KR20210093155A - Novel compound, preparation method thereof, and use thereof - Google Patents

Abstract

The present invention relates to a novel compound, a manufacturing method thereof, a use thereof, wherein the compound exhibits excellent inhibitory activity on Pin1, so that a pharmaceutical composition containing the compound as an active component can be usefully used for preventing or treating cancer, inflammatory diseases or metabolic diseases.

Description

Novel compound, preparation method thereof, and use thereof {Novel compound, preparation method thereof, and use thereof}

The present invention relates to a pharmaceutical composition for the prevention or treatment of cancer, inflammatory disease or metabolic disease, specifically, a cancer containing a compound that inhibits Pin1 (Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) as an active ingredient; It relates to a pharmaceutical composition for preventing or treating inflammatory diseases or metabolic diseases.

Proryl isomerase, Pin1 (Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) is an enzyme that binds to the phosphorylated Ser/Thr-Pro site and catalyzes the cis/trans isomerization of proline residue amides. (Lu PJ et al Science 1999, Feb 26;283(5406):1325-8). During the intracellular signaling process, phosphorylation occurs at serine, Ser, threonine, Thr, and tyrosine residues of proteins. After this phosphorylation reaction, Pin1 undergoes a variety of changes through cis/trans isomerization of proline residue amides. By changing the structure of the proteins, these proteins can begin to function in the cell.

According to the studies so far, the Pin1 enzyme is known to be involved in the onset and progression of inflammatory diseases, metabolic diseases, and cancer. In particular, Pin1 enzyme is involved in cancer induction beta-catenin, AKT, AR, CyclinD1, Plk, NF-kB, Stat3, Myc, c-Jun, c-Fos, c-Myb, Raf-1, HIF-1, Nanog , Notch1, Oct4, etc., activates 56 oncogenes, and inhibits the activity of 26 cancer-suppressor genes, including ATR, Bax, Btk, FADD, Fbw7, and PML, thereby inducing cancer metastasis and cancer angiogenesis in the overall cancer development mechanism. As this has been reported, many studies have been conducted on the Pin1 protein as a target for diagnosis and prognostic factors for cancer and the development of useful new anticancer drugs ( Nature reviews. Cancer 2016, 16, 463-478, Cell Death and Disease 2018, 9 , 883 ).

As reported through the study of surgically excised samples, Pin1 is known to be highly expressed in various types of cancer, including colorectal cancer, cervical cancer, breast cancer, lung cancer, pancreatic cancer, stomach cancer, and liver cancer. In fact, it has been reported that transgenic mice overexpressing Pin1 exhibit a cancer-causing phenotype. And it is known that using a specific inhibitor or siRNA can induce mitotic arrest and apoptosis in Pin1 knockdown cancer cells and inhibit the stem cell properties of cancer. In particular, Pin1 enzyme has the function of inducing self-renewal, metastasis and tumorigenesis of breast cancer stem cells.

When Pin1 overexpression occurs, differentiation from human mammary epithelial cells into stem cells and epithelial to mesenchymal transition occurs, that is, in order to break the adhesion to surrounding cells during invasive growth and metastasis of cancer cells and move through blood vessels or lymphatic vessels. , it is known that the cell-to-cell bond is loosened, the skeleton of the cell changes, and progresses to the phenomenon of acquiring motility. Pin1 enzyme is known as an important factor in self-renewal of stem cells by maintaining the stability of Nanog, Oct4, and Myc proteins.

Although Pin1 is involved in many mechanisms in the body as described above, it is known that Pin1 knockout mice grow normally without any major problems, so Pin1 inhibition is not expected to have a significant effect on the human body. However, in the brain, there are reports that Pin1 can help in the treatment of Alzheimer's disease, while it works in reverse in Parkinson's disease, so there are still many unknowns. In conclusion, Pin1 is Overall, it plays a very important role in cancer development, and inhibiting it in areas other than the brain is very useful for effective and safe cancer treatment.

And when Pin1 is inhibited or Pin1 gene expression is knocked down, the production of prostaglandin E2 and nitric oxide stimulated with lipopolysaccharide (LPS) and nicotine is attenuated, and also cyclooxygenase-2 (COX-2), inducible nitric oxide It has been reported that synthase (iNOS) expression is also attenuated, thereby having an anti-inflammatory effect (Journal of Dental Research, 2015, Vol. 94(2) 371-380). In addition, when Pin1 is attached to CRTC2, the generation of the CBP-CRTC2-CREB complex that promotes gluconeogenesis is suppressed, so it is well known that CRTC2 is regulated according to the level of Pin1 expression and can be involved in the regulation of glucose metabolism (J Biol Chem. 2010 Oct. 22;285(43):33018-27). Therefore, agents that affect Pin1 expression or activity can be used as therapeutic agents for metabolic diseases such as inflammatory diseases or diabetes.

Accordingly, the present inventors performed pharmaceutical chemical synthesis and biological and pharmaceutical evaluation of the synthesized compounds to discover compounds that inhibit Pin1 activity, and through this, found compounds showing excellent anticancer effects by strongly inhibiting Pin1, and , the present invention was completed. In addition, it is determined that the compounds of the present invention can be used as therapeutic agents for these diseases based on the role of Pin1 in inflammatory and metabolic diseases.

An object of the present invention is 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.

Another object of the present invention is to provide a method for preparing the compound.

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

Another object of the present invention is to provide a health functional food composition for the prevention or improvement of cancer, inflammatory disease or metabolic disease containing the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

In order to achieve the above object,

According to one aspect of the present invention, there is provided a compound represented by the following formula (1), an isomer thereof, or a pharmaceutically acceptable salt thereof:

[Formula 1]

In Formula 1,

Ar is 6-10 membered aryl or 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O;

R ¹ and R ² are each independently hydrogen, halogen or 5 to 8 membered heterocycloalkyl C _1-5 alkoxy comprising at least one N;

R ³ is hydrogen, halogen, unsubstituted or substituted straight or branched C _1-8 alkoxy, unsubstituted or substituted straight or branched C _1-8 alkyl, NR ^a1 R ^a2 , OR ^a3 , wherein R ^a1 , R ^a2 and R ^a3 are each independently hydrogen, at least one selected from the group consisting of unsubstituted or substituted straight or branched C _1-8 alkyl, unsubstituted or substituted phenyl, or N, S and O 5 to 8 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,

In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are each independently 4 to 8 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 4 to 8 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 6 substituted with one or more substituents selected from the group consisting of atom cycloalkyl, halogen, hydroxy and sulfonyl, wherein the substituted alkoxy and substituted alkyl are each independently 3 to 6 membered cycloalkyl together with the carbon being substituted can be further substituted to form

Said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-5 alkyl unsubstituted or substituted with one or more halogen, straight or branched C _1-5 alkylcarbonyl, NR ^b1 R ^b2 , halogen , substituted with one or more substituents selected from the group consisting of hydroxy and oxo,

wherein R ^b1 and R ^b2 are each independently hydrogen, straight-chain or branched C _1-6 alkyl;

