkyl or C3-C10 cycloalkyl; R' is hydrogen or C1-C10 alkyl; L 2a is a single bond, C1-C10 alkylene or C3-C10 cycloalkylene, and L 2a The alkylene or cycloalkylene may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, halogen and haloC1-C10 alkyl; R 2c is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylthio, C3-C10 cycloalkylthio, C6-C12 arylthio, C1-C10 alkylsulfonyl, C3-C10 cycloalkylsulfonyl, C6-C12 arylsulfonyl, hydroxyC1-C10 alkyl, C6-C12 aryloxy, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl, C1-C10 alkoxyC1-C10 alkoxy or C1-C10 alkoxyC1-C10 alkoxyC1-C10 alkyl, and the R 2c Alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, alkylthio, cycloalkylthio, arylthio, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, alkoxy, alkoxyalkyl or alkoxyalkoxyalkyl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkylamino, C1-C10 alkylcarbonyl, C3-C10 cycloalkylcarbonyl, aminocarbonyl, C1-C10 alkylaminocarbonyl and -L'-Ar'; L' is a single bond or C1-C10 alkylene; Ar' is C1-C10 heteroaryl or C3-C10 cycloalkyl which is optionally substituted with C1-C10 alkyl; R 2d is hydrogen or C1-C10 alkyl; R 2e is hydrogen, C1-C10 alkyl, C1-C10 alkoxyC1-C10 alkyl, C6-C12 aryl, aminoC1-C10 alkyl, C1-C10 alkylaminoC1-C10 alkyl, C6-C12 arylsulfonyl, C1-C10 heteroarylsulfonyl, hydroxyC3-C10 cycloalkyl, -L''-R'', -C(=O)-R''' or -C(=O)-NR''''R''''; L'' is C1-C10 alkylene or C3-C10 cycloalkylene; R'' is C3-C10 heterocycloalkyl, C1-C10 heteroaryl, C1-C10 alkylcarbonylamino, C1-C10 alkylsulfonylamino or hydroxy, and the heterocycloalkyl or heteroaryl of R'' may be further substituted with C1-C10 alkyl; R''' is C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkoxyC1-C10 alkyl or C1-C10 alkylaminoC1-C10 alkyl; R'''' and R''''' are each independently hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl or C1-C10 alkoxyC1-C10 alkyl; L 2b is C1-C10 alkylene or C3-C10 cycloalkylene; R 2f is amino or C3-C10 heterocycloalkyl; R 2g is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C1-C10 heteroaryl, and R 2g The alkyl, cycloalkyl, aryl or heteroaryl may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and C6-C12 aryl; R 2h is C1-C10 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C1-C10 alkoxy, C3-C10 cycloalkoxy or C6-C12 aryloxy; R 11 Inland R 13 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, haloC1-C10 alkyl or haloC1-C10 alkoxy; Ar 1 silver , or and; R 1 Silver C1-C10 alkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, -NR 1a R 1b , halogen, C1-C10 alkylcarbonyl, -NH-SO2-R 1d or -NH-C(=O)-R 1e and; R 1a and R 1b are each independently hydrogen, C1-C10 alkyl, haloC1-C10 alkyl or hydroxyC1-C10 alkyl; R 1d and R 1e are each independently C1-C10 alkyl, haloC1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl, C1-C10 alkoxyC1-C10 alkyl or haloC1-C10 alkoxyC1-C10 alkyl; the alkyl, cycloalkyl and alkoxy of R1 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl and hydroxy; R a and R b are each independently C1-C10 alkyl, -NH-R aa , -NH-C(=O)-NH-L aa -R bb or -NH-C(=O)-OL aa -R bb , and only the above R a and R b At least one of R is C1-C10 alkyl; aa is hydrogen, C1-C10 alkylcarbonyl or C1-C10 alkylsulfonyl; L aa is C1-C10 alkylene or C3-C10 cycloalkylene; R bb is hydrogen, amino or hydroxy; R c is hydrogen or C1-C10 alkyl; R d and R e are each independently C1-C10 heteroaryl, C3-C10 heterocycloalkylcarbonyl or -C(=O)-NH-R f and the above R d and R e The heteroaryl of R may be further substituted with C1-C10 alkyl; f is hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, haloC3-C10 cycloalkyl or C3-C10 heterocycloalkyl, and R f The alkyl or cycloalkyl of may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, haloC1-C10 alkyl, amino, hydroxy, C1-C10 alkoxycarbonylamino, C1-C10 alkylaminocarbonylamino, C1-C10 alkylcarbonylamino, C3-C10 heterocycloalkyl, carboxylic acid, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfonylamino and C1-C10 alkylaminocarbonyloxy.

