Novel tricyclic derivative compounds and uses thereof

Abstract

The present disclosure relates to a novel tricyclic derivative compound and a use thereof, and more particularly, to a novel tricyclic derivative compound having methionine adenylyltransferase 2A (MAT2A) inhibitory activity and a use thereof.

Description

Technical Field

[0001] The present disclosure relates to novel tricyclic-derived compounds and their uses, and more particularly, to novel tricyclic-derived compounds having methionine adenosyltransferase 2A (MAT2A) inhibitory activity and their uses. Background Art

[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 a rate-limiting process in the methionine cycle. SAM is a propylamine donor in polyamine biosynthesis, the major methyl donor for DNA methylation, and is involved in gene transcription and cell 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 recycled to produce adenosine monophosphate, and 5-methylthioribose-1-phosphate is converted to methionine and formate. Due to this recycling pathway, MTA can be provided as an alternative purine source, for example, when the synthesis of new purines is blocked using an antimetabolite such as L-alanosine.

[0004] Many human and murine malignant cells lack MTAP activity. In addition to being found in tissue culture cells, such deficiencies also exist 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 lymphoma, and mesothelioma.

[0005] The inventors of the present disclosure have completed the present disclosure by developing novel tricyclic-derived compounds having MAT2A inhibitory activity and their uses.

[0006] [Prior Art Documents]

[0007] [Patent Documents]

[0008] (Patent Document 1) Korean Published Patent No. 10-2022-0051301

[0009] (Patent Document 2) Korean Published Patent No. 10-2022-0050832

[0010] (Patent Document 3) Korean Published Patent No. 10-2021-0103498

[0011] (Patent Document 4) Korean Published Patent No. 10-2018-0100125

[0012] (Patent Document 5) Korean Published Patent No. 10-2019-0046921

[0013] (Patent Document 6) Korean Published Patent No. 10-2020-0138769 Summary of the Invention

[0014] Technical Problem

[0015] One objective of the present disclosure is to provide a novel tricyclic derivative compound.

[0016] Another objective of the present disclosure is to provide a pharmaceutical composition for treating or preventing methionine adenosyltransferase 2A (MAT2A)-related diseases or disorders, the pharmaceutical composition comprising the aforementioned compound as an active ingredient.

[0017] Other objectives and advantages of the present disclosure will become apparent from the following embodiments in conjunction with the appended claims. Anything not set forth herein can be readily recognized and inferred by those skilled in the art of the present disclosure or similar fields, and is hereby omitted.

[0018] Solution to the Problem

[0019] One embodiment of the present disclosure provides a compound selected from the following Compound of Formula 1, its enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0020] [Formula 1]

[0021]

[0022] Another embodiment of the present disclosure provides a pharmaceutical composition for treating or preventing methionine adenosyltransferase 2A (MAT2A)-related diseases or disorders, the pharmaceutical composition comprising a compound as an active ingredient, the compound selected from the Compound of Formula 1, its enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0023] Advantageous effects of the present disclosure

[0024] The novel tricyclic derivative compound having the structure of Formula 1 according to an embodiment of the present disclosure and the pharmaceutical composition containing the same are effective against methionine adenosyltransferase 2A (MAT2A)-related diseases or disorders and can be used as therapeutic agents. Detailed description of specific embodiments

[0025] The present disclosure will be described in more detail below.

[0026] Unless otherwise defined, all technical terms used in the present disclosure are used in the manner commonly understood by those skilled in the relevant art of the present disclosure. In addition, although suitable methods or samples are described herein, similar or equivalent methods are also included within the scope of the present disclosure.

[0027] An embodiment of the present disclosure provides a compound selected from the following Formula 1 compound and its enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0028] [Formula 1]

[0029]

[0030] Wherein, in Formula 1 above,

[0031] X and Z can each independently be N or CH; and

[0032] Y can be CR 3 ; and

[0033] R 3 can be 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, heterocyclic group, heterocyclic oxy, heterocyclic amino, heterocyclic oxyalkoxy or heterocyclic oxyalkylamino,

[0034] wherein each of the aryl, heteroaryl or heterocyclic group can independently be

[0035] unsubstituted or substituted with 1 to 3 groups selected from alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, halogen, cyano, hydroxyalkyl, alkoxyalkyl and aminoalkyl;

[0036] and may each independently be H, cycloalkyl, aryl, heteroaryl or heterocyclic group,

[0037] each of cycloalkyl, aryl, heteroaryl or heterocyclic group may be monocyclic, bicyclic or polycyclic,

[0038] wherein cycloalkyl, aryl, heteroaryl or heterocyclic group may be unsubstituted or substituted by 1 to 3 groups independently selected from the following R 2 selected;

[0039] L may be C 1-3 alkylene, O, NH, N(C 1-3 alkyl), S, SO, SO 2 or a bond;

[0040] R 2 may be alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, alkanesulfonyl, halogen, cyano, carboxyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, sulfonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocyclic carbonyl or ureido; and

[0041] R 1 may be H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, substituted aminoalkyl, aminocarbonylalkyl or aminosulfonylalkyl.

[0042] Definition

[0043] Unless otherwise specified, as used herein, the term "alkyl" refers to a straight-chain or branched-chain hydrocarbon residue which may be substituted or unsubstituted. For example, alkyl may be a straight-chain saturated monovalent hydrocarbon group having 1 to 6 carbon atoms or a branched-chain saturated monovalent hydrocarbon group having 3 to 6 carbon atoms. For example, alkyl may be, but is not limited to, methyl, ethyl, propyl, butyl, pentyl or isopropyl, isobutyl or tert-butyl, etc. Those skilled in the art should recognize that the term "alkyl" may include "alkylene".

[0044] Unless otherwise specified, as used herein, the term "alkylene" refers to a straight-chain or branched-chain hydrocarbon residue which may be substituted or unsubstituted. For example, alkylene may be a straight-chain saturated divalent hydrocarbon group having 1 to 6 carbon atoms or a branched-chain saturated divalent hydrocarbon group having 3 to 6 carbon atoms. For example, alkylene may be, but is not limited to, methylene, ethylene, propylene, 1-methylpropylene, 2-methylpropylene, butylene, pentylene, etc. For example, C 1-3 alkylene may include any form in which any hydrogen is substituted or unsubstituted, such as any form in which any hydrogen is unsubstituted or substituted by C 1-3 alkyl.

[0045] Unless otherwise specified, as used herein, the term "alkenyl" refers to an alkyl group having one or more double bonds, which may be substituted or unsubstituted. For example, alkenyl may be, but is not limited to, prop-1-enyl, but-1-enyl, but-2-enyl, 3-methylbut-1-enyl, pent-1-enyl, etc.

[0046] Unless otherwise specified, as used herein, the term "alkynyl" refers to an alkyl group having one or more triple bonds, which may be substituted or unsubstituted. For example, alkynyl may be, but is not limited to, ethynyl, propynyl, butynyl, pentynyl, hexynyl, or branched-chain alkynyl, etc.

[0047] Unless otherwise specified, as used herein, the term "alkoxy" refers to a group having a straight-chain or branched-chain hydrocarbon residue linked by an oxygen bond, which may be substituted or unsubstituted. For example, alkoxy may be, but is not limited to, methoxy, ethoxy, propoxy, and butoxy, or isopropoxy, isobutoxy, or tert-butoxy, etc.

[0048] Unless otherwise specified, as used herein, the term "alkylthio" refers to an -SR group, where R is an alkyl group as defined herein. For example, alkylthio may be, but is not limited to, methylthio, ethylthio, etc.

[0049] Unless otherwise specified, as used herein, the term "alkylsulfonyl" refers to an -SO 2 R group, where R is an alkyl group as defined herein. For example, alkylsulfonyl may be, but is not limited to, methylsulfonyl, ethylsulfonyl, etc.

[0050] Unless otherwise specified, as used herein, the term "aminosulfonyl" refers to an -SO 2 NH 2 group.

[0051] Unless otherwise specified, as used herein, the term "alkylaminosulfonyl" refers to an -SO 2 NHR group, where R is an alkyl group as defined herein. For example, alkylaminosulfonyl may be, but is not limited to, methylaminosulfonyl, ethylaminosulfonyl, etc.

[0052] Unless otherwise specified, as used herein, the term "dialkylaminosulfonyl" refers to an -SO 2 NR'R" group, where R' and R" are each an alkyl group as defined herein.

[0053] As used herein, the term "halogen" refers to F, Cl, Br, or I.

[0054] Unless otherwise specified, as used herein, the term "haloalkyl" refers to a group containing mono-haloalkyl and poly-haloalkyl, which may be substituted or unsubstituted. For example, haloalkyl may be, but is not limited to, -CH2 Cl, -CF 3 , -CHF 2 , -CH 2 CF 3 , -CF 2 CF 3 , -CF(CH 3 ) 2 etc.

[0055] Unless otherwise indicated, as used herein, the term "haloalkoxy" refers to an -OR group, where R is a haloalkyl group as defined herein. By way of example, haloalkoxy may be, but is not limited to, -OCF 3 , -OCHF 2 etc.

[0056] Unless otherwise indicated, as used herein, the term "haloalkoxyalkyl" refers to an alkyl group substituted with a haloalkoxy group as defined above. By way of example, haloalkoxyalkyl may be, but is not limited to, a halo C 1-6 alkoxyalkyl containing a total of 1 to 6 carbon atoms.

[0057] By way of example, haloalkoxyalkyl may be, but is not limited to, trifluoromethoxymethyl, trifluoroethoxyethyl, etc.

[0058] Unless otherwise indicated, as used herein, the term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic, bicyclic, or polycyclic hydrocarbon ring that may be substituted or unsubstituted. By way of example, cycloalkyl may be, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, indenyl, or tetrahydronaphthyl, etc. Cycloalkyl includes bridged cycloalkyl, fused cycloalkyl, or spirocycloalkyl.

[0059] Unless otherwise indicated, as used herein, the term "bridged cycloalkyl" refers to two rings that share two non-adjacent common ring atoms. Bridged cycloalkyl may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyl based on the number of rings. By way of example, bridged cycloalkyl may be, but is not limited to etc.

[0060] Unless otherwise indicated, as used herein, the term "fused cycloalkyl" refers to rings that share an adjacent pair of carbon atoms with another ring, and one or more rings may share one or more double bonds, provided that none of these rings has a complete conjugated π electron system. By way of example, fused cycloalkyl may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused cycloalkyl depending on the number of rings. By way of example, fused cycloalkyl may be, but is not limited to etc.

[0061] Unless otherwise indicated, as used herein, the term "spiro" refers to two rings sharing one atom, and the two rings are not bridged. Unless otherwise indicated, as used herein, the term "spirobonded" refers to a linking group sharing one atom.

[0062] Unless otherwise indicated, as used herein, the term "spiroalkyl" refers to a saturated carbocyclic compound containing two rings, where the two rings share only one carbon atom as part of the ring. By way of example, spiroalkyl can be, but is not limited to

[0063] etc.

[0064] As used herein, the term "cyano" refers to the -CN group.

[0065] As used herein, the term "ureido" refers to -NH-CO-NH 2 group.

[0066] As used herein, the term "amino" refers to -NH 2 group. As used herein, the terms "alkylamino", "haloalkylamino", "dialkylamino", "hydroxyalkylamino", "alkoxyalkylamino", "aminoalkylamino", "sulfonylamino", "heteroarylamino", "heterocyclicamino", and "heterocyclicoxyalkylamino" refer to certain N-substituted organic groups each bearing an alkyl, haloalkyl, dialkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, sulfonyl, heteroaryl, heterocyclic, and heterocyclicoxyalkyl substituent, respectively. By way of example, alkylamino can be, but is not limited to, methylamino, ethylamino, or propylamino, etc. By way of example, haloalkylamino can be, but is not limited to, trifluoromethylamino or trifluoroethylamino, etc.

[0067] Unless otherwise indicated, as used herein, the term "alkylcarbonyl" refers to a -C(O)R group, where R is an alkyl as defined herein. By way of example, alkylcarbonyl can include, but is not limited to, C 1-6 alkylcarbonyl. By way of example, alkylcarbonyl can be, but is not limited to, methylcarbonyl, ethylcarbonyl, etc.

[0068] Unless otherwise indicated, as used herein, the term "alkoxycarbonyl" refers to a -C(O)OR group, where R is an alkyl as defined herein. By way of example, alkoxycarbonyl can include, but is not limited to, C 1-6 alkoxycarbonyl. By way of example, alkoxycarbonyl can be, but is not limited to, methoxycarbonyl, ethoxycarbonyl, etc.

[0069] Unless otherwise indicated, as used herein, the term "aminocarbonyl" refers to -CONH 2 group.

[0070] Unless otherwise indicated, as used herein, the term "alkylaminocarbonyl" refers to a -CONHR group, where R is an alkyl group as defined herein. By way of example, alkylaminocarbonyl can include, but is not limited to, C 1-6 alkylaminocarbonyl. By way of example, alkylaminocarbonyl can be, but is not limited to, methylaminocarbonyl, ethylaminocarbonyl, etc.

[0071] Unless otherwise indicated, as used herein, the term "dialkylaminocarbonyl" refers to a -CONR'R" group, where R' and R" are each an alkyl group as defined herein. By way of example, dialkylaminocarbonyl can include, but is not limited to, (C 1-6 alkyl) 2 aminocarbonyl.

[0072] Unless otherwise indicated, as used herein, the term "heterocycliccarbonyl" refers to a -C(O)R group, where R is a heterocyclic group as defined herein.

[0073] Unless otherwise indicated, as used herein, the term "aminosulfonylalkyl" refers to -alkyl-S(=O) 2 -NH 2 , where alkyl is as defined herein.

[0074] Unless otherwise indicated, as used herein, the term "aminocarbonylalkyl" refers to -alkylene-(C=O)-NH 2 .

[0075] As used herein, the term "hydroxyalkyl" refers to an alkyl group substituted with an -OH group. By way of example, hydroxyalkyl can be, but is not limited to, hydroxymethyl, 2-hydroxy-ethyl, 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, etc.

[0076] As used herein, the term "hydroxyalkoxy" refers to an -OR group, where R is a hydroxyalkyl group as defined herein. By way of example, hydroxyalkoxy can be, but is not limited to, hydroxyethoxy, hydroxypropoxy, etc.

[0077] As used herein, the term "alkylamino" refers to an -NHR group, where R is an alkyl group as defined herein. By way of example, alkylamino can be, but is not limited to, methylamino, ethylamino, propylamino, or isopropylamino, etc.

[0078] As used herein, the term "dialkylamino" refers to an -NR'R" group, where R' and R" are each an alkyl group as defined herein. By way of example, dialkylamino can include, but is not limited to, (C 1-6 alkyl)2 -amino group. For example, a dialkylamino group may include but is not limited to a dimethylamino group, a diethylamino group, or a methylethylamino group.

[0079] As used herein, the term "hydroxyalkylamino" refers to an -NR'R" group, where R' is hydrogen or an alkyl group as defined herein, and R" is a hydroxyalkyl group as defined herein. For example, a hydroxyalkylamino group may be but is not limited to a hydroxyethylamino group, a hydroxypropylamino group, etc.

[0080] Unless otherwise specified, as used herein, the term "haloC 1-6 alkylamino" refers to a group of the formula -NH-C 1-6 alkyl, where when the available valence permits, the C 1-6 alkyl moiety is partially or fully substituted by halogen atoms, that is, it refers to a group of the formula -NH-C 1-6 alkyl-halo.

[0081] Unless otherwise specified, as used herein, the term "(haloC 1-6 alkyl) 2 amino" refers to a group of the formula -N-(C 1-6 alkyl-halo) 2 ).

[0082] Unless otherwise specified, as used herein, the term "C 1-6 alkoxyC 1-6 alkylamino" refers to a group of the formula -NH-C 1-6 alkyl, where the C 1-6 alkyl moiety is partially or fully substituted by C 1-6 alkoxy, that is, it refers to a group of the formula -NH-C 1-6 alkyl-C 1-6 alkoxy.

[0083] Unless otherwise specified, as used herein, the term "aminoC 1-6 alkylamino" refers to a group of the formula -NH-C 1-6 alkyl, where the C 1-6 alkyl moiety is partially or fully substituted by an amino group, that is, it refers to a group of the formula -NH-C 1-6 alkyl-amino.

[0084] Unless otherwise specified, as used herein, the term "sulfonylamino" refers to a group -NR'S(O) 2 R", where R' and R" are each hydrogen, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a cycloalkyl group, or a heterocyclic group.

[0085] Unless otherwise specified, as used herein, the term "alkanesulfonamido" refers to -NHS(O) 2An R group, where R is an alkyl group as defined herein.

[0086] Unless otherwise specified, as used herein, the term "alkoxyalkyl" refers to an R'-O-R" group, where R' and R" are each an alkyl group as defined herein. For example, alkoxyalkyl can be, but is not limited to, 2-methoxyethyl, 1-methoxypropyl, 2-methoxypropyl, or 3-methoxypropyl, 2-ethoxyethyl, etc. Unless otherwise specified, as used herein, the term "C 1-6 alkoxyalkyl" refers to an alkyl-O-alkyl ether having a total number of 1 to 6 carbons.

[0087] As used herein, the term "alkoxyalkoxy" refers to an -OR group, where R is an alkoxyalkyl as defined herein. For example, alkoxyalkoxy can be, but is not limited to, methoxyethoxy, ethoxypropoxy, etc.

[0088] Unless otherwise specified, as used herein, the term "aminoalkyl" refers to a straight-chain or branched-chain saturated alkyl group represented by -NR'R", where R' and R" are each an alkyl group as defined herein.

[0089] In one embodiment, R' and R" can be substituted with haloalkyl, hydroxyalkyl, alkoxyalkyl, or alkylcarbonyl.

[0090] Aminoalkyl can be, for example but not limited to, aminomethyl, aminoethyl, methylaminomethyl, etc.

[0091] As used herein, the term "aminoalkoxy" refers to an -OR group, where R is an aminoalkyl as defined herein. For example, aminoalkoxy can be, but is not limited to, aminoethoxy, methylaminopropoxy, dimethylaminoethoxy, diethylaminopropoxy, etc.

[0092] Unless otherwise specified, as used herein, the term "aryl" refers to a monocyclic, bicyclic, or polycyclic aromatic hydrocarbon group that can be substituted or unsubstituted. For example, aryl can include, but is not limited to, C 6-10 aryl. Double bonds can alternate (resonate) between adjacent carbon atoms or suitable heteroatoms. For example, aryl can be, but is not limited to, phenyl, biphenyl, naphthyl, tolylcarbonyl, or naphthalenyl, etc.

[0093] As used herein, the term "hetero" refers to an atom selected from B, N, O, S, P(=O), Si, and P.

[0094] Unless otherwise indicated, as used herein, the term "heteroaryl" refers to a monocyclic, bicyclic, or polycyclic aromatic group, which may be substituted or unsubstituted and contains one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. For example, heteroaryl may include, but is not limited to, C 4-10 heteroaryl. For example, monocyclic heteroaryl may be, but is not limited to, pyridyl, imidazolyl, thiazolyl, oxazolyl, phenylthio, furyl, pyrrolyl, isoxazolyl, pyrazolyl, triazolyl, thiadiazolyl, tetrazolyl, oxadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, etc. For example, bicyclic heteroaryl may be, but is not limited to, indolyl, benzophenylthio, benzofuryl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, purinyl, furanopyridyl, etc.

[0095] Unless otherwise indicated, as used herein, the term "heteroaryloxy" refers to an -OR group, where R is a heteroaryl as defined herein. For example, heteroaryloxy may include, but is not limited to, C 4-10 heteroaryloxy.

[0096] Unless otherwise indicated, as used herein, the term "heterocyclic group" refers to a saturated or partially unsaturated monocyclic, bicyclic, or polycyclic carbon atom ring structure group, which may be substituted or unsubstituted and contains one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. For example, heterocyclic group may be, but is not limited to or similar groups, etc. In addition, for example, heterocyclic group may be, but is not limited to, 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-indazolyl, tetrahydro-indazolyl, dihydro-isoindolyl, dihydro-benzofuryl, tetrahydro-benzofuryl, dihydro-benzothienyl, tetrahydro-benzothienyl, dihydro-benzimidazolyl, tetrahydro-benzimidazolyl, dihydro-benzoxazolyl, dihydropyridyl, dihydroquinolinyl, benzodioxynyl (such as 1,4-benzodioxane) or benzodioxolyl (such as 1,3-benzodioxole), etc. Heterocyclic group includes bridged heterocyclic group, fused heterocyclic group or spiro heterocyclic group. For example, fused heterocyclic group may be, but is not limited to etc.

[0097] Unless otherwise indicated, as used herein, 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.

[0098] Unless otherwise indicated, as used herein, the term "fused heterocycloalkyl" refers to a fused cycloalkyl containing one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P.

[0099] Unless otherwise indicated, as used herein, 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, heterospirocycloalkyl can be, but is not limited to etc.

[0100] Unless otherwise indicated, as used herein, the term "heterocyclyloxy" refers to an -OR group, where R is a heterocyclic group as defined herein. For example, heterocyclyloxy can be, but is not limited to, pyrrol-2-yloxy, pyrrol-3-yloxy, piperidin-2-yloxy, piperidin-3-yloxy, piperazin-2-yloxy, or piperidin-4-yloxy, etc.

[0101] Unless otherwise indicated, as used herein, the term "heterocyclic amino" refers to an -NHR group, where R is a heterocyclic group as defined herein. For example, heterocyclic amino can be, but is not limited to, pyrrol-2-ylamino, pyrrol-3-ylamino, piperidin-2-ylamino, piperidin-3-ylamino, piperazin-2-ylamino, or piperidin-4-ylamino, etc.

[0102] Unless otherwise indicated, as used herein, the term "heterocyclyloxyalkoxy" refers to an -OR group, where R is a heterocyclic group 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, etc.

[0103] As used herein, the term "heterocyclyloxyalkanamine" refers to an -NR-(alkylene)-R' group, where R' is hydrogen or an alkyl as defined herein, and R" is a heterocyclyloxy as defined herein. For example, heterocyclyloxyalkanamine can be, but is not limited to, oxetanyloxyethylamine, piperidyloxyethylamine, etc.

[0104] Unless otherwise specified, as used herein, the term "heterocycloalkyl" refers to a monocyclic (which may be substituted or unsubstituted) cycloalkyl that contains one or more heteroatoms selected from B, N, O, S, P(=O), Si, and P. For example, heterocycloalkyl may be, but is not limited to, piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, thiomorpholinyl, imidazolidinyl, or tetrahydrofuranyl, etc.

[0105] As used herein, the term "stereoisomer" may refer to a compound or a salt thereof of the present disclosure that has the same chemical formula or molecular formula but is optically or spatially different, and includes enantiomers or diastereomers.

[0106] As used herein, the term "enantiomer" refers to two stereoisomers of a compound that are non-superimposable mirror images of each other.

[0107] As used herein, the term "diastereomer" refers to a stereoisomer having two or more chiral centers whose molecules are not mirror images of each other.

[0108] The compounds of the present disclosure may contain asymmetric or chiral centers and may thus exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of the present disclosure (such as diastereomers, enantiomers, and racemic mixtures) are considered to form part of the present disclosure. A 50:50 mixture of enantiomers is called a racemic mixture or racemate.

[0109] As used herein, the term "solvate" may refer to a compound or a salt thereof of the present disclosure that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Suitable solvents may include volatile, non-toxic, and / or solvents suitable for human administration. A "solvate" may include a molecular complex that contains a compound and one or more pharmaceutically acceptable solvent molecules, such as ethanol.

[0110] As used herein, the term "hydrate" refers to a complex in which the solvent molecule is water.

[0111] As used herein, the term "pharmaceutically acceptable salt" refers to a pharmaceutically acceptable organic or inorganic salt that can be prepared by any suitable method applicable to those skilled in the art. For example, when the compound of the present disclosure is a base, the required pharmaceutically acceptable salt can be prepared by any suitable method applicable to those skilled in the art, such as by treating the free base with an inorganic acid or an organic acid.

[0112] In one embodiment, in the above formula 1,

[0113] and may each independently be 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 heterocyclic, bridged C 6-14 heterocyclic, fused C 1-10 heterocyclic or C 6-14 spiroheterocyclic group.

[0114] In one embodiment, in Formula 1 above,

[0115] X and Z may each independently be N or CH;

[0116] Y may be CR 3a ;

[0117] R 3a may be H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylsulfonyl, hydroxy, halogen, halo C 1-6 alkyl, halo C 1-6 alkoxy, C 3-10 cycloalkyl, cyano, amino, C 1-6 alkylamino, halo C 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 1-10 aryl, C 5-10 heteroaryl, C 5-10 heteroaryloxy, C 4-10 heteroarylamino, C 1-10 heterocyclic, C1-10 heterocyclic group oxy, C 1-10 heterocyclic group amino, C 1-10 heterocyclic group oxyalkoxy or C 1-10 heterocyclic group oxyalkylamino,

[0118] wherein C 6-10 aryl, C 4-10 heteroaryl or C 1-10 each of the heterocyclic groups may independently be,

[0119] unsubstituted or substituted with 1 to 3 groups selected from C 1-6 alkyl, C 3-10 cycloalkyl, halo C 1-6 alkyl, halo C 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;

[0120] and may each independently be 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 heterocyclic group, bridged C 6-14 heterocyclic group, fused C 1-10 heterocyclic group or C 6-14 spiroheterocyclic group, wherein C 6-10 aryl, C 4-10 heteroaryl or C 1-10 heterocyclic group is unsubstituted or substituted with 1 to 3 groups independently selected from the following R 2a ;

[0121] L may be C 1-3 alkylene, O, NH, NCH 3 、S、SO、SO 2 or a bond;

[0122] R 2a may be C 1-6 alkyl, C 3-10 cycloalkyl, halo C 1-6 alkyl, halo C 1-6 alkylamino, halo C 1-6 alkoxy, C 1-6 alkoxy, hydroxy, C 1-6Alkylsulfonyl, halogen, cyano, carboxyl, 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 Heterocyclic carbonyl or ureido; and

[0123] R 1 May be H, C 1-6 Alkyl, halo C 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 Alkyl.

[0124] In one embodiment, in the above formula (1),

[0125] X and Z may each independently be N or CH;

[0126] Y may be CR 3b ;

[0127] R 3b May be H, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Alkoxy, hydroxy, halogen, halo C 1-6 Alkyl, C 3-6 Cycloalkyl, amino, C 1-3 Alkylamino, halo C 1-6 Alkylamino or C 2-6 Heterocyclic group;

[0128] And May each independently be H, C 6-10 Aryl, C 4-10 Heteroaryl or C 1-10 Heterocyclic group, wherein C 6-10 Aryl, C 4-10 Heteroaryl or fused C 1-10 Heterocyclic group may be unsubstituted or substituted by 1 to 3 groups independently selected from the following R 2b ;

[0129] L can be C 1-6 alkylene, O, NH, NCH 3 , S, SO, SO 2 or a bond;

[0130] R 2b can be C 1-6 alkyl, haloalkyl C 1-3 alkyl, haloalkyl C 1-3 alkoxy, C 1-6 alkoxy, hydroxyl or halogen; and

[0131] R 1 can be H or C 1-6 alkyl.

[0132] In one embodiment, in the above formula 1,

[0133] X and Z can each independently be N or CH;

[0134] Y can be CR 3c ;

[0135] R 3c can be H, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, hydroxyl, halogen, haloalkyl C 1-3 alkyl, C 3-6 cycloalkyl, amino, C 1-3 alkylamino, haloalkyl C 1-3 alkylamino or C 2-6 heterocyclic group;

[0136] and can each independently be H, phenyl, pyridyl, imidazolyl, pyrrolidinyl, indolyl, naphthyl, benzodioxynyl or benzodioxolyl, where and can be unsubstituted or substituted by 1 to 3 groups independently selected from C 1-3 alkyl, haloalkyl C 1-3 alkyl, haloalkyl C 1-3 alkoxy, C 1-3 alkoxy, hydroxyl and halogen;

[0137] L can be C 1-3 alkylene, O, NH, NCH 3 , S, SO, SO 2 or a bond; and

[0138] R 1 can be H or C1-3 Alkyl

[0139] In one embodiment, in Formula 1 above,

[0140] and may each independently be H, phenyl, pyridyl, imidazolyl, pyrrolidine,

[0141] wherein and may be unsubstituted or substituted by 1 to 3 groups independently selected from C 1-3 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, C 1-3 alkoxy, hydroxy and halogen.

[0142] In one embodiment, in Formula 1 above,

[0143] may be phenyl or pyridyl, and

[0144] may be unsubstituted or substituted by 1 to 3 groups independently selected from C 1-3 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, C 1-3 alkoxy and halogen;

[0145] may be H, phenyl, pyridyl, imidazolyl, pyrrolidinyl or and

[0146] may be unsubstituted or substituted by 1 to 3 groups independently selected from C 1-3 alkyl, halo C 1-3 alkoxy, C 1-3 alkoxy, hydroxy and halogen;

[0147] X and Z may each independently be N or CH;

[0148] Y may be CR 3c where R 3c may be H, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, hydroxy, halogen, halo C 1-3 alkyl, C 3-6 cycloalkyl, amino, C 1-3 alkylamino, halo C 1-3 alkylamino or C 2-6 heterocyclic group;

[0149] L may be methylene, ethylene, O, NH, NCH 3 , S, SO or SO 2 ; and / or

[0150] R 1 may be H or methyl.

[0151] In one embodiment,

[0152] X and Z may each independently be N or CH;

[0153] Y may be CR 3c , wherein R 3c may be H, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, hydroxy, halogen, halo C 1-3 alkyl, C 3-6 cycloalkyl, amino, C 1-3 alkylamino, halo C 1-3 alkylamino or C 2-6 heterocyclic group;

[0154] may be phenyl or pyridyl;

[0155] may be H, phenyl, pyridyl, imidazolyl, pyrrolidinyl or

[0156] wherein and may each independently

[0157] be unsubstituted or substituted by 1 to 3 groups independently selected from C 1-3 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, C 1-3 alkoxy, hydroxy and halogen;

[0158] L may be methylene, ethylene, O, NH, NCH 3 , S, SO or SO 2 ; and

[0159] R 1 may be H or methyl.

[0160] In one embodiment, the compound may be selected from the group consisting of the following compounds and their enantiomers, diastereomers, solvates and hydrates and their pharmaceutically acceptable salts.

[0161] 1) 2-Benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0162] 2) 7-Chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0163] 3) 7-Chloro-2-(4-hydroxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0164] 4) 7-Chloro-2-(3-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0165] 5) 7-Chloro-2-(2-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0166] 6) 7-Chloro-2-(4-chlorobenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0167] 7) 7-Chloro-1-methyl-5-phenyl-2-(pyridin-4-ylmethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0168] 8) 7-Chloro-2-(3,4-dimethoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0169] 9) 7-Chloro-1-methyl-2-phenethyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0170] 10) 7-Chloro-2-(4-methoxyphenyl)-1-methyl-5-(o-tolyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0171] 11) 2-Benzyl-7-chloro-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0172] 12) 2-((1H-Imidazol-1-yl)methyl)-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0173] 13) 7-Chloro-2-((3-methoxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0174] 14) 7-Chloro-2-((3-hydroxypyrrolidin-1-yl)methyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0175] 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;

[0176] 16) 7-Chloro-5-(4-chloro-3-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0177] 17) 7-Chloro-5-(3-chloro-4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0178] 18) 7-Chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0179] 19) 7-Chloro-2-((4-methoxyphenyl)sulfonyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0180] 20) 7-Chloro-2-((4-methoxyphenyl)sulfinyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0181] 21) 7-Chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0182] 22) 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0183] 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;

[0184] 24) 7-chloro-5-(2-cyclopropylpyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0185] 25) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)phenyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0186] 26) 7-chloro-5-(2-chlorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0187] 27) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0188] 28) 7-chloro-2-(4-fluorobenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0189] 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;

[0190] 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;

[0191] 31) 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0192] 32) 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0193] 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;

[0194] 34) 7-chloro-5-(4-methoxyphenyl)-2-((4-methoxyphenyl)thio)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0195] 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;

[0196] 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;

[0197] 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;

[0198] 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;

[0199] 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;

[0200] 40) 7-chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0201] 41) 7-chloro-2-((4-methoxyphenyl)(methyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0202] 42) 7-chloro-2-(4-methoxyphenoxy)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0203] 43) 7-hydroxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0204] 44) 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-vinyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0205] 45) 7-Ethyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0206] 46) 7-Cyclopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0207] 47) 7-Ethynyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0208] 48) 7-Isopropyl-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0209] 49) 2-(4-Methoxybenzyl)-1,7-dimethyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0210] 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;

[0211] 51) 7-Methoxy-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0212] 52) 7-Amino-2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0213] 53) 2-(4-Methoxybenzyl)-1-methyl-7-(methylamino)-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one;

[0214] 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;

[0215] 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;

[0216] 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;

[0217] 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;

[0218] 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;

[0219] 59) 2-((4-Methoxyphenyl)sulfanyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one;

[0220] 60) 2-((4-Fluorophenyl)sulfanyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one;

[0221] 61) 2-((4-Methoxyphenyl)sulfanyl)-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;

[0222] 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;

[0223] 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;

[0224] 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;

[0225] 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

[0226] 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.

[0227] Another embodiment of the present disclosure provides a pharmaceutical composition for treating or preventing methionine adenosyltransferase 2A (MAT2A)-related diseases or disorders, the pharmaceutical composition comprising a compound as an active ingredient, the compound being selected from the compounds of formula 1 and their enantiomers, diastereomers, solvates, and hydrates and their pharmaceutically acceptable salts.

[0228] In one embodiment, the composition may exhibit MAT2A inhibitory activity.

[0229] In one embodiment, the composition may be used to treat cancer. For example, the cancer may be a solid tumor.

[0230] In one embodiment, the composition may be used to treat methionine adenosylphosphate phosphorylase (MTAP)-deficient cancer.

[0231] In one embodiment, the pharmaceutical composition may comprise a therapeutically effective amount of a compound selected from the compounds of formula 1 and their enantiomers, diastereomers, solvates, and hydrates and their pharmaceutically acceptable salts.

[0232] As used herein, the term "therapeutically effective amount" refers to an amount of a compound of the present disclosure that treats or prevents a specific disease, condition, or disorder; alleviates, ameliorates, or eliminates one or more symptoms of a specific disease, condition, or disorder; or prevents or delays the onset of one or more symptoms of a specific disease, condition, or disorder.

[0233] A physician of ordinary skill in the relevant art can readily determine and prescribe the effective required dose of the pharmaceutical composition. For example, the pharmaceutical composition may comprise, but is not limited to, from 0.0001 milligrams to 10 grams of the compound.

[0234] In one embodiment, in addition to the active ingredient, the pharmaceutical composition may further comprise pharmaceutically acceptable additives. The additives may be, for example but not limited to, diluents, disintegrants, binders, lubricants, surfactants, suspending agents or emulsifying agents, etc.

[0235] The pharmaceutical compositions of the present disclosure can be formulated according to conventional methods and can be prepared into various oral dosage forms, such as tablets, pills, powders, capsules, syrups, emulsions, microemulsions, or parenteral dosage forms, such as intramuscular, intravenous or subcutaneous administration.

[0236] Another embodiment of the present disclosure provides a method of treatment by administering a pharmaceutical composition to an individual suffering from a MAT2A-related disease or disorder, the pharmaceutical composition comprising a compound as an active ingredient selected from the compounds of formula 1 and their enantiomers, diastereomers, solvates and hydrates and their pharmaceutically acceptable salts.

[0237] As used herein, the terms "treating" or "curing" refer to inhibiting a disease, e.g., inhibiting the disease, disorder or condition of an individual who is experiencing or exhibiting a lesion or symptom of the disease, disorder or condition, i.e., preventing or reversing the further development of the lesion and / or symptom, or ameliorating the disease, e.g., reducing the severity of the disease.

[0238] As used herein, the terms "preventing" or "prophylactic" refer to preventing a disease, e.g., preventing the disease, disorder or condition of an individual who may be susceptible to the disease, disorder or condition but has not yet experienced or exhibited a lesion or symptom of the disease.

[0239] As used herein, the terms "subject" or "individual" can be a vertebrate, such as a mammal, fish, bird, reptile or amphibian. For example, the individual can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig or rodent.

[0240] As used herein, the terms "administering" and "administration" refer to any method of providing the disclosed composition to an individual.

[0241] The dosage, frequency of dosing, or method of administration of the compounds or pharmaceutical compositions according to an embodiment may vary depending on the individual being treated, the severity of the disease or condition, the rate of administration, and the diagnosis of the prescribing physician. For example, a typical dosage for an individual weighing 70 kg may be administered in an amount of from 0.0001 mg to 10 g per day, such as from 1 mg to 1 g per day. The frequency of dosing may be administered one to several times, such as 1 to 4 times, or according to a dosing / withdrawal schedule, and the method of administration may be by oral or parenteral routes. For example, the compounds or pharmaceutical compositions according to an embodiment may be administered by oral or parenteral routes in an amount in the range of 0.1 mg / kg (body weight) to 100 mg / kg.

[0242] The physician may start with an amount lower than that required to achieve the desired therapeutic effect and gradually increase the dosage of the compounds or pharmaceutical compositions of the present disclosure administered to the individual until the desired effect is achieved.

[0243] Another embodiment of the present disclosure provides a kit comprising a compound as an active ingredient, the compound being selected from the compounds of Formula 1 and their enantiomers, diastereomers, solvates, and hydrates and their pharmaceutically acceptable salts.

[0244] In one embodiment, the therapeutic agent may be a drug for treating MAT2A-related diseases or disorders, such as a drug for treating cancer. For example, the therapeutic agent may be a chemotherapeutic agent for treating cancer.

[0245] In one embodiment, the therapeutic agent may be a chemotherapeutic agent, an antimetabolite, an antimitotic agent, an alkylating agent, a DNA-damaging agent, an antitumor antibiotic, a platinum coordination complex, a proteasome inhibitor, a hormone and hormone analog, an immunosuppressant, an anti-angiogenic compound and a vascular endothelial growth factor inhibitor, a fibroblast growth factor inhibitor, an epidermal growth factor receptor inhibitor, an antibody, a checkpoint inhibitor, a corticosteroid, a DNA repair enzyme inhibitor, a therapeutic agent for autoimmune diseases, a therapeutic agent for diabetes, a therapeutic agent for liver diseases, a therapeutic agent for cardiovascular disorders, a therapeutic agent for metabolic disorders, an antiviral agent, or an ophthalmic agent.

[0246] In one embodiment, the compounds, compositions, and kits of the present disclosure may be administered alone or simultaneously, separately, or sequentially with at least one other therapeutic agent.

[0247] In the context of the present disclosure, unless the context clearly indicates otherwise, the singular form of a word may include the plural, and vice versa.

[0248] Even if not explicitly stated, the numerical values given herein should be considered to include the meaning of "about". As used herein, the term "about" means within 5% of a value or range, preferably within 1% to 2%.

[0249] As used herein, a numerical range indicated by the term "to" means a range that includes the values written before and after the term "to" as the lower and upper limits, respectively.

[0250] As used herein, the terms "having", "may have", "include", or "may include" refer to the presence of a specific feature (e.g., a number, or a component, such as a constituent), and do not exclude the presence of additional features.

[0251] The contents of all publications incorporated herein by reference are incorporated herein by reference in their entirety.

[0252] Hereinafter, the present disclosure will be described in further detail by the following examples and experimental examples. However, these examples and examples are only intended to illustrate the present disclosure and are not intended to limit the scope of the present disclosure in any way.

[0253] <Synthesis Example 1>

[0254] Example 1: 2-Benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0255]

[0256] [Process 1] Preparation of methyl 2-amino-4-chlorobenzoate

[0257]

[0258] 2-Amino-4-chlorobenzoic acid (10 g, 57.12 mmol), potassium carbonate (11.90 g, 85.67 mmol), and methyl iodide (3.63 mL, 57.12 mmol) were sequentially added to N,N-dimethylformamide (200 mL), and the reaction solution was stirred at room temperature for 2 hours. Water was added to the reaction product and stirred at room temperature for 2 hours. The resulting solid was collected by filtration, washed with water, and dried to obtain the title compound (8.72 g, 82.3%).

[0259] [Process 2] Preparation of methyl 4-chloro-2-(phenylamino)benzoate

[0260]

[0261] 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(II) acetate (215 mg, 0.94 mmol), and xantphos (1.09 g, 1.88 mmol) synthesized in the above [Process 1] were added to toluene (88 mL). After purging with nitrogen, the mixture was refluxed at 100 °C for 12 hours. After cooling the reaction product 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%).

[0262] [Process 3] Preparation of methyl 4-chloro-2-(N-phenylacetamido)benzoate

[0263]

[0264] Methyl 4-chloro-2-(phenylamino)benzoate (7.56 g, 28.89 mmol) synthesized in the above [Process 2] was dissolved in acetic acid (60 mL). Subsequently, acetic anhydride (54.62 mL, 577.76 mmol) was added and the mixture was refluxed at 120 °C for 23 hours. The reaction product was cooled to room temperature, then poured into ice water and stirred for 30 minutes. The resulting solid was collected by filtration, washed with water and dried to obtain the title compound (8.32 g, 94.82%), which was used without further purification.

[0265] [Process 4] Preparation of 7-chloro-4-hydroxy-1-phenylquinolin-2(1H)-one

[0266]

[0267] Tetrahydrofuran (125 mL) was added to methyl 4-chloro-2-(N-phenylacetamido)benzoate (8.32 g, 27.39 mmol) synthesized in the above [Process 3], and the reaction solution was cooled to -78 °C. A 1 M solution of potassium bis(trimethylsilyl)amide in tetrahydrofuran was slowly added dropwise to the reaction solution over 1 hour. The reaction product was concentrated, water was added, and the mixture was acidified with 6 N hydrochloric acid. The resulting solid was collected by filtration and washed with excess water. The solid was stirred in diethyl ether for 30 minutes, collected by filtration and dried to obtain the title compound (6.02 g, 80.89%), which was used without further purification.

[0268] [Process 5] Preparation of 7-chloro-4-hydroxy-3-nitro-1-phenylquinolin-2(1H)-one

[0269]

[0270] Acetic acid (100 mL), nitric acid (6.2 mL, 88.63 mmol), and sodium nitrite (312 mg, 4.43 mmol) were added to 7-chloro-4-hydroxy-1-phenylquinolin-2(1H)-one (6.02 g, 22.16 mmol) synthesized in the above [Process 4], and the mixture was stirred at room temperature for 2 h. The reaction product was poured into ice water and stirred for 1 h. The resulting solid was collected by filtration, washed with excess water, and dried to obtain the title compound (6.5 g, 92.63%).

[0271] [Process 6] Preparation of 4,7-dichloro-3-nitro-1-phenylquinolin-2(1H)-one

[0272]

[0273] Phosphorus oxychloride (65 mL, 683.41 mmol) was added to 7-chloro-4-hydroxy-3-nitro-1-phenylquinolin-2(1H)-one (6.5 g, 20.52 mmol) synthesized in the above [Process 5]. After cooling the reaction solution to 0 °C, triethylamine (6.5 mL, 46.17 mmol) was slowly added dropwise.

[0274] Subsequently, the mixture was refluxed at 110 °C for 1 h. The reaction product was cooled to room temperature, then poured into ice water and stirred for 1 h. The resulting solid was collected by filtration, washed with excess water, and dried to obtain the title compound (5.76 g, 83.67%).

[0275] [Process 7] Preparation of 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one

[0276]

[0277] 4,7-Dichloro-3-nitro-1-phenylquinolin-2(1H)-one (5.76 g, 17.17 mmol) synthesized in the above [Process 6] was dissolved in dichloromethane, and then methylamine hydrochloride (1.42 g, 20.61 mmol) and triethylamine (7.26 mL, 51.52 mmol) were added. The reaction solution was stirred at room temperature for 1 h, concentrated, and then water was added and stirred for 1 h. The resulting solid was collected by filtration, washed with excess water, and dried to obtain the title compound (5.05 g, 89.19%).