또는

이고, 여기서 R^c는 수소, 또는 L² 및 이들이 결합한 질소와 함께 N를 포함하는 5 내지 8 원자의 헤테로시클로알킬렌을 형성하고;L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form a 5 to 8 membered heterocycloalkylene comprising N;

L ² is a single bond, unsubstituted or straight or branched C _1-8 alkylene, C _3-8 cycloalkylene or phenylene substituted with one of hydroxy and oxo;

Z is unsubstituted or substituted C _6-10 aryl, unsubstituted or 5 to 9 membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S and O this fused C _3-8 cycloalkyl, 4 to 8 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 5 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 5 to 5 containing at least one heteroatom selected from the group consisting of N, S and O to 9 membered unsubstituted or substituted heteroaryl C _1-5 alkyl,

The substituted aryl is an unsubstituted or substituted heterocycloalkyl of 4 to 8 members or straight or branched chain containing one or more heteroatoms selected from the group consisting of halogen, phenyl, carboxy, N, S and O. substituted with C _{1-8 alkoxycarbonyl,}

In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently linear or branched C _1-5 alkyl, straight or branched C _1-8 alkoxy, phenyl, benzyl, halogen, hydride It is substituted with one or more substituents selected from the group consisting of hydroxy or oxo.

According to another aspect of the present invention, as shown in Scheme 1 below,

Provided is a method for preparing a compound represented by Formula 1, comprising reacting a compound represented by Formula 2 with a compound represented by Formula 3 to prepare a compound represented by Formula 1:

[Scheme 1]

In 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; and

J ² is amine or piperidine.

According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating cancer, inflammatory disease or metabolic disease, comprising the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient .

According to another aspect of the present invention, there is provided a health functional food for the prevention or improvement of cancer, inflammatory disease or metabolic disease containing the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. .

According to another aspect of the present invention, cancer, inflammation comprising the step of administering to a subject in need of a pharmaceutical composition or a health functional food composition containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient A method for preventing or treating a disease or metabolic disease is provided.

According to another aspect of the present invention, in the prevention or treatment of cancer, inflammatory disease or metabolic disease, the pharmaceutical composition or health functional food composition containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof provide use.

Since the novel compound according to the present invention exhibits excellent inhibitory activity against Pin1, a pharmaceutical composition comprising it as an active ingredient can be usefully used for the prevention or treatment of cancer, inflammatory disease or metabolic disease.

Hereinafter, the present invention will be described in detail.

One aspect of the present invention provides a compound represented by the following formula (1), an isomer thereof, or a pharmaceutically acceptable salt thereof.

[Formula 1]

In Formula 1,

Ar is 6-10 membered aryl or 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O;

R ¹ and R ² are each independently hydrogen, halogen or 5 to 8 membered heterocycloalkyl C _1-5 alkoxy comprising at least one N;

R ³ is hydrogen, halogen, unsubstituted or substituted straight or branched C _1-8 alkoxy, unsubstituted or substituted straight or branched C _1-8 alkyl, NR ^a1 R ^a2 , OR ^a3 , wherein R ^a1 , R ^a2 and R ^a3 are each independently hydrogen, unsubstituted or substituted straight or branched chain C _1-8 alkyl, unsubstituted or substituted phenyl, or at least one selected from the group consisting of N, S and O 5 to 8 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,

In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are each independently 4 to 8 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 4 to 8 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 6 substituted with one or more substituents selected from the group consisting of atom cycloalkyl, halogen, hydroxy and sulfonyl, wherein the substituted alkoxy and substituted alkyl are each independently 3 to 6 membered cycloalkyl together with the carbon being substituted can be further substituted to form

Said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-5 alkyl unsubstituted or substituted with one or more halogen, straight or branched C _1-5 alkylcarbonyl, NR ^b1 R ^b2 , halogen , substituted with one or more substituents selected from the group consisting of hydroxy and oxo,

wherein R ^b1 and R ^b2 are each independently hydrogen, straight-chain or branched C _1-6 alkyl;

또는

이고, 여기서 R^c는 수소, 또는 L² 및 이들이 결합한 질소와 함께 N를 포함하는 5 내지 8 원자의 헤테로시클로알킬렌을 형성하고;L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form a 5 to 8 membered heterocycloalkylene comprising N;

L ² is a single bond, unsubstituted or straight or branched C _1-8 alkylene, C _3-8 cycloalkylene or phenylene substituted with one of hydroxy and oxo;

Z is unsubstituted or substituted C _6-10 aryl, unsubstituted or 5 to 9 membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S and O this fused C _3-8 cycloalkyl, 4 to 8 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 5 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 5 to 5 containing at least one heteroatom selected from the group consisting of N, S and O to 9 membered unsubstituted or substituted heteroaryl C _1-5 alkyl,

The substituted aryl is an unsubstituted or substituted heterocycloalkyl of 4 to 8 members or straight or branched chain containing one or more heteroatoms selected from the group consisting of halogen, phenyl, carboxy, N, S and O. substituted with C _{1-8 alkoxycarbonyl,}

In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently linear or branched C _1-5 alkyl, straight or branched C _1-8 alkoxy, phenyl, benzyl, halogen, hydride It is substituted with one or more substituents selected from the group consisting of hydroxy or oxo.

In Formula 1,

Ar is 6 to 10 membered aryl or 5 to 6 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O;

R ¹ and R ² are each independently hydrogen or fluorine;

R ³ is hydrogen, bromine, unsubstituted or substituted straight or branched C _1-6 alkoxy, unsubstituted or substituted straight or branched C _1-6 alkyl, NR ^a1 R ^a2 , OR ^ac , wherein R ^a1 , R ^a2 and R ^a3 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted straight or branched chain C _1-6 alkyl, unsubstituted or substituted phenyl, or N, S and O 5 to 7 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,

In this case, the substituted alkoxy, substituted alkyl, substituted phenyl and substituted heteroaryl are each independently 4 to 7 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 4 to 7 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 5 atom is substituted with one or more substituents selected from the group consisting of cycloalkyl, fluorine, bromine, hydroxy and sulfonyl, or wherein said substituted alkoxy and substituted alkyl are each independently 3 to 5 together with the carbon being substituted may be further substituted to form a cycloalkyl of atoms;

wherein said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-4 alkyl unsubstituted or substituted with one or more halogen, straight or branched C _1-4 alkylcarbonyl, NR ^b1 R ^b2 , chlorine , substituted with one or more substituents selected from the group consisting of fluorine, bromine, hydroxy and oxo,

wherein R ^b1 and R ^b2 are each independently hydrogen, straight-chain or branched C _1-3 alkyl;

또는

이고, 여기서 R^c는 수소, 또는 L² 및 이들이 결합한 질소와 함께 피페리디닐렌을 형성하고;L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form piperidinylene;

L ² is a single bond, unsubstituted or straight or branched C _1-6 alkylene, C _4-6 cycloalkylene or phenylene substituted with one of hydroxy and oxo;

Z is unsubstituted or substituted C _6-9 aryl, unsubstituted or 5 to 9 membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S and O This fused C _4-7 cycloalkyl, 5 to 6 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 6 to 9-membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 6 to 6 containing at least one heteroatom selected from the group consisting of N, S and O to 9 membered unsubstituted or substituted heteroaryl C _1-4 alkyl;

said substituted aryl is substituted with chlorine, phenyl, carboxy, morpholinyl or straight or branched C _1-3 alkoxycarbonyl,

In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently straight or branched C _1-4 alkyl, straight or branched C _1-4 alkoxy, benzyl, phenyl, fluorine, chlorine , bromine, may be substituted with one or more substituents selected from the group consisting of hydroxy or oxo.