11. In paragraph 7, The above R 2 A compound selected from the following structures, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

12. In paragraph 1, A compound selected from the group consisting of: a hydrate thereof, a solvate thereof, an isomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof: (1)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylphenyl)tetrahydrofuran-3-carboxamide, (2)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylphenyl)-3-(piperidin-1-yl)propanamide, (3) 1-(2-(dimethylamino)acetamido)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3-methylphenyl)cyclobutanecarboxamide, (4) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylphenyl)butanamide, (5)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylphenyl)-3-(piperidin-1-yl)propanamide, (6)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3-methylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide, (7) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)tetrahydrofuran-3-carboxamide, (8)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-2-(2-methoxyethoxy)acetamide, (9) 2-acetamido-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)acetamide, (10)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-2-methoxyacetamide, (11) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)acetamide, (12)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)tetrahydro-2H-pyran-4-carboxamide, (13) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)tetrahydrofuran-2-carboxamide, (14)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide, (15)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (16)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide, (17)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (18) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)butanamide, (19)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-fluorophenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide, (20)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-(2-methoxyethoxy)acetamide, (21) 2-acetamido-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)acetamide, (22)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-methoxyacetamide, (23) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)acetamide, (24) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)tetrahydrofuran-2-carboxamide, (25)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide, (26)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (27)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide, (28)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (29) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)tetrahydrofuran-3-carboxamide, (30) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)butanamide, (31)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide, (32)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-hydroxyacetamide, (33)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-2-(3,3-dimethylureido)acetamide, (34) (S)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-1-methylpyrrolidine-2-carboxamide, (35)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide, (36)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (37)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (38)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide, (39)N-(4-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide, (40)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide, (41)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide, (42)N-(4-(3-acetamido-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (43)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (44)N-(4-(3-acetamido-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (45)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (46)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-methoxypropanamide, (47)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-morpholinopropanamide, (48)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (49)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(piperidin-1-yl)propanamide, (50)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (51)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (52)N-(4-(3-(butylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (53)N-(4-(3-(3-chloropropylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (54)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-methylethylsulfonamido)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (55)N-(4-(3-(cyclopropanesulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-3-(1H-imidazol-1-yl)propanamide, (56) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-3,5-dimethylphenyl)acetamide, (57) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)acetamide, (58) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-3,5-dimethylphenyl)butanamide, (59) 2-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-methylethylsulfonamido)phenoxy)-3,5-dimethylphenyl)acetamide, (60)N-(4-(3-(cyclopropanesulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-2-(dimethylamino)acetamide, (61)N-(4-(3-(cyclopropanesulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide, (62) 1-(2-(dimethylamino)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (63) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-isopentylurea, (64) 2-(dimethylamino)ethyl (4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate, (65) Isopentyl (4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate, (66) Phenyl(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate, (67) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-((1r,4r)-4-hydroxycyclohexyl)urea, (68) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (69) Methyl (4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)carbamate, (70) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-methylurea, (71) 1-(2-aminoethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (72) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-hydroxyethyl)urea, (73) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-methoxyethyl)urea, (74) 1-(2-(diethylamino)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (75) 1-(2-aminoethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-1-methylurea, (76) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(piperidin-1-yl)ethyl)urea, (77) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-((tetrahydrofuran-2-yl)methyl)urea, (78) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(4-methylpiperazin-1-yl)ethyl)urea, (79)N-(2-(3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)ureido)ethyl)acetamide, (80)N-(2-(3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)ureido)ethyl)methanesulfonamide, (81) 1-(3-(dimethylamino)propyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (82) 1-(2-(1H-imidazol-1-yl)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (83) 1-(2-(1H-pyrrol-1-yl)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (84) 1-(2-(1H-pyrazol-1-yl)ethyl)-3-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)urea, (85) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(pyrrolidin-1-yl)ethyl)urea, (86) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-morpholinoethyl)urea, (87) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-(2-(methylamino)ethyl)urea, (88) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-ethylurea, (89)N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)morpholine-4-carboxamide, (90) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-isopropylurea, (91) 1-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)-3-phenylurea, (92) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-3,5-dimethylisoxazole, (93) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(trifluoromethyl)phenoxy)-3,5-dimethylphenyl)butanamide, (94)N-(4-(3-(difluoromethyl)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide, (95)N-(4-(3-acetyl-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-3,5-dimethylphenyl)-4-(dimethylamino)butanamide, (96) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-hydroxyethyl)phenoxy)-3,5-dimethylphenyl)butanamide, (97) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(1-fluoroethyl)phenoxy)-3,5-dimethylphenyl)butanamide, (98) 