Novel compound, preparation method thereof, and use thereof

Abstract

To provide a novel compound that inhibits Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1), an isomer thereof or a pharmaceutically acceptable salt thereof, and methods of preparing them; and a pharmaceutical composition comprising the compound, the isomer thereof or the pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of cancer, inflammatory disease or metabolic disease.SOLUTION: The present invention provides a compound represented by the formula 1 in the figure, an isomer thereof or a pharmaceutically acceptable salt thereof. In the formula: Ar is aryl or heteroaryl; R1 and R2 are hydrogen, halogen or heterocycloalkyl alkoxy; R3 is hydrogen, halogen, alkoxy, or the like; L1 is a sulfonamide or a sulfinamide; L2 is a single bond, alkylene, or the like; and Z is aryl, cycloalkyl fused with heteroaryl, or the like.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a pharmaceutical composition for the prevention or treatment of cancer, inflammatory diseases, or metabolic diseases, and in particular to a pharmaceutical composition comprising, as an active ingredient, a compound that inhibits Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) for the prevention or treatment of cancer, inflammatory diseases, or metabolic diseases. [Background technology]

[0002] The prolyl isomerase Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) is an enzyme that catalyzes the cis / trans isomerization of proline amide residues by binding to phosphorylated Ser / Thr-Pro sites (Non-Patent Document 1). During intracellular signaling processes, serine (Ser), threonine (Thr), and tyrosine (Tyr) residues in proteins are phosphorylated. After this phosphorylation, Pin1 changes the structure of various proteins by cis / trans isomerization of proline amide residues, allowing these proteins to initiate their functions within cells.

[0003] Previous studies have shown that the Pin1 enzyme is involved in the development and progression of inflammatory diseases, metabolic diseases, and cancer. In particular, the Pin1 enzyme has been reported to activate 56 oncogenes involved in carcinogenesis, such as beta-catenin, AKT, AR, CyclinD1, Plk, NF-kB, Stat3, Myc, c-Jun, c-Fos, c-Myb, Raf-1, HIF-1, Nanog, Notch1, and Oct4, and to inhibit the activity of 26 tumor suppressor genes, such as ATR, Bax, Btk, FADD, Fbw7, and PML, thereby inducing cancer metastasis and angiogenesis throughout the entire cancer development mechanism. Therefore, much research has been conducted on the Pin1 protein as a cancer diagnostic reagent, a prognostic factor, and a target for the development of useful new anticancer drugs (Non-Patent Document 2, Non-Patent Document 3).

[0004] Studies using surgically resected specimens have shown that Pin1 is highly expressed in various types of cancer, including colon, cervical, breast, lung, pancreatic, gastric, and liver cancers. Indeed, transgenic mice overexpressing Pin1 have been reported to exhibit oncogenic phenotypes. Furthermore, cancer cells knocked down with Pin1 using specific inhibitors or siRNA can induce mitotic arrest and apoptosis, suppressing cancer stem cell properties. In particular, the Pin1 enzyme functions to induce self-renewal, metastasis, and tumorigenesis of breast cancer stem cells.

[0005] Overexpression of Pin1 induces differentiation of human breast epithelial cells into pseudostem cells, resulting in an epithelial-to-mesenchymal transition. In other words, as cancer cells invasively grow and metastasize, they break adhesions with surrounding cells and migrate through blood or lymphatic vessels, loosening cell-cell bonds, altering the cell cytoskeleton, and acquiring motility. The Pin1 enzyme is known to be a key factor in stem cell self-renewal and maintains the stability of Nanog, Oct4, and Myc proteins.

[0006] As mentioned above, Pin1 is involved in many mechanisms in the body, but Pin1 knockout mice are known to grow well without any major problems. Therefore, it is expected that inhibiting Pin1 will not have a significant effect on the human body. However, although there are reports that Pin1 may be useful in treating Alzheimer's disease in the brain, there are also reports that it has the opposite effect in Parkinson's disease, and many aspects remain to be identified. In conclusion, Pin1 plays a very important role in cancer development overall, and Pin1 is involved in areas other than the brain. Inhibition of n1 is highly useful for the effective and safe treatment of cancer.

[0007] Furthermore, it has been reported that inhibition of Pin1 or knockdown of Pin1 gene expression attenuates the production of prostaglandin E2 and nitric oxide stimulated by lipopolysaccharide (LPS) and nicotine, and also attenuates the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), resulting in an anti-inflammatory effect (Non-Patent Document 4). It is well known that attachment of Pin1 to CRTC2 inhibits the production of the CBP-CRTC2-CREB complex, which promotes gluconeogenesis, and therefore CRTC2 can be regulated depending on the expression level of Pin1 and may therefore be involved in the regulation of glucose metabolism (Non-Patent Document 5). Therefore, drugs that affect the expression or activity of Pin1 can be used as therapeutic agents for inflammatory diseases or metabolic diseases such as diabetes.

[0008] Therefore, the present inventors conducted pharmaceutical chemical synthesis and biological and pharmacological evaluation of the synthesized compounds to discover compounds that inhibit the activity of Pin1. As a result, the present inventors discovered compounds that exhibit excellent anti-cancer effects by potently inhibiting Pin1, and completed the present invention. Furthermore, based on the role of Pin1 in inflammatory diseases and metabolic diseases, the compounds of the present invention are believed to be usable as therapeutic agents for diseases. [Prior art documents] [Non-patent literature]

[0009] [Non-Patent Document 1] Lu, et al. Science 1999, 283(5406):1325-8 [Non-patent document 2] Nature reviews Cancer 2016, 16:463-478 [Non-patent document 3] Cell Death and Disease 2018, 9:883 [Non-patent document 4] Journal of Dental Research, 2015, 94(2):371-380 [Non-patent document 5] J. Biol. Chem., 2010, 285(43):33018-27 Summary of the Invention [Problem to be solved by the invention]

[0010] An object of the present invention is to provide novel compounds that inhibit Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1), its isomers, or pharmaceutically acceptable salts thereof.

[0011] Another object of the present invention is to provide a process for preparing the above compounds.

[0012] Another object of the present invention is to provide a pharmaceutical composition comprising the above compound, its isomer or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of cancer, an inflammatory disease or a metabolic disease.

[0013] Another object of the present invention is to provide a health functional food composition comprising the above compound, its isomer or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or amelioration of cancer, inflammatory diseases or metabolic diseases. [Means for solving the problem]

[0014] In order to achieve the above object, in one aspect of the present invention, there is provided a compound represented by formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof: (Formula 1) [ka] (In formula 1, Ar is a 6- to 10-membered aryl or a 5- to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; R 1 and R 2are independently hydrogen, halogen, or a 5- to 8-membered heterocycloalkyl group containing at least one N. 1~5 is an alkoxy; R 3 is hydrogen, halogen, unsubstituted or substituted straight or branched chain C 1~8 Alkoxy, unsubstituted or substituted straight or branched chain C 1~8 Alkyl, NR a1 R a2 OR a3 and R a1 , R a2 and R a3 are independently hydrogen, unsubstituted or substituted straight or branched chain C 1~8 alkyl, unsubstituted or substituted phenyl, or 5- to 8-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, 4- to 8-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR b1 R b2 , 3- to 6-membered cycloalkyl, halogen, hydroxy, and sulfonyl, or said substituted alkoxy and substituted alkyl can be further substituted to form 3- to 6-membered cycloalkyl, each independently having a substituted carbon; The substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyls that are unsubstituted or substituted with one or more halogens. 1~5 Alkyl, straight or branched chain C 1~5 Alkylcarbonyl, NR b1 R b2 , substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and oxo; R b1 and R b2are independently hydrogen or straight or branched chain C 1~6 is alkyl, L 1 teeth, [ka] or [ka] where R c is hydrogen or L 2 which together with the nitrogen to which they are attached form an N-containing 5- to 8-membered heterocycloalkylene; L 2 is a single bond, straight or branched chain C 1~8 Alkylene, unsubstituted or substituted with either hydroxy and oxo 3~8 is cycloalkylene or phenylene; Z is unsubstituted or substituted C 6~10 aryl, unsubstituted or containing one or more heteroatoms selected from the group consisting of N, S, and O; C fused to a 5- to 9-membered unsubstituted or substituted heteroaryl containing 3~8 cycloalkyl, a 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O; a 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O 1~5 is alkyl, The substituted aryl is a 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of halogen, phenyl, carboxy, N, S, and O, or a straight-chain or branched C 1~8 substituted with alkoxycarbonyl, In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched-chain C 1~5 Alkyl, straight or branched chain C 1~8 substituted independently with one or more substituents selected from the group consisting of alkoxy, phenyl, benzyl, halogen, hydroxy, or oxo.

[0015] In another aspect, the present invention provides a method for preparing a compound represented by formula 1, comprising the step of reacting a compound represented by formula 2 with a compound represented by formula 3 to prepare the compound represented by formula 1, as shown in the following reaction scheme 1: (Reaction Scheme 1) [ka] (In Reaction Scheme 1, Ar, R 1 , R 2 , R 3 , L 1 , L 2 and Z are as defined in formula 1 of claim 1; J 1 is chlorosulfone or carboxy; J 2 is an amine or piperidine).

[0016] In another aspect, the present invention provides a pharmaceutical composition comprising a compound represented by formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of cancer, an inflammatory disease, or a metabolic disease.

[0017] In another aspect, the present invention provides a health functional food composition comprising a compound represented by formula 1, its isomer, or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or amelioration of cancer, inflammatory diseases, or metabolic diseases.

[0018] In another aspect, the present invention provides a method for preventing or treating cancer, an inflammatory disease, or a metabolic disease, the method comprising the step of administering to a subject in need thereof a pharmaceutical composition or a health functional food composition comprising a compound represented by formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0019] In another aspect of the present invention, the present invention provides use of a pharmaceutical composition or a health functional food composition comprising a compound represented by formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient in the prevention or treatment of cancer, inflammatory diseases or metabolic diseases. [Effects of the Invention]

[0020] Since the novel compound according to the present invention exhibits excellent inhibitory activity against Pin1, a pharmaceutical composition containing the compound as an active ingredient can be effectively used for the prevention or treatment of cancer, inflammatory diseases or metabolic diseases. DETAILED DESCRIPTION OF THE INVENTION

[0021] The present invention will be described in detail below.

[0022] In one aspect of the present invention, the present invention provides a compound represented by formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof: (Formula 1) [ka] (In formula 1, Ar is a 6- to 10-membered aryl or a 5- to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; R 1 and R 2 are independently hydrogen, halogen, or a 5- to 8-membered heterocycloalkyl group containing at least one N. 1~5 is an alkoxy; R 3 is hydrogen, halogen, unsubstituted or substituted straight or branched chain C 1~8Alkoxy, unsubstituted or substituted straight or branched chain C 1~8 Alkyl, NR a1 R a2 OR a3 and R a1 , R a2 and R a3 are independently hydrogen, unsubstituted or substituted straight or branched chain C 1~8 alkyl, unsubstituted or substituted phenyl, or 5- to 8-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, 4- to 8-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR b1 R b2 , 3- to 6-membered cycloalkyl, halogen, hydroxy, and sulfonyl, or the substituted alkoxy and substituted alkyl can be further substituted to form 3- to 6-membered cycloalkyl, each independently having a substituted carbon; Substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyl groups that are unsubstituted or substituted with one or more halogens. 1~5 Alkyl, straight or branched chain C 1~5 Alkylcarbonyl, NR b1 R b2 , substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and oxo; R b1 and R b2 are independently hydrogen or straight or branched chain C 1~6 is alkyl, L 1 teeth, [ka] or [ka] where R c is hydrogen or L 2 which together with the nitrogen to which they are attached form an N-containing 5- to 8-membered heterocycloalkylene; L 2 is a single bond, straight or branched chain C 1~8 Alkylene, unsubstituted or substituted with either hydroxy and oxo 3~8 is cycloalkylene or phenylene; Z is unsubstituted or substituted C 6~10 aryl, C fused to a 5- to 9-membered unsubstituted or substituted heteroaryl that is unsubstituted or contains one or more heteroatoms selected from the group consisting of N, S, and O 3~8 cycloalkyl, a 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O; a 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O 1~5 is alkyl, The substituted aryl is a 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of halogen, phenyl, carboxy, N, S, and O, or a straight-chain or branched C 1~8 substituted with alkoxycarbonyl, In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched C 1~5 Alkyl, straight or branched chain C 1~8 substituted independently with one or more substituents selected from the group consisting of alkoxy, phenyl, benzyl, halogen, hydroxy, or oxo.

[0023] Ar is a 6- to 10-membered aryl or 5- to 6-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; R 1 and R 2 are independently hydrogen or fluorine, R 3 is hydrogen, bromine, unsubstituted or substituted straight or branched chain C 1~6 Alkoxy, unsubstituted or substituted straight or branched chain C 1~6 Alkyl, NR a1 R a2 OR a3 and R a1 , R a2 and R a3 are independently hydrogen, unsubstituted or substituted straight or branched chain C 1~6 alkyl, unsubstituted or substituted phenyl, or 5- to 7-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of 4- to 7-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, 4- to 7-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR b1 R b2 , 3- to 5-membered cycloalkyl, fluorine, bromine, hydroxy, and sulfonyl, or the substituted alkoxy and substituted alkyl can be further substituted to form a 3- to 5-membered cycloalkyl, each independently having a substituted carbon; Substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyl groups that are unsubstituted or substituted with one or more halogens. 1~4 Alkyl, straight or branched chain C 1~4 Alkylcarbonyl, NR b1 R b2, substituted with one or more substituents selected from the group consisting of chlorine, fluorine, bromine, hydroxy, and oxo; R b1 and R b2 are independently hydrogen or straight or branched chain C 1~3 It is an alkyl , L 1 teeth, [ka] or [ka] where R c is hydrogen or L 2 which together with the nitrogen to which they are attached form a piperidinylene, L 2 is a single bond, straight or branched chain C 1~6 Alkylene, unsubstituted or substituted with either hydroxy and oxo 4~6 is cycloalkylene or phenylene; Z is unsubstituted or substituted C 6~9 aryl, C fused to a 5- to 9-membered unsubstituted or substituted heteroaryl that is unsubstituted or contains one or more heteroatoms selected from the group consisting of N, S, and O 4~7 cycloalkyl, 5- to 6-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O; a 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O 1~4 is alkyl, Substituted aryl is chlorine, phenyl, carboxy, morpholinyl, or a straight or branched C 1~3 substituted with alkoxycarbonyl, In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched C 1~4 Alkyl, straight or branched chain C 1~4 2. The compound of claim 1, its isomer, or a pharmaceutically acceptable salt thereof, which is independently substituted with one or more substituents selected from the group consisting of alkoxy, benzyl, phenyl, fluorine, chlorine, bromine, hydroxy, or oxo.

[0024] Ar is phenyl, naphthyl, pyridine or thiazole; R 1 and R 2 are independently hydrogen or fluorine, R 3 is hydrogen, bromine, unsubstituted or substituted straight or branched chain C 1~5 Alkoxy, unsubstituted or substituted straight or branched chain C 1~5 Alkyl, NR a1 R a2 OR a3 and R a1 , R a2 and R a3 are independently hydrogen, unsubstituted or substituted straight or branched chain C 1~5 alkyl, unsubstituted or substituted phenyl, or 5- to 6-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of 4- to 7-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, 5- to 7-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR b1 R b2, 3- to 4-membered cycloalkyl, fluorine, bromine, hydroxy, and sulfonyl, or the substituted alkoxy and substituted alkyl can be further substituted to form a cyclopropyl having each independently substituted carbon; Substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyls that are unsubstituted or substituted with one or more fluorines. 1~3 Alkyl, straight or branched chain C 1~4 Alkylcarbonyl, NR b1 R b2 , substituted with one or more substituents selected from the group consisting of chlorine, fluorine, bromine, hydroxy, and oxo; R b1 and R b2 are independently hydrogen, methyl or ethyl; L 1 teeth, [ka] or [ka] where R c is hydrogen or L 2 which together with the nitrogen to which they are attached form a piperidinylene, L 2 is a single bond, straight or branched chain C 1~4 alkylene, cyclohexylene or phenylene unsubstituted or substituted with either hydroxy or oxo; Z is unsubstituted or substituted phenyl, cyclohexyl, naphthyl, C fused to a 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O 5~6 cycloalkyl, 5- to 6-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O; a 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O 1~3 is alkyl, substituted phenyl is substituted with chlorine, phenyl, carboxy, morpholinyl, or methoxycarbonyl; In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched C 1~3 2. The compound of claim 1, its isomer, or a pharmaceutically acceptable salt thereof, each independently substituted with one or more substituents selected from the group consisting of alkyl, methoxy, benzyl, phenyl, fluorine, chlorine, bromine, hydroxy, or oxo.

[0025] Ar is phenyl, naphthyl, pyridine or thiazole; R 1 and R 2 are independently hydrogen or fluorine, R 3 are hydrogen, bromine, [ka] TIFF2025128234000013.tif235170TIFF2025128234000014.tif236170TIFF2025128234000015.tif248170TIFF2025128234000016.tif243170TIFF2025128234000017.tif164170TIFF2025128234000018.tif219170TIFF2025128234000019.tif220170TIFF2025128234000020.tif222170TIFF2025128234000021.tif91170 L 1 teeth, [ka] and L 2 is a single bond, [ka] and Z is [ka] TIFF2025128234000025.tif207170TIFF2025128234000026.tif198170, its isomer or a pharmaceutically acceptable salt thereof according to claim 1.