In Formula 1,

Ar is phenyl, naphthyl, pyridine or thiazole;

R ¹ and R ² are each independently hydrogen or fluorine;

R ³ is hydrogen, bromine, unsubstituted or substituted straight or branched C _1-5 alkoxy, unsubstituted or substituted straight or branched C _1-5 alkyl, NR ^a1 R ^a2 , OR ^a3 , wherein R ^a1 , R ^a2 and R ^a3 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted straight or branched C _1-5 alkyl, unsubstituted or substituted phenyl, or N, S and O 5 to 6 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,

In this case, the substituted alkoxy, substituted alkyl, substituted phenyl and substituted heteroaryl are each independently 4 to 7 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 5 to 7 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 4 atom is substituted with one or more substituents selected from the group consisting of cycloalkyl, fluorine, bromine, hydroxy and sulfonyl, wherein said substituted alkoxy and substituted alkyl are each independently taken together with the carbon being substituted to form a cyclopropyl; can be further substituted,

wherein said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-3 alkyl unsubstituted or substituted with one or more fluorine, straight or branched C _1-4 alkylcarbonyl, NR ^b1 R ^b2 , chlorine , substituted with one or more substituents selected from the group consisting of fluorine, bromine, hydroxy and oxo,

wherein R ^b1 and R ^b2 are each independently hydrogen, methyl or ethyl;

또는

이고, 여기서 R^c는 수소, 또는 L² 및 이들이 결합한 질소와 함께 피페리디닐렌을 형성하고;L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form piperidinylene;

L ² is a single bond, unsubstituted or straight or branched C _1-4 alkylene, cyclohexylene or phenylene substituted with one of hydroxy and oxo;

Z is an unsubstituted or substituted 5 to 9 membered unsubstituted or substituted heteroaryl containing at least one hetero atom selected from the group consisting of unsubstituted or substituted phenyl, cyclohexyl, naphthyl, N, S and O; fused C _5-6 cycloalkyl, 5 to 6 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 6 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 6 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 6 to 9 membered unsubstituted or substituted heteroaryl C _1-3 alkyl;

wherein said substituted phenyl is substituted with chlorine, phenyl, carboxy, morpholinyl or methoxycarbonyl;

In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently linear or branched C _1-3 alkyl, methoxy, benzyl, phenyl, fluorine, chlorine, bromine, hydroxy or oxo. It may be substituted with one or more substituents selected from the group consisting of.

In Formula 1,

Ar is phenyl, naphthyl, pyridine or thiazole;

R ¹ and R ² are each independently hydrogen or fluorine;

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can be

Examples of the compound represented by Formula 1 according to the present invention include 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-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide;

<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-indol-3-yl)propyl)-4-(2-(piperidin-1-yl)ethoxy)benzenesulfonamide;

<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)piperazine-1- 1) 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)benzene sulfonamides;

<82> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,4-difluoropiperidin-1-yl)propoxy)benzenesulfone amides;

<83> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)propoxy)benzenesulfone amides;

<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 amides;

<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-fluorobenzene sulfonamides;

<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)benzene sulfonamides;

<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)benzenesulfone amides;

<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)benzene sulfonamides;

<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)benzene sulfonamides;

<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)benzenesulfone amides;

<138> 4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfone amides;

<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)benzenesulfone amides;

<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)benzenesulfone amides;

<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) pro oxy)benzenesulfonamide;

<170> N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzene sulfonamides;

<171> (R) -N- (3- (5-chloro-1H-indol-3-yl) propyl) -4- (2-hydroxy-3- (4-methylpiperazin-1-yl) pro oxy)benzenesulfonamide;

<172> (R)-N-(3-(5-chloro-1H-yn-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzene sulfonamides;

<173> (S) -N- (3- (5-chloro-1H-indol-3-yl) propyl) -4- (2-hydroxy-3- (4-methylpiperazin-1-yl) pro oxy)benzenesulfonamide;

<174> (S)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzene sulfonamides;

<175> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dimethyl-1H-imidazol-1-yl)propoxy)benzenesulfone amides;

<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)prop oxy)benzenesulfonamide;

<182> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzene sulfonamides;

<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)benzene sulfonamides;

<190> 4-(3-(piperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide.

The compound represented by Formula 1 of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. It is obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids, etc., and organic acids such as acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid and the like. Examples of such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, sube Late, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate and the like.

The acid addition salt according to the present invention can be prepared by a conventional method, for example, a precipitate formed by dissolving the derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. and adding an organic or inorganic acid It can be prepared by filtration and drying, or it can be prepared by distilling the solvent and excess acid under reduced pressure, followed by drying and crystallization in an organic solvent.

In addition, bases can be used to prepare pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as the metal salt. The corresponding salt is also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable negative salt (eg silver nitrate).

Furthermore, the present invention includes not only the compound represented by Formula 1 and pharmaceutically acceptable salts thereof, but also solvates, isomers, hydrates, and the like, which can be prepared therefrom.

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

The compound represented by Formula 1 according to the present invention may be prepared according to the preparation method shown in the following examples, but this is only an example, and the present invention is not limited thereto, and methods well known to those skilled in the art may be used for each preparation step.

In addition, another aspect of the present invention is as shown in Scheme 1 below,

There is provided 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 above.

[Scheme 1]

In 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; and

J ² is amine or piperidine.

Hereinafter, the manufacturing method represented by Scheme 1 will be described in detail.

In the method for preparing a compound represented by Formula 1 according to the present invention, the step of Scheme 1 is a step of preparing a compound represented by Formula 1 by reacting a compound represented by Formula 2 with a compound represented by Formula 3 . Specifically, it is a step in which the compound represented by Formula 1 is formed by reacting chlorosulfone or carboxy of the compound represented by Chemical Formula 2 with the amine of the compound represented by Chemical Formula 3.