4-(dimethylamino)-N-(4-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-hydroxypropan-2-yl)phenoxy)-3,5-dimethylphenyl)butanamide, (99)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-2-(dimethylamino)acetamide, (100) 2-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)acetamide, (101)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide, (102) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-2-methylphenyl)butanamide, (103) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)butanamide, (104)N-(5-(3-(butylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-4-(dimethylamino)butanamide, (105) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(2-methoxyacetamido)phenoxy)-2-methylphenyl)butanamide, (106) 4-(dimethylamino)-N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-isobutyramidophenoxy)-2-methylphenyl)butanamide, (107)N-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropanecarboxamide, (108)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide, (109)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide, (110)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-(piperidin-1-yl)propanamide, (111)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-morpholinopropanamide, (112)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-morpholinopropanamide, (113)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide, (114)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide, (115)N-(5-(3-(butylsulfonamido)-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-(1H-imidazol-1-yl)propanamide, (116)N-(5-(3-amino-5-(3,5-dimethylisoxazol-4-yl)phenoxy)-2-methylphenyl)-3-methoxypropanamide, (117)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(methylsulfonamido)phenoxy)-2-methylphenyl)-3-methoxypropanamide, (118)N-(5-(3-(3,5-dimethylisoxazol-4-yl)-5-(ethylsulfonamido)phenoxy)-2-methylphenyl)-3-methoxypropanamide, (119) 4-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (120) 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (121) 4-(3-(4-(4-(dimethylamino)butanamido)-2,6-dimethylmenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (122) 4-(3-(4-(3-(1H-imidazol-1-yl)propanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (123) 4-(3-(2,6-dimethyl-4-(3-(piperidin-1-yl)propanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (124) 4-(3-(2,6-dimethyl-4-(3-(pyrrolidin-1-yl)propanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (125) 4-(3-(2,6-dimethyl-4-(3-(4-methylpiperazin-1-yl)propanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (126) 4-(3-(4-acetamido-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (127)N-Ethyl-4-(3-(4-(2-methoxyacetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (128) 4-(3-(2,6-dimethyl-4-(4-(piperidin-1-yl)butanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (129) 4-(3-(4-(3-(dimethylamino)propanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (130) 4-(3-(4-(4-(1H-imidazol-1-yl)butanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (131) 4-(3-(2,6-dimethyl-4-(4-(pyrrolidin-1-yl)butanamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (132) 4-(3-(2,6-dimethyl-4-(2-(pyrrolidin-1-yl)acetamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (133) tert-butyl(4-((4-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)amino)-4-oxobutyl)carbamate, (134) tert-butyl(2-((4-(3-(2-(ethylcarbamoyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-methylphenoxy)-3,5-dimethylphenyl)amino)-2-oxoethyl)carbamate, (135) 4-(3-(4-(4-aminobutanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide hydrochloride, (136) 4-(3-(4-(2-aminoacetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide hydrochloride, (137) 4-(3-(4-(2-(1H-imidazol-1-yl)acetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (138) 4-(3-(2,6-dimethyl-4-(5-methylhexamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (139) 4-(3-(4-(5-(dimethylamino)pentanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (140) 4-(3-(2,6-dimethyl-4-(pyrrolidine-1-carboxamido)phenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (141) 4-(3-amino-5-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (142) 4-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-(methylsulfonamido)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (143)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (144) tert-butyl ((1r,4r)-4-(4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate, (145) tert-butyl ((1r,4r)-4-(4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate, (146) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (147)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (148)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (149) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (150) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (151) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (152) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (153) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (154) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (155)N-Cyclopropyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (156) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1s,4s)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (157)N-(4,4-difluorocyclohexyl)-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (158)N-((1r,4r)-4-acetamidocyclohexyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (159) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-cyclohexyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (160) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-cyclopropyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (161) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-(3,3-dimethylureido)cyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (162) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1s,4s)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (163) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(4,4-difluorocyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (164) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(1-(trifluoromethyl)cyclopropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (165) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (166) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(2,2,2-trifluoroethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (167) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2-hydroxyethyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (168) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(3-hydroxypropyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (169) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2,2-difluoro-1-methylcyclopropyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (170) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (171)N-((1S,3S)-3-aminocyclohexyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (172)N-((1S,3S)-3-aminocyclopentyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (173)N-((1R,3R)-3-aminocyclopentyl)-4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (174) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-N-((1S,3S)-3-(methylsulfonamido)cyclopentyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (175) (1r,4r)-4-(4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid, (176) (1r,4r)-4-(4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid, (177) (1r,4r)-Methyl 4-(4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylate, (178) (1r,4r)-Methyl 4-(4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexanecarboxylate, (179) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1S,3S)-3-hydroxycyclopentyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (180) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1S,3S)-3-hydroxycyclopentyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (181) 4-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-6-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-7(6H)-one, (182)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (183) 4-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (184)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(1-hydroxycyclopropyl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (185)N-Ethyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (186) 4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (187)N-Cyclopropyl-4-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (188) 4-(3-amino-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (189)N-Ethyl-6-methyl-4-(3-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)-5-(methylsulfonamido)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (190)N-Ethyl-6-methyl-4-(3-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)-5-(ethylsulfonamido)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (191) 4-(3-(3-amino-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (192) 4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (193)N-Ethyl-6-methyl-4-(3-methyl-5-(4-methyl-3-(4-(piperidin-1-yl)butanamido)phenoxy)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (194)N-Ethyl-6-methyl-4-(3-methyl-5-(4-methyl-3-(3-(piperidin-1-yl)propanamido)phenoxy)phenyl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (195) 4-(3-(3-(3-(1H-imidazol-1-yl)propanamido)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (196) 4-(3-(3-(2-(dimethylamino)acetamido)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (197)N-Ethyl-4-(3-(3-(2-methoxyacetamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (198) 4-(3-(3-acetamido-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (199)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (200)N-((1s,4s)-4-aminocyclohexyl)-4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (201)N-(bicyclo[1.1.1]pentan-1-yl)-4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (202) 4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (203) 4-(3-(3-(4-(dimethylamino)butanamido)-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (204) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(5-methyl-1H-pyrrol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide, (205) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(4-methyl-1H-imidazol-2-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide, (206) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-2-(3-methyl-1H-1,2,4-triazol-5-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide, (207) 4-(dimethylamino)-N-(2-methyl-5-(3-methyl-5-(6-methyl-7-oxo-2-(1H-tetrazol-5-yl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy)phenyl)butanamide, (208) 4-(3-(3-((3-(dimethylamino)propyl)carbamoyl)-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (209)N-Ethyl-4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (210) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (211) tert-butyl((1r,4r)-4-(4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate, (212) tert-butyl((1r,4r)-4-(4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamido)cyclohexyl)carbamate, (213)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (214)N-((1r,4r)-4-aminocyclohexyl)-4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (215) 4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (216) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (217) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-cyclopropyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (218) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-((1s,4s)-4-hydroxycyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (219) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-(4,4-difluorocyclohexyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (220) 4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (221) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-propyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (222) 4-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (223) 4-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-6-methyl-7-oxo-N-(3,3,3-trifluoropropyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (224) 4-(3-(3-chloro-4-methylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-ethyl-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide, (225) 7-(3-(4-amino-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (226) 7-(3-(4-(2-(dimethylamino)acetamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (227) 7-(3-(4-(3-(1H-imidazol-1-yl)propanamido)-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (228)N-Ethyl-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (229) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (230) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (231)N-((1r,4r)-4-aminocyclohexyl)-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (232) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (233) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2-hydroxyethyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (234) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(3-hydroxypropyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (235) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(3-hydroxypropyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (236) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-N-(2-hydroxyethyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (237) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-propyl-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (238) 7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-propyl-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (239) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-N-((1r,3r)-3-hydroxycyclobutyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (240) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-(tetrahydro-2H-pyran-4-yl)-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (241) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-N-((tetrahydro-2H-pyran-4-yl)methyl)-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (242) (1r,4r)-4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid, (243) (1r,4r)-4-(7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid, (244) 4-(7-(3-(4-chloro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylate, (245) (1r,4r)-Methyl 4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylate, (246)N-Ethyl-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (247) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(trifluoromethyl)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (248) 7-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (249) 7-(3-cyclopropyl-5-(4-fluoro-2,6-dimethylphenoxy)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (250)N-Ethyl-7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (251) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N,5-dimethyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (252) 7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (253) (1r,4r)-4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylic acid, (254) (1r,4r)-Methyl 4-(7-(3-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamido)cyclohexanecarboxylate, (255)N-Ethyl-7-(3-(3-fluoro-4-methylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (256) 7-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-ethyl-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (257) 7-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, (258)N-((1r,4r)-4-aminocyclohexyl)-7-(3-(3-chloro-4-methylphenoxy)-5-methylphenyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide, and (259) 7-(3-(3-Fluoro-4-methylphenoxy)-5-methylphenyl)-N-((1r,4r)-4-hydroxycyclohexyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carboxamide.

13. A pharmaceutical composition for the prevention or treatment of a disease selected from the group consisting of diabetes, metabolic syndrome, fibrosis, inflammatory disease, kidney disease, and cancer, containing as an active ingredient a compound according to any one of claims 1 to 12, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof.

14. In paragraph 13, The pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.

15. A bromodomain inhibitor containing a compound according to any one of claims 1 to 12, a hydrate thereof, a solvate thereof, an isomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

16. A method for preventing or treating diseases and disorders responsive to inhibition of a bromodomain-containing protein, comprising administering to a subject suffering from or at risk of developing a disease or disorder responsive to inhibition of a bromodomain-containing protein a compound according to any one of claims 1 to 12, a hydrate thereof, a solvate thereof, an isomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof.

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