Novel heterobicyclic compounds for inhibiting yap-tead interaction and pharmaceutical compositions comprising same

Abstract

The present invention relates to: a compound selected from a compound of chemical formula 1, the optical isomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof; a preparation method therefor; and uses thereof.

Description

Novel heterocyclic compounds for inhibiting YAP-TEAD interactions and pharmaceutical compositions containing the same

[0001] The present invention relates to a pharmaceutical composition comprising a heterocyclic compound that inhibits the binding of a Yes associated protein (YAP) to a transcriptional enhancer associate domain (TEAD). The compound according to the present invention can directly inhibit the YAP-TEAD binding in the Hippo pathway, which plays a key role in the development of cancer.

[0002] The Hippo signaling cascade is an important pathway for oncogenesis and tumor maintenance. YAP and tafazzin (TAZ) are transcriptional co-activators of the Hippo pathway network and regulate cell proliferation, migration, and apoptosis. Inactivation of the Hippo signaling pathway promotes the nuclear translocation of YAP / TAZ, where YAP / TAZ interacts with transcription enhancer-associated domain (TEAD) transcription factors to co-activate the expression of target genes and promote cell proliferation. Target genes closely correlated with oncogenesis, such as connective tissue growth factor (CTGF), Cyr61, AXL receptor tyrosine kinase, and MYC, are regulated by TEAD. Furthermore, TEAD has been shown to be overexpressed in breast cancer stem cells as well as in breast, ovarian, germ cell tumors, renal cell carcinoma, medulloblastoma, and gastric cancer. Overactivation of YAP and TAZ and / or mutations in one or more members of the Hippo pathway network are associated with numerous cancers. Additionally, recent studies have reported that YAP overexpression or amplification is associated with epithelial-mesenchymal transition (EMT) phenotypic changes for resistance to the EGFR tyrosine kinase inhibitors Tarceva (erlotinib), Iressa (gefitinib), or Tagrisso (osimertinib).

[0003] The inventors completed the present invention by developing a novel heterocyclic compound for inhibiting YAP-TEAD protein interactions.

[0004] [Prior Art Literature]

[0005] [Patent Literature]

[0006] (Patent Document 1) International Published Patent WO2019 / 040380

[0007] (Patent Document 1) International Published Patent WO2020 / 243415

[0008] [Non-patent literature]

[0009] (Non-patent literature 1) Semin. Cancer Biol. 2022, 85, 33

[0010] (Non-patent literature 2) Nat. Rev. Drug Discov. 2014, 13(1), 63

[0011] (Non-patent literature 3) Cancer Res. 2011, 71(3), 873

[0012] (Non-patent literature 4) J. Cell Mol. Med. 2017, 21(11), 2663

[0013] (Non-patent literature 5) Cancer Cell 2020, 37,104

[0014] (Non-patent literature 6) Cells2021, 10,2715

[0015] (Non-patent literature 7) Genes Cancer 2017, 8(3-4), 497

[0016] One aspect of the present invention is to provide a novel heterocyclic compound having excellent inhibitory activity against YAP-TEAD binding in the Hippo pathway, which plays a key role in the development of cancer.

[0017] Another aspect of the present invention is to provide a pharmaceutical composition for treating or preventing a related disease caused by dysregulation of the Hippo signaling pathway, specifically TEAD activation, comprising the above compound as an active ingredient.

[0018] Other aspects and advantages of the present application will become more apparent from the following detailed description together with the appended claims. Content not described herein is omitted, as it can be sufficiently recognized and inferred by those skilled in the art within the field of the present application or a similar field.

[0019] One aspect of the present invention provides a compound of Formula 1 below, or an optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof.

[0020] [Chemical Formula 1]

[0021]

[0022] According to one embodiment of the present invention, a pharmaceutical composition for treating or preventing dysregulation of the Hippo signaling pathway, specifically a related disease caused by TEAD activation, is provided, comprising the compound, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof as an active ingredient.

[0023] The novel heterocyclic compound having the structure of Formula 1 in the present invention has excellent inhibitory activity against YAP-TEAD binding, is effective against various diseases associated with the Hippo pathway, which plays a key role in the development of cancer, and can be usefully used as a therapeutic agent.

[0024] The present invention will be described in more detail below.

[0025] All technical terms used in this invention, unless otherwise defined, are used in the sense generally understood by those skilled in the art in the relevant field of this invention. Additionally, while preferred methods or samples are described herein, similar or equivalents are also included within the scope of this invention.

[0026] definition

[0027] In this specification, the term "halogen" may be F, Cl, Br, or I.

[0028] In this specification, the term “alkyl” refers to a monovalent group derived from a saturated hydrocarbon by removing one hydrogen atom, unless otherwise noted. The alkyl comprises a straight-chain, branched, or cyclic hydrocarbon residue that may be substituted or unsubstituted, and may be, for example, methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, or t-butyl (or tert-butyl), but is not limited thereto.

[0029] Unless otherwise noted, the term “alkenyl” refers to a monovalent group derived from a hydrocarbon by removing one hydrogen atom and comprises one or more unsaturated regions and at least one carbon-carbon double bond. The alkenyl comprises an alkyl group containing one or more double bonds that may be substituted or unsubstituted, and may be, for example, prop-1-en, but-1-en, but-2-en, 3-methylbut-1-en, or pent-1-en, but is not limited thereto.

[0030] In this specification, the term "alkynyl" refers to a monovalent group derived from a hydrocarbon by removing one hydrogen atom, unless otherwise noted, and comprises one or more unsaturated regions, namely at least one carbon-carbon triple bond. The alkynyl may be -C≡CH, -CH2C≡CH, or -CH2CH2CH2C≡C-, but is not limited thereto.

[0031] As used herein, the term "alkylene" refers to a straight-chain, branched, or cyclic saturated divalent hydrocarbon group having two monovalent radical centers derived by removing two hydrogen atoms from the same or two different carbon atoms of a parent alkane. An alkylene is (-CH2-) pIt can also be represented as (p is any integer), and may be, for example, methylene (-CH2-), 1,1-ethyl (-CH(CH3)-), 1,2-ethyl (-CH2CH2-), 1,1-propyl (-CH(CH2CH3)-), 1,2-propyl (-CH2CH(CH3)-), 1,3-propyl (-CH2CH2CH2-), or 1,4-butyl (-CH2CH2CH2CH2-), but is not limited thereto.

[0032] As used herein, the term "alkenylene" refers to a divalent group derived from an alkenyl by removing one hydrogen atom. In other words, alkenylene refers to a straight-chain, branched, or cyclic unsaturated divalent hydrocarbon group having two monovalent radical centers derived by removing two hydrogen atoms from the same or two different carbon atoms of a parent alkene. For example, alkenylene may be methylene (-CH=) or 1,2-ethylene (-CH=CH-), but is not limited thereto.

[0033] As used herein, the term "alkynylene" refers to a divalent group derived from an alkyne by removing one hydrogen atom. In other words, alkynylene refers to a straight-chain, branched, or cyclic unsaturated divalent hydrocarbon group having two monovalent radical centers derived by removing two hydrogen atoms from the same or two different carbon atoms of a parent alkyne. For example, alkynylene may be -C≡C-, -CH2C≡C-, or -CH2CH2CH2C≡C-, but is not limited thereto.

[0034] In this specification, the term "cycloalkyl" refers to a saturated hydrocarbon ring comprising a monocyclic ring and a polycyclic ring that may be substituted or unsubstituted unless otherwise noted. Examples may include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. Additionally, the term cycloalkyl includes spirocycloalkyl, fused cycloalkyl, or bridged cycloalkyl.

[0035] In this specification, the term "cycloalkenyl" refers to a hydrocarbon ring comprising one or more carbon-carbon double bonds unless otherwise noted. Examples may include, but are not limited to, cyclopropene, cyclobutene, cyclopentene, cyclohexene, cycloheptene, or cyclooctene.

[0036] Unless otherwise noted, the term "spiro" refers to two rings sharing one atom, where the two rings are not connected by a bridge. Unless otherwise noted, the term "spiro linkage" refers to a linker sharing one atom.

[0037] In this specification, the term "spirocycloalkyl" refers, unless otherwise noted, to a saturated carbon ring compound comprising two rings, wherein both rings share only one carbon atom as part of the ring. For example, spirocycloalkyl is , , , , , , , or It may be, but is not limited to, etc.

[0038] In this specification, the term "fused cycloalkyl" refers, unless otherwise noted, to a structure in which each ring shares an adjacent pair of carbon atoms with another ring, and one or more rings may share one or more double bonds, but none of these rings possess a complete conjugated π-electron system. For example, fused cycloalkyls may be classified into dicyclic, tricyclic, tetracyclic, or polycyclic fused cycloalkyls depending on the number of rings. For example, , , , or It may be, but is not limited to, etc.

[0039] In this specification, the term "bridged cycloalkyl" refers to two rings sharing two non-adjacent common ring atoms unless otherwise noted. Bridged cycloalkyls may be classified into bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyls depending on the number of rings. For example, , , , or It may be, but is not limited to, etc.

[0040] In this specification, the term “heterocycloalkyl” refers to a substituent having a saturated, monocyclic or polycyclic heterocyclic structure that may be substituted or unsubstituted, comprising one or more heteroatoms selected from N, O, and S, unless otherwise noted. Examples may include piperidine, piperazine, morpholine, pyrrolidine, thiomorpholine, imidazolidine, or tetrahydrofuran, but are not limited thereto.

[0041] In this specification, the term “heterocycloalkenyl” refers, unless otherwise noted, to a hydrocarbon ring comprising a monocyclic ring and a polycyclic ring, comprising one or more carbon-carbon double bonds and one or more heteroatoms selected from N, O, and S. Examples may include, but are not limited to, pyrroline, dihydropyran, or tetrahydrothiophene.

[0042] Unless otherwise noted, the term "haloalkyl" refers to an alkyl group in which one or more hydrogen atoms of the alkyl group are substituted with a halogen, and includes monohaloalkyl and polyhaloalkyl. Examples may include, but are not limited to, trifluoromethyl (-CF3), chloromethyl (-CH2Cl), bromoethyl (-CH2CH2Br), dichloromethyl (-CHCl2), or chloropropyl (-CH2CH2CH2Cl).