In this case, the step is not particularly limited as long as it is a method for preparing the compound represented by Formula 1, and is included in the scope of the present invention, but the compound represented by Formula 2 includes a group that is easy to accept electrons such as sulfone and chloro ( chloro) can be understood as a compound having a leaving group that is easy to react such as chloro) or a compound having a carboxyl capable of reacting with an amine to form an amide, and the compound represented by Formula 3 is a nucleophilic substitution reaction or an amide formation reaction It can be understood as an amine capable of A compound having an electron-accepting group and a leaving group and an amine having sufficient nucleophilicity to react therewith undergo a nucleophilic substitution reaction, or carboxy and an amine undergo an amide-forming reaction to prepare a final compound. .

More specifically, it can be understood with reference to the preparation method of the compound of the present invention below, but a person skilled in the art of organic synthesis can think of each reaction condition (reaction temperature, time, atmospheric condition, pressure condition, etc.) reaction conditions) can be changed, and it can be understood that the invention is not limited thereto, and the compounds and derivatives thereof used in each step can be changed therefrom other than those disclosed, that is, simply by modifying or changing the substituents or It is to be understood to include derivatives that have been modified such as to eliminate, and are encompassed by the present invention.

Preferred embodiments of the manufacturing method include the manufacturing methods disclosed in Examples 1 to 190 below, but the present invention is not limited thereto.

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

The compound represented by Formula 1 according to the present invention, an isomer thereof, or a pharmaceutically acceptable salt thereof may inhibit Pin1 (Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1).

Pin1, a proryl isomerase, is an enzyme that binds to the phosphorylated Ser/Thr-Pro site and catalyzes the cis/trans isomerization of proline residue amides. It is known to be involved in the onset and progression of diseases and cancers.

In particular, it has been reported that Pin1 activates 56 oncogenes involved in cancer induction and inhibits the activity of 26 cancer suppressor genes, thereby inducing cancer metastasis and cancer angiogenesis in the overall mechanism of cancer development.

And when Pin1 is inhibited or Pin1 gene expression is knocked down, the production of prostaglandin E2 and nitric oxide stimulated with lipopolysaccharide (LPS) and nicotine is attenuated, and also cyclooxygenase-2 (COX-2), inducible nitric oxide Since the expression of synthase (iNOS) is also weakened, it is known that it has an anti-inflammatory effect.

In addition, it is well known that when Pin1 is attached to CRTC2, the generation of the CBP-CRTC2-CREB complex that promotes gluconeogenesis is inhibited, so that CRTC2 is regulated according to the level of Pin1 expression and can be involved in glucose metabolism regulation.

Therefore, agents that affect Pin1 expression or activity can be used as therapeutic agents for metabolic diseases such as cancer, inflammatory diseases, or diabetes.

Accordingly, the compound represented by Formula 1 according to the present invention, an isomer thereof, or a pharmaceutically acceptable salt thereof is a pharmaceutical composition for preventing or treating cancer, inflammatory disease or metabolic disease containing the same as an active ingredient, or cancer, It can be usefully used as a health functional food for the prevention or improvement of inflammatory diseases or metabolic diseases.

The cancer is pseudomyxoma, intrahepatic biliary tract cancer, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, labial cancer, mycosis fungoides, acute myeloid leukemia, acute lymphoblastic 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 myelogenous leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, ampulla Barter cancer, bladder cancer, peritoneal cancer , parathyroid cancer, adrenal cancer, nasal sinus cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, juvenile brain cancer, juvenile lymphoma, juvenile leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, renal pelvic cancer, kidney cancer, heart cancer, Duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureter cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoma, gastrointestinal stromal cancer, Wilm Breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational villous disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoma, vaginal cancer, spinal cord cancer, acoustic 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, hematological cancer and thymus cancer It may be at least one selected from the group consisting of.

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

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.

And, another aspect of the present invention provides a health functional food for the prevention or improvement of cancer, inflammatory disease or metabolic disease containing the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. .

As used herein, the term “prevention” may refer to any action that inhibits or delays the onset of neurological diseases by administering the pharmaceutical composition according to the present invention to an individual.

As used in the present invention, the term "treatment" may refer to any action to improve or benefit symptoms of a nervous system disease by administering the pharmaceutical composition according to the present invention to an individual.

When the composition of the present invention is used as a pharmaceutical, a pharmaceutical composition containing the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient may be administered according to the following oral or parenteral administration procedures. It may be formulated and administered in an oral dosage form, but is not limited thereto.

Formulations for oral administration include, for example, tablets, pills, hard/soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, troches, and the like. , dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg silica, talc, stearic acid and its magnesium or calcium salts and/or polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt. It may contain disintegrants or boiling mixtures and/or absorbents, coloring, flavoring and sweetening agents.

When the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof is used as a pharmaceutical composition for the prevention or treatment of cancer, inflammatory disease, or metabolic disease, it is administered as an individual therapeutic agent, or in combination with another therapeutic agent in use. It can be used by administration.

A pharmaceutical composition comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient may be administered parenterally, and parenteral administration is administered by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. depending on how

At this time, in order to formulate a formulation for parenteral administration, the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof is mixed with water together with a stabilizer or buffer to prepare a solution or suspension, which is then prepared in an ampoule or It may be prepared in vial unit dosage form. The composition may be sterilized and/or contain adjuvants such as preservatives, stabilizers, thickeners, wetting agents or emulsification promoters, salts and/or buffers for regulating osmotic pressure and/or other therapeutically useful substances and may contain other therapeutically useful substances such as dispersion, gelation, etc. It can be formulated according to a conventional method.

The dosage for the human body of the pharmaceutical composition containing the compound represented by Formula 1 as an active ingredient may vary depending on the formulation method, the patient's age, weight, sex, dosage form, health status and disease degree, preferably can be administered through oral or parenteral routes in an amount of 0.001 to 1000 mg/kg/day by dividing a certain time interval several times a day, preferably 1 to 3 times a day, according to the judgment of a doctor or pharmacist .

The pharmaceutical composition of the present invention can be used as a single agent. In addition, it may be prepared and used as a combination formulation by additionally including one or more other therapeutic agents.

In another aspect, the present invention provides a method for preventing or treating cancer, inflammatory disease or metabolic disease, comprising administering the pharmaceutical composition to an individual in need in an effective amount. The pharmaceutical composition refers to a pharmaceutical composition for the prevention or treatment of cancer, inflammatory disease or metabolic disease, comprising the compound of Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

In another aspect, in the prevention or treatment of cancer, inflammatory disease or metabolic disease, a pharmaceutical composition or health functional food composition containing the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof provide use.

Hereinafter, the present invention will be described in detail by way of Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples and Experimental Examples.

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

Step 1: Preparation of (E)-4-(2-isocyanovinyl)-1,1'-biphenyl

Sodium hydride 60% wt (0.263 g, 6.59 mmol) was dissolved in anhydrous tetrahydrofuran (13 ml), and then 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, followed by stirring at room temperature for 30 minutes. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. (E)-4-(2-isocyanovinyl)-1,1'-biphenyl was obtained as a white solid without further purification.