[0026] The compound according to claim 1, wherein the compound represented by formula 1 is selected from the group consisting of the following compounds, an isomer thereof, or a pharmaceutically acceptable salt thereof: <1> N-(3-([1,1'-biphenyl]-4-yl)propyl)-4-butoxybenzenesulfonamide; <2> 4-Butoxy-N-(3-(4-isopropylpiperazin-1-yl)propyl)benzenesulfonamide; <3> 4-Butoxy-N-(3-(4-chlorophenyl)propyl)benzenesulfonamide; <4> 4-Butoxy-N-(3-cyclohexylpropyl)benzenesulfonamide; <5> 4-Butoxy-N-(3-(pyridin-3-yl)propyl)benzenesulfonate Mido; <6> 4-Butoxy-N-(3-morpholinopropyl)benzenesulfonamide; <7> 4-Butoxy-N-(4-morpholinophenethyl)benzenesulfonamide; <8> 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid; <9> Methyl 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoate; <10> N-(2-(4-benzylpiperidin-1-yl)ethyl)-4-butoxybenzenesulfonamide; <11> 4-Butoxy-N-(3-hydroxy-3-phenylpropyl)benzenesulfonamide; <12> 4-Butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide; <13> 4-Butoxy-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzenesulfonamide; <14> 4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide; <15> 4-(3-(dimethylamino)propoxy)-N-(3-phenylpropyl)benzenesulfonamide; <16> Methyl 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoate; <17> 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoic acid; <18> 4-(3-(dimethylamino)propoxy)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzenesulfonamide; <19> 4-Butoxy-N-(3-(naphthalen-1-yl)propyl)benzenesulfonamide; <20> N-(3-(1H-indol-3-yl)propyl)-4-butoxybenzenesulfonamide; <21> N-(3-(1H-indol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)benzenesulfonamide; <22> N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <23> N-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-4-butoxybenzenesulfonamide; <24> N-(2-(1H-indol-3-yl)ethyl)-4-butoxybenzenesulfonamide; <25> N-(2-(1H-indol-2-yl)ethyl)-4-butoxybenzenesulfonamide; <26> N-(3-(1H-indol-3-yl)propyl)-4-(isopentyloxy)benzenesulfonamide; <27> N-(3-(1H-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide; <28> N-(3-(1H-benzo[d]imidazol-2-yl)propyl)-4-butoxybenzenesulfonamide; <29> 4-Butoxy-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)benzenesulfonamide; <30> N-(3-(1H-indol-3-yl)propyl)-4-(3-morpholinopropoxy)benzenesulfonamide; <31> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <32> N-(3-(1H-indol-1-yl)propyl)-4-butoxybenzenesulfonamide; <33> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-butoxybenzenesulfonamide; <34> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-butoxybenzenesulfonamide; <35> N-(3-(1H-indol-3-yl)propyl)-4-(3-(diethylamino)propoxy)benzenesulfonamide; <36> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-ethylpiperazin-1-yl)propoxy)benzenesulfonamide; <37> N-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <38> N-(2-(1H-indol-2-yl)ethyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <39> N-(3-(1H-indol-1-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <40> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <41> N-(3-(1H-indol-1-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <42> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <43> N-(3-(1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <44> N-(3-(1H-indol-3-yl)propyl)-4-(3-(2-oxopyrrolidin-1-yl)propoxy)benzenesulfonamide; <45> N-(3-(1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <46> 4-(3-(dimethylamino)propoxy)-N-(3-(1-methyl-1H-indol-3-yl)propyl)benzenesulfonamide; <47> N-(3-(1H-indol-3-yl)propyl)-4-bromobenzenesulfonamide; <48> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-isopropylpiperazin-1-yl)propoxy)benzenesulfonamide; <49> N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <50> N-(2-(1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <51> N-(2-(1H-indol-3-yl)ethyl)-4-(3-(4-isopropylpiperazin-1-yl)propoxy)benzenesulfonamide; <52> N-(3-(1H-indol-3-yl)propyl)-4-(2-(4-methylpiperazin-1-yl)ethoxy)benzenesulfonamide; <53> N-(3-(1H-indol-3-yl)propyl)-4-(2-(4-isopropylpiperazin-1-yl)ethoxy)benzenesulfonamide; <54> N-(2-(2-methyl-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <55> N-(3-(1H-indol-3-yl)propyl)-4-(2-(1-methylpiperidin-4-yl)ethoxy)benzenesulfonamide; <56> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <57> 3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <58> N-(3-(2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <59> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide; <60> N-(3-(1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide; <61> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <62> N-(3-(1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <63> 4-(3-(4-ethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide; <64> 5-Methoxy-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <65> 5-methyl-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <66> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <67> N-(3-(5-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <68> N-(3-(5-methoxy-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <69> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide; <70> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <71> 5-fluoro-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <72> 4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide; <73> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-isobutyrylpiperazin-1-yl)propoxy)benzenesulfonamide; <74> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)propoxy)benzenesulfonamide; <75> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide; <76> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)propoxy)benzenesulfonamide; <77> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfonamide; <78> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-chloropiperidin-1-yl)propoxy)benzenesulfonamide; <79> N-(3-(5-chloro-1H-indol-3-yl)propyl)-6-(3-(piperazin-1-yl)propoxy)pyridine-3-sulfonamide; <80> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-fluoropiperidin-1-yl)propoxy)benzenesulfonamide; <81> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-(trifluoromethyl)piperidin-1-yl)propoxy)benzenesulfonamide; <82> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,4-difluoropiperidin-1-yl)propoxy)benzenesulfonamide; <83> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)propoxy)benzenesulfonamide; <84> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <85> N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <86> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfonamide; <87> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <88> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-4-yl)propyl)amino)benzenesulfonamide; <89> N-(3-(1H-indol-3-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <90> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-1-yl)butyl)benzenesulfonamide; <91> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperazin-1-yl)butyl)benzenesulfonamide; <92> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide; <93> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide; <94> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperidin-4-yl)propoxy)benzenesulfonamide; <95> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <96> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <97> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide; <98> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzenesulfonamide; <99> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-4-yl)butyl)benzenesulfonamide; <100> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyrrolidin-1-yl)propoxy)benzenesulfonamide; <101> 4-(3-(azepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <102> 4-(3-(1,4-diazepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <103> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfone amide; <104> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <105> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide; <106> 4-(3-(1,4-diazepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluorobenzenesulfonamide; <107> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <108> (R)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <109> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <110> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)benzenesulfonamide; <111> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3,4-dimethylpiperazin-1-yl)propoxy)benzenesulfonamide; <112> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(4-methylpiperazin-1-yl)butyl)benzenesulfonamide; <113> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)propyl)amino)benzenesulfonamide; <114> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-1-yl)propyl)amino)benzenesulfonamide; <115> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(1-methylpiperidin-4-yl)butyl)benzenesulfonamide; <116> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)methoxy)benzenesulfonamide; <117> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-(piperazin-1-ylmethyl)cyclopropyl)methoxy)benzenesulfonamide; <118> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide; <119> 4-(3-bromophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <120> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)phenoxy)benzenesulfonamide; <121> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)phenoxy)benzenesulfonamide; <122> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)phenoxy)benzenesulfonamide; <123> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide ; <124> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)phenyl)amino)benzenesulfonamide; <125> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)pyrimidin-2-yl)amino)benzenesulfonamide; <126> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-morpholinophenyl)amino)benzenesulfonamide; <127> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(piperazin-1-yl)pyrimidin-2-yl)amino)benzenesulfonamide; <128> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-morpholinophenoxy)benzenesulfonamide; <129> 4-(3-(1,4-diazepan-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <130> 4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <131> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <132> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-(piperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <133> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <134> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(piperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <135> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyrrolidin-1-yl)phenoxy)benzenesulfonamide; <136> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)phenoxy)benzenesulfonamide; <137> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-fluoro-5-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide; <138> 4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <139> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-hydroxypiperidin-1-yl)phenyl)amino)benzenesulfonamide; <140> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-chloro-4-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <141> 4-((4,6-bis(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <142> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-( (4-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide; <143> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzamide; <144> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzamide; <145> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(methylsulfonyl)propoxy)benzenesulfonamide; <146> N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfonamide; <147> N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <148> 4-(4-(1H-imidazol-1-yl)butyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <149> N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <150> N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <151> N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <152> N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <153> N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <154> N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <155> N-(3-(5-phenyl-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <156> 4-(3-(4-methylpiperazin-1-yl)propoxy)-N-(3-(5-phenyl-1H-indol-3-yl)propyl)benzenesulfonamide; <157> N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <158> N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <159> N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <160> 4-(3-(1H-1,2,4-triazol-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <161> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(2-methyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <162> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-3-oxopiperazin-1-yl)propoxy)benzenesulfonamide; <163> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-oxopiperazin-1-yl)propoxy)benzenesulfonamide; <164> N-(3-(5,7-dichloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <165> N-(3-(5,7-dichloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <166> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dichloro-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <167> N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <168> N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <169> N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <170> N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <171> (R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <172> (R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzenesulfonamide; <173> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <174> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzenesulfonamide; <175> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dimethyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <176> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(2,4,5-trimethyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <177> N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <178> N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <179> N-(3-(5-chloro-1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <180> N-(3-(5-chloro-1H-indol-3-yl)cyclohexyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <181> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <182> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonate amide; <183> N-(3-(5,6-dichloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <184> N-(3-(5,6-dichloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <185> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyridin-4-yloxy)propyl)benzenesulfonamide; <186> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propyl)benzenesulfonamide; <187> N-((6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <188> N-((6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <189> 4-(3-(4-methylpiperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide; <190> 4-(3-(piperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide.

[0027] The compound represented by Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and the salt is preferably an acid addition salt formed with a pharmaceutically acceptable free acid. In this specification, acid addition salts are defined as salts formed with inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, and phosphorous acid; non-toxic organic acids such as aliphatic mono / dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates, alkandioates, aromatic acids, and aliphatic / aromatic sulfonic acids; or can be obtained from organic acids such as acetic acid, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, and fumaric acid. Pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, and the like. Examples are benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, terephthalates, benzenesulfonates, toluenesulfonates, chlorobenzenesulfonates, xylenesulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, hydroxybutyrates, glycolates, malates, tartrates, methanesulfonates, propanesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, and mandelates.

[0028] The acid addition salts according to the present invention can be prepared by conventional methods known to those skilled in the art. For example, the derivative represented by Formula 1 is dissolved in an organic solvent such as methanol, ethanol, acetone, dichloromethane, or acetonitrile, and an organic or inorganic acid is added thereto to induce precipitation. The precipitate is then filtered and dried to obtain a salt. Alternatively, the solvent and excess acid are distilled off under reduced pressure, followed by drying to obtain a salt. Alternatively, the precipitate is crystallized in an organic solvent to obtain a salt.

[0029] Pharmaceutically acceptable metal salts can be prepared using a base. Alkali metal or alkaline earth metal salts can be obtained by the following process: dissolving a compound in a solution of excess alkali metal hydroxide or alkaline earth metal hydroxide, filtering the insoluble compound salt, evaporating the remaining solution, and drying it. At this time, it is preferable to prepare metal salts in the pharmaceutically suitable form of sodium, potassium, or calcium salts. Corresponding silver salts can also be prepared by reacting an alkali metal or alkaline earth metal salt with an appropriate silver salt (e.g., silver nitrate).

[0030] Furthermore, the present invention includes not only the compounds represented by formula 1 and pharmaceutically acceptable salts thereof, but also solvates, isomers, hydrates, etc. that can be prepared therefrom.

[0031] The term "isomer" refers to a compound of the present invention or a salt thereof that has the same chemical or molecular formula but is structurally or sterically different. Such isomers include tautomers, structural isomers such as R or S isomers having asymmetric carbon centers, stereoisomers such as geometric isomers (trans, cis), and optical isomers. All of these isomers and mixtures thereof are also included within the scope of the present invention.

[0032] The compound represented by formula 1 of the present invention can be prepared according to the preparation methods shown in the following examples, but these are only examples and are not intended to limit the scope of the invention, and each preparation step can be carried out using methods well known to those skilled in the art.

[0033] In another aspect, the present invention provides a method for preparing a compound of formula 1, comprising the step of reacting a compound of formula 2 with a compound of formula 3 to prepare the compound of formula 1, as shown in Reaction Scheme 1 below: (Reaction Scheme 1) [ka]

[0034] In Reaction Scheme 1, Ar, R 1, R 2 , R 3 , L 1 , L 2 and Z are as defined in Formula 1 above; J 1 is chlorosulfone or carboxy; J 2 is an amine or piperidine.

[0035] The preparation method shown in Reaction Scheme 1 will be explained in detail below.

[0036] In the method of preparing the compound of formula 1 of the present invention, the step of Reaction Scheme 1 is a step of reacting a compound of formula 2 with a compound of formula 3 to prepare the compound of formula 1. In particular, this is a step of reacting the chlorosulfone or carboxy of the compound of formula 2 with the amine of the compound of formula 3 to form the compound of formula 1.

[0037] In this case, this step is not particularly limited as long as it is a method for preparing a compound represented by formula 1 and is within the scope of the present invention. The compound represented by formula 2 is a compound having an electron-accepting group such as sulfone and an easily reactive leaving group such as chloro, or a compound reacting with an amine. The compound of formula 3 can be understood as a compound having a carboxyl group capable of forming an amide in response to the carboxyl group, and the compound of formula 3 can be understood as an amine capable of undergoing a nucleophilic substitution reaction or an amide-forming reaction, but is not necessarily limited thereto. The final compound is prepared by nucleophilic substitution between a compound having an electron-accepting group and a leaving group and an amine having sufficient nucleophilicity to react with the compound, or by amide-forming reaction between a carboxyl group and an amine.

[0038] More specifically, these can be understood by referring to the preparation methods of the example compounds of the present invention, but each reaction condition (such as reaction temperature, time, atmospheric conditions, pressure conditions, etc., which can be considered by a person skilled in the art of organic synthesis) can be changed. The present invention is not limited thereto, and it can be understood that the compounds and derivatives thereof used in each step include, in addition to those disclosed in the present invention, modified derivatives that can be modified by simply modifying, changing, or removing substituents.

[0039] Preferred embodiments of the preparation method include the preparation methods disclosed in the following Examples 1 to 190, but the present invention is not limited to these.

[0040] In another aspect, the present invention provides a pharmaceutical composition comprising a compound represented by formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of cancer, an inflammatory disease, or a metabolic disease.

[0041] The compound represented by formula 1 according to the present invention, its isomer or a pharmaceutically acceptable salt thereof can inhibit Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1).

[0042] Pin1, a prolyl isomerase, is an enzyme that catalyzes the cis / trans isomerization of proline residue amides by binding to phosphorylated Ser / Thr-Pro sites. Previous studies have shown that Pin1 is involved in the development and progression of inflammatory diseases, metabolic diseases, and cancer.

[0043] In particular, Pin1 has been reported to activate 56 oncogenes involved in carcinogenesis and inhibit the activity of 26 tumor suppressor genes, thereby inducing cancer metastasis and cancer angiogenesis throughout the entire cancer development mechanism.

[0044] Furthermore, it has been reported that inhibition of Pin1 or knockdown of Pin1 gene expression attenuates the production of prostaglandin E2 and nitric oxide stimulated by lipopolysaccharide (LPS) and nicotine, and also attenuates the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), resulting in an anti-inflammatory effect.

[0045] It is well known that CRTC2 can be regulated according to the expression level of Pin1, as attachment of Pin1 to CRTC2 inhibits the production of the CBP-CRTC2-CREB complex that promotes gluconeogenesis, and therefore may be involved in the regulation of glucose metabolism.

[0046] Therefore, drugs that affect the expression or activity of Pin1 can be used as therapeutic agents for cancer, inflammatory diseases, or metabolic diseases such as diabetes.

[0047] Therefore, the compound represented by formula 1 according to the present invention, its isomer, or a pharmaceutically acceptable salt thereof can be used in a pharmaceutical composition for preventing or treating cancer, inflammatory diseases, or metabolic diseases, or in a pharmaceutical composition for preventing or improving cancer, inflammatory diseases, or metabolic diseases containing the compound as an active ingredient. It can be effectively used as a health functional food to improve the health of the body.

[0048] Cancers include pseudomyxoma, intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphocytic leukemia, basal cell carcinoma, ovarian epithelial cancer, ovarian germ cell cancer, male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colorectal cancer, chronic myeloid leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, ampulla of Vater cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, nasal cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, childhood brain cancer, childhood lymphoma, childhood leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, renal cancer, kidney cancer, heart cancer, duodenal cancer, malignant The cancer may be at least one selected from the group consisting of soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureteral cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, stomach cancer, gastric carcinoma, gastrointestinal stromal cancer, Wilms' cancer, breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoid tumor, vaginal cancer, spinal cancer, vestibular schwannoma, pancreatic cancer, salivary gland cancer, Kaposi's sarcoma, Paget's disease, tonsil cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, laryngeal cancer, pleural cancer, blood cancer, and thymic cancer.

[0049] The inflammatory disease may be at least one selected from the group consisting of arthritis, encephalomyelitis, meningitis, peritonitis, osteomyelitis, encephalitis, ankylosing spondylitis, vasculitis, uveitis, ileitis, atherosclerosis, myositis, leukocyte injury, inflammatory bowel disease, ulcerative colitis, retinal detachment, retinitis pigmentosa, macular degeneration, pancreatitis, atopic dermatitis, gout, vasculitis, non-alcoholic steatohepatitis, primary sclerosing cholangitis, nephritis, intra-abdominal disease, sepsis, systemic inflammatory response syndrome, myocardial infarction, allergic disease, asthma, atopic dermatitis, Wegener's granulomatosis, pulmonary sarcoidosis, Behcet's disease, chronic obstructive pulmonary disease, and periodontitis.

[0050] The metabolic disease may be at least one selected from the group consisting of obesity, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, arteriosclerosis, fatty liver, gout, stroke, and heart disease.

[0051] In another aspect, the present invention provides a health functional food comprising a compound represented by formula 1, its isomer, or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or amelioration of cancer, inflammatory diseases, or metabolic diseases.

[0052] The term "prevention" as used in the present invention refers to any action of suppressing or delaying the onset of a neurological disorder by administering the pharmaceutical composition according to the present invention to a subject.

[0053] The term "treatment" as used herein refers to any effect of improving or benefiting from the symptoms of a neurological disorder by administering a pharmaceutical composition according to the present invention to a subject.

[0054] When the composition of the present invention is used as a pharmaceutical, the pharmaceutical composition containing the compound represented by formula 1, its isomer, or a pharmaceutically acceptable salt thereof as an active ingredient may be formulated and administered in various oral or parenteral forms as follows, but is not necessarily limited thereto, for clinical administration.

[0055] Oral administration preparations are exemplified by tablets, pills, hard / soft capsules, solutions, suspensions, emulsions, syrups, granules, elixirs, and troches. These preparations contain, in addition to the active ingredient, diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and / or glycine), and lubricants (e.g., silica, talc, stearic acid and its magnesium or calcium salts, and / or polyethylene glycol). The tablets may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone, and may further contain, if necessary, a disintegrating agent such as starch, agarose, alginic acid or its sodium salt, or an azeotropic mixture and / or an absorbent, a coloring agent, a flavoring agent, and a sweetener.

[0056] When the compound represented by formula 1, its isomer, or a pharmaceutically acceptable salt thereof is used as a pharmaceutical composition for the prevention or treatment of cancer, an inflammatory disease, or a metabolic disease, it can be administered as an individual therapeutic agent or can be used in combination with other therapeutic agents that are currently being used.

[0057] A pharmaceutical composition comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient can be administered parenterally, and parenteral administration includes subcutaneous injection, intravenous injection, intramuscular injection, or intrapleural injection.

