Novel hetero-bicyclic compound for inhibiting YAP-TEAD interaction and pharmaceutical composition comprising same

Abstract

Provided are a compound selected from the group consisting of compounds of Formula 1, mirror isomers, non-mirror isomers, solvates and hydrates thereof, and pharmaceutically acceptable salts thereof, a preparation method and uses thereof.

Description

Technical Field

[0001] The present disclosure relates to a pharmaceutical composition comprising a heterobicyclic compound that inhibits Yes-associated protein (YAP)-transcription enhancer-associated domain (TEAD) binding, wherein the compounds according to the present disclosure can directly inhibit YAP-TEAD binding in the Hippo pathway that plays a key role in cancer development. Background Art

[0002] The Hippo signaling cascade is an important pathway for cancer generation 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 translocation of YAP / TAZ to the nucleus, where YAP / TAZ interacts with the transcription enhancer-associated domain (TEAD) transcription factor, co-activates the expression of target genes, and promotes cell proliferation. TEAD regulates target genes that are strongly associated with tumor development, such as connective tissue growth factor (CTGF) and Cyr61, AXL receptor tyrosine kinase, and MYC. It has also been confirmed that TEAD is overexpressed in breast cancer stem cells and breast cancer, ovarian cancer, germ cell tumors, renal cell carcinoma, medulloblastoma, and gastric cancer, etc. Overactivation of YAP and TAZ and / or mutations in one or more members of the Hippo pathway network have been associated with various cancers. In addition, recent studies have reported that resistance to EGFR tyrosine kinase inhibitors Tarceva (erlotinib), Iressa (gefitinib), or Tagrisso (osimertinib) and epithelial-mesenchymal transition (EMT) phenotype changes are associated with YAP overexpression or amplification.

[0003] The inventors of the present disclosure have completed the present disclosure by developing novel heterobicyclic compounds for inhibiting YAP-TEAD protein interaction.

[0004] Prior Art

[0005] Patent Documents

[0006] (Patent Document 1) International Publication No. WO2019 / 040380

[0007] (Patent Document 2) International Publication No. WO2020 / 243415

[0008] Non-Patent Documents

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

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

[0011] (Non - Patent Document 3) Cancer Res. 2011, 71(3), 873

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

[0013] (Non - Patent Document 5) Cancer Cell 2020, 37, 104

[0014] (Non - Patent Document 6) Cells 2021, 10, 2715

[0015] (Non - Patent Document 7) Genes Cancer 2017, 8(3 - 4), 497 Summary of the Invention

[0016] Technical Problem

[0017] An object of the present disclosure is to provide novel heterobicyclic compounds having a high inhibitory activity against YAP - TEAD binding in the Hippo pathway, which plays a key role in cancer development.

[0018] Another object of the present disclosure is to provide a pharmaceutical composition comprising the aforementioned compound as an active ingredient for treating or preventing related diseases caused by dysregulation of the Hippo signaling pathway, specifically caused by TEAD activation.

[0019] Other objects and advantages of the present application will become apparent from the following detailed description and the appended claims. Anything not described herein can be easily recognized and inferred by those skilled in the art from this application or similar fields, and is omitted herein.

[0020] Solution to the Problem

[0021] According to an embodiment of the present disclosure, there is provided a compound selected from the group consisting of compounds of Formula 1, their enantiomers, diastereomers, solvates and hydrates, and pharmaceutically acceptable salts thereof.

[0022] [Formula 1]

[0023]

[0024] According to an embodiment of the present disclosure, there is provided a pharmaceutical composition for treating or preventing related diseases caused by abnormal regulation of the Hippo signaling pathway, specifically caused by TEAD activation. The pharmaceutical composition comprises a compound selected from the group consisting of a compound of Formula 1, its enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof as an active ingredient.

[0025] Advantageous effects of the present disclosure

[0026] The novel heterobicyclic compound having the structure of Formula 1 of the present disclosure has excellent inhibitory activity against YAP-TEAD binding and can be used as a therapeutic agent for various diseases involving the Hippo pathway, which plays a key role in cancer development. Detailed description of specific embodiments

[0027] Detailed description of preferred embodiments

[0028] The present disclosure is described in more detail below.

[0029] Unless otherwise defined, all technical terms used in the present disclosure are used as 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.

[0030] According to an embodiment of the present disclosure, there is provided a compound selected from the group consisting of a compound of Formula 1 below, its enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0031] [Formula 1]

[0032]

[0033] In Formula 1 above,

[0034] R 1 and R 2 may each independently be hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-6 carbocyclic group or halogenated C 1-6 alkyl;

[0035] R 3 may be hydrogen, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy or cyano;

[0036] may be a carbocyclic group or a heterocyclic group;

[0037] may be C 6-10 aryl or C 4-10 heteroaryl;

[0038] L 1 may be absent, may be bonded, or may be C 1-3 alkylene or halogen-substituted C 1-3 alkylene;

[0039] each R 4 and each R 5 may independently be hydrogen, halogen, cyano, amino, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyalkyl, halo C 1-6 alkoxy, mono(C 1-3 alkyl)substituted carbamoyl (-(CO)-NH(C 1-3 alkyl)), di-(C 1-3 alkyl)substituted carbamoyl (-(CO)-N(C 1-3 alkyl) 2 ), C 1-3 alkylsulfinyl (-(SO)-(C 1-3 alkyl)), C 1-3 alkylsulfonyl (-SO 2 -(C 1-3 alkyl)), substituted or unsubstituted C 3-6 carbocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted C 2-6 heterocyclic group or substituted or unsubstituted C 4-10 heteroaryl;

[0040] X and Y may each independently be -C- or -N-; and

[0041] m and n may each independently be an integer from 0 to 3.

[0042] As used herein, the term "halogen" may be F, Cl, Br or I.

[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. Alkyl may be, for example, methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl or tert-butyl, but is not limited thereto.

[0044] As used herein, the term "alkylene" refers to a divalent straight-chain or branched-chain hydrocarbon group having (-CH 2 -) p . p may be any integer.

[0045] Unless otherwise indicated, as used herein, the term "alkenyl" refers to an alkyl group that includes one or more double bonds and may be substituted or unsubstituted. Alkenyl can be, for example, prop-1-enyl, but-1-enyl, but-2-enyl, 3-methylbut-1-enyl, or pent-1-enyl, etc., but is not limited thereto.

[0046] Unless otherwise indicated, as used herein, the term "cycloalkyl" refers to saturated monocyclic and polycyclic hydrocarbon rings typically having the stated number of carbon atoms, including rings that may be substituted or unsubstituted. Cycloalkyl can be, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, etc., but is not limited thereto.

[0047] Unless otherwise indicated, as used herein, the term "heterocycloalkyl" refers to a monocyclic cycloalkyl group that may be substituted or unsubstituted and includes one or more heteroatoms selected from N, O, and S. Heterocycloalkyl can be, for example, piperidinyl, piperazinyl, pyrrolidinyl, thiomorpholinyl, imidazolidinyl, tetrahydrofuranyl, or similar groups, etc., but is not limited thereto. azinyl, pyrrolidinyl, thio morpholinyl, imidazolidinyl, tetrahydrofuranyl, or similar groups, etc., but is not limited thereto.

[0048] Unless otherwise indicated, as used herein, the term "haloalkyl" refers to a mono-haloalkyl and poly-haloalkyl group that may be substituted or unsubstituted. The terms halogen and alkyl are as defined above.

[0049] Unless otherwise indicated, as used herein, the term "alkoxy" refers to a straight-chain or branched-chain hydrocarbon residue that is connected by oxygen and may be substituted or unsubstituted. Alkoxy can be, for example, methoxy, ethoxy, propoxy, butoxy, isopropoxy, isobutoxy, or tert-butoxy, etc., but is not limited thereto.

[0050] As used herein, the term "alkoxyalkyl" refers to an alkyl group in which one or more hydrogen atoms of the alkyl are substituted by an alkoxy group. Alkoxyalkyl can be, for example, methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, methoxypropyl, ethoxypropyl, and isopropoxymethyl, etc., but is not limited thereto.

[0051] Unless otherwise indicated, as used herein, the term "aryl" refers to an aromatic group that may be substituted or unsubstituted and may include, for example, C 3-10 aryl, C 3-8 aryl, or C 3-6 aryl, in which double bonds are alternately (resonantly) present between adjacent carbon atoms or suitable heteroatoms. By way of example, it can be phenyl, biphenyl, naphthyl, toluoyl, or naphthalenyl, etc., but is not limited thereto.

[0052] Unless otherwise specified, as used herein, the term "heteroaryl" may refer to any monocyclic or bicyclic aromatic group, which may be substituted or unsubstituted and includes one or more heteroatoms selected from N, O and S. For example, a monocyclic heteroaryl group may be pyridyl, imidazolyl, thiazolyl, oxazolyl, thienyl, furanyl, pyrrolyl, isocyanate Azolyl, pyrazolyl, triazolyl, thiadiazolyl, tetrazolyl, Oxazolyl, phthalide pyrimidinyl or pyridinyl For example, the bicyclic heteroaryl group can be indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzo Azolyl, benzyl oxazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, quinolyl, isoquinolyl, purinyl or pyropyridinyl, etc.

[0053] Unless otherwise specified, as used herein, the term "carbocyclyl" refers to a substituent including carbon ring atoms, which has a structure of a saturated carbocyclyl (e.g., "cycloalkyl"), a partially saturated carbocyclyl (e.g., "cycloalkenyl"), or a completely unsaturated carbocyclyl (e.g., "aryl"). The carbocyclyl may have a single ring (monocyclic) or a polycyclic structure. As used herein, the carbocyclyl includes, for example, 3 to 14 carbon ring atoms, or, for example, 3 to 8 carbon ring atoms, and may be saturated, unsaturated, or aromatic. In this article, ring atoms are atoms bonded together to form one or more rings of the carbocyclyl substituent. For example, a saturated carbocyclyl may be cyclopropyl, cyclopentyl, or cyclohexyl, etc., but is not limited thereto. For example, an unsaturated carbocyclyl may include three or fewer double bonds. For example, an aromatic carbocyclyl may be phenyl. In addition, the term "carbocyclic group" may include fused carbocyclic group combinations, and may be, for example, naphthyl, phenanthrenyl, dihydroindenyl, indenyl, etc., but is not limited thereto.

[0054] Unless otherwise specified, as used herein, the term "heterocyclic group" refers to a substituent that includes at least one heteroatom and ring atoms, and has the structure of a saturated heterocyclic group (such as "heteroalkyl"), a partially saturated heterocyclic group (such as "heteroalkenyl"), or a fully unsaturated heterocyclic group (such as "heteroaryl"). The heterocyclic group can have a single ring (monocyclic) or a polycyclic structure. As used herein, the heterocyclic group includes, for example, a total of 3 to 14 ring atoms, 6 to 14 ring atoms, or for example a total of 3 to 8 ring atoms, and can be saturated, unsaturated, or aromatized. In this text, ring atoms are atoms bonded together to form one or more rings of the heterocyclic group substituent. For example, at least one of the ring atoms is nitrogen, oxygen, or sulfur, and the remaining ring atoms are independently selected from the group consisting of carbon, nitrogen, oxygen, and sulfur. For example, the ring atoms of the heterocyclic group can include 4 or fewer heteroatoms, such as N, O, and S, for example a total of 3 to 14 ring atoms, or for example a total of 5 to 7 ring atoms, and can be saturated, unsaturated, or aromatized. For example, the heterocyclic group can be furyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, dioxolanyl, azolyl, thiazolyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, iso azolyl, isothiazolyl, diazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, piperidyl, di alkyl, olinyl, dithialkyl, thio olinyl, thia yl, pyrimidinyl, py yl, pi yl, sulfolanyl, tri yl, azetidinyl, azetidinyl, thiazetidinyl, diazetidinyl, or thiazolinyl, but not limited thereto. Additionally, the term heterocyclic group can include fused heterocyclic groups, such as can be benzimidazolinyl, benzo azolyl, imidazopyridyl, benzo yl, benzothi yl, azolopyridyl, quinolinyl, quinazolinyl, qui azolinyl, dihydroquinazolinyl, benzothiazolyl, phthalimido, benzofuryl, benzodiazetidinyl, indolyl, or isoindolyl, but not limited thereto. The "heterocyclic group" can be a carbon-linked group or a heteroatom-linked group. For example, the N-linked heterocyclic groups of the heteroatom-linked group include but is not limited thereto. Unless otherwise indicated, as used herein, the term "fused heteroaryl" refers to a linked substituted or unsubstituted ring system in which the heteroaryl is fused to another aryl, heteroaryl, or heterocycloalkyl. For example, the fused heteroaryl can form a 5+5 membered, 5+6 membered, 5+7 membered, 6+6 membered, or 6+7 membered fused ring system. Additionally, the fused heteroaryl can be, for example and the like, but is not limited thereto.

[0055] As used herein, any substituent can be selected from, for example, cyano, amino, hydroxy, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, and halo C 1-6 alkoxy, but is not limited thereto.

[0056] For example, a substituted C 3-6 carbocyclic group, C 6-10 aryl, C 2-6 heterocyclic group, C 4-10 heteroaryl, C 3-6 cycloalkyl, or C 2-6 heterocycloalkyl can be substituted with any one of the substituents selected from one or more hydrogen atoms of an alkyl group, halogen, cyano, amino, hydroxy, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, and halo C 1-6 alkoxy, but is not limited thereto.

[0057] As used herein, the term "stereoisomer" can refer to a compound or a salt thereof of the present disclosure that has the same chemical formula or molecular formula but is different optically or spatially, and can include enantiomers or diastereomers.

[0058] As used herein, the term "enantiomer" refers to two stereoisomers of a compound that are non-overlapping mirror images of each other.

[0059] As used herein, the term "diastereomer" refers to stereoisomers having two or more chiral centers and molecules that are not mirror images of each other.

[0060] The compounds of the present disclosure can include asymmetric or chiral centers and can 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.

[0061] As used herein, the term "solvate" may refer to a compound or a salt thereof of the present disclosure, including a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Suitable solvents may include solvents that are volatile, non-toxic, and / or suitable for administration to humans. A "solvate" may include a molecular complex comprising a compound and one or more pharmaceutically acceptable solvent molecules (such as ethanol).

[0062] As used herein, the term "hydrate" refers to a complex in which the solvent molecule is water.

[0063] 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 desired 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.

[0064] In one embodiment, is C 6-10 aryl, C 1-10 heteroaryl, C 6-14 fused heteroaryl, or C 2-6 heterocyclic group,

[0065] wherein C 1-10 heteroaryl, C 6-14 fused heteroaryl or C 2-6 heterocyclic group may include 1 to 4 heteroatoms each independently selected from N, O, and S.

[0066] In one embodiment, may be phenyl, pyridyl, pyr yl, pyrazolyl, imidazolyl, thienyl, furyl, oxazolyl, azetidinyl or

[0067] refers to a single bond or a double bond.

[0068] For example, may be

[0069] In one embodiment, may be phenyl or pyridyl.

[0070] In one embodiment, R 1 and R 2 may each independently be hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl or halo C 1-6Alkyl.

[0071] In one embodiment, L 1 is a single bond; and

[0072] each R 4 and each R 5 may independently be selected from hydrogen, halogen, cyano, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyalkyl, halo C 1-6 alkoxy, mono(C 1-3 alkyl)substituted carbamoyl (-(CO)-NH(C 1-3 alkyl)), di-(C 1-3 alkyl)substituted carbamoyl (-(CO)-N(C 1-3 alkyl) 2 ), C 1-3 alkylsulfonyl (-(SO 2 -(C 1-3 alkyl)), substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 6-10 aryl, or substituted or unsubstituted C 2-6 heterocycloalkyl.

[0073] In one embodiment, L 1 is C 1-3 alkylene; and

[0074] each R 4 and each R 5 may independently be selected from hydrogen, halogen, cyano, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, di-(C 1-3 alkyl)substituted carbamoyl (-(CO)-N(C 1-3 alkyl) 2 ), C 1-3 alkylsulfonyl (-(SO 2 -(C 1-3 alkyl)), substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 6-10 aryl, or substituted or unsubstituted C 2-6 heterocycloalkyl.

[0075] In one embodiment, R 5 may each be hydrogen, halogen, cyano, C 1-6 alkyl, halo C 1-6 alkyl, C1-6 Alkoxy, halo C 1-6 Alkoxy, C 3-6 Cycloalkyl or phenyl; or

[0076] C substituted with any one or more substituents 3-6 Cycloalkyl or phenyl, and the substituents are selected from halogen, cyano, C 1-6 Alkyl, halo C 1-6 Alkyl, C 1-6 Alkoxy and halo C 1-6 Alkoxy.

[0077] In one embodiment, R 5 can each be hydrogen, halogen, cyano, methyl, ethyl, propyl, tert-butyl, trifluoromethyl, trifluoromethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl.

[0078] In one embodiment, the compound can be a compound selected from the following compounds, their enantiomers, diastereomers, solvates and hydrates, and their pharmaceutically acceptable salts.

[0079] 1) N-Methyl-3-(3-methylpyr -2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0080] 2) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0081] 3) N-Methyl-3-(1-methyl-1H-pyrazol-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0082] 4) N-Methyl-3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0083] 5) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-sulfonamide;

[0084] 6) 3-(1-Isopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0085] 7) N-Ethyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0086] 8) N-Methyl-3-(pyridin-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0087] 9) N-Methyl-3-(5-methylthiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0088] 10) N-Methyl-3-(5-methylfuran-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0089] 11) 3-(1-Ethyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0090] 12) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indole-5-sulfonamide;

[0091] 13) 3-(2-Fluorophenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0092] 14) 1-(4-Chlorophenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide;

[0093] 15) N-Methyl-3-(pyridin-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0094] 16) 3-(1-Chlorobutyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0095] 17) N-Methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0096] 18) 1-(4-Cyclohexylphenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide;

[0097] 19) N,N-Dimethyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0098] 20) 3-(3-Fluoropyridin-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0099] 21) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(3-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0100] 22) 1-(4-Cyanophenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide;

[0101] 23) 3-(Furan-3-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0102] 24) N-Methyl-3-(5-methylfuran-2-yl)-1-phenyl-1H-indole-5-sulfonamide;

[0103] 25) 3-(2,3-Difluorophenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0104] 26) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-phenyl-1H-indole-5-sulfonamide;

[0105] 27) 1-(3-Chloro-4-(trifluoromethyl)phenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide;

[0106] 28) 3-(1-Cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0107] 29) 3-(1H-Imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0108] 30) 3-(1-(2-Fluorophenyl)-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0109] 31) 3-(Furan-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0110] 32) N-Methyl-3-(2-methyl oxazole-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0111] 33) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide;

[0112] 34) N-Methyl-3-(5-(trifluoromethyl)furan-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0113] 35) N-Methyl-3-(1-(oxetan-3-yl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0114] 36) 3-(5-Chlorofuran-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0115] 37) N-Methyl-3-(1-(2,2,2-trifluoroethyl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0116] 38) 3-(1-(2-Methoxyethyl)-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0117] 39) N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(p-tolyl)-1H-indole-5-sulfonamide;

[0118] 40) 1-(4-(tert-Butyl)phenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide;

[0119] 41) N-Methyl-3-( azol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0120] 42) 3-(1-Cyclopropyl-1H-imidazol-4-yl)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-N-methyl-1H-indole-5-sulfonamide;

[0121] 43) 3-(1-Cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonamide (3-(1-cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-sulfonamide);

[0122] 44) 3-(1-Cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide;

[0123] 45) 3-(6,7-Dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0124] 46) 3-(3-Fluoroazetidin-1-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide;

[0125] 47) N,N-Dimethyl-2-(4-(5-(N-methylaminosulfonyl)-1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)-1H-imidazol-1-yl)acetamide; and

[0126] 48) N-Methyl-3-(1-(2-(methylsulfonyl)ethyl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide.

[0127] According to an embodiment of the present disclosure, there is provided a pharmaceutical composition for treating or preventing diseases associated with abnormal regulation of the Hippo signaling pathway, specifically diseases caused by TEAD activation. The pharmaceutical composition comprises a compound selected from the group consisting of compounds of formula 1, their enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof as an active ingredient.

[0128] In one embodiment, the composition may exhibit inhibitory activity against the binding of Yes-associated protein (YAP)-transcription enhancer associated domain (TEAD).

[0129] In one embodiment, the composition can be used to treat cancers or tumors that can be treated by exhibiting inhibitory activity against YAP-TEAD binding.

[0130] In one embodiment, the pharmaceutical composition may comprise a therapeutically effective amount of a compound selected from the group consisting of compounds of formula 1, their enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0131] As used herein, the term "therapeutically effective amount" refers to an amount of a compound of the present disclosure that treats or prevents a particular disease, condition, or disorder; alleviates, ameliorates, or eliminates one or more symptoms of a particular disease, condition, or disorder; or prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder.

[0132] A physician with ordinary knowledge in the relevant field can easily determine and prescribe the effective required dose of a pharmaceutical composition. For example, the pharmaceutical composition may include from 0.0001 mg to 10 g of the compound, but is not limited thereto.

[0133] In one embodiment, in addition to the active ingredient, the pharmaceutical composition may further include pharmaceutically acceptable additives. The additives may be, for example, diluents, disintegrants, binders, lubricants, surfactants, suspending agents or emulsifying agents, etc., but are not limited thereto.

[0134] The pharmaceutical composition of the present disclosure can be formulated according to common 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.

[0135] Another embodiment of the present disclosure provides a method for monitoring the administration of the pharmaceutical composition to an individual suffering from a disease associated with abnormal regulation of the Hippo signaling pathway, specifically caused by TEAD activation. The pharmaceutical composition includes a compound selected from the group consisting of compounds of Formula 1, their enantiomers, diastereomers, solvates and hydrates, and pharmaceutically acceptable salts thereof as the active ingredient.

[0136] As used herein, the terms "treat" or "cure" refer to inhibiting a disease, such as inhibiting a disease, condition or disorder in an individual who experiences or exhibits a lesion or symptom of the disease, condition or disorder, such as preventing or reversing the further development of the lesion and / or symptom, or improving the disease, such as reducing the severity of the disease.

[0137] As used herein, the terms "prevent" or "prophylaxis" refer to preventing a disease, such as preventing a disease, condition or disorder in an individual who may be susceptible to the disease, condition or disorder, but has not yet experienced or exhibited a lesion or symptom of the disease.

[0138] As used herein, the term "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, dairy cow, cat, guinea pig or rodent.

[0139] As used herein, the terms "administer" and "administration" refer to any method of providing the disclosed composition to an individual.

[0140] The dosage, dosing frequency, or method of administration of a compound or pharmaceutical composition 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 a 70 kg individual may be administered in an amount of 0.0001 mg to 10 g per day, such as 1 mg to 1 g per day. The dosing frequency 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 oral or parenteral. For example, a compound or pharmaceutical composition according to an embodiment may be administered orally or parenterally in an amount within the range of 0.1 to 100 mg / kg (body weight).

[0141] The physician may start at a level lower than that required to achieve the desired therapeutic effect and gradually increase the dosage of the compound or pharmaceutical composition of the present disclosure administered to the individual until the desired effect is achieved.

[0142] Another embodiment of the present disclosure provides a kit comprising a compound selected from the group consisting of a compound of Formula 1, a pharmaceutically acceptable salt thereof, enantiomers, diastereomers, hydrates, and solvates as an active ingredient.

[0143] In one embodiment, the therapeutic agent may be a drug for treating a related disease caused by abnormal regulation of the Hippo signaling pathway (specifically, TEAD activation), such as a drug for treating cancer. For example, the therapeutic agent may be a chemotherapeutic agent for treating cancer.

[0144] 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.

[0145] 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.

[0146] Even if not explicitly stated, numerical values given herein should be considered to include the meaning of "about". As used herein, the term "about" means within 5% of a specific value or range, preferably within 1% to 2%.

[0147] As used herein, a numerical range indicated by the term "to" refers to a range that includes the values written before and after the term "to" as the lower and upper limits, respectively.

[0148] As used herein, the terms "having", "may have", "including", or "may include" mean the presence of a specific feature (e.g., a number, or a component, such as an ingredient), and do not exclude the presence of other features.

[0149] The contents of all disclosures incorporated herein by reference are incorporated herein by reference in their entirety.

[0150] In the following, the method for preparing the compound of Formula 1 will be described in detail.

[0151] The compound of Formula 1 according to the present disclosure can be prepared according to the synthetic method shown in Reaction 1.

[0152] [Reaction 1]

[0153]

[0154] [Process-1]

[0155] At 0 °C to 5 °C, under cooling conditions, the starting material (e.g., PG-indoline; 1 equivalent, standard equivalent) was slowly added to chlorosulfonic acid (7.5 equivalents). After raising the reaction temperature to room temperature, the reaction mixture was heated at 70 °C to react. After confirming the completion of the reaction, the reaction solution was slowly added dropwise to water cooled to 0 °C to 5 °C, and the formed solid was collected by filtration to obtain the target compound A.

[0156] [Process-2]

[0157] Triethylamine (2 equivalents) was added to the reaction solution in which A (1 equivalent, standard equivalent) prepared in the above [Process-1] was dissolved in dichloromethane. The corresponding amine solution (2 equivalents) was added dropwise thereto and the reaction solution was stirred under reflux. After confirming the completion of the reaction, the reaction mixture was cooled to room temperature, and the formed solid was collected by filtration to obtain the target compound B.

[0158] [Process-3]

[0159] The compound B (1 equivalent, standard equivalent) obtained in the above [Process-2] was dissolved in methanol, and concentrated HCl (4 equivalents) was added thereto. The reaction solution was stirred overnight at room temperature, heated to 80 °C, and stirred for another 2 hours. After confirming the completion of the reaction, the internal temperature was lowered to room temperature, water was added, and an aqueous sodium hydroxide solution was slowly added dropwise to adjust the pH to 3 to 4. The formed solid was collected by filtration to obtain the target compound C.

[0160] [Process-4]

[0161] The compound C (1 equivalent, standard equivalent) obtained in the above [Process-3] was dissolved in dichloromethane, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 1 equivalent) was added thereto. Then, the reaction solution was stirred overnight at room temperature. After confirming the completion of the reaction, the reaction solution was filtered through diatomaceous earth and washed with dichloromethane. The residue obtained after concentration under reduced pressure was purified by MPLC to obtain the target compound D.

[0162] [Process-5]

[0163] Dissolve the compound D (1 equivalent, standard equivalent) obtained from the above [Process - 4] in dimethylformamide, and add the corresponding halogen - substituted B derivative (1.5 equivalents) and potassium carbonate (2.5 equivalents) thereto. Subsequently, add copper(I) iodide (0.2 equivalent), and stir the reaction solution at room temperature overnight. After confirming the completion of the reaction, cool the reaction mixture to room temperature and add water thereto, followed by extraction with ethyl acetate. The obtained organic layer is dehydrated with anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer is concentrated under reduced pressure. The obtained residue is purified by MPLC to obtain the target compound E.

[0164] [Process-6]

[0165] Dissolve the compound E (1 equivalent, standard equivalent) obtained from the above [Process - 5] in dimethylformamide, and slowly add N - bromosuccinimide (1 equivalent) dropwise thereto. Then, stir the reaction solution at room temperature. After confirming the completion of the reaction, add water and then perform extraction with ethyl acetate. The organic layer is dehydrated with anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer is concentrated under reduced pressure. The obtained residue is purified by MPLC to obtain the target compound F.

[0166] [Process-7]

[0167] Perform a Stille coupling reaction or a Suzuki coupling reaction on the compound F (1 equivalent, standard equivalent) obtained from the above [Process - 6] with the corresponding A - stannane derivative and A - borane derivative (2 equivalents). After the completion of the reaction, wash the organic layer with water, dehydrate it with anhydrous sodium sulfate, filter it under reduced pressure, and concentrate the filtered organic layer under reduced pressure. The obtained residue is purified by MPLC to obtain the target compound G.

[0168] In Reaction 1, R 1 、R 2 、R 3 、R 4 、R 5 、X, Y, m, n, L 1 、 and are respectively defined as in the above formula 1, but are not limited thereto, and can be changed within the scope understood by those skilled in the art.

[0169] The compound of formula 1 according to an embodiment of the present disclosure can be prepared according to the method shown in Reaction 1 above, but not limited thereto. Those with ordinary knowledge in the field of organic compounds can appropriately adjust the specific reaction path, reaction conditions, reaction amounts, etc.

[0170] Hereinafter, the present disclosure will be described in further detail via 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.

[0171] Example 1: N-Methyl-3-(3-methylpyr -2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0172] [Process-1] Preparation of 1-acetylindoline-5-sulfonyl chloride

[0173]

[0174] At 0 °C to 5 °C, 1-indolin-1-yl ethanone (30 g, 124.07 mmol) was added in small portions to chlorosulfonic acid (62 mL, 930.5 mmol) over 15 minutes. After the temperature was raised to room temperature, the reaction mixture was heated to 70 °C for 90 minutes. After confirming the completion of the reaction, the reaction solution was slowly added dropwise to water cooled to 0 °C to 5 °C. The formed solid was collected by filtration, washed several times with water and dried at 50 °C to obtain 27 g (55% yield) of the title compound.

[0175] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 7.96 - 7.93 (m, 1H), 7.43 - 7.38 (m, 2H), 4.10 (t, J = 8.5 Hz, 2H), 3.13 (t, J = 8.5 Hz, 2H), 2.16 (s, 3H).

[0176] [Process-2] Preparation of 1-acetyl-N-methylindoline-5-sulfonamide

[0177]

[0178] 1-Acetylindoline-5-sulfonyl chloride (20 g, 77 mmol) obtained from the above [Process-1] was dissolved in 60 mL of dichloromethane and triethylamine (21.5 mL, 154 mmol) was added thereto. A 2 M methylamine tetrahydrofuran solution (77 mL, 154 mmol) was added dropwise to this mixture, and the reaction solution was refluxed and stirred. After confirming the completion of the reaction, the mixture was cooled to room temperature. The formed solid was collected by filtration, washed several times with water and dried at 50 °C to obtain 18.8 g (96% yield) of the title compound.

[0179] 1 H-NMR(300MHz, DMSO-d 6 ): δ 8.16 - 8.14 (m, 1H), 7.60 - 7.57 (m, 2H), 7.30 (s, 1H), 4.16 (t, J=8.6 Hz, 2H), 3.21 (t, J=8.5 Hz, 2H), 2.39 (s, 3H), 2.19 (s, 3H).

[0180] [Process-3] Preparation of N-methyl-1H-indoline-5-sulfonamide

[0181]

[0182] The 1-acetyl-N-methylindoline-5-sulfonamide (6.2 g, 24.2 mmol) obtained from the above [Process-2] was dissolved in 72 mL of methanol, and concentrated HCl (8.1 mL, 97.5 mmol) was added thereto. The reaction solution was stirred overnight at room temperature and then stirred at 80 °C for 2 hours. After confirming the completion of the reaction, the internal temperature was lowered to room temperature, 100 mL of water was added, and then 1N aqueous sodium hydroxide solution was slowly added dropwise to adjust to pH 3 to 4. The formed solid was collected by filtration, washed several times with water and dried at 50 °C to obtain 3.4 g (66% yield) of the title compound.

[0183] 1 H-NMR(300MHz, CDCl 3 ): δ 7.56 - 7.53 (m, 2H), 6.66 - 6.61 (m, 1H), 4.17 (brs, 1H), 3.71 (t, J=8.6 Hz, 2H), 3.11 (t, J=8.5 Hz, 2H), 2.64 (d, J=5.5 Hz, 3H), 1.59 (brs, 1H).

[0184] [Process-4] Preparation of N-methyl-1H-indole-5-sulfonamide

[0185]

[0186] The N-methyl-1H-indoline-5-sulfonamide (3.3 g, 15.5 mmol) prepared from the above [Process-3] was dissolved in 30 mL of dichloromethane, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 3.5 g, 15.5 mmol) was added thereto. Then, the reaction solution was stirred overnight at room temperature. After the completion of the reaction, the reaction solution was filtered through diatomaceous earth and washed with dichloromethane. The residue obtained after concentration under reduced pressure was purified by MPLC (ethyl acetate:hexane = 1:3 (v / v)) to obtain 1.9 g (58% yield) of the title compound.

[0187] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.52 (s, 1H), 8.26 - 8.25 (m, 1H), 7.77 - 7.68 (m, 1H), 7.53 - 7.51 (m, 1H), 7.39 - 7.37 (m, 1H), 6.72 - 6.71 (m, 1H), 4.24 (brs, 1H), 2.67 (d, J = 5.5 Hz, 3H).

[0188] [Process-5] Preparation of N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0189]

[0190] The N-methyl-1H-indole-5-sulfonamide (1.9 g, 9.04 mmol) obtained from the above [Process-4] was dissolved in 20 mL of dimethylformamide, and 4-bromobenzotrifluoride (3.08 g, 13.6 mmol) and potassium carbonate (7.36 g, 22.6 mmol) were added thereto, followed by the addition of copper(I) iodide (344 mg, 1.8 mmol). The reaction solution was stirred overnight at 130 °C. After completion of the reaction, the mixture was cooled to room temperature, 100 mL of water was added thereto, and then it was extracted three times with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 1.2 g (37% yield) of the title compound.

[0191] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.31 (s, 1H), 7.87 - 7.84 (m, 2H), 7.76 - 7.73 (m, 1H), 7.67 - 7.51 (m, 3H), 7.49 (s, 1H), 6.88 - 6.87 (m, 1H), 4.35 - 4.11 (m, 1H), 2.70 (d, J = 5.5 Hz, 3H).

[0192] [Process-6] Preparation of 3-bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0193]

[0194] The N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide (520 mg, 1.47 mmol) obtained from the above [Process-5] was dissolved in 30 mL of dimethylformamide, and N-bromosuccinimide (261 mg, 1.47 mmol) was slowly added dropwise thereto. The reaction solution was stirred at room temperature for 3 hours to complete the reaction, 100 mL of water was added thereto, and then it was extracted three times with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 420 mg (66% yield) of the title compound.

[0195] 1 H-NMR(300MHz,CDCl 3 ):δ8.26-8.25(m,1H),7.89-7.79(m,3H),7.67-7.62(m,3H),7.55(s,1H),4.41-4.26(m,1H),2.72(s,3H).

[0196] [Process-7] Preparation of N-methyl-3-(3-methylpyr -2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole- 5-sulfonamide

[0197]

[0198] The 3-bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide (50 mg, 0.12 mmol) obtained from the above [Process-6] was dissolved in 2 mL of N,N-dimethylacetamide and copper(II) chloride (3 mg, 0.02 mmol), and cesium fluoride (53 mg, 0.35 mmol), [1,1'-bis(diphenylphosphino)ferrocenediyl]dichloropalladium([Pd(dppf)Cl 2 )(16 mg, 0.02 mmol) and tributyl-(3-methylpyr -2-yl)stannane (88 mg, 0.23 mmol) were added thereto respectively. The reaction solution was stirred at 120 °C overnight to complete the reaction, 20 mL of water was added thereto, and then it was extracted three times with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure. The resulting residue was purified by MPLC (dichloromethane:methanol = 20:1 (v / v)) to obtain 18 mg (6% yield) of the title compound.

[0199] 1 H-NMR(300MHz,CDCl 3): δ 8.77 (s, 1H), 8.59 (s, 1H), 8.45 (s, 1H), 7.83 - 7.80 (m, 2H), 7.68 - 7.65 (m, 3H), 4.88 - 4.87 (m, 1H), 2.80 (s, 3H), 2.67 (s, 3H).

[0200] MS (ESI + , m / z): 447.1 [M + H] +

[0201] Example 2: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0202]

[0203] Except for using tributyl-(1-methylimidazol-4-yl)stannane (171 mg, 0.46 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above, the procedure of Example 1 was repeated to obtain 30 mg (30% yield) of the title compound. -2-yl)stannane, the procedure of Example 1 was repeated to obtain 30 mg (30% yield) of the title compound.

[0204] 1 1H-NMR (300 MHz, CDCl 3 ): δ 8.56 (s, 1H), 7.94 (s, 1H), 7.77 - 7.76 (m, 6H), 7.54 (s, 1H), 7.37 (s, 1H), 4.83 - 4.81 (m, 1H), 3.81 (s, 3H), 2.69 (d, J = 5.4 Hz, 3H).

[0205] MS (ESI + , m / z): 435.1 [M + H] +

[0206] Example 3: N-Methyl-3-(1-methyl-1H-pyrazol-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0207]

[0208] 3-Bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide (50 mg, 0.11 mmol) obtained from [Process-6] of Example 1 above was dissolved in 2.5 mL of 1,4-di in an alkane:water (1:4, v / v) mixture, and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (27 mg, 0.12 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium([Pd(dppf)Cl 2 )(9 mg, 0.01 mmol), and sodium carbonate (24 mg, 0.23 mmol) were added thereto. After stirring the reaction solution at 100 °C overnight to complete the reaction, the reaction solution was cooled to room temperature, 10 mL of water was added thereto, and then the mixture was extracted three times with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 15 mg (30% yield) of the title compound.

[0209] 1 H-NMR (300 MHz, CD 3 OD): δ 8.75 (s, 1H), 8.05 (s, 1H), 7.95 - 7.92 (m, 2H), 7.87 - 7.84 (m, 2H), 7.80 - 7.73 (m, 2H), 7.67 - 7.66 (m, 1H), 6.67 (s, 1H), 4.00 (s, 3H), 2.54 (s, 3H).

[0210] MS (ESI + , m / z): 435.2 [M+H] +

[0211] Example 4: N-Methyl-3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0212]

[0213] The procedure of Example 3 was repeated except that 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (27 mg, 0.13 mmol) was used instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above, to obtain 11 mg (21% yield) of the title compound.

[0214] 1 H-NMR (300 MHz, CDCl 3): δ 8.35 (s, 1H), 7.86 - 7.83 (m, 2H), 7.78 - 7.74 (m, 3H), 7.67 - 7.60 (m, 3H), 7.55 (s, 1H), 4.03 (s, 3H), 2.67 (d, J = 5.5 Hz, 3H).

[0215] MS (ESI + , m / z): 435.2 [M + H] +

[0216] Example 5: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-sulfonamide

[0217]

[0218] Except using 1-bromo-4-(trifluoromethoxy)benzene (443 mg, 1.78 mmol) instead of 4-bromobenzotrifluoride in [Process-5] of Example 1 above, using tributyl-(1-methylimidazol-4-yl)stannane (223 mg, 0.60 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7], and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 20 mg (14% yield) of the title compound. -2-yl)stannane and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 20 mg (14% yield) of the title compound.

[0219] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.50 (d, J = 1.6 Hz, 1H), 7.86 (s, 1H), 7.74 - 7.70 (m, 1H), 7.61 - 7.53 (m, 4H), 7.43 - 7.40 (m, 2H), 7.31 (s, 1H), 4.31 - 4.29 (m, 1H), 3.80 (s, 3H), 2.66 (d, J = 5.5 Hz, 3H).

[0220] MS (ESI + , m / z): 451.2 [M + H] +

[0221] Example 6: 3-(1-Isopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0222]

[0223] Except using tributyl-(1-isopropylimidazol-4-yl)stannane (95 mg, 0.23 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 39 mg (71% yield) of the title compound. -2-yl)stannane and repeating the procedure of Example 1 except using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, 39 mg (71% yield) of the title compound was obtained.

[0224] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.14 (d, J = 1.1 Hz, 1H), 7.89 - 7.78 (m, 4H), 7.70 - 7.67 (m, 3H), 7.50 (s, 1H), 7.18 (s, 1H), 4.39 - 4.29 (m, 2H), 2.66 (d, J = 5.4 Hz, 3H), 1.48 (d, J = 6.8 Hz, 6H).

[0225] MS (ESI + , m / z): 463.2 [M+H] +

[0226] Example 7: N-Ethyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0227]

[0228] Except using 2M ethylamine in tetrahydrofuran solution (27 mL) instead of 2M methylamine in tetrahydrofuran solution in [Process-2] of Example 1 above and using tributyl-(1-methylimidazol-4-yl)stannane (171 mg, 0.46 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7], the procedure of Example 1 was repeated to obtain 17 mg (17% yield) of the title compound. -2-yl)stannane, the procedure of Example 1 was repeated to obtain 17 mg (17% yield) of the title compound.

[0229] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.74 (s, 1H), 8.16 (s, 1H), 8.01 - 7.94 (m, 4H), 7.84 - 7.81 (m, 1H), 7.74 (s, 1H), 7.70 - 7.67 (m, 1H), 7.56 (s, 1H), 7.48 - 7.44 (m, 1H), 3.76 (s, 3H), 2.80 - 2.76 (m, 2H), 0.98 (t, J = 7.3 Hz, 3H).

[0230] MS (ESI+ , m / z): 449.1 [M+H] +

[0231] Example 8: N-Methyl-3-(pyridin-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0232]

[0233] Except for using tributyl-(2-pyridyl)stannane (85 mg, 0.23 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above and using ethyl acetate:hexane = 1:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 7 mg (14% yield) of the title compound. -2-yl)stannane and using ethyl acetate:hexane = 1:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 7 mg (14% yield) of the title compound.

[0234] 1 1H-NMR (300 MHz, DMSO-d 6 ): δ 9.15 (s, 1H), 8.73 - 8.71 (m, 2H), 8.04 - 8.01 (m, 5H), 7.98 - 7.83 (m, 2H), 7.72 - 7.68 (m, 1H), 7.40 - 7.39 (m, 1H), 7.30 - 7.26 (m, 1H), 2.42 (d, J = 4.8 Hz, 3H).

[0235] MS (ESI + , m / z): 432.2 [M+H] +

[0236] Example 9: N-Methyl-3-(5-methylthiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0237]

[0238] Except for using 4,4,5,5-tetramethyl-2-(5-methyl-2-thienyl)-1,3,2-dioxaborolane (29 mg, 0.12 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above, the procedure of Example 3 was repeated to obtain 26 mg (52% yield) of the title compound.

[0239] 1 1H-NMR (300 MHz, CDCl 3): δ 8.54 (s, 1H), 7.86 - 7.84 (m, 2H), 7.78 - 7.75 (m, 1H), 7.67 - 7.62 (m, 3H), 7.59 (s, 1H), 7.15 - 7.14 (m, 1H), 6.82 - 6.81 (m, 1H), 4.30 - 4.25 (m, 1H), 2.69 - 2.67 (m, 3H), 2.56 - 2.55 (m, 3H).

[0240] MS(ESI + , m / z): 451.2 [M + H] +

[0241] Example 10: N-Methyl-3-(5-methylfuran-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0242]

[0243] Except for using 4,4,5,5-tetramethyl-2-(5-methyl-2-furyl)-1,3,2-dioxaborolane (27 mg, 0.12 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above, the procedure of Example 3 was repeated to obtain 29 mg (50% yield) of the title compound.

[0244] 1 H-NMR(300 MHz, CDCl 3 ): δ 8.54 - 8.53 (m, 1H), 7.86 - 7.83 (m, 2H), 7.78 - 7.62 (m, 5H), 6.60 - 6.59 (m, 1H), 6.14 - 6.12 (m, 1H), 4.31 - 4.26 (m, 1H), 2.70 - 2.68 (m, 3H), 2.41 (s, 3H).

[0245] MS(ESI + , m / z): 435.20 [M + H] +

[0246] Example 11: 3-(1-Ethyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0247]

[0248] Except for using tributyl-(1-ethylimidazol-4-yl)stannane (73 mg, 0.18 mmol) instead of tributyl-(3-methylpy Except for using stannane with -2- group, repeat the procedure of Example 1 to obtain 9 mg (17% yield) of the title compound.

[0249] 1 H-NMR(300MHz,CDCl 3 ):δ8.52(s,1H),7.92(s,1H),7.84(d,J=8.9Hz,2H),7.73-7.66(m,4H),7.60-7.59(m,2H),7.35(s,1H),4.12-4.09(m,2H),2.67(d,J=5.4Hz,3H),1.25(s,3H).

[0250] MS(ESI + ,m / z):449.2[M+H] +

[0251] Example 12: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indole-5-sulfonamide

[0252]

[0253] Except for using 2-bromo-5-(trifluoromethyl)pyridine (427 mg, 1.85 mmol) instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5 above, repeat the procedure of Example 5 to obtain 21 mg (34% yield) of the title compound.

[0254] 1 H-NMR(300MHz,CD 3 OD):δ8.90(s,1H),8.78-8.75(m,1H),8.44(s,1H),8.34(s,1H),8.29-8.25(m,1H),7.91-7.88(m,1H),7.83-7.79(m,2H),7.58(s,1H)3.85(s,3H),2.55(s,3H).

[0255] MS(ESI + ,m / z):436.2[M+H] +

[0256] Example 13: 3-(2-Fluorophenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0257]

[0258] The procedure of Example 3 was repeated except that (2-fluorophenyl)boronic acid (21 mg, 0.15 mmol) was used instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above to afford 5.5 mg (10% yield) of the title compound.

[0259] 1 H-NMR(300MHz,CDCl 3 ): δ 8.40 (s, 1H), 7.87 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 1.8 Hz, 1H), 7.77 - 7.66 (m, 5H), 7.36 - 7.28 (m, 3H), 4.26 - 4.24 (m, 1H), 2.67 (d, J = 5.5 Hz, 3H).

[0260] MS(ESI + , m / z): 449.2 [M+H] +

[0261] Example 14: 1-(4-chlorophenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide

[0262]

[0263] The procedure of Example 5 was repeated except that 1-bromo-4-chloro-benzene (344 mg, 1.78 mmol) was used instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5 above to afford 10 mg (15% yield) of the title compound.

[0264] 1 H-NMR(300MHz,CDCl 3 ): δ 8.52 (d, J = 1.5 Hz, 1H), 7.87 (s, 1H), 7.75 - 7.72 (m, 1H), 7.61 - 7.47 (m, 6H), 7.33 (d, J = 7.0 Hz, 1H), 4.44 - 4.39 (m, 1H), 3.82 (s, 3H), 2.69 (d, J = 5.4 Hz, 3H).

[0265] MS(ESI + , m / z): 401.1 [M+H] +

[0266] Example 15: N-methyl-3-(pyridin-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0267]

[0268] Except using tributyl-(4-pyridyl)stannane (73 mg, 0.19 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above, the procedure of Example 1 was repeated to obtain 5 mg (9% yield) of the title compound.

[0269] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.54 (s, 1H), 8.32 (s, 1H), 7.99 - 7.89 (m, 8H), 7.87 - 7.83 (m, 2H), 2.54 (s, 3H).

[0270] MS (ESI + , m / z): 432.2 [M + H] +

[0271] Example 16: 3-(1-Chlorobutyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0272]

[0273] Except using tributyl-(1-cyclobutylimidazol-4-yl)stannane (95 mg, 0.23 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 5 mg (9% yield) of the title compound.

[0274] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.53 (d, J = 1.2 Hz, 1H), 7.91 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.76 - 7.60 (m, 5H), 7.38 (d, J = 1.1 Hz, 1H), 4.72 - 4.66 (m, 1H), 4.33 - 4.29 (m, 1H), 2.67 (d, J = 5.4 Hz, 3H), 2.61 - 2.55 (m, 2H), 2.51 - 2.45 (m, 2H), 2.09 - 1.95 (m, 2H).

[0275] MS (ESI + , m / z): 475.2 [M + H] +

[0276] Example 17: N-Methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0277]

[0278] The procedure of Example 3 was repeated except that phenylboronic acid (20 mg, 0.16 mmol) was used instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above to afford 14 mg (28% yield) of the title compound.

[0279] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.51 (s, 1H), 7.86 (d, J = 8.6 Hz, 2H), 7.99 (d, J = 1.8 Hz, 1H), 7.77 - 7.61 (m, 5H), 7.54 (s, 1H), 7.51 - 7.49 (m, 2H), 7.42 - 7.39 (m, 1H), 4.28 - 4.23 (m, 1H), 2.66 (d, J = 1.8 Hz, 3H).

[0280] MS (ESI + , m / z): 431.2 [M+H] +

[0281] Example 18: 1-(4-Cyclohexylphenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide

[0282]

[0283] The procedure of Example 5 was repeated except that 1-bromo-4-cyclohexyl-benzene (439 mg, 1.78 mmol) was used instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5 above to afford 18 mg (29% yield) of the title compound.

[0284] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.41 (s, 1H), 7.84 - 7.79 (m, 2H), 7.68 - 7.61 (m, 2H), 7.58 (s, 1H), 7.52 - 7.36 (m, 4H), 4.58 - 4.54 (m, 1H), 3.83 (s, 3H), 2.65 - 2.59 (m, 1H), 2.51 (s, 3H), 1.94 - 1.88 (m, 4H), 1.81 - 1.77 (m, 1H), 1.58 - 1.31 (m, 5H).

[0285] MS(ESI + , m / z): 449.2 [M+H] +

[0286] Example 19: N,N-Dimethyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0287]

[0288] Except for using 2M dimethylamine in tetrahydrofuran solution (17.3 mL, 34.7 mmol) instead of 2M methylamine in tetrahydrofuran solution and using tributyl-(1-methylimidazol-4-yl)stannane (112 mg, 0.3 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-2] of Example 1 above , the procedure of Example 1 was repeated to obtain 19 mg (19% yield) of the title compound.

[0289] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.68 (s, 1H), 8.18 (s, 1H), 8.00 - 7.92 (m, 4H), 7.87 - 7.84 (m, 1H), 7.74 (s, 1H), 7.63 - 7.59 (m, 1H), 7.58 (s, 1H), 3.74 (s, 3H), 2.62 (s, 6H).

[0290] MS(ESI + , m / z): 449.2 [M+H] +

[0291] Example 20: 3-(3-Fluoropyridin-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0292]

[0293] Except for using tributyl-(3-fluoro-2-pyridyl)stannane (89 mg, 0.23 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above and using ethyl acetate:hexane = 1:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification , the procedure of Example 1 was repeated to obtain 19 mg (35% yield) of the title compound.

[0294] 1 H-NMR (300 MHz, DMSO-d 6): δ 8.75 (s, 1H), 8.59 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H), 8.25 (s, 1H), 8.05 - 7.97 (m, 4H), 7.91 - 7.83 (m, 2H), 7.76 - 7.72 (m, 1H), 7.43 - 7.41 (m, 1H), 2.40 (d, J = 4.8 Hz, 3H).

[0295] MS (ESI + , m / z): 450.3 [M + H] +

[0296] Example 21: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(3-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0297]

[0298] The procedure of Example 5 was repeated except that 3-bromobenzotrifluoride (490 mg, 2.14 mmol) was used instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5 above to give 20 mg (22% yield) of the title compound.

[0299] 1 1H-NMR (300 MHz, DMSO-d 6 ): δ 8.73 (s, 1H), 8.16 (s, 1H), 8.04 - 8.02 (m, 2H), 7.88 - 7.86 (m, 2H), 7.66 - 7.65 (m, 2H), 7.64 - 7.63 (m, 1H), 7.55 - 7.54 (m, 1H), 7.35 - 7.34 (m, 1H), 3.74 (s, 3H), 2.40 (d, J = 4.9 Hz, 3H).

[0300] MS (ESI + , m / z): 435.2 [M + H] +

[0301] Example 22: 1-(4-Cyanophenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide

[0302]

[0303] The procedure of Example 5 was repeated except that 4-iodobenzonitrile (500 mg, 2.14 mmol) was used instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5 above to give 25 mg (50% yield) of the title compound.

[0304] 1H-NMR(300MHz, DMSO-d 6 ): δ 8.73 - 8.72 (m, 1H), 8.16 (s, 1H), 8.10 - 8.07 (m, 2H), 7.93 - 7.83 (m, 3H), 7.74 (s, 1H), 7.68 - 7.64 (m, 1H), 7.56 (s, 1H), 7.39 - 7.34 (m, 1H), 3.75 (s, 3H), 2.40 (d, J=4.9Hz, 3H).

[0305] MS(ESI + , m / z): 392.2 [M + H] +

[0306] Example 23: 3-(Furan-3-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0307]

[0308] The procedure of Example 3 was repeated except that 3-furanboronic acid (21 mg, 0.18 mmol) was used instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above to obtain 13 mg (19% yield) of the title compound.

[0309] 1 H-NMR(300MHz, DMSO-d 6 ): δ 8.28 - 8.23 (m, 3H), 8.01 - 7.92 (m, 4H), 7.87 - 7.83 (m, 2H), 7.71 - 7.68 (m, 1H), 7.50 - 7.30 (m, 1H), 7.02 (s, 1H), 2.40 (d, J=4.8Hz, 3H).

[0310] MS(ESI + , m / z): 421.2 [M + H] +

[0311] Example 24: N-Methyl-3-(5-methylfuran-2-yl)-1-phenyl-1H-indole-5-sulfonamide

[0312]

[0313] The procedure of Example 10 was repeated except that bromobenzene (339 mg, 2.14 mmol) was used instead of 4-bromobenzotrifluoride in Example 10 above to obtain 5 mg (9% yield) of the title compound.

[0314] 1H-NMR(300MHz, DMSO-d 6 ): δ 8.40 (s, 1H), 8.12 (s, 1H), 7.74 - 7.60 (m, 6H), 7.52 - 7.46 (m, 1H), 7.47 - 7.42 (m, 1H), 6.69 - 6.68 (m, 1H), 6.26 - 6.25 (m, 1H), 2.42 (s, 3H), 2.40 (d, J=4.8Hz, 3H).

[0315] MS(ESI + , m / z): 367.2 [M + H] +

[0316] Example 25: 3-(2,3-Difluorophenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0317]

[0318] Except for using 2,3-difluorophenylboronic acid (32 mg, 0.21 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above, the procedure of Example 3 was repeated to obtain 10 mg (14% yield) of the title compound.

[0319] 1 H-NMR(300MHz, CDCl 3 ): δ 8.39 (s, 1H), 7.88 (d, J=8.6Hz, 2H), 7.81 - 7.67 (m, 5H), 7.49 - 7.44 (m, 1H), 7.24 - 7.18 (m, 2H), 4.29 - 4.25 (m, 1H), 2.68 (d, J=5.5Hz, 3H).

[0320] MS(ESI + , m / z): 467.2 [M + H] +

[0321] Example 26: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-phenyl-1H-indole-5-sulfonamide

[0322]

[0323] Except for using bromobenzene (339 mg, 2.14 mmol) instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5 above, the procedure of Example 5 was repeated to obtain 22 mg (35% yield) of the title compound.

[0324] 1H-NMR(300MHz, DMSO-d 6 ): δ 8.69 (s, 1H), 8.03 (s, 1H), 7.71 - 7.60 (m, 7H), 7.53 (s, 1H), 7.53 - 7.52 (m, 1H), 7.49 - 7.46 (m, 1H), 3.74 (s, 3H), 2.40 (d, J = 4.8Hz, 3H).

[0325] MS(ESI + , m / z): 367.2 [M + H] +

[0326] Example 27: 1-(3-Chloro-4-(trifluoromethyl)phenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide

[0327]

[0328] Except for using 4-bromo-2-chloro-1-(trifluoromethyl)benzene (566 mg, 2.14 mmol) instead of 1-bromo-4-(trifluoromethoxy)benzene in Example 5, the procedure of Example 5 was repeated to obtain 2.5 mg (3% yield) of the title compound.

[0329] 1 H-NMR(300MHz, CDCl 3 ): δ 8.51 - 8.50 (m, 1H), 7.91 - 7.87 (m, 2H), 7.80 - 7.66 (m, 3H), 7.58 - 7.56 (m, 2H), 7.33 (s, 1H), 4.63 - 4.61 (m, 1H), 3.80 (s, 3H), 2.66 (d, J = 4.9Hz, 3H).

[0330] MS(ESI + , m / z): 469.2 [M + H] +

[0331] Example 28: 3-(1-Cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0332]

[0333] Except for using tributyl-(1-cyclopropylimidazol-4-yl)stannane (73 mg, 0.18 mmol) instead of tributyl-(3-methylpyr -2-yl)stannane and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 3 mg (5% yield) of the title compound.

[0334] 1 H-NMR(300MHz,DMSO-d 6 ):δ8.75(d,J = 1.6Hz,1H),8.16(s,1H),8.00 - 7.90(m,4H),7.85 - 7.81(m,2H),7.67 - 7.62(m,2H),7.37 - 7.35(m,1H),3.62 - 3.55(m,1H),2.41(d,J = 4.8Hz,3H),1.03 - 0.99(m,4H).

[0335] MS(ESI + ,m / z):461.1[M + H] +

[0336] Example 29: 3-(1H-Imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0337]

[0338] Except using tert-butyl 4-(tributylstannyl)-1H-imidazole-1-carboxylate (150 mg, 0.33 mmol) instead of tributyl-(3-methylpyr -2-yl)stannane and using ethyl acetate:hexane = 4:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 14 mg (20% yield) of the title compound.

[0339] 1 H-NMR(300MHz,DMSO-d 6 ):δ12.2(brs,1H),8.73(s,1H),8.16(s,1H),7.99 - 7.90(m,4H),7.84 - 7.82(m,2H),7.67 - 7.65(m,1H),7.57(s,1H),7.36 - 7.34(m,1H),2.41(d,J = 4.8Hz,3H).

[0340] MS(ESI + ,m / z):421.2[M + H] +

[0341] Example 30: 3-(1-(2-fluorophenyl)-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0342]

[0343] In the above Example 1, in [Process-7], tributyl-[1-[(2-fluorophenyl)methyl]imidazol-4-yl]stannane (86 mg, 0.18 mmol) was used instead of tributyl-(3-methylpyridine) The procedure of Example 1 was repeated, except that ethyl acetate:hexane=1:1 (v / v) was used instead of dichloromethane:methanol=20:1 (v / v) during the purification, to obtain 9 mg (13% yield) of the title compound.

[0344] 1 H-NMR (300MHz, CDCl 3 ): δ8.53(d,J=1.4Hz,1H),7.89(s,1H),7.83(d,J=8.4Hz,2H),7.76-7.72(m,1H),7.67-7.64(m,4 H),7.36-7.35(m,2H),7.20-7.11(m,3H),5.27(s,2H),4.32-4.30(m,1H),2.66(d,J=5.5Hz,3H).

[0345] MS (ESI + ,m / z):529.3[M+H] +

[0346] Example 31: 3-(Furan-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0347]

[0348] The procedure of Example 3 was repeated except using 2-(2-furyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (31 mg, 0.16 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan in the above Example 3 to obtain 16 mg (32% yield) of the title compound.

[0349] 1 H-NMR (300 MHz, DMSO-d 6): δ 8.47 (d, J = 1.4 Hz, 1H), 8.35 (s, 1H), 8.02 - 7.94 (m, 4H), 7.87 - 7.83 (m, 2H), 7.71 (dd, J = 8.8, 1.7 Hz, 1H), 7.50 - 7.41 (m, 1H), 6.86 (d, J = 3.9 Hz, 1H), 6.67 (d, J = 1.9 Hz, 1H), 2.41 (s, 3H).

[0350] MS (ESI + , m / z): 421.2 [M + H] +

[0351] Example 32: N-Methyl-3-(2-methyl -1,2,4-oxazol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0352]

[0353] Except for using 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1,2,4-oxazole (27 mg, 0.13 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above, the procedure of Example 3 was repeated to obtain 4 mg (8% yield) of the title compound.

[0354] 1 1H-NMR (300 MHz, DMSO-d 6 ): δ 8.37 - 8.36 (m, 2H), 8.02 - 7.95 (m, 4H), 7.89 - 7.86 (m, 1H), 7.75 - 7.72 (m, 1H), 7.46 (s, 2H), 2.53 (s, 3H), 2.42 (d, J = 3.1 Hz, 3H).

[0355] MS (ESI + , m / z): 436.3 [M + H] +

[0356] Example 33: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide

[0357]

[0358] [Process-1] Preparation of indoline-6-sulfonic acid

[0359]

[0360] Indoline (10 g, 83.9 mmol) was added dropwise to 46 mL of sulfuric acid at 0 °C to 5 °C and stirred at 135 °C for one hour. After confirming the completion of the reaction, the mixture was cooled to room temperature, and the formed solid was filtered to synthesize 6.7 g (40% yield) of indoline-6-sulfonic acid.

[0361] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 7.63 - 7.61 (m, 2H), 7.43 - 7.41 (m, 1H), 3.77 - 3.72 (m, 2H), 3.22 - 3.17 (m, 2H).

[0362] [Process-2] Preparation of 1-acetylindoline-6-sulfonic acid

[0363]

[0364] Indoline-6-sulfonic acid (4.6 g, 23.1 mmol) was added to acetic anhydride (3.3 mL, 34.6 mmol) and pyridine (11.2 mL, 138.5 mmol) and stirred overnight at 100 °C. After completion of the reaction, the mixture was cooled to room temperature, ethyl acetate was added, and the mixture was washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure to synthesize 4.1 g (74% yield) of 1-acetylindoline-6-sulfonic acid.

[0365] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.33 (s, 1H), 7.28 - 7.25 (m, 1H), 7.16 - 7.14 (m, 1H), 4.12 - 4.08 (m, 2H), 3.13 - 3.08 (m, 2H), 2.16 (s, 3H).

[0366] [Process-3] Preparation of N-methylindoline-6-sulfonamide

[0367]

[0368] 1-Acetylindoline-6-sulfonic acid (4 g, 16.6 mmol) was dissolved in 50 mL of acetonitrile, to which a catalytic amount of dimethylformamide and POCl 3(8 mL, 85 mmol). The mixture was refluxed and heated for 1 hour, concentrated and then placed on ice, and the solid formed was filtered to obtain 1-acetylindoline-6-sulfonyl chloride as a brown solid, which was used in the next process without further purification. 1-Acetylindoline-6-sulfonyl chloride was dissolved in dichloromethane, 2M methylamine (23 mL, 69.3 mmol) was added thereto, and the mixture was stirred at room temperature for 3 hours. After confirming the completion of the reaction, the solvent was removed by reducing the pressure, and then 40 mL of methanol and concentrated HCl (3 mL, 92.4 mmol) were added thereto and stirred at 80 °C. After confirming the completion of the reaction, ethyl acetate was added and washed with water. The organic layer was dried over anhydrous sodium sulfate and filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure and purified with dichloromethane:methanol = 10:1 (v / v) to obtain 2.6 g (53% yield) of the title compound.

[0369] 1 H-NMR(300MHz,CDCl 3 ): δ 7.19 - 7.18 (m, 2H), 7.04 (s, 1H), 3.66 (t, J = 8.5 Hz, 2H), 3.01 (t, J = 8.5 Hz, 2H), 2.66 (d, J = 3.3 Hz, 3H).

[0370] [Process-4] Preparation of N-methyl-1H-indole-6-sulfonamide

[0371]

[0372] N-Methylindoline-6-sulfonamide (1.8 g, 8.5 mmol) prepared in the above [Process-3] was dissolved in 20 mL of dichloromethane, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 1.9 g, 8.5 mmol) was added thereto, and the reaction solution was stirred overnight at room temperature. After the completion of the reaction, the reaction solution was filtered through diatomaceous earth and washed with dichloromethane. After concentration under reduced pressure, the resulting residue was purified by MPLC (ethyl acetate:hexane = 1:10 (v / v)) to obtain 1.9 g (58% yield) of the title compound.

[0373] 1 H-NMR(300MHz,CDCl 3 ): δ 8.10 (s, 1H), 7.70 - 7.56 (m, 1H), 7.55 - 7.52 (m, 1H), 7.40 - 7.38 (m, 1H), 6.57 - 6.56 (m, 1H), 4.99 - 4.97 (m, 1H), 2.55 (d, J = 5.3 Hz, 3H).

[0374] [Process-5] Preparation of N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-ind ole-6-sulfonamide

[0375]

[0376] The procedure of Example 2 was repeated except using N-methyl-1H-indole-6-sulfonamide (1 g, 4.75 mmol) instead of N-methyl-1H-indole-5-sulfonamide in Example 2 above to afford 18 mg (16% yield) of the title compound.

[0377] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.39 - 8.28 (m, 1H), 8.37 (s, 1H), 8.04 - 8.02 (m, 3H), 7.93 - 7.90 (m, 2H), 7.72 (s, 1H), 7.65 - 7.62 (m, 2H), 7.38 - 7.36 (m, 1H), 3.73 (s, 3H), 2.40 (d, J = 6.0 Hz, 3H).

[0378] MS (ESI + , m / z): 435.1 [M+H] +

[0379] Example 34: N-Methyl-3-(5-(trifluoromethyl)furan-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0380]

[0381] The procedure of Example 3 was repeated except using 4,4,5,5-tetramethyl-2-(5-(trifluoromethyl)furan-2-yl)-1,3,2-dioxaborolane (68 mg, 0.25 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above to afford 30 mg (25% yield) of the title compound.

[0382] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.55 (s, 1H), 8.45 (d, J = 1.3 Hz, 1H), 8.03 - 7.97 (m, 4H), 7.90 - 7.87 (m, 1H), 7.77 - 7.73 (m, 1H), 7.48 - 7.42 (m, 2H), 7.07 (d, J = 3.6 Hz, 1H), 2.43 (d, J = 2.9 Hz, 3H).

[0383] MS (ESI + , m / z): 489.4 [M+H]+

[0384] Example 35: N-Methyl-3-(1-(oxetan-3-yl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0385]

[0386] Except using 1-(oxetan-3-yl)-4-(tributylstannyl)-1H-imidazole (209 mg, 0.51 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above, the procedure of Example 1 was repeated to obtain 5 mg (4% yield) of the title compound. -2-yl)stannane, the procedure of Example 1 was repeated to obtain 5 mg (4% yield) of the title compound.

[0387] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.56 (s, 1H), 7.92 (s, 1H), 7.86 - 7.84 (m, 2H), 7.78 - 7.75 (m, 2H), 7.70 - 7.69 (m, 2H), 7.67 - 7.66 (m, 1H), 7.61 - 7.60 (m, 1H), 5.40 - 5.39 (m, 1H), 5.19 (t, J = 7.1 Hz, 2H), 5.00 - 4.96 (m, 2H), 4.35 - 4.33 (m, 1H), 2.69 (d, J = 5.5 Hz, 3H).

[0388] MS (ESI + , m / z): 477.2 [M+H] +

[0389] Example 36: 3-(5-Chlorofuran-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0390]

[0391] Except using 2-(5-chloro-2-furyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (74 mg, 0.32 mmol) instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above, the procedure of Example 3 was repeated to obtain 4 mg (3% yield) of the title compound.

[0392] 1 H-NMR (300 MHz, DMSO-d 6): δ 8.39 (s, 1H), 8.02 - 7.84 (m, 6H), 7.74 (d, J = 1.6 Hz, 1H), 7.47 - 7.45 (m, 1H), 6.94 (d, J = 3.4 Hz, 1H), 6.69 (d, J = 3.4 Hz, 1H), 2.42 (d, J = 4.4 Hz, 3H).

[0393] MS(ESI + , m / z): 455.0 [M + H] +

[0394] Example 37: N-Methyl-3-(1-(2,2,2-trifluoroethyl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0395]

[0396] Except using tributyl-[1-[(2-fluoroethyl)imidazol-4-yl]stannane (158 mg, 0.36 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process - 7] of Example 1 above and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 30 mg (26% yield) of the title compound.

[0397] 1 1H-NMR (300 MHz, DMSO-d 6 ): δ 8.73 (d, J = 1.4 Hz, 1H), 8.26 (s, 1H), 8.00 - 7.92 (m, 5H), 7.86 (d, J = 8.8 Hz, 1H), 7.69 - 7.65 (m, 2H), 7.36 - 7.35 (m, 1H), 5.18 - 5.11 (m, 2H), 2.41 (d, J = 5.1 Hz, 3H).

[0398] MS(ESI + , m / z): 503.4 [M + H] +

[0399] Example 38: 3-(1-(2-Methoxyethyl)-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0400]

[0401] ​Except for using tributyl-[1-(2-methoxyethyl)imidazol-4-yl)stannane (316 mg, 0.76 mmol) instead of tributyl-(3-methylpyr -2-yl)stannane in [Process-7] of Example 1 above, the procedure of Example 1 was repeated to obtain 30 mg (24% yield) of the title compound.

[0402] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.74 (s, 1H), 8.16 (s, 1H), 7.99 - 7.91 (m, 4H), 7.85 - 7.82 (m, 1H), 7.77 (s, 1H), 7.68 - 7.64 (m, 1H), 7.60 (s, 1H), 7.36 - 7.34 (m, 1H), 4.22 (t, J = 5.0 Hz, 2H), 3.67 (t, J = 5.2 Hz, 2H), 3.29 (s, 3H), 2.41 (d, J = 5.0 Hz, 3H).

[0403] MS (ESI + , m / z): 479.2 [M+H] +

[0404] Example 39: N-Methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(p-tolyl)-1H-indole-5-sulfonamide

[0405]

[0406] Except for using 1-bromo-4-methyl-benzene (747 mg, 4.28 mmol) instead of 4-bromobenzotrifluoride in [Process-5] of Example 1 above, using tributyl-(1-methylimidazol-4-yl)stannane (132 mg, 0.35 mmol) instead of tributyl-(3-methylpyr -2-yl)stannane in [Process-7], and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 16 mg (23% yield) of the title compound.

[0407] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.69 (d, J = 1.2 Hz, 1H), 7.98 (s, 1H), 7.71 - 7.70 (m, 1H), 7.66 - 7.52 (m, 5H), 7.43 - 7.40 (m, 2H), 7.30 - 7.28 (m, 1H), 3.74 (s, 3H), 2.41 - 2.39 (m, 6H).

[0408] MS(ESI + , m / z): 381.2 [M+H] +

[0409] Example 40: 1-(4-(tert-Butyl)phenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide

[0410]

[0411] Except using 1-bromo-4-tert-butyl-benzene (979 mg, 4.41 mmol) instead of 4-bromobenzotrifluoride in [Process-5] of Example 1 above, using tributyl-(1-methylimidazol-4-yl)stannane (176 mg, 0.47 mmol) instead of tributyl-(3-methylpyr -2-yl)stannane in [Process-7] and using ethyl acetate:hexane = 2:1 (v / v) instead of dichloromethane:methanol = 20:1 (v / v) during purification, the procedure of Example 1 was repeated to obtain 50 mg (48% yield) of the title compound.

[0412] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.70 (d, J = 1.4 Hz, 1H), 8.01 (s, 1H), 7.73 - 7.57 (m, 7H), 7.52 (d, J = 1.2 Hz, 1H), 7.31 (s, 1H), 3.75 (s, 3H), 2.41 (d, J = 4.6 Hz, 3H), 1.38 (s, 9H).

[0413] MS(ESI + , m / z): 423.2 [M+H] +

[0414] Example 41: N-methyl-3-( azol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0415]

[0416] Except using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) The procedure of Example 3 was repeated except that 1-cyclopropyl-1H-imidazole (189 mg, 0.97 mmol) was used instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above and ethyl acetate:hexane = 2:1 (v / v) was used instead of ethyl acetate:hexane = 1:1 (v / v) during purification to afford 16 mg (5% yield) of the title compound.

[0417] 1 H-NMR(300MHz,CDCl 3 ): δ 8.52 (s, 1H), 7.99 (s, 1H), 7.90 - 7.80 (m, 4H), 7.69 - 7.65 (m, 3H), 7.42 (s, 1H), 4.34 (brs, 1H), 2.71 (d, J = 5.5 Hz, 3H).

[0418] MS(ESI + , m / z): 422.1 [M + H] +

[0419] Example 42: 3-(1-Cyclopropyl-1H-imidazol-4-yl)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-N-methyl-1H-indole-5-sulfonamide

[0420]

[0421] The procedure of Example 28 was repeated except that 1-bromo-2-fluoro-4-(trifluoromethyl)benzene (367 mg, 1.42 mmol) was used instead of 4-bromobenzotrifluoride in Example 28 above to afford 11 mg (6% yield) of the title compound.

[0422] 1 H-NMR(300MHz,CDCl 3 ): δ 8.55 (s, 1H), 7.84 (s, 1H), 7.83 - 7.77 (m, 4H), 7.63 - 7.40 (m, 2H), 4.46 - 4.44 (m, 1H), 3.49 - 3.44 (m, 1H), 2.71 (t, J = 5.4 Hz, 1H), 2.70 (d, J = 5.4 Hz, 3H), 0.87 - 0.85 (m, 4H).

[0423] MS(ESI + , m / z): 479.1 [M + H] +

[0424] Example 43: 3-(1-Cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonamide

[0425]

[0426] [Process-1] Preparation of 5-bromo-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine

[0427]

[0428] 5-Bromo-1H-pyrrolo[2,3-b]pyridine (1 g, 5.07 mmol) was dissolved in 5 mL of 1,4-dioxane, and then racemic trans-1,2-diaminocyclohexane (0.013 mL, 0.10 mmol), copper(I) iodide (1.9 mg, 0.01 mmol), potassium tripolyphosphate (538 mg, 2.54 mmol), and 1-iodo-4-(trifluoromethyl)benzene (1.42 g, 5.07 mmol) were added sequentially, and the reaction solution was refluxed and stirred overnight under nitrogen. After completion of the reaction, the mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate. The residue obtained after concentration under reduced pressure was subjected to extraction with ethyl acetate. The organic layer thus obtained was dried over anhydrous sodium 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 = 1:9 (v / v)) to give 800 mg (46% yield) of the title compound.

[0429] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.39 (d, J = 2.2 Hz, 1H), 8.09 (d, J = 2.2 Hz, 1H), 7.93 - 7.90 (m, 2H), 7.78 - 7.75 (m, 2H), 7.55 (d, J = 3.7 Hz, 1H), 6.62 (d, J = 3.7 Hz, 1H).

[0430] [Process-2] Preparation of 5-(benzylthio)-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine

[0431]

[0432] ​5-Bromo-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine (800 mg, 2.34 mmol) obtained from the above [Process-1] was dissolved in 10 mL of toluene, and then benzyl mercaptan (0.27 mL, 2.34 mmol), [bis(dibenzylideneacetone)palladium(0)] (214 mg, 0.23 mmol), xantphos (271 mg, 0.47 mmol) and N,N-diisopropylethylamine (1.22 mL, 7.03 mmol) were added, and the reaction solution was refluxed and stirred overnight. After confirming the completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 = 1:9 (v / v)) to obtain 900 mg (98% yield) of the title compound.

[0433] 1 H-NMR(300MHz,CDCl 3 ):δ8.36(s,1H),7.98-7.92(m,3H),7.81-7.78(m,2H),7.56(d,J=3.7Hz,1H),7.29-7.19(m,5H),6.62(d,J=3.7Hz,1H),4.07(s,2H).

[0434] [Process-3] Preparation of 1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonyl chloride

[0435]

[0436] 5-(Benzylthio)-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine (900 mg, 2.34 mmol) obtained from the above [Process-2] was dissolved in 19.8 mL of acetic acid:water = 10:1 (v / v), and N-chlorosuccinimide (937 mg, 7.02 mmol) was slowly added thereto while cooling to 0 °C to 5 °C. The reaction mixture was stirred at 0 °C to 5 °C for 15 minutes. The temperature was raised to room temperature and then the mixture was stirred overnight. After confirming the completion of the reaction, the mixture was subjected to extraction with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 = 1:9 (v / v)) to obtain 380 mg (45% yield) of the title compound.

[0437] 1 H-NMR(300MHz,CDCl 3): δ 9.01 (d, J = 2.3 Hz, 1H), 8.66 (d, J = 2.3 Hz, 1H), 7.95 - 7.92 (m, 2H), 7.86 - 7.83 (m, 2H), 7.77 (d, J = 3.7 Hz, 1H), 6.92 (d, J = 3.7 Hz, 1H).

[0438] [Process-4] Preparation of N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonamide

[0439]

[0440] 1-(4-(Trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonyl chloride (380 mg, 1.05 mmol) obtained from the above [Process - 3] was dissolved in 7.6 mL of dichloromethane, and 2 M methylamine in tetrahydrofuran solution (4.2 mL, 2.10 mmol) was added dropwise thereto and stirred overnight at room temperature. After completion of the reaction, the mixture was subjected to extraction with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 = 1:2 (v / v)) to give 370 mg (44% yield) of the title compound.

[0441] 1 H-NMR (300 MHz, CDCl 3 ): δ 8.85 (d, J = 2.1 Hz, 1H), 8.50 (d, J = 2.1 Hz, 1H), 7.96 - 7.93 (m, 2H), 7.84 - 7.81 (m, 2H), 7.70 (d, J = 3.7 Hz, 1H), 6.83 (d, J = 3.7 Hz, 1H), 4.41 - 4.35 (m, 1H), 2.73 (d, J = 5.4 Hz, 3H).

[0442] [Process-5] Preparation of 3-bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5- sulfonamide

[0443]

[0444] The N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonamide (370 mg, 1.04 mmol) obtained from the above [Process-4] was dissolved in 7.4 mL of dimethylformamide, and N-bromosuccinimide (198 mg, 1.09 mmol) was slowly added dropwise thereto. The reaction solution was stirred at room temperature for 1.5 hours to complete the reaction, 100 mL of water was added thereto, and then it was extracted three times with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 = 1:3 (v / v)) to obtain 190 mg (42% yield) of the title compound.

[0445] 1 H-NMR(300MHz,CDCl 3 ):δ8.87(s,1H),8.46(d,J=2.1Hz,1H),7.92-7.89(m,2H),7.84-7.81(m,2H),7.74(s,1H),4.50-4.48(m,1H),2.74(d,J=5.4Hz,3H).

[0446] [Process-6] 3-(1-cyclo-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo [2,3-b]pyridine-5-sulfonamide

[0447]

[0448] The 3-bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonamide (70 mg, 0.16 mmol) obtained from the above [Process-5] was dissolved in 1.4 mL of dimethylacetamide, and then copper(II) chloride (3.2 mg, 0.03 mmol), cesium fluoride (74 mg, 0.48 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (23 mg, 0.03 mmol) and tributyl-(1-cyclopropylimidazol-4-yl)stannane (103 mg, 0.25 mmol) were added. Then the reaction solution was stirred at 100 °C overnight. After the reaction was completed, water was added and then it was extracted three times with ethyl acetate. Thus, the organic layer was dehydrated over anhydrous sodium sulfate, filtered under reduced pressure, and the filtered organic layer was concentrated under reduced pressure, and the resulting residue was purified by MPLC (dichloromethane:methanol = 20:1 (v / v)) to obtain 4 mg (5% yield) of the title compound.

[0449] 1 H-NMR(300MHz,DMSO-d 6): δ 9.01 (d, J = 2.2 Hz, 1H), 8.74 (d, J = 2.2 Hz, 1H), 8.54 (s, 1H), 8.26 - 8.25 (m, 2H), 8.12 (s, 1H), 8.00 - 7.97 (m, 2H), 7.90 - 7.83 (m, 1H), 7.63 - 7.61 (m, 1H), 3.69 - 3.61 (m, 1H), 2.45 (s, 3H), 1.08 - 1.02 (m, 4H).

[0450] MS(ESI + , m / z): 462.2 [M+H] +

[0451] Example 44: 3-(1-Cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide

[0452]

[0453] Except for using 5-bromo-1H-indazole (5 g, 25.4 mmol) instead of 5-bromo-1H-pyrrolo[2,3-b]pyridine in [Process-1] of Example 43 above, the procedure of Example 43 was repeated to obtain 11 mg (9% yield) of the title compound.

[0454] 1 1H-NMR (300 MHz, DMSO-d 6 ): δ 9.01 (s, 1H), 8.34 - 8.21 (m, 3H), 8.12 - 8.01 (m, 3H), 7.91 - 7.64 (m, 2H), 7.52 (s, 1H), 3.69 - 3.61 (m, 1H), 2.28 - 2.27 (m, 3H), 1.10 - 0.98 (m, 4H).

[0455] MS(ESI + , m / z): 462.1 [M+H] +

[0456] Example 45: 3-(6,7-Dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0457]

[0458] The procedure of Example 3 was repeated except that 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (43 mg, 0.17 mmol) was used instead of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in Example 3 above to afford 26 mg (34% yield) of the title compound.

[0459] 1 H-NMR(300MHz,DMSO-d 6 ): δ 8.69 (d, J = 1.4 Hz, 1H), 8.13 (s, 1H), 7.99 - 7.91 (m, 4H), 7.83 (d, J = 8.9 Hz, 1H), 7.67 - 7.64 (m, 1H), 7.52 (s, 1H), 7.37 - 7.35 (m, 1H), 4.04 (t, J = 6.8 Hz, 2H), 2.84 (t, J = 7.3 Hz, 2H), 2.59 - 2.56 (m, 2H), 2.40 (d, J = 4.4 Hz, 3H).

[0460] MS(ESI + , m / z): 461.1 [M + H] +

[0461] Example 46: 3-(3-Fluoroazetidin-1-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0462]

[0463] 3-Bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide (200 mg, 0.46 mmol) obtained in the above Example 1 [Process - 6] was dissolved in 4 mL of 1,4-d ane, and then 3-fluoroazetidine hydrochloride (63 mg, 0.55 mmol), tris(dibenzylideneacetone)dipalladium(0) ([Pd 2 (dba) 3 (21 mg, 0.02 mmol), xantphos (40 mg, 0.06 mmol) and cesium carbonate (455 mg, 1.38 mmol) were added thereto. The reaction solution was stirred at 110 °C for 4 hours to complete the reaction, 10 mL of water was added thereto, and then the mixture was extracted three times with ethyl acetate. The organic layer thus obtained was dehydrated over anhydrous sodium 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 = 1:3 (v / v)) to afford 10 mg (5% yield) of the title compound.

[0464] 1 H-NMR(300MHz, DMSO-d 6 ): δ 7.94 - 7.93 (m, 3H), 7.91 - 7.79 (m, 3H), 7.63 - 7.59 (m, 1H), 7.36 (s, 1H), 5.64 - 5.40 (m, 1H), 4.37 - 4.25 (m, 2H), 4.06 - 3.93 (m, 2H), 2.40 - 2.38 (m, 3H).

[0465] MS(ESI + , m / z): 428.1 [M + H] +

[0466] Example 47: N,N-Dimethyl-2-(4-(5-(N-methylsulfamoyl)-1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)-1H-imidazol-1-yl)acetamide

[0467]

[0468] Except for using N,N-dimethyl-2-(4-(tributylstannyl)-1H-imidazol-1-yl)acetamide (326 mg, 0.74 mmol) instead of tributyl-(3-methylpyridin-2-yl)tin in [Process - 7] of Example 1 above, the procedure of Example 1 was repeated to obtain 50 mg (27% yield) of the title compound. -2-yl)tin in [Process - 7] of Example 1 above, the procedure of Example 1 was repeated to obtain 50 mg (27% yield) of the title compound.

[0469] 1 H-NMR(300MHz, DMSO-d 6 ): δ 8.70 (d, J = 1.5 Hz, 1H), 8.16 (s, 1H), 8.00 - 7.92 (m, 4H), 7.85 - 7.82 (m, 1H), 7.68 (s, 1H), 7.68 - 7.64 (m, 1H), 7.49 (s, 1H), 7.36 - 7.35 (m, 1H), 5.09 (s, 2H), 3.06 (s, 3H), 2.89 (s, 3H), 2.41 (d, J = 5.0 Hz, 3H).

[0470] MS(ESI + , m / z): 506.1 [M + H] +

[0471] Example 48: N-Methyl-3-(1-(2-(methylsulfonyl)ethyl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide

[0472]

[0473] Except using 1-(2-(methylsulfonyl)ethyl)-4-(tributylstannyl)-1H-imidazole (510 mg, 1.10 mmol) instead of tributyl-(3-methylpyridin-2-yl)stannane in [Process-7] of Example 1 above, the procedure of Example 1 was repeated to obtain 65 mg (21% yield) of the title compound. -2-yl)stannane in [Process-7] of Example 1 above, the procedure of Example 1 was repeated to obtain 65 mg (21% yield) of the title compound.

[0474] 1 H-NMR (300 MHz, DMSO-d 6 ): δ 8.70 (d, J = 1.4 Hz, 1H), 8.22 (s, 1H), 8.19 - 7.95 (m, 4H), 7.92 - 7.82 (m, 2H), 7.75 - 7.65 (m, 2H), 7.38 - 7.33 (m, 1H), 4.52 (t, J = 7.0 Hz, 2H), 3.77 (t, J = 7.4 Hz, 2H), 2.96 (s, 3H), 2.41 (d, J = 5.0 Hz, 3H).

[0475] MS (ESI + , m / z): 527.1 [M + H] +

[0476] Experimental Example 1: TEAD Reporter Activity Inhibition Test

[0477] Measure the ability of the synthesized compound to inhibit the transcription of the TEAD target gene. This evaluation method measures the transcriptional activity of TEAD as follows: Using the MCF7 cell line (BPS Bioscience, Inc., USA) in which the firefly luciferase reporter gene has been introduced into the specific binding structure GTIIC (5'-ACATTCCA-3') of TEAD, measure the luciferase bioluminescence exhibited when TEAD binds to the target gene and activates transcription. 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, and Geneticin was excluded when testing the inhibition of TEAD reporter activity. 4×10 4 cells / 100 μl were dispensed into white 96-well plates and cultured for 6 hours. 50 μl of the test compound diluted to 3X concentration was mixed into each well. After culturing the cells for 24 hours, using the ONE-Glo luciferase assay system (Promega, E6120), according to the manufacturer's protocol, measure the luciferase signal based on bioluminescence. Use GraphPad Prism 9 to calculate the 50% inhibition value (IC 50 ) of TEAD transcriptional activity.

[0478] If the IC 50 value is less than 100 nM, it is designated as A; if it is at least 100 nM but less than 500 nM, it is designated as B; and if it is 500 nM or greater, it is designated as C.

[0479] [Table 1]

[0480] Synthesize compound <![CDATA[IC 50 ,nM]]> Synthesize compound <![CDATA[IC 50 ,nM]]> 1 C 25 A 2 A 26 C 3 B 27 A 4 B 28 A 5 B 29 B 6 C 30 A 7 B 31 A 8 A 32 A 9 B 33 B 10 A 34 B 11 A 35 B 12 B 36 B 13 A 37 A 14 B 38 A 15 B 39 B 16 A 40 A 17 B 41 B 18 C 42 A 19 C 43 A 20 A 44 A 21 B 45 A 22 C 46 A 23 A 47 C 24 B 48 B

[0481] Experimental Example 2: Cell Growth Inhibition Test

[0482] It was confirmed that the synthetic compound inhibits the cell growth of NCI-H226 cells. NCI-H226 is a mesothelioma cancer cell line lacking the NF2 gene and is cultured in RPMI 1640 medium supplemented with 10% FBS and 1% penicillin / streptomycin. The cultured cells were dispensed at 0.7×10 3 cells / 100 μl into 96-well plates and cultured for 24 hours. Then, 100 μl of the test compound diluted to 2X concentration was mixed into each well and cultured for 6 days. The cell growth inhibition was measured using the SRB test method, and the 50% inhibition value (GI 50 ) of the compound on cell growth was calculated using GraphPad Prism 9.

[0483] If the GI 50 value is less than 100 nM, it is designated as A, and if it is 100 nM or greater, it is designated as B.

[0484] [Table 2]

[0485] Synthesize compound <![CDATA[GI 50 ,nM]]> Synthesize compound <![CDATA[GI 50 ,nM]]> 2 A 28 A 8 A 31 A 10 A 32 A 11 A 38 A 13 B 42 A 16 A 43 A 20 A 44 A 23 A

[0486] So far, the present disclosure has been examined with a focus on specific embodiments. Those skilled in the art to which the present disclosure pertains can 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 group consisting of a compound of the following formula 1, its mirror image isomers, diastereomers, solvates and hydrates, and pharmaceutically acceptable salts thereof: [Formula 1] in, In the above formula 1, R 1 and R 2 are independently hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Carbocyclic or halogenated 1-6 alkyl; R 3 For hydrogen, halogen, C 1-6 Alkyl, halogen C 1-6 Alkyl, C 1-6 Alkoxy or cyano; is a carbocyclic group or a heterocyclic group; C 6-10 Aryl or C 4-10 heteroaryl; L 1 is absent, bonded, or C 1-3 Alkylene, or halogen-substituted C 1-3 Alkylene; Each R 4 And each R 5 are independently hydrogen, halogen, cyano, amine, C 1-6 Alkyl, halogen C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, halogen C 1-6 Alkoxy, mono-(C 1-3 Alkyl) substituted carbamoyl (-(CO)-NH(C 1-3 alkyl)), di-(C 1-3 Alkyl) substituted carbamoyl (-(CO)-N(C 1-3 alkyl) 2 ), C 1-3 Alkylsulfinyl (-(SO)-(C 1-3 Alkyl)), C 1-3 Alkylsulfonyl (-SO 2 -(C 1-3 alkyl)), substituted or unsubstituted C 3-6 Carbocyclic group, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted C 2-6 Heterocyclic group, substituted or unsubstituted C 4-10 heteroaryl; X and Y are each independently -C- or -N-; and m and n are each independently an integer of 0 to 3.

2. The compound according to claim 1, wherein C 6-10 Aryl, C 1-10 Heteroaryl, C 6-14 Fused heteroaryl, or C 2-6 Heterocyclic group, Among them C 1-10 Heteroaryl, C 6-14 Fused heteroaryl or C 2-6 The heterocyclyl group contains 1 to 4 heteroatoms each independently selected from N, O and S.

3. A compound according to claim 1, wherein Phenyl, pyridyl, pyridinyl yl, pyrazolyl, imidazolyl, thienyl, furanyl, Azolyl, azetidinyl, or 4. A compound according to claim 1, wherein It is phenyl or pyridyl.

5. The compound according to claim 1, wherein R 1 and R 2 are independently hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl or halogen C 1-6 alkyl.

6. The compound according to claim 1, wherein L 1 is a single bond; Each R 4 And each R 5 are independently hydrogen, halogen, cyano, C 1-6 Alkyl, halogen C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, halogen C 1-6 Alkoxy, mono-(C 1-3 Alkyl) substituted carbamoyl (-(CO)-NH(C 1-3 alkyl)), di-(C 1-3 Alkyl) substituted carbamoyl (-(CO)-N(C 1-3 alkyl) 2 ), C 1-3 Alkylsulfonyl (-SO 2 -(C 1-3 alkyl)), substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 6-10 Aryl, or substituted or unsubstituted C 2-6 Heterocycloalkyl.

7. The compound according to claim 1, wherein L 1 C 1-3 Alkylene; Each R 4 And each R 5 are independently hydrogen, halogen, cyano, C 1-6 Alkyl, halogen C 1-6 Alkyl, C 1-6 Alkoxy, halogen C 1-6 Alkoxy, di-(C 1-3 Alkyl) substituted carbamoyl (-(CO)-N(C 1-3 alkyl) 2 ), C 1-3 Alkylsulfonyl (-SO 2 -(C 1-3 alkyl)), substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 6-10 Aryl, or substituted or unsubstituted C 2-6 Heterocycloalkyl.

8. A compound according to claim 1, wherein R 5 Each is hydrogen, halogen, cyano, C 1-6 Alkyl, halogen C 1-6 Alkyl, C 1-6 Alkoxy, halogen C 1-6 Alkoxy, C 3-6 Cycloalkyl, or phenyl, or C substituted with any one or more substituents selected from the following 3-6 Cycloalkyl or phenyl: halogen, cyano, C 1-6 Alkyl, halogen C 1-6 Alkyl, C 1-6 Alkoxy and halogen C 1-6 Alkoxy.

9. The compound according to claim 1, wherein R 5 Each is hydrogen, halogen, cyano, methyl, ethyl, propyl, tert-butyl, trifluoromethyl, trifluoromethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl.

10. The compound according to claim 1, wherein the compound is selected from the following compounds, their mirror image isomers, diastereomers, solvates and hydrates, and pharmaceutically acceptable salts thereof: N-methyl-3-(3-methylpyridine -2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-pyrazol-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-sulfonamide; 3-(1-Isopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-ethyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(pyridin-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(5-methylthiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(5-methylfuran-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(1-ethyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indole-5-sulfonamide; 3-(2-Fluorophenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 1-(4-chlorophenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide; N-methyl-3-(pyridin-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(1-cyclobutyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 1-(4-cyclohexylphenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide; N,N-dimethyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(3-fluoropyridin-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(3-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 1-(4-cyanophenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide; 3-(Furan-3-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(5-methylfuran-2-yl)-1-phenyl-1H-indole-5-sulfonamide; 3-(2,3-difluorophenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-phenyl-1H-indole-5-sulfonamide; 1-(3-chloro-4-(trifluoromethyl)phenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide; 3-(1-cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(1-(2-fluorophenyl)-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(Furan-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(2-methyl oxazol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide; N-methyl-3-(5-(trifluoromethyl)furan-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-(oxetan-3-yl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(5-chlorofuran-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-(2,2,2-trifluoroethyl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(1-(2-methoxyethyl)-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1-(p-tolyl)-1H-indole-5-sulfonamide; 1-(4-(tert-butyl)phenyl)-N-methyl-3-(1-methyl-1H-imidazol-4-yl)-1H-indole-5-sulfonamide; N-methyl-3-( oxazol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(1-cyclopropyl-1H-imidazol-4-yl)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-N-methyl-1H-indole-5-sulfonamide; 3-(1-cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-sulfonamide; 3-(1-cyclopropyl-1H-imidazol-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide; 3-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; 3-(3-Fluoroazetidin-1-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide; N,N-dimethyl-2-(4-(5-(N-methylsulfamoyl)-1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)-1H-imidazol-1-yl)acetamide; and N-methyl-3-(1-(2-(methylsulfonyl)ethyl)-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-sulfonamide.

11. A pharmaceutical composition for treating or preventing diseases caused by transcription enhancer associated domain (TEAD) activation, comprising a compound according to any one of claims 1 to 10 as an active ingredient, wherein the compound is selected from the group consisting of the compounds, their mirror image isomers, diastereomers, solvates and hydrates, and pharmaceutically acceptable salts thereof. 12 . The pharmaceutical composition according to claim 11 , wherein the pharmaceutical composition exhibits inhibitory activity against Yes-associated protein (YAP)-transcriptional enhancer associated domain (TEAD) binding.

13. The pharmaceutical composition according to claim 11, wherein the pharmaceutical composition is used to treat cancer or tumor that can be treated by exhibiting inhibitory activity against YAP-TEAD binding.

Images