[0278] [Process 8] Preparation of 3-amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one

[0279]

[0280] Raney-nickel (5.39 g, 45.95 mmol), dichloromethane (60 mL) / methanol (30 mL) were added to 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one (5.05 g, 15.32 mmol) synthesized in the above [Process 7], and a hydrogen balloon was equipped. The reaction solution was stirred at room temperature for 16 h, filtered through diatomaceous earth, and purified by silica gel column chromatography to obtain the title compound (2.16 g, 47.05%).

[0281] [Process 9] Preparation of N-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-phenylacetamide

[0282]

[0283] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (40 mg, 0.13 mmol) synthesized in the above [Process 8] was dissolved in dichloromethane (1 mL), cooled to 0 °C, and triethylamine (21 μL, 0.15 mmol) and 2-phenylacetyl chloride (18 μL, 0.13 mmol) were slowly added dropwise. The reaction solution was stirred at room temperature for 1 h and extracted with dichloromethane by adding water. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. Purification was carried out using silica gel column chromatography to obtain the title compound (15.3 mg, 27.44%).

[0284] [Process 10] Preparation of 2-benzyl-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0285]

[0286] N-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-phenylacetamide (15 mg, 0.04 mmol) synthesized in the above [Process 9] was dissolved in 1,4-dioxane (0.5 mL), and 2N sodium hydroxide (0.5 mL) was added. The reaction solution was stirred at 120 °C for 2 h. After the reaction was completed, the reaction solution 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 obtain the title compound (13.2 mg, 78.5%).

[0287] Example 2: 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0288]

[0289] The same reaction was carried out using 2-(4-methoxyphenyl)acetyl chloride in place of 2-phenylacetyl chloride in [Process 9] of Example 1 to obtain the title compound (8.7 mg, 15.17%).

[0290] Example 3: 7-Chloro-2-(4-hydroxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0291]

[0292] 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), cooled to 0 °C, and boron tribromide (9 μL, 0.1 mmol) was slowly added dropwise. The reaction solution was stirred at room temperature for 1 hour, poured into ice water, then saturated aqueous sodium bicarbonate was added and extraction was carried out with dichloromethane. The separated organic layer was dried over anhydrous magnesium sulfate and concentrated by vacuum distillation. Then it was purified by silica gel column chromatography to obtain the title compound (3.4 mg, 17.18%).

[0293] Example 4: 7-Chloro-2-(3-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0294]

[0295] The same reaction was carried out using 2-(3-methoxyphenyl)acetyl chloride in place of 2-phenylacetyl chloride in [Process 9] of Example 1 up to [Process 10] to obtain the title compound (22 mg, 30.68%).

[0296] Example 5: 7-Chloro-2-(2-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0297]

[0298] The same reaction was carried out using 2-(2-methoxyphenyl)acetyl chloride in place of 2-phenylacetyl chloride in [Process 9] of Example 1 up to [Process 10] to obtain the title compound (15 mg, 20.92%).

[0299] Example 6: 7-Chloro-2-(4-chlorobenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0300]

[0301] 2-(4-Chlorophenyl)acetyl chloride was used to replace 2-phenylacetyl chloride in [Process 9] of Example 1 for the same reaction up to [Process 10] to obtain the title compound (12.9 mg, 64.46%).

[0302] Example 7: 7-Chloro-1-methyl-5-phenyl-2-(pyridin-4-ylmethyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0303]

[0304] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (20 mg, 0.06 mmol) synthesized in [Process 8] of Example 1 was dissolved in N,N-dimethylformamide (1 mL), and then 4-pyridylacetic acid hydrochloride (12.4 mg, 0.07 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridine 3-oxide hexafluorophosphate (HATU) (50.7 mg, 0.13 mmol) and diisopropylethylamine (43 mg, 0.33 mmol) were added. The reaction solution was stirred at room temperature for 16 h and extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. The same reaction was carried out up to [Process 10] without purification to obtain the title compound (8 mg, 21.50%).

[0305] Example 8: 7-Chloro-2-(3,4-dimethoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0306]

[0307] 2-(3,4-Dimethoxyphenyl)acetyl chloride was used to replace 2-phenylacetyl chloride in [Process 9] of Example 1 for the same reaction up to [Process 10] to obtain the title compound (37 mg, 46.59%).

[0308] Example 9: 7-Chloro-1-methyl-2-phenethyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0309]

[0310] Using 3-benzoyl chloride to replace 2-phenylacetyl chloride in [Process 9] of Example 1 to conduct the same reaction until [Process 10] to obtain the title compound (16.4 mg, 60.05%).

[0311] Example 10: 7-Chloro-2-(4-methoxyphenyl)-1-methyl-5-(o-tolyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0312]

[0313] Using 1-bromo-2-methylbenzene to replace bromobenzene in [Process 2] of Example 1 and using 2-(4-methoxyphenyl)acetyl chloride to replace 2-phenylacetyl chloride in [Process 9] of Example 1 to conduct the same reaction until [Process 10] to obtain the title compound (45.6 mg, 78.56%).

[0314] Example 11: 2-Benzyl-7-chloro-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0315]

[0316] Except that in [Process 7] of Example 1, the compound was dissolved in tetrahydrofuran instead of dichloromethane and ammonia water was added instead of methylamine hydrochloride and triethylamine, the same reaction was conducted to synthesize 4-amino-7-chloro-3-nitro-1-phenylquinolin-2(1H)-one to obtain the title compound (2 mg, 41.87%).

[0317] According to an embodiment of the present disclosure, the compound of Formula 1 can be a compound selected from the group consisting of the compounds listed in the following [Table 1].

[0318] [Table 1]

[0319]

[0320]

[0321] <Synthesis Example 2>

[0322] 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

[0323] [Process 1] Preparation of 7-chloro-2-(chloromethyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0324]

[0325] 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 [Process 8] of Example 1, and the mixture was stirred at 100 °C for 1 h. The reaction solution was concentrated by cooling to room temperature and stirred in diethyl ether for 1 h. The resulting solid was collected by filtration and washed with diethyl ether to obtain the title compound (152.6 mg, 98.23%), which was used without further purification.

[0326] [Process 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

[0327]

[0328] Imidazole (7.7 mg, 0.11 mmol) was dissolved in N,N-dimethylformamide (0.2 mL), cooled to 0 °C, and sodium hydride (6.7 mg, 0.17 mmol) was added portionwise under nitrogen. After stirring for 30 min, 7-chloro-2-(chloromethyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (20 mg, 0.06 mmol) synthesized in [Process 1] was slowly added dropwise to the above mixture dissolved in N,N-dimethylformamide (0.3 mL). The reaction solution was stirred at room temperature for 30 min, then ice water was added and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate and distilled under vacuum. The concentrated reactant was purified by silica gel column chromatography to obtain the title compound (4.4 mg, 20.22%).

[0329] 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

[0330]

[0331] The same reaction was carried out except that 3-methoxypyrrolidine was used instead of imidazole in [Process 2] of Example 12 to obtain the title compound (30.5 mg, 51.67%).

[0332] 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

[0333]

[0334] Except for using 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] to replace 7-chloro-2-(4-methoxybenzyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in Example 3, the same reaction was carried out to obtain the title compound (12.4 mg, 64.13%).

[0335] <Synthesis Example 3>

[0336] 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

[0337]

[0338] [Process 1] Preparation of 6-chloro-2-(phenylamino)nicotinic acid

[0339]

[0340] Aniline (6.15 g, 65.3 mmol) was diluted with tetrahydrofuran (60 mL) and the reaction solution was cooled to -75 °C. Then, 1 M lithium bis(trimethylsilyl)amide in tetrahydrofuran solution (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 to this mixture, and the reaction solution was stirred at room temperature for 16 hours. After the reaction was completed, 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, then vacuum filtered and vacuum distilled. The obtained residue was separated by silica gel column chromatography to obtain the title compound (3.7 g, 48%).

[0341] [Process 2] Preparation of (1H-benzo[d][1,2,3]triazol-1-yl)(6-chloro-2-(phenylamino)pyridin-3-yl)methanone

[0342]

[0343] 6-Chloro-2-(phenylamino)nicotinic acid (3.70 g, 14.9 mmol), 1,2,3-benzotriazole (1.81 g, 14.9 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (2.85 g, 14.9 mmol) synthesized in the above [Process 1] were sequentially added to dichloromethane (13 mL), and the reaction solution was stirred at room temperature for 16 hours. After the reaction was completed, the mixture was diluted with dichloromethane and washed with distilled water. The separated organic layer was dried over anhydrous sodium sulfate, followed by vacuum filtration and vacuum distillation. The obtained residue was separated by silica gel column chromatography to obtain the title compound (3.83 g, 74%).

[0344] [Process 3] Preparation of Ethyl 3-(6-chloro-2-(phenylamino)pyridin-3-yl)-3-hydroxypropionate

[0345]

[0346] Ethyl acetate (1.45 g, 16.5 mmol) was diluted with tetrahydrofuran (30 mL), cooled to -78 °C, and 2N lithium diisopropylamide in tetrahydrofuran / heptane / benzene solution (12.1 mL, 24.2 mmol) was slowly added dropwise. The reaction solution was stirred at -78 °C for 1 hour, and then a diluted 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) synthesized in the above [Process 2] in tetrahydrofuran (10 mL) was added dropwise, and the mixture was stirred at the same temperature for 2 hours, followed by stirring at room temperature for 16 hours. After the reaction was completed, the mixture was diluted with ethyl acetate and washed with 1N aqueous hydrochloric acid. The separated organic layer was dried over anhydrous sodium sulfate, followed by vacuum filtration and vacuum distillation. The obtained residue was separated by silica gel column chromatography to obtain the title compound (1.3 g, 29%).

[0347] [Process 4] Preparation of 7-Chloro-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one

[0348]

[0349] To a solution of ethyl 3-(6-chloro-2-(phenylamino)pyridin-3-yl)-3-(oxiran-2-yl)propanoate (1.30 g, 4.08 mmol), which was synthesized in the above [Process 3], was added 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), and the mixture was stirred at 120 °C for 2 h. After completion of the reaction, 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, followed by vacuum filtration and vacuum distillation. The obtained residue was separated by silica gel column chromatography to give the title compound (1.1 g, 98%).

[0350] [Process 5] Preparation of 7-chloro-4-hydroxy-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one

[0351]

[0352] The same procedure was carried out except that 7-chloro-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one, which was synthesized in the above [Process 4], was used instead of 7-chloro-4-hydroxy-1-phenylquinolin-2(1H)-one in [Process 5] of Example 1 to give the title compound (450 mg, 39%).

[0353] [Process 6] Preparation of 4,7-dichloro-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one

[0354]

[0355] The same procedure was carried out except that 7-chloro-4-hydroxy-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one, which was synthesized in the above [Process 5], was used instead of 7-chloro-4-hydroxy-3-nitro-1-phenylquinolin-2(1H)-one in [Process 6] of Example 1 to give the title compound (460 mg, 97%).

[0356] [Process 7] Preparation of 7-chloro-4-(methylamino)-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one

[0357]

[0358] The same reaction was carried out except that 4,7-dichloro-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one, which was synthesized in the above [Process 6], was used instead of 4,7-dichloro-3-nitro-1-phenylquinolin-2(1H)-one in [Process 7] of Example 1 to give the title compound (347 mg, 80.15%).

[0359] [Process 8] Preparation of 4-(methylamino)-3-nitro-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one

[0360]

[0361] Dissolve 7-chloro-4-(methylamino)-3-nitro-1-phenyl-1,8-naphthyridin-2(1H)-one (160 mg, 0.48 mmol) synthesized in the above [Process 7] in N-methylpyrrolidone (2 mL), then add 2,2,2-trifluoroethylamine (0.78 mL, 9.62 mmol), N,N-diisopropylethylamine (0.42 mL, 2.40 mmol), and stir the mixture in a microwave reactor at 160 °C for 3 hours. After cooling to room temperature, add water to the reaction product and extract with ethyl acetate. The obtained organic layer is dried over anhydrous sodium sulfate and distilled under vacuum.

[0362] [Process 9] Preparation of 3-amino-4-(methylamino)-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one

[0363]

[0364] Perform the same reaction except using 4-(methylamino)-3-nitro-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one synthesized in the above [Process 8] to replace 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one in [Process 8] of Example 1 to obtain the title compound (76 mg, 58.35%).

[0365] [Process 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

[0366]

[0367] Dissolve 3-amino-4-(methylamino)-1-phenyl-7-((2,2,2-trifluoroethyl)amino)-1,8-naphthyridin-2(1H)-one (76 mg, 0.21 mmol) synthesized in the above [Process 9] in N,N-dimethylformamide (1 mL), then add 2-(4-methoxyphenyl)acetic acid (38.24 mg, 0.23 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridine 3 - Oxohexafluorophosphate (HATU) (159.07 mg, 0.42 mmol), diisopropylethylamine (135.18 mg, 1.05 mmol). The reaction solution was stirred at room temperature for 5 hours and extracted with ethyl acetate by adding water. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation to obtain the title compound (104 mg, 97.19%), which was carried on to the next reaction [Process 11] without further purification.

[0368] [Process 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

[0369]

[0370] 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 the above [Process 10] was used instead of N-(7 - chloro - 4-(methylamino)-2 - oxo - 1 - phenyl - 1,2 - dihydroquinolin - 3 - yl)-2 - phenylacetamide in [Process 10] of Example 1 to obtain the title compound (6.2 mg, 5.49%).

[0371] <Synthesis Example 4>

[0372] 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

[0373]

[0374] [Process 1] Preparation of 7 - Chloro - 4 - hydroxy - 3 - nitroquinolin - 2(1H)-one

[0375]

[0376] 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 sequentially added to tetrahydrofuran (120 mL), and the reaction solution was stirred at 55 °C for 16 h. After the reaction was completed, the mixture was cooled to room temperature and the solvent was distilled off under reduced pressure. The obtained residue was diluted with water and washed with diethyl ether to remove the organic layer, and the remaining aqueous layer was adjusted to pH 2 to 3 with 1N aqueous hydrochloric acid, and the resulting solid was collected by filtration, washed with methanol and excess water, and dried to obtain the title compound (5.6 g, 38%).

[0377] [Process 2] Preparation of 2,4,7-trichloro-3-nitroquinoline

[0378]

[0379] Phosphoryl chloride (10.8 mL, 116 mmol) was added to 7-chloro-4-hydroxy-3-nitroquinolin-2(1H)-one (995 mg, 4.14 mmol) synthesized in the above [Process 1], the reaction solution was cooled to 0 °C, and triethylamine (0.98 mL, 7.04 mmol) was slowly added dropwise. The reaction mixture was refluxed at 100 °C for 4 h, and the reaction solution was cooled to room temperature, poured into ice water, and extracted with ethyl acetate for the first time. After adjusting the pH to 7 to 8 with saturated sodium bicarbonate solution, the mixture was extracted with dichloromethane for the second time. The obtained organic layer was dried over anhydrous sodium sulfate, followed by vacuum filtration and vacuum distillation to obtain the title compound (1.15 g, 100%).

[0380] [Process 3] Preparation of 2,7-dichloro-N-methyl-3-nitroquinolin-4-amine

[0381]

[0382] The same method was carried out except that 2,4,7-trichloro-3-nitroquinoline synthesized in the above [Process 2] was used instead of 4,7-dichloro-3-nitro-1-phenylquinolin-2(1H)-one in [Process 7] of Example 1 to obtain the title compound (740 mg, 64%).

[0383] [Process 4] Preparation of 2,7-dichloro-N4-methylquinoline-3,4-diamine

[0384]

[0385] The same procedure was carried out to obtain the title compound (470 mg, 71%) except that 2,7-dichloro-N-methyl-3-nitroquinolin-4-amine synthesized in the above [Process 3] was used to replace 7-chloro-4-(methylamino)-3-nitro-1-phenylquinolin-2(1H)-one in [Process 8] of Example 1.

[0386] [Process 5] Preparation of N-(2,7-dichloro-4-(methylamino)quinolin-3-yl)-2-(4-methoxyphenyl)acetamide

[0387]

[0388] 2,7-Dichloro-N4-methylquinoline-3,4-diamine (530 mg, 2.19 mmol) synthesized in the above [Process 4], 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) were diluted with N,N-dimethylformamide (5 mL), then N,N-diisopropylethylamine (849 mg, 6.57 mmol) was added and the mixture was stirred at room temperature for 16 h. After completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was separated by vacuum distillation and the obtained residue was dissolved in a mixed solvent of hexane:ethyl acetate (4:1 (v / v), 20 mL), and the resulting solid was filtered to obtain the title compound (570 mg, 67%).

[0389] [Process 6] Preparation of 4,7-dichloro-2-(4-methoxybenzyl)-1-methyl-1H-imidazo[4,5-c]quinoline

[0390]

[0391] N-(2,7-Dichloro-4-(methylamino)quinolin-3-yl)-2-(4-methoxyphenyl)acetamide (520 mg, 1.40 mmol) synthesized in the above [Process 5] was diluted with 1,4-dioxane (9.7 mL) and water (9.7 mL), then sodium hydroxide (520 mg, 1.40 mmol) was added and the above mixture was stirred at 100 °C for 1 h. After completion of the reaction, the reaction solution was cooled to room temperature and adjusted to pH 7 - 8 with 1N aqueous hydrochloric acid, and the solvent was removed by vacuum distillation. The resulting solid from the addition of saturated sodium bicarbonate solution was collected by filtration, washed with water and dried to obtain the title compound (520 mg, 96%).

[0392] [Process 7] Preparation of 7-chloro-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0393]

[0394] 5N aqueous hydrochloric acid solution (7 mL) and ethanol (17 mL) were added to 4,7-dichloro-2-(4-methoxybenzyl)-1-methyl-1H-imidazo[4,5-c]quinoline (520 mg, 1.40 mmol) synthesized in the above [Process 6], and the reaction solution was stirred at 100 °C for 4 hours. After completion of the reaction, the reaction solution was cooled to room temperature and adjusted to pH 7 to 8 with saturated aqueous sodium bicarbonate solution and water, and stirred for 10 minutes. The resulting solid was collected by filtration, washed with water and dried to obtain the title compound (440 mg, 89%).

[0395] [Process 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

[0396]

[0397] 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 the above [Process 7] was dissolved in dimethyl sulfoxide (1 mL), and then 4-chloro-3-fluorophenylboronic acid (40 mg, 0.23 mmol), pyridine (0.04 mL, 0.45 mmol), molecular sieve (4 Å) and cobalt(II) acetate (42 mg, 0.23 mmol) were added, and the mixture was stirred in an open vial at 80 °C for 16 hours. After cooling the reaction product to room temperature, water was added to the reaction product and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and vacuum distilled. Purification was carried out using silica gel column chromatography to obtain the title compound (2.7 mg, 4.95%).

[0398] 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

[0399]

[0400] The same reaction was carried out using 3-chloro-4-fluorophenylboronic acid instead of 4-chloro-3-fluorophenylboronic acid in the [Process 8] of Example 16 to obtain the title compound (2.6 mg, 4.77%).

[0401] <Synthesis Example 5>

[0402] Example 18: 7-Chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0403] [Process 1] Preparation of 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0404]

[0405] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (300 mg, 1.00 mmol) synthesized in [Process 8] of Example 1 was dissolved in triethyl orthoformate (3.4 mL, 20.02 mmol) and stirred at 120 °C for 2 hours. After completion of the reaction, the reaction solution 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%).

[0406] [Process 2] Preparation of 7-chloro-2-((4-methoxyphenyl)thio)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0407]

[0408] 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (100 mg, 0.32 mmol) synthesized in the above [Process 1] was dissolved in dimethylformamide (3 mL), and then 4-methoxythiophenol (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 solution was stirred at 140 °C for 3 days, and after completion of the reaction, the reaction solution was cooled to room temperature, then water was added and extraction was carried out with ethyl acetate. The separated organic layer was dried over magnesium sulfate and concentrated by vacuum distillation. Then it was purified by silica gel column chromatography and crystallized from methanol to obtain the title compound (29 mg, 20.0%).

[0409] Example 19: 7-Chloro-2-((4-methoxyphenyl)sulfonyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0410]

[0411] Example 20: 7-chloro-2-((4-methoxyphenyl)sulfinyl)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0412]

[0413] Dissolve 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 in dichloromethane (0.56 mL), cool to 0 °C, and then slowly add 3-chloroperoxybenzoic acid (19 mg, 0.08 mmol). Stir the reaction solution at 0 °C for 30 minutes, and after completion of the reaction, add a saturated aqueous solution of sodium thiosulfate and extract with dichloromethane. The separated organic layer is dried over anhydrous magnesium sulfate and concentrated by vacuum distillation. Then, it is purified by silica gel column chromatography to obtain [the 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 [the 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%) respectively.

[0414] According to an embodiment of the present disclosure, the compound of Formula 1 may be a compound selected from the group consisting of the compounds listed in the following [Table 2].

[0415] [Table 2]

[0416]

[0417]

[0418] <Synthesis Example 6>

[0419] [Intermediate 6-1] 2-(4-methoxybenzyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0420]

[0421] 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 sequentially added to anhydrous 1,4-dioxane. After purging with argon, 1-(chloromethyl)-4-methoxybenzene (1.02 g, 6.38 mmol) was added, and the mixture was refluxed at 120 °C for 18 h. After cooling the reaction product to room temperature, the solid was filtered and washed with dichloromethane. The filtrate was concentrated and purified by silica gel column chromatography to afford the title compound (725 mg, 45.76%).

[0422] [Intermediate 6-2] Ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0423]

[0424] [Process 1] Preparation of ethyl 1-methyl-1H-imidazole-4-carboxylate

[0425]

[0426] 1-Ethylimidazole-4-carboxylic acid (10 g, 77.71 mmol) was dissolved in ethanol (100 mL), cooled to 0 °C, and thionyl chloride (20 mL, 77.71 mmol) was slowly added dropwise over 15 min. The mixture was refluxed at 80 °C for 14 h. The reaction product 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 then concentrated under reduced pressure. The resulting residue (10.7 g, 89.3%) was used in the subsequent reaction without further purification.

[0427] [Process 2] Preparation of ethyl 2-bromo-1-methyl-1H-imidazole-4-carboxylate

[0428]

[0429] Ethyl 1-methyl-1H-imidazole-4-carboxylate (6.3 g, 40.9 mmol) obtained in [Process 1] was dissolved in tetrahydrofuran (63 mL) and cooled to 0 °C, followed by addition of N-bromosuccinimide (11.1 g, 61.3 mmol) and potassium tripolyphosphate (13.0 g, 61.3 mmol). The reaction solution was stirred at room temperature for 12 h, then saturated aqueous sodium thiosulfate was added and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate and distilled under vacuum. The resulting residue was purified by silica gel column chromatography to afford the title compound (6.3 g, 66.1%).

[0430] [Process 3] Preparation of Ethyl 2-(4-Methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0431]

[0432] Dissolve ethyl 2-bromo-1-methyl-1H-imidazole-4-carboxylate (11.0 g, 47.2 mmol) obtained in [Process 2] in anhydrous 1,4-dioxane, and then sequentially add [Intermediate 6-1] 2-(4-methoxybenzyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (23.4 g, 94.4 mmol), potassium tripolyphosphate (30.1 g, 142 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.09 g, 1.42 mmol) synthesized above. Replace the mixed solution with nitrogen for 30 minutes, and then reflux at 120 °C for 48 hours. Cool the reaction product to room temperature, then add water and extract with ethyl acetate. The separated organic layer is dried over anhydrous magnesium sulfate and distilled under vacuum. The obtained residue is purified by silica gel column chromatography to obtain the title compound (5.24 g, 40.47%).

[0433] [Process 4] Preparation of Ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0434]

[0435] Dissolve ethyl 2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (1.27 g, 4.63 mmol) obtained in [Process 3] in dichloromethane (12.7 mL), and cool to 0 °C, then add N-bromosuccinimide (832 mg, 4.63 mmol). Stir the reaction solution at room temperature for 12 hours, then add a saturated aqueous solution of sodium thiosulfate and extract with dichloromethane. The separated organic layer is dried over anhydrous magnesium sulfate and distilled under vacuum. The obtained residue is purified by silica gel column chromatography to obtain the title compound (1.27 g, 77.7%).

[0436] [Intermediate 6-3] Ethyl 5-bromo-1-methyl-1H-imidazole-4-carboxylate

[0437]

[0438] Ethyl 1-methyl-1H-imidazole-4-carboxylate (7.43 g, 48.2 mmol) obtained in [Process 1] was dissolved in dichloromethane (2 mL) and cooled to 0 °C, followed by the addition of N-bromosuccinimide (13 g, 72.3 mmol). The reaction solution was stirred at room temperature for 12 hours, followed by the addition of a saturated aqueous solution of sodium thiosulfate and extraction with dichloromethane. The separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (3.73 g, 33.2%).

[0439] 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

[0440]

[0441] [Process 1] Preparation of 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

[0442]

[0443] 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 hours. The reaction product was cooled to room temperature, followed by the addition of water and then extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (9.1 g, 94.5%).

[0444] [Process 2] Preparation of ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0445]

[0446] 5-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (511 mg, 2.02 mmol) obtained in [Process 1] and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (475 mg, 1.34 mmol) obtained in [Intermediate 6-1] were added to 1,4-dioxane (4.75 mL) and water (0.95 mL), and nitrogen was displaced. Subsequently, potassium tripolyphosphate (571 mg, 2.69 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (31 mg, 0.04 mmol) were added. The mixed solution was refluxed at 100 °C for 20 hours and cooled to room temperature after the reaction was completed. Water was added to the reaction product and extracted with ethyl acetate, and the separated organic layer was dried over anhydrous magnesium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (115 mg, 21.4%).

[0447] [Process 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

[0448]

[0449] Ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (115 mg, 0.29 mmol) obtained in [Process 2] was added to toluene (2.9 mL), and then 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 in sequence. Nitrogen was displaced, and the mixture was refluxed at 100 °C for 18 hours. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth and distilled under vacuum. The filtrate was concentrated, stirred again in ethyl acetate and filtered under vacuum, and the obtained solid was purified by silica gel column chromatography to obtain the title compound (43 mg, 33.6%).

[0450] Example 22: 2-(4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0451]

[0452] 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) and 10% palladium / carbon (14.4 mg) synthesized in [Process 3] of Synthesis Example 6 were dissolved in methanol (0.43 mL), and a hydrogen balloon was attached. The reaction solution was stirred at room temperature for 14 hours and additionally at 40 °C for 2 hours, and then cooled to room temperature after the reaction was completed. The reaction mixture was filtered through diatomaceous earth and vacuum distilled, and the obtained residue was purified by silica gel column chromatography to obtain the title compound (12 mg, 65.03%).

[0453] 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

[0454]

[0455] The same reaction was carried out using 3-bromo-2-(trifluoromethyl)pyridine in place of 3-bromo-2-methylpyridine in [Process 3] of Example 21 to obtain the title compound (15 mg, 21.03%).

[0456] 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

[0457]

[0458] The same reaction was carried out using 3-bromo-2-cyclopropyl-pyridine in place of 3-bromo-2-methylpyridine in [Process 3] of Example 21 to obtain the title compound (6 mg, 8.91%).

[0459] Example 25: 7-Chloro-2-(4-methoxybenzyl)-1-methyl-5-(2-(trifluoromethyl)phenyl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0460]

[0461] The same reaction was carried out using 1-bromo-2-(trifluoromethyl)benzene in place of 3-bromo-2-methylpyridine in [Process 3] of Example 21 to obtain the title compound (25.7 mg, 24.82%).

[0462] Example 26: 7-Chloro-5-(2-chlorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0463]

[0464] Using 1-bromo-2-chlorobenzene to replace 3-bromo-2-methylpyridine in [Process 3] of Example 21, the same reaction was carried out to obtain the title compound (16.7 mg, 17.38%).

[0465] 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

[0466]

[0467] Using ethyl 5-(2-amino-4-(trifluoromethyl)phenyl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate to replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21, the same reaction was carried out to obtain the title compound (36.4 mg, 39.65%).

[0468] 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

[0469]

[0470] Using ethyl 5-(2-amino-4-chlorophenyl)-2-(4-fluorobenzyl)-1-methyl-1H-imidazole-4-carboxylate to replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21, the same reaction was carried out to obtain the title compound (18.2 mg, 24.82%).

[0471] 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

[0472]

[0473] Replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21 with ethyl 5-(2-amino-4-chlorophenyl)-2-(benzo[d][1,3]dioxol-5-ylmethyl)-1-methyl-1H-imidazole-4-carboxylate, and carry out the same reaction to obtain the title compound (33.5 mg, 29.18%).

[0474] 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

[0475]

[0476] Replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21 with ethyl 5-(2-amino-4-chlorophenyl)-2-(3,4-difluorobenzyl)-1-methyl-1H-imidazole-4-carboxylate, and carry out the same reaction to obtain the title compound (16 mg, 21.82%).

[0477] Example 31: 7-Chloro-2-(4-methoxybenzyl)-1-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0478]

[0479] Replace 3-bromo-2-methylpyridine in [Process 3] of Example 21 with 3-bromopyridine, and carry out the same reaction to obtain the title compound (11 mg, 12.76%).

[0480] Example 32: 7-Chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0481]

[0482] 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), and nitrogen was displaced. Subsequently, cesium fluoride (95 mg, 0.61 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (16 mg, 0.02 mmol) were added. The mixed solution was refluxed at 100 °C for 72 hours and cooled to room temperature after the reaction was completed. Water was added to the reaction product and extracted with dichloromethane and methanol, and the separated organic layer was dried over anhydrous magnesium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain the title compound (3.5 mg, 3.88%).

[0483] 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

[0484]

[0485] Using ethyl 5-(2-amino-4-chlorophenyl)-2-(4-difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate to replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21, the same reaction was carried out to obtain the title compound (12 mg, 10.88%).

[0486] Example 34: 7-Chloro-5-(4-methoxyphenyl)-2-((4-methoxyphenyl)thio)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0487]

[0488] Using 7-chloro-5-(4-methoxyphenyl)-1-methyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one to replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in [Process 2] of Example 18, the same reaction was carried out to obtain the title compound (8 mg, 18.95%).

[0489] 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

[0490]

[0491] Replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in [Process 2] of Example 18 with 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one, and carry out the same reaction to obtain the title compound (65 mg, 18.24%).

[0492] 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

[0493]

[0494] Replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxythiophenol in [Process 2] of Example 18 with 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-fluorothiophenol, and carry out the same reaction to obtain the title compound (18 mg, 8.50%).

[0495] 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

[0496]

[0497] Replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxythiophenol in [Process 2] of Example 18 with 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 3,4-difluorothiophenol, and carry out the same reaction to obtain the title compound (37 mg, 24.50%).

[0498] 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

[0499]

[0500] Using 7-chloro-1-methyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and benzo[d][1,3]dioxole-5-thiol to replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxythiophenol in [Process 2] of Example 18, performing the same reaction to obtain the title compound (37 mg, 25.20%).

[0501] 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

[0502]

[0503] 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 to replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxythiophenol in [Process 2] of Example 18, performing the same reaction to obtain the title compound (9.5 mg, 6.58%).

[0504] Example 40: 7-Chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0505]

[0506] [Process 1] Preparation of 1-(7-chloro-4-(methylamino)-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-3-(4-methoxyphenyl)urea

[0507]

[0508] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (200 mg, 0.67 mmol) synthesized in [Process 8] of Example 1 and 4-methoxyphenyl isocyanate (0.1 mL, 0.80 mmol) were added to dichloromethane (3 mL), and the reaction solution was stirred at room temperature for 16 h and at 70 °C for 4 h. The reaction solution was concentrated by vacuum distillation and then purified by silica gel column chromatography to obtain the title compound (130 mg, 43.40%).

[0509] [Process 2] Preparation of 7-chloro-2-((4-methoxyphenyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0510]

[0511] 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 [Process 1] above was added to phosphoryl chloride (1 mL), and the reaction solution was stirred at 80 °C for 2 h. The reaction solution was adjusted to pH 7 to 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 vacuum distillation. Purification was carried out by silica gel column chromatography to obtain the title compound (12.8 mg, 24.64%).

[0512] Example 41: 7-Chloro-2-((4-methoxyphenyl)(methyl)amino)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0513]

[0514] [Process 1] Preparation of 7-chloro-2-hydroxy-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0515]

[0516] 3-Amino-7-chloro-4-(methylamino)-1-phenylquinolin-2(1H)-one (150 mg, 0.50 mmol), triphosgene (189 mg, 0.60 mmol), and triethylamine (0.14 mL, 1.00 mmol) synthesized in [Process 8] of Example 1 were added to tetrahydrofuran (5 mL), and the reaction solution was stirred at room temperature for 20 hours. The reaction solution was adjusted to pH 7 to 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 vacuum distillation. Then it was purified by silica gel column chromatography to obtain the title compound (86.9 mg, 53.31%).

[0517] [Process 2] Preparation of 2-Bromo-7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0518]

[0519] 7-Chloro-2-hydroxy-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one (60 mg, 0.18 mmol) and phosphoryl bromide (5.6 g, 18.4 mmol) synthesized in [Process 1] above were added to toluene (1 mL), and the reaction solution was stirred at 110 °C for 2 days. The reaction solution was adjusted to pH 7 to 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 vacuum distillation, and purified by silica gel column chromatography to obtain the title compound (13.7 mg, 19.14%).

[0520] [Process 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

[0521]

[0522] 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 the above [Process 2], 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 racemic-BINAP (8.4 mg, 0.013 mmol) were added to toluene (0.4 mL). After purging with nitrogen, the mixture was refluxed at 100 °C for 16 hours. After the reaction product was cooled to room temperature, the solid was filtered and washed with dichloromethane:methanol = 10:1 (v / v). The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (6.8 mg, 34.94%).

[0523] Example 42: 7-Chloro-2-(4-methoxyphenoxy)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0524]

[0525] [Process 1] Preparation of 2,7-dichloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0526]

[0527] Phosphorus oxychloride (0.35 mL, 3.68 mmol) was added to 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 [Process 1] of Example 41, and the mixture was refluxed at 120 °C for 3 days. The reaction product was cooled to room temperature and then vacuum distilled. Subsequently, a saturated aqueous solution of sodium bicarbonate was added, and the mixture was extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous sodium sulfate, concentrated by vacuum distillation, and purified by silica gel column chromatography to obtain the title compound (15 mg, 70.98%).

[0528] [Process 2] Preparation of 7-chloro-2-(4-methoxyphenoxy)-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0529]

[0530] 4-Methoxyphenol (218.58 mg, 1.74 mmol) and cesium carbonate (28.68 mg, 0.09 mmol) were added to 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 the above [Process 1], and the mixture was refluxed at 140 °C for 24 hours. The reaction product was cooled to room temperature and purified by silica gel column chromatography to obtain the title compound (6 mg, 31.88%).

[0531] According to an embodiment of the present disclosure, the compound of Formula 1 may be a compound selected from the group consisting of the compounds listed in the following [Table 3].

[0532] [Table 3]

[0533]

[0534]

[0535]

[0536]

[0537]

[0538] <Synthesis Example 7>

[0539] [Intermediate 7-1] Ethyl 5-iodo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0540]

[0541] Ethyl 2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (1 g, 3.65 mmol) obtained in [Process 3] of [Intermediate 6-2] was dissolved in N,N-dimethylformamide (20 mL), and then N-iodosuccinimide (2.54 g, 10.94 mmol) was added. The reaction solution was refluxed at 100 °C for 17 hours, then cooled to room temperature, and then a saturated aqueous solution of sodium thiosulfate was added and extraction was carried out with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (1.4 g, 95.96%).

[0542]

[0543] [Process 1] Preparation of 4-iodo-3-nitrophenol

[0544]

[0545] 4-Amino-3-nitrophenol (10.3 g, 64.89 mmol) was dissolved in 38% aqueous hydrochloric acid (5 mL), cooled to 0 °C, and an aqueous solution (20 mL) of sodium nitrite (9.14 g, 129.77 mmol) was slowly added dropwise. After stirring for 1 hour at 0 °C, an aqueous solution (40 mL) of potassium iodide (21.54 g, 129.77 mmol) was slowly added dropwise. After the reaction solution was stirred at room temperature for 15 hours, the resulting solid was collected by filtration, washed with excess water and dried to obtain the title compound (16.5 g, 95.96%).

[0546] [Process 2] Preparation of 4-(benzyloxy)-1-iodo-2-nitrobenzene

[0547]

[0548] 4-Iodo-3-nitrophenol (16.5 g, 62.26 mmol) obtained in the above [Process 1] was dissolved in acetone (165 mL), followed by addition of potassium carbonate (17.30 g, 124.52 mmol) and benzyl bromide (8.31 mL, 68.49 mmol). The reaction solution was stirred at room temperature for 18 hours, and the resulting solid was removed by filtration, and the filtrate was vacuum distilled. Water was added and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate, then vacuum filtered and vacuum distilled to obtain the title compound (21 g, 94.98%).

[0549] [Process 3] Preparation of 5-(benzyloxy)-2-iodoaniline

[0550]

[0551] 4-(Benzyloxy)-1-iodo-2-nitrobenzene (5 g, 14.08 mmol) obtained in the above [Process 2] was dissolved in methanol (37.5 mL), and then activated carbon (845 mg, 70.40 mmol) and iron(III) chloride (235 mg, 1.41 mmol) were added. After purging with nitrogen, the mixture was stirred at 70 °C for 10 minutes. After cooling the reaction solution to room temperature, hydrazine monohydrate (3.48 mL, 70.40 mmol) was slowly added dropwise. The reaction solution was refluxed at 70 °C for 21 hours, then cooled to room temperature and filtered through diatomaceous earth. The filtrate was distilled under vacuum, then water was added and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate, then filtered under vacuum and distilled under vacuum. The obtained residue was dissolved in ethyl acetate (40 mL), then 4N hydrochloric acid 1,4-dioxane solution (20 mL) was added, and 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 obtain the title compound (3.22 g, 63.25%).

[0552] [Process 4] Preparation of 5-(benzyloxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

[0553]

[0554] 5-(Benzyloxy)-2-iodoaniline hydrochloride (3.22 g, 8.90 mmol) obtained in the above [Process 3] was added to anhydrous 1,4-dioxane (48.3 mL) to displace nitrogen, then 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 added. The mixed solution was refluxed at 100 °C for 14 hours, and after completion of the reaction, it was cooled to room temperature. Saturated aqueous ammonium chloride solution was added to the reaction product and the mixture was extracted with ethyl acetate, and the separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (1 g, 34.53%).

[0555] [Process 5] Preparation of ethyl 5-(2-amino-4-(benzyloxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0556]

[0557] 5-(Benzyloxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (2.68 g, 8.25 mmol) and [Intermediate 7-1] ethyl 5-iodo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (3 g, 7.50 mmol) synthesized in the above [Process 4] were added to anhydrous 1,4-dioxane (30 mL) and water (15 mL), and nitrogen was displaced. Subsequently, sodium bicarbonate (1.9 g, 22.49 mmol) and tetrakis(triphenylphosphine)palladium(0) (446 mg, 0.37 mmol) were added. The mixed solution was refluxed at 90 °C for 14 hours and cooled to room temperature after the reaction was completed. A saturated aqueous solution of ammonium chloride was added to the reaction product and extracted with ethyl acetate, and the separated organic layer was dried over anhydrous sodium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain the title compound (1.4 g, 39.61%).

[0558] [Process 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

[0559]

[0560] Using ethyl 5-(2-amino-4-(benzyloxy)phenyl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate to replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21, the same reaction was carried out to obtain the title compound (1.4 g, 91.28%).

[0561] [Process 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]

[0562]

[0563] 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 the above [Process 6]. The mixed solution was refluxed at 140 °C for 7 hours and then cooled to room temperature after the reaction was completed. The reaction product was distilled under vacuum, and then saturated aqueous sodium bicarbonate solution was added, stirred for 30 minutes, and extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (630 mg, 54.51%).

[0564] [Process 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

[0565]

[0566] 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 the above [Process 7] was dissolved in dichloromethane (1.5 mL), and then 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 solution was stirred at room temperature for 4 hours and then distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (196 mg, 100%).

[0567] [Process 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]

[0568]

[0569] (4-Methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-oxido-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate (196 mg, 0.35 mmol) synthesized in the above [Process 8] was dissolved in anhydrous 1,4-dioxane (2 mL), purged with argon, and then 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 mixed solution was refluxed at 100 °C for 2 hours and then cooled to room temperature after the reaction was completed. Water was added to the reaction product and extracted with ethyl acetate, and the separated organic layer was dried over anhydrous sodium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain the title compound (145 mg, 94.66%).

[0570] [Process 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]

[0571]

[0572] 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 the above [Process 9] and 10% palladium / carbon (177 mg) were dissolved in methanol (3.32 mL), and a hydrogen balloon was equipped. The reaction solution was stirred at room temperature for 3 hours. The reaction mixture was filtered through diatomaceous earth and vacuum distilled, and the obtained residue was purified by silica gel column chromatography to obtain the title compound (63 mg, 43.25%).

[0573] 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

[0574]

[0575] Using cyclopropylboronic acid instead of 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane in [Process 9] of <Synthesis Example 7>, the same reaction was carried out to obtain the title compound (5 mg, 65.79%).

[0576] 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

[0577]

[0578] 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 [Process 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 mixed solution was stirred at 40 °C for 18 hours. After completion of the reaction, the reaction product was cooled to room temperature, then water was added and extraction was performed with ethyl acetate, and the separated organic layer was dried over anhydrous sodium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain 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%).

[0579] 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 the mixture was stirred at room temperature for 16 hours. After completion of the reaction, water was added to the reaction product and extraction was performed with dichloromethane, and the separated organic layer was dried over anhydrous sodium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain the title compound (2.4 mg, 19.19%).

[0580] 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

[0581]

[0582] Replace 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-7-ethenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in [Process 10] of <Synthesis Example 7> with 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 carry out the same reaction to obtain the title compound (11.5 mg, 77.55%).

[0583] Example 49: 2-(4-Methoxybenzyl)-1,7-dimethyl-5-(2-methylpyridin-3-yl)-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one

[0584]

[0585] Replace 4,4,5,5-tetramethyl-2-ethenyl-1,3,2-dioxaborolane in [Process 9] of <Synthesis Example 7> with 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane, and carry out the same reaction to obtain the title compound (3 mg, 37.19%).

[0586] 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

[0587]

[0588] Dissolve 2-(4-methoxybenzyl)-1-methyl-5-(2-methylpyridin-3-yl)-4-syloxy-4,5-dihydro-1H-imidazo[4,5-c]quinolin-7-yl trifluoromethanesulfonate (10 mg, 0.02 mmol), cesium carbonate (11.78 mg, 0.04 mmol), palladium acetate (0.41 mg, 0.002 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (1.7 mg, 0.002 mmol), and pyrrolidine (0.005 mL, 0.05 mmol) synthesized in [Process 8] of <Synthesis Example 7> in anhydrous 1,4-dioxane (0.2 mL), and displace with argon. Reflux the mixed solution at 100 °C for 1 hour, and cool to room temperature after the reaction is completed. Add water to the reaction product and extract with ethyl acetate, and separate the organic layer, dry over anhydrous sodium sulfate, and distill under vacuum. The obtained residue is purified by silica gel column chromatography to obtain the title compound (2 mg, 23.29%).

[0589] 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

[0590]

[0591] 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) synthesized in [Process 7] of <Synthesis Example 7> was dissolved in N,N-dimethylformamide (0.23 mL), and then potassium carbonate (6.5 mg, 0.05 mmol) and iodomethane (0.003 mL, 0.05 mmol) were added. The mixed solution was stirred at room temperature for 1 hour, then water and ethyl acetate were added, and extraction was carried out with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (4.3 mg, 41.63%).

[0592] 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

[0593]

[0594] 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), cesium carbonate (117.85 mg, 0.36 mmol), palladium acetate (4.1 mg, 0.02 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (17.24 mg, 0.03 mmol), and diphenylketimine (0.15 mL, 0.90 mmol) synthesized in [Process 8] of <Synthesis Example 7> were dissolved in anhydrous 1,4-dioxane (1 mL), and purged with argon. The mixed solution was refluxed at 100 °C for 2 hours, and after the reaction was completed, it was cooled to room temperature. The reaction product was distilled under vacuum and purified by silica gel column chromatography to obtain 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).

[0595] The obtained intermediate was dissolved in tetrahydrofuran (1 mL) and 1N aqueous hydrochloric acid solution (0.1 mL), and stirred at room temperature for 30 minutes. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (39 mg, 51.19%).

[0596] 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

[0597]

[0598] 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 in methanol solution (0.05 mL), and 10% palladium / 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 diatomaceous earth and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (4 mg, 38.72%).

[0599] 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

[0600]

[0601] Using ethyl 5-(2-amino-4-ethylphenyl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate to replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21, the same reaction was carried out to obtain the title compound (290 mg, 52.50%).

[0602] 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

[0603]

[0604] Replace ethyl 5-(2-amino-4-chlorophenyl)-2-(3-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in [Process 3] of Example 21 with ethyl 5-(2-amino-4-methoxyphenyl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate, and perform the same reaction to obtain the title compound (124 mg, 61.69%).

[0605] According to an embodiment of the present disclosure, the compound of formula 1 can be a compound selected from the group consisting of the compounds listed in the following [Table 4].

[0606] [Table 4]

[0607]

[0608]

[0609]

[0610] <Synthesis Example 8>

[0611] 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

[0612]

[0613] [Process 1] Preparation of (2-fluoro-6-(trifluoromethyl)pyridin-3-yl)boronic acid

[0614]

[0615] Dissolve 2-fluoro-6-(trifluoromethyl)pyridine (15 g, 80.04 mmol) in anhydrous tetrahydrofuran (150 mL), and displace with nitrogen. Cool the mixed solution to -78 °C, and then slowly add dropwise 2.0 M lithium diisopropylamide solution (53.43 mL, 106.85 mmol) and stir at the same temperature for 1 hour. Slowly add dropwise trimethyl borate (12 mL, 106.85 mmol) and stir at room temperature for 22 hours. Add 5 wt% aqueous sodium hydroxide solution (200 mL) to the reaction solution, then neutralize with 5 N aqueous hydrochloric acid solution and extract with ethyl acetate. The separated organic layer is dried over anhydrous sodium sulfate and distilled under vacuum to obtain the title compound (16 g, 86.01%).

[0616] [Process 2] Preparation of Ethyl 5-(2-Fluoro-6-(trifluoromethyl)pyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate

[0617]

[0618] (2-Fluoro-6-(trifluoromethyl)pyridin-3-yl)boronic acid (1.18 g, 5.66 mmol) synthesized in [Process 1] and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate (1.00 g, 2.83 mmol) obtained from [Intermediate 6-2] were added to anhydrous 1,4-dioxane (10 mL) and water (1 mL), and nitrogen was displaced. Subsequently, 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 mixed solution was refluxed at 120 °C for 14 hours and cooled to room temperature after the reaction was completed. Water was added to the reaction product and extraction was performed with dichloromethane and methanol, and the separated organic layer was dried over anhydrous magnesium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain the title compound (539 mg, 43.53%).

[0619] [Process 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

[0620]

[0621] 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 the above [Process 2] and 4-(difluoromethoxy)aniline (45 mg, 0.27 mmol) were dissolved in anhydrous tetrahydrofuran (2.28 mL), and nitrogen was displaced. The mixed solution was cooled to 0 °C, and a 1.0 M lithium bis(trimethylsilyl)amide solution in tetrahydrofuran (0.69 mL, 0.69 mmol) was slowly added dropwise. The mixed solution was stirred at room temperature for 1 hour, and after the reaction was completed, water was added and extraction was performed with dichloromethane and methanol. The separated organic layer was dried over anhydrous magnesium sulfate and vacuum distilled. The obtained residue was purified by silica gel column chromatography to obtain the title compound (17.8 mg, 14.68%).

[0622] 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

[0623]

[0624] Using 2-methylpyridin-3-amine to replace 4-(difluoromethoxy)aniline in [Process 3] of <Synthesis Example 8>, the same reaction was carried out to obtain the title compound (27.3 mg, 19.16%).

[0625] 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

[0626]

[0627] 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 to replace ethyl 5-(2-fluoro-6-(trifluoromethyl)pyridin-3-yl)-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate and 4-(difluoromethoxy)aniline in [Process 3] of <Synthesis Example 8>, the same reaction was carried out to obtain the title compound (150 mg, 68.88%).

[0628] 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

[0629]

[0630] Using 1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,5-dihydro-4H-imidazo[4,5-c][1,8]naphthyridin-4-one to replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in [Process 2] of Example 18, the same reaction was carried out to obtain the title compound (81 mg, 71.42%).

[0631] 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

[0632]

[0633] Using 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 to replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one and 4-methoxybenzenethiol in [Process 2] of Example 18, the same reaction was carried out to obtain the title compound (70 mg, 64.76%).

[0634] 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

[0635]

[0636] [Process 1] Preparation of 5-bromo-2-(trifluoromethyl)pyrimidin-4(3H)-one

[0637]

[0638] Dissolve 2-(trifluoromethyl)pyrimidin-4(3H)-one (6.18 g, 35.8 mmol) in N,N-dimethylformamide (50 mL), and then add N-bromosuccinimide (7.80 g, 42.9 mmol). Stir the mixed solution at 40 °C for 22 h, and cool to room temperature after the reaction is completed. Add water to the reaction solution and extract with ethyl acetate. The separated organic layer is dried over anhydrous sodium sulfate and distilled under vacuum to obtain the title compound (8.69 g, 100%).

[0639] [Process 2] Preparation of 5-bromo-N-(2-methylpyridin-3-yl)-2-(trifluoromethyl)pyrimidin-4-amine

[0640]

[0641] Dissolve 5-bromo-2-(trifluoromethyl)pyrimidin-4(3H)-one (8.69 g, 35.76 mmol) synthesized in the above [Process 1] in tetrahydrofuran (86.9 mL), then add 2,6-dimethylpyridine (6.3 mL, 53.6 mmol) and cool to -78 °C. After 30 minutes, slowly add trifluoromethanesulfonic anhydride (8.0 mL, 46.5 mmol) dropwise at the same temperature, and stir at 0 °C for 3 hours. Add 2-methylpyridin-3-amine (11.8 g, 107 mmol) to the reaction solution and reflux at 70 °C for 4 hours. After the reaction is completed, cool the reaction solution to room temperature, add water to the reaction solution and extract with ethyl acetate, and separate the organic layer, dry over anhydrous sodium sulfate and distill under vacuum. The obtained residue is purified by silica gel column chromatography to obtain the title compound (5.47 g, 45.92%).

[0642] [Process 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

[0643]

[0644] Add 5-bromo-N-(2-methylpyridin-3-yl)-2-(trifluoromethyl)pyrimidin-4-amine (717 mg, 1.50 mmol) synthesized in the above [Process 2] to anhydrous 1,4-dioxane (5 mL) to displace nitrogen, then add 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). Reflux the mixed solution at 100 °C for 19 hours, and cool to room temperature after the reaction is completed. Add water to the reaction product and extract with ethyl acetate, and separate the organic layer, dry over anhydrous magnesium sulfate and distill under vacuum. The obtained residue is purified by silica gel column chromatography to obtain the title compound (240 mg, 29.33%).

[0645] [Process 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

[0646]

[0647] 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 the above [Process 3] was added to 1,4-dioxane (1 mL) and water (0.1 mL) to displace nitrogen, and then ethyl 5-bromo-1-methyl-1H-imidazole-4-carboxylate (245 mg, 1.05 mmol) obtained from [Intermediate 6-3], cesium fluoride (493 mg, 3.15 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (70.5 mg, 0.11 mmol) were added. The mixed solution was refluxed at 100 °C for 18 hours and cooled to room temperature after the reaction was completed. Water was added to the reaction product and extracted with ethyl acetate, and the separated organic layer was dried over anhydrous magnesium sulfate and distilled under vacuum. The obtained residue was purified by silica gel column chromatography to obtain the title compound (17 mg, 4.49%).

[0648] [Process 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

[0649]

[0650] 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 to replace 7-chloro-1-methyl-5-phenyl-1,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one in [Process 2] of Example 18, the same reaction was carried out to obtain the title compound (7.8 mg, 33.16%).

[0651] 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

[0652]

[0653] [Process 1] Preparation of 5-bromo-N-(2-methylpyridin-3-yl)-2-(methylthio)pyrimidin-4-amine

[0654]

[0655] 2-Methylpyridin-3-amine (994 mg, 9.00 mmol) was dissolved in tetrahydrofuran (14 mL) and cooled to 0 °C. At the same temperature, sodium hydride (720 mg, 18.00 mmol) was added and stirred at room temperature for 30 minutes. The reaction solution 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 the mixture was refluxed at 55 °C for 15 hours. After completion of the reaction, the mixture was cooled to room temperature, then water was added and the resulting solid was collected by filtration and washed with excess water. The obtained residue was purified by silica gel column chromatography to give the title compound (1.0 g, 38%).

[0656] [Process 2] Preparation of 5-bromo-N-(2-methylpyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-amine

[0657]

[0658] 5-Bromo-N-(2-methylpyridin-3-yl)-2-(methylthio)pyrimidin-4-amine (500 mg, 1.61 mmol) synthesized in the above [Process 1] was added to dichloromethane (5 mL) and cooled to 0 °C. 3-Chloroperoxybenzoic acid (1.19 g, 4.82 mmol) was added slowly and stirred at room temperature for 1 hour. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added and extracted with dichloromethane and methanol. The separated organic layer was dried over anhydrous magnesium sulfate and distilled in vacuo to give the title compound (395 mg, 71.69%).

[0659] [Process 3] Preparation of 5-bromo-2-ethoxy-N-(2-methylpyridin-3-yl)pyrimidin-4-amine

[0660]

[0661] 5-Bromo-N-(2-methylpyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-amine (395 mg, 1.15 mmol) synthesized in the above [Process 2] was dissolved in tetrahydrofuran (11.5 mL), and then a 21 wt% sodium ethoxide ethanol solution (447 mg, 1.38 mmol) was added dropwise. The mixed solution was stirred at room temperature for 2 hours. After completion of the reaction, the mixed solution was distilled in vacuo, and the obtained residue was purified by silica gel column chromatography to give the title compound (245 mg, 68.8%).

[0662] [Process 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

[0663]

[0664] Replace 5-bromo-2-ethoxy-N-(2-methylpyridin-3-yl)pyrimidin-4-amine in [Process 3] of Example 61 with 5-bromo-N-(2-methylpyridin-3-yl)-2-(trifluoromethyl)pyrimidin-4-amine, and carry out the same reaction to obtain the title compound (57 mg, 20.19%).

[0665] [Process 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

[0666]

[0667] Replace 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 in [Process 4] of Example 61 with 2-ethoxy-N-(2-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-amine obtained from [Intermediate 6-2] and ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate, and carry out the same reaction to obtain the title compound (12.5 mg, 17.11%).

[0668] <Synthesis Example 9>

[0669] 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

[0670]

[0671] [Process 1] Preparation of 3-bromo-2-chloro-6-methoxypyridine

[0672]

[0673] 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 above mixture and the reactants were refluxed at 100 °C for 3 h. The reaction product was cooled to room temperature, then water was added, followed by extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. Purification was carried out using silica gel column chromatography to obtain the title compound (5.4 g, 71.52%).

[0674] [Process 2] Preparation of 2-chloro-6-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

[0675]

[0676] 3-Bromo-2-chloro-6-methoxypyridine (6.3 g, 28.3 mmol) synthesized in the above [Process 1], 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), and after purging with nitrogen, the mixture was refluxed at 100 °C for 20 h. After the reaction product was cooled to room temperature, the solid was filtered and washed with dichloromethane:methanol = 10:1 (v / v). The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (4.5 g, 58.95%).

[0677] [Process 3] Preparation of ethyl 5-(2-chloro-6-methoxypyridin-3-yl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate

[0678]

[0679] 2-Chloro-6-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.9 g, 10.6 mmol) and 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 RuPhos Pd G3 (468 mg, 0.53 mmol) synthesized in the above [Process 2] were added to 1,4-dioxane (20 mL) and water (2 mL), and after purging with nitrogen, the mixture was refluxed at 120 °C for 17 hours. After the reaction product was cooled to room temperature, 6M potassium carbonate solution (2 mL) was added, followed by water and extraction with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. The filtrate was concentrated and purified by silica gel column chromatography to obtain the title compound (1.4 g, 58.73%).

[0680] [Process 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

[0681]

[0682] Ethyl 5-(2-chloro-6-methoxypyridin-3-yl)-2-(4-(difluoromethoxy)benzyl)-1-methyl-1H-imidazole-4-carboxylate (1.4 g, 3.12 mmol) and 3-aminomethylpyridine (379 mg, 3.43 mmol) synthesized in the above [Process 3] were added to anhydrous tetrahydrofuran (31 mL), and an argon balloon was equipped. The reaction solution was cooled to -78 °C, and 1M lithium bis(trimethylsilyl)amide in tetrahydrofuran solution (6.9 mL, 6.87 mmol) was slowly added dropwise. The reaction solution was stirred at room temperature for 1 hour and extracted with ethyl acetate by adding water. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. Purification was carried out using silica gel column chromatography to obtain the title compound (1.46 g, 90.94%).

[0683] [Process 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

[0684]

[0685] At 0 °C, 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) and sodium hydride (199 mg, 4.98 mmol) synthesized in the above [Process 4] were added to N,N-dimethylformamide (12 mL), and the reaction solution was stirred at room temperature for 30 minutes. Water and saturated aqueous ammonium chloride solution were added to the reaction solution and extracted with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. Purification was carried out using silica gel column chromatography to obtain the title compound (633 mg, 53.17%).

[0686] 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

[0687]

[0688] The same reaction was carried out except that ethyl 5-bromo-2-[[4-(difluoromethoxy)phenyl]methyl]-1-methyl-imidazole-4-carboxylate [Intermediate 6-2 of Synthesis Example 6] was used instead of ethyl 5-bromo-2-(4-methoxybenzyl)-1-methyl-1H-imidazole-4-carboxylate in Example 63 to obtain the title compound (223 mg, 67.82%).

[0689] <Synthesis Example 10>

[0690] 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

[0691]

[0692] [Process 1] Preparation of ethyl 7-chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate

[0693]

[0694] Add 2 to 3 drops of N,N-dimethylformamide to the reaction solution in which 2,6-dichloronicotinic acid (4.63 g, 23.6 mmol) is dissolved in dichloromethane (75 mL), and slowly add oxalyl chloride (5.79 mL, 67.50 mmol) dropwise. Stir the mixture at room temperature for 3 hours. Remove the solvent by distillation and add tetrahydrofuran (30 mL). The reaction product is immediately used for the next reaction. (Reaction solution A).

[0695] Dissolve ethyl 3-((2-methylpyridin-3-yl)amino)-3-oxopropionate (5.0 g, 22.50 mmol) in tetrahydrofuran (120 mL), and slowly add sodium hydride (3.6 g, 90.00 mmol) dropwise. Stir at room temperature for 30 minutes and cool to 0 °C. Add the above reaction solution A dropwise to the cooled reaction solution, and slowly raise the temperature to room temperature. Stir for 2 hours and then stir and reflux at 80 °C for 12 hours. Cool the reaction product to room temperature, then add 3N aqueous hydrochloric acid to adjust the pH to acidic, and extract with ethyl acetate. Wash the extracted organic layer with water, dry over anhydrous sodium sulfate, and then concentrate under reduced pressure. The obtained residue (6.5 g, 80.3%) is used for the subsequent reaction without a purification procedure.

[0696] [Process 2] Preparation of 7-chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one

[0697]

[0698] Add 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 [Process 1] to trifluoroacetic acid (40 mL) / 35% hydrochloric acid (40 mL), and stir and reflux at 100 °C for 4 hours. Cool the reaction product to room temperature, concentrate in vacuo, neutralize with saturated aqueous sodium carbonate (pH = 6) and extract with ethyl acetate. Dry the separated organic layer over anhydrous sodium sulfate, filter and concentrate. Add ethyl acetate (50 mL) to the concentrate again, and vacuum filter the resulting solid to obtain the title compound (3.44 g, 48%).

[0699] [Process 3] Preparation of 4-hydroxy-1-(2-methylpyridin-3-yl)-7-vinyl-1,8-naphthyridin-2(1H)-one

[0700]

[0701] 7-Chloro-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one (900 mg, 3.13 mmol) and tributyl(vinyl)tin (1.0 mL, 3.44 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (264 mg, 0.31 mmol) synthesized in the above [Process 2] were added to 1,4-dioxane (31 mL), and after purging with nitrogen, the mixture was refluxed at 110 °C for 15 h. A saturated aqueous solution of potassium fluoride was added to the reaction product, and the mixture was stirred at room temperature for 2 h. The reaction mixture was filtered through diatomaceous earth, and then water was added and extraction was carried out with ethyl acetate. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. Purification was carried out using silica gel column chromatography to obtain the title compound (358 mg, 40.94%).

[0702] [Process 4] Preparation of 7-ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one

[0703]

[0704] Palladium on activated carbon (Pd / C) (164 mg, 0.15 mmol) in 10% and methanol (26 mL) were added to 4-hydroxy-1-(2-methylpyridin-3-yl)-7-vinyl-1,8-naphthyridin-2(1H)-one (358 mg, 1.28 mmol) synthesized in the above [Process 3], and a hydrogen balloon was equipped. The reaction solution was stirred at room temperature for 16 h, filtered through diatomaceous earth, and purified by silica gel column chromatography to obtain the title compound (224 mg, 62.09%).

[0705] [Process 5] Preparation of 7-ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one

[0706]

[0707] 7-Ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one (606 mg, 2.15 mmol) and sodium nitrite (30 mg, 0.43 mmol) synthesized in the above [Process 4] were added to acetic acid (4 mL), and then fuming nitric acid (0.85 mL, 18.3 mmol) was slowly added dropwise to the reaction solution. The mixture was stirred at 50 °C for 20 min, cooled to room temperature, poured into ice water and stirred for 30 min. The resulting solid was collected by filtration, washed with water and dried to obtain the title compound (340 mg, 48.35%).

[0708] [Process 6] Preparation of 4-chloro-7-ethyl-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one

[0709]

[0710] 7-Ethyl-4-hydroxy-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one (347 mg, 1.06 mmol) synthesized in the above [Process 5], 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 solution was stirred at 100 °C for 2 hours. The reaction product was concentrated by vacuum distillation and dried to obtain the title compound (367 mg, 99.99%).

[0711] [Process 7] Preparation of 7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one

[0712]

[0713] 4-Chloro-7-ethyl-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one (367 mg, 1.06 mmol) synthesized in the above [Process 6], methylamine hydrochloride (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 solution was stirred at room temperature for 16 hours. After drying the reaction product and adding water, the resulting solid was collected by filtration, washed with water and dried to obtain the title compound (330 mg, 91.26%).

[0714] [Process 8] Preparation of 3-amino-7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one

[0715]

[0716] Raney nickel (114 mg, 0.97 mmol), dichloromethane (9 mL) / methanol (3 mL) were added to 7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-3-nitro-1,8-naphthyridin-2(1H)-one (330 mg, 0.97 mmol) synthesized in the above [Process 7], and a hydrogen balloon was equipped. The reaction solution was stirred at room temperature for 16 hours, filtered through diatomaceous earth, and purified by silica gel column chromatography to obtain the title compound (228 mg, 75.74%).

[0717] [Process 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

[0718]

[0719] 3-Amino-7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one (134 mg, 0.43 mmol) synthesized in the above [Process 8], 2-[4-(difluoromethoxy)phenyl]acetic acid (87.6 mg, 0.43 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridine 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), and the reaction solution was stirred at room temperature for 1 hour. The reaction solution was extracted with ethyl acetate in the presence of water. The separated organic layer was dried over anhydrous sodium sulfate and concentrated by vacuum distillation. Acetic acid (1 mL) was added to the concentrated mixture, and the reaction solution was stirred at 100 °C for 16 hours. The reaction product was dried by vacuum distillation and purified by silica gel column chromatography to obtain the title compound (164 mg, 79.48%).

[0720] 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

[0721]

[0722] 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 to replace 3-amino-7-ethyl-4-(methylamino)-1-(2-methylpyridin-3-yl)-1,8-naphthyridin-2(1H)-one and 2-(4-methoxyphenyl)acetic acid in [Process 9] of Example 65, the same reaction was carried out to obtain the title compound (184 mg, 52.28%).

[0723] According to an embodiment of the present disclosure, the compound of formula 1 can be a compound selected from the group consisting of the compounds listed in the following [Table 5].

[0724] [Table 5]

[0725]

[0726]

[0727] Experimental Example 1: Cell Growth Inhibition Test Test the cell growth inhibition of the above synthetic compounds against HCT116 cells.

[0728] Maintain HCT116 MTAP- / - (homozygous gene knockout of the MTAP gene in HCT116 MTAP-WT cells by the CRISPER / Cas9 method) cells in RPMI 1640 medium containing 10% FBS and 1% penicillin-streptomycin. Seed approximately 5×10 2 cells into a 96-well plate and treat with the test compounds. (0.64 nM - 2,000 nM, for HCT116 MTAP- / - cells, 6 dose points, 5-fold and 6 days) Measure cell growth by SRB staining and detect absorbance at 540 nm on a Synergy TM NEO microplate reader. Calculate the 50% growth inhibition value (GI 50 ) of the cell line using GraphPad Prism V9 software.

[0729] The results of Experimental Example 1 are shown in the following [Table 6].

[0730] Label GI 50 values less than 100 nM as A, at least 100 nM but less than 500 nM as B, at least 500 nM but less than 1 μM as C, and 1 μM or greater as D.

[0731] [Table 6]

[0732] Compound number <![CDATA[Growth inhibition of HCT116 MTAP- / - cells (GI 50 , nM)]]> 1 B 2 A 3 D 4 A 5 B 6 B 7 D 8 B 9 D 10 A 11 C 12 D 15 D 16 D 17 D 18 A 19 C 20 C 21 A 22 C 23 B 24 B 25 B 26 B 27 A 28 A 29 A 30 A 31 A 32 D 33 A 34 D 35 A 36 A 37 A 38 A 39 A 40 D 41 D 42 D 43 D 44 A 45 A 46 A 47 A 48 B 49 B 50 D 51 A 52 C 53 A 54 A 55 A 56 D 57 A 58 A 59 A 60 B 61 A 62 D 63 A 64 A 65 A 66 A

[0733] So far, the present disclosure has been reviewed with respect to specific embodiments. Those skilled in the art to which the present disclosure pertains will understand that the present disclosure can be implemented in a modified form without departing from the basic features of the present disclosure. Therefore, the disclosed embodiments should be considered from an illustrative rather than a restrictive perspective. The scope of the present disclosure is indicated in the claims rather than the foregoing description, and all differences within the equivalent scope should be construed as being included in the present disclosure.

Claims

1. A compound selected from the following compound of Formula 1, its enantiomers, diastereomers, solvates and hydrates, and pharmaceutically acceptable salts thereof: [Formula 1] Wherein, In the above Formula 1, X and Z are each independently N or CH; Y is CR 3 ; 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, heterocyclic group, heterocyclic oxy group, heterocyclic amino group, heterocyclic oxyalkoxy or heterocyclic oxyalkylamino, Wherein each of the aryl, heteroaryl or heterocyclic group is independently unsubstituted or substituted by 1 to 3 groups selected from alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, halo, cyano, hydroxyalkyl, alkoxyalkyl and aminoalkyl; and each independently is H, cycloalkyl, aryl, or heteroaryl, heterocyclic group each of the cycloalkyl, aryl, heteroaryl or heterocyclic group is monocyclic, bicyclic or polycyclic, wherein the cycloalkyl, aryl, heteroaryl or heterocyclic group is unsubstituted or substituted with 1 to 3 groups independently selected from the following R 2 selected; L is C 1-3 an alkylene, O, NH, N(C 1-3 alkyl), S, SO, SO 2 or a bond; R 2 is alkyl, cycloalkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, alkanesulfonyl, halogen, cyano, carboxyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, sulfonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocyclic carbonyl or ureido; and R 1 is H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, substituted aminoalkyl, aminocarbonylalkyl or aminosulfonylalkyl.

2. The compound according to claim 1, wherein and each independently is 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 heterocyclic group, bridged C 6-14 heterocyclic group, fused C 1-10 heterocyclic group or C 6-14 spiroheterocyclic group.

3. The compound according to claim 1, wherein X and Z are each independently N or CH; Y is CR 3a ; 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 alkylsulfonyl, hydroxy, halogen, haloalkyl C 1-6 alkyl, haloalkyl C 1-6 alkoxy, C 3-10 cycloalkyl, cyano, amino, C 1-6 alkylamino, haloalkyl C 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 heterocyclic group, C 1-10 heterocyclic oxy, C 1-10 heterocyclic amino, C 1-10 heterocyclic oxyalkoxy or C 1-10 heterocyclic oxyalkylamino, wherein C 6-10 aryl, C 4-10 heteroaryl or C 1-10 each of the heterocyclic groups is independently, Unsubstituted or substituted with one to three groups selected from C 1-6 alkyl, C 3-10 cycloalkyl, halo C 1-6 alkyl, halo C 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; and each independently is 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 heterocyclic group, bridged C 6-14 heterocyclic group, fused C 1-10 heterocyclic group or C 6-14 spiroheterocyclic group, wherein C 6-10 aryl, C 4-10 heteroaryl or C 1-10 the heterocyclic group is unsubstituted or substituted by 1 to 3 groups independently selected from the following R 2a selected; 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, halo C 1-6 alkyl, halo C 1-6 alkylamino, halo C 1-6 alkoxy, C 1-6 alkoxy, hydroxy, C 1-6 alkylsulfonyl, 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 heterocyclic carbonyl or ureido; and R 1 is H, C 1-6 alkyl, halo C 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 alkyl.

4. The compound according to claim 1, wherein X and Z are each independently N or CH; Y is CR 3b ; R 3b is H, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, hydroxy, halogen, haloalkyl C 1-6 alkyl, C 3-6 cycloalkyl, amino, C 1-3 alkylamino, haloalkyl C 1-6 alkylamino or C 2-6 heterocyclic group; and each independently is H, C 6-10 aryl, C 4-10 heteroaryl or C 1-10 heterocyclic group, wherein C 6-10 aryl, C 4-10 heteroaryl or fused C 1-10 heterocyclic group is unsubstituted or substituted by 1 to 3 groups independently selected from the following R 2b selected; L is C 1-6 alkylene, O, NH, NCH 3 , S, SO, SO 2 or a bond; R 2b is C 1-6 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, C 1-6 alkoxy, hydroxy or halogen; and R 1 is H or C 1-6 alkyl group.

5. The compound according to claim 1, wherein X and Z are each independently N or CH; Y is CR 3c ; R 3c is H, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, hydroxy, halogen, halo C 1-3 alkyl, C 3-6 cycloalkyl, amino, C 1-3 alkylamino, halo C 1-3 alkylamino or C 2-6 heterocyclic group; and each independently is H, phenyl, pyridyl, imidazolyl, pyrrolidinyl, indolyl, naphthyl, benzodioxynyl or benzodioxolyl, wherein and is unsubstituted or substituted by 1 to 3 groups independently selected from C 1-3 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, C 1-3 alkoxy, hydroxy and halogen; L is C 1-3 alkylene, O, NH, NCH 3 , S, SO, SO 2 or a bond; and R 1 is H or C 1-3 alkyl group.

6. The compound according to claim 1, wherein X and Z are each independently N or CH; Y is CR 3c , wherein R 3c is H, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, hydroxy, halogen, haloalkyl C 1-3 alkyl, C 3-6 cycloalkyl, amino, C 1-3 alkylamino, haloalkyl C 1-3 alkylamino or C 2-6 heterocyclic group; is phenyl or pyridyl; is H, phenyl, pyridyl, imidazolyl, pyrrolidinyl or wherein and each independently Unsubstituted or substituted by one to three groups independently selected from C 1-3 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, C 1-3 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 according to claim 1, wherein the compound is selected from the group consisting of the following compounds, their enantiomers, diastereomers, solvates and 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-ethenyl-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 methionine adenosyltransferase 2A-related diseases or disorders, comprising a compound as an active ingredient, which is selected from the group consisting of the compounds as described in any one of claims 1 to 7, their enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

9. The pharmaceutical composition for treating or preventing methionine adenosyltransferase 2A-related diseases or disorders according to claim 8, wherein the pharmaceutical composition exhibits MATA2A inhibitory activity.

10. The pharmaceutical composition for treating or preventing methionine adenosyltransferase 2A-related diseases or disorders according to claim 8, wherein the pharmaceutical composition is used for treating cancer.

11. The pharmaceutical composition for treating or preventing methionine adenosyltransferase 2A-related diseases or disorders according to claim 8, wherein the pharmaceutical composition is used for treating methionine adenosylphosphorylase-deficient cancer.

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