[0058] To prepare a compound of Formula 1, its isomer, or a pharmaceutically acceptable salt thereof as a formulation for parenteral administration, the compound of Formula 1, its isomer, or a pharmaceutically acceptable salt thereof is mixed with a stabilizer or buffer in water to produce a solution or suspension, which is then formulated into an ampule or vial. The compositions herein can be sterilized and further contain preservatives, stabilizers, wetting powders or emulsifiers, salts and / or buffers for adjusting osmotic pressure, and other therapeutically useful materials, and the compositions can be formulated according to conventional methods such as dispersion and gelation.

[0059] The dosage of a pharmaceutical composition containing the compound of Formula 1 as an active ingredient to a human body can be determined depending on the formulation method, age, body weight, sex, administration method, health condition, and severity of the disease. The preferred dosage of the composition of the present invention is 0.001 mg / kg to 1000 mg / kg per day, and can be administered orally or parenterally several times a day, or preferably once to three times a day, at the discretion of a physician or pharmacist.

[0060] The pharmaceutical composition of the present invention can be used as a single preparation. The pharmaceutical composition of the present invention can also be prepared and used as a combined preparation further comprising one or more other therapeutic agents.

[0061] In another aspect, the present invention provides a method for treating cancer, an inflammatory disease, or a metabolic disease, comprising administering the pharmaceutical composition to a subject in need thereof. The pharmaceutical composition is for the prevention or treatment of cancer, an inflammatory disease, or a metabolic disease, and refers to a pharmaceutical composition comprising the compound represented by Formula 1, its isomer, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0062] In another aspect of the present invention, the present invention provides use of a pharmaceutical composition or a health functional food composition comprising a compound represented by formula 1, its isomer or a pharmaceutically acceptable salt thereof as an active ingredient in the prevention or treatment of cancer, inflammatory diseases or metabolic diseases. [Example]

[0063] The present invention will now be described in detail with reference to the following examples and experimental examples.

[0064] However, the following examples and experimental examples are only for the purpose of illustrating the present invention, and the contents of the present invention are not limited thereto.

[0065] Example 1 Preparation of N-(3-([1,1'-biphenyl]-4-yl)propyl)-4-butoxybenzenesulfonamide [ka]

[0066] Step 1: Preparation of (E)-4-(2-isocyanovinyl)-1,1'-biphenyl [ka]

[0067] Sodium hydride (60 wt%, 0.263 g, 6.59 mmol) was dissolved in anhydrous tetrahydrofuran (13 mL) and diethyl(cyanomethyl)phosphonate (0.977 mL, 6.04 mmol) was added dropwise at 0°C. [1,1'-biphenyl]-4-carbaldehyde (1 g, 5.49 mmol) was added dropwise to the reaction mixture, followed by stirring at room temperature for 30 minutes. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. As a result, (E)-4-(2-isocyanovinyl)-1,1'-biphenyl was obtained as a white solid without further purification.

[0068] Step 2: Preparation of 3-([1,1'-biphenyl]-4-yl)propanenitrile [ka]

[0069] The compound prepared in Step 1 above (1.126 g, 5.49 mmol) was dissolved in ethyl acetate:methanol (1:1) (24 ml), and Pd / C (10 wt%) was added dropwise at 0°C, followed by stirring at room temperature under a hydrogen atmosphere for 12 hours. Upon completion of the reaction, the reaction mixture was filtered through Celite, and the solvent was removed under reduced pressure. As a result, 3-([1,1'-biphenyl]-4-yl)propanenitrile was obtained as a white solid without further purification.

[0070] Step 3: Preparation of 3-([1,1'-biphenyl]-4-yl)propan-1-amine [ka]

[0071] The compound 3-([1,1'-biphenyl]-4-yl)propanenitrile (1.137 g, 5.49 mmol) synthesized in step 2 above was dissolved in anhydrous tetrahydrofuran (10 ml), and 1 M lithium aluminum hydride (10.97 ml, 10.97 mmol) was added dropwise thereto at 0°C, followed by stirring at room temperature for 2 hours. Water was added dropwise to terminate the reaction, and the reaction mixture was The mixture was filtered and the solvent was removed under reduced pressure to give 3-([1,1'-biphenyl]-4-yl)propan-1-amine as a sticky yellow compound without further purification.

[0072] Step 4: Preparation of N-(3-([1,1'-biphenyl]-4-yl)propyl)-4-butoxybenzenesulfonamide [ka]

[0073] 4-Butoxybenzenesulfonyl chloride (40 μL, 0.200 mmol) was dissolved in dichloromethane (1 mL), and 3-([1,1'-biphenyl]-4-yl)propan-1-amine (127 mg, 0.601 mmol) synthesized in Step 3 above was added thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to obtain the target compound (14.4 mg, 16%, white solid).

[0074] The compounds of Examples 2 to 7 were prepared in a manner similar to that described in Step 4 of Example 1.

[0075] Example 8: Preparation of 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid [ka]

[0076] Step 1: Preparation of methyl 4-(2-((4-butoxyphenyl)sulfonamido)ethyl)benzoate [ka]

[0077] The target compound (6.7 mg, 28%, white solid) was obtained in a similar manner to that described in Step 4 of Example 1.

[0078] Step 2: Preparation of 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid [ka]

[0079] The compound methyl 4-(2-((4-butoxyphenyl)sulfonamido)ethyl)benzoate (23 mg, 0.059 mmol) prepared in Step 1 above was dissolved in methanol (0.5 ml), and 4 M aqueous potassium hydroxide solution (0.147 ml, 0.588 mmol) was added dropwise thereto, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was neutralized with 1 M aqueous HCl solution. The reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to obtain the target compound (3.4 g, 15%, white solid).

[0080] The compound of Example 9 was prepared in a similar manner as described in Step 1 of Example 8.

[0081] Example 10: Preparation of N-(2-(4-benzylpiperidin-1-yl)ethyl)-4-butoxybenzenesulfonamide [ka]

[0082] Step 1: Preparation of tert-butyl (2-(4-benzylpiperidin-1-yl)ethyl)carbamate [ka]

[0083] 4-Benzylpiperidine (8 g, 45.6 mmol) and potassium carbonate (K2CO3) (9.46 g, 68.5 mmol) were dissolved in DMF (228 ml) and stirred at room temperature for 5 minutes. tert-Butyl (2-bromoethyl)carbamate (12.27 g, 54.8 mmol) was added dropwise to the reaction mixture, followed by stirring at 60 °C for 12 hours. tert-Butyl (2-bromoethyl)carbamate (12.27 g, 54.8 mmol) was added dropwise again to the reaction mixture, followed by stirring at 60 °C for 12 hours. Upon completion of the reaction, 1 M aqueous HCl solution was added dropwise, followed by extraction with dichloromethane. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then separated and purified by MPLC to obtain tert-butyl (2-(4-benzylpiperidin-1-yl)ethyl)carbamate (12.9 g, 89%, white solid).

[0084] Step 2: Preparation of 2-(4-benzylpiperidin-1-yl)ethanamine diHCl salt [ka]

[0085] tert-Butyl (2-(4-benzylpiperidin-1-yl)ethyl)carbamate (12.9 g, 40.5 mmol), prepared in Step 1 above, was directly treated with 4 M HCl in dioxane (10.13 ml, 40.5 mmol), followed by stirring at room temperature for 2 hours. Upon completion of the reaction, excess HCl was removed under reduced pressure to give 2-(4-benzylpiperidin-1-yl)ethanamine diHCl salt (8.9 g, 75%, white solid).

[0086] Step 3: Preparation of N-(2-(4-benzylpiperidin-1-yl)ethyl)-4-butoxybenzenesulfonamide [ka]

[0087] Using the compound prepared in Step 2 above, the target compound (7.6 mg, 14%, clear oil) was obtained in the same manner as described in Step 4 of Example 1.

[0088] The compound of Example 11 was prepared in a manner similar to that described in Step 4 of Example 1.

[0089] Example 12: Preparation of 4-butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide [ka]

[0090] Step 1: Preparation of (4-butoxy-N-(3-hydroxy-3-phenylpropyl)benzenesulfonamide [ka]

[0091] The target compound was obtained in a similar manner to that described in step 4 of Example 1.

[0092] Step 2: Preparation of 4-butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide [ka]

[0093] The compound prepared in step 1 above (30 mg, 0.121 mmol) was dissolved in dichloromethane (0.5 mL), and manganese(IV) oxide (31.1 mg, 0.358 mmol) was added dropwise thereto, followed by stirring at room temperature for 12 hours. Upon completion of the reaction, the reaction mixture was filtered through Celite and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to yield the target compound (9.2 mg, 71%, white solid).

[0094] The compound of Example 13 was prepared in a manner similar to that described in Step 4 of Example 1.

[0095] Example 14: Preparation of 4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide [ka]

[0096] Step 1: Preparation of N,N-dimethyl-3-phenoxypropan-1-amine [ka]

[0097] Phenol (600 mg, 6.38 mmol), 3-(dimethylamino)propan-1-ol (0.88 mL, 7.44 mmol), and triphenylphosphine (2.508 g, 9.56 mmol) were dissolved in tetrahydrofuran (12 mL) at 0 °C, and diethyl azodicarboxylate solution (DEAD) (4.34 mL, 9.56 mmol) was added dropwise thereto. The mixture was then stirred at room temperature for 12 hours under a nitrogen atmosphere. Upon completion of the reaction, the solvent was removed under reduced pressure. The reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give N,N-dimethyl-3-phenoxypropan-1-amine (922 mg, 81%, yellow oil).

[0098] Step 2: Preparation of 4-(3-(dimethylamino)propoxy)benzene-1-sulfonyl chloride [ka]

[0099] N,N-dimethyl-3-phenoxypropan-1-amine (9 The resulting 4-(3-(dimethylamino)propoxy)benzene-1-sulfonyl chloride (451 mg, 32%, yellow solid) was obtained without further purification.

[0100] Step 3: Preparation of 4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide [ka]

[0101] 4-(3-(dimethylamino)propoxy)benzene-1-sulfonyl chloride (100 mg, 0.318 mmol) prepared in Step 2 above was dissolved in dichloromethane (2 mL), and 2-phenylethanamine (116 mg, 0.955 mmol) and potassium carbonate (KCO) (48.4 mg, 0.35 mmol) were added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (88 mg, 75%, clear oil).

[0102] The compounds of Example 15 and Example 16 were prepared in a manner similar to that described in Step 3 of Example 14.

[0103] Example 17 Preparation of 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoic acid [ka]

[0104] Step 1: Preparation of methyl 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoate [ka]

[0105] The target compound was prepared in a manner similar to that described in step 3 of Example 14.

[0106] Step 2: Preparation of 4-(2-(4-(3-(dimethylamino)propoxyphenylsulfonamido)ethyl)benzoic acid [ka]

[0107] The compound prepared in Step 1 above (58 mg, 0.138 mmol) was dissolved in methanol (1 ml) and 4 M aqueous potassium hydroxide (0.69 ml, 2.76 mmol) was added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was neutralized with 1 M aqueous HCl, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by preparative TLC to yield the target compound (1.7 mg, 3%, white solid).

[0108] The compound of Example 18 was prepared in a manner similar to that described in Step 3 of Example 14.

[0109] Example 19: Preparation of 4-butoxy-N-(3-(naphthalen-1-yl)propyl)benzenesulfonamide [ka]

[0110] Step 1: Preparation of tert-butyl (3-(naphthalen-1-yl)propyl)carbamate [ka]

[0111] tert-Butyl allylcarbamate (1 g, 6.36 mmol) was dissolved in tetrahydrofuran (6 mL) and 9-BBN (10 mmol) dissolved in 0.5 M tetrahydrofuran was added dropwise thereto, followed by stirring at room temperature for 2.5 hours. 1-Iodonaphthalene (0.925 mL, 6.36 mmol), PdCl(dppf)-CHCl(308 mg, 0.377 mmol), and 1 M aqueous sodium hydroxide (10 mL) were added dropwise thereto and then stirred at room temperature for 3 hours. PdCl(dppf)-CHCl(55 mg, 0.07 mmol) was added dropwise thereto and then stirred at room temperature for 14 hours. Upon completion of the reaction, saturated aqueous ammonium chloride solution was added dropwise thereto, and the reaction mixture was extracted with ethyl acetate, dried over magnesium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then separated and purified by MPLC to give a compound (1.6 g). The compound was added dropwise to a mixture of tetrahydrofuran (20 ml), 15% aqueous sodium hydroxide (5 ml), and 30% hydrogen peroxide (10 ml) at 0°C, followed by stirring at the same temperature for 2 hours. After the reaction was completed, ethyl acetate was added dropwise thereto, and the reaction mixture was washed with a supersaturated aqueous sodium bicarbonate solution and brine, and then treated with anhydrous magnesium sulfate. After drying over sodium, the solvent was removed under reduced pressure, and the reaction mixture was purified by MPLC to obtain tert-butyl (3-(naphthalen-1-yl)propyl)carbamate (1.4 g, 77%).

[0112] Step 2: Preparation of 3-(naphthalen-1-yl)propan-1-amine [ka]

[0113] tert-Butyl (3-(naphthalen-1-yl)propyl)carbamate (1.4 g, 4.9 mmol) prepared in Step 1 above was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (10 mL, 130 mmol) was added dropwise thereto, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was neutralized by the dropwise addition of 10% aqueous sodium hydroxide solution. The reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 3-(naphthalen-1-yl)propan-1-amine (925 mg, 100%).

[0114] Step 3: Preparation of 4-butoxy-N-(3-(naphthalen-1-yl)propyl)benzenesulfonamide [ka]

[0115] Using the compound prepared in Step 2 above, the target compound (66 mg, 82%, transparent solid) was obtained in the same manner as described in Step 4 of Example 1.

[0116] The compound of Example 20 was prepared in a manner similar to that described in Step 4 of Example 1.

[0117] Example 21: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)benzenesulfonamide [ka]

[0118] Step 1: Preparation of N,N-dimethyl-2-phenoxyethan-1-amine [ka]

[0119] Phenol (500 mg, 5.31 mmol), 2-(dimethylamino)ethane-1- A solution of 521 mg (5.84 mmol) of methylalcohol and 2.089 g (797 mmol) of triphenylphosphine in 20 ml of tetrahydrofuran was added dropwise to the solution at 0°C. The mixture was then stirred at room temperature for 12 hours under a nitrogen atmosphere. Upon completion of the reaction, the solvent was removed under reduced pressure. The reaction mixture was extracted with dichloromethane, and the organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give N,N-dimethyl-2-phenoxyethan-1-amine (870 mg, 99%, yellow solid).

[0120] Step 2: Preparation of 4-(2-(dimethylamino)ethoxy)benzenesulfonyl chloride [ka]

[0121] N,N-Dimethyl-3-phenoxyethan-1-amine (533 mg, 3.23 mmol) prepared in Step 1 above was dissolved in dichloromethane (3 mL), and chlorosulfonic acid (0.858 mL, 12.90 mmol) was added dropwise at 0°C, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, ice was added. The reaction mixture was extracted with dichloromethane and neutralized with supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. This resulted in 4-(2-(dimethylamino)ethoxy)benzenesulfonyl chloride (622 mg, 73%, yellow oil) without further purification.

[0122] Step 3: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)benzenesulfonamide [ka]

[0123] 4-(2-(dimethylamino)ethoxy)benzenesulfonyl chloride (45 mg, 0.171 mmol) prepared in Step 2 above was dissolved in dichloromethane, and 3-(1H-indol-3-yl)propan-1-amine (131 mg, 0.751 mmol) was added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (11 mg, 17%, yellow solid).

[0124] The compound of Example 22 was prepared in a manner similar to that described in Example 14.

[0125] The compounds of Examples 23 to 25 were prepared in a manner similar to that described in Step 4 of Example 1.

[0126] Example 26: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(isopentyloxy)benzenesulfonamide [ka]

[0127] 4-(Isopentyloxy)benzenesulfonyl chloride (20 mg, 0.076 mmol) was dissolved in dichloromethane (1.5 mL) and 3-(1H-indol-3-yl)propan-1-amine (30 mg, 0.172 mmol) was added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (26 mg, 85%, yellow solid).

[0128] Example 27: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide [ka]

[0129] 4-(Pentyloxy)benzenesulfonyl chloride (20 mg, 0.076 mmol) was dissolved in dichloromethane, and 3-(1H-indol-3-yl)propan-1-amine (30 mg, 0.172 mmol) was added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (25 mg, 81%, white solid).

[0130] The compound of Example 28 was prepared in a manner similar to that described in Step 4 of Example 1.

[0131] Example 29: Preparation of 4-butoxy-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)benzenesulfonamide [ka]

[0132] 4-Butoxybenzenesulfonyl chloride (50 mg, 0.201 mmol) was dissolved in dichloromethane (1 mL), and 3-(2-aminoethyl)-1H-indol-5-ol hydrochloride (128 mg, 0.603 mmol) and triethylamine (0.084 mL, 0.603 mmol) were added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (10.2 mg, 13%, white solid).

[0133] Example 30 Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-morpholinopropoxy)benzenesulfonamide [ka]

[0134] Step 1: Preparation of 4-(3-phenoxypropyl)morpholine [ka]

[0135] Phenol (600 mg, 6.38 mmol), 4-(3-hydroxypropyl)morpholine (1.11 g, 7.65 mmol), and triphenylphosphine (2.5 g, 9.56 mmol) were dissolved in tetrahydrofuran (16 mL) at 0 °C, and diethyl azodicarboxylate solution (DEAD) (4.34 mL, 9.56 mmol) was added dropwise thereto. The mixture was then stirred at room temperature for 12 hours under a nitrogen atmosphere. Upon completion of the reaction, the solvent was removed under reduced pressure. The reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was then removed under reduced pressure. The reaction mixture was then purified by MPLC to yield 4-(3-phenoxypropyl)morpholine (1.41 g, 100%, clear oil).

[0136] Step 2: Preparation of 4-(3-morpholinopropoxy)benzene-1-sulfonyl chloride [ka]

[0137] 4-(3-phenoxypropyl)morpholine (1.41 g, 6.38 mmol) prepared in Step 1 above was dissolved in dichloromethane (12 mL), and chlorosulfonic acid (1.69 mL, 25.5 mmol) was added thereto at 0°C, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, ice was added thereto. The reaction mixture was extracted with dichloromethane and neutralized with a supersaturated aqueous solution of sodium carbonate. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. As a result, 4-(3-morpholinopropoxy)benzene-1-sulfonyl chloride (2.22 g, 67%, yellow solid) was obtained without further purification.

[0138] Step 3: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-morpholinopropoxy)benzenesulfonamide [ka]

[0139] 4-(3-morpholinopropoxy)benzene-1-sulfonyl chloride (150 mg, 0.469 mmol) prepared in Step 2 above was dissolved in dichloromethane (1.5 mL) and 3-(1H-indol-3-yl)propan-1-amine (245 mg, 1.407 mmol) and potassium carbonate (194 mg, 1.407 mmol) were added dropwise, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to yield the target compound (10.6 mg, 5%, yellow solid).

[0140] Example 31 Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0141] Step 1: Preparation of 4-(3-bromopropoxy)benzene-1-sulfonyl chloride [ka]

[0142] (3-Bromopropoxy)benzene (1 g, 4.65 mmol) was dissolved in dichloromethane (15 ml), and chlorosulfonic acid (1.236 ml, 18.60 mmol) was added dropwise at 0°C, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, ice was added. The reaction mixture was extracted with dichloromethane and neutralized with supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. As a result, 4-(3-bromopropoxy)benzene-1-sulfonyl chloride (1.1 g, 38%, yellow solid) was obtained without further purification.

[0143] Step 2: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-bromopropoxy)benzenesulfonamide [ka]

[0144] 4-(3-Bromopropoxy)benzene-1-sulfonyl chloride (538 mg, 1.716 mmol) prepared in Step 1 above was dissolved in dichloromethane (5 mL), and 3-(1H-indol-3-yl)propan-1-amine (897 mg, 5.15 mmol) and potassium carbonate (KCO) (711 mg, 5.15 mmol) were added dropwise thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to yield N-(3H-(1H-indol-3-yl)propyl)-4-(3-bromopropoxy)benzenesulfonamide (230 mg, 29%, white solid).

[0145] Step 3: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0146] N-(3-(1H-indol-3-yl)propyl)-4-(3-bromopropoxy)benzenesulfonamide (175 mg, 0.388 mmol) prepared in Step 2 above was dissolved in ethanol (1.5 mL), and 1-methylpiperazine (0.172 mL, 1.551 mmol) and potassium carbonate (KCO) (80 mg, 0.582 mmol) were added dropwise thereto, followed by stirring at 70 °C for 12 h. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (66 mg, 36%, white solid).

[0147] The compounds of Examples 23 to 25 were prepared in a manner similar to that described in Step 4 of Example 1.

[0148] The compounds of Example 34 and Example 35 were prepared in a manner similar to that described in Example 30.

[0149] The compound of Example 36 was prepared in a manner similar to that described in Example 31.

[0150] The compounds of Examples 37 to 40 were prepared in a manner similar to that described in Example 14.

[0151] The compounds of Example 41 and Example 42 were prepared in a manner similar to that described in Example 30.

[0152] The compounds of Examples 43 to 45 were prepared in a manner similar to that described in Example 31.

[0153] Example 46: Preparation of 4-(3-(dimethylamino)propoxy)-N-(3-(1-methyl-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0154] Step 1: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide was prepared in a manner similar to that described in Example 14.

[0155] Step 2: Preparation of 4-(3-(dimethylamino)propoxy)-N-(3-(1-methyl-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0156] N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide (150 mg, 0.981 mmol) prepared in Step 1 above was dissolved in DMF (1 mL) and sodium hydride (60%) (51.5 mg, 1.287 mmol) was added dropwise at −20°C, followed by stirring for 30 minutes. At the same temperature, iodomethane (23 μL, 0.368 mmol) dissolved in DMF (0.1 mL) was slowly added dropwise, followed by stirring at room temperature for 12 hours. Upon completion of the reaction, the reaction mixture was extracted with ethyl acetate and neutralized with supersaturated aqueous ammonium chloride solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (13.7 mg, 8%, clear oil).

[0157] Example 47: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-bromobenzenesulfonamide [ka]

[0158] Step 1: Preparation of 4-bromobenzene-1-sulfonyl chloride [ka]

[0159] Bromobenzene (0.067 ml, 0.637 mmol) was dissolved in dichloromethane (2 ml), and chlorosulfonic acid (0.169 ml, 2.55 mmol) was added dropwise at 0°C, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, ice was added. The reaction mixture was extracted with dichloromethane and neutralized with a supersaturated aqueous solution of sodium carbonate. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. As a result, 4-bromobenzene-1-sulfonyl chloride (74 mg, 45%, white solid) was obtained without further purification.

[0160] Step 2: Preparation of N-(3-(1H-indol-3-yl)propyl)-4-bromobenzenesulfonamide [ka]

[0161] 4-Bromobenzene-1-sulfonyl chloride (74 mg, 0.29 mmol) prepared in Step 1 above was dissolved in dichloromethane (1 mL) and 3-(1H-indol-3-yl)propan-1-amine (151 mg, 0.869 mmol) and potassium carbonate (K2CO3) (120 mg, 0.869 mmol) were added dropwise, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane, and the organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to yield the target compound (71 mg, 62%, white solid).

[0162] The compounds of Examples 48 to 54 were prepared in a manner similar to that described in Example 31.

[0163] The compound of Example 55 was prepared in a manner similar to that described in Example 30.

[0164] The compounds of Examples 56 to 58 were prepared in a manner similar to that described in Example 31.

[0165] The compounds of Example 59 and Example 60 were prepared in a manner similar to that described in Example 30.

[0166] The compound of Example 61 was prepared in a manner similar to that described in Example 31.

[0167] The compound of Example 62 was prepared in a manner similar to that described in Example 30.

[0168] The compounds of Examples 63 to 71 were prepared in a manner similar to that described in Example 31.

[0169] Example 72 Preparation of 4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0170] Step 1: Preparation of (2S,6R)-tert-butyl 4-(3-(4-(N-(3-(5-fluoro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)-2,6-dimethylpiperazine-1-carboxylate (2S,6R)-tert-butyl 4-(3-(4-(N-(3-(5-fluoro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)-2,6-dimethylpiperazine-1-carboxylate was prepared in a manner similar to that described in Example 31.

[0171] Step 2: Preparation of 4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0172] (2S,6R)-tert-butyl 4-(3-(4-(N-(3-(5-fluoro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)-2,6-dimethylpiperazine-1-carboxylate (80 mg, 0.133 mmol) prepared in Step 1 above was dissolved in dichloromethane (1 mL), and trifluoroacetic acid (0.2 mL, 2.65 mmol) was added thereto at room temperature, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, ice was added thereto. The reaction mixture was extracted with ethyl acetate and neutralized with a supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to obtain the target compound (5.2 mg, 7%, white solid).

[0173] The compounds of Examples 73 to 76 were prepared in a manner similar to that described in Example 31. .

[0174] Example 77 Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfonamide [ka]

[0175] Step 1: Preparation of tert-butyl (1-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)azetidin-3-yl)(methyl)carbamate tert-Butyl (1-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)azetidin-3-yl(methyl)carbamate was prepared in a manner similar to that described in Example 31.

[0176] Step 2: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfonamide [ka]

[0177] Using the tert-butyl azetidin-3-yl(methyl)carbamate prepared in Step 1 above, tert-butyl (1-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)azetidin-3-yl)(methyl)carbamate (38 mg, 0.064 mmol) was dissolved in dichloromethane (0.5 mL), and trifluoroacetic acid (0.2 mL, 2.61 mmol) was added dropwise at room temperature, followed by stirring at room temperature for 2 hours. Upon completion of the reaction, ice was added. The reaction mixture was extracted with ethyl acetate and neutralized with supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then purified by MPLC to give the target compound (7 mg, 22%, yellow solid).

[0178] The compound of Example 78 was prepared in a manner similar to that described in Example 31.

[0179] Example 79: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-6-(3-(piperazin-1-yl)propoxy)pyridine-3-sulfonamide [ka]

[0180] Step 1: Preparation of tert-butyl-4-(3-((5-bromopyridin-2-yl)oxy)propylpiperazine-1-carboxylate [ka]

[0181] 5-Bromo-2-fluoropyridine (0.326 ml, 2.84 mmol) was dissolved in DMF (12 ml), and sodium hydride 60 wt% (0.159 g, 3.98 mmol) was added dropwise thereto at 0°C, followed by stirring for 5 minutes. tert-Butyl-4-(3-hydroxypropyl)piperazine-1-carboxylate was added dropwise thereto, and the mixture was stirred at 70°C for 6 hours. Upon completion of the reaction, ice was added thereto. The reaction mixture was extracted with dichloromethane and neutralized with a supersaturated aqueous solution of sodium carbonate. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. As a result, tert-butyl-4-(3-((5-bromopyridin-2-yl)oxy)propylpiperazine-1-carboxylate (1.35 g, 110%) was obtained without further purification.

[0182] Step 2: Preparation of tert-butyl 4-(3-((5-((4-methoxybenzyl)thio)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate [ka]

[0183] tert-Butyl-4-(3-(((5-bromopyridin-2-yl)oxy)propylpiperazine-1-carboxylate (0.52 g, 1.3 mmol) prepared in step 1 above was dissolved in 1,4-dioxane (12 ml), and (4-methoxyphenyl)methanethiol (0.199 ml, 1.23 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.681 ml, 3.90 mmol) were added dropwise thereto, followed by reaction for 5 minutes in a nitrogen atmosphere. Pd(dba) (9.91 mg, 0.032 mmol), Xantphos (0.038 g, 0.065 mmol) and tert-butyl-4-(3-hydroxypropyl)piperazine-1-carboxylate were added dropwise thereto, followed by reaction at 150° C. in a Biotage microwave for 30 minutes. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane and neutralized with supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. As a result, tert-butyl 4-(3-((5-((4-methoxyphenyl)-2-methyl-4-(3-hydroxypropyl ... Benzyl)thio)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate (0.51 g, 51.8%) was obtained.

[0184] Step 3: Preparation of tert-butyl 4-(3-((5-(chlorosulfonyl)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate [ka]

[0185] tert-Butyl 4-(3-((5-((4-methoxybenzyl)thio)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate (0.469 g, 0.99 mmol) prepared in Step 2 above was dissolved in acetic acid (8 ml) and water (2 ml), and N-chlorosuccinimide (0.529 g, 3.96 mmol) was added dropwise thereto, followed by reaction at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane and neutralized with supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. As a result, tert-butyl 4-(3-(((5-(chlorosulfonyl)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate (0.25 g, 60%) was obtained without further purification.

[0186] Step 4: Preparation of tert-butyl 4-(3-((5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate [ka]

[0187] tert-Butyl 4-(3-((5-(chlorosulfonyl)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate (0.1 g, 0.238 mmol) prepared in Step 3 above was dissolved in DMF (2 ml), and 3-(5-chloro-1H-indol-3-yl)propan-1-amine (0.055 g, 0.262 mmol) and potassium carbonate (0.066 g, 0.476 mmol) were added dropwise thereto, followed by stirring at room temperature for 2 hours. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane and neutralized with supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The reaction mixture was then separated and purified by preparative TLC to obtain tert-butyl 4-(3-(5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate (18 mg, 12.8%).

[0188] Step 5: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-6-(3-(piperazin-1-yl)propoxy)pyridine-3-sulfonamide [ka]

[0189] 4-(3-((5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)pyridin-2-yl)oxy)propyl)piperazine-1-carboxylate (18 mg, 0.034 mmol) prepared in Step 4 above was dissolved in tetrahydrofuran (1 mL), and trifluoroacetic acid (0.5 mL, 6.49 mmol) was added dropwise thereto at room temperature, followed by stirring at room temperature for 2 hours. Upon completion of the reaction, ice was added thereto. The reaction mixture was extracted with ethyl acetate and neutralized with a supersaturated aqueous sodium carbonate solution. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The reaction mixture was then separated and purified by preparative TLC to obtain the target compound (4.5 mg, 30%).

[0190] The compounds of Examples 80 to 84 were prepared in a manner similar to that described in Example 31.

[0191] Example 85: Preparation of N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0192] Step 1: Preparation of 3-(1H-indol-3-yl)cyclohexan-1-one [ka]

[0193] 1H-Indole (1 g, 8.54 mmol) and cyclohex-2-enone (1.64 g, 17.1 mmol) were dissolved in CHCN (30 mL), and Sc(OTf) (0.42 g, 0.854 mmol) was added thereto, followed by stirring at 30 °C under N atmosphere for 3 h. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by preparative HPLC to give the target compound (805 mg, 44%).

[0194] Step 2: Preparation of 3-(1H-indol-3-yl)cyclohexan-1-amine [ka]

[0195] 3-(1H-indol-3-yl)cyclohexan-1-one (800 mg, 3.75 mmol) prepared in Step 1 above was dissolved in dichloroethane (10 mL) and acetic acid (0.5 mL). Ammonium acetate (8.67 g, 113 mmol) was added at room temperature and stirred for 2 hours. Sodium triacetoxyborohydride (3.18 g, 15.0 mmol) was then added at room temperature and stirred for 5 hours. Upon completion of the reaction, the mixture was concentrated under reduced pressure, and the resulting reaction mixture was purified by MPLC to give the target compound (250 mg, 31%, yellow solid).

[0196] Step 3: Preparation of N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-bromopropoxy)benzenesulfonamide [ka]

[0197] The target compound (100 mg, 46%, white solid) was obtained in the same manner as in Step 2 of Example 31 using 3-(1H-indol-3-yl)cyclohexane-1-amine (105 mg, 0.491 mmol) prepared in Step 2 above and 4-(3-bromopropoxy)benzenesulfonyl chloride (140 mg, 0.446 mmol) obtained in the same manner as in Step 2 of Example 31.

[0198] Step 4: Preparation of N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0199] The target compound (21.6 mg, 69% yield) was obtained as a white solid in the same manner as described in Step 3 of Example 31 using N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-bromopropoxy)benzenesulfonamide (30 mg, 0.061 mmol) prepared in Step 3 above and 1-methylpiperazine (24.5 mg, 0.244 mmol).

[0200] Example 86: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfonamide [ka]

[0201] Step 1: Preparation of 4-(3-bromopropoxy)naphthalene-1-sulfonic acid sodium(I) salt [ka]

[0202] 4-Hydroxynaphthalene-1-sulfonic acid sodium salt (I) (0.3 g, 1.218 mmol) was dissolved in ethanol (2.5 mL), 1,3-dibromopropane (0.211 mL, 2.071 mmol), tetrabutylammonium sulfate (0.033 g, 0.097 mmol), and aqueous potassium hydroxide (1.56 mL, 1.218 mmol) were added, and the mixture was heated to reflux for 3 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, redissolved in ethanol, and concentrated again. Hot methanol was added to the reaction solution, and the insoluble material was filtered. The filtrate was concentrated. The resulting solid was washed with dichloromethane and filtered to give the target compound (0.4 g, 99%, white solid).

[0203] Step 2: Preparation of 4-(3-bromopropoxy)naphthalene-1-sulfonyl chloride [ka]

[0204] To the compound prepared in Step 1 above (0.2 g, 0.545 mmol) was added thionyl chloride (0.286 mL, 3.92 mmol) and dimethylformamide (1.91 μL), followed by heating to reflux for 4 hours. Upon completion of the reaction, the temperature was lowered to room temperature, and the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and used in the next step without further purification.

[0205] Step 3: Preparation of 4-(3-bromopropoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)naphthalene-1-sulfonamide [ka]

[0206] The target compound was prepared in a similar manner to that described in step 2 of Example 31.

[0207] Step 4: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfonamide [ka]

[0208] The target compound was prepared in a similar manner to that described in step 3 of Example 31.

[0209] The compound of Example 87 was prepared in a manner similar to that described in Example 31.

[0210] Example 88: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-4-yl)propyl)amino)benzenesulfonamide [ka]

[0211] Step 1: Preparation of tert-butyl-4-(3-oxopropyl)piperidine-1-carboxylate [ka]

[0212] tert-Butyl-4-(3-hydroxypropyl)piperidine-1-carboxylate (0.3 g, 1.233 mmol) was dissolved in dichloromethane (6 ml), and Dess-Martin periodinane (0.680 g, 1.603 mmol) was added thereto at 0°C. The mixture was then stirred at room temperature for 4 hours. Upon completion of the reaction, the reaction solution was filtered, and the filtrate was washed with aqueous sodium bicarbonate and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by MPLC to give the target compound (0.24 g, 79%, clear oil).

[0213] Step 2: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-nitrobenzenesulfonamide [ka]

[0214] The target compound was prepared in a similar manner to that described in step 2 of Example 31.

[0215] Step 3: Preparation of 4-amino-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0216] The compound prepared in Step 2 above (0.72 g, 1.840 mmol) was dissolved in ethyl acetate (12 ml), and tin(II) chloride dihydrate (4.15 g, 18.40 mmol) was added thereto, followed by heating at 60° C. for 5 hours. Upon completion of the reaction, aqueous ammonia was added to the reaction solution to adjust the pH to 5, and sodium carbonate was added to adjust the pH to 7. The reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure and used in the next step without further purification.

[0217] Step 4: Preparation of tert-butyl 4-(3-((4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenyl)amino)propyl)piperidine-1-carboxylate [ka]

[0218] The compound prepared in Step 3 above (0.05 g, 0.137 mmol) was dissolved in dichloroethane (1 mL), and the compound prepared in Step 1 above (0.046 g, 0.192 mmol) and acetic acid (0.024 mL, 0.412 mmol) were added thereto, followed by stirring at room temperature for 1 hour. Sodium triacetoxyborohydride (0.087 g, 0.412 mmol) was added thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, purified by preparative HPLC, and neutralized with aqueous sodium bicarbonate to give the target compound (0.017 g, 5%, yellow solid).

[0219] Step 5: N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(( Preparation of 3-(piperidin-4-yl)propyl)amino)benzenesulfonamide [ka]

[0220] The target compound was prepared in a manner similar to that described in step 5 of Example 79.

[0221] Example 89: Preparation of N-(3-(1H-indol-3-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0222] Step 1: Preparation of 3-(3-nitrophenyl)-1H-indole [ka]

[0223] N-(2-ethynylphenyl)-2,2,2-trifluoroacetamide and 1-iodo-3-nitrobenzene were dissolved in DMSO and treated with excess K2CO3 in the presence of a catalytic amount of Pd2(dba)3 to give the target compound, 3-(3-nitrophenyl-1H-indole).

[0224] Step 2: Preparation of 3-(1H-indol-3-yl)aniline [ka]

[0225] The compound prepared in Step 1 above (0.047 g, 0.197 mmol) was dissolved in methanol (2 mL), and Pd / C (0.004 g, 3.76 μmol) was added. The mixture was then stirred under hydrogen gas at room temperature for 3 hours. Upon completion of the reaction, the reaction solution was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure and used in the next step without further purification.

[0226] Step 3: Preparation of N-(3-(1H-indol-3-yl)phenyl)-4-(3-bromopropoxy)benzenesulfonamide [ka]

[0227] The compound prepared in Step 2 above (0.041 g, 0.197 mmol) was dissolved in pyridine (1 ml), and the compound prepared in Step 1 of Example 31 (0.068 g, 0.217 mmol) was added thereto at 0° C., followed by stirring at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to give the target compound (0.047 g, 49%, yellow solid).

[0228] Step 4: Preparation of N-(3-(1H-indol-3-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0229] The target compound was prepared in a similar manner to that described in step 3 of Example 31.

