Novel tricycle derivative compound and its use

Abstract

The present invention relates to novel tricycle derivative compounds and uses thereof, and more specifically to novel tricycle derivative compounds having methionine adenosyltransferase 2A (MAT2A) inhibitory activity and uses thereof.

Description

[Technical Field]

[0001] The present invention relates to novel tricycle derivative compounds and uses thereof, and more specifically to novel tricycle derivative compounds having methionine adenosyltransferase 2A (MAT2A) inhibitory activity and uses thereof. [Background technology]

[0002] Methionine adenosyltransferase (MAT), also known as S-adenosylmethionine synthase, is a cellular enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM or AdoMet) from methionine and ATP and is considered to be the rate-limiting step in the methionine cycle. SAM is a propylamino donor in polyamine biosynthesis, the major methyl donor for DNA methylation, and is involved in gene transcription and cellular proliferation as well as the production of secondary metabolites.

[0003] Methylthioadenosine phosphorylase (MTAP) is an enzyme found in all normal tissues that catalyzes the conversion of methylthioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Adenine is salvaged to produce adenosine monophosphate, and 5-methylthioribose-1-phosphate is converted to methionine and formate. Because of this salvage pathway, MTA can serve as an alternative purine source when de novo purine synthesis is blocked, for example, using antimetabolites such as L-alanosine.

[0004] Many human and mouse malignant cells lack MTAP activity. MTAP deficiency is not only found in tissue culture cells; such deficiency is also present in primary leukemia, glioma, melanoma, pancreatic cancer, non-small cell lung cancer (NSCLC), bladder cancer, astrocytoma, osteosarcoma, head and neck cancer, myxoid chondrosarcoma, ovarian cancer, endometrial cancer, breast cancer, soft tissue sarcoma, non-Hodgkin's lymphoma, and mesothelioma.

[0005] The present inventors have developed novel tricycle derivative compounds having MAT2A inhibitory activity and uses thereof, and have completed the present invention. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Korean Patent Publication No. 10-2022-0051301 [Patent Document 2] Korean Patent Publication No. 10-2022-0050832 [Patent Document 3] Korean Patent Publication No. 10-2021-0103498 [Patent Document 4] Korean Patent Publication No. 10-2018-0100125 [Patent Document 5] Korean Patent Publication No. 10-2019-0046921 [Patent Document 6] Korean Patent Publication No. 10-2020-0138769 Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide novel tricycle derivative compounds.

[0008] Another object of the present invention is to provide a pharmaceutical composition for treating or preventing a MAT2A-associated disease or disorder, which comprises the compound as an active ingredient.

[0009] Other objects and advantages of the present application will become more apparent from the following detailed description, taken in conjunction with the claims. Contents not described in this specification are fully understood and can be inferred by those skilled in the art in the present application or in a similar technical field, and therefore, the description thereof will be omitted. [Means for solving the problem]

[0010] An embodiment of the present invention provides a compound selected from the group consisting of compounds of the following Chemical Formula 1, optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof: [ka]

[0011] Another embodiment of the present invention provides a pharmaceutical composition for treating or preventing a MAT2A-related disease or disorder, comprising, as an active ingredient, a compound selected from the compound of Formula 1, its optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof. [Effects of the Invention]

[0012] A novel tricycle derivative compound having the structure of Chemical Formula 1 according to one embodiment of the present invention and a pharmaceutical composition containing the same are effective against MAT2A-related diseases or disorders and can be usefully used as a therapeutic agent therefor. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention will now be described in further detail.

[0014] Unless otherwise defined, all technical terms used in the present invention have the meanings commonly understood by those of ordinary skill in the art in the field related to the present invention. In addition, although preferred methods and samples are described in this specification, similar or equivalent methods and samples are also included in the scope of the present invention.

[0015] An embodiment of the present invention provides a compound selected from the group consisting of compounds of the following Chemical Formula 1, optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof: [ka]

[0016] In the above Chemical Formula 1, X and Z are each independently N or CH; Y is CR 3 and;

[0017] R 3 is H, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfonyl, hydroxy, halogen, haloalkyl, haloalkoxy, cycloalkyl, cyano, amino, alkylamino, haloalkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxyalkyl, hydroxyalkoxy, hydroxyalkylamino, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aminoalkyl, aminoalkoxy, aminoalkylamino, aryl, heteroaryl, heteroaryloxy, heteroarylamino, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyloxyalkoxy or heterocyclyloxyalkylamino;

[0018] wherein aryl, heteroaryl, or heterocyclyl is unsubstituted or substituted with one to three selected from alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, halo, cyano, hydroxyalkyl, alkoxyalkyl, and aminoalkyl; [ka] are each independently H, cycloalkyl, aryl, heteroaryl, or heterocyclyl;

[0019] wherein said cycloalkyl, aryl, heteroaryl, or heterocyclyl may each be monocyclic, bicyclic, or polycyclic;

[0020] Here, cycloalkyl, aryl, heteroaryl or heterocyclyl is defined as R 2 or unsubstituted with 1 to 3 independently selected from:

[0021] L is C 1-3 Alkylene, O, NH, N(C 1-3 alkyl), S, SO, SO2 or a bond;

[0022] R 2 is alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, alkylsulfonyl, halogen, cyano, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, sulfonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocyclylcarbonyl or ureido;

[0023] R 1 is H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, substituted aminoalkyl, aminocarbonylalkyl, or aminosulfonylalkyl.

[0024] definition As used herein, the term "alkyl," unless otherwise specified, refers to a substituted or unsubstituted straight-chain or branched hydrocarbon residue. For example, it can be a straight-chain saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. Examples include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, or t-butyl. Those skilled in the art will recognize that the term "alkyl" can include "alkylene."

[0025] As used herein, the term "alkylene," unless otherwise specified, refers to a substituted or unsubstituted straight-chain or branched hydrocarbon residue. For example, it can be a straight-chain saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. Examples include, but are not limited to, methylene, ethylene, propylene, 1-methylpropylene, 2-methylpropylene, butylene, pentylene, etc. For example, C 1-3 Alkylene may be in the form in which any one hydrogen is substituted or unsubstituted, for example, C 1-3 Alkyl may include substituted or unsubstituted forms.

[0026] As used herein, unless otherwise specified, the term "alkenyl" refers to a substituted or unsubstituted alkyl group containing one or more double bonds, such as, but not limited to, prop-1-ene, but-1-ene, but-2-ene, 3-methylbut-1-ene, or pent-1-ene.

[0027] As used herein, unless otherwise specified, the term "alkynyl" refers to a substituted or unsubstituted alkyl group containing one or more triple bonds, such as, but not limited to, ethynyl, propynyl, butynyl, pentynyl, hexynyl, or branched chain alkynyl groups.

[0028] The term "alkoxy," as used herein, unless otherwise specified, refers to a radical of a substituted or unsubstituted straight or branched chain hydrocarbon residue linked by an oxygen, such as, but not limited to, methoxy, ethoxy, propoxy, and butoxy, or isopropoxy, isobutoxy, or t-butoxy.

[0029] The term "alkylthio," as used herein, unless otherwise stated, refers to an -SR radical where R is alkyl as defined herein, including but not limited to methylthio, ethylthio, etc.

[0030] As used herein, unless otherwise stated, the term "alkylsulfonyl" refers to a -SO2R radical where R is alkyl as defined herein, such as, but not limited to, methylsulfonyl, ethylsulfonyl, etc.

[0031] The term "aminosulfonyl," as used herein, unless otherwise specified, refers to the -SO2NH2 radical.

[0032] The term "alkylaminosulfonyl," as used herein, unless otherwise indicated, refers to a -S0NHR radical where R is alkyl as defined herein, such as, but not limited to, methylaminosulfonyl, ethylaminosulfonyl, etc.

[0033] The term "dialkylaminosulfonyl," as used herein, unless otherwise stated, refers to a -SO2NR'R" radical, where R', R" are each alkyl as defined herein.

[0034] As used herein, the term "halogen" refers to F, Cl, Br, or I.

[0035] As used herein, unless otherwise specified, the term "haloalkyl" includes substituted or unsubstituted monohaloalkyl and polyhaloalkyl, such as, but not limited to, -CH2Cl, -CF3, -CHF2, -CH2CF3, -CF2CF3, -CF(CH3)2, etc.

[0036] As used herein, unless otherwise stated, the term "haloalkoxy" refers to an -OR radical where R is haloalkyl as defined herein, including but not limited to, -OCF3, -OCHF2.

[0037] As used herein, unless otherwise specified, the term "haloalkoxyalkyl" refers to an alkyl group substituted with haloalkoxy as defined above, including, but not limited to, haloC1-6alkoxyalkyl containing a total of 1 to 6 carbon atoms.

[0038] For example, trifluoromethoxymethyl, trifluoroethoxyethyl, etc., but are not limited thereto.

[0039] The term "cycloalkyl," as used herein, unless otherwise specified, refers to a substituted or unsubstituted, saturated or partially unsaturated, monocyclic, bicyclic, or polycyclic hydrocarbon ring, such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, indenyl, or tetrahydronaphthalenyl. The term cycloalkyl includes bridged, fused, or spirocycloalkyl.

[0040] As used herein, the term "bridged cycloalkyl," unless otherwise specified, refers to two rings that share two common ring atoms that are not adjacent. Bridged cycloalkyls are divided into bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyls depending on the number of rings. For example, [ka] There are also, but are not limited to, these.

[0041] As used herein, unless otherwise specified, the term "fused cycloalkyl" refers to a ring in which each ring shares an adjacent pair of carbon atoms with another ring, and one or more rings may share one or more double bonds, but none of the rings has a completely conjugated π-electron system. For example, fused cycloalkyls are classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused cycloalkyls depending on the number of rings. For example, [ka] There are also, but are not limited to, these.

[0042] As used herein, unless otherwise specified, the term "spiro" refers to two rings that share one atom and are not bridged. As used herein, the term "spiro linkage" refers to a linking group that shares one atom, unless otherwise specified.

[0043] The term "spirocycloalkyl," as used herein, unless otherwise specified, refers to a saturated carbocycle compound containing two rings, where both rings share only one carbon atom as part of the ring. For example, [ka] There are also, but are not limited to, these.

[0044] As used herein, the term "cyano" refers to the group --CN.

[0045] The term "ureido" as used herein refers to the radical -NH-CO-NH2.

[0046] As used herein, the term "amino" refers to the -NH group. As used herein, the terms "alkylamino," "haloalkylamino," "dialkylamino," "hydroxyalkylamino," "alkoxyalkylamino," "aminoalkylamino," "sulfonylamino," "heteroarylamino," "heterocyclylamino," and "heterocyclyloxyalkylamino" refer to specific N-substituted organic radicals having alkyl, haloalkyl, dialkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, sulfonyl, heteroaryl, heterocyclyl, and heterocyclyloxyalkyl substituents, respectively. For example, alkylamino can also be, but is not limited to, methylamino, ethylamino, or propylamino. For example, haloalkylamino can also be, but is not limited to, trifluoromethylamino or trifluoroethylamino.

[0047] As used herein, unless otherwise specified, the term "alkylcarbonyl" refers to a -C(O)R radical, where R is alkyl as defined herein. For example, C 1-6 Alkylcarbonyl may include, but is not limited to, for example, methylcarbonyl, ethylcarbonyl, and the like.

[0048] As used herein, unless otherwise specified, the term "alkoxycarbonyl" refers to a -C(O)OR radical, where R is alkyl as defined herein. For example, C 1-6 Alkoxycarbonyl may include, but is not limited to, for example, methoxycarbonyl, ethoxycarbonyl, and the like.

[0049] As used herein, unless otherwise specified, the term "aminocarbonyl" refers to the -CONH2 radical.

[0050] As used herein, unless otherwise specified, the term "alkylaminocarbonyl" refers to a -CONHR radical where R is alkyl as defined herein. For example, C 1-6 These may include, but are not limited to, alkylaminocarbonyl, such as, but not limited to, methylaminocarbonyl, ethylaminocarbonyl, and the like.

[0051] As used herein, unless otherwise stated, the term "dialkylaminocarbonyl" refers to a -CONR'R" radical, where R'R" are each alkyl as defined herein. For example, (C 1-6 The alkyl group may include, but is not limited to, 2-aminocarbonyl.

[0052] As used herein, unless otherwise stated, the term "heterocyclylcarbonyl" refers to a -C(O)R radical where R is heterocyclyl as defined herein.

[0053] As used herein, unless otherwise stated, the term "aminosulfonylalkyl" refers to -alkyl-S(=O)2-NH2, where alkyl is as defined herein.

[0054] As used herein, unless otherwise specified, the term "aminocarbonylalkyl" refers to -alkylene-(C=O)-NH2.

[0055] As used herein, the term "hydroxyalkyl" refers to an alkyl group substituted with an -OH group, such as, but not limited to, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 1-(hydroxymethyl)-2-methylpropyl, 3-hydroxybutyl, 4-hydroxybutyl, 2,3-dihydroxypropyl, 1-(hydroxymethyl)-2-hydroxyethyl, 2,3-dihydroxybutyl, or 3,4-dihydroxybutyl.

[0056] As used herein, the term "hydroxyalkoxy" refers to an -OR radical where R is hydroxyalkyl as defined herein, such as, but not limited to, hydroxyethyloxy, hydroxypropyloxy, and the like.

[0057] As used herein, the term "alkylamino" refers to an -NHR radical where R is alkyl as defined herein, such as, but not limited to, methylamino, ethylamino, propylamino, or isopropylamino.

[0058] As used herein, the term "dialkylamino" refers to a -NR'R" radical, where R' and R" are each alkyl as defined herein. For example, (C 1-6 The alkyl groups may include, but are not limited to, dimethylamino, diethylamino, or methylethylamino.

[0059] As used herein, the term "hydroxyalkylamino" refers to an -NR'R" radical where R' is hydrogen or alkyl as defined herein and R" is hydroxyalkyl as defined herein, such as, but not limited to, hydroxyethylamino, hydroxypropylamino, and the like.

[0060] As used herein, the term "halo C" 1-6 "Alkylamino" means, unless otherwise specified, a group having the chemical formula -NH-C 1-6 Alkyl, where C 1-6 Alkyl may be partially or fully substituted with halogen atoms, where allowed by available valences, i.e., groups of the formula -NH-C 1-6 Refers to alkyl-halo radicals.

[0061] As used herein, the term "(halo C 1-6 Unless otherwise specified, "amino" refers to a group having the chemical formula -N-(C 1-6 alkyl-halo)2 radicals.

[0062] As used herein, the term "C 1-6 Alkoxy C 1-6 "Alkylamino" means, unless otherwise specified, a group having the chemical formula -NH-C 1-6 Alkyl, where C 1-6 Alkyl is C 1-6 Partially or fully substituted with alkoxy, i.e., with the formula -NH-C 1-6 Alkyl-C 1-6 Refers to the alkoxy radical.

[0063] As used herein, the term "amino C 1-6 "Alkylamino" means, unless otherwise specified, a group having the chemical formula -NH-C 1-6 Alkyl, where C 1-6 Alkyl may be partially or fully substituted with amino, i.e., the group has the formula -NH-C 1-6 Refers to alkyl-amino radicals.

[0064] The term "sulfonylamino," as used herein, unless otherwise stated, refers to the radical --NR'S(O)2R" where R' and R" are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl.

[0065] As used herein, unless otherwise specified, the term "alkylsulfonylamino" refers to the radical --NHS(O)2R, where R is alkyl as defined herein.