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

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

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

After dissolving 3-([1,1'-biphenyl]-4-yl)propanenitrile (1.137 g, 5.49 mmol) synthesized in step 2 in anhydrous tetrahydrofuran (10 ml), slowly at 0°C Lithium aluminum hydride 1M (10.97 ml, 10.97 mmol) was added dropwise. The reaction was stirred at room temperature for 2 hours. After completion of the reaction by adding water dropwise, filtration was performed using a filter and the solvent was removed under reduced pressure. 3-([1,1'-biphenyl]-4-yl)propan-1-amine was obtained as a sticky yellow compound without further purification.

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

After dissolving 4-butoxy benzenesulfonyl chloride (40 μl, 0.200 mmol) in dichloromethane (1 ml), 3-([1,1'-biphenyl]-4-yl) synthesized in step 3 above Propan-1-amine (127 mg, 0.601 mmol) was added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (14.4 mg, 16%, white solid).

Examples 2 to 7 were prepared in a manner similar to step 4 of Example 1.

<Example 8> Preparation of 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid

Step 1: Preparation of methyl 4-(2-((4-butoxyphenyl)sulfonamido)ethyl)benzoate

The target compound (6.7 mg, 28%, white solid) was obtained in a manner similar to step 4 of Example 1 above.

Step 2: Preparation of 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid

After dissolving the compound methyl 4-(2-((4-butoxyphenyl)sulfonamido)ethyl)benzoate (23 mg, 0.059 mmol) prepared in step 1 in methanol (0.5 ml), 4M potassium hydroxy Aqueous seed solution (0.147 ml, 0.588 mmol) was added dropwise. It was stirred at room temperature for 3 hours, and after completion of the reaction, it was neutralized using 1M HCl aqueous solution. After extraction with dichloromethane, the organic layer was washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (3.4 g, 15%, white solid).

Example 9 was prepared in the same manner as in step 1 of Example 8.

<Example 10> Preparation of N-(2-(4-benzylpiperidin-1-yl)ethyl)-4-butoxybenzenesulfonamide

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

4-benzylpiperidine (8 g, 45.6 mmol) and potassium carbonate (K ₂ CO ₃ ) (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, and the mixture was stirred at 60° C. for 12 hours. Tert-butyl (2-bromoethyl) carbamate 12.27 g, 54.8 mmol) was added dropwise to the reaction product, and then stirred at 60° C. for 12 hours. After completion of the reaction, 1M HCl aqueous solution was added dropwise, and the mixture was extracted with dichloromethane. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Then, the reaction mixture was separated and purified by MPLC to give tert-butyl(2-(4-benzylpiperidin-1-yl)ethyl)carbamate (12.9 g, 89%, white solid).

Step 2: Preparation of 2-(4-benzylpiperidin-1-yl)ethanamine 2 HCl salt

4M HCl dioxane solution (10.13 ml, 40.5 mmol) was directly added to tert-butyl (2-(4-benzylpiperidin-1-yl)ethyl)carbamate (12.9 g, 40.5 mmol) prepared in step 1 above. After treatment, the mixture was stirred at room temperature for 2 hours. After completion of the reaction, excess HCl was removed under reduced pressure. Obtained 2-(4-benzylpiperidin-1-yl)ethanamine 2HCl salt (8.9 g, 75%, white solid).

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

Using the compound prepared in step 2, the target compound (7.6 mg, 14%, clear oil) was obtained in a similar manner to step 4 of Example 1.

Example 11 was prepared in a manner similar to step 4 of Example 1.

<Example 12> Preparation of 4-butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide

Step 1: Preparation of (4-butoxy-N-(3-hydroxy-3-phenylpropyl)benzenesulfonamide

A target compound was prepared in a manner similar to step 4 of Example 1.

Step 2: Preparation of 4-butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide

The compound prepared in step 1 (30 mg, 0.121 mmol) was dissolved in dichloromethane (0.5 ml), and then manganese (IV) oxide (31.1 mg, 0.358 mmol) was added dropwise. The reaction was stirred at room temperature for 12 hours. After completion of the reaction, the mixture was filtered through celite and the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (9.2 mg, 71 %, white solid).

Example 13 was prepared in a manner similar to step 4 of Example 1.

<Example 14> Preparation of 4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide

Step 1: Preparation of N,N-dimethyl-3-phenoxypropan-1-amine

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

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

After dissolving N,N-dimethyl-3-phenoxypropan-1-amine (922 mg, 5.14 mmol) prepared in step 1 in dichloromethane (6 ml), chlorosulfonic acid (1.37 ml) at 0 ° C. , 20.57 mmol) was added dropwise and stirred at room temperature for 3 hours. After completion of the reaction, ice was added dropwise. It was extracted with dichloromethane, and neutralized using a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. 4-(3-(dimethylamino)propoxy)benzene-1-sulfonyl chloride (451 mg, 32%, yellow solid) was obtained without further purification.

Step 3: Preparation of 4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide

After dissolving 4-(3-(dimethylamino)propoxy)benzene-1-sulfonyl chloride (100 mg, 0.318 mmol) prepared in step 2 in dichloromethane (2 ml), 2-phenylethanamine ( 116 mg, 0.955 mmol) and potassium carbonate (K ₂ CO ₃ ) (48.4 mg, 0.35 mmol) were added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (88 mg, 75%, clear oil).

Examples 15 and 16 were prepared in a manner similar to step 3 of Example 14 above.

<Example 17> Preparation of 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoic acid

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

A target compound was prepared in a manner similar to step 3 of Example 14.

Step 2: Preparation of 4-(2-(4-(3-(dimethylamino)propoxyphenylsulfonamido)ethyl)benzoic acid

The compound prepared in step 1 (58 mg, 0.138 mmol) was dissolved in methanol (1 ml), and then a 4M aqueous potassium hydroxide solution (0.69 ml, 2.76 mmol) was added dropwise to react at room temperature for 1 hour. After completion of the reaction, neutralized with 1M HCl aqueous solution, extracted with dichloromethane, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by prep TLC to obtain the target compound (1.7 mg, 3%, white solid).

Example 18 was prepared in a manner similar to step 3 of Example 14.

<Example 19> Preparation of 4-butoxy-N-(3-(naphthalen-1-yl)propyl)benzenesulfonamide

Step 1: Preparation of tert-butyl (3- (naphthalen-1-yl) propyl) carbamate

tert-Butylallylcarbamate (1 g, 6.36 mmol) was dissolved in tetrahydrofuran (6 ml), and then 9-BBN (10 mmol) dissolved in 0.5 M tetrahydrofuran was added dropwise. After the reaction was stirred at room temperature for 2.5 hours, 1-iodonaphthalene (0.925 ml, 6.36 mmol), PdCl ₂ (dppf)-CH ₂ Cl ₂ (308 mg, 0.377 mmol), 1M aqueous sodium hydroxide solution (10 ml) was added. was added dropwise. After stirring the reaction product at room temperature for 3 hours, PdCl ₂ (dppf)-CH ₂ Cl ₂ (55 mg, 0.07 mmol) was added dropwise and stirred at room temperature for 14 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added dropwise, extracted with ethyl acetate, dried over magnesium sulfate, and the solvent was removed under reduced pressure. Thereafter, the compound (1.6 g) obtained by separating and purifying the reaction mixture by MPLC was added dropwise to a mixture of tetrahydrofuran (20 ml), 15% aqueous sodium hydroxide solution (5 ml) and 30% hydrogen peroxide (10 ml) at 0° C. and stirred at the same temperature for 2 hours. After completion of the reaction, ethyl acetate was added dropwise, washed sequentially with a supersaturated aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain tert-butyl(3-(naphthalen-1-yl)propyl)carbamate (1.4 g, 77%).