[0230] Example 90: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-1-yl)butyl)benzenesulfonamide [ka]

[0231] Step 1: Preparation of 4-(4-bromobutyl)benzene-1-sulfonyl chloride [ka]

[0232] The target compound (1.4 g, 96%, white solid) was obtained in the same manner as described in Step 1 of Example 31 using (4-bromobutyl)benzene (1.0 g, 4.69 mmol) and chlorosulfonic acid (0.936 ml, 14.1 mmol).

[0233] Step 2: Preparation of 4-(4-bromobutyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonylamide [ka]

[0234] 4-(4-Bromobutyl)benzene-1-sulfonyl chloride (300 mg, 0.963 mmol) prepared in Step 1 above was dissolved in dichloromethane (5 mL), and 3-(5-chloro-1H-indol-3-yl)propan-1-amine (211 mg, 1.01 mmol) and triethylamine (0.268 mL, 1.93 mmol) were added at room temperature, followed by stirring for 3 hours. Upon completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC to give the target compound (330 mg, 71%, white solid).

[0235] Step 3: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-1-yl)butyl)benzenesulfonamide [ka]

[0236] Using 4-(4-bromobutyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonylamide (30 mg, 0.062 mmol) prepared in Step 2 above, piperidine (15.9 mg, 0.186 mmol) and potassium carbonate (12.9 mg, 0.093 mmol), the target compound (16 mg, 53%, white solid) was obtained in the same manner as described in Step 3 of Example 31.

[0237] The compound of Example 91 was prepared in a manner similar to that described in Example 90.

[0238] Example 92: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide [ka]

[0239] Step 1: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-hydroxybenzenesulfonamide [ka]

[0240] 4-Hydroxybenzene-1-sulfonyl chloride (0.5 g, 2.60 mmol) was dissolved in dichloromethane (8.7 mL), and 3-(5-chloro-1H-indol-3-yl)propan-1-amine (0.596 g, 2.86 mmol) and triethylamine (0.724 mL, 5.19 mmol) were added thereto, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (0.19 g, 21%, white solid).

[0241] Step 2: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide [ka]

[0242] The compound prepared in Step 1 above (0.05 g, 0.137 mmol) was dissolved in tetrahydrofuran (1.5 mL) under nitrogen gas at 0 °C, and 3-(1-methylpiperidin-4-yl)propan-1-ol (0.026 g, 0.164 mmol), PPh3 (0.054 g, 0.206 mmol), and DEAD (0.093 mL, 0.206 mmol) were added thereto, followed by stirring for 1 hour. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, purified by preparative HPLC, and neutralized with aqueous sodium bicarbonate to give the target compound (0.004 g, 7%, white solid).

[0243] Example 93: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide [ka]

[0244] The compound (0.035 g, 0.061 mmol) prepared in the same manner as in Example 92 was dissolved in dichloromethane (2 ml), and trifluoroacetic acid (1 ml, 12 0.98 mmol) was added, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, purified by preparative HPLC, and neutralized by adding aqueous sodium bicarbonate solution to give the target compound (0.01 g, 37%, white solid).

[0245] The compound of Example 94 was prepared in a manner similar to that described in Example 93.

[0246] The compounds of Example 95 and Example 96 were prepared in a manner similar to that described in Example 94.

[0247] The compound of Example 97 was prepared in a manner similar to that described in Example 31.

[0248] Example 98: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzenesulfonamide [ka]

[0249] The compound (0.05 g, 0.136 mmol) prepared in a manner similar to that described in Step 2 of Example 47 was dissolved in dimethylformamide (1 ml), and 3-(4-methylpiperazin-1-yl)propan-1-amine (0.043 g, 0.273 mmol) and potassium carbonate (0.021 g, 0.150 mmol) were added thereto, followed by stirring at 100° C. for 3 days. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, purified by preparative HPLC, and neutralized by adding aqueous sodium bicarbonate solution to obtain the target compound (0.01 g, 16%, white solid).

[0250] Example 99: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-4-yl)butyl)benzenesulfonamide [ka]

[0251] Step 1: Preparation of tert-butyl 4-(but-3-en-1-yl)piperidine-1-carboxylate [ka]

[0252] Methyltriphenylphosphonium bromide (1.184 g, 3.32 mmol) was dissolved in anhydrous tetrahydrofuran (2 ml), and lithium bistrimethylsilylamide (3.32 ml, 3.32 mmol) was slowly added thereto at 0 °C. tert-Butyl 4-(3-oxopropyl)piperidine-1-carboxylate (0.4 g, 1.66 mmol) prepared in Step 1 of Example 88 was dissolved in anhydrous tetrahydrofuran (2 ml) and slowly added dropwise thereto at 0 °C. The mixture was stirred at 0 °C for 30 minutes and then at room temperature for 20 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, washed with brine, and extracted with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by MPLC to give the target compound (0.2 g, 50%, clear oil).

[0253] Step 2: Preparation of tert-butyl 4-(4-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenyl)butyl)piperidine-1-carboxylate [ka]

[0254] tert-Butyl 4-(but-3-en-1-yl)piperidine-1-carboxylate (50 mg, 0.209 mmol), prepared in Step 2 above, was dissolved in anhydrous tetrahydrofuran (1.5 mL) and 9-borabicyclo[3.3.1]nonane (0.796 mL, 0.398 mmol) was added at room temperature. The reaction mixture was gradually heated and stirred under reflux for 1 hour. Upon completion of the reaction, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was dissolved in 1,4-dioxane (1.5 mL) and 4-bromo-N-(3-(5-chloro-1H-indol-3)-yl)propyl)benzenesulfonamide (85 mg, 0.199 mmol), prepared in a manner similar to that described in Step 2 of Example 90, and 1 M aqueous sodium carbonate solution (0.597 mL, 0.597 mmol) were added. Pd(PPh3)4 (23 mg, 0.02 mmol) was added to the reaction mixture, and the mixture was gradually heated and stirred at 90 °C for 3 h. Upon completion of the reaction, the reaction mixture was cooled to room temperature, filtered through Celite, concentrated under reduced pressure, and purified by preparative HPLC to give the target compound (15 mg, 13%, yellow solid).

[0255] Step 3: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-4-yl)butyl)benzenesulfonamide [ka]

[0256] tert-Butyl 4-(4-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenyl)butyl)piperidine-1-carboxylate (15 mg, 0.013 mmol) prepared in Step 2 above was dissolved in dichloromethane (2 mL), and trifluoroacetic acid (1 mL, 13.1 mmol) was added thereto at room temperature, followed by stirring for 1 hour. Upon completion of the reaction, the mixture was concentrated and the resulting residue was dissolved in supersaturated charcoal. The mixture was neutralized with aqueous sodium hydrogen carbonate and then extracted with ethyl acetate. The extracted organic layer was washed with distilled water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the target compound (5 mg, 56%, white solid).

[0257] The compounds of Examples 100 to 102 were prepared in a manner similar to that described in Example 31.

[0258] Example 103: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0259] Step 1: Preparation of 1-(3-bromopropoxy)-2-fluorobenzene [ka]

[0260] 2-Fluorophenol (5 g, 44.6 mmol) was dissolved in acetonitrile (74 ml), and 1,3-dibromopropane (90 g, 446 mmol) and potassium carbonate (6.16 g, 44.6 mmol) were added thereto, followed by stirring for 16 hours at 80° C. Upon completion of the reaction, the reaction solution was filtered and concentrated under reduced pressure, and used in the next step without further purification.

[0261] Step 2: Preparation of 4-(3-bromopropoxy)-3-fluorobenzenesulfonyl chloride [ka]

[0262] The compound prepared in Step 1 above (5 g, 19.31 mmol) was dissolved in dichloromethane (38 ml), and chlorosulfonic acid (5.13 ml, 77 mmol) was added thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and neutralized with aqueous sodium carbonate at 0° C. The organic layer residue was dried over anhydrous sodium sulfate, filtered, and concentrated, and used in the next step without further purification.

[0263] Step 3: Preparation of 4-(3-bromopropoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluorobenzenesulfonamide [ka]

[0264] The compound prepared in step 2 above (1 g, 3.02 mmol) was dissolved in dichloromethane (6 ml), and 3-(5-chloro-1H-indol-3-yl)propan-1-amine (0.818 g, 3.92 mmol) and potassium carbonate (0.542 g, 3.92 mmol) were added thereto, followed by stirring at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (1.1 g, 77%, white solid).

[0265] Step 4: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0266] The compound prepared in step 3 above (0.05 g, 0.099 mmol) was dissolved in ethanol (1 ml), and potassium carbonate (0.021 g, 0.149 mmol) and 1-methylpiperazine (0.020 g, 0.198 mmol) were added thereto, followed by stirring at 70° C. for 16 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, purified by preparative HPLC, and then neutralized with aqueous sodium bicarbonate to give the target compound (0.011 g, 22%, white solid).

[0267] The compounds of Examples 104 to 106 were prepared in a manner similar to that described in Example 103.

[0268] Example 107: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0269] The target compound (15 mg, 72%) was obtained as a pale yellow solid in the same manner as described in Step 4 of Example 99 using tert-butyl 4-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)-2-methylpiperazine-1-carboxylate (25 mg, 0.041 mmol) obtained in the same manner as described in Example 31 and trifluoroacetic acid (1 ml, 13.1 mmol).

[0270] The compounds of Examples 108 to 111 were prepared in a manner similar to that described in Example 107.

[0271] The compound of Example 112 was prepared in a manner similar to that described in Example 90.

[0272] Example 113: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)propyl)amino)benzenesulfonamide [ka]

[0273] The compound (0.0142 g, 0.024 mmol) prepared in the same manner as in Example 98 was dissolved in dichloromethane (2 ml), and trifluoroacetic acid (1 ml, 12.98 mmol) was added thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, purified by preparative HPLC, and neutralized by adding aqueous sodium bicarbonate solution to obtain the target compound (0.005 g, 50%, white solid).

[0274] The compound of Example 114 was prepared in a manner similar to that described in Example 98.

[0275] The compound of Example 115 was prepared in the same manner as described in Steps 1 to 3 of Example 99. Made.

[0276] Example 116 Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)methoxy)benzenesulfonamide [ka]

[0277] Step 1: Preparation of (1-(((tert-butyldimethylsilyl)oxy)methyl)cyclopropyl)methanol [ka]

[0278] Cyclopropane-1,1-diyldimethanol (5 g, 49.0 mmol) was dissolved in dichloromethane (130 mL) and imidazole (5 g, 73.4 mmol) and tert-butyldimethylsilyl chloride (7.75 g, 51.4 mmol) were added. The reaction mixture was stirred at 0 °C for 30 minutes and then at room temperature for 16 hours. Upon completion of the reaction, the reaction mixture was neutralized with supersaturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extracted organic layer was washed with distilled water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The reaction mixture was purified by MPLC to give the target compound (4.7 g, 44%, clear oil).

[0279] Step 2: Preparation of ((1-(bromomethyl)cyclopropyl)methoxy)(tert-butyl)dimethylsilane [ka]

[0280] (1-(((tert-Butyldimethylsilyl)oxy)methyl)cyclopropyl)methanol (1.1 g, 5.08 mmol), prepared in Step 1 above, was dissolved in dichloromethane (10 ml), and carbon tetrabromide (1.85 g, 5.59 mmol) and triphenylphosphine (1.47 g, 5.59 mmol) were added. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 16 hours. Upon completion, the reaction mixture was concentrated under reduced pressure and purified by MPLC to give the target compound (1 g, 70%, clear oil).

[0281] Step 3: Preparation of (1-(bromomethyl)cyclopropyl)methanol [ka]

[0282] ((1-(bromomethyl)cyclopropyl)methoxy)(tert-butyl)dimethylsilane (1 g, 3.58 mmol) prepared in step 2 above was dissolved in acetic acid / tetrahydrofuran / distilled water (12 ml / 4 ml / 4 ml) and then stirred at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was neutralized with supersaturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extracted organic layer was washed with distilled water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting reaction mixture was purified by MPLC to give the target compound (0.3 mg, 51%, yellow oil).

[0283] Step 4: Preparation of 4-((1-(bromomethyl)cyclopropyl)methoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0284] The target compound (45 mg, 48%, yellow solid) was obtained in the same manner as described in Step 2 of Example 92 using (1-(bromomethyl)cyclopropyl)methanol (30 mg, 0.182 mmol) prepared in Step 3 above, N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-hydroxybenzenesulfonamide (66 mg, 0.182 mmol), triphenylphosphine (72 mg, 0.273 mmol), and diethyl azodicarbonate (0.124 ml, 0.273 mmol).

[0285] Step 5: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)methoxy)benzenesulfonamide [ka]

[0286] The target compound (12.3 mg, 59%, yellow solid) was obtained in the same manner as in Step 3 of Example 31 using 4-((1-(bromomethyl)cyclopropyl)methoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide (20 mg, 0.039 mmol) prepared in Step 4 above, 1-methylpiperazine (0.013 ml, 0.117 mmol), and potassium carbonate (8.1 mg, 0.059 mmol).

[0287] The compound of Example 117 was prepared in a manner similar to that described in Example 116.

[0288] Example 118: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide [ka]

[0289] Step 1: Preparation of 4-(3-bromophenoxy)benzenesulfonic acid [ka]

[0290] 1-Bromo-3-phenoxybenzene (300 mg, 1.20 mmol) was dissolved in dichloromethane, and chlorosulfonic acid (0.088 ml, 1.33 mmol) was slowly added thereto at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure to give the target compound (395 mg, 100%, yellow oil).

[0291] Step 2: Preparation of 4-(3-bromophenoxy)benzenesulfonyl chloride [ka]

[0292] 4-(3-Bromophenoxy)benzenesulfonic acid (395 mg, 1.20 mmol) prepared in Step 1 above was dissolved in SnCl₂·HO (3 mL, 41.4 mmol) at 0 °C and stirred. Two drops of diformamide were then added at 0 °C, and the reaction mixture was gradually heated and stirred under reflux for 2 h. Upon completion, the reaction mixture was cooled to room temperature, concentrated under reduced pressure, and purified by MPLC to give the target compound (380 mg, 91%, yellow oil).

[0293] Step 3: Preparation of 4-(3-bromophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0294] The target compound (170 mg, 76%, yellow solid) was obtained in a similar manner to that described in Step 2 of Example 90 using 4-(3-bromophenoxy)benzenesulfonyl chloride (150 mg, 0.432 mmol) prepared in Step 2 above, 3-(5-chloro-1H-indol-3-yl)propan-1-amine (90 mg, 0.432 mmol), and triethylamine (0.090 ml, 0.647 mmol).

[0295] Step 4: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide [ka]

[0296] 4-(3-bromophenoxy)-N-(3-(5-chloro-1-methylpropyl)methyl)-N ...bromophenoxy)methyl)-N-(3-bromophenoxy)methyl)-N-(3-bromophenoxy)methyl)-N-(3-bromophenoxy)methyl)-N-(3- H-Indol-3-yl)propyl)benzenesulfonamide (90 mg, 0.173 mmol) was dissolved in 1,4-dioxane (1.5 mL), and t-BuOK (29.1 mg, 0.260 mmol) and 1-methylpiperazine (0.03 mL, 0.260 mmol) were added at room temperature. The reaction mixture was heated to 70 °C, stirred, and degassed using a nitrogen balloon for 5 minutes. Pd(t-BuP) (8 mg, 0.016 mmol) was added, followed by stirring at reflux for 3 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature, filtered, concentrated through Celite, and purified by preparative HPLC. The resulting trifluoroacetate compound was neutralized with supersaturated aqueous sodium bicarbonate and extracted with 10% methanol / dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the target compound (6.5 mg, 53%, white solid).

[0297] The compound of Example 119 was prepared in a manner similar to that described in Steps 1-3 of Example 118.

[0298] The compounds of Examples 120 to 122 were prepared in a manner similar to that described in Example 118.

[0299] Example 123: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide [ka]

[0300] The compound (0.05 g, 0.117 mmol) prepared in a similar manner to that described in Step 2 of Example 47 was dissolved in 2-butanol (1.5 ml), and 3-(4-methylpiperazin-1-yl)aniline (0.02 g, 0.117 mmol) and potassium carbonate (0.08 g, 0.584 mmol) were added thereto, followed by degassing for 1 minute. Pd2(dba)3 (0.01 g, 0.012 mmol) and Xphos (0.005 g, 0.012 mmol) were then added thereto at 80 °C, followed by stirring at 100 °C for 1 hour. Upon completion of the reaction, the reaction solution was filtered through Celite and washed with ethyl acetate and dichloromethane. The filtrate was concentrated under reduced pressure, purified by preparative HPLC, and neutralized with aqueous sodium bicarbonate to give the target compound (0.023 g, 37%, yellow solid).

[0301] The compounds of Examples 124 to 127 were prepared in a manner similar to that described in Example 123.

[0302] The compounds of Example 128 and Example 129 were prepared in a manner similar to that described in Example 119.

[0303] Example 130: 4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy) Preparation of -N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0304] Step 1: Preparation of 1,3-dibromo-5-phenoxybenzene [ka]

[0305] Phenol (100 mg, 1.06 mmol) was dissolved in N-methyl-2-pyrrolidinone (2 mL), and cesium carbonate (173 mg, 0.531 mmol), 1,3-dibromo-5-fluorobenzene (0.201 mL, 1.59 mmol), TMHDA (0.057 mL, 0.266 mmol), and CuCl (52.6 mg, 0.531 mmol) were added at room temperature. The reaction mixture was degassed at room temperature using a nitrogen balloon and then stirred for 20 minutes. The reaction mixture was gradually heated and stirred at 120 °C for 16 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature, filtered through Celite, extracted with ethyl acetate, and concentrated under reduced pressure. The resulting reaction mixture was purified by MPLC to give the target compound (220 mg, 63%, yellow solid).

[0306] Step 2: Preparation of 4-(3,5-dibromophenoxy)benzenesulfonic acid [ka]

[0307] Using 1,3-dibromo-5-phenoxybenzene (220 mg, 0.671 mmol) prepared in Step 1 above and chlorosulfonic acid (0.049 ml, 0.738 mmol), the target compound (274 mg, 100%, yellow solid) was obtained in the same manner as described in Step 1 of Example 118.

[0308] Step 3: Preparation of 4-(3,5-dibromophenoxy)benzenesulfonyl chloride [ka]

[0309] Using 4-(3,5-dibromophenoxy)benzenesulfonic acid (274 mg, 0.671 mmol) prepared in step 2 above and thionyl chloride (4 ml, 55.1 mmol), The target compound (230 mg, 80%, yellow solid) was obtained in the same manner as described in Step 2 of Example 118.

[0310] Step 4: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3,5-dibromophenoxy)benzenesulfonamide [ka]

[0311] The target compound (300 mg, 93%, white solid) was obtained in the same manner as described in Step 2 of Example 90 using 4-(3,5-dibromophenoxy)benzenesulfonyl chloride (230 mg, 0.539 mmol) prepared in Step 3 above, 3-(5-chloro-1H-indol-3-yl)propan-1-amine (118 mg, 0.566 mmol), and triethylamine (0.113 ml, 0.809 mmol).

[0312] Step 5: Preparation of 4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0313] The target compound (5 mg, 9%, yellow solid) was obtained in the same manner as described in Step 4 of Example 118 using N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3,5-dibromophenoxy)benzenesulfonamide (50 mg, 0.084 mmol) prepared in Step 4 above, 1-methylpiperazine (0.037 mL, 0.334 mmol), potassium tert-butoxide (37.5 mg, 0.334 mmol), and Pd(t-BuP) (8.54 mg, 0.017 mmol).

[0314] The compounds of Examples 131 to 134 were prepared in a manner similar to that described in Example 123.

[0315] The compounds of Example 135 and Example 136 were prepared in a manner similar to that described in Example 118.

[0316] The compound of Example 137 was prepared in a manner similar to that described in Example 138.

[0317] Example 138: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide [ka]

[0318] Step 1: Preparation of 1-bromo-3-fluoro-5-phenoxybenzene [ka]

[0319] The target compound (0.45 g, 32%, clear oil) was obtained in a similar manner to that described in Step 1 of Example 130 using phenol (0.5 g, 5.31 mmol), cesium carbonate (0.866 g, 2.66 mmol), 1-bromo-3,5-difluorobenzene (1.54 g, 7.97 mmol), TMHDA (0.284 mL, 1.33 mmol), and CuCl (0.263 mg, 2.66 mmol).

[0320] Step 2: Preparation of 4-(3-bromo-5-fluorophenoxy)benzene-1-sulfonyl chloride [ka]

[0321] The target compound (0.44 g, 71%, yellow oil) was obtained in the same manner as described in Step 1 of Example 31 using 1-bromo-3-fluoro-5-phenoxybenzene (0.45 g, 1.685 mmol) prepared in Step 1 above and chlorosulfonic acid (0.123 ml, 1.853 mmol).

[0322] Step 3: Preparation of 4-(3-bromo5-fluorophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0323] The target compound (300 mg, 93%, yellow solid) was obtained in the same manner as described in Step 2 of Example 90 using 4-(3-bromo-5-fluorophenoxy)benzene-1-sulfonyl chloride (200 mg, 0.547 mmol) prepared in Step 2 above, 3-(5-chloro-1H-indol-3-yl)propan-1-amine (115 mg, 0.553 mmol) and triethylamine (0.114 ml, 0.821 mmol).

[0324] Step 4: 4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N Preparation of -(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0325] 4-(3-Bromo-5-fluorophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide (30 mg, 0.056 mmol) prepared in Step 3 above was dissolved in dimethyl sulfoxide (1 mL), and 1-methylpiperazine (0.025 mL, 0.223 mmol) and potassium carbonate (30.8 mg, 0.223 mmol) were added thereto at room temperature. The reaction mixture was then heated to 120°C and stirred for 16 hours. Upon completion of the reaction, the mixture was cooled to room temperature, washed with distilled water and brine, and extracted with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by preparative HPLC. The resulting trifluoroacetate compound was neutralized by the addition of supersaturated aqueous sodium bicarbonate solution, followed by extraction with 10% methanol / dichloromethane solution. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure to give the target compound (6.2 mg, 22%, ivory solid).

[0326] The compounds of Examples 139 to 142 were prepared in a manner similar to that described in Example 123.

[0327] Example 143: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzamide [ka]

[0328] Step 1: Preparation of methyl 4-(3-bromopropoxy)benzoate [ka]

[0329] Methyl 4-hydroxybenzoate (0.5 g, 3.29 mmol) was dissolved in acetonitrile (10 mL) and 1,3-dibromopropane (0.995 g, 4.93 mmol) and potassium carbonate (0.681 g, 4.93 mmol) were added. The reaction mixture was heated to 80 °C and stirred for 5 hours. Upon completion of the reaction, the mixture was cooled to room temperature, filtered through Celite, and concentrated under reduced pressure. The resulting residue was purified by MPLC to give the target compound (0.7 g, 78%, clear oil).

[0330] Step 2: Preparation of 4-(3-bromopropoxy)benzoic acid [ka]

[0331] Methyl 4-(3-bromopropoxy)benzoate (0.7 g, 2.56 mmol) prepared in Step 1 above was dissolved in tetrahydrofuran / methanol / distilled water (6.0 mL / 3 mL / 3 mL), and LiOH·HO (0.323 g, 7.69 mmol) was added at room temperature. The reaction mixture was then heated to 50 °C and stirred for 2 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the pH was adjusted to 2 by the slow dropwise addition of 1N aqueous hydrochloric acid. The resulting solid was washed with distilled water and dried in vacuo to yield the target compound (0.35 g, 53%, white solid).

[0332] Step 3: Preparation of 4-(3-bromopropoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzamide [ka]

[0333] 4-(3-Bromopropoxy)benzoic acid (0.1 g, 0.386 mmol) prepared in Step 2 above was dissolved in dichloromethane (2 mL) and 3-(5-chloro-1H-indol-3-yl)propan-1-amine (0.081 g, 0.390 mmol), HATU (0.294 g, 0.772 mmol), and N,N-diisopropylethylamine (0.15 g, 1.158 mmol) were added at room temperature, followed by stirring at room temperature for 16 hours. Upon completion of the reaction, the mixture was washed with distilled water and extracted with dichloromethane. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by MPLC to give the target compound (0.1 g, 58%, ivory solid).

[0334] Step 4: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzamide [ka]

[0335] The target compound (8 mg, 38%, ivory solid) was obtained in the same manner as in Step 3 of Example 31 using 4-(3-bromopropoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzamide (20 mg, 0.044 mmol) prepared in Step 3 above, 1-methylpiperazine (0.02 ml, 0.178 mmol), and potassium carbonate (12.3 mg, 0.089 mmol).

[0336] The compound of Example 144 was prepared in a manner similar to that described in Example 143.

[0337] The compound of Example 145 was prepared in a manner similar to that described in Example 92.

[0338] Example 146: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfonamide [ka]

[0339] Step 1: Preparation of 2-chloro-N-(3-(5-chloro-1H-indol-3-yl)propyl)thiazole-5-sulfonamide [ka]

[0340] The target compound was prepared in a similar manner to that described in step 2 of Example 31.

[0341] Step 2: Preparation of tert-butyl 4-(3-((5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)thiazol-2-yl)amino)propyl)piperazine-1-carboxylate [ka]

[0342] 2-Chloro-N-(3-(5-chloro-1H-indol-3-yl)propyl)thiazole-5-sulfonamide (30 mg, 0.077 mmol), prepared in Step 1 above, was dissolved in dimethylformamide, and tert-butyl 4-(3-aminopropyl)piperazine-1-carboxylate (28 mg, 0.115 mmol) and DIPEA (0.022 mL, 0.154 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, the solvent was removed under reduced pressure, and the reaction mixture was then separated and purified by MPLC to give the target compound (37 mg, 81%, yellow solid).

[0343] Step 3: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfonamide [ka]

[0344] The target compound (30 mg, 97%, pale yellow solid) was obtained in a similar manner to that described in Step 3 of Example 99.

[0345] Example 147: Preparation of N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0346] Step 1: Preparation of 3-(5-chloro-2-methyl-1H-indol-3-yl)propan-1-amine hydrochloride [ka]

[0347] Chlorophenylhydrazine (1.40 g, 9.81 mmol) and 6-chlorohexen-2-one (1.10 g, 8.17 mmol) were dissolved in ethanol (30 mL) and then refluxed for 20 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the solvent was removed under reduced pressure to give 3-(5-chloro-2-methyl-1H-indol-3-yl)propan-1-amine hydrochloride (2.114 g, quantitative, pale yellow solid).

[0348] Step 2: Preparation of 4-(3-bromopropoxy)-N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)benzenesulfonamide [ka]

[0349] 3-(5-chloro-2-methyl-1H-indol-3-yl)propan-1-amine hydrochloride (0.413 g, 1.59 mmol) prepared in Step 1 above was dissolved in ethylene chloride (6 mL) and triethylamine (0.444 mL, 3.19 mmol) was added dropwise thereto, followed by stirring for 5 minutes. 4-(3-bromopropoxy)benzene-1-sulfonyl chloride (0.200 g, 0.638 mmol) was added dropwise thereto and then stirred at room temperature for 1 hour. Water was added dropwise to quench the reaction, followed by extraction with dichloromethane. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The mixture was then purified by MPLC to obtain the target compound (177 mg, 56%, brown solid).

[0350] Step 3: N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl Preparation of )-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0351] The target compound (19.8 mg, 64%, pale yellow solid) was obtained in a similar manner to that described in Step 3 of Example 31.

[0352] Example 148: Preparation of N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0353] 4-(4-Bromobutyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonylamide (30 mg, 0.062 mmol) prepared in Step 2 of Example 90 was dissolved in acetonitrile, and potassium carbonate (25.7 mg, 0.186 mmol) and 1H-imidazole (8.44 mg, 0.124 mmol) were added thereto at room temperature, followed by stirring at 60°C for 4 hours. Upon completion of the reaction, the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure and then purified by MPLC to obtain the target compound (13 mg, 45%, white solid).

[0354] Example 149: Preparation of N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0355] Step 1: Preparation of 2-((5-chloro-1H-indol-3-yl)methyl)aniline [ka]

[0356] 5-Chloro-1H-indole (1 g, 6.60 mmol) and (2-aminophenyl)methanol (0.812 g, 6.60 mmol) were dissolved in 1,2-dichloroethane (20 mL). Trifluoroacetic acid (0.151 mL, 1.979 mmol) was added at room temperature, followed by stirring at 50 °C for 16 hours. After cooling to room temperature, the reaction was quenched by the dropwise addition of supersaturated aqueous sodium carbonate solution, followed by extraction with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and purified by MPLC to obtain the target compound (0.55 g, 33%, yellow solid).

[0357] Step 2: Preparation of 4-(3-bromopropoxy)-N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)benzenesulfonamide [ka]

[0358] The target compound was obtained in a similar manner to that described in Step 2 of Example 31.

[0359] Step 3: Preparation of N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0360] The target compound (13.2 mg, 64%, pale yellow solid) was obtained in a similar manner to that described in Example 148.

[0361] The compound of Example 150 was prepared in a manner similar to that described in Example 149.

[0362] Example 151 Preparation of N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0363] Step 1: Preparation of 4-((5-chloro-1H-indol-3-yl)butan-2-one [ka]

[0364] 5-Chloro-1H-indole (1 g, 6.60 mmol) was dissolved in distilled water (20 mL), and 3-buten-2-one (1.387 g, 19.79 mmol) and trifluoromethanesulfonic acid (10 mg, 0.066 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the mixture was washed with supersaturated aqueous sodium carbonate and then extracted with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and then purified by MPLC to obtain the target compound (0.64 g, 44%, pale yellow solid).

[0365] Step 2: Preparation of 4-(5-chloro-1H-indol-3-yl)butan-2-amine [ka]

[0366] 4-((5-chloro-1H-indol-3-yl)butan-2-one (200 mg, 0.902 mmol) prepared in Step 1 above was dissolved in methanol (8 mL), and ammonium acetate (695 mg, 9.02 mmol) and sodium cyanoborohydride (283 mg, 4.51 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the mixture was washed with a supersaturated aqueous sodium carbonate solution and then extracted with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and purified by MPLC to obtain the target compound (0.2 g, 100%, pale yellow oil).

[0367] Step 3: Preparation of 4-(3-bromopropoxy)-N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)benzenesulfonamide [ka]

[0368] The target compound was obtained in a similar manner to that described in Step 2 of Example 31.

[0369] Step 4: Preparation of N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0370] The target compound (16 mg, 77%, white solid) was obtained in a similar manner to that described in Example 149.

[0371] The compound of Example 152 was prepared in a manner similar to that described in Example 151.

[0372] Example 153: Preparation of N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0373] Step 1: Preparation of 3-(5-bromo-1H-indol-3-yl)propan-1-ol [ka]

[0374] (4-Bromophenyl)hydrazine hydrochloride (1 g, 4.47 mmol) was dissolved in acetonitrile (10 mL) and 4% aqueous sulfuric acid solution (10 mL) was added thereto. 3,4-Dihydro-2H-pyran (0.40 mL, 4.47 mmol) was slowly added thereto at 100°C for 2 minutes, followed by stirring at 100°C for 2 hours. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (0.61 g, 54%).

[0375] Step 2: Preparation of 5-bromo-3-(3-bromopropyl)-1H-indole [ka]

[0376] The compound prepared in Step 1 above (0.31 g, 1.231 mmol) was dissolved in dichloromethane (2 mL), and carbon tetrabromide (0.49 g, 1.477 mmol) and triphenylphosphine (0.38 g, 1.477 mmol) were added thereto at 0° C. The reaction mixture was stirred for 30 minutes and then at room temperature for 4 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by MPLC to give the target compound (0.29 g, 77%).

[0377] Step 3: Preparation of 3-(3-azidopropyl)-5-bromo-1H-indole [ka]

[0378] The compound prepared in step 2 above (0.99 g, 3.25 mmol) was dissolved in dimethylformamide (11 ml), and sodium azide (1.05 g, 16.24 mmol) was added thereto, followed by stirring at room temperature for 4 hours. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (0.54 g, 62%).

[0379] Step 4: Preparation of 3-(5-bromo-1H-indol-3-yl)propan-1-amine [ka]

[0380] The compound prepared in step 3 above (0.1 g, 0.358 mmol) was dissolved in tetrahydrofuran (3 ml) and water (0.2 ml), to which triphenylphosphine (0.47 g, 1.791 mmol) was added, followed by stirring at room temperature for 16 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (0.075 g, 83%).

[0381] Step 5: Preparation of N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-bromopropoxy)benzenesulfonamide [ka]

[0382] The compound prepared in Step 1 of Example 31 (0.094 g, 0.299 mmol) was dissolved in dichloromethane (1 ml), and the compound prepared in Step 4 above (0.075 g, 0.299 mmol) and potassium carbonate (0.124 g, 0.896 mmol) were added thereto, followed by stirring at room temperature for 1 hour. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (0.12 g, 80%).

[0383] Step 6: Preparation of N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0384] The compound prepared in Step 5 above (0.06 g, 0.113 mmol) was dissolved in ethanol (1.5 ml), potassium carbonate (0.031 g, 0.226 mmol) and piperazine (0.02 g, 0.339 mmol) were added, and the mixture was stirred at 70 °C for 16 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, diluted with dichloromethane, and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, purified by preparative HPLC, and neutralized with aqueous sodium bicarbonate to give the target compound (0.032 g, 53%, yellow solid).

[0385] The compounds of Examples 154 to 156 were prepared in a manner similar to that described in Example 153.

[0386] The compound of Example 147 was prepared in a manner similar to that described in Example 147.

[0387] The compounds of Example 158 and Example 159 were prepared in a manner similar to that described in Example 31.

[0388] The compounds of Example 160 and Example 161 were prepared in a manner similar to that described in Example 148.

[0389] The compounds of Example 162 and Example 163 were prepared in a manner similar to that described in Example 31.

[0390] The compounds of Example 164 and Example 165 were prepared in a manner similar to that described in Example 153.

[0391] The compound of Example 148 was prepared in a manner similar to that described in Example 148.

[0392] Example 167: Preparation of N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0393] Step 1: Preparation of (cyanomethyl)triphenylphosphonium [ka]

[0394] 2-Bromoacetonitrile (1.328 mL, 19.06 mmol) was dissolved in dichloromethane (80 mL), and triphenylphosphine (5 g, 19.06 mmol) was added thereto at room temperature, followed by stirring for 6 hours. Upon completion of the reaction, the mixture was washed with diethyl ether without further purification to give the target compound (7 g, 96%, white solid).

[0395] Step 2: Preparation of (E)-3-(5-chloro-1H-indazol-3-yl)acrylonitrile [ka]

[0396] The (cyanomethyl)triphenylphosphonium (3.17 g, 8.31 mmol) prepared in Step 1 above was dissolved in anhydrous tetrahydrofuran (10 mL) and sodium tert-butoxide (0.8 g, 8.31 mmol) was added at -78 °C, followed by stirring for 30 minutes. 5-Chloro-1H-indazole-3-carbaldehyde (1.0 g, 5.44 mmol) was dissolved in anhydrous tetrahydrofuran at -78 °C and added. The reaction mixture was slowly warmed to room temperature and stirred for 1 hour. Upon completion of the reaction, the mixture was washed with supersaturated aqueous ammonium chloride and extracted with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and purified by MPLC to obtain the target compound (0.3 g, 27%, pale yellow solid).

[0397] Step 3: Preparation of 3-(5-chloro-1H-indazol-3-yl)propan-1-amine [ka]

[0398] (E)-3-(5-chloro-1H-indazol-3-yl)acrylonitrile (300 mg, 1.473 mmol) prepared in Step 2 above was dissolved in ether (5 mL) and LAH (168 mg, 4.42 mmol) was added thereto at −78° C. The reaction mixture was slowly warmed to room temperature and then stirred for 2 hours. The reaction was terminated by the addition of LAH (112 mg, 2.95 mmol). Upon completion of the reaction, the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure and purified by MPLC to give the target compound (200 mg, 65%, yellow oil).

[0399] Step 4: Preparation of 4-(-bromopropoxy)-N-(3-(5-chloro-1H-indazol-3-yl)propyl)benzenesulfonamide [ka]

[0400] The target compound (75 mg, 18%, white solid) was prepared in a similar manner to that described in Step 2 of Example 31.

[0401] Step 5: Preparation of N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0402] The target compound (13.3 mg, 85%, pale yellow solid) was obtained in a similar manner to that described in Example 148.

[0403] The compounds of Examples 168 to 170 were prepared in a manner similar to that described in Example 167.

[0404] Example 171: Preparation of (R)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0405] Step 1: Preparation of (R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(oxiran-2-ylmethoxy)benzenesulfonamide [ka]

[0406] The compound prepared in Step 1 of Example 92 (0.41 g, 1.026 mmol) was dissolved in dimethylformamide (3.4 ml), to which (R)-2-(chloromethyl)oxirane (0.095 g, 1.026 mmol) and potassium carbonate (0.21 g, 1.539 mmol) were added, followed by stirring at 60° C. for 16 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and then purified by MPLC to give the target compound (0.16 g, 37%).

[0407] Step 2: Preparation of (R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0408] The compound prepared in step 1 above (0.083 g, 0.198 mmol) was dissolved in acetone (1 ml), to which 1-methylpiperazine (0.19 g, 1.981 mmol) and potassium carbonate (0.274 g, 1.981 mmol) were added, followed by stirring at 80° C. for 16 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, purified by preparative HPLC, and neutralized with aqueous sodium bicarbonate to give the target compound (0.030 g, 30%, yellow solid).

[0409] The compounds of Examples 172 to 174 were prepared in a manner similar to that described in Example 171.

[0410] The compounds of Example 175 and Example 176 were prepared in a manner similar to that described in Example 148.

[0411] Example 177: Preparation of N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0412] Step 1: Preparation of 4-(3-bromopropoxy)-N-(3-(5-chloro-1H-indazol-3-yl)propyl)benzenesulfonamide [ka]

[0413] The target compound was obtained in a manner similar to that described in Step 2 of Example 31 using (6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methanamine, which was prepared in a manner similar to that described in the reference (WO 2006 / 89053).

[0414] Step 2: N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazole-3 Preparation of) 4-(3-(4-methylpiperazin-1-yl)propoxy) benzenesulfonamide [ka]

[0415] The target compound (6.3 mg, 20%, pale yellow solid) was obtained in a similar manner to that described in Example 148.

[0416] The compound of Example 178 was prepared in a manner similar to that described in Example 177.

[0417] The compounds of Example 179 and Example 180 were prepared in a manner similar to that described in Example 85.

[0418] Example 181: Preparation of N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0419] Step 1: Preparation of N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-methylbenzenesulfonamide [ka]

[0420] 5-Chloro-1H-indole (0.400 g, 5.28 mmol) and N-(2-(2-hydroxypropan-2-yl)phenyl)-4-methylbenzenesulfonamide (0.967 g, 3.17 mmol) were dissolved in 1,2-dichloroethane (40 mL), and PdCl₂·(CH₃CN)₂ (0.0340 g, 0.132 mmol) was added. The mixture was stirred under nitrogen for 3 h. Upon completion of the reaction, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The product was purified by MPLC to give the target compound (1.02 g, 88%, white solid).

[0421] Step 2: 2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl) Preparation of aniline [ka]

[0422] N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-methylbenzenesulfonamide (0.540 g, 1.23 mmol) prepared in Step 1 above was dissolved in sulfuric acid (6 mL) and stirred at room temperature for 40 minutes. Ice was added to the reaction product to terminate the reaction, and then 2N aqueous sodium hydroxide solution was added dropwise to neutralize. The reaction mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and then purified by MPLC to obtain the target compound (0.175 g, 50%, pale yellow solid).

[0423] Step 3: Preparation of 4-(3-bromopropoxy)-N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)benzenesulfonamide [ka]

[0424] The target compound was obtained in a similar manner to that described in Step 2 of Example 31.

[0425] Step 4: Preparation of N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide [ka]

[0426] The target compound (17.2 mg, 33%, pale yellow solid) was obtained in a similar manner to that described in Example 148.

[0427] The compound of Example 182 was prepared in a manner similar to that described in Example 181.

[0428] The compounds of Example 183 and Example 184 were prepared in a manner similar to that described in Example 153.

[0429] Example 185: Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyridin-4-yloxy)propyl)benzenesulfonamide [ka]

[0430] The target compound (18.5 mg, 60%, white solid) was obtained in a similar manner to that described in Example 148 using 4-(3-bromopropyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide, which was prepared in a similar manner to that described in Steps 1 and 2 of Example 90.

[0431] The compound of Example 186 was prepared in a manner similar to that described in Example 185.

[0432] The compounds of Examples 187 to 190 were prepared in a manner similar to that described in Example 177.

[0433] Compound names, structural formulas, and 1The results of the 1 H NMR and MS analyses are summarized in Table 1 below.

[0434] [Table 1] TIFF2025128234000197.tif238170TIFF2025128234000198.tif238170TIFF2025128234000199.tif238170TIFF2025128234000200.tif238170TIFF2025128234000201.tif238170TIFF2025128234000202.tif238170TIFF2025128234000203.tif221170TIFF2025128234000204.tif238170TIFF2025128234000205.tif238170TIFF2025128234000206.tif238170TIFF2025128234000207.tif238170TIFF2025128234000208.tif221170TIFF2025128234000209.tif238170TIFF2025128234000210.tif238170TIFF2025128234000211.tif238170TIFF2025128234000212.tif238170TIFF2025128234000213.tif238170TIFF2025128234000214.tif238170TIFF2025128234000215.tif238170TIFF2025128234000216.tif238170TIFF2025128234000217.tif218170TIFF2025128234000218.tif238170TIFF2025128234000219.tif238170TIFF2025128234000220.tif238170TIFF2025128234000221.tif238170TIFF2025128234000222.tif238170TIFF2025128234000223.tif222170TIFF2025128234000224.tif216170TIFF2025128234000225.tif238170TIFF2025128234000226.tif238170TIFF2025128234000227.tif238170TIFF2025128234000228.tif238170TIFF2025128234000229.tif238170TIFF2025128234000230.tif220170TIFF2025128234000231.tif238170TIFF2025128 234000232.tif215170TIFF2025128234000233.tif220170TIFF2025128234000234.tif238170T IFF2025128234000235.tif238170TIFF2025128234000236.tif238170TIFF2025128234000237. tif238170TIFF2025128234000238.tif217170TIFF2025128234000239.tif238170TIFF2025128 234000240.tif238170TIFF2025128234000241.tif225170TIFF2025128234000242.tif238170T IFF2025128234000243.tif217170TIFF2025128234000244.tif238170TIFF2025128234000245. tif238170TIFF2025128234000246.tif212170TIFF2025128234000247.tif238170TIFF2025128 234000248.tif238170TIFF2025128234000249.tif238170TIFF2025128234000250.tif145170.

[0435] <Conditions for analysis and purification> (LC-MS analysis conditions) Equipment name: Shimadzu LCMS-2020 Column: ACE Excel2 C18, 75 x 2.1 mm Mobile phase: acetonitrile / H2O + 0.1% TFA Flow rate: 0.5mL / min UV detector: 254 nm

[0436] (MPLC purification conditions) Device name: CombiFlash (trademark) Rf+ UV detector: 254 nm

[0437] (Preparative HPLC purification conditions) Equipment name: Gilson GX-281, 321 pump, UV / VIS-155 Column: Luna™ 10 νM C18(2) 100 Å, 250 x 21.2 mm Mobile phase: Acetonitrile / 0.1% TFA H2O Flow rate: 18mL / min UV detector: 254 nm

[0438] ( 1 H NMR) Equipment name:Bruker Avance(400MHz)

[0439] <Experimental Example 1> Evaluation of Pin1 enzyme inhibitory activity In order to evaluate the Pin1 enzyme inhibitory activity of the compound represented by formula 1 according to the present invention, the following experiment was carried out, the results of which are shown in Table 2 below.

[0440] The enzymatic activity of Pin1 protein was measured using Anaspec's Sensolyte Green Pi Measurements were performed using the n1 assay kit. The substrate was diluted 1:100 with buffer to a concentration of 1 μM, and the protein was diluted 1:20 with buffer to a concentration of 50 μg / ml. The color-developing solution was then diluted 1:100 in buffer.

[0441] The compounds prepared in each example were diluted with DMSO and prepared using buffer at concentrations of 100 μM, 10 μM, 1 μM, or 0.1 μM. 10 μl of each compound prepared in each example, diluted to four concentrations according to the method described above, 10 μl of Pin1 protein, and 30 μl of color-developing solution were sequentially added to each well of a black 96-well plate, followed by the addition of 50 μl of substrate. Finally, 50 μl of substrate was added to each well of the plate, and the plate was shaken for 10 seconds before the enzyme reaction was initiated.

[0442] The plate was then incubated in a light-free environment at room temperature for 2 hours, and the fluorescence value at 490 nm / 520 nm wavelength was measured using a Synergy Neo (Tecan) instrument. Table 2 below shows the results, which are divided into grades A to D according to the concentration (μM) at which Pin1 enzyme activity is inhibited.

[0443] [Table 2] TIFF2025128234000252.tif87170

[0444] As shown in Table 2, Example 56, Example 61, Example 66, Example 70, Example 75, Example 77, Example 79, Example 83, Example 86, Example 87, Example 88, Example 90, Example 91, Example 92, Example 93, Example 98, Example 99, Example 100, Example 101, Example 102, Example 103, Example 104, Example 105, Example 106, Example 107, Example 108, Example 109, Example 112, Example 113, Example 114, Example 115, Example 116, Example 117, Example 118, Example 121, Example 123, Example 124, Example 125, Example 127, Example 130, Example 133, Example 134, Example 137, Example 138, Example 140, Example 14 1, Example 143, Example 145, Example 146, Example 147, Example 148, Example 149, Example 150, Example 151, Example 152, Example 153, Example 154, Example 158, Example 159, Example 160, Example 161, Example 164, Example 165, Example 166, Example 167, Example 168, Example 169, Example 170, Example 171, Example 172, Example 173, Example 174, Example 175, Example 176, Example 177, Example 178, Example 183, Example 184, Example 185, Example 186, Example 187, Example 188, Example 189, or Example 190 compound was treated, and it was confirmed that Pin1 inhibitory activity was exhibited at a concentration of less than 1 μM.

[0445] The above results indicate that the compounds of the examples of the present invention are excellent at inhibiting the Pin1 enzyme, and therefore, it can be seen that the benzenesulfonamide derivative compounds of the present invention can be effectively used as pharmaceutical compositions for the prevention or treatment of cancer.

[0446] <Experimental Example 2> Evaluation of protein expression suppression ability in MDA-MB 231 triple-negative breast cancer cell line To confirm the ability of the compound of formula 1 according to the present invention to inhibit protein expression in MDA-MB 231 triple-negative breast cancer cell line, the following experiment was carried out, the results of which are shown in Table 3 below.

[0447] MDA-MB-231 cells were cultured in RPMI medium supplemented with 10% FBS and 1% penicillin / streptomycin in a 5% CO 2 incubator at 37°C.

[0448] Cells were washed with PBS once daily and replaced with fresh medium. One day before the experiment, cells grown to at least 90% confluency were detached using trypsin / EDTA and seeded into 6-well plates at a density of 100,000 cells per well.

[0449] The next day after culturing, the cells were treated with the compound prepared in each Example at a concentration of 10 μM, or with DMSO as a control at a concentration of 0.1% of the total, followed by incubation for 72 hours. After 72 hours, the cells were washed twice with PBS, scraped, and centrifuged at 13,000 rpm for 3 minutes to remove all the supernatant, and only the cells were collected.

[0450] RIPA buffer (containing 1x protease and phosphatase inhibitors) was added to the prepared cells (80 μl / well), and the plate was shaken every 5 minutes for a total of 15 minutes to disrupt the cells. The disrupted cells were centrifuged at 13,000 rpm for 15 minutes, and the supernatant protein was collected. The resulting protein was quantified using a BCA protein quantification kit (Pierce, MA, USA), and a total of 10 μg of protein was used for Western blotting.

[0451] Protein samples were separated by 10% SDS-PAGE and transferred to a PVDF membrane. Anti-human cyclin D1 antibody (Cell signaling) and anti-vinculin antibody were bound to the protein samples, and protein expression was measured using ECL reagents and an LAS4000 instrument. The results were quantified and analyzed using ImageJ. The results were compared with those of a DMSO-treated control group. The proteins are classified into grades A to D according to the amount of protein compared, as shown in Table 3 below.

[0452] [Table 3]

[0453] As shown in Table 3, when treated with the compounds of Example 35, Example 61, Example 66, Example 70, Example 75, Example 77, Example 78, Example 79, Example 81, Example 83, Example 91, Example 92, Example 93, Example 98, Example 99 or Example 121, the expression level of the MDA-MB 231 triple-negative breast cancer cell line protein was found to be less than 35% compared to the DMSO-treated control group.

[0454] The above results show that the compounds of the examples of the present invention have excellent ability to inhibit the expression of MDA-MB 231 triple-negative breast cancer cell line protein, and therefore, it can be seen that the benzenesulfonamide derivative compounds of the present invention can be effectively used as pharmaceutical compositions for preventing or treating cancer.

[0455] <Experimental Example 3> Evaluation of cell viability of MCF7 cells, MCF7-SP cells, A2780 cells, or A2780-SP cells In order to confirm the inhibitory effect of the compound represented by formula 1 according to the present invention on the proliferation of MCF7 cells, MCF7-SP cells, A2780 cells, or A2780-SP cells, the following experiments were carried out, the results of which are shown in Tables 4 and 5 below.

[0456] MCF7 cells (breast cancer cells) were seeded into 96-well plates at a density of 3000 viable cells per well and cultured in DMEM / high glucose medium supplemented with 10% FBS and 1% penicillin / streptomycin.

[0457] The next day after culturing, the cells were treated with a compound of Example 71, Example 76, Example 80, Example 84, Example 92, Example 99, Example 100, or Example 119, and then cultured for 3 days. Cell viability was measured using Cell-titer Glo (Promega, Wisconsin, USA). The plate was evaluated and luciferase activity was detected using a Tecan plate reader (Biocompare, USA).

[0458] Meanwhile, MCF7-SP cells (breast cancer stem cells) were seeded into ultra-low attachment round-bottom 96-well plates (corning) at a density of 1500 viable cells per well and cultured in cancer stem cell medium. Cancer stem cell medium consisted of neurobasal medium supplemented with 20 ng / ml bFGF, 10 ng / ml EGF, 2.5 ng / ml amphotericin B, HEPES, Glutamax, and B27.

[0459] The day after culturing, the cells were treated with a compound of Example 71, Example 76, Example 80, Example 84, Example 92, Example 99, Example 100, or Example 119, and then cultured for 8 days. Compound-containing medium was added again on day 4. Sphere viability was assessed using Cell-titer Glo (Promega, Wisconsin, USA) and measured using a Tecan plate reader. Luciferase activity was detected using a ELISA kit (Biocompare, USA).

[0460] Furthermore, A2780 cells (ovarian cancer cells) were seeded into a 96-well plate at a density of 3000 viable cells per well and cultured in RPMI-1640 medium supplemented with 10% FBS and 1% penicillin / streptomycin.

[0461] The next day after culturing, the cells were treated with the compounds of Examples 57 and 69 to 144, followed by culturing for 3 days. Cell viability was assessed by Cell-titer Glo (Promega, Wisconsin, USA) and the cells were analyzed using a Tecan plate reader (Biocompare, USA). Luciferase activity was detected.

[0462] Meanwhile, A2780-SP cells (ovarian cancer stem cells) were seeded into an ultra-low attachment round-bottom 96-well plate (corning) at a density of 1500 viable cells per well and cultured in cancer stem cell medium. The cancer stem cell medium consisted of neurobasal medium supplemented with 20 ng / ml bFGF, 10 ng / ml EGF, 2.5 ng / ml amphotericin B, HEPES, Glutamax, and B27.

[0463] The next day after culturing, the cells were treated with the compounds of Examples 57 and 69 to 144, and then cultured for 8 days. The medium containing the compounds was added again on the fourth day. The viability of the spheres was evaluated. Cell-titer Glo (Promega, Wisconsin, USA) was used for evaluation. Luciferase activity was detected using a n plate reader (Biocompare, USA).

[0464] [Table 4]

[0465] [Table 5]

[0466] As shown in Table 4, when treated with the compound of Example 70, Example 75, Example 83, Example 91, Example 99 or Example 118, the MCF7 cell concentration was less than 10 μM, and when treated with the compound of Example 70, Example 83, Example 91, Example 99 or Example 118, the MCF7-SP cell concentration was less than 10 μM.

[0467] As shown in Table 5, when the compound of Example 56, Example 59, Example 61, Example 66, Example 70, Example 75, Example 83, Example 93, Example 98, Example 99, Example 100, Example 106, Example 108, Example 109, Example 121, Example 123, Example 124, Example 130, Example 153, Example 154, Example 164, Example 165, Example 167, Example 169, Example 170, Example 173, Example 175, Example 176, Example 177, or Example 178 was treated, the A2780 cell concentration was less than 10 μM, and Example 103, Example 104, Example 105, Example 106, Example 108, Example 109, Example 110, Example 111, Example 112, Example 115, Example 118, Example 121, Example 134, Example 150, Example 151, Example 152, Example 153, Example 154, Example 157, Example 158, Example 159, Example 161, Example 164, Example 165, Example 167, Example 168, Example 169, Example 170, Example 171, Example 172, Example 173, Example 174, Example 175, Example 176, Example 177, Example 178, Example 183, Example 184, Example 186, Example 187, Example 188, Example 189, or Example 190 The concentration of the compound when treated was less than 1 μM.

[0468] The above results indicate that the compounds of the examples of the present invention have excellent inhibitory effects on the proliferation of MCF7 cells, MCF7-SP cells, A2780 cells, or A2780-SP cells, and therefore the benzenesulfonamide derivative compounds of the present invention can be effectively used as pharmaceutical compositions for preventing or treating cancer.

Claims

1. A compound represented by formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof: (Formula 1) 【Chemical 1】 (In formula 1, Ar is a 6- to 10-membered aryl or 5- to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; R １ and R ２ are independently hydrogen, halogen, or a 5- to 8-membered heterocycloalkyl C containing at least one N. １～５ is an alkoxy, R ３ is hydrogen, halogen, unsubstituted or substituted straight or branched chain C １～８ Alkoxy, unsubstituted or substituted straight or branched chain C １～８ Alkyl, NR ａ１ R ａ２ , or OR ａ３ and R ａ１ , R ａ２ and R ａ３ are independently hydrogen, unsubstituted or substituted straight or branched chain C １～８ alkyl, unsubstituted or substituted phenyl, or 5- to 8-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of N, S, and O, unsubstituted or substituted 4- to 8-membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, unsubstituted or substituted 4- to 8-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR ｂ１ R ｂ２ , 3- to 6-membered cycloalkyl, halogen, hydroxy, and sulfonyl, or said substituted alkoxy and substituted alkyl can be further substituted to form 3- to 6-membered cycloalkyl, each independently having a substituted carbon; The substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyls that are unsubstituted or substituted with one or more halogens. １～５ Alkyl, straight or branched chain C １～５ Alkylcarbonyl, NR ｂ１ R ｂ２ , substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and oxo; R ｂ１ and R ｂ２ are independently hydrogen or straight or branched chain C １～６ is alkyl, L １ teeth, 【Chemistry 2】 or 【Chemistry 3】 wherein R ｃ is hydrogen or L ２ which together with the nitrogen to which they are attached form an N-containing 5- to 8-membered heterocycloalkylene; L ２ is a single bond, a straight or branched chain C １～８ alkylene, unsubstituted or substituted with either hydroxy and oxo; ３～８ is cycloalkylene or phenylene; Z is unsubstituted or substituted C ６～１０ aryl, C fused to a 5- to 9-membered unsubstituted or substituted heteroaryl that is unsubstituted or contains one or more heteroatoms selected from the group consisting of N, S, and O ３～８ cycloalkyl, 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O; a 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 5- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; １～５ is alkyl, The substituted aryl is a 4- to 8-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of halogen, phenyl, carboxy, N, S, and O, or a straight or branched C １～８ substituted with alkoxycarbonyl, In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched C １～５ Alkyl, straight or branched chain C １～８ independently substituted with one or more substituents selected from the group consisting of alkoxy, phenyl, benzyl, halogen, hydroxy, or oxo).

2. Ar is a 6- to 10-membered aryl or 5- to 6-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; R １ and R ２ are independently hydrogen or fluorine, R ３ is hydrogen, bromine, unsubstituted or substituted straight or branched chain C １～６ Alkoxy, unsubstituted or substituted straight or branched chain C １～６ Alkyl, NR ａ１ R ａ２ , or OR ａ３ and R ａ１ , R ａ２ and R ａ３ are independently hydrogen, unsubstituted or substituted straight or branched chain C １～６ alkyl, unsubstituted or substituted phenyl, or 5- to 7-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of N, S, and O, unsubstituted or substituted 4- to 7-membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, unsubstituted or substituted 4- to 7-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR ｂ１ R ｂ２ , 3- to 5-membered cycloalkyl, fluorine, bromine, hydroxy, and sulfonyl, or said substituted alkoxy and substituted alkyl can be further substituted to form 3- to 5-membered cycloalkyl, each independently having a substituted carbon; The substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyls that are unsubstituted or substituted with one or more halogens. １～４ Alkyl, straight or branched chain C １～４ Alkylcarbonyl, NR ｂ１ R ｂ２ , substituted with one or more substituents selected from the group consisting of chlorine, fluorine, bromine, hydroxy, and oxo; R ｂ１ and R ｂ２ are independently hydrogen or straight or branched chain C １～３ is alkyl, L １ teeth, 【Chemistry 4】 or 【Chemistry 5】 wherein R ｃ is hydrogen or L ２ which together with the nitrogen to which they are attached form a piperidinylene, L ２ is a single bond, a straight or branched chain C １～６ alkylene, unsubstituted or substituted with either hydroxy and oxo ４～６ is cycloalkylene or phenylene; Z is unsubstituted or substituted C ６～９ aryl, C fused to a 5- to 9-membered unsubstituted or substituted heteroaryl that is unsubstituted or contains one or more heteroatoms selected from the group consisting of N, S, and O ４～７ cycloalkyl, 5- to 6-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S and O; a 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; １～４ is alkyl, The substituted aryl may be chlorine, phenyl, carboxy, morpholinyl, or a straight or branched C １～３ substituted with alkoxycarbonyl, In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched C １～４ Alkyl, straight or branched chain C １～４ 2. The compound of claim 1, its isomer, or a pharmaceutically acceptable salt thereof, which is independently substituted with one or more substituents selected from the group consisting of alkoxy, benzyl, phenyl, fluorine, chlorine, bromine, hydroxy, or oxo.

3. Ar is phenyl, naphthyl, pyridine or thiazole; R １ and R ２ are independently hydrogen or fluorine, R ３ is hydrogen, bromine, unsubstituted or substituted straight or branched chain C １～５ Alkoxy, unsubstituted or substituted straight or branched chain C １～５ Alkyl, NR ａ１ R ａ２ , or OR ａ３ and R ａ１ , R ａ２ and R ａ３ are independently hydrogen, unsubstituted or substituted straight or branched chain C １～５ alkyl, unsubstituted or substituted phenyl, or 5- to 6-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are independently selected from the group consisting of N, S, and O, unsubstituted or substituted 4- to 7-membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S, and O, unsubstituted or substituted 5- to 7-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O, NR ｂ１ R ｂ２ , 3- to 4-membered cycloalkyl, fluorine, bromine, hydroxy, and sulfonyl, or said substituted alkoxy and substituted alkyl may each independently be further substituted to form a substituted carbocyclopropyl; The substituted heterocycloalkyl and substituted heteroaryl are straight or branched chain C alkyls that are unsubstituted or substituted with one or more fluorines. １～３ Alkyl, straight or branched chain C １～４ Alkylcarbonyl, NR ｂ１ R ｂ２ , substituted with one or more substituents selected from the group consisting of chlorine, fluorine, bromine, hydroxy, and oxo; R ｂ１ and R ｂ２ are independently hydrogen, methyl or ethyl; L １ teeth, 【Chemistry 6】 or 【Chemistry 7】 wherein R ｃ is hydrogen or L ２ which together with the nitrogen to which they are attached form a piperidinylene, L ２ is a single bond, a straight or branched chain C １～４ alkylene, cyclohexylene or phenylene unsubstituted or substituted with either hydroxy or oxo; Z is unsubstituted or substituted phenyl, cyclohexyl, naphthyl, C5-6 cycloalkyl fused to a 5-9 membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S and O; 5- to 6-membered unsubstituted or substituted heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, S and O; a 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; or 6- to 9-membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S, and O; １～３ is alkyl, the substituted phenyl is substituted with chlorine, phenyl, carboxy, morpholinyl, or methoxycarbonyl; In this case, the substituted heterocycloalkyl, substituted heteroaryl, and substituted heteroarylalkyl are straight-chain or branched C １～３ 2. The compound of claim 1, its isomer, or a pharmaceutically acceptable salt thereof, which is independently substituted with one or more substituents selected from the group consisting of alkyl, methoxy, benzyl, phenyl, fluorine, chlorine, bromine, hydroxy, or oxo.

4. Ar is phenyl, naphthyl, pyridine or thiazole; R １ and R ２ are independently hydrogen or fluorine, R ３ are hydrogen, bromine, 【Chemistry 8】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 and L １ teeth, 【Chemistry 9】 and L ２ is a single bond, 【Chemistry 10】 and Z is 【Chemistry 11】 【change】 【change】 【change】 2. The compound according to claim 1, its isomer or a pharmaceutically acceptable salt thereof, wherein:

5. The compound of claim 1, its isomer or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula 1 is selected from the group consisting of the following compounds: <1> N-(3-([1,1'-biphenyl]-4-yl)propyl)-4-butoxybenzenesulfonamide; <2> 4-butoxy-N-(3-(4-isopropylpiperazin-1-yl)propyl)benzenesulfonamide; <3> 4-butoxy-N-(3-(4-chlorophenyl)propyl)benzenesulfonamide; <4> 4-butoxy-N-(3-cyclohexylpropyl)benzenesulfonamide; <5> 4-butoxy-N-(3-(pyridin-3-yl)propyl)benzenesulfonamide; <6> 4-butoxy-N-(3-morpholinopropyl)benzenesulfonamide; <7> 4-butoxy-N-(4-morpholinophenethyl)benzenesulfonamide; <8> 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid; <9> Methyl 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoate; <10> N-(2-(4-benzylpiperidin-1-yl)ethyl)-4-butoxybenzenesulfonamide; <11> 4-butoxy-N-(3-hydroxy-3-phenylpropyl)benzenesulfonamide; <12> 4-butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide; <13> 4-butoxy-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzenesulfonamide; <14> 4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide; <15> 4-(3-(dimethylamino)propoxy)-N-(3-phenylpropyl)benzenesulfonamide; <16> Methyl 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoate; <17> 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoic acid; <18> 4-(3-(dimethylamino)propoxy)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzenesulfonamide; <19> 4-butoxy-N-(3-(naphthalen-1-yl)propyl)benzenesulfonamide; <20> N-(3-(1H-indol-3-yl)propyl)-4-butoxybenzenesulfonamide; <21> N-(3-(1H-indol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)benzenesulfonamide; <22> N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <23> N-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-4-butoxybenzenesulfonamide; <24> N-(2-(1H-indol-3-yl)ethyl)-4-butoxybenzenesulfonamide; <25> N-(2-(1H-indol-2-yl)ethyl)-4-butoxybenzenesulfonamide; <26> N-(3-(1H-indol-3-yl)propyl)-4-(isopentyloxy)benzenesulfonamide; <27> N-(3-(1H-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide; <28> N-(3-(1H-benzo[d]imidazol-2-yl)propyl)-4-butoxybenzenesulfonamide; <29> 4-butoxy-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)benzenesulfonamide; <30> N-(3-(1H-indol-3-yl)propyl)-4-(3-morpholinopropoxy)benzenesulfonamide; <31> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <32> N-(3-(1H-indol-1-yl)propyl)-4-butoxybenzenesulfonamide; <33> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-benzo[d]imidazol-1-yl)propyl Toxobenzenesulfonamide; <34> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-butoxybenzenesulfonamide; <35> N-(3-(1H-indol-3-yl)propyl)-4-(3-(diethylamino)propoxy)benzenesulfonamide; <36> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-ethylpiperazin-1-yl)propoxy)benzenesulfonamide; <37> N-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <38> N-(2-(1H-indol-2-yl)ethyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <39> N-(3-(1H-indol-1-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <40> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide; <41> N-(3-(1H-indol-1-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <42> N-(3-(1H-benzo[d]imidazol-1-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <43> N-(3-(1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <44> N-(3-(1H-indol-3-yl)propyl)-4-(3-(2-oxopyrrolidin-1-yl)propoxy)benzenesulfonamide; <45> N-(3-(1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <46> 4-(3-(dimethylamino)propoxy)-N-(3-(1-methyl-1H-indol-3-yl)propyl)benzenesulfonamide; <47> N-(3-(1H-indol-3-yl)propyl)-4-bromobenzenesulfonamide; <48> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-isopropylpiperazin-1-yl)propoxy)benzenesulfonamide; <49> N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <50> N-(2-(1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <51> N-(2-(1H-indol-3-yl)ethyl)-4-(3-(4-isopropylpiperazin-1-yl)propoxy)benzenesulfonamide; <52> N-(3-(1H-indol-3-yl)propyl)-4-(2-(4-methylpiperazin-1-yl)ethoxy)benzenesulfonamide; <53> N-(3-(1H-indol-3-yl)propyl)-4-(2-(4-isopropylpiperazin-1-yl)ethoxy)benzenesulfonamide; <54> N-(2-(2-methyl-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <55> N-(3-(1H-indol-3-yl)propyl)-4-(2-(1-methylpiperidin-4-yl)ethoxy)benzenesulfonamide; <56> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <57> 3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <58> N-(3-(2-methyl-1H-indol-3-yl)propyl)-4-(3 -(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <59> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide; <60> N-(3-(1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide; <61> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <62> N-(3-(1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <63> 4-(3-(4-ethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide; <64> 5-methoxy-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <65> 5-methyl-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <66> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <67> N-(3-(5-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <68> N-(3-(5-methoxy-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <69> N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide; <70> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <71> 5-fluoro-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole; <72> 4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide; <73> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-isobutyrylpiperazin-1-yl)propoxy)benzenesulfonamide; <74> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)propoxy)benzenesulfonamide; <75> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide; <76> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)propoxy)benzenesulfonamide; <77> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfonamide; <78> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-chloropiperidin-1-yl)propoxy)benzenesulfonamide; <79> N-(3-(5-chloro-1H-indol-3-yl)propyl)-6-(3-(piperazin-1-yl)propoxy)pyridine-3-sulfonamide; <80> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-fluoropiperidin-1-yl)propoxy)benzenesulfonamide; <81> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3 -(4-(trifluoromethyl)piperidin-1-yl)propoxy)benzenesulfonamide; <82> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,4-difluoropiperidin-1-yl)propoxy)benzenesulfonamide; <83> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)propoxy)benzenesulfonamide; <84> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <85> N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <86> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfonamide; <87> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <88> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-4-yl)propyl)amino)benzenesulfonamide; <89> N-(3-(1H-indol-3-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <90> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-1-yl)butyl)benzenesulfonamide; <91> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperazin-1-yl)butyl)benzenesulfonamide; <92> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide; <93> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide; <94> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperidin-4-yl)propoxy)benzenesulfonamide; <95> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperidin-1-yl)propoxy)benzenesulfonamide; <96> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <97> N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide; <98> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzenesulfonamide; <99> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-4-yl)butyl)benzenesulfonamide; <100> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyrrolidin-1-yl)propoxy)benzenesulfonamide; <101> 4-(3-(azepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <102> 4-(3-(1,4-diazepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <103> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <104> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <105> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide; <106> 4-(3-(1,4-diazepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluorobenzenesulfonamide; <107> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <108> (R)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <109> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <110> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)benzenesulfonamide; <111> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3,4-dimethylpiperazin-1-yl)propoxy)benzenesulfonamide; <112> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(4-methylpiperazin-1-yl)butyl)benzenesulfonamide; <113> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)propyl)amino)benzenesulfonamide; <114> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-1-yl)propyl)amino)benzenesulfonamide; <115> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(1-methylpiperidin-4-yl)butyl)benzenesulfonamide; <116> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)methoxy)benzenesulfonamide; <117> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-(piperazin-1-ylmethyl)cyclopropyl)methoxy)benzenesulfonamide; <118> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide; <119> 4-(3-bromophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <120> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)phenoxy)benzenesulfonamide; <121> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)phenoxy)benzenesulfonamide; <122> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)phenoxy)benzenesulfonamide; <123> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide; <124> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)phenyl)amino)benzenesulfonamide; <125> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)pyrimidin-2-yl)amino)benzenesulfonamide; <126> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-morpholinophenyl)amino)benzenesulfonamide; <127> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(piperazin-1-yl)pyrimidin-2-yl)amino)benzenesulfonamide; <128> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-morpholinophenoxy)benzenesulfonamide; <129> 4-(3-(1,4-diazepan-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <130> 4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <131> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <132> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-(piperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <133> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <134> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(piperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <135> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyrrolidin-1-yl)phenoxy)benzenesulfonamide; <136> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)phenoxy)benzenesulfonamide; <137> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-fluoro-5-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide; <138> 4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <139> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-hydroxypiperidin-1-yl)phenyl)amino)benzenesulfonamide; <140> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-chloro-4-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide; <141> 4-((4,6-bis(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <142> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide; <143> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-( 3-(4-methylpiperazin-1-yl)propoxy)benzamide; <144> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzamide; <145> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(methylsulfonyl)propoxy)benzenesulfonamide; <146> N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfonamide; <147> N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <148> 4-(4-(1H-imidazol-1-yl)butyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <149> N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <150> N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <151> N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <152> N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <153> N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <154> N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <155> N-(3-(5-phenyl-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <156> 4-(3-(4-methylpiperazin-1-yl)propoxy)-N-(3-(5-phenyl-1H-indol-3-yl)propyl)benzenesulfonamide; <157> N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <158> N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <159> N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <160> 4-(3-(1H-1,2,4-triazol-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide; <161> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(2-methyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <162> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-3-oxopiperazin-1-yl)propoxy)benzenesulfonamide; <163> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-oxopiperazin-1-yl)propoxy)benzenesulfonamide; <164> N-(3-(5,7-dichloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <165>N-(3-(5,7-dichloro-1H-indol-3-yl)propyl)- 4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <166> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dichloro-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <167> N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <168> N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <169> N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <170> N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <171> (R)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <172> (R)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzenesulfonamide; <173> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <174> (S)—N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzenesulfonamide; <175> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dimethyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <176> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(2,4,5-trimethyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide; <177> N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <178> N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <179> N-(3-(5-chloro-1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <180> N-(3-(5-chloro-1H-indol-3-yl)cyclohexyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <181> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <182> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <183> N-(3-(5,6-dichloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <184> N-(3-(5,6-dichloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <185> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyridin-4-yloxy)propyl)benzenesulfonamide; <186> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propyl)benzenesulfonamide; <187> N-((6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide; <188> N-((6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide; <189> 4-(3-(4-methylpiperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide; <190> 4-(3-(piperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide.

6. A method for preparing a compound represented by formula 1, comprising the step of reacting a compound represented by formula 2 with a compound represented by formula 3 to prepare a compound represented by formula 1, as shown in the following reaction scheme 1: (Reaction Scheme 1) 【Chemistry 12】 (In Reaction Scheme 1, Ar, R １ , R ２ , R ３ , L １ , L ２ and Z are as defined in formula 1 of claim 1; J １ is chlorosulfone or carboxy; J ２ is an amine or piperidine).

7. A pharmaceutical composition comprising a compound represented by formula 1 according to claim 1, its isomer or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of cancer, inflammatory diseases or metabolic diseases.

8. 8. The pharmaceutical composition of claim 7, wherein the compound inhibits Pin1 (peptidyl-prolyl cis-trans isomerase NIMA interaction 1).

9. The cancer is selected from the group consisting of pseudomyxoma, intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphocytic leukemia, basal cell carcinoma, ovarian epithelial cancer, ovarian germ cell cancer, male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colorectal cancer, chronic myeloid leukemia, chronic lymphocytic leukemia, retinoblastoma, tumor, choroidal melanoma, ampulla of Vater cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, nasal cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, childhood brain cancer, childhood lymphoma, childhood leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, renal cancer, kidney cancer, heart cancer, duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureteral cancer, urethral cancer 8. The pharmaceutical composition of claim 7, wherein the cancer is at least one selected from the group consisting of cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoma, gastrointestinal stromal cancer, Wilms' carcinoma, breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoid tumor, vaginal cancer, spinal cancer, vestibular schwannoma, pancreatic cancer, salivary gland cancer, Kaposi's sarcoma, Paget's disease, tonsil cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, laryngeal cancer, pleural cancer, blood cancer, and thymic cancer.

10. 8. The pharmaceutical composition according to claim 7, wherein the inflammatory disease is at least one selected from the group consisting of arthritis, encephalomyelitis, meningitis, peritonitis, osteomyelitis, encephalitis, ankylosing spondylitis, vasculitis, uveitis, ileitis, atherosclerosis, myositis, leukocyte injury, inflammatory bowel disease, ulcerative colitis, retinal detachment, retinitis pigmentosa, macular degeneration, pancreatitis, atopic dermatitis, gout, vasculitis, non-alcoholic steatohepatitis, primary sclerosing cholangitis, nephritis, intraperitoneal disease, sepsis, systemic inflammatory response syndrome, myocardial infarction, allergic disease, asthma, atopic dermatitis, Wegener's granulomatosis, pulmonary sarcoidosis, Behcet's disease, chronic obstructive pulmonary disease, and periodontitis.

11. 8. The pharmaceutical composition according to claim 7, wherein the metabolic disease is at least one selected from the group consisting of obesity, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, arteriosclerosis, fatty liver, gout, stroke, and heart disease.

12. A health functional food comprising the compound represented by formula 1 according to claim 1, its isomer or a pharmaceutically acceptable salt thereof as an active ingredient for preventing or improving cancer, inflammatory diseases or metabolic diseases.

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