[0066] The term "alkoxyalkyl," as used herein, unless otherwise specified, refers to an R'-OR" radical, where R' and R" are each alkyl as defined herein. Examples include, but are not limited to, 2-methoxyethyl, 1-, 2-, or 3-methoxypropyl, 2-ethoxyethyl, and the like. The term "C 1-6 The term "alkoxyalkyl," unless otherwise specified, refers to an alkyl-O-alkyl ether having from 1 to 6 total carbon atoms.

[0067] As used herein, the term "alkoxyalkoxy" refers to an -OR radical where R is alkoxyalkyl as defined herein, such as, but not limited to, methoxyethyloxy, ethyloxypropyloxy, and the like.

[0068] The term "aminoalkyl," as used herein, unless otherwise specified, refers to a straight or branched chain saturated alkyl group designated as --NR'R", where R' and R" are each alkyl as defined herein.

[0069] In one embodiment, R′ and R″ may be substituted with haloalkyl, hydroxyalkyl, alkoxyalkyl, or alkylcarbonyl.

[0070] The aminoalkyl may be, for example, aminomethyl, aminoethyl, methylaminomethyl, etc., but is not limited thereto.

[0071] As used herein, the term "aminoalkoxy" refers to an -OR radical where R is aminoalkyl as defined herein, such as, but not limited to, aminoethyloxy, methylaminopropyloxy, dimethylaminoethyloxy, diethylaminopropyloxy, and the like.

[0072] As used herein, unless otherwise specified, the term "aryl" refers to a substituted or unsubstituted monocyclic, bicyclic, or polycyclic aromatic hydrocarbon radical. For example, C 6-10 Aryl includes, but is not limited to, alternating (resonating) double bonds between adjacent carbon atoms or suitable heteroatoms, such as, but not limited to, phenyl, biphenyl, naphthyl, toluyl, or naphthalenyl.

[0073] The term "hetero" as used herein refers to an atom selected from B, N, O, S, P(=O), Si and P.

[0074] The term "heteroaryl," as used herein, unless otherwise specified, refers to a substituted or unsubstituted monocyclic, bicyclic, or polycyclic aromatic radical containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. For example, C 4-10 Heteroaryls can include, but are not limited to, for example, monocyclic heteroaryls such as pyridinyl, imidazolyl, thiazolyl, oxazolyl, thiophenyl, furanyl, pyrrolyl, isoxazolyl, pyrazolyl, triazolyl, thiadiazolyl, tetrazolyl, oxadiazolyl, pyridazinyl, pyrimidinyl, or pyrazinyl. For example, bicyclic heteroaryls can include, but are not limited to, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzthiadiazolyl, benztriazolyl, quinolinyl, isoquinolinyl, purinyl, or furopyridinyl.

[0075] As used herein, unless otherwise stated, the term "heteroaryloxy" refers to an -OR radical where R is heteroaryl as defined herein. For example, C 4-10 These may include, but are not limited to, heteroaryloxy.

[0076] The term "heterocyclyl," as used herein, unless otherwise indicated, refers to a substituted or unsubstituted, saturated or partially unsaturated, monocyclic, bicyclic, or polycyclic carbon atom ring structure radical containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. For example, a heterocyclyl includes: [ka] or groups similar thereto, but are not limited thereto. Also, examples thereof include azetidinyl, pyrrolinyl, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl, isothiazolinyl, isothiazolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, triazolinyl, triazolidinyl, oxadiazolinyl, oxadiazolidinyl, thiadiazolinyl, thiadiazolidinyl, tetrazolinyl, tetrazolidinyl, piperazinyl, piperidinyl, morpholinyl, thiomorpholinyl, dihydro The term heterocyclyl includes, but is not limited to, indazolyl, tetrahydroindazolyl, dihydroisoindolyl, dihydrobenzofuranyl, tetrahydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, dihydrobenzimidazolyl, tetrahydrobenzimidazolyl, dihydrobenzoxazolyl, dihydropyridinyl, dihydroquinolinyl, benzodioxinyl (e.g., 1,4-benzodioxane), or benzodioxolyl (e.g., 1,3-benzodioxole). The term heterocyclyl includes bridged, fused, or spiroheterocyclyl. For example, a fused heterocyclyl is: [ka] There are also, but are not limited to, these. As used herein, unless otherwise specified, the term "bridged heterocycloalkyl" refers to a bridged cycloalkyl containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. The term "fused heterocycloalkyl," as used herein, unless otherwise specified, refers to a fused cycloalkyl containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. As used herein, unless otherwise specified, the term "heterospirocycloalkyl" refers to a spirocycloalkyl containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. For example, [ka] There are also, but are not limited to, these.

[0077] As used herein, unless otherwise specified, the term "heterocyclyloxy" refers to an -OR radical where R is heterocyclyl as defined herein, such as, but not limited to, pyrrol-2-yloxy, pyrrol-3-yloxy, piperidin-2-yloxy, piperidin-3-yloxy, piperazin-2-yloxy, or piperidin-4-yloxy.

[0078] The term "heterocyclylamino," as used herein, unless otherwise specified, refers to an -NHR radical where R is heterocyclyl as defined herein, such as, but not limited to, pyrrol-2-ylamino, pyrrol-3-ylamino, piperidin-2-ylamino, piperidin-3-ylamino, piperazin-2-ylamino, or piperidin-4-ylamino.

[0079] As used herein, unless otherwise specified, the term "heterocyclyloxyalkoxy" refers to an -OR radical where R is heterocyclyl as defined herein. For example, heterocyclyloxyalkoxy can be, but is not limited to, pyrrol-2-yloxymethoxy, pyrrol-3-yloxyethoxy, piperidin-2-yloxyethoxy, piperidin-3-yloxyethoxy, piperazin-2-yloxymethoxy, or piperidin-4-yloxyethoxy.

[0080] As used herein, the term "heterocyclyloxyalkylamino" refers to an -NR-(alkylene)-R' radical where R' is hydrogen or alkyl as defined herein and R" is heterocyclyloxy as defined herein, for example, but not limited to, oxetanyloxyethylamino, piperidinyloxyethylamino, and the like.

[0081] As used herein, unless otherwise specified, the term "heterocycloalkyl" refers to a monocyclic substituted or unsubstituted cyclic alkyl containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. Examples include, but are not limited to, piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, thiomorpholinyl, imidazolidinyl, or tetrahydrofuryl.

[0082] As used herein, the term "stereoisomer" means a compound of the present invention or a salt thereof that has the same chemical or molecular formula but is optically or sterically different, and includes optical isomers or diastereomers.

[0083] As used herein, the term "enantiomers" refers to two stereoisomers of a compound which are non-superimposable mirror images of one another.

[0084] As used herein, the term "diastereomer" refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another.

[0085] The compounds of the present invention contain asymmetric or chiral centers and therefore may exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of the present invention, such as diastereomers, enantiomers, and racemic mixtures, are considered to be part of the present invention. A 50:50 mixture of enantiomers is referred to as a racemic mixture or racemate.

[0086] As used herein, the term "solvate" refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Preferred solvents are those that are volatile, non-toxic, and / or suitable for administration to humans. The "solvate" may include a molecular complex containing the compound and one or more pharmaceutically acceptable solvent molecules, such as ethanol.

[0087] The term "hydrate" as used herein refers to a complex where the solvent molecule is water.

[0088] As used herein, the term "pharmaceutically acceptable salt" refers to a pharmaceutically acceptable organic or inorganic salt, which may be prepared by any suitable method available to those skilled in the art. For example, if the compound of the present invention is a base, the desired pharmaceutically acceptable salt may be prepared by any suitable method available to those skilled in the art, such as by treating the free base with an inorganic or organic acid.

[0089] In one embodiment, in Formula 1, [ka] are independently H, C 3-10 Cycloalkyl, Bridged C 8-16 Cycloalkyl, fused C 3-10 Cycloalkyl, C 8-16 Spirocycloalkyl, C 6-10 Aryl, C 4-10 Heteroaryl, C 1-10 Heterocyclyl, Bridged C 6-14 Heterocyclyl, fused C 1-10 Heterocyclyl or C 6-14 Also spiroheterocyclyl.

[0090] In one embodiment, in Formula 1, X and Z are each independently N or CH;

[0091] Y is CR3a and;

[0092] R 3a is H, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkyl sulfonyl, hydroxy, halogen, haloC 1-6 Alkyl, HaloC 1-6 Alkoxy, C 3-10 Cycloalkyl, cyano, amino, C 1-6 Alkylamino, HaloC 1-6 Alkylamino, C 2-12 Dialkylamino, C 1-6 Alkyl carbonyl, C 1-6 Alkoxycarbonyl, aminocarbonyl, C 1-6 Alkylaminocarbonyl, C 2-12 Dialkylaminocarbonyl, hydroxy C 1-6 Alkyl, hydroxy C 1-6 Alkoxy, Hydroxy C 1-6 Alkylamino, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkylamino, Amino C 1-6 Alkyl, Amino C 1-6 Alkoxy, Amino C 1-6 Alkylamino, C 6-10 Aryl, C 5-10 Heteroaryl, C 5-10 Heteroaryloxy, C 4-10 Heteroarylamino, C 1-10 Heterocyclyl, C 1-10 Heterocyclyloxy, C 1-10 Heterocyclylamino, C 1-10 Heterocyclyloxyalkoxy or C 1-10 heterocyclyloxyalkylamino,

[0093] where C6-10 Aryl, C 4-10 Heteroaryl or C 1-10 Each heterocyclyl is independently C 1-6 Alkyl, C 3-10 Cycloalkyl, HaloC 1-6 Alkyl, HaloC 1-6 Alkoxy, C 1-6 Alkoxy, hydroxy, halogen, cyano, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl and Amino C 1-6 unsubstituted or substituted with 1 to 3 alkyl groups; [ka] are independently H, C 3-10 Cycloalkyl, Bridged C 8-16 Cycloalkyl, fused C 3-10 Cycloalkyl, C 8-16 Spirocycloalkyl, C 6-10 Aryl, C 4-10 Heteroaryl, C 1-10 Heterocyclyl, Bridged C 6-14 Heterocyclyl, fused C 1-10 Heterocyclyl, or C 6-14 spiroheterocyclyl, where C 6-10 Aryl, C 4-10 Heteroaryl or C 1-10 Heterocyclyl is represented by the following R 2a or unsubstituted with 1 to 3 independently selected from:

[0094] L is C 1-3 alkylene, O, NH, NCH3, S, SO, SO2 or a bond;

[0095] R 2a is C 1-6 Alkyl, C 3-10 Cycloalkyl, HaloC 1-6 Alkyl, HaloC 1-6 Alkylamino, HaloC1-6 Alkoxy, C 1-6 Alkoxy, hydroxy, C 1-6 Alkyl sulfonyl, halogen, cyano, carboxy, C 1-6 Alkoxycarbonyl, Hydroxy C 1-6 Alkyl, C 1-6 Alkoxyalkyl, Amino C 1-6 Alkyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, (C 1-6 Alkyl)2aminosulfonyl, sulfonylamino, aminocarbonyl, C 1-6 Alkylaminocarbonyl, (C 1-6 Alkyl)2 aminocarbonyl, C 1-10 heterocyclylcarbonyl, or ureido;

[0096] R 1 is H, C 1-6 Alkyl, HaloC 1-6 Alkyl, hydroxy C 1-6 Alkyl, C 1-6 Alkoxyalkyl, Amino C 1-6 Alkyl, substituted amino C 1-6 Alkyl, Aminocarbonyl C 1-6 Alkyl or aminosulfonyl C 1-6 It is also alkyl.

[0097] In one embodiment, in Formula 1, X and Z are each independently N or CH;

[0098] Y is CR 3b and;

[0099] R 3b is H, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Alkoxy, hydroxy, halogen, haloC 1-6 Alkyl, C 3-6 Cycloalkyl, Amino, C 1-3 Alkylamino, HaloC 1-6 Alkylamino or C2-6 is heterocyclyl, [ka] are independently H, C 6-10 Aryl, C 4-10 Heteroaryl or C 1-10 heterocyclyl, where C 6-10 Aryl, C 4-10 Heteroaryl or fused C 1-10 Heterocyclyl is represented by the following R 2b or unsubstituted with 1 to 3 independently selected from:

[0100] L is C 1-6 alkylene, O, NH, NCH3, S, SO, SO2 or a bond;

[0101] R 2b is C 1-6 Alkyl, HaloC 1-3 Alkyl, HaloC 1-3 Alkoxy, C 1-6 alkoxy, hydroxy, or halogen;

[0102] R 1 is H or C 1-6 It is also alkyl.

[0103] In one embodiment, in Formula 1, X and Z are each independently N or CH;

[0104] Y is CR 3c and;

[0105] R 3c is H, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Alkoxy, hydroxy, halogen, haloC 1-3 Alkyl, C 3-6 Cycloalkyl, Amino, C 1-3 Alkylamino, HaloC1-3 Alkylamino or C 2-6 is heterocyclyl, [ka] are each independently H, phenyl, pyridinyl, imidazolyl, pyrrolidinyl, indolyl, naphthalenyl, benzodioxinyl, or benzodioxolyl, [ka] is C 1-3 Alkyl, HaloC 1-3 Alkyl, HaloC 1-3 Alkoxy, C 1-3 unsubstituted or substituted with one to three independently selected from alkoxy, hydroxy, and halogen;

[0106] L is C 1-3 alkylene, O, NH, NCH3, S, SO, SO2 or a bond; R 1 is H or C 1-3 It is also alkyl.

[0107] In one embodiment, in Formula 1, [ka] are each independently H, phenyl, pyridinyl, imidazolyl, pyrrolidine, [ka] and At this time, [ka] is C 1-3 Alkyl, HaloC 1-3 Alkyl, HaloC 1-3 Alkoxy, C 1-3It may be unsubstituted or substituted with one to three independently selected from alkoxy, hydroxy, and halogen.

[0108] In one embodiment, in Formula 1, [ka] is phenyl or pyridinyl,

[0109] C 1-3 Alkyl, HaloC 1-3 Alkyl, HaloC 1-3 Alkoxy, C 1-3 unsubstituted or substituted with 1 to 3 independently selected from alkoxy and halogen; [ka] is H, phenyl, pyridinyl, imidazolyl, pyrrolidinyl, or [ka] and

[0110] C 1-3 Alkyl, HaloC 1-3 Alkoxy, C 1-3 unsubstituted or substituted with 1 to 3 independently selected from alkoxy, hydroxy, and halogen;

[0111] X and Z are each independently N or CH;

[0112] Y is CR 3c In this case, R 3c is H, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Alkoxy, hydroxy, halogen, haloC 1-3 Alkyl, C 3-6 Cycloalkyl, Amino, C 1-3Alkylamino, HaloC 1-3 Alkylamino or C 2-6 Also heterocyclyl;

[0113] L is also methylene, ethylene, O, NH, NCH3, S, SO, or SO2; and / or

[0114] R 1 is also H or methyl.

[0115] In one embodiment,

[0116] X and Z are each independently N or CH;

[0117] Y is CR 3c In this case, R 3c is H, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Alkoxy, hydroxy, halogen, haloC 1-3 Alkyl, C 3-6 Cycloalkyl, Amino, C 1-3 Alkylamino, HaloC 1-3 Alkylamino or C 2-6 is heterocyclyl; [ka] is phenyl or pyridinyl, [ka] is H, phenyl, pyridinyl, imidazolyl, pyrrolidinyl, or [ka] and At this time, [ka] are each independently C 1-3 Alkyl, HaloC 1-3 Alkyl, HaloC 1-3 Alkoxy, C 1-3 unsubstituted or substituted with one to three independently selected from alkoxy, hydroxy, and halogen;

[0118] L is methylene, ethylene, O, NH, NCH3, S, SO, or SO2; R 1 is also H or methyl.

[0119] In one embodiment, the compound may be selected from the group consisting of the following compounds, their optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof: 1) 2-benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 2) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 3) 7-chloro-2-(4-hydroxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 4) 7-chloro-2-(3-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 5) 7-chloro-2-(2-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 6) 7-chloro-2-(4-chlorobenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 7) 7-chloro-1-methyl-5-phenyl-2-(pyridin-4-ylmethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 8) 7-chloro-2-(3,4-dimethoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 9) 7-chloro-1-methyl-2-phenethyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 10) 7-chloro-2-(4-methoxyphenyl)-1-methyl-5-(o-tolyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 11) 2-benzyl-7-chloro-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 12) 2-((1H-imidazol-1-yl)methyl)-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 13) 7-chloro-2-((3-methoxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 14) 7-chloro-2-((3-hydroxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 15) 2-(4-Methoxybenzyl)-1-methyl-5-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 16) 7-chloro-5-(4-chloro-3-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 17) 7-chloro-5-(3-chloro-4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 18) 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 19) 7-chloro-2-((4-methoxyphenyl)sulfonyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 20) 7-chloro-2-((4-methoxyphenyl)sulfinyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 21) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 22) 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 23) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 24) 7-chloro-5-(2-cyclopropylpyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 25) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)phenyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 26) 7-chloro-5-(2-chlorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 27) 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 28) 7-chloro-2-(4-fluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 29) 2-(benzo[d][1,3]dioxol-5-ylmethyl)-7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 30) 7-chloro-2-(3,4-difluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 31) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 32) 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 33) 7-chloro-2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 34) 7-chloro-5-(4-methoxyphenyl)-2-((4-methoxyphenyl)thio)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 35) 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 36) 7-chloro-2-((4-fluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 37) 7-chloro-2-((3,4-difluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 38) 2-(benzo[d][1,3]dioxol-5-ylthio)-7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 39) 7-chloro-2-((2,4-difluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 40) 7-chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 41) 7-chloro-2-((4-methoxyphenyl)(methyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 42) 7-chloro-2-(4-methoxyphenoxyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 43) 7-Hydroxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 44) 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-vinyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 45) 7-Ethyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 46) 7-Cyclopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 47) 7-ethynyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 48) 7-Isopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 49) 2-(4-Methoxybenzyl)-1,7-dimethyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 50) 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(pyrrolidin-1-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 51) 7-Methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 52) 7-amino 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 53) 2-(4-Methoxybenzyl)-1-methyl-7-(methylamino)-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 54) 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 55) 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 56) 5-(4-(difluoromethoxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 57) 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 58) 2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 59) 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 60) 2-((4-fluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 61) 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one; 62) 7-Ethoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one; 63) 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 64) 7-Methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 65) 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; and 66) 7-Cyclopropyl-2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one.

[0120] Another embodiment of the present invention provides a pharmaceutical composition for treating or preventing a disease or disorder associated with methionine adenosyltransferase 2A (MAT2A), comprising, as an active ingredient, a compound selected from the group consisting of a compound of Formula 1 or an embodiment thereof, an optical isomer, a diastereomer, a solvate, a hydrate, and a pharmaceutically acceptable salt thereof.

[0121] In one embodiment, the composition may exhibit MAT2A inhibitory activity.

[0122] In one embodiment, the composition is for treating cancer, for example, the cancer is a solid tumor.

[0123] In one embodiment, the composition is also for treating methylthioadenosine phosphorylase (MTAP)-deficient cancers.

[0124] In one embodiment, the pharmaceutical composition may comprise a therapeutically effective amount of a compound selected from the compound of Formula 1, its optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0125] As used herein, the term "therapeutically effective amount" refers to an amount of a compound of the present invention that treats or prevents a particular disease, condition, or disorder, attenuates, ameliorate, or eliminates one or more symptoms of a particular disease, condition, or disorder, or prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder.

[0126] A physician having ordinary skill in the relevant art can easily determine and prescribe the effective required dosage for the pharmaceutical composition. For example, the pharmaceutical composition may contain, but is not limited to, 0.0001 mg to 10 g of the compound.

[0127] In one embodiment, the pharmaceutical composition may further comprise pharmaceutically acceptable additives other than the active ingredient, such as, but not limited to, diluents, disintegrants, binders, lubricants, surfactants, suspending agents, or emulsifiers.

[0128] The pharmaceutical compositions of the present invention can be formulated by conventional methods and prepared into various oral dosage forms such as tablets, pills, powders, capsules, syrups, emulsions, microemulsions, etc., or parenteral dosage forms such as intramuscular, intravenous, or subcutaneous administration.

[0129] Another embodiment of the present invention provides a method for treating a subject suffering from a MAT2A-related disease or disorder, comprising administering a compound selected from the compound of Formula 1, its optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof, or a pharmaceutical composition containing the compound as an active ingredient.

[0130] As used herein, the term "treat" or "treatment" refers to inhibiting a disease, e.g., inhibiting a disease, condition, or disorder in an individual experiencing or exhibiting pathology or symptoms of the disease, condition, or disorder, i.e., preventing further development of or reversing the pathology and / or symptoms, or ameliorating the disease, e.g., reducing disease severity.

[0131] As used herein, the term "preventing" or "prevention" refers to preventing a disease, for example, preventing a disease, condition, or disorder in an individual who may be predisposed to the disease, condition, or disorder, but who has not yet experienced or exhibited pathology or symptoms of the disease.

[0132] As used herein, the term "subject" or "individual" refers to a vertebrate, such as a mammal, fish, bird, reptile, or amphibian. For example, the subject may be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent.

[0133] As used herein, the terms "administer" and "administration" refer to any method of providing the disclosed compositions to a subject.

[0134] The dosage, frequency, or method of administration of a compound or pharmaceutical composition according to an embodiment may vary depending on the subject being treated, the severity of the disease or condition, the rate of administration, and the discretion of the prescribing physician. For example, the dosage for a normal 70 kg person may be 0.0001 mg to 10 g, e.g., 1 mg to 1 g, per day. The dosage may be one to several times, e.g., 1 to 4 times, or on an on / off schedule, and may be administered orally or parenterally. For example, a compound or pharmaceutical composition according to an embodiment may be administered orally or parenterally in an amount ranging from 0.1 to 100 mg / kg body weight.

[0135] A physician may gradually increase the dose of a compound or pharmaceutical composition of the present invention administered to a subject, starting from a level lower than that required to achieve the desired therapeutic effect, until the intended effect is achieved.

[0136] Another embodiment of the present invention provides a kit comprising, as an active ingredient, a compound selected from the compound of Formula 1, its optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0137] In one embodiment, the therapeutic agent is also a drug for treating a MAT2A-related disease or disorder, such as a drug for treating cancer, e.g., a chemotherapy drug for treating cancer.

[0138] In one embodiment, the therapeutic agent is a chemotherapeutic agent, antimetabolite, antimitotic agent, alkylating agent, DNA damaging agent, antitumor antibiotic, platinum complex, proteasome inhibitor, hormone and hormone analog, immunosuppressant, antiangiogenic compound, vascular endothelial growth factor inhibitor, fibroblast growth factor inhibitor, epidermal growth factor receptor inhibitor, antibody, checkpoint inhibitor, corticosteroid, DNA repair enzyme inhibitor, therapeutic agent for autoimmune disease, therapeutic agent for diabetes, therapeutic agent for liver disease, therapeutic agent for cardiovascular disease, therapeutic agent for metabolic disorder, antiviral agent, or ophthalmological therapeutic agent.

[0139] In one embodiment, the compounds, compositions and kits of the present invention may be administered alone or simultaneously with at least one other therapeutic agent, either separately or sequentially. In the context of the present invention, the singular forms of words include the plural and vice versa, unless the context clearly dictates otherwise.

[0140] Numerical values ​​described herein are considered to include the meaning of "about" even if not explicitly stated. As used herein, the term "about" refers to a value within 5% of a given value or range, preferably within 1% to 2% of the given value or range.

[0141] In this specification, numerical ranges expressed using the term "to" refer to ranges that include the numerical values ​​stated before and after the term "to" as the lower and upper limits, respectively.

[0142] As used herein, the terms "have," "can have," "include," or "can include" indicate the presence of a given feature (e.g., a value or a component such as a component) and do not exclude the presence of additional features.

[0143] The contents of all publications referenced herein are hereby incorporated by reference in their entirety.

[0144] The present invention will be explained in more detail below with reference to the following examples and experimental examples, which are intended to aid in the understanding of the present invention and are not intended to limit the scope of the present invention in any way.

[0145] <Synthesis Example 1> Example 1: 2-benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0146] [Step 1] Preparation of methyl 2-amino-4-chlorobenzoate [ka]

[0147] 2-amino - 4-Chlorobenzoic acid (10 g, 57.12 mmol), potassium carbonate (11.90 g, 85.67 mmol), and iodomethane (3.63 mL, 57.12 mmol) were added sequentially to N,N-dimethylformamide (200 mL), and the reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours. The resulting solid was collected by filtration, washed with water, and dried to give the title compound (8.72 g, 82.3%).

[0148] [Step 2] Preparation of methyl 4-chloro-2-(phenylamino)benzoate [ka]

[0149] Methyl 2-amino -4-Chlorobenzoate (8.72 g, 47.0 mmol), bromobenzene (4.99 mL, 47.0 mmol), cesium carbonate (23.20 g, 70.5 mmol), palladium acetate (215 mg, 0.94 mmol), and Xantphos (1.09 g, 1.88 mmol) were added to toluene (88 mL) and purged with nitrogen gas. The mixture was refluxed at 100°C for 12 hours. After cooling the reaction mixture to room temperature, the solid was filtered and washed with dichloromethane. The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (8.56 g, 69.57%).

[0150] [Step 3] Preparation of methyl 4-chloro-2-(N-phenylacetamido)benzoate [ka]

[0151] Methyl 4-chloro-2-(phenylamino)benzoate (7.56 g, 28.89 mmol) synthesized in Step 2 above was dissolved in acetic acid (60 mL), and acetic anhydride (54.62 mL, 577.76 mmol) was added. The mixture was refluxed at 120 °C for 23 hours. The reaction mixture was cooled to room temperature, poured into ice water, and stirred for 30 minutes. The resulting solid was collected by filtration, washed with water, and dried to give the title compound (8.32 g, 94.82%), which was used without further purification.

[0152] [Step 4] Preparation of 7-chloro-4-hydroxy-1-phenylquinolin-2(1H)-one [ka]

[0153] Tetrahydrofuran (125 mL) was added to methyl 4-chloro-2-(N-phenylacetamido)benzoate (8.32 g, 27.39 mmol) synthesized in Step 3 above, and the reaction mixture was cooled to -78°C. A 1 M solution of potassium bis(trimethylsilyl)amide in tetrahydrofuran was slowly added dropwise to the reaction mixture over 1 hour. The reaction mixture was concentrated, water was added, and the mixture was acidified with 6N hydrochloric acid. The resulting solid was collected by filtration and washed with an excess of water. The solid was stirred with diethyl ether for 30 minutes, collected by filtration, and dried to give the title compound (6.02 g, 80.89%), which was used without further purification.

[0154] [Step 5] Preparation of 7-chloro-4-hydroxy-3-nitro-1-phenylquinolin-2(1H)-one [ka]

[0155] To the 7-chloro-4-hydroxy-1-phenylquinolin-2(1H)-one (6.02 g, 22.16 mmol) synthesized in Step 4 above, acetic acid (100 mL), nitric acid (6.2 mL, 88.63 mmol), and sodium nitrite (312 mg, 4.43 mmol) were added and stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and stirred for 1 hour. The resulting solid was collected by filtration, washed with excess water, and dried to give the title compound (6.5 g, 92.63%).

[0156] [Step 6] Preparation of 4,7-dichloro-3-nitro-1-phenylquinolin-2(1H)-one [ka]

[0157] To the 7-chloro-4-hydroxy-3-nitro-1-phenylquinolin-2(1H)-one (6.5 g, 20.52 mmol) synthesized in Step 5 above, phosphorus oxychloride (65 mL, 683.41 mmol) was added. The reaction mixture was cooled to 0°C, and triethylamine (6.5 mL, 46.17 mmol) was added dropwise.

[0158] The mixture was refluxed at 110°C for 1 hour. The reaction mixture was cooled to room temperature, poured into ice water, and stirred for 1 hour. The resulting solid was collected by filtration, washed with excess water, and dried to give the title compound (5.76g, 83.67%).

[0159] [Step 7] Preparation of 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one [ka]

[0160] 4,7-Dichloro-3-nitro-1-phenylquinolin-2(1H)-one (5.76 g, 17.17 mmol) synthesized in Step 6 above was dissolved in dichloromethane, followed by the addition of methylamine hydrochloride (1.42 g, 20.61 mmol) and triethylamine (7.26 mL, 51.52 mmol). The reaction mixture was stirred at room temperature for 1 hour and concentrated. Water was then added and the mixture was stirred for 1 hour. The resulting solid was collected by filtration, washed with excess water, and dried to give the title compound (5.05 g, 89.19%).

[0161] [Step 8] Preparation of 3-amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one [ka]

[0162] To the 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one (5.05 g, 15.32 mmol) synthesized in Step 7 above, Raney nickel (5.39 g, 45.95 mmol) and dichloromethane (60 mL) / methanol (30 mL) were added, and a hydrogen balloon was attached. The reaction mixture was stirred at room temperature for 16 hours, filtered through Celite, and purified by silica gel column chromatography to obtain the title compound (2.16 g, 47.05%).

[0163] [Step 9] Preparation of N-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-phenylacetamide [ka]

[0164] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (40 mg, 0.13 mmol) synthesized in Step 8 above was dissolved in dichloromethane (1 mL) and cooled to 0°C. Triethylamine (21 μL, 0.15 mmol) and 2-phenylacetyl chloride (18 μL, 0.13 mmol) were then added dropwise. The reaction mixture was stirred at room temperature for 1 hour, water was added, and the mixture was extracted with dichloromethane. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Purification using silica gel column chromatography afforded the title compound (15.3 mg, 27.44%).

[0165] [Step 10] Preparation of 2-benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0166] N-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-phenylacetamide (15 mg, 0.04 mmol) synthesized in Step 9 above was dissolved in 1,4-dioxane (0.5 mL) and 2N sodium hydroxide (0.5 mL) was added. The reaction mixture was stirred at 120°C for 2 hours. After completion of the reaction, the mixture was cooled to 0°C and neutralized with 1N hydrochloric acid. The resulting solid was collected by filtration, washed with excess water, and dried to give the title compound (13.2 mg, 78.5%).

[0167] Example 2: 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0168] The same reaction was carried out using 2-(4-methoxyphenyl)acetyl chloride instead of 2-phenylacetyl chloride in Step 9 of Example 1 to obtain the title compound (8.7 mg, 15.17%).

[0169] Example 3: 7-chloro-2-(4-hydroxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0170] 7-Chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [the title compound of Example 2] (20 mg, 0.05 mmol) was dissolved in dichloromethane (0.5 mL) and cooled to 0°C. Boric acid tribromide (9 μL, 0.1 mmol) was then added dropwise. The reaction mixture was stirred at room temperature for 1 hour and poured into ice water. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with dichloromethane. The separated organic layer was dried over anhydrous magnesium sulfate and concentrated by distillation under reduced pressure. Purification by silica gel column chromatography afforded the title compound (3.4 mg, 17.18%).

[0171] Example 4: 7-chloro-2-(3-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0172] The same reaction was carried out up to [Step 10] in Example 1, except that 2-(3-methoxyphenyl)acetyl chloride was used instead of 2-phenylacetyl chloride in [Step 9], to obtain the title compound (22 mg, 30.68%).

[0173] Example 5: 7-chloro-2-(2-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0174] The same reaction was carried out up to [Step 10] in Example 1, except that 2-(2-methoxyphenyl)acetyl chloride was used instead of 2-phenylacetyl chloride in [Step 9], to obtain the title compound (15 mg, 20.92%).

[0175] Example 6: 7-chloro-2-(4-chlorobenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0176] The same reaction was carried out up to [Step 10] in Example 1, except that 2-(4-chlorophenyl)acetyl chloride was used instead of 2-phenylacetyl chloride in [Step 9], to obtain the title compound (12.9 mg, 64.46%).

[0177] Example 7: 7-Chloro-1-methyl-5-phenyl-2-(pyridin-4-ylmethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0178] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (20 mg, 0.06 mmol) synthesized in Step 8 of Example 1 was dissolved in N,N-dimethylformamide (1 mL) and 4-pyridylacetic acid hydrochloride (12.4 mg, 0.07 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (50.7 mg, 0.13 mmol), and diisopropylethylamine (43 mg, 0.33 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours, followed by addition of water and extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. The same reaction was carried out up to Step 10 without further purification to obtain the title compound (8 mg, 21.50%).

[0179] Example 8: 7-chloro-2-(3,4-dimethoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0180] The same reaction was carried out up to [Step 10] in Example 1, except that 2-(3,4-dimethoxyphenyl)acetyl chloride was used instead of 2-phenylacetyl chloride in [Step 9], to obtain the title compound (37 mg, 46.59%).

[0181] Example 9: 7-Chloro-1-methyl-2-phenethyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0182] The same reactions were carried out up to [Step 10] in Example 1, except that 3-phenylpropanoyl chloride was used instead of 2-phenylacetyl chloride in [Step 9], to obtain the title compound (16.4 mg, 60.05%).

[0183] Example 10: 7-chloro-2-(4-methoxyphenyl)-1-methyl-5-(o-tolyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0184] The same reaction was carried out up to [Step 10] using 1-bromo-2-methylbenzene instead of bromobenzene in [Step 2] of Example 1 and 2-(4-methoxyphenyl)acetyl chloride instead of 2-phenylacetyl chloride in [Step 9] of Example 1 to obtain the title compound (45.6 mg, 78.56%).

[0185] Example 11: 2-Benzyl-7-chloro-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0186] The same reaction was carried out as in Step 7 of Example 1, except that 4-amino-7-chloro-3-nitro-1-phenylquinolin-2(1H)-one was synthesized by dissolving the compound in tetrahydrofuran instead of dichloromethane and adding aqueous ammonia instead of methylamine hydrochloride and triethylamine to obtain the title compound (2 mg, 41.87%). According to an embodiment of the present invention, the compound of Formula 1 is a compound selected from the group consisting of the compounds listed in Table 1 below. [Table 1-1] [Table 1-2]

[0187] <Synthesis Example 2> Example 12: 2-((1H-imidazol-1-yl)methyl)-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0188] [Step 1] Preparation of 7-chloro-2-(chloromethyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0189] 2-Chloro-1,1,1-trimethoxyethane (0.25 mL, 1.84 mmol) and p-toluenesulfonic acid monohydrate (8.25 mg, 0.04 mmol) were added to 3-amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one, synthesized in Step 8 of Example 1, and the mixture was stirred at 100°C for 1 hour. After cooling to room temperature, the reaction mixture was concentrated and stirred with diethyl ether for 1 hour. The resulting solid was collected by filtration and washed with diethyl ether to give the title compound (152.6 mg, 98.23%), which was used without further purification.

[0190] [Step 2] Preparation of 2-((1H-imidazol-1-yl)methyl)-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0191] Imidazole (7.7 mg, 0.11 mmol) was dissolved in N,N-dimethylformamide (0.2 mL) and cooled to 0 °C. Sodium hydride (6.7 mg, 0.17 mmol) was added in portions under nitrogen. After stirring for 30 minutes, the mixture was dissolved in N,N-dimethylformamide (0.3 mL) and 7-chloro-2-(chloromethyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (20 mg, 0.06 mmol) prepared in [Step 1] was added dropwise. The reaction mixture was stirred at room temperature for 30 minutes, then ice water was added and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The concentrated reaction mixture was purified by silica gel column chromatography to yield the title compound (4.4 mg, 20.22%).

[0192] Example 13: 7-chloro-2-((3-methoxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0193] The same reaction was carried out as in Example 12 [Step 2], except that 3-methoxypyrrolidine was used instead of imidazole, to give the title compound (30.5 mg, 51.67%).

[0194] Example 14: 7-chloro-2-((3-hydroxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0195] The same reaction was performed, except that 7-chloro-2-((3-methoxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (the title compound of Example 13) was used instead of 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in Example 3, to give the title compound (12.4 mg, 64.13%).

[0196] <Synthesis Example 3> Example 15: 2-(4-Methoxybenzyl)-1-methyl-5-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0197] [Step 1] Preparation of 6-chloro-2-(phenylamino)nicotinic acid [ka]

[0198] Aniline (6.15 g, 65.3 mmol) was diluted with tetrahydrofuran (60 mL). The reaction mixture was cooled to -75°C, and then a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (16.7 g, 100 mmol) was added dropwise and stirred for 1 hour. 2,6-Dichloronicotinic acid (6.00 g, 31.3 mmol) was added, and the reaction mixture was stirred at room temperature for 16 hours. After the reaction was complete, the mixture was diluted with ethyl acetate and washed with 1 N aqueous hydrochloric acid and saturated brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (3.7 g, 48%).

[0199] [Step 2] Preparation of (1H-benzo[d][1,2,3]triazol-1-yl)(6-chloro-2-(phenylamino)pyridin-3-yl)methanone [ka]

[0200] 6-Chloro-2-(phenylamino)nicotinic acid (3.70 g, 14.9 mmol) synthesized in Step 1 above, 1,2,3-benzotriazole (1.81 g, 14.9 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (2.85 g, 14.9 mmol) were sequentially added to dichloromethane (13 mL), and the reaction mixture was stirred at room temperature for 16 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed with distilled water. The separated organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (3.83 g, 74%).

[0201] [Step 3] Preparation of ethyl 3-(6-chloro-2-(phenylamino)pyridin-3-yl)-3-oxopropanoate [ka]

[0202] Ethyl acetate (1.45 g, 16.5 mmol) was diluted with tetrahydrofuran (30 mL) and cooled to -78 °C. A 2N solution of lithium diisopropylamide in tetrahydrofuran / heptane / benzene (12.1 mL, 24.2 mmol) was then added dropwise. The reaction mixture was stirred at -78 °C for 1 hour, and then a solution of (1H-benzo[d][1,2,3]triazol-1-yl)(6-chloro-2-(phenylamino)pyridin-3-yl)methanone (3.83 g, 11.0 mmol) prepared in Step 2 above in tetrahydrofuran (10 mL) was added dropwise. The mixture was stirred at the same temperature for 2 hours and then at room temperature for 16 hours. After the reaction was complete, the mixture was diluted with ethyl acetate and washed with 1N aqueous hydrochloric acid. The separated organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (1.3 g, 29%).

[0203] [Step 4] Preparation of 7-chloro-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one [ka]

[0204] N,N-Diisopropylethylamine (4.62 mL, 26.5 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (0.61 mL, 4.08 mmol) were added to ethyl 3-(6-chloro-2-(phenylamino)pyridin-3-yl)-3-oxopropanoate (1.30 g, 4.08 mmol) synthesized in Step 3 above, and the mixture was stirred at 120°C for 2 hours. After the reaction was completed, the resulting reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with 1N aqueous hydrochloric acid. The separated organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (1.1 g, 98%).

[0205] [Step 5] Preparation of 7-chloro-4-hydroxy-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one [ka]

[0206] The same procedure was carried out as in Example 1 [Step 5], except that 7-chloro-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one synthesized in [Step 4] above was used instead of 7-chloro-4-hydroxy-1-phenylquinolin-2(1H)-one, to obtain the title compound (450 mg, 39%).

[0207] [Step 6] Preparation of 4,7-dichloro-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one [ka]

[0208] The same procedure was carried out as in Example 1 [Step 6], except that 7-chloro-4-hydroxy-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one synthesized in [Step 5] above was used instead of 7-chloro-4-hydroxy-3-nitro-1-phenylquinolin-2(1H)-one, to obtain the title compound (460 mg, 97%).

[0209] [Step 7] Preparation of 7-chloro-4-(methylamino)-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one [ka]

[0210] The same reaction was carried out as in Example 1 [Step 7], except that 4,7-dichloro-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one synthesized in [Step 6] above was used instead of 4,7-dichloro-3-nitro-1-phenylquinolin-2(1H)-one to obtain the title compound (347 mg, 80.15%).

[0211] [Step 8] Preparation of 4-(methylamino)-3-nitro-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one [ka]

[0212] 7-Chloro-4-(methylamino)-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one (160 mg, 0.48 mmol) synthesized in Step 7 above was dissolved in N-methylpyrrolidone (2 mL), and 2,2,2-trifluoroethylamine (0.78 mL, 9.62 mmol) and N,N-diisopropylethylamine (0.42 mL, 2.40 mmol) were added. The mixture was then stirred at 160 °C in a microwave reactor for 3 hours. After cooling to room temperature, water was added to the reaction product, which was then extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure.

[0213] [Step 9] Preparation of 3-amino 4-(methylamino)-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one [ka]

[0214] The same reaction was carried out in Step 8 of Example 1, except that 4-(methylamino)-3-nitro-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one synthesized in Step 8 above was used instead of 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one, to obtain the title compound (76 mg, 58.35%).

[0215] [Step 10] Preparation of 2-(4-methoxyphenyl)-N-(4-(methylamino)-2-oxo-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,2-dihydro-1,8-naphthyridin-3-yl)acetamide [ka]

[0216] 3-Amino4-(methylamino)-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one (76 mg, 0.21 mmol) synthesized in [Step 9] above was dissolved in N,N-dimethylformamide (1 mL), and 2-(4-methoxyphenyl)acetic acid (38.24 mg, 0.23 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (159.07 mg, 0.42 mmol), and diisopropylethylamine (135.18 mg, 1.05 mmol) were added. The reaction mixture was stirred at room temperature for 5 hours, water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure to give the title compound (104 mg, 97.19%), which was used in [Step 11] without further purification.

[0217] [Step 11] Preparation of 2-(4-methoxybenzyl)-1-methyl-5-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0218] The same reaction was carried out except that 2-(4-methoxyphenyl)-N-(4-(methylamino)-2-oxo-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,2-dihydro-1,8-naphthyridin-3-yl)acetamide synthesized in [Step 10] above was used instead of N-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-phenylacetamide from [Step 10] of Example 1, to obtain the title compound (6.2 mg, 5.49%).

[0219] <Synthesis Example 4> Example 16: 7-chloro-5-(4-chloro-3-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0220] [Step 1] Preparation of 7-chloro-4-hydroxy-3-nitroquinolin-2(1H)-one [ka]

[0221] 7-Chloro-2H-benzo[d][1,3]oxazine-2,4(1H)-dione (12.0 g, 60.7 mmol), ethyl nitroacetate (12.5 g, 91.1 mmol), and triethylamine (12.7 mL, 91.1 mmol) were added sequentially to tetrahydrofuran (120 mL), and the reaction mixture was stirred at 55°C for 16 hours. After the reaction was complete, the mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. The resulting residue was diluted with water and washed with diethyl ether. The organic layer was removed, and the remaining aqueous layer was adjusted to pH 2-3 with 1N aqueous hydrochloric acid. The resulting solid was collected by filtration, washed with methanol and excess water, and dried to give the title compound (5.6 g, 38%).

[0222] [Step 2] Preparation of 2,4,7-trichloro-3-nitroquinoline [ka]

[0223] To the 7-chloro-4-hydroxy-3-nitroquinolin-2(1H)-one (995 mg, 4.14 mmol) synthesized in Step 1 above, phosphoryl chloride (10.8 mL, 116 mmol) was added, and the reaction mixture was cooled to 0°C. Triethylamine (0.98 mL, 7.04 mmol) was then slowly added dropwise. The reaction mixture was refluxed at 100°C for 4 hours, cooled to room temperature, poured into ice water, and extracted with ethyl acetate. The pH was adjusted to 7-8 with saturated sodium bicarbonate solution, and then extracted with dichloromethane. The resulting organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and distilled under reduced pressure to obtain the title compound (1.15 g, 100%).

[0224] [Step 3] Preparation of 2,7-dichloro-N-methyl-3-nitroquinolin-4-amine [ka]

[0225] The same procedure was carried out as in Example 1 [Step 7], except that 2,4,7-trichloro-3-nitroquinoline synthesized in [Step 2] above was used instead of 4,7-dichloro-3-nitro-1-phenylquinolin-2(1H)-one, to obtain the title compound (740 mg, 64%).

[0226] [Step 4] Preparation of 2,7-dichloro-N4-methylquinoline-3,4-diamine [ka]

[0227] The same procedure was carried out as in Example 1 [Step 8], except that 2,7-dichloro-N-methyl-3-nitroquinolin-4-amine synthesized in [Step 3] above was used instead of 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one, to obtain the title compound (470 mg, 71%).

[0228] [Step 5] Preparation of N-(2,7-dichloro-4-(methylamino)quinolin-3-yl)-2-(4-methoxyphenyl)acetamide [ka]

[0229] 2,7-Dichloro-N4-methylquinoline-3,4-diamine (530 mg, 2.19 mmol), 2-(4-methoxyphenyl)acetic acid (400 mg, 2.41 mmol), and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (1.25 g, 3.28 mmol) prepared in Step 4 above were diluted with N,N-dimethylformamide (5 mL). N,N-Diisopropylethylamine (849 mg, 6.57 mmol) was added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water. The separated organic layer was distilled under reduced pressure, and the resulting residue was dissolved in a hexane:ethyl acetate (4:1 (volume ratio), 20 mL) mixture. The resulting solid was filtered to obtain the title compound (570 mg, 67%).

[0230] [Step 6] Preparation of 4,7-dichloro-2-(4-methoxybenzyl)-1-methyl-1H-imidazo[4,5-c]quinoline [ka]

[0231] N-(2,7-dichloro-4-(methylamino)quinolin-3-yl)-2-(4-methoxyphenyl)acetamide (520 mg, 1.40 mmol) synthesized in Step 5 above was diluted with 1,4-dioxane (9.7 mL) and water (9.7 mL). Sodium hydroxide (520 mg, 1.40 mmol) was then added and the mixture was stirred at 100°C for 1 hour. After the reaction was completed, the reaction mixture was cooled to room temperature and adjusted to pH 7-8 with 1N aqueous hydrochloric acid. The solvent was then removed by distillation under reduced pressure. The solid produced by adding saturated sodium bicarbonate solution was collected by filtration, washed with water, and dried to obtain the title compound (520 mg, 96%).

[0232] [Step 7] Preparation of 7-chloro-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0233] JPEG2025533273000072.jpg4769

[0234] 4,7-Dichloro-2-(4-methoxybenzyl)-1-methyl-1H-imidazo[4,5-c]quinoline (520 mg, 1.40 mmol) synthesized in Step 6 above was added to 5N aqueous hydrochloric acid (7 mL) and ethanol (17 mL), and the reaction mixture was stirred at 100°C for 4 hours. After the reaction was complete, the reaction mixture was cooled to room temperature and mixed with saturated aqueous sodium bicarbonate and water to adjust the pH to 7-8, followed by stirring for 10 minutes. The resulting solid was collected by filtration, washed with water, and dried to yield the title compound (440 mg, 89%).

[0235] [Step 8] Preparation of 7-chloro-5-(4-chloro-3-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0236] 7-Chloro-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (40 mg, 0.11 mmol) synthesized in Step 7 above was dissolved in dimethyl sulfoxide (1 mL) and 4-chloro-3-fluorophenylboronic acid (40 mg, 0.23 mmol), pyridine (0.04 mL, 0.45 mmol), molecular sieves (4 Å), and cobalt(II) acetate (42 mg, 0.23 mmol) were added. The mixture was stirred at 80 °C for 16 hours in an open vial. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. Purification by silica gel column chromatography afforded the title compound (2.7 mg, 4.95%).

[0237] Example 17: 7-chloro-5-(3-chloro-4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0238] The same reaction was carried out using 3-chloro-4-fluorophenylboronic acid instead of 4-chloro-3-fluorophenylboronic acid in Step 8 of Example 16 to give the title compound (2.6 mg, 4.77%).

[0239] <Synthesis Example 5> Example 18: 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0240] [Step 1] Preparation of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0241] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (300 mg, 1.00 mmol) synthesized in Step 8 of Example 1 was dissolved in triethyl orthoformate (3.4 mL, 20.02 mmol) and stirred at 120° C. for 2 hours. After the reaction was completed, the mixture was cooled to room temperature, and the resulting solid was collected by filtration, washed with ethyl acetate, and dried to obtain the title compound (265 mg, 85.5%).

[0242] [Step 2] 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0243] 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (100 mg, 0.32 mmol) synthesized in Step 1 above was dissolved in dimethylformamide (3 mL) and 4-methoxybenzenethiol (67.9 mg, 0.48 mmol), copper(I) chloride (32.3 mg, 0.32 mmol), 1,10-phenanthroline (59.4 mg, 0.32 mmol), and sodium carbonate (86.4 mg, 0.81 mmol) were added. The reaction mixture was stirred at 140 °C for 3 days. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over magnesium sulfate and concentrated by distillation under reduced pressure. The product was purified by silica gel column chromatography and crystallized from methanol to give the title compound (29 mg, 20.0%).

[0244] Example 19: 7-chloro-2-((4-methoxyphenyl)sulfonyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0245] Example 20: 7-chloro-2-((4-methoxyphenyl)sulfinyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0246] 7-Chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (25 mg, 0.06 mmol) synthesized in Example 18 above was dissolved in dichloromethane (0.56 mL) and cooled to 0°C. 3-Chloroperoxycarboxylic acid (19 mg, 0.08 mmol) was then slowly added. The reaction mixture was stirred at 0°C for 30 minutes, and upon completion of the reaction, saturated aqueous sodium thiosulfate was added, followed by extraction with dichloromethane. The separated organic layer was dried over anhydrous magnesium sulfate and concentrated by distillation under reduced pressure. Purification by silica gel column chromatography gave [title compound of Example 19] 7-chloro-2-((4-methoxyphenyl)sulfonyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (15 mg, 56.0%) and [title compound of Example 20] 7-chloro-2-((4-methoxyphenyl)sulfinyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (8 mg, 25.9%).

[0247] According to an embodiment of the present invention, the compound of Formula 1 is a compound selected from the group consisting of the compounds listed in Table 2 below. [Table 2-1] [Table 2-2]

[0248] <Synthesis Example 6> [Intermediate 6-1] 2-(4-Methoxybenzyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ka]

[0249] Bis(pinacolato)diboron (1.99 g, 7.66 mmol), potassium carbonate (2.66 g, 19.2 mmol), and tetrakis(triphenylphosphine)palladium(0) (369 mg, 0.32 mmol) were added sequentially to anhydrous 1,4-dioxane. After purging with argon gas, 1-(chloromethyl)-4-methoxybenzene (1.02 g, 6.38 mmol) was added, and the mixture was refluxed at 120 °C for 18 hours. After cooling the reaction mixture to room temperature, the solid was filtered and washed with dichloromethane. The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (725 mg, 45.76%).

[0250] [Intermediate 6-2] Ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0251] [Step 1] Preparation of ethyl 1-methyl-1H-imidazole-4-carboxylate [ka]

[0252] 1-Methylimidazole-4-carboxylic acid (10 g, 77.71 mmol) was dissolved in ethanol (100 mL) and cooled to 0°C. Thionyl chloride (20 mL, 77.71 mmol) was added dropwise slowly over 15 minutes. The mixture was refluxed at 80°C for 14 hours. The reaction mixture was cooled to room temperature, neutralized with saturated aqueous sodium bicarbonate (200 mL), and extracted with dichloromethane. The separated organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue (10.7 g, 89.3%) was used in the next reaction without further purification.

[0253] [Step 2] Preparation of ethyl 2-bromo-1-methyl-1H-imidazole-4-carboxylate [ka]

[0254] Ethyl 1-methyl-1H-imidazole-4-carboxylate (6.3 g, 40.9 mmol) obtained in [Step 1] was dissolved in tetrahydrofuran (63 mL), cooled to 0 °C, and N-bromosuccinimide (11.1 g, 61.3 mmol) and potassium triphosphate (13.0 g, 61.3 mmol) were added. The reaction mixture was stirred at room temperature for 12 hours, then saturated aqueous sodium thiosulfate was added and extracted with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (6.3 g, 66.1%).

[0255] [Step 3] Preparation of ethyl 2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0256] Ethyl 2-bromo-1-methyl-1H-imidazole-4-carboxylate (11.0 g, 47.2 mmol) obtained in [Step 2] was dissolved in anhydrous 1,4-dioxane, and the above-synthesized [Intermediate 6-1] 2-(4-methoxybenzyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (23.4 g, 94.4 mmol), potassium triphosphate (30.1 g, 142 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.09 g, 1.42 mmol) were sequentially added. The mixture was purged with nitrogen gas for 30 minutes and then refluxed at 120 °C for 48 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (5.24 g, 40.47%).

[0257] [Step 4] Preparation of ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0258] Ethyl 2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (1.27 g, 4.63 mmol) obtained in [Step 3] was dissolved in dichloromethane (12.7 mL), cooled to 0 °C, and N-bromosuccinimide (832 mg, 4.63 mmol) was added. The reaction mixture was stirred at room temperature for 12 hours, after which saturated aqueous sodium thiosulfate was added and the mixture was extracted with dichloromethane. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (1.27 g, 77.7%).

[0259] [Intermediate 6-3] Ethyl 5-bromo-1-methyl-1H-imidazole-4-carboxylate [ka]

[0260] Ethyl 1-methyl-1H-imidazole-4-carboxylate (7.43 g, 48.2 mmol) obtained in [Step 1] was dissolved in dichloromethane (2 mL), cooled to 0 °C, and N-bromosuccinimide (13 g, 72.3 mmol) was added. The reaction mixture was stirred at room temperature for 12 hours, then saturated aqueous sodium thiosulfate was added and extracted with dichloromethane. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (3.73 g, 33.2%).

[0261] Example 21: 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0262] [Step 1] Preparation of 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline [ka]

[0263] 2-Bromo-5-chloroaniline (8 g, 37.98 mmol), bis(pinacolato)diboron (17.71 g, 68.3 mmol), potassium acetate (7.53 g, 75.9 mmol), and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride·dichloromethane complex (1.57 g, 1.90 mmol) were added to dimethyl sulfoxide (100 mL) and stirred at 85 °C for 3 h. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (9.1 g, 94.5%).

[0264] [Step 2] Preparation of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0265] 5-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (511 mg, 2.02 mmol) obtained in [Step 1] and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (475 mg, 1.34 mmol) obtained in [Intermediate 6-2] were added to 1,4-dioxane (4.75 mL) and water (0.95 mL). The mixture was purged with nitrogen gas, and then potassium triphosphate (571 mg, 2.69 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (31 mg, 0.04 mmol) were added. The mixture was refluxed at 100 °C for 20 hours, and then cooled to room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (115 mg, 21.4%).

[0266] [Step 3] Preparation of 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0267] Ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (115 mg, 0.29 mmol) obtained in [Step 2] was added to toluene (2.9 mL), and 3-bromo-2-methylpyridine (0.05 mL, 0.43 mmol), cesium carbonate (189 mg, 0.58 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.03 mmol), and Xantphos (17 mg, 0.03 mmol) were added sequentially. The mixture was then refluxed at 100 °C for 18 hours under nitrogen. The reaction mixture was cooled to room temperature, filtered through Celite, and distilled under reduced pressure. The filtrate was concentrated and stirred again with ethyl acetate. The resulting solid was filtered under reduced pressure and purified by silica gel column chromatography to give the title compound (43 mg, 33.6%).

[0268] Example 22: 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0269] 7-Chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (20 mg, 0.05 mmol) synthesized in [Step 3] of [Synthesis Example 6] and 10% palladium on carbon (14.4 mg) were dissolved in methanol (0.43 mL) and then a hydrogen balloon was attached. The reaction mixture was stirred at room temperature for 14 hours and then at 40 °C for another 2 hours. After completion of the reaction, the mixture was cooled to room temperature. The reaction mixture was filtered through Celite and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (12 mg, 65.03%).

[0270] Example 23: 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0271] The same reaction was carried out using 3-bromo-2-(trifluoromethyl)pyridine instead of 3-bromo-2-methylpyridine in Step 3 of Example 21 to obtain the title compound (15 mg, 21.03%).

[0272] Example 24: 7-chloro-5-(2-cyclopropylpyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0273] The same reaction was carried out using 3-bromo-2-cyclopropyl-pyridine instead of 3-bromo-2-methylpyridine in Step 3 of Example 21 to give the title compound (6 mg, 8.91%).

[0274] Example 25: 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)phenyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0275] The same reaction was carried out using 1-bromo-2-(trifluoromethyl)benzene instead of 3-bromo-2-methylpyridine in Step 3 of Example 21 to obtain the title compound (25.7 mg, 24.82%).

[0276] Example 26: 7-chloro-5-(2-chlorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0277] The same reaction was carried out using 1-bromo-2-chlorobenzene instead of 3-bromo-2-methylpyridine in Step 3 of Example 21 to obtain the title compound (16.7 mg, 17.38%).

[0278] Example 27: 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0279] The same reaction was carried out using ethyl 5-(2-amino-4-(trifluoromethyl)phenyl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (36.4 mg, 39.65%).

[0280] Example 28: 7-chloro-2-(4-fluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0281] The same reaction was carried out using ethyl 5-(2-amino-4-chlorophenyl)-2-(4-fluorobenzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (18.2 mg, 24.82%).

[0282] Example 29: 2-(benzo[d][1,3]dioxol-5-ylmethyl)-7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0283] The same reaction was carried out using ethyl 5-(2-amino-4-chlorophenyl)-2-(benzo[d][1,3]dioxol-5-ylmethyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (33.5 mg, 29.18%).

[0284] Example 30: 7-chloro-2-(3,4-difluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0285] The same reaction was performed using ethyl 5-(2-amino-4-chlorophenyl)-2-(3,4-difluorobenzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (16 mg, 21.82%).

[0286] Example 31: 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0287] The same reaction was carried out using 3-bromopyridine instead of 3-bromo-2-methylpyridine in Step 3 of Example 21 to give the title compound (11 mg, 12.76%).

[0288] Example 32: 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0289] 5-Chloro-N-(4-fluorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (70 mg, 0.20 mmol) and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (106 mg, 0.30 mmol) obtained in [Intermediate 6-2] were added to 1,4-dioxane (1 mL) and water (0.1 mL). The mixture was purged with nitrogen gas, and then cesium fluoride (95 mg, 0.61 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (16 mg, 0.02 mmol) were added. The mixture was refluxed at 100 °C for 72 hours, and then cooled to room temperature. Water was added to the reaction mixture, which was then extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (3.5 mg, 3.88%).

[0290] Example 33: 7-chloro-2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0291] The same reaction was performed using ethyl 5-(2-amino-4-chlorophenyl)-2-(4-difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (12 mg, 10.88%).

[0292] Example 34: 7-chloro-5-(4-methoxyphenyl)-2-((4-methoxyphenyl)thio)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0293] The same reaction was carried out in Step 2 of Example 18 using 7-chloro-5-(4-methoxyphenyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one to obtain the title compound (8 mg, 18.95%). Example 35: 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0294] The same reaction was carried out in Step 2 of Example 18 using 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one to obtain the title compound (65 mg, 18.24%).

[0295] Example 36: 7-chloro-2-((4-fluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0296] In Step 2 of Example 18, the same reaction was carried out using 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-fluorobenzenethiol instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxybenzenethiol to obtain the title compound (18 mg, 8.50%).

[0297] Example 37: 7-chloro-2-((3,4-difluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0298] The same reaction was carried out using 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 3,4-difluorobenzenethiol instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxybenzenethiol in [Step 2] of Example 18 to obtain the title compound (37 mg, 24.50%).

[0299] Example 38: 2-(benzo[d][1,3]dioxol-5-ylthio)-7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0300] The same reaction was carried out using 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and benzo[d][1,3]dioxole-5-thiol instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxybenzenethiol in [Step 2] of Example 18 to obtain the title compound (37 mg, 25.20%).

[0301] Example 39: 7-chloro-2-((2,4-difluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0302] The same reaction was carried out using 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 2,4-difluorobenzenethiol instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxybenzenethiol in [Step 2] of Example 18 to obtain the title compound (9.5 mg, 6.58%).

[0303] Example 40: 7-chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0304] [Step 1] Preparation of 1-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-3-(4-methoxyphenyl)urea [ka]

[0305] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (200 mg, 0.67 mmol) synthesized in Step 8 of Example 1 and 4-methoxyphenyl isocyanate (0.1 mL, 0.80 mmol) were added to dichloromethane (3 mL), and the reaction mixture was stirred at room temperature for 16 hours and then at 70°C for 4 hours. The reaction mixture was concentrated by distillation under reduced pressure and purified using silica gel column chromatography to obtain the title compound (130 mg, 43.40%).

[0306] [Step 2] Preparation of 7-chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0307] 1-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-3-(4-methoxyphenyl)urea (48 mg, 0.11 mmol) synthesized in Step 1 above was added to phosphoryl chloride (1 mL), and the reaction mixture was stirred at 80°C for 2 hours. The reaction mixture was adjusted to pH 7-8 with saturated sodium bicarbonate solution at room temperature and then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Purification using silica gel column chromatography afforded the title compound (12.8 mg, 24.64%).

[0308] Example 41: 7-chloro-2-((4-methoxyphenyl)(methyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0309] [Step 1] Preparation of 7-chloro-2-hydroxy-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0310] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (150 mg, 0.50 mmol), synthesized in Step 8 of Example 1, triphosgene (189 mg, 0.60 mmol), and triethylamine (0.14 mL, 1.00 mmol) were added to tetrahydrofuran (5 mL) and the reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was adjusted to pH 7-8 with saturated sodium bicarbonate solution at room temperature and then extracted with dichloromethane:methanol = 20:1 (volume ratio). The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Purification by silica gel column chromatography afforded the title compound (86.9 mg, 53.31%).

[0311] [Step 2] Preparation of 2-bromo-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0312] 7-Chloro-2-hydroxy-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (60 mg, 0.18 mmol) synthesized in Step 1 above and phosphoryl bromide (5.6 g, 18.4 mmol) were added to toluene (1 mL), and the reaction mixture was stirred at 110°C for 2 days. The reaction mixture was adjusted to pH 7-8 with saturated sodium bicarbonate solution at room temperature and then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate, concentrated by distillation under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (13.7 mg, 19.14%).