Step 2: Preparation of 3-(naphthalen-1-yl)propan-1-amine

After dissolving tert-butyl(3-(naphthalen-1-yl)propyl)carbamate (1.4 g, 4.9 mmol) prepared in step 1 in dichloromethane (20 ml), trifluoroacetic acid ( 10 ml, 130 mmol) was added dropwise and stirred at room temperature for 3 hours. After completion of the reaction, 10% aqueous sodium hydroxide solution was added dropwise to neutralize, extracted with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove 3-(naphthalene-1). -yl)propan-1-amine (925 mg, 100%) was obtained.

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

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

Example 20 was prepared in a manner similar to step 4 of Example 1 above.

<Example 21> Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)benzenesulfonamide

Step 1: Preparation of N,N-dimethyl-2-phenoxythan-1-amine

Phenol (500 mg, 5.31 mmol) with 2-(dimethylamino)ethan-1-ol (521 mg, 5.84 mmol) and triphenylphosphine (2.089 g, 797 mmol) were mixed with tetrahydrofuran (20 ml) at 0 °C. ), diethyl azodicarboxylate solution (DEAD) (3.61 ml, 7.97 mmol) was added dropwise. The reaction was stirred at room temperature for 12 hours under a nitrogen stream. After completion of the reaction, the solvent was removed under reduced pressure. After extraction with dichloromethane, the organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain N,N-dimethyl-2-phenoxythan-1-amine (870 mg, 99%, yellow solid).

Step 2: Preparation of 4-(2-(dimethylamino)ethoxy)benzenesulfonyl chloride

After dissolving N,N-dimethyl-2-phenoxyethan-1-amine (533 mg, 3.23 mmol) prepared in step 1 in dichloromethane (3 ml), chlorosulfonic acid (0.858 ml) at 0 ° C. , 12.90 mmol) was added dropwise and stirred at room temperature for 3 hours. After completion of the reaction, ice was added dropwise. It was extracted with dichloromethane, and neutralized using a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. 4-(2-(dimethylamino)ethoxy)benzenesulfonyl chloride (622 mg, 73 %, yellow oil) was obtained without further purification.

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

After dissolving 4-(2-(dimethylamino)ethoxy)benzenesulfonyl chloride (45 mg, 0.171 mmol) prepared in step 2 in dichloromethane, 3-(1H-indol-3-yl)propane- 1-amine (131 mg, 0.751 mmol) was added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (11 mg, 17%, yellow solid).

Example 22 was prepared in a manner similar to Example 14 above.

Examples 23 to 25 were prepared in a manner similar to step 4 of Example 1 above.

<Example 26> Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(isopentyloxy)benzenesulfonamide

4-(Isopentyloxy)benzenesulfonyl chloride (20 mg, 0.076 mmol) was dissolved in dichloromethane (1.5 ml) and then 3-(1H-indol-3-yl)propan-1-amine (30 mg, 0.172) mmol) was added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (26 mg, 85%, yellow solid).

<Example 27> Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide

4-(pentyloxy)benzenesulfonyl chloride (20 mg, 0.076 mmol) was dissolved in dichloromethane, and then 3-(1H-indol-3-yl)propan-1-amine (30 mg, 0.172 mmol) was added dropwise. . The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (25 mg, 81%, white solid).

Example 28 was prepared in a manner similar to step 4 of Example 1.

<Example 29> Preparation of 4-butoxy-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)benzenesulfonamide

4-Butoxybenzenesulfonylchloride (50 mg, 0.201 mmol) was dissolved in dichloromethane (1 ml) and then 3-(2-aminoethyl)-1H-indole-5-olhydrochloride (128 mg, 0.603 mmol) ) and triethylamine (0.084 ml, 0.603 mmol) were added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (10.2 mg, 13%, white solid).

<Example 30> Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-morpholinopropoxy)benzenesulfonamide

Step 1: Preparation of 4-(3-phenoxypropyl)morpholine

Phenol (600 mg, 6.38 mmol) with 4-(3-hydroxypropyl)morpholine (1.11 g, 7.65 mmol) and triphenylphosphine (2.5 g, 9.56 mmol) were mixed with tetrahydrofuran (16 ml) at 0° C. After dissolving in , diethyl azodicarboxylate solution (DEAD) (4.34 ml, 9.56 mmol) was added dropwise. The reaction was stirred at room temperature for 12 hours under a nitrogen stream. After completion of the reaction, the solvent was removed under reduced pressure. After extraction with dichloromethane, the organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Then, the reaction mixture was separated and purified by MPLC to give 4-(3-phenoxypropyl)morpholine (1.41 g, 100%, clear oil).

Step 2: Preparation of 4-(3-morpholinopropoxy)benzene-1-sulfonyl chloride

After dissolving 4-(3-phenoxypropyl)morpholine (1.41 g, 6.38 mmol) prepared in step 1 in dichloromethane (12 ml), chlorosulfonic acid (1.69 ml, 25.5 mmol) was added at 0° C. It was added dropwise and stirred at room temperature for 3 hours. After completion of the reaction, ice was added dropwise. It was extracted with dichloromethane, and neutralized using a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. 4-(3-morpholinopropoxy)benzene-1-sulfonyl chloride (2.22 g, 67%, yellow solid) was obtained without further purification.

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

After dissolving 4-(3-morpholinopropoxy)benzene-1-sulfonyl chloride (150 mg, 0.469 mmol) prepared in step 2 in dichloromethane (1.5 ml), 3-(1H-indole-3 -yl)propan-1-amine (245 mg, 1.407 mmol) and potassium carbonate (194 mg, 1.407 mmol) were added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (10.6 mg, 5%, yellow solid).

<Example 31> Preparation of N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide

Step 1: Preparation of 4-(3-bromopropoxy)benzene-1-sulfonyl chloride

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

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

After dissolving 4-(3-bromopropoxy)benzene-1-sulfonylchloride (538 mg, 1.716 mmol) prepared in step 1 in dichloromethane (5 ml), 3-(1H-indole-3- yl)propan-1-amine (897 mg, 5.15 mmol) and potassium carbonate (K ₂ CO ₃ ) (711 mg, 5.15 mmol) were added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. Then, the reaction mixture was separated and purified by MPLC to obtain N-(3-(1H-indol-3-yl)propyl)-4-(3-bromopropoxy)benzenesulfonamide (230 mg, 29%, white solid) ) was obtained.