[0043] In this specification, the term "alkoxyalkyl" refers to an alkyl group in which one or more hydrogen atoms of the alkyl group are substituted with an alkoxy. For example, (C 1-6 Alkoxy)C 1-6 The alkyl group consists of one or more C 1-6 C substituted with an alkoxy 1-6 It represents an alkyl group. For example, it may be methoxymethyl (-CH2-O-CH3), ethoxymethyl (-CH2-O-CH2CH3), methoxyethyl (-CH2CH2-O-CH3 or -CH(O-CH3)CH3), ethoxyethyl (-CH2CH2-O-CH2CH3 or -CH(O-CH2CH3)CH3), methoxypropyl (-CH2CH2CH2-O-CH3), ethoxypropyl (-CH2CH2CH2-O-CH2CH3), or isopropoxymethyl (-CH2-O-CH(CH3)2), but is not limited thereto.

[0044] Unless otherwise noted, the term "hydroxyalkyl" refers to an alkyl group in which one or more hydrogen atoms of the alkyl group are substituted with hydroxy (-OH), and includes straight-chain or branched forms, and may be, for example, hydroxymethyl (-CH2OH), hydroxyethyl (-CH2CH2OH or -CH2(OH)CH3), or hydroxypropyl (-CH2CH2CH2OH, -CH(OH)CH2CH3, or -CH2CH2(OH)CH3), but is not limited thereto.

[0045] In this specification, the term “alkoxy” refers to a straight-chain or branched hydrocarbon residue connected to oxygen, which may be substituted or unsubstituted unless otherwise noted. Examples may include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, isopropoxy, isobutoxy, or t-butoxy.

[0046] In this specification, the term "haloalkoxy" refers to an alkoxy in which one or more hydrogen atoms of the alkoxy group are substituted with a halogen. Examples include, but are not limited to, trifluoromethoxy (-OCF3), trifluoromethoxymethyl (-OCH2-CF3), difluorochloromethoxy (-OCF2Cl), or chloroethoxy (-OCH2CH2Cl).

[0047] In this specification, the term "aryl" refers to an aromatic group that may be substituted or unsubstituted unless otherwise noted, e.g., C 3-10 Aril, C 3-8 Aryl, or C 3-6 It may include an aryl group, and double bonds alternate (resonate) between adjacent carbon atoms or suitable heteroatoms, and this includes not only a monocyclic ring but also a polycyclic ring structure. For example, it may be phenyl, biphenyl, naphthyl, toluyl, or naphthalenyl, but is not limited thereto.

[0048] In this specification, the term “heteroaryl” refers to an aromatic group comprising a monocyclic ring and a polycyclic ring, which may be substituted or unsubstituted, and which comprises one or more heteroatoms selected from N, O, and S unless otherwise noted. For example, a monocyclic heteroaryl may be, but is not limited to, pyridinyl, imidazoleyl, thiazoleyl, oxazoleyl, thiopheneyl, furanyl, pyrroleyl, isooxazoleyl, pyrazolyl, triazoleyl, thiadiazoleyl, tetrazoleyl, oxadiazoleyl, pyridazineyl, pyrimidinyl, or pyrazineyl. For example, polycyclic heteroaryls, such as bicyclic heteroaryls consisting of two rings, may be indole yl, benzothiophenyl, benzofuran yl, benzimidazole yl, benzoxazole yl, benzisoxazole yl, benzthiazole yl, benzthiadiazole yl, benztriazole yl, quinoline yl, indazole yl, isoquinoline yl, purine yl, or furopyridine yl (e.g., furo[2,3-b]pyridine yl), but are not limited thereto.

[0049] In this specification, the term "carbocyl" refers to a substituent having a saturated, partially saturated, or unsaturated ring structure comprising only carbon ring atoms, unless otherwise noted. For example, the saturated ring structure of the carbocyl includes "cycloalkyl," the partially saturated ring structure includes "cycloalkenyl," or the unsaturated ring structure includes "aryl." The carbocyl may have a monocyclic or polycyclic ring structure. In this specification, the atoms within the ring of the carbocyl may be, for example, 3 to 14, or for example, 3 to 8, and may have a saturated, unsaturated, or aromatic structure. Here, ring atoms are atoms that are bonded together to form a ring or rings of the carbocyl substituent. For example, saturated carbocyl groups (e.g., cycloalkyl) may be cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, but are not limited thereto. The unsaturated carbocyclyll may contain, for example, three or fewer double bonds. The aromatic carbocyclyll group may be, for example, phenyl. Additionally, the carbocyclyll may contain a polycyclic structure in which two or more carbon rings are fused, and may be, for example, naphthyl, phenanthryl, indanyl, or indenyl, but is not limited thereto.

[0050] In this specification, the term "heterocyclil" refers, unless otherwise noted, to a substituent having a saturated, partially saturated, or unsaturated ring structure comprising at least one heteroatom and a ring atom. For example, the saturated ring structure of the heterocyclil includes "heterocycloalkyl," the partially saturated ring structure includes "heterocycloalkenyl," and the unsaturated ring structure includes "heteroaryl." The heterocyclil may have a monocyclic or polycyclic ring structure. In this specification, the atoms within the ring of the heterocyclil may be, for example, a total of 3 to 14, for example, 6 to 14, or for example, a total of 3 to 8, and may have a saturated, unsaturated, or aromatic structure. Here, the ring atom is an atom that is bonded together to form a ring or rings of the heterocyclil substituent. For example, at least one of the ring atoms is N, O, or S, and the remaining ring atoms are independently selected from the group consisting of C, N, O, and S. For example, four or fewer atoms within the ring of the heterocyclil may be heteroatoms such as N, O, and S, for example, a total of 3 to 14, or for example, a total of 5 to 7, and may have a saturated, unsaturated, or aromatic structure. For example, the above heterocyclil may be imidazole, pyrazol, triazole, tetrazol, oxazol, thiazole, isoxazol, isothiazol, oxadiazole, thiadiazole, pyrrole, pyrroline, pyrrolidine, pyrazolin, pyrazolidin, furan, thiophene, pyran, pyridine, pyridazine, pyridazine, pyrimidine, triazine, piperidine, piperazine, morpholinyl, thiomorpholinyl, dioxane, dioxolalan, dithian, sulfolane, imidazolin, imidazolidin, azepine, diazepine, oxazepine, or thiazepine, but is not limited thereto.Additionally, the term heterocyclyl may include a spiro ring (e.g., spiroheterocycloalkyl) or a fused ring (e.g., fused heterocyclyl group) structure.

[0051] In this specification, the term "spiroheterocycloalkyl" refers to an alkyl substituent having a spiro ring structure comprising at least one heteroatom selected from N, O, and S, unless otherwise noted. Spiroheterocycloalkyls are, for example, 1-oxa-6-azaspiro[3.3]heptane, 1-oxa-6-azaspiro[3.4]octane, 1-oxa-7-azaspiro[4.3]heptane, 1-oxa-7-azaspiro[4.4]nonane, 1,6-dioxaspiro[3.3]heptane, 1,6-diazaspiro[3.3]heptane, It may be 1-oxa-6-thiaspiro[3.3]heptane, 1-thia-6-azaspiro[3.3]heptane, etc., but is not limited thereto.

[0052] The term "fused heterocyclil" refers to a substituent in which a ring structure comprising at least one heteroatom selected from N, O, and S is fused to a carbon ring unless otherwise noted. Fused heterocyclils may be, for example, benzimidazoline, benzoxazole, imidazopyridine, benzoxazine, benzothiazine, oxazolopyridine, quinoline, quinazolin, quinoxazolin, dihydroquinazolin, benzothiazol, phthalimidyl, benzofuran, benzodiazepine, indole, or isoindole, but are not limited thereto.

[0053] In this specification, the term “fused heteroaryl” refers, unless otherwise noted, to a substituted or unsubstituted ring system in which a heteroaryl group is fused with another aryl, heteroaryl, or heterocycloalkyl group. For example, a fused heteroaryl may form a fused ring system such as a 5+5, 5+6, 5+7, 6+6, or 6+7 ring, but is not limited thereto.

[0054] In addition, "heterocyclils" can be connected to other parts through carbon linkers or heteroatom linkers (e.g., N-links). For example, among the heteroatom linkers, an N-linked heterocyclil , , ,or It may be, but is not limited to, etc. For example, among the heteroatom linkers, N-linked spiroheterocycloalkyl It may be, but is not limited to, etc.

[0055] The compounds mentioned herein may be substituted or unsubstituted with any substituent. Any substituents in this specification are, for example, halogen, cyano (-CN), amino, hydroxy, oxo (=O), C 1-6 alkylamino, di(C 1-3 Alkyl)amino, C 1-6 Alkyl (e.g., methyl, ethyl, n-propyl, or isopropyl), halo-C 1-6 Alkyl (e.g., trifluoromethyl), C 3-6 Cycloalkyl (e.g., cyclohexyl group), haloC 3-6 Cycloalkyl, C 1-6 Alkoxy, Hydroxy C 1-6 Alkyl, C 1-6 Alkoxyalkyl, haloC 1-6 Alkoxy, amido (-CONH2), sulfonyl, sulfonamido, carboxyl, C 1-6 Alkylsulfonyl, C 2-4 Alkenyl, C 2-4Alkynyl, phenyl, benzyl, pyridine, azetidine, pyrrolidine, dioxolane, thiophene, piperidine, piperazine, tetrazole, quinoline, indole, C 2-6 Heterocyclil, or C 4-10 It may be heteroaryls, etc., but is not limited thereto. For example, a substituted alkyl, a substituted carbocyl, a substituted aryl, a substituted heterocyclyl, or a substituted heteroaryl may have one or more hydrogen atoms substituted with any of the aforementioned substituents, but is not limited thereto.

[0056] In this specification, the term "stereoisomer" refers to a compound of the present invention or a salt thereof that has the same chemical formula or molecular formula but is optically or stereochemically different, and includes optical isomers or diastereomers.

[0057] In this specification, the term "optical isomer" refers to two stereoisomers of a compound that are mirror images of each other and do not overlap.

[0058] In this specification, the term "diastereomer" refers to a stereoisomer having two or more chiral centers, the molecules of which are not mirror images of each other.

[0059] The compounds of the present invention may contain asymmetric or chiral centers and thus may exist in different stereoisomer forms. All stereoisomer forms of the compounds of the present invention, such as diastereomers, optical isomers, and racemic mixtures, are considered to constitute part of the present invention. A 50:50 mixture of optical isomers is called a racemic mixture or racemic mixture.

[0060] In this specification, the term "solvent" may mean a compound of the present invention or a salt thereof comprising stoichiometric or non-stoichiometric amounts of solvent bound by non-covalent intermolecular forces. Preferred solvents thereof may be volatile, non-toxic, and / or solvents suitable for administration to humans. The "solvent" may comprise a molecular complex comprising said compound and one or more pharmaceutically acceptable solvent molecules, e.g., ethanol.

[0061] In this specification, the term "hydrate" refers to a complex in which the solvent molecule is water.

[0062] In this specification, the term "pharmaceuticalally acceptable salt" refers to a pharmaceutically acceptable organic or inorganic salt and may be prepared by any suitable method useful to those skilled in the art. For example, if the compound of the present invention is a base, the desired pharmaceutically acceptable salt may be prepared by any suitable method useful to those skilled in the art, for example, by treating said free base with an inorganic acid or an organic acid.

[0063] In this specification, the term "therapeutic effective amount" refers to an amount of the compound of the present invention that treats or prevents a specific disease, condition, or disorder, alleviates, improves, 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.

[0064] In this specification, the terms “treating” or “treating” mean inhibiting a disease, e.g., in an individual experiencing or exhibiting a pathology or sign of a disease, condition, or disorder, such as preventing or reversing the further occurrence of the pathology and / or sign, or improving a disease, e.g., reducing the severity of the disease.

[0065] In this specification, the terms “preventing” or “prevention” mean preventing a disease, for example, preventing a disease, condition, or disorder in an individual who may have a predisposition to a disease, condition, or disorder but has not yet experienced or exhibited the pathology or signs of the disease.

[0066] In this specification, the terms “object” or “individual” may be vertebrates such as mammals, fish, birds, reptiles, or amphibians. For example, the object may be a human, a non-human primate, a horse, a pig, a rabbit, a dog, a sheep, a goat, a cow, a cat, a guinea pig, or a rodent.

[0067] As used herein, the terms "administering" and "administering" refer to any method of providing the disclosed composition to a subject.

[0068] In the context of the present invention, the singular form of a word may include the plural unless the context explicitly indicates otherwise, and vice versa.

[0069] The numerical values ​​described in this specification are deemed to include the meaning of "about" unless explicitly stated. The term "about" as used in this specification means within 5% of a predetermined value or range, preferably within 1% to 2%.

[0070] In this specification, a numerical range indicated by the term "to" refers to a range that includes the values ​​described before and after the term "to" as a lower limit and an upper limit, respectively.

[0071] Expressions such as "have," "may have," "include," or "may include" as used in this specification refer to the existence of such features (e.g., numerical values ​​or components, etc.) and do not exclude the existence of additional features.

[0072] The contents of all publications cited as references in this specification are incorporated by reference in their entirety.

[0073]

[0074] Novel heterobicyclic compound

[0075] One aspect of the present invention provides a compound of Formula 1 below, or an optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof.

[0076] [Chemical Formula 1]

[0077]

[0078] In the above chemical formula 1,

[0079] X 1 and X 3 are independently O, S, C, N, C(R 4 ), C(R 4a )(R 4b ), and N(R 4a Selected from );

[0080] X 2 , X 5 , and X 6 C, N, and C(R) are each independently 5 ), C(R 5a )(R 5b ), and N(R 5a Selected from,

[0081] X 4 , X 7 , X 8 , and X 9 C, N, and C(R) are independently C, N, and C(R 6 Selected from );

[0082] L 1 Silver bond, -O-, -S-, -NH-, C 1-3 Alkylene, or C 2-6 It is alkenylene;

[0083] L 2 is a bond, C 1-3 Alkylene, or 1 to 3 R 7 C that is replaced by 1-3It is an alkylene;

[0084] R 1 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aryl, and C 1-9 Selected from heteroaryls,

[0085] Here, R 1 is R 8 Substituted or unsubstituted with 1 to 3 substituents independently selected from each;

[0086] R 2 is hydrogen, halogen, or C 1-6 It is alkyl;

[0087] R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aryl, monocyclic C 1-9 Heteroaryl, and bicyclic C 4-14 Selected from heteroaryls,

[0088] Here, R 3 is R 9 Substituted or unsubstituted with 1 to 3 substituents independently selected from each;

[0089] R 4 , R 4a , R 4b , R 5 , R 5a, R 5b , R 6 , and R 7 Each independently consists of hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Halocycloalkyl, C 6-10 Aril, C 1-9 Heteroaryl, and C 2-9 Selected from heterocycloalkyl;

[0090] R 8 and R 9 are hydrogen, halogen, oxo, cyano, hydroxy, and C, respectively. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, -(CH2) n -C 3-6 Cycloalkyl, -NH-C 3-6 Cycloalkyl, Hydroxy C 1-6 Alkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, -(CH2) n -C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aril, -(CH2) n -C 6-10 Aryl, monocyclic C 1-9 Heteroaryl, -(CH2) n -C 1-9 Heteroaryl, bicyclic C 4-14 Heteroaryl, hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), C 1-3 Alkoxy(C 2-9 Heterocycloalkyl), -OR 10 , -SR10 , -SF5, -N(R 10 )(R 11 ), , -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 10 )C(O)N(R 10 )(R 11 ), -N(R 10 )C(O)OR 10 , -N(R 10 )SO2R 10 , -C(O)R 10 , -S(O)R 10 , -OC(O)R 10 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 10 )C(O)R 10 , -SO2R 10 , -SO2N(R 10 )(R 11 ), -N=S(=O)(R 10 )(R 11 ), -S(=O)(=NH)N(R 10 )(R 11 ), -S(=O)(=NH)C(R 10 )(R 11 ), -S(=O)(=NR 10 )(R 11 ), -CH2C(O)N(R 10 )(R 11 ), -CH2N(R 10 )C(O)R 11 , -CH2SO2R 10 , or -CH2SO2N(R 10 )(R 11 ) and;

[0091] R 10 and R 11 are hydrogen, C, respectively 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Haloalkyl, C 1-6Alkoxy, (C 1-6 Alkoxy)C 1-6 Alkyl, hydroxy C 1-6 Alkyl, C 3-10 Cycloalkyl, -(CH2) n -C 3-6 Cycloalkyl, -NH-C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -(CH2) n -C 2-9 Heterocycloalkyl, C 6-10 Aril, -(CH2) n -C 6-10 Aril, C 1-9 Heteroaryl, and -(CH2) n -C 1-9 Selected from heteroaryls;

[0092] Or optionally R 10 and R 11 are connected to each other C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 5-12 Forming a spiroheterocycloalkyl group,

[0093] Here, R 10 and R 11 C formed by connecting to each other 3-6 Cycloalkyl, C 2-9 Heterocycle Kill, or C 5-12 Spiroheterocycloalkyls are each

[0094] Hydrogen, Halogen, Oxo, Cyano, Hydroxy, C 1-6 Alkyl, hydroxy C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Substituted or unsubstituted with 1 to 3 substituents each independently selected from heteroaryls;

[0095] All atoms represent a single or double bond that satisfies the valence required for bonding.

[0096] In one embodiment, the compound may be a compound of Formula 1-1 below, or an optical isomer, diastereomer, solvate, hydrate, or a pharmaceutically acceptable salt thereof.

[0097] [Chemical Formula 1-1]

[0098]

[0099] In the above chemical formula 1-1, the definition of the substituent is the same as that described in chemical formula 1.

[0100] In one implementation example,

[0101] X 1 is CH, N, O, S, N(C 1-6 alkyl), N(C 1-6 haloalkyl), or N(C 3-10 cycloalkyl) and;

[0102] X 2 is CH and;

[0103] X 3 is O, S, N, N(C 1-6 alkyl), or CH and;

[0104] X 4 is C and;

[0105] X 5 is N or CH and;

[0106] X 6 is N or CH and;

[0107] X 7 is C and;

[0108] n is 1 to 3.

[0109] In one embodiment, the compound may be any one of the following chemical formulas 1a to 1g, or an optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof.

[0110] [Chemical Formula 1a]

[0111]

[0112] [Chemical Formula 1b]

[0113]

[0114] [Chemical Formula 1c]

[0115]

[0116] [Chemical Formula 1d]

[0117]

[0118] [Chemical Formula 1e]

[0119]

[0120] [Chemical Formula 1f]

[0121]

[0122] [Chemical formula 1g]

[0123]

[0124] In the above chemical formulas 1a to 1g,

[0125] R 4c is hydrogen, halogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or C 1-6 It is a haloalkyl;

[0126] L 1 , L 2 , R 1 , and R 3 The definition of is the same as in claim 1.

[0127] In one implementation example,

[0128] L 1 is a bond or -O- and;

[0129] R 1 C 3-10 Cycloalkenyl, C 6-10 Aryl, or C 1-9 It is heteroaryl, and

[0130] Here, R 1 Silver, hydrogen, halogen, cyano, hydroxy, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, and C 1-6 It may be substituted or unsubstituted with 1 to 3 substituents independently selected from each of the haloalkoxy.

[0131] In one implementation example,

[0132] -L 1 -R 1 silver

[0133] , , , , , and It is one of the selected from among;

[0134] Here, R 8a are hydrogen, halogen, and C, respectively. 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 Cycloalkyl, C 1-3 Alkoxy, or C 1-3 It could be a haloalkoxy.

[0135] In one implementation example,

[0136] L 2 is a bond, C 1-3 Alkylene, or C 1-3 C substituted with alkyl 1-3 It is an alkylene;

[0137] R 3 C is a straight-chain or branched type 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, Monocyclic C 1-9 Heteroaryl, or cyclic C 4-14 It is heteroaryl, and

[0138] Here, R 3 -OR10c , -N(R 10c )(R 10d ), halogen, C 1-6 Alkyl, C 2-9 Heterocycloalkyl, hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), and C 1-3 Alkoxy(C 2-9 Substituted or unsubstituted with 1 to 3 substituents each independently selected from heterocycloalkyl;

[0139] R 10c and R 10d is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, Hydroxy C 1-6 Alkyl, (C 1-3 Alkoxy)C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Each is independently selected from heteroaryls;

[0140] Or optionally R 10c and R 10d are connected to each other C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 5-12 Forming a spiroheterocycloalkyl group,

[0141] Here, R 10c and R 10d C formed by connecting to each other 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 5-12 Spiroheterocycloalkyls are each

[0142] Halogen, Cyano, Hydroxy, Hydroxy C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6Alkoxy, and C 1-6 It may be substituted or unsubstituted with 1 to 3 substituents independently selected from each of the haloalkoxy.

[0143] In one implementation example,

[0144] R 10c is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, Hydroxy C 1-6 Alkyl, (C 1-3 Alkoxy)C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Each is independently selected from heteroaryls;

[0145] R 10d is hydrogen, C 1-6 Alkyl, and C 1-6 They may be independently selected from haloalkyls.

[0146] In one implementation example,

[0147] R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aryl, Monocyclic C 1-9 Heteroaryl, and cyclic C 4-14 Selected from heteroaryls,

[0148] Here, R 3 Silver halogen, oxo, cyano, hydroxy, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6Haloalkyl, hydroxy C 1-6 Alkyl, amino group, -NH(C 1-6 alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -NH(hydroxy C 1-6 alkyl), -N(C 1-6 Alkyl)(hydroxy C 1-6 alkyl), -NH(C 1-6 alkoxy), -NH(C 1-6 Alkoxy C 1-6 alkyl), -N(C 1-6 Alkyl)(C 1-6 Alkoxy C 1-6 alkyl), -O-(C 1-6 alkyl), -O-(hydroxy C 1-6 alkyl), -O-(C 1-6 Alkoxy C 1-6 alkyl), hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), and C 1-3 Alkoxy(C 2-9 Heterocycloalkyl), C 3-10 Cycloalkyl, -CH2-C 3-6 Cycloalkyl, -NH-C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aril, -CH2-C 6-10 Aril, C 1-9 Heteroaryl, -CH2-C 1-9 Heteroaryl, -OR 10a (e.g., methoxy(-OCH3), ethoxy(-OC2H5)), -SR 10a (e.g., mercapto(-SH)), -SF5(perfluorosulfonyl), -N(R 10a )(R 10b ) (e.g., dimethylamine(-N(CH3)2)), diethylamine(-N(C2H5)2)), -C(O)OR 10a (e.g., -COOCH3, -COOC2H5), -OC(O)N(R 10a )(R 10b ) (e.g., -OC(O)N(CH3)2), -N(R10a )C(O)N(R 10a )(R 10b ) (e.g., (-N(CH3)C(O)N(CH3)--2), -C(O)N(R 10a )(R 10b ) (e.g., -CONH2, -CON(CH3)2), and -SO2R 10a It may be substituted or unsubstituted with 1 to 3 substituents independently selected from (e.g., -SO2CH3), -SO2C2H5).

[0149] In one implementation example,

[0150] L 2 is a bond, C 1-3 Alkylene, or C 1-3 C substituted with alkyl 1-3 It is an alkylene;

[0151] R 3 silver straight chain C 1-6 Alkyl, branched C 3-6 Alkyl, pyridine, pyrimidine, pyrazine, pyrazole, pyridazine, pyrrole, imidazole, triazine, thiazole, oxazole, isoxazole, or indazole, and

[0152] Here, R 3 Silver is a halogen, C 1-6 Alkyl, amino group, -NH(C 1-6 alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -NH(hydroxy C 1-6 alkyl), -NH(cycloC 1-6 alkyl), -N(C 1-6 Alkyl)(hydroxy C 1-6 alkyl), -NH(C 1-6 alkoxy), -NH(C 1-6 Alkoxy C 1-6 alkyl), -N(C 1-6 Alkyl)(C 1-6 Alkoxy C 1-6 alkyl), -O-(C 1-6 alkyl), -O-(hydroxy C 1-6 alkyl), -O-(C 1-6 Alkoxy C 1-6 alkyl), C 2-9Heterocycloalkyl, hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), C 1-3 Alkoxy(C 2-9 Heterocycloalkyl), and C 5-12 It may be substituted or unsubstituted with 1 to 3 substituents independently selected from spiroheterocycloalkyl.

[0153] In one implementation example,

[0154] -L 2 -R 3 silver , , , , , , , , , , , and It is one of the selected from among;

[0155] Here, R 12 Silver, hydrogen, fluorine, chlorine, bromine, iodine, , , , , , , , , , , , , , , , , , , , , and It is one of the selected from among;

[0156] R 13 Silver is hydrogen, halogen, or C 1-3 It may be an alkyl.

[0157] In one implementation example,

[0158] X 1 CH, N, N(methyl), N(ethyl), N(propyl), N(butyl), N(cyclopropyl), N(cyclobutyl), O, S, or N(C 1-4 haloalkyl) and;

[0159] X 2 is CH and;

[0160] X 3 is O, S, N, or CH;

[0161] X 4 and X 7 is C and;

[0162] X 5 and X 6 is N or CH and;

[0163] X 8 is N or CH and;

[0164] X 9 is N or CH and;

[0165] L 1 is a bond or -O- and;

[0166] L 2 is a bond, methylene, or C 1-3 It is an alkyl-substituted methylene;

[0167] R 1 is cyclohexene, phenyl, or pyridine, and

[0168] Here, R 1 Silver is a halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, and C 3-6 Substituted or unsubstituted with 1 to 3 substituents each independently selected from cycloalkyl;

[0169] R 2 is hydrogen;

[0170] R 3 silver straight chain C 1-3Alkyl, branched C 3-6 It is an alkyl, pyridine, pyrimidine, pyrazine, pyrazol, or pyridazine, and

[0171] Here, R 3 Silver is a halogen, C 1-3 Alkyl, amino group, -NH(C 1-3 alkyl), -N(C 1-3 Alkyl)(C 1-3 alkyl), -N(C 1-3 Alkyl)(hydroxy C 1-3 alkyl), -NH(hydroxy C 1-3 Alkyl), -NH-cycloC 1-6 Alkyl, -NH(C 1-3 alkoxy), -NH(C 1-3 Alkoxy C 1-3 alkyl), -N(C 1-3 Alkyl)(C 1-3 Alkoxy C 1-3 alkyl), -O-(C 1-3 alkyl), -O-(hydroxy C 1-3 alkyl), -O-(C 1-3 Alkoxy C 1-3 Alkyl), azetidineyl, pyrrolidineyl, morpholineyl, piperidineyl, piperazineyl, hydroxyazetidineyl, C 1-3 Alkoxiazetidine yl, hydroxypyrrolidine yl, C 1-3 It may be substituted or unsubstituted with 1 to 3 substituents independently selected from alkoxypyrrolidinyl, hydroxypiperidinyl, hydroxymorpholineyl, hydroxypiperazineyl, indazole, and oxazaspiro[3.3]heptanyl.

[0172] In one implementation example, R 3 is pyridine, pyrimidine, pyrazine, pyrazole (e.g., 1-methylpyrazole), or pyridazine, and

[0173] Here, R 3 Silver is a halogen, C 1-3 Alkyl, amino group, -NH(C 1-3 alkyl), -N(C 1-3 Alkyl)(C 1-3 alkyl), -N(C 1-3 Alkyl)(hydroxy C 1-3 alkyl)(e.g. ), -NH(hydroxy C 1-3 alkyl), -NH(cycloC 1-6 alkyl), -NH(C 1-3 alkoxy), -NH(C 1-3 Alkoxy C 1-3 alkyl)(e.g. ), -N(C 1-3 Alkyl)(C 1-3 Alkoxy C 1-3 alkyl)(e.g. ), -O-(C 1-3 alkyl)(e.g. ), -O-(hydroxy C 1-3 alkyl)(e.g. ), -O-(C 1-3 Alkoxy C 1-3 alkyl)(e.g. , -OCH2CH2OCH3), azetidine yl, pyrrolidine yl, morpholine yl, piperidine yl, piperazine yl, hydroxyazetidine yl, C 1-3 Alkoxiazetidine yl, hydroxypyrrolidine yl, C 1-3 Alkoxypyrrolidine yl, hydroxypiperidine yl, hydroxymorpholine yl, hydroxypiperazine yl, indazole, and oxazaspiro[3.3]heptan yl ( It may be substituted or unsubstituted with 1 to 3 substituents independently selected from each of the ).

[0174] In one implementation example,

[0175] The above compound may be any one of the compounds selected from the group consisting of 1) to 85) below, or an optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof:

[0176] 1) 4-(9-methyl-6-phenyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0177] 2) 4-(6-(4-(fluorophenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0178] 3) 4-(6-(4-(chlorophenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0179] 4) 4-(6-(4-(difluoromethyl)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0180] 5) 4-(6-(4-(cyclopropylphenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0181] 6) 4-(6-(4-(tert-butyl)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0182] 7) 4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0183] 8) 4-(6-(4,4-dimethylcyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0184] 9) 5-(9-methyl-6-(4-(trifluoromethyl)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0185] 10) 4-(9-methyl-6-(4-(trifluoromethyl)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0186] 11) 4-(6-(4-(chlorodifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2 (methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0187] 12) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0188] 13) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyridine-4-yl)methyl)pyridine-2(1H)-one;

[0189] 14) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((4-(methylamino)pyrimidine-2-yl)methyl)pyridine-2(1H)-one;

[0190] 15) 4-(6-(2-fluoro-4-(trifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0191] 16) 4-(6-(3-chloro-4-(trifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0192] 17) 4-(9-methyl-6-(2-methyl-4-(trifluoromethyl)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0193] 18) 1-((2-(dimethylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0194] 19) 1-((2-aminopyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0195] 20) 1-((2-(isopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0196] 21) 4-(6-(4-(chlorodifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(isopropylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0197] 22) 1-((2-(cyclopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0198] 23) 1-((2-(cyclobutylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0199] 24) 1-((2-(cyclopentylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0200] 25) 1-((2-(cyclopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0201] 26) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0202] 27) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0203] 28) 4-(6-(4,4-dimethylcyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(isopropylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0204] 29) 4-(6-(4,4-dimethylcyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0205] 30) 1-((2-((2-hydroxyethyl)(methyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0206] 31) 1-((2-((2-methoxyethyl)(methyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0207] 32) 4-(6-(4-(chlorodifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0208] 33) 1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0209] 34) 1-((2-(3-hydroxyazetidine-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0210] 35) 1-((2-(3-methoxyazetidine-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0211] 36) (S)-1-((2-(3-hydroxypyrrolidin-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0212] 37) 1-((2-(3-methoxypyrrolidin-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0213] 38) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-morpholinopyrimidine-4-yl)methyl)pyrimidine-2(1H)-one;

[0214] 39) 1-((2-(2-oxa-6-azaspiro[3,3]heptane-6-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0215] 40) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one;

[0216] 41) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridazine-3-ylmethyl)pyridine-2(1H)-one;

[0217] 42) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(1-(pyridine-2-yl)ethyl)pyridine-2(1H)-one;

[0218] 43) 4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one;

[0219] 44) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridine-3-ylmethyl)pyridine-2(1H)-one;

[0220] 45) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridine-4-ylmethyl)pyridine-2(1H)-one;

[0221] 46) 1-((1-methyl-1H-pyrazole-3-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0222] 47) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((6-(methylamino)pyridine-2-yl)methyl)pyridine-2(1H)-one;

[0223] 48) 4-(1-methyl-4-(4-(trifluoromethoxy)phenyl)-1H-imidazo[4,5-c]pyridine-6-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0224] 49) 4-(4-(2-fluoro-4-(trifluoromethoxy)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-6-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0225] 50) 1-((2-(2-methoxyethyl)amino)-pyrimidine-4-yl)methyl)-4-(1-methyl-4-(4-(trifluoromethoxy)phenyl)-1H-imidazo[4,5-c]pyridine-6-yl)pyridine-2(1H)-one;

[0226] 51) 1-((2-(isopropylamino)-pyrimidine-4-yl)methyl)-4-(1-methyl-4-(4-(trifluoromethoxy)phenyl)-1H-imidazo[4,5-c]pyridine-6-yl)pyridine-2(1H)-one;

[0227] 52) 4-(3-methyl-7-(4-(trifluoromethoxy)phenyl)-3H-imidazo[4,5-b]pyridine-5-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0228] 53) 4-(9-cyclopropyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0229] 54) 4-(9-cyclopropyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((1-methyl-1H-pyrazole-3-yl)methyl)pyridine-2(1H)-one;

[0230] 55) 4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0231] 56) 1-((2-(2-methoxyethyl)amino)-pyrimidine-4-yl)methyl)-4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)pyridine-2(1H)-one;

[0232] 57) 1-((2-(isopropylamino)pyrimidine-4-yl)methyl)-4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)pyridine-2(1H)-one;

[0233] 58) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)pyridine-2(1H)-one;

[0234] 59) 4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one;

[0235] 60) 1-((2-(methylamino)pyrimidine-4-yl)methyl)-4-(4-(4-(trifluoromethoxy)phenyl)thieno[3,2-d]pyrimidine-2-yl)pyridine-2(1H)-one;

[0236] 61) 1-((2-(methylamino)pyrimidine-4-yl)methyl)-4-(4-(4-(trifluoromethoxy)phenyl)furo[3,2-d]pyrimidine-2-yl)pyridine-2(1H)-one;

[0237] 62) 1-((2-(methylamino)pyrimidine-4-yl)methyl)-4-(7-(4-(trifluoromethoxy)phenyl)thiazolo[5,4-d]pyrimidine-5-yl)pyridine-2(1H)-one;

[0238] 63) 1-((2-methoxypyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0239] 64) 1-((2-(2-methoxyethoxy)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0240] 65) 1-((2-(2-hydroxyethoxy)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0241] 66) 1-((2-chloropyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one;

[0242] 67) 4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0243] 68) 4-(6-(4-chlorophenoxy)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0244] 69) 4-(9-methyl-6-(p-tolyloxy)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0245] 70) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)pyridine-2(1H)-one;

[0246] 71) 4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one;

[0247] 72) 1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)pyridine-2(1H)-one;

[0248] 73) 4-(9-cyclopropyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0249] 74) 1-((2-(cyclopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)pyridine-2(1H)-one;

[0250] 75) 4-(7-methyl-4-(4-(trifluoromethyl)phenoxy)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0251] 76) 4-(9-methyl-6-(6-(trifluoromethoxy)pyridine-3-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0252] 77) 1-((1H-indazole-7-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one hydrochloride;

[0253] 78) 4-((4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-2-oxopyridine-1(2H)-yl)methyl)pyrimidine-2-carboxaamide;

[0254] 79) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(oxazole-2-ylmethyl)pyridine-2(1H)-one;

[0255] 80) 4-(6-(cyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0256] 81) (R)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0257] 82) (S)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0258] 83) 4-(6-(cyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one;

[0259] 84) 4-(6-(4,4-difluorocyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; and

[0260] 85) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methyleneamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one.

[0261]

[0262] Pharmaceutical composition, treatment method, use, and kit

[0263] Another aspect of the present invention provides a pharmaceutical composition for treating or preventing a related disease caused by transcriptional enhancer associate domain (TEAD) activation, comprising as an active ingredient a compound of Formula 1, or an optical isomer, diastereomer, solvate, hydrate, or a pharmaceutically acceptable salt thereof.

[0264] In one embodiment, the composition may exhibit activity that inhibits the binding of Yes associated protein (YAP) to transcriptional enhancer associate domain (TEAD).

[0265] In one embodiment, the composition can treat cancer or tumors by exhibiting inhibitory activity against YAP-TEAD binding.

[0266] For example, the composition may contain the compound, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof in a therapeutically effective amount.

[0267] For example, a physician with ordinary knowledge in the relevant technical field can easily determine and prescribe an effective required dose of the pharmaceutical composition. For example, the pharmaceutical composition may contain the compound in an amount of 0.0001 mg to 10 g, but is not limited thereto.

[0268] For example, the above pharmaceutical composition may further include pharmaceutically acceptable additives in addition to the active ingredient. The additives may be, for example, diluents, disintegrants, binders, lubricants, surfactants, suspending agents, or emulsifiers, but are not limited thereto.

[0269] For example, the above pharmaceutical composition can be formulated according to conventional methods and can be prepared in various oral administration forms such as tablets, pills, powders, capsules, syrups, emulsions, microemulsions, or parenteral administration forms such as intramuscular, intravenous, or subcutaneous administration.

[0270] Another aspect of the present invention provides a treatment method for administering the compound, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same as an active ingredient, to a subject suffering from a disorder of the Hippo signaling pathway, specifically a related disease caused by TEAD activation.

[0271] For example, the dosage, frequency, or method of administration of a compound or pharmaceutical composition may vary depending on the subject being treated, the severity of the disease or condition, the rate of administration, and the judgment of the prescribing physician. Additionally, the physician may start at a level lower than that required to achieve the target therapeutic effect and gradually increase the dose of the compound or pharmaceutical composition of the present invention administered to the subject until the intended effect is achieved.

[0272] Another aspect of the present invention provides a kit comprising the compound, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same as an active ingredient.

[0273] For example, the above compounds, compositions, and kits may be administered individually or sequentially, either alone or simultaneously with at least one other therapeutic agent.

[0274] [Chemical Formula 1]

[0275]

[0276] [Chemical Formula 1-1]

[0277]

[0278]

[0279] Hereinafter, a method for preparing the compound of Formula 1 above will be explained in detail by way of example. The compound of Formula 1 according to the present invention can be prepared according to the synthesis method shown in Reaction Scheme 1.

[0280] [Reaction Equation 1]

[0281]

[0282] [Step-1]

[0283] 1,4-dioxane and water (10:1 v / v) are added to bicyclyl A (1 equivalent, reference equivalent), followed by the addition of a boronic acid derivative (1.2 equivalents) and potassium phosphate (2.0 equivalents), and then (1,1'-bis(diphenylphosphine)ferrocein)dichloropalladium(II) (0.1 equivalents). The reaction mixture is heated and reacted. After confirming that the reaction is complete, it is cooled to room temperature, water is added, and the mixture is extracted with ethyl acetate. The organic layer is dried with anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer is concentrated under reduced pressure. The resulting residue is purified by MPLC to obtain the target compound B.

[0284] [Step-2]

[0285] B (1 equivalent, reference equivalent) prepared in [Step-1] above is dissolved in 1,4-dioxane and water (5:1 v / v), a boronic acid derivative (2.0 equivalents) and potassium carbonate (3.0 equivalents) are added, and then (1,1'-bis(diphenylphosphine)ferrocein)dichloropalladium(II) (0.2 equivalents) is added. The reaction mixture is heated and stirred overnight. After the reaction is complete, it is cooled to room temperature, water is added, and then extracted with ethyl acetate. The organic layer is dried with anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer is concentrated under reduced pressure. The resulting residue is purified by MPLC to obtain the target compound C.

[0286] [Step-3]

[0287] C (1 equivalent, reference equivalent) prepared in [Step-2] above is dissolved in N,N-dimethylformimide, lithium chloride (5.0 equivalents) and p-toluenesulfonic acid (5.0 equivalents) are added, the reaction mixture is heated, and stirred overnight. After the reaction is complete, it is cooled to room temperature and water is added. Then, the organic layer is dried with anhydrous sodium sulfate using a solution of dichloromethane and methanol mixed in a 3:1 ratio, filtered under reduced pressure, and the organic layer is concentrated under reduced pressure. Dichloromethane is added to the obtained residue, stirred at room temperature, and filtered to obtain the target compound D.

[0288] [Step-4]

[0289] D (1 equivalent, reference equivalent) prepared in [Step-3] above is dissolved in N,N-dimethylformimide, and the corresponding R3-L2-Halo substituent (2.0 equivalents) and potassium carbonate (2.0 equivalents) are added, after which the reaction mixture is heated and stirred. When the reaction is complete, water is added and the mixture is extracted with dichloromethane, and the organic layer is dried with anhydrous magnesium sulfate. The mixture is filtered under reduced pressure, the filtered organic layer is concentrated under reduced pressure, acetone is added to the resulting residue, and the solid obtained by stirring at room temperature is filtered to obtain the target compound E.

[0290] [Step-5]

[0291] Optionally, E (1 equivalent, reference equivalent) prepared in [Step-4] above is added to methanol, and a nucleophilic substitution substituent (8.0 equivalents, e.g., methylamine) is added. The reaction mixture is reacted under heating, and after the reaction is complete, the reaction mixture is concentrated. Methanol is added to the resulting residue and stirred at room temperature for 1 hour, then filtered under reduced pressure to obtain the target compound F.

[0292]

[0293] X in the above reaction equation 1 1 To X 9 , L 1 , L 2 , R 1 to R 3 The definitions of each are as defined in Chemical Formula 1 above, but are not limited to these and may be modified within the scope understandable to those skilled in the art.

[0294] The dotted line indicates a single bond or a double bond.

[0295]

[0296] [Example]

[0297] Example 1: 4-(9-methyl-6-phenyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one

[0298]

[0299] [Step-1] Preparation of 2-chloro-9-methyl-6-phenyl-9H-purine

[0300]

[0301] 2,6-dichloro-9-methyl-9H-purine (500 mg, 2.46 mmol) was dissolved in 5 mL of 1,4-dioxane and 0.5 mL of water, and phenylboronic acid (360 mg, 2.95 mmol) and potassium phosphate (1.04 g, 4.92 mmol) were added, followed by the addition of (1,1'-bis(diphenylphosphine)ferrocein)dichloropalladium(II) (180 mg, 0.25 mmol). The reaction mixture was stirred overnight at 80°C. After confirming that the reaction was complete, the mixture was cooled to room temperature, 10 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure. The obtained residue was purified by MPLC (ethyl acetate:hexane = 2:8 (v / v)) to obtain 277 mg of the title compound (46% yield).

[0302] 1 H-NMR (300 MHz, DMSO-d6): δ8.88-8.67 (m, 2H), 8.67 (s, 1H), 7.61-7.58 (m, 3H), 3.84 (s, 3H).

[0303]

[0304] [Step-2] Preparation of 2-(2-methoxypyridine-4-yl)-9-methyl-6-phenyl-9H-purine

[0305]

[0306] The 2-chloro-9-methyl-6-phenyl-9H-purine (275 mg, 1.12 mmol) obtained in [Step-1] above was dissolved in 5 mL of 1,4-dioxane and 1 mL of water, and 2-methoxypyridine-4-voronic acid (343 mg, 2.24 mmol) and potassium carbonate (466 mg, 3.37 mmol) were added, followed by the addition of (1,1'-bis(diphenylphosphine)ferrocein)dichloropalladium(II) (183 mg, 0.22 mmol). The reaction mixture was stirred overnight at 80°C. After the reaction was complete, it was cooled to room temperature, 2 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure. 1.4 mL of dichloromethane and 0.5 mL of hexane were added to the obtained residue and stirred at room temperature for 1 hour. The reaction mixture was filtered under reduced pressure to obtain 261 mg of the title compound (73% yield).

[0307] 1 H-NMR (300 MHz, DMSO-d6): δ9.08-9.04 (m, 2H), 8.71 (s, 1H), 8.36-8.34 (m, 1H), 8.05-8.03 (m, 1H), 7.84-7.83 (m, 1H), 7.63-7.60 (m, 3H), 3.96-3.94 (m, 6H).

[0308]

[0309] [Step-3] Preparation of 4-(9-methyl-6-phenyl-9H-purine-2-yl)pyridine-2(1H)-one

[0310]

[0311] In [Step-2] above, 2-(2-methoxypyridine-4-yl)-9-methyl-6-phenyl-9H-purine (260 mg, 0.82 mmol) was dissolved in 100 mL of N,N-dimethylformimide, and lithium chloride (173 mg, 4.09 mmol) and p-toluenesulfonic acid monohydrate (779 mg, 4.09 mmol) were added. The reaction mixture was stirred overnight at 100°C. After the reaction was complete, 5 mL of water was added, and the mixture was extracted three times with a solution of dichloromethane and methanol mixed in a 3:1 ratio. The organic layer was dried with anhydrous magnesium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure. 5 mL of dichloromethane was added to the resulting residue, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered under reduced pressure to obtain 208 mg of the title compound (83% yield).

[0312] 1 H-NMR (300 MHz, DMSO-d6): δ9.08-9.04 (m, 2H), 8.71 (s, 1H), 7.63-7.60 (m, 3H), 7.52-7.49 (m, 2H), 7.29-7.26 (m, 1H), 3.93 (s, 3H).

[0313]

[0314] [Step-4] Preparation of 1-((2-chloropyrimidine-4-yl)methyl)-4-(9-methyl-6-phenyl-9H-purine-2-yl)pyridine-2(1H)-one

[0315]

[0316] 4-(9-methyl-6-phenyl-9H-purine-2-yl)pyridine-2(1H)-one (205 mg, 0.67 mmol) obtained in [Step-3] above was dissolved in 2 mL of N,N-dimethylformimide, and 2-chloro-4-(chloromethyl)pyrimidine (220 mg, 1.35 mmol) and potassium carbonate (186 mg, 1.35 mmol) were added. The reaction mixture was stirred overnight at 50°C. After the reaction was complete, water was added and extracted three times with dichloromethane. The organic layer was dried with anhydrous magnesium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure. 2 mL of acetone was added to the resulting residue and stirred at room temperature for 1 hour. The reaction mixture was filtered under reduced pressure to obtain 84 mg of the title compound (29% yield).

[0317] 1 H-NMR (300 MHz, DMSO-d6): δ9.08-9.04 (m, 2H), 8.76-8.73 (m, 2H), 7.99 (d,J= 0.01 Hz, 1H), 7.65-7.59 (m, 4H), 7.44-7.41 (m, 2H), 5.32 (s, 2H), 3.93 (s, 3H).

[0318]

[0319] [Step-5] Preparation of 4-(9-methyl-6-phenyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one

[0320]

[0321] 1-((2-chloropyrimidine-4-yl)methyl)-4-(9-methyl-6-phenyl-9H-purine-2-yl)pyridine-2(1H)-one (84 mg, 0.19 mmol) obtained in [Step-4] above was dissolved in 2 mL of methanol, and 2 M methylamine tetrahydrofuran solution (0.8 mL, 1.52 mmol) was added. The reaction mixture was stirred at 50°C for 5 hours. After the reaction was complete, the reaction mixture was concentrated. 1 mL of methanol was added to the resulting residue, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered under reduced pressure to obtain 32 mg of the title compound (39% yield).

[0322] 1 H-NMR (300 MHz, DMSO-d6): δ9.08-9.04 (m, 2H), 8.76 (s, 1H), 8.20 (s, 1H), 7.94-7.91 (m, 1H), 7.65-7.59 (m, 4H), 7.40-7.38 (m, 1H), 7.06 (s,1H), 6.30-6.29 (m, 1H) 5.07 (s, 2H), 3.95 (s, 3H), 2.74 (s, 3H).

[0323] MS (ESI + , m / z): 425.4 [M+H] +

[0324] The compounds of Examples 2 to 66 shown in Table 1 below were each prepared using the same or similar method as the method of Example 1 above.

[0325] [Table 1]

[0326]

[0327]

[0328]

[0329]

[0330]

[0331]

[0332]

[0333]

[0334]

[0335]

[0336]

[0337]

[0338]

[0339]

[0340]

[0341]

[0342]

[0343]

[0344]

[0345]

[0346]

[0347] Example 67: 4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one

[0348]

[0349] [Step-1] Preparation of 2-chloro-9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine

[0350]

[0351] 2,6-dichloro-9-methyl-9H-purine (2.0 g, 9.7 mmol) was dissolved in 40 mL of N,N-dimethylformimide, and 4-(trifluoromethyl)phenol (1.8 g, 10.6 mmol) and potassium carbonate (1.04 g, 4.9 mmol) were added. The reaction mixture was stirred at 60°C for 2.5 hours. After confirming that the reaction was complete, it was cooled to room temperature, 10 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure. The resulting residue was purified by MPLC (ethyl acetate:hexane = 1:1 (v / v)) to obtain 2.6 g of the title compound (82% yield).

[0352] 1 H-NMR (300 MHz, DMSO-d6): δ8.53 (s, 1H), 7.90 (d,J=8.4 Hz, 2H), 7.59 (d,J=8.4 Hz, 2H), 3.84 (s, 3H).

[0353]

[0354] [Step-2] Preparation of 4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one

[0355]

[0356] 9 mg of the title compound (19% yield) was obtained by repeating the process from [Step-2] to [Step-5] of Example 1, except that in [Step-3] of Example 1, stirring was performed at 90°C instead of 120°C, and in [Step-5], a 2M methylamine tetrahydrofuran solution (0.2 mL, 0.5 mmol) was used and stirring was performed at 25°C instead of 50°C.

[0357] 1H-NMR (300 MHz, DMSO-d6): δ8.61 (s, 1H), 8.18 (d,J= 5.7 Hz, 1H), 7.93-7.83 (m, 3H), 7.65 (d,J= 8.1 Hz, 2H), 7.11-6.97 (m, 3H), 6.25-6.23 (m, 1H), 4.99 (s, 2H), 3.95 (s, 3H), 2.72 (d,J= 4.5 Hz, 3H).

[0358] MS (ESI + , m / z): 509.5 [M+H] +

[0359]

[0360] The compounds of Examples 68 to 85 shown in Table 2 below were each prepared using the same or similar method as the method of Example 67 above.

[0361] [Table 2]

[0362]

[0363]

[0364]

[0365]

[0366]

[0367]

[0368]

[0369] [Experimental Example]

[0370] Experimental Example 1: TEAD Reporter Activity Inhibition Test

[0371] The transcriptional repressive ability of TEAD on target genes with respect to the above synthetic compounds was measured. This evaluation method measures the transcriptional activity of TEAD by measuring the luciferase luminescence expressed when TEAD binds to a target gene and activates transcription, using the MCF7 cell line (BPS Bioscience, Inc., USA), in which the firefly luciferase reporter gene was introduced into GTIIC (5'-ACATTCCA-3'), a specific binding structure of TEAD. The cell line was cultured in MEM medium supplemented with 10% FBS, 1% Penicillin / Streptomycin, 1% non-essential amino acids, 10 μg / ml insulin, and 400 μg / ml Geneticin; Geneticin was excluded during the TEAD reporter activity inhibition test. 4 x 10 4 The compounds were dispensed into white 96-well plates at a dose of 100 μl per well and incubated for 6 hours. 50 μl of the experimental compound, diluted to 3X concentration, was mixed into each well. After 24 hours of incubation, the luciferase signal was measured by luminescence using the ONE-Glo luciferase assay system (Promega, E6120) according to the manufacturer's protocol. The 50% inhibition value (IC10) for TEAD transcriptional activity was calculated. 50 ) was calculated using GraphPad Prism 9.

[0372] IC 50 If the value is less than 50 nM, it is represented as +++; if it is 50 or more and less than 100 nM, it is represented as ++; and if it is 100 nM or more, it is represented as +.

[0373] [Table 3]

[0374]

[0375]

[0376] The present invention has been described above with reference to specific embodiments. Those skilled in the art will understand that the present invention may be embodied in modified forms without departing from the essential characteristics of the invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the invention is defined by the claims, not by the foregoing description, and all variations within the scope of the claims should be interpreted as being included in the invention.

Claims

1. Compounds of Formula 1 below, or optical isomers, diastereomers, solvates, hydrates, or pharmaceutically acceptable salts thereof: [Chemical Formula 1] In the above chemical formula 1, X 1 and X 3 are independently O, S, C, N, C(R 4 ), C(R 4a )(R 4b ), and N(R 4a Selected from ); X 2 , X 5 , and X 6 C, N, and C(R) are each independently 5 ), C(R 5a )(R 5b ), and N(R 5a Selected from, X 4 , X 7 , X 8 , and X 9 C, N, and C(R) are independently C, N, and C(R 6 Selected from ); L 1 Silver bond, -O-, -S-, -NH-, C 1-3 Alkylene, or C 2-6 It is alkenylene; L 2 is a bond, C 1-3 Alkylene, or 1 to 3 R 7 C that is replaced by 1-3 It is an alkylene; R 1 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aryl, and C 1-9 Selected from heteroaryls, Here, R 1 is R 8 Substituted or unsubstituted with 1 to 3 substituents independently selected from each; R 2 is hydrogen, halogen, or C 1-6 It is alkyl; R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aryl, monocyclic C 1-9 Heteroaryl, and bicyclic C 4-14 Selected from heteroaryls, Here, R 3 is R 9 Substituted or unsubstituted with 1 to 3 substituents independently selected from each; R 4 , R 4a , R 4b , R 5 , R 5a , R 5b , R 6 , and R 7 Each independently consists of hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 3-10 Halocycloalkyl, C 6-10 Aril, C 1-9 Heteroaryl, and C 2-9 Selected from heterocycloalkyl; R 8 and R 9 are hydrogen, halogen, oxo, cyano, hydroxy, and C, respectively. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, -(CH2) n -C 3-6 Cycloalkyl, -NH-C 3-6 Cycloalkyl, Hydroxy C 1-6 Alkyl, C 3-10 Cycloalkenyl, C 2-9 Heterocycloalkyl, -(CH2) n -C 2-9 Heterocycloalkyl, C 2-9 Heterocycloalkenyl, C 6-10 Aril, -(CH2) n -C 6-10 Aryl, monocyclic C 1-9 Heteroaryl, -(CH2) n -C 1-9 Heteroaryl, bicyclic C 4-14 Heteroaryl, hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), C 1-3 Alkoxy(C 2-9 Heterocycloalkyl), -OR 10 , -SR 10 , -SF5, , -N(R 10 )(R 11 ), -C(O)OR 10 , -OC(O)N(R 10 )(R 11 ), -N(R 10 )C(O)N(R 10 )(R 11 ), -N(R 10 )C(O)OR 10 , -N(R 10 )SO2R 10 , -C(O)R 10 , -S(O)R 10 , -OC(O)R 10 , -C(O)N(R 10 )(R 11 ), -C(O)C(O)N(R 10 )(R 11 ), -N(R 10 )C(O)R 10 , -SO2R 10 , -SO2N(R 10 )(R 11 ), -N=S(=O)(R 10 )(R 11 ), -S(=O)(=NH)N(R 10 )(R 11 ), -S(=O)(=NH)C(R 10 )(R 11 ), -S(=O)(=NR 10 )(R 11 ), -CH2C(O)N(R 10 )(R 11 ), -CH2N(R 10 )C(O)R 11 , -CH2SO2R 10 , 또는 -CH2SO2N(R 10 )(R 11 )이고; R 10 and R 11 are hydrogen, C, respectively 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, (C 1-6 Alkoxy)C 1-6 Alkyl, hydroxy C 1-6 Alkyl, C 3-10 Cycloalkyl, -(CH2) n -C 3-6 Cycloalkyl, -NH-C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, -(CH2) n -C 2-9 Heterocycloalkyl, C 6-10 Aril, -(CH2) n -C 6-10 Aril, C 1-9 Heteroaryl, and -(CH2) n -C 1-9 Selected from heteroaryls; Or optionally R 10 and R 11 are connected to each other C 3-6 Cycloalkyl C 2-9 Heterocycloalkyl, or C 5-12 Forming a spiroheterocycloalkyl; Here, R 10 and R 11 C formed by connecting to each other 3-6 Cycloalkyl, C 2-9 Heterocycle Kill, or C 5-12 Spiroheterocycloalkyls are each Hydrogen, Halogen, Oxo, Cyano, Hydroxy, C 1-6 Alkyl, hydroxy C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Substituted or unsubstituted with 1 to 3 substituents each independently selected from heteroaryls; n is 1 to 3 and; All atoms represent a single or double bond that satisfies the valence required for bonding.

2. In Claim 1, X 1 is CH, N, O, S, N(C 1-6 alkyl), N(C 1-6 haloalkyl), or N(C 3-10 cycloalkyl) and; X 2 is CH and; X 3 is O, S, N, N(C 1-6 alkyl), or CH and; X 4 is C and; X 5 is N or CH and; X 6 is N or CH and; X 7 is C and; X 8 is N or CH and; X 9 is a compound that is N or CH.

3. In Claim 1, The above compound is any one of the following chemical formulas 1a to 1g, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof: [Chemical Formula 1a] [Chemical Formula 1b] [Chemical Formula 1c] [Chemical Formula 1d] [Chemical Formula 1e] [Chemical Formula 1f] [Chemical formula 1g] In the above chemical formulas 1a to 1g, R 4c is hydrogen, halogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or C 1-6 It is a haloalkyl; L 1 , L 2 , R 1 , and R 3 The definition of is the same as in claim 1.

4. In Claim 1, L 1 is a bond or -O- and; R 1 C 3-10 Cycloalkenyl, C 6-10 Aryl, or C 1-9 It is heteroaryl, and Here, R 1 Silver, hydrogen, halogen, cyano, hydroxy, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, and C 1-6 A compound that is substituted or unsubstituted with 1 to 3 substituents each independently selected from haloalkoxy.

5. In Claim 1, -L 1 -R 1 silver , , , , , and It is one of the selected from among; Here, R 8a are hydrogen, halogen, and C, respectively. 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 Cycloalkyl, C 1-3 Alkoxy, or C 1-3 A compound that is a haloalkoxy.

6. In Claim 1, L 2 is a bond, C 1-3 Alkylene, or C 1-3 C substituted with alkyl 1-3 It is an alkylene; R 3 C is a straight-chain or branched type 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, Monocyclic C 1-9 Heteroaryl, or cyclic C 4-14 It is heteroaryl, and Here, R 3 -OR 10c , -N(R 10c )(R 10d ), halogen, C 1-6 Alkyl, C 2-9 Heterocycloalkyl, hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), and C 1-3 Alkoxy(C 2-9 Substituted or unsubstituted with 1 to 3 substituents each independently selected from heterocycloalkyl; R 10c and R 10d is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, Hydroxy C 1-6 Alkyl, (C 1-3 Alkoxy)C 1-3 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Each is independently selected from heteroaryls; Or optionally R 10c and R 10d are connected to each other C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 5-12 Forming a spiroheterocycloalkyl group, Here, R 10c and R 10d C formed by connecting to each other 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, or C 5-12 Spiroheterocycloalkyls are each Halogen, Cyano, Hydroxy, Hydroxy C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, and C 1-6 A compound that is substituted or unsubstituted with 1 to 3 substituents each independently selected from haloalkoxy.

7. In Claim 1, L 2 is a bond, C 1-3 Alkylene, or C 1-3 C substituted with alkyl 1-3 It is an alkylene; R 3 silver straight chain C 1-6 Alkyl, branched C 3-6 Alkyl, pyridine, pyrimidine, pyrazine, pyrazole, pyridazine, pyrrole, imidazole, triazine, thiazole, oxazole, isoxazole, or indazole, and Here, R 3 Silver is a halogen, C 1-6 Alkyl, amino group, -NH(C 1-6 alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -NH(hydroxy C 1-6 alkyl), -NH(cycloC 1-6 alkyl), -N(C 1-6 Alkyl)(hydroxy C 1-6 alkyl), -NH(C 1-6 alkoxy), -NH(C 1-6 Alkoxy C 1-6 alkyl), -N(C 1-6 Alkyl)(C 1-6 Alkoxy C 1-6 alkyl), -O-(C 1-6 alkyl), -O-(hydroxy C 1-6 alkyl), -O-(C 1-6 Alkoxy C 1-6 alkyl), C 2-9 Heterocycloalkyl, hydroxy(C 2-9 Heterocycloalkyl), hydroxy C 1-6 Alkyl(C 2-9 Heterocycloalkyl), C 1-3 Alkoxy(C 2-9 Heterocycloalkyl), and C 5-12 A compound that is substituted or unsubstituted with 1 to 3 substituents each independently selected from spiroheterocycloalkyl.

8. In Claim 1, -L 2 -R 3 silver , , , , , , , , , , , and It is one of the selected from among; Here, R 12 Silver, hydrogen, fluorine, chlorine, bromine, iodine, , , , , , , , , , , , , , , , , , , , , and It is one of the selected from among; R 13 Silver is hydrogen, halogen, or C 1-3 A compound that is an alkyl.

9. In Claim 1, X 1 CH, N, N(methyl), N(ethyl), N(propyl), N(butyl), N(cyclopropyl), N(cyclobutyl), O, S, or N(C 1-4 haloalkyl) and; X 2 is CH and; X 3 is O, S, N, or CH; X 4 and X 7 is C and; X 5 and X 6 is N or CH and; X 8 is N or CH and; X 9 is N or CH and; L 1 is a bond or -O- and; L 2 is a bond, methylene, or C 1-3 It is an alkyl-substituted methylene; R 1 is cyclohexene, phenyl, or pyridine, and Here, R 1 Silver is a halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, and C 3-6 Substituted or unsubstituted with 1 to 3 independently selected substituents from cycloalkyl; R 2 is hydrogen; R 3 silver straight chain C 1-3 Alkyl, branched C 3-6 It is an alkyl, pyridine, pyrimidine, pyrazine, pyrazol, or pyridazine, and Here, R 3 Silver is a halogen, C 1-3 Alkyl, amino group, -NH(C 1-3 alkyl), -N(C 1-3 Alkyl)(C 1-3 alkyl), -N(C 1-3 Alkyl)(hydroxy C 1-3 alkyl), -NH(hydroxy C 1-3 alkyl), -NH(cycloC 1-6 alkyl), -NH(C 1-3 alkoxy), -NH(C 1-3 Alkoxy C 1-3 alkyl), -N(C 1-3 Alkyl)(C 1-3 Alkoxy C 1-3 alkyl), -O-(C 1-3 alkyl), -O-(hydroxy C 1-3 alkyl), -O-(C 1-3 Alkoxy C 1-3 Alkyl), azetidineyl, pyrrolidineyl, morpholineyl, piperidineyl, piperazineyl, hydroxyazetidineyl, C 1-3 Alkoxiazetidine yl, hydroxypyrrolidine yl, C 1-3 A compound that is substituted or unsubstituted with 1 to 3 substituents independently selected from alkoxypyrrolidinyl, hydroxypiperidinyl, hydroxymorpholineyl, hydroxypiperazineyl, indazole, and oxazaspiro[3.3]heptanyl.

10. The compound of claim 1 selected from the group consisting of 1) to 85) below, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof: 1) 4-(9-methyl-6-phenyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 2) 4-(6-(4-(fluorophenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 3) 4-(6-(4-(chlorophenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 4) 4-(6-(4-(difluoromethyl)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 5) 4-(6-(4-(cyclopropylphenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 6) 4-(6-(4-(tert-butyl)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 7) 4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 8) 4-(6-(4,4-dimethylcyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 9) 5-(9-methyl-6-(4-(trifluoromethyl)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 10) 4-(9-methyl-6-(4-(trifluoromethyl)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 11) 4-(6-(4-(chlorodifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2 (methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 12) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 13) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyridine-4-yl)methyl)pyridine-2(1H)-one; 14) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((4-(methylamino)pyrimidine-2-yl)methyl)pyridine-2(1H)-one; 15) 4-(6-(2-fluoro-4-(trifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 16) 4-(6-(3-chloro-4-(trifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 17) 4-(9-methyl-6-(2-methyl-4-(trifluoromethyl)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 18) 1-((2-(dimethylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 19) 1-((2-aminopyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 20) 1-((2-(isopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 21) 4-(6-(4-(chlorodifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-(isopropylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 22) 1-((2-(cyclopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 23) 1-((2-(cyclobutylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 24) 1-((2-(cyclopentylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 25) 1-((2-(cyclopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)pyridine-2(1H)-one; 26) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 27) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)pyridine-2(1H)-one; 28) 4-(6-(4,4-dimethylcyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(isopropylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 29) 4-(6-(4,4-dimethylcyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 30) 1-((2-((2-hydroxyethyl)(methyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 31) 1-((2-((2-methoxyethyl)(methyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 32) 4-(6-(4-(chlorodifluoromethoxy)phenyl)-9-methyl-9H-purine-2-yl)-1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 33) 1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 34) 1-((2-(3-hydroxyazetidine-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 35) 1-((2-(3-methoxyazetidine-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 36) (S)-1-((2-(3-hydroxypyrrolidin-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 37) 1-((2-(3-methoxypyrrolidin-1-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 38) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-morpholinopyrimidine-4-yl)methyl)pyrimidine-2(1H)-one; 39) 1-((2-(2-oxa-6-azaspiro[3,3]heptane-6-yl)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 40) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one; 41) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridazine-3-ylmethyl)pyridine-2(1H)-one; 42) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(1-(pyridine-2-yl)ethyl)pyridine-2(1H)-one; 43) 4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one; 44) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridine-3-ylmethyl)pyridine-2(1H)-one; 45) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(pyridine-4-ylmethyl)pyridine-2(1H)-one; 46) 1-((1-methyl-1H-pyrazole-3-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 47) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((6-(methylamino)pyridine-2-yl)methyl)pyridine-2(1H)-one; 48) 4-(1-methyl-4-(4-(trifluoromethoxy)phenyl)-1H-imidazo[4,5-c]pyridine-6-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 49) 4-(4-(2-fluoro-4-(trifluoromethoxy)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-6-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 50) 1-((2-(2-methoxyethyl)amino)-pyrimidine-4-yl)methyl)-4-(1-methyl-4-(4-(trifluoromethoxy)phenyl)-1H-imidazo[4,5-c]pyridine-6-yl)pyridine-2(1H)-one; 51) 1-((2-(isopropylamino)-pyrimidine-4-yl)methyl)-4-(1-methyl-4-(4-(trifluoromethoxy)phenyl)-1H-imidazo[4,5-c]pyridine-6-yl)pyridine-2(1H)-one; 52) 4-(3-methyl-7-(4-(trifluoromethoxy)phenyl)-3H-imidazo[4,5-b]pyridine-5-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 53) 4-(9-cyclopropyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 54) 4-(9-cyclopropyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((1-methyl-1H-pyrazole-3-yl)methyl)pyridine-2(1H)-one; 55) 4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 56) 1-((2-(2-methoxyethyl)amino)-pyrimidine-4-yl)methyl)-4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)pyridine-2(1H)-one; 57) 1-((2-(isopropylamino)pyrimidine-4-yl)methyl)-4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)pyridine-2(1H)-one; 58) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)pyridine-2(1H)-one; 59) 4-(7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one; 60) 1-((2-(methylamino)pyrimidine-4-yl)methyl)-4-(4-(4-(trifluoromethoxy)phenyl)thieno[3,2-d]pyrimidine-2-yl)pyridine-2(1H)-one; 61) 1-((2-(methylamino)pyrimidine-4-yl)methyl)-4-(4-(4-(trifluoromethoxy)phenyl)furo[3,2-d]pyrimidine-2-yl)pyridine-2(1H)-one; 62) 1-((2-(methylamino)pyrimidine-4-yl)methyl)-4-(7-(4-(trifluoromethoxy)phenyl)thiazolo[5,4-d]pyrimidine-5-yl)pyridine-2(1H)-one; 63) 1-((2-methoxypyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 64) 1-((2-(2-methoxyethoxy)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 65) 1-((2-(2-hydroxyethoxy)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 66) 1-((2-chloropyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one; 67) 4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 68) 4-(6-(4-chlorophenoxy)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 69) 4-(9-methyl-6-(p-tolyloxy)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 70) 1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)pyridine-2(1H)-one; 71) 4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)-1-(pyridine-2-ylmethyl)pyridine-2(1H)-one; 72) 1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)pyridine-2(1H)-one; 73) 4-(9-cyclopropyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-((2-hydroxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 74) 1-((2-(cyclopropylamino)pyrimidine-4-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethyl)phenoxy)-9H-purine-2-yl)pyridine-2(1H)-one; 75) 4-(7-methyl-4-(4-(trifluoromethyl)phenoxy)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 76) 4-(9-methyl-6-(6-(trifluoromethoxy)pyridine-3-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 77) 1-((1H-indazole-7-yl)methyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)pyridine-2(1H)-one hydrochloride; 78) 4-((4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-2-oxopyridine-1(2H)-yl)methyl)pyrimidine-2-carboxaamide; 79) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-(oxazole-2-ylmethyl)pyridine-2(1H)-one; 80) 4-(6-(cyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 81) (R)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 82) (S)-4-(9-methyl-6-(4-(trifluoromethyl)cyclohex-1-en-1-yl)-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 83) 4-(6-(cyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-((2-methoxyethyl)amino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; 84) 4-(6-(4,4-difluorocyclohex-1-en-1-yl)-9-methyl-9H-purine-2-yl)-1-((2-(methylamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one; and 85) 4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-yl)-1-((2-(methyleneamino)pyrimidine-4-yl)methyl)pyridine-2(1H)-one.

11. A pharmaceutical composition for treating or preventing a related disease caused by transcriptional enhancer associate domain (TEAD) activation, comprising as an active ingredient the compound of Claim 1, or its optical isomer, diastereomer, solvate, hydrate, or pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of claim 11, wherein the composition exhibits activity that inhibits Yes associated protein (YAP)-transcriptional enhancer associate domain (TEAD) binding.

13. The pharmaceutical composition of claim 11 for treating cancer or tumors that can be treated by exhibiting inhibitory activity against YAP-TEAD binding.

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