[0313] [Step 3] Preparation of 7-chloro-2-((4-methoxyphenyl)(methyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0314] 2-Bromo-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (17 mg, 0.04 mmol) synthesized in [Step 2] above, 4-methoxy-N-methylaniline (12 mg, 0.09 mmol), cesium carbonate (29 mg, 0.09 mmol), tris(dibenzylideneacetone)dipalladium(0) (4 mg, 0.004 mmol), and rac-BINAP (8.4 mg, 0.013 mmol) were added to toluene (0.4 mL) and purged with nitrogen gas. The mixture was refluxed at 100°C for 16 hours. After cooling to room temperature, the reaction product was filtered and washed with dichloromethane:methanol = 10:1 (volume ratio). The filtrate was concentrated and purified by silica gel column chromatography to give the title compound (6.8 mg, 34.94%).

[0315] Example 42: 7-chloro-2-(4-methoxyphenoxy)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0316] [Step 1] Preparation of 2,7-dichloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0317] 7-chloro-2-hydroxy-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (20 mg, 0.06 mmol) synthesized in Step 1 of Example 41 was added with phosphorus oxychloride (0.35 mL, 3.68 mmol) and refluxed at 120°C for 3 days. The reaction product was cooled to room temperature and distilled under reduced pressure. Saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous sodium sulfate, distilled under reduced pressure, concentrated, and purified by silica gel column chromatography to obtain the title compound (15 mg, 70.98%).

[0318] [Step 2] Preparation of 7-chloro-2-(4-methoxyphenoxy)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0319] 2,7-Dichloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (15 mg, 0.04 mmol) synthesized in [Step 1] above was added with 4-methoxyphenol (218.58 mg, 1.74 mmol) and cesium carbonate (28.68 mg, 0.09 mmol) and refluxed at 140 °C for 24 hours. The reaction product was cooled to room temperature and purified using silica gel column chromatography to obtain the title compound (6 mg, 31.88%).

[0320] According to an embodiment of the present invention, the compound of Formula 1 is a compound selected from the group consisting of the compounds listed in Table 3 below. [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5]

[0321] <Synthesis Example 7> [Intermediate 7-1] Ethyl 5-iodo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0322] Ethyl 2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (1 g, 3.65 mmol) obtained in [Step 3] of [Intermediate 6-2] was dissolved in N,N-dimethylformamide (20 mL) and N-iodosuccinimide (2.54 g, 10.94 mmol) was added. The reaction mixture was refluxed at 100 °C for 17 hours, cooled to room temperature, and saturated aqueous sodium thiosulfate was added. The mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (1.4 g, 95.96%). [ka]

[0323] [Step 1] Preparation of 4-iodo-3-nitrophenol [ka]

[0324] 4-Amino-3-nitrophenol (10.3 g, 64.89 mmol) was dissolved in 38% aqueous hydrochloric acid (5 mL) and cooled to 0°C. A solution of sodium nitrite (9.14 g, 129.77 mmol) in water (20 mL) was then added dropwise. After stirring at 0°C for 1 hour, a solution of potassium iodide (21.54 g, 129.77 mmol) in water (40 mL) was added dropwise. The reaction mixture was stirred at room temperature for 15 hours, after which the resulting solid was collected by filtration, washed with excess water, and dried to give the title compound (16.5 g, 95.96%).

[0325] [Step 2] Preparation of 4-(benzyloxy)-1-iodo-2-nitrobenzene [ka]

[0326] 4-Iodo-3-nitrophenol (16.5 g, 62.26 mmol) obtained in Step 1 above was dissolved in acetone (165 mL), and potassium carbonate (17.30 g, 124.52 mmol) and benzyl bromide (8.31 mL, 68.49 mmol) were added. The reaction mixture was stirred at room temperature for 18 hours, after which the resulting solid was removed by filtration, and the filtrate was distilled under reduced pressure. Water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and distilled under reduced pressure to obtain the title compound (21 g, 94.98%).

[0327] [Step 3] Preparation of 5-(benzyloxy)-2-iodoaniline [ka]

[0328] 4-(benzyloxy)-1-iodo-2-nitrobenzene (5 g, 14.08 mmol) obtained in Step 2 above was dissolved in methanol (37.5 mL), activated carbon (845 mg, 70.40 mmol) and iron(III) chloride (235 mg, 1.41 mmol) were added, and the mixture was purged with nitrogen gas and stirred at 70°C for 10 minutes. The reaction mixture was cooled to room temperature, and hydrazine monohydrate (3.48 mL, 70.40 mmol) was slowly added dropwise. The reaction mixture was refluxed at 70°C for 21 hours, cooled to room temperature, and filtered through Celite. The filtrate was evaporated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and evaporated under reduced pressure. The resulting residue was dissolved in ethyl acetate (40 mL), and 4N hydrochloric acid in 1,4-dioxane (20 mL) was added. The mixture was stirred at room temperature for 30 minutes. The resulting solid was collected by filtration, washed with excess ethyl acetate, and dried to give the title compound (3.22 g, 63.25%).

[0329] [Step 4] Preparation of 5-(benzyloxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline [ka]

[0330] 5-(Benzyloxy)-2-iodoaniline hydrochloride (3.22 g, 8.90 mmol) obtained in Step 3 above was added to anhydrous 1,4-dioxane (48.3 mL) and purged with nitrogen. Triethylamine (6.27 mL, 44.52 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (368 mg, 0.44 mmol), and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.52 g, 26.71 mmol) were then added. The mixture was refluxed at 100 °C for 14 hours. After completion of the reaction, the mixture was cooled to room temperature. Saturated aqueous ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (1 g, 34.53%).

[0331] [Step 5] Preparation of ethyl 5-(2-amino-4-(benzyloxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0332] 5-(benzyloxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (2.68 g, 8.25 mmol) synthesized in [Step 4] above and [Intermediate 7-1] ethyl 5-iodo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (3 g, 7.50 mmol) were added to anhydrous 1,4-dioxane (30 mL) and water (15 mL). The mixture was purged with nitrogen gas, and sodium bicarbonate (1.9 g, 22.49 mmol) and tetrakis(triphenylphosphine)palladium(0) (446 mg, 0.37 mmol) were added. The mixture was refluxed at 90 °C for 14 hours. After completion of the reaction, the mixture was cooled to room temperature. The reaction mixture was added with saturated aqueous ammonium chloride and extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (1.4 g, 39.61%).

[0333] [Step 6] Preparation of 7-(benzyloxy)-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0334] The same reaction was carried out using ethyl 5-(2-amino-4-(benzyloxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (1.4 g, 91.28%).

[0335] [Step 7] Preparation of 7-hydroxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [Example 43] [ka]

[0336] Acetic acid (1 mL) and 38% aqueous hydrochloric acid (1 mL) were added to 7-(benzyloxy)-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (1.4 g, 2.71 mmol) synthesized in Step 6 above. The mixture was refluxed at 140°C for 7 hours. After completion of the reaction, the mixture was cooled to room temperature. The reaction mixture was distilled under reduced pressure, followed by the addition of saturated aqueous sodium bicarbonate solution and stirring for 30 minutes. The mixture was then extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (630 mg, 54.51%).

[0337] [Step 8] Preparation of 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate [ka]

[0338] 7-Hydroxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (150 mg, 0.35 mmol) synthesized in Step 7 above was dissolved in dichloromethane (1.5 mL), and triethylamine (0.10 mL, 0.70 mmol) and 1,1,1-trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (192 mg, 0.53 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours and then distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (196 mg, 100%).

[0339] [Step 9] Preparation of 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-vinyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [Example 44] [ka]

[0340] (4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate (196 mg, 0.35 mmol) synthesized in Step 8 above was dissolved in anhydrous 1,4-dioxane (2 mL). After purging with argon gas, potassium carbonate (146 mg, 1.05 mmol), tetrakis(triphenylphosphine)palladium(0) (41.8 mg, 0.04 mmol), and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.09 mL, 0.53 mmol) were added. The mixture was refluxed at 100 °C for 2 hours, and then cooled to room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (145 mg, 94.66%).

[0341] [Step 10] Preparation of 7-ethyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [Example 45] [ka]

[0342] 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-vinyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (145 mg, 0.33 mmol) synthesized in Step 9 above and 10% palladium on carbon (177 mg) were dissolved in methanol (3.32 mL) and then a hydrogen balloon was attached. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered through Celite and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (63 mg, 43.25%).

[0343] Example 46: 7-Cyclopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0344] The same reaction was carried out using cyclopropylboronic acid instead of 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane in [Step 9] of <Synthesis Example 7> to obtain the title compound (5 mg, 65.79%).

[0345] Example 47: 7-ethynyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0346] 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate (20 mg, 0.04 mmol) synthesized in [Step 8] of <Synthesis Example 7>, ethynyltrimethylsilane (0.02 mL, 0.18 mmol), tetrakis(triphenylphosphine)palladium(0) (4.3 mg, 0.004 mmol), cuprous iodide (0.68 mg, 0.004 mmol), and trimethylamine (0.01 mL, 0.07 mmol) were dissolved in N,N-dimethylformamide (1 mL), and the mixture was stirred at 40° C. for 18 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-((trimethylsilyl)ethynyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (14 mg, 77.16%).

[0347] 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-((trimethylsilyl)ethynyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (14 mg, 0.03 mmol) and potassium carbonate (38 mg, 0.28 mmol) were dissolved in methanol (0.28 mL) and stirred at room temperature for 16 hours. After completion of the reaction, water was added to the reaction mixture, which was then extracted with dichloromethane. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (2.4 mg, 19.19%).

[0348] Example 48: 7-Isopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0349] In <Synthesis Example 7> [Step 10], 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-vinyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one was used instead of 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(prop-1-en-2-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one, and the same reaction was carried out to obtain the title compound (11.5 mg, 77.55%).

[0350] Example 49: 2-(4-Methoxybenzyl)-1,7-dimethyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0351] The same reaction was carried out using 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane instead of 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane in [Step 9] of <Synthesis Example 7> to obtain the title compound (3 mg, 37.19%).

[0352] Example 50: 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(pyrrolidin-1-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0353] 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate (10 mg, 0.02 mmol) synthesized in [Step 8] of <Synthesis Example 7>, cesium carbonate (11.78 mg, 0.04 mmol), palladium acetate (0.41 mg, 0.002 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (1.7 mg, 0.002 mmol), and pyrrolidine (0.005 mL, 0.05 mmol) were dissolved in anhydrous 1,4-dioxane (0.2 mL) and then purged with argon gas. The mixture was refluxed at 100°C for 1 hour, and then cooled to room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (2 mg, 23.29%).

[0354] Example 51: 7-Methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0355] 7-Hydroxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (10 mg, 0.03 mmol) prepared in Step 7 of Synthesis Example 7 was dissolved in N,N-dimethylformamide (0.23 mL), followed by the addition of potassium carbonate (6.5 mg, 0.05 mmol) and methyl iodide (0.003 mL, 0.05 mmol). The mixture was stirred at room temperature for 1 hour, and then water and ethyl acetate were added. The mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (4.3 mg, 41.63%).

[0356] Example 52: 7-amino-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0357] 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate (100 mg, 0.18 mmol) synthesized in [Step 8] of <Synthesis Example 7>, cesium carbonate (117.85 mg, 0.36 mmol), palladium acetate (4.1 mg, 0.02 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (17.24 mg, 0.03 mmol), and benzophenone imine (0.15 mL, 0.90 mmol) were dissolved in anhydrous 1,4-dioxane (1 mL) and then purged with argon gas. The mixture was refluxed at 100°C for 2 hours, and then cooled to room temperature. The reaction product was distilled under reduced pressure and purified by silica gel column chromatography to give 7-((diphenylmethylene)amino)-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (63.8 mg).

[0358] The resulting intermediate was dissolved in tetrahydrofuran (1 mL) and 1N aqueous hydrochloric acid (0.1 mL) and stirred at room temperature for 30 minutes. After the reaction was completed, saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (39 mg, 51.19%).

[0359] Example 53: 2-(4-Methoxybenzyl)-1-methyl-7-(methylamino)-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0360] 7-Amino-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (10 mg, 0.02 mmol) synthesized in Example 52, 25 wt% sodium methoxide methanol solution (0.05 mL), and 10% palladium on carbon (0.5 mg, 0.0005 mmol) were dissolved in methanol (0.5 mL) and refluxed at 130 °C for 3 days. After completion of the reaction, the mixture was cooled to room temperature. The reaction mixture was filtered through Celite and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (4 mg, 38.72%).

[0361] Example 54: 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0362] The same reaction was performed using ethyl 5-(2-amino-4-ethylphenyl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (290 mg, 52.50%).

[0363] Example 55: 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one [ka]

[0364] The same reaction was performed using ethyl 5-(2-amino-4-methoxyphenyl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate instead of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Step 3 of Example 21 to obtain the title compound (124 mg, 61.69%).

[0365] According to an embodiment of the present invention, the compound of Formula 1 is a compound selected from the group consisting of the compounds listed in Table 4 below. [Table 4-1] [Table 4-2] [Table 4-3]

[0366] <Synthesis Example 8> Example 56: 5-(4-(difluoromethoxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0367] [Step 1] Preparation of (2-fluoro-6-(trifluoromethyl)pyridin-3-yl)boronic acid [ka]

[0368] 2-Fluoro-6-(trifluoromethyl)pyridine (15 g, 80.04 mmol) was dissolved in anhydrous tetrahydrofuran (150 mL) and then purged with nitrogen gas. The mixture was cooled to -78 °C, and then 2.0 M lithium diisopropylamide solution (53.43 mL, 106.85 mmol) was slowly added dropwise and stirred at the same temperature for 1 hour. Trimethylboronic acid (12 mL, 106.85 mmol) was slowly added dropwise and stirred at room temperature for 22 hours. 5 wt% aqueous sodium hydroxide solution (200 mL) was added to the reaction mixture, which was then neutralized with 5 N aqueous hydrochloric acid and extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain the title compound (16 g, 86.01%).

[0369] [Step 2] Preparation of ethyl 5-(2-fluoro-6-(trifluoromethyl)pyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0370] (2-Fluoro-6-(trifluoromethyl)pyridin-3-yl)boronic acid (1.18 g, 5.66 mmol) synthesized in [Step 1] above and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (1.00 g, 2.83 mmol) obtained in [Intermediate 6-2] were added to anhydrous 1,4-dioxane (10 mL) and water (1 mL), and the atmosphere was replaced with nitrogen gas. Cesium carbonate (1.11 g, 7.08 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (67.4 mg, 0.14 mmol), and (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (123 mg, 0.14 mmol) were added. The mixture was refluxed at 120 °C for 14 hours. After completion of the reaction, it was cooled to room temperature. Water was added to the reaction mixture, which was then extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (539 mg, 43.53%).

[0371] [Step 3] Preparation of 5-(4-(difluoromethoxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0372] Ethyl 5-(2-fluoro-6-(trifluoromethyl)pyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (100 mg, 0.23 mmol) synthesized in Step 2 above and 4-(difluoromethoxy)aniline (45 mg, 0.27 mmol) were dissolved in anhydrous tetrahydrofuran (2.28 mL) and then purged with nitrogen. The mixture was cooled to 0 °C, and 1.0 M lithium bis(trimethylsilyl)amide tetrahydrofuran solution (0.69 mL, 0.69 mmol) was slowly added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, water was added and the mixture was extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (17.8 mg, 14.68%).

[0373] Example 57: 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0374] The same reaction was carried out using 2-methylpyridin-3-amine instead of 4-(difluoromethoxy)aniline in [Step 3] of <Synthesis Example 8> to obtain the title compound (27.3 mg, 19.16%).

[0375] Example 58: 2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0376] In [Step 3] of <Synthesis Example 8>, the same reaction was carried out using ethyl 2-(4-(difluoromethoxy)benzyl)-5-(2-fluoro-6-(trifluoromethyl)pyridin-3-yl)-1-methyl-1H-imidazole-4-carboxylate and 2-methylpyridin-3-amine instead of ethyl 5-(2-fluoro-6-(trifluoromethyl)pyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate and 4-(difluoromethoxy)aniline to obtain the title compound (150 mg, 68.88%).

[0377] Example 59: 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0378] The same reaction was carried out in Step 2 of Example 18 using 1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one to obtain the title compound (81 mg, 71.42%).

[0379] Example 60: 2-((4-fluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0380] In Step 2 of Example 18, 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxybenzenethiol were replaced with 1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one and 4-fluorobenzenethiol, and the same reaction was carried out to obtain the title compound (70 mg, 64.76%).

[0381] Example 61: 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one

[0382] JPEG2025533273000159.jpg72154

[0383] [Step 1] Preparation of 5-bromo-2-(trifluoromethyl)pyrimidin-4(3H)-one [ka]

[0384] 2-(Trifluoromethyl)pyrimidin-4(3H)-one (6.18 g, 35.8 mmol) was dissolved in N,N-dimethylformamide (50 mL), and N-bromosuccinimide (7.80 g, 42.9 mmol) was added. The mixture was stirred at 40°C for 22 hours, and after the reaction was completed, it was cooled to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain the title compound (8.69 g, 100%).

[0385] [Step 2] Preparation of 5-bromo-N-(2-methylpyridin-3-yl)-2-(trifluoromethyl)pyrimidin-4-amine [ka]

[0386] 5-Bromo-2-(trifluoromethyl)pyrimidin-4(3H)-one (8.69 g, 35.76 mmol) synthesized in Step 1 above was dissolved in tetrahydrofuran (86.9 mL), and 2,6-lutidine (6.3 mL, 53.6 mmol) was added. The mixture was cooled to -78 °C. After 30 minutes, trifluoromethanesulfonic anhydride (8.0 mL, 46.5 mmol) was added dropwise at the same temperature and stirred at 0 °C for 3 hours. 2-Methylpyridin-3-amine (11.8 g, 107 mmol) was added to the reaction mixture, and the mixture was refluxed at 70 °C for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (5.47 g, 45.92%).

[0387] [Step 3] Preparation of N-(2-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyrimidin-4-amine [ka]

[0388] 5-Bromo-N-(2-methylpyridin-3-yl)-2-(trifluoromethyl)pyrimidin-4-amine (717 mg, 1.50 mmol) synthesized in Step 2 above was added to anhydrous 1,4-dioxane (5 mL) and purged with nitrogen. Bis(pinacolato)diboron (837 mg, 3.23 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (166 mg, 0.22 mmol), and potassium acetate (640 mg, 6.46 mmol) were then added. The mixture was refluxed at 100 °C for 19 hours. After completion of the reaction, the mixture was cooled to room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to yield the title compound (240 mg, 29.33%).

[0389] [Step 4] Preparation of 1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one [ka]

[0390] N-(2-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyrimidin-4-amine (798 mg, 1.05 mmol) synthesized in [Step 3] above was added to 1,4-dioxane (1 mL) and water (0.1 mL) and the mixture was purged with nitrogen gas. The mixture was then added with ethyl 5-bromo-1-methyl-1H-imidazole-4-carboxylate (245 mg, 1.05 mmol), cesium fluoride (493 mg, 3.15 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (70.5 mg, 0.11 mmol). The mixture was refluxed at 100 °C for 18 hours, and then cooled to room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (17 mg, 4.49%).

[0391] [Step 5] Preparation of 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one [ka]

[0392] The same reaction was carried out in Step 2 of Example 18 using 1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one instead of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one to obtain the title compound (7.8 mg, 33.16%).

[0393] Example 62: 7-Ethoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one [ka]

[0394] [Step 1] Preparation of 5-bromo-N-(2-methylpyridin-3-yl)-2-(methylthio)pyrimidin-4-amine [ka]

[0395] 2-Methylpyridin-3-amine (994 mg, 9.00 mmol) was dissolved in tetrahydrofuran (14 mL) and cooled to 0 °C. Sodium hydride (720 mg, 18.00 mmol) was added at the same temperature and stirred at room temperature for 30 minutes. The reaction mixture was cooled to 0 °C, and a solution of 5-bromo-4-chloro-2-(methylthio)pyrimidine (2 g, 8.18 mmol) in tetrahydrofuran (6 mL) was added dropwise and refluxed at 55 °C for 15 hours. After the reaction was complete, the mixture was cooled to room temperature, water was added, and the resulting solid was collected by filtration and washed with excess water. The resulting residue was purified by silica gel column chromatography to yield the title compound (1.0 g, 38%).

[0396] [Step 2] Preparation of 5-bromo-N-(2-methylpyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-amine [ka]

[0397] 5-Bromo-N-(2-methylpyridin-3-yl)-2-(methylthio)pyrimidin-4-amine (500 mg, 1.61 mmol) synthesized in Step 1 above was added to dichloromethane (5 mL) and cooled to 0°C. 3-Chloroperbenzoic acid (1.19 g, 4.82 mmol) was slowly added and stirred at room temperature for 1 hour. After the reaction was completed, saturated aqueous sodium bicarbonate was added, and the mixture was extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to obtain the title compound (395 mg, 71.69%).

[0398] [Step 3] Preparation of 5-bromo-2-ethoxy-N-(2-methylpyridin-3-yl)pyrimidin-4-amine [ka]

[0399] 5-Bromo-N-(2-methylpyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-amine (395 mg, 1.15 mmol) synthesized in Step 2 above was dissolved in tetrahydrofuran (11.5 mL), and then 21 wt% sodium ethoxide ethanol solution (447 mg, 1.38 mmol) was added dropwise. The mixture was stirred at room temperature for 2 hours. After completion of the reaction, the residue obtained by vacuum distillation was purified by silica gel column chromatography to obtain the title compound (245 mg, 68.8%).

[0400] [Step 4] Preparation of 2-ethoxy-N-(2-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-amine [ka]

[0401] The same reaction was carried out using 5-bromo-2-ethoxy-N-(2-methylpyridin-3-yl)pyrimidin-4-amine instead of 5-bromo-N-(2-methylpyridin-3-yl)-2-(trifluoromethyl)pyrimidin-4-amine in Step 3 of Example 61 to obtain the title compound (57 mg, 20.19%).

[0402] [Step 5] Preparation of 7-ethoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one [ka]

[0403] In Step 4 of Example 61, N-(2-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyrimidin-4-amine and ethyl 5-bromo-1-methyl-1H-imidazole-4-carboxylate was used in place of 2-ethoxy-N-(2-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-amine and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate obtained in [Intermediate 6-2]. The same reaction was carried out to obtain the title compound (12.5 mg, 17.11%).

[0404] <Synthesis Example 9> Example 63: 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0405] [Step 1] Preparation of 3-bromo-2-chloro-6-methoxypyridine [ka]

[0406] 2-Chloro-6-methoxypyridine (4.1 mL, 34.1 mmol) and benzoyl peroxide (551 mg, 1.7 mmol) were added to acetonitrile (20 mL). N-bromosuccinimide (9.2 g, 51.2 mmol) was added to the mixture, and the reaction mixture was refluxed at 100°C for 3 hours. After cooling to room temperature, the reaction mixture was added with water and extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. The product was purified using silica gel column chromatography to obtain the title compound (5.4 g, 71.52%).

[0407] [Step 2] Preparation of 2-chloro-6-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

[0408] JPEG2025533273000173.jpg3960

[0409] 3-Bromo-2-chloro-6-methoxypyridine (6.3 g, 28.3 mmol) synthesized in Step 1 above, bis(pinacolato)diboron (11 g, 42.4 mmol), potassium acetate (5.6 g, 56.5 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (4.4 g, 5.65 mmol) were added to anhydrous 1,4-dioxane (57 mL). After purging with nitrogen gas, the mixture was refluxed at 100°C for 20 hours. After cooling the reaction mixture to room temperature, the solid was filtered and washed with dichloromethane:methanol = 10:1 (volume ratio). The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (4.5 g, 58.95%).

[0410] [Step 3] Preparation of ethyl 5-(2-chloro-6-methoxypyridin-3-yl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate [ka]

[0411] 2-Chloro-6-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.9 g, 10.6 mmol) synthesized in [Step 2] above, ethyl 5-bromo-2-[[4-(difluoromethoxy)phenyl]methyl]-1-methyl-imidazole-4-carboxylate (2.1 g, 5.31 mmol), cesium fluoride (4.2 g, 26.6 mmol), RuPhos (253 mg, 0.53 mmol), and RuPhosPdG (468 mg, 0.53 mmol) were added to 1,4-dioxane (20 mL) and water (2 mL). After purging with nitrogen gas, the mixture was refluxed at 120 °C for 17 hours. After cooling the reaction mixture to room temperature, 6M potassium carbonate solution (2 mL) was added, followed by the addition of water and extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (1.4 g, 58.73%).

[0412] [Step 4] Preparation of 5-(2-chloro-6-methoxypyridin-3-yl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-N-(2-methylpyridin-3-yl)-1H-imidazole-4-carboxamide [ka]

[0413] Ethyl 5-(2-chloro-6-methoxypyridin-3-yl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate (1.4 g, 3.12 mmol) synthesized in Step 3 above and 3-aminopicoline (379 mg, 3.43 mmol) were added to anhydrous tetrahydrofuran (31 mL) and an argon balloon was attached. The reaction mixture was cooled to -78 °C, and a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (6.9 mL, 6.87 mmol) was slowly added dropwise. The reaction mixture was stirred at room temperature for 1 hour, followed by the addition of water and extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Purification using silica gel column chromatography afforded the title compound (1.46 g, 90.94%).

[0414] [Step 5] Preparation of 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0415] 5-(2-chloro-6-methoxypyridin-3-yl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-N-(2-methylpyridin-3-yl)-1H-imidazole-4-carboxamide (1.3 g, 2.49 mmol) synthesized in Step 4 above and sodium hydride (199 mg, 4.98 mmol) were added to N,N-dimethylformamide (12 mL) at 0°C, and the reaction mixture was stirred at room temperature for 30 minutes. Water and saturated aqueous ammonium chloride solution were added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Purification using silica gel column chromatography afforded the title compound (633 mg, 53.17%).

[0416] Example 64: 7-Methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0417] The same reaction was carried out except that ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate [Intermediate 6-2 in Synthesis Example 6] was used instead of ethyl 5-bromo-2-[[4-(difluoromethoxy)phenyl]methyl]-1-methyl-imidazole-4-carboxylate in Example 63, to obtain the title compound (223 mg, 67.82%).

[0418] <Synthesis Example 10> Example 65: 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0419] [Step 1] Preparation of ethyl 7-chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate [ka]

[0420] A reaction solution of 2,6-dichloronicotinic acid (4.63 g, 23.6 mmol) dissolved in dichloromethane (75 mL) was added with 2-3 drops of N,N-dimethylformamide, and oxalyl chloride (5.79 mL, 67.50 mmol) was slowly added dropwise. The mixture was then stirred at room temperature for 3 hours. After the solvent was distilled off, the reaction product was immediately used in the next reaction after adding tetrahydrofuran (30 mL). (Reaction Solution A)

[0421] Ethyl 3-((2-methylpyridin-3-yl)amino)-3-oxopropanoate (5.0 g, 22.50 mmol) was dissolved in tetrahydrofuran (120 mL), and sodium hydride (3.6 g, 90.00 mmol) was slowly added dropwise. The mixture was stirred at room temperature for 30 minutes and then cooled to 0°C. Reaction solution A was added dropwise to the cooled reaction solution, and the mixture was gradually heated to room temperature and stirred for 2 hours. After that, the mixture was refluxed with stirring at 80°C for 12 hours. The reaction solution was cooled to room temperature, and the pH was adjusted to acidic by adding 3N aqueous hydrochloric acid, followed by extraction with ethyl acetate. The extracted organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue (6.5 g, 80.3%) was used in the next reaction without further purification.

[0422] [Step 2] Preparation of 7-chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one [ka]

[0423] Ethyl 7-chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate (8.94 g, 24.8 mmol) synthesized in [Step 1] was added to trifluoroacetic acid (40 mL) / 35% hydrochloric acid (40 mL) and refluxed with stirring at 100°C for 4 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, neutralized with saturated aqueous sodium carbonate (pH = 6), and extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Ethyl acetate (50 mL) was added to the concentrate again, and the resulting solid was filtered under reduced pressure to obtain the title compound (3.44 g, 48%).

[0424] [Step 3] Preparation of 4-hydroxy-1-(2-methylpyridin-3-yl)-7-vinyl-1,8-naphthyridin-2(1H)-one [ka]

[0425] 7-Chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one (900 mg, 3.13 mmol) synthesized in Step 2 above, tributyl(vinyl)tin (1.0 mL, 3.44 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (264 mg, 0.31 mmol) were added to 1,4-dioxane (31 mL) and purged with nitrogen. The mixture was refluxed at 110 °C for 15 hours. A saturated aqueous solution of potassium fluoride was added to the reaction mixture and stirred at room temperature for 2 hours. The reaction mixture was filtered through Celite, water was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Purification using silica gel column chromatography afforded the title compound (358 mg, 40.94%).

[0426] [Step 4] Preparation of 7-ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one

[0427] JPEG2025533273000182.jpg4959

[0428] 4-Hydroxy-1-(2-methylpyridin-3-yl)-7-vinyl-1,8-naphthyridin-2(1H)-one (358 mg, 1.28 mmol) synthesized in Step 3 above was added to 10% palladium in activated carbon (Pd / C) (164 mg, 0.15 mmol) and methanol (26 mL), and a hydrogen balloon was attached. The reaction mixture was stirred at room temperature for 16 hours, filtered through Celite, and purified by silica gel column chromatography to obtain the title compound (224 mg, 62.09%).

[0429] [Step 5] Preparation of 7-ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one [ka]

[0430] 7-Ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one (606 mg, 2.15 mmol) synthesized in Step 4 above and sodium nitrite (30 mg, 0.43 mmol) were added to acetic acid (4 mL), and fuming nitric acid (0.85 mL, 18.3 mmol) was slowly added dropwise to the reaction mixture. The mixture was stirred at 50°C for 20 minutes, cooled to room temperature, poured into ice water, and stirred for 30 minutes. The resulting solid was collected by filtration, washed with water, and dried to give the title compound (340 mg, 48.35%).

[0431] [Step 6] Preparation of 4-chloro-7-ethyl-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one [ka]

[0432] 7-Ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one (347 mg, 1.06 mmol) synthesized in Step 5 above, phosphoryl chloride (0.61 mL, 6.38 mmol), and N,N-diisopropylethylamine (0.56 mL, 3.19 mmol) were added to toluene (11 mL), and the reaction mixture was stirred at 100° C. for 2 hours. The reaction product was concentrated by distillation under reduced pressure and dried to obtain the title compound (367 mg, 99.99%).

[0433] [Step 7] Preparation of 7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one [ka]

[0434] 4-Chloro-7-ethyl-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one (367 mg, 1.06 mmol), methylamine chloride hydrate (87.97 mg, 1.28 mmol), and N,N-diisopropylethylamine (1.68 mL, 9.58 mmol) were added to dichloromethane (11 mL) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was dried and water was added. The resulting solid was collected by filtration, washed with water, and dried to give the title compound (330 mg, 91.26%).

[0435] [Step 8] Preparation of 3-amino-7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one [ka]

[0436] To the 7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one (330 mg, 0.97 mmol) synthesized in Step 7 above, Raney nickel (114 mg, 0.97 mmol) and dichloromethane (9 mL) / methanol (3 mL) were added, and a hydrogen balloon was attached. The reaction mixture was stirred at room temperature for 16 hours, filtered through Celite, and purified by silica gel column chromatography to obtain the title compound (228 mg, 75.74%).

[0437] [Step 9] Preparation of 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0438] 3-Amino-7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one (134 mg, 0.43 mmol), 2-[4-(difluoromethoxy)phenyl]acetic acid (87.6 mg, 0.43 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (181 mg, 0.48 mmol), and triethylamine (0.18 mL, 1.30 mmol) were sequentially added to N,N-dimethylformamide (4.3 mL). The reaction mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by distillation under reduced pressure. Acetic acid (1 mL) was added to the concentrated mixture, and the reaction mixture was stirred at 100° C. for 16 hours. The reaction product was dried by distillation under reduced pressure and purified by silica gel column chromatography to obtain the title compound (164 mg, 79.48%).

[0439] Example 66: 7-Cyclopropyl-2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one [ka]

[0440] In Step 9 of Example 65, the same reaction was performed using 3-amino-7-cyclopropyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one and 2-(4-(difluoromethoxy)phenyl)acetic acid instead of 3-amino-7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one and 2-(4-methoxyphenyl)acetic acid to obtain the title compound (184 mg, 52.28%).

[0441] According to an embodiment of the present invention, the compound of Formula 1 is a compound selected from the group consisting of the compounds listed in Table 5 below. [Table 5-1] [Table 5-2] [Table 5-3]

[0442] Experimental Example 1: Cell growth inhibition test The synthetic compounds were confirmed to inhibit cell growth of HCT116 cells. HCT116 MTAP- / - (homozygous knockout of the MTAP gene in HCT116 MTAP-WT cells by the CRISPER / Cas9 method) cells were maintained in RPMI1640 medium containing 10% FBS and 1% penicillin-streptomycin. Approximately 5x10 2Cells were seeded into 96-well plates and treated with test compounds (0.64 nM-2,000 nM, 6 dose points for 5 and 6 days on HCT116 MTAP- / - cells). Cell growth was measured by SRB staining and analyzed by Synergy TM The absorbance was detected at 540 nm using a NEO microplate reader. 50 ) was calculated using GraphPad Prism V9 software.

[0443] The results of Experimental Example 1 are shown in Table 6 below.

[0444] G.I. 50 Values ​​were designated as A if they were less than 100 nM, B if they were 100 nM or more but less than 500 nM, C if they were 500 nM or more but less than 1 μM, and D if they were 1 μM or more. [Table 6-1] [Table 6-2]

[0445] The present invention has been described above with reference to specific embodiments. Those skilled in the art will understand that the present invention can be embodied in various modified forms without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the claims, not the foregoing description, and all variations within the scope of the claims should be construed as being within the scope of the present invention.

Claims

1. A compound selected from the group consisting of compounds of the following formula 1, their optical isomers, diastereomers, solvates, hydrates and pharmaceutically acceptable salts thereof: 【Chemical 1】 In the above Chemical Formula 1, X and Z are each independently N or CH; Y is CR ３ and R ３ is H, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfonyl, hydroxy, halogen, haloalkyl, haloalkoxy, cycloalkyl, cyano, amino, alkylamino, haloalkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxyalkyl, hydroxyalkoxy, hydroxyalkylamino, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aminoalkyl, aminoalkoxy, aminoalkylamino, aryl, heteroaryl, heteroaryloxy, heteroarylamino, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclyloxyalkoxy or heterocyclyloxyalkylamino; wherein aryl, heteroaryl, or heterocyclyl is unsubstituted or substituted with one to three selected from alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, halo, cyano, hydroxyalkyl, alkoxyalkyl, and aminoalkyl; 【Chemistry 2】 are each independently H, cycloalkyl, aryl, or heteroaryl, heterocyclyl; wherein said cycloalkyl, aryl, heteroaryl, or heterocyclyl may each be monocyclic, bicyclic, or polycyclic; Here, cycloalkyl, aryl, heteroaryl or heterocyclyl is defined as R ２ or unsubstituted with 1 to 3 independently selected from: L is C １－３ Alkylene, O, NH, N(C １－３ alkyl), S, SO, SO ２ or a bond; R ２ is alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, alkylsulfonyl, halogen, cyano, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, sulfonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocyclylcarbonyl or ureido; R １ is H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, substituted aminoalkyl, aminocarbonylalkyl, or aminosulfonylalkyl. 【Request 2】 【Chemical 3】 are each independently H, C ３－１０ Cycloalkyl, Bridged C ８－１６ Cycloalkyl, fused C ３－１０ Cycloalkyl, C ８－１６ Spirocycloalkyl, C ６－１０ Aryl, C ４－１０ Heteroaryl, C １－１０ Heterocyclyl, Bridged C ６－１４ Heterocyclyl, fused C １－１０ Heterocyclyl or C ６－１４ The compound of claim 1 which is a spiroheterocyclyl.

3. X and Z are each independently N or CH; Y is CR ３ａ and R ３ａ is H, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C １－６ Alkylthio, C １－６ Alkyl sulfonyl, hydroxy, halogen, haloC １－６ Alkyl, haloC １－６ Alkoxy, C ３－１０ Cycloalkyl, cyano, amino, C １－６ Alkylamino, HaloC １－６ Alkylamino, C ２－１２ Dialkylamino, C １－６ Alkylcarbonyl, C １－６ Alkoxycarbonyl, aminocarbonyl, C １－６ Alkylaminocarbonyl, C ２－１２ Dialkylaminocarbonyl, hydroxy C １－６ Alkyl, hydroxy C １－６ Alkoxy, hydroxy C １－６ Alkylamino, C １－６ Alkoxy C １－６ Alkyl, C １－６ Alkoxy C １－６ Alkoxy, C １－６ Alkoxy C １－６ Alkylamino, Amino C １－６ Alkyl, Amino C １－６ Alkoxy, Amino C １－６ Alkylamino, C ６－１０ Aryl, C ５－１０ Heteroaryl, C ５－１０ Heteroaryloxy, C ４－１０ Heteroarylamino, C １－１０ Heterocyclyl, C １－１０ Heterocyclyloxy, C １－１０ Heterocyclylamino, C １－１０ heterocyclyloxyalkoxy or C １－１０ heterocyclyloxyalkylamino, Here, C ６－１０ Aryl, C ４－１０ Heteroaryl or C １－１０ Each heterocyclyl is independently C １－６ Alkyl, C ３－１０ Cycloalkyl, haloC １－６ Alkyl, haloC １－６ Alkoxy, C １－６ Alkoxy, hydroxy, halogen, cyano, hydroxy C １－６ Alkyl, C １－６ Alkoxy C １－６ Alkyl and Amino C １－６ alkyl, or unsubstituted; 【Chemistry 4】 are each independently H, C ３－１０ Cycloalkyl, Bridged C ８－１６ Cycloalkyl, fused C ３－１０ Cycloalkyl, C ８－１６ Spirocycloalkyl, C ６－１０ Aryl, C ４－１０ Heteroaryl, C １－１０ Heterocyclyl, Bridged C ６－１４ Heterocyclyl, fused C １－１０ Heterocyclyl or C ６－１４ spiroheterocyclyl, wherein C ６－１０ Aryl, C ４－１０ Heteroaryl or C １－１０ Heterocyclyl is represented by the following R ２ａ or unsubstituted with 1 to 3 independently selected from: L is C １－３ Alkylene, O, NH, NCH ３ , S, SO, SO ２ or a bond; R ２ａ is C １－６ Alkyl, C ３－１０ Cycloalkyl, haloC １－６ Alkyl, haloC １－６ Alkylamino, HaloC １－６ Alkoxy, C １－６ Alkoxy, hydroxy, C １－６ Alkyl sulfonyl, halogen, cyano, carboxy, C １－６ Alkoxycarbonyl, hydroxy C １－６ Alkyl, C １－６ Alkoxyalkyl, Amino C １－６ Alkyl, aminosulfonyl, C １－６ alkylaminosulfonyl, (C １－６ alkyl) ２ Aminosulfonyl, sulfonylamino, aminocarbonyl, C １－６ alkylaminocarbonyl, (C １－６ alkyl) ２ Aminocarbonyl, C １－１０ heterocyclylcarbonyl, or ureido; R １ is H, C １－６ Alkyl, haloC １－６ Alkyl, hydroxy C １－６ Alkyl, C １－６ Alkoxyalkyl, Amino C １－６ Alkyl, substituted amino C １－６ Alkyl, aminocarbonyl C １－６ Alkyl, or aminosulfonyl C １－６ The compound of claim 1 , wherein the aryl group is alkyl.

4. X and Z are each independently N or CH; Y is CR ３ｂ and R ３ｂ is H, C ２－４ Alkenyl, C ２－４ Alkynyl, C １－３ Alkoxy, hydroxy, halogen, haloC １－６ Alkyl, C ３－６ Cycloalkyl, amino, C １－３ Alkylamino, HaloC １－６ alkylamino, or C ２－６ is heterocyclyl, 【Chemistry 5】 are each independently H, C ６－１０ Aryl, C ４－１０ Heteroaryl, or C １－１０ heterocyclyl, wherein C ６－１０ Aryl, C ４－１０ Heteroaryl or fused C １－１０ Heterocyclyl is represented by the following R ２ｂ or unsubstituted with 1 to 3 independently selected from: L is C １－６ Alkylene, O, NH, NCH ３ , S, SO, SO ２ or a bond; R ２ｂ is C １－６ Alkyl, haloC １－３ Alkyl, haloC １－３ Alkoxy, C １－６ alkoxy, hydroxy, or halogen; R １ is H or C １－６ The compound of claim 1 , wherein the aryl group is alkyl.

5. X and Z are each independently N or CH; Y is CR ３ｃ and R ３ｃ is H, C ２－４ Alkenyl, C ２－４ Alkynyl, C １－３ Alkoxy, hydroxy, halogen, haloC １－３ Alkyl, C ３－６ Cycloalkyl, amino, C １－３ Alkylamino, HaloC １－３ alkylamino, or C ２－６ is heterocyclyl, 【Chemistry 6】 are each independently H, phenyl, pyridinyl, imidazolyl, pyrrolidinyl, indolyl, naphthalenyl, benzodioxinyl, or benzodioxolyl, 【Chemistry 7】 is C １－３ Alkyl, haloC １－３ Alkyl, haloC １－３ Alkoxy, C １－３ unsubstituted or substituted with one to three independently selected from alkoxy, hydroxy, and halogen; L is C １－３ Alkylene, O, NH, NCH ３ , S, SO, SO ２ or a bond; R １ is H or C １－３ The compound of claim 1 , wherein the aryl group is alkyl.

6. X and Z are each independently N or CH; Y is CR ３ｃ In this case, R ３ｃ is H, C ２－４ Alkenyl, C ２－４ Alkynyl, C １－３ Alkoxy, hydroxy, halogen, haloC １－３ Alkyl, C ３－６ Cycloalkyl, amino, C １－３ Alkylamino, HaloC １－３ alkylamino, or C ２－６ is heterocyclyl; 【Chemistry 8】 is phenyl or pyridinyl, 【Chemistry 9】 is H, phenyl, pyridinyl, imidazolyl, pyrrolidinyl, or 【Chemistry 10】 In this case, 【Chemistry 11】 are each independently C １－３ Alkyl, haloC １－３ Alkyl, haloC １－３ Alkoxy, C １－３ unsubstituted or substituted with one to three independently selected from alkoxy, hydroxy, and halogen; L is methylene, ethylene, O, NH, NCH ３ , S, SO, or SO ２ and R １ is H or methyl.

7. The compound of claim 1, wherein the compound is selected from the group consisting of the following compounds, their optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof: 1) 2-benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 2) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 3) 7-chloro-2-(4-hydroxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 4) 7-chloro-2-(3-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 5) 7-chloro-2-(2-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 6) 7-chloro-2-(4-chlorobenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 7) 7-chloro-1-methyl-5-phenyl-2-(pyridin-4-ylmethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 8) 7-chloro-2-(3,4-dimethoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 9) 7-chloro-1-methyl-2-phenethyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 10) 7-chloro-2-(4-methoxyphenyl)-1-methyl-5-(o-tolyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 11) 2-benzyl-7-chloro-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 12) 2-((1H-imidazol-1-yl)methyl)-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 13) 7-chloro-2-((3-methoxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 14) 7-chloro-2-((3-hydroxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 15) 2-(4-methoxybenzyl)-1-methyl-5-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 16) 7-chloro-5-(4-chloro-3-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 17) 7-chloro-5-(3-chloro-4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 18) 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 19) 7-chloro-2-((4-methoxyphenyl)sulfonyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 20) 7-chloro-2-((4-methoxyphenyl)sulfinyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 21) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 22) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 23) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 24) 7-chloro-5-(2-cyclopropylpyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 25) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)phenyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 26) 7-chloro-5-(2-chlorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 27) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 28) 7-chloro-2-(4-fluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 29) 2-(benzo[d][1,3]dioxol-5-ylmethyl)-7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 30) 7-chloro-2-(3,4-difluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 31) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 32) 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 33) 7-chloro-2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 34) 7-chloro-5-(4-methoxyphenyl)-2-((4-methoxyphenyl)thio)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 35) 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 36) 7-chloro-2-((4-fluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 37) 7-chloro-2-((3,4-difluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 38) 2-(benzo[d][1,3]dioxol-5-ylthio)-7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 39) 7-chloro-2-((2,4-difluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 40) 7-chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 41) 7-chloro-2-((4-methoxyphenyl)(methyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 42) 7-chloro-2-(4-methoxyphenoxy)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 43) 7-hydroxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 44) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-vinyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 45) 7-ethyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 46) 7-cyclopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 47) 7-ethynyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 48) 7-isopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 49) 2-(4-methoxybenzyl)-1,7-dimethyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 50) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(pyrrolidin-1-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 51) 7-methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 52) 7-amino-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 53) 2-(4-methoxybenzyl)-1-methyl-7-(methylamino)-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 54) 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 55) 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one; 56) 5-(4-(difluoromethoxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 57) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 58) 2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 59) 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 60) 2-((4-fluorophenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 61) 2-((4-methoxyphenyl)thio)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one; 62) 7-ethoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4',5':4,5]pyrido[2,3-d]pyrimidin-4-one; 63) 2-(4-(difluoromethoxy)benzyl)-7-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 64) 7-Methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; 65) 2-(4-(difluoromethoxy)benzyl)-7-ethyl-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one; and 66) 7-Cyclopropyl-2-(4-(difluoromethoxy)benzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one.

8. A pharmaceutical composition for treating or preventing a disease or disorder associated with methionine adenosyltransferase 2A (MAT2A), comprising, as an active ingredient, a compound selected from the group consisting of the compound according to any one of claims 1 to 7, its optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

9. The pharmaceutical composition of claim 8, wherein the composition exhibits MAT2A inhibitory activity.

10. The pharmaceutical composition of claim 8 , wherein the composition is for treating cancer.

11. The pharmaceutical composition according to claim 8, wherein the composition is for treating methylthioadenosine phosphorylase (MTAP)-deficient cancer.

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