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

N-(3-(1H-indol-3-yl)propyl)-4-(3-bromopropoxy)benzenesulfonamide (175 mg, 0.388 mmol) prepared in step 2 was dissolved in ethanol (1.5 ml) After dissolution, 1-methylpiperazine (0.172 ml, 1.551 mmol) and potassium carbonate (K ₂ CO ₃ ) (80 mg, 0.582 mmol) were added dropwise. Stirred at 70° C. for 12 hours. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed with water and brine in that order, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (66 mg, 36%, white solid).

Examples 32 and 33 were prepared in a manner similar to step 4 of Example 1 above.

Examples 34 and 35 were prepared in a manner similar to that of Example 30.

Example 36 was prepared in a manner similar to Example 31 above.

Examples 37 to 40 were prepared in a manner similar to that of Example 14.

Examples 41 and 42 were prepared in a manner similar to Example 30 above.

Examples 43 to 45 were prepared in a manner similar to that of Example 31.

<Example 46> Preparation of 4-(3-(dimethylamino)propoxy)-N-(3-(1-methyl-1H-indol-3-yl)propyl)benzenesulfonamide

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 similar manner to Example 14.

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

N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide (150 mg, 0.981 mmol) prepared in step 1 above was mixed with DMF (1 ml), sodium hydride (60%) (51.5 mg, 1.287 mmol) was added dropwise at -20°C and stirred for 30 minutes. Iodomethane (23 μl, 0.368 mmol) dissolved in DMF (0.1 ml) at the same temperature was slowly added dropwise. The reaction was stirred at room temperature for 12 hours. After completion of the reaction, extraction was performed with ethyl acetate, followed by neutralization using a supersaturated aqueous ammonium chloride solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Then, the reaction mixture was separated and purified by MPLC to obtain the target compound (13.7 mg, 8%, clear oil). .

<Example 47> Preparation of N-(3-(1H-indol-3-yl)propyl)-4-bromobenzenesulfonamide

Step 1: Preparation of 4-bromobenzene-1-sulfonyl chloride

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

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

After dissolving 4-bromobenzene-1-sulfonyl chloride (74 mg, 0.29 mmol) prepared in step 1 in dichloromethane (1 ml), 3-(1H-indol-3-yl)propan-1- Amine (151 mg, 0.869 mmol) and potassium carbonate (K ₂ CO ₃ ) (120 mg, 0.869 mmol) were added dropwise. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, extraction was performed with dichloromethane, and the organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (71 mg, 62%, white solid).

Examples 48 to 54 were prepared in a manner similar to Example 31 above.

Example 55 was prepared in a manner similar to Example 30 above.

Examples 56 to 58 were prepared in a manner similar to that of Example 31.

Examples 59 and 60 were prepared in a manner similar to that of Example 30 above.

Example 61 was prepared in a manner similar to Example 31 above.

Example 62 was prepared in a manner similar to Example 30 above.

Examples 63 to 71 were prepared in a manner similar to that of Example 31.

<Example 72> 4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indole-3) Preparation of -yl) propyl) benzenesulfonamide

Step 1: (2S,6R)-tert-Butyl 4-(3-(4-(N-(3-(5-fluoro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl) Preparation of -2,6-dimethylpiperazine-1-carboxylate

In a similar manner to Example 31 above (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.

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

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

Examples 73 to 76 were prepared in a manner similar to that of Example 31.

<Example 77> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfone Preparation of amides

Step 1: tert-butyl(1-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)azetidin-3-yl ) (methyl) carbamate preparation

Tert-butyl (1-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)ase Tidin-3-yl)(methyl)carbamate was prepared.

Step 2: N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfonamide manufacturing

Using tert-butylazetidin-3-yl (methyl) carbamate prepared in step 1 above, tert-butyl (1- (3- (4- (N- (3- (5-chloro-1H-indole-) 3-yl)propyl)sulfamoyl)phenoxy)propyl)azetidin-3-yl)(methyl)carbamate (38 mg, 0.064 mmol) was dissolved in dichloromethane (0.5 ml), and then trifluoro Acetic acid (0.2 ml, 2.61 mmol) was added dropwise and stirred at room temperature for 2 hours. After completion of the reaction, ice was added dropwise. It was extracted with ethyl acetate and neutralized using a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Thereafter, the reaction mixture was separated and purified by MPLC to obtain the target compound (7 mg, 22%, yellow solid).

Example 78 was prepared in a manner similar to Example 31 above.

<Example 79> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-6-(3-(piperazin-1-yl)propoxy)pyridine-3-sulfonamide

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

After 5-bromo-2-fluoropyridine (0.326 ml, 2.84 mmol) was dissolved in DMF (12 ml), 60% wt of sodium hydride (0.159 g, 3.98 mmol) was added dropwise at 0° C. and stirred for 5 minutes. After mixing, tert-butyl-4-(3-hydroxypropyl)piperazine-1-carboxylate was added dropwise and stirred at 70° C. for 6 hours. After completion of the reaction, ice was added dropwise. It was extracted with dichloromethane, and neutralized using a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Tert-butyl-4-(3-((5-bromopyridin-2-yl)oxy)propyl piperazine-1-carboxylate (1.35 g, 110%) was obtained without further purification.

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

Tert-butyl-4-(3-((5-bromopyridin-2-yl)oxy)propyl perazine-1-carboxylate (0.52 g, 1.3 mmol) prepared in step 1 above was mixed with 1.4-dioxane ( 12 ml), (4-methoxyphenyl)methanethiol (0.199 ml, 1.23 mmol), N-ethyl-N-isopropylpropan-2-amine (0.681 ml, 3.90 mmol) were added dropwise and nitrogen After stirring for 5 minutes under a _{pressure drop, Pd 2} (dba) ₃ (9.91 mg, 0.032 mmol) and Xantphos (0.038 g, 0.065 mmol) were added dropwise and tert-butyl-4-(3-hydroxypropyl)piperazine-1- Carboxylate was added dropwise and reacted with Biotage microwave for 30 minutes at 150° C. After completion of the reaction, the mixture was extracted with dichloromethane and neutralized with a supersaturated aqueous sodium carbonate solution.The organic layer was washed with water and brine in that order. , dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure without further purification tert-butyl 4-(3-((5-((4-methoxybenzyl)thio)pyridin-2-yl)oxy) Obtained propyl)piperazine-1-carboxylate (0.51 g, 51.8%).

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

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

Step 4: tert-Butyl 4-(3-((5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)pyridin-2-yl)oxy)propyl)pipe Preparation of razine-1-carboxylate

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 mixed with DMF (2 ml), 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 at room temperature reacted for 2 hours. After completion of the reaction, the mixture was extracted with dichloromethane, and neutralized with a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Then, the reaction mixture was separated and purified by Prep TLC to tert-butyl 4-(3-((5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)pyridine- 2-yl)oxy)propyl)piperazine-1-carboxylate (18 mg, 12.8%) was obtained.

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

4-(3-((5-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)pyridin-2-yl)oxy)propyl)pipette prepared in step 4 above After dissolving razine-1-carboxylate (18 mg, 0.034 mmol) in tetrahydrofuran (1 ml), trifluoroacetic acid (0.5 ml, 6.49 mmol) was added dropwise at room temperature, followed by stirring at room temperature for 2 hours. . After completion of the reaction, ice was added dropwise. It was extracted with ethyl acetate and neutralized using a supersaturated aqueous sodium carbonate solution. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Then, the reaction mixture was separated and purified by Prep TLC to obtain the target compound (4.5 mg, 30%).

Examples 80 to 84 were prepared in a manner similar to that of Example 31.

<Example 85> Preparation of N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide

Step 1: Preparation of 3-(1H-indol-3-yl)cyclohexan-1-one

In a solution of 1H-indole (1 g, 8.54 mmol) and cyclohex-2-enone (1.64 g, 17.1 mmol) in CH ₃ CN (30 ml), Sc(OTf) ₃ (0.42 g, 0.854 mmol) was added. The reaction mixture was stirred at 30° C. under _{N 2 atmosphere for 3 hours.} After completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by Prep HPLC to obtain the target compound (805 mg, 44%).

Step 2: Preparation of 3-(1H-indol-3-yl)cyclohexan-1-amine

3-(1H-indol-3-yl)cyclohexan-1-one (800 mg, 3.75 mmol) prepared in step 1 was dissolved in dichloroethane (10 ml) and acetic acid (0.5 ml), and then at room temperature Ammonium acetate (8.67 g, 113 mmol) was added and stirred for 2 h. Then, sodium triacetoxyborohydride (3.18 g, 15.0 mmol) was added at room temperature and stirred for 5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the obtained reaction mixture was separated and purified by MPLC to obtain the target compound (250 mg, 31%, yellow solid).

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

3-(1H-indol-3-yl)cyclohexan-1-amine (105 mg, 0.491 mmol) prepared in step 2 above and 4-(3-bromorph obtained in a similar manner to step 2 of Example 31 above) [Example 31-Step 2] was carried out similarly to [Example 31-Step 2] using ropoxy)benzenesulfonylchloride (140 mg, 0.446 mmol) to obtain the target compound (100 mg, 46%, white solid).

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

N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-bromopropoxy)benzenesulfonamide (30 mg, 0.061 mmol) prepared in step 3 and 1-methylpiperazine (24.5 mg, 0.244 mmol) was used to obtain the target compound (21.6 mg, 69% yield) as a white solid in a similar manner to step 3 of Example 31.

<Example 86> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfone Preparation of amides

Step 1: Preparation of 4-(3-bromopropoxy)naphthalene-1-sulfonate, sodium (I) salt

4-Hydroxynaphthalene-1-sulfonate, sodium (I) salt (0.3 g, 1.218 mmol) was dissolved in ethanol (2.5 ml) followed by 1,3-dibromopropane (0.211 ml, 2.071 mmol), After addition of tetrabutyl ammonium sulfate (0.033 g, 0.097 mmol) and aqueous potassium hydroxide solution (1.56 ml, 1.218 mmol), the mixture was heated to reflux for 3 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, dissolved again in ethanol, and concentrated once again. After hot methanol was added to the reaction solution, the insoluble material was filtered, the filtered solution was concentrated, and the resulting solid was washed with dichloromethane and filtered to prepare the target compound (0.4 g, 99%, white solid). did.

Step 2: Preparation of 4-(3-bromopropoxy)naphthalene-1-sulfonylchloride

Thionyl chloride (0.286 ml, 3.92 mmol) and dimethylformamide (1.91 μl) were added to the compound prepared in step 1 (0.2 g, 0.545 mmol), and then heated to reflux for 4 hours. After the reaction was completed, the temperature was lowered to room temperature, diluted with ethyl acetate, and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and used in the next step without further purification.

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

A target compound was prepared in a manner similar to step 2 of Example 31.

Step 4: N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfonamide manufacturing

A target compound was prepared in a manner similar to step 3 of Example 31.

Example 87 was prepared in a manner similar to Example 31 above.

<Example 88> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-4-yl)propyl)amino)benzenesulfonamide

Step 1: Preparation of tert-butyl-4-(3-oxopropyl)piperidine-1-carboxylate

Tert-butyl-4-(3-hydroxypropyl)piperidine-1-carboxylate (0.3 g, 1.233 mmol) was dissolved in dichloromethane (6 ml), followed by Dess-Martin Periodinane (0.680) at 0° C. g, 1.603 mmol) and stirred at room temperature for 4 hours. After the reaction was completed, the reaction solution was filtered, and the filtered solution was washed with an aqueous sodium hydrogen carbonate solution and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to give the desired compound (0.24 g, 79%, clear oil).

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

A target compound was prepared in a manner similar to step 2 of Example 31.

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

After dissolving the compound (0.72 g, 1.840 mmol) prepared in step 2 in ethyl acetate (12 ml), tin (II) chloride and dihydrate (4.15 g, 18.40 mmol) were added, and 5 hours at 60°C heated while After completion of the reaction, aqueous ammonia was added to the reaction solution to make pH 5, sodium carbonate was added to make pH 7, filtered through celite, and the filtrate was concentrated under reduced pressure and used in the next step without further purification. .

Step 4: tert-Butyl 4-(3-((4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenyl)amino)propyl)piperidine-1 -Preparation of carboxylate

After dissolving the compound prepared in step 3 (0.05 g, 0.137 mmol) in dichloroethane (1 ml), the compound prepared in step 1 (0.046 g, 0.192 mmol) and acetic acid (0.024 ml, 0.412 mmol) were added After addition and stirring at room temperature for 1 hour, sodium triacetoxyborohydride (0.087 g, 0.412 mmol) was added and stirred at room temperature for 1 hour. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.017 g, 5% yellow solid).

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

A target compound was prepared in a manner similar to step 5 of Example 79.

<Example 89> Preparation of N-(3-(1H-indol-3-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide

Step 1: Preparation of 3-(3-nitrophenyl)-1H-indole

N-(2-ethynylphenyl)-2,2,2-trifluoroacetamide and 1-iodo-3-nitrobenzene were dissolved in DMSO solvent and catalytic amount of Pd ₂ (dba) for 1 hour at room temperature _{In the} presence of _{3, K 2} CO ₃ was treated in excess to obtain 3-(3-nitrophenyl-1H-indole) as a target compound.

Step 2: Preparation of 3-(1H-indol-3-yl)aniline

The compound prepared in step 1 (0.047 g, 0.197 mmol) was dissolved in methanol (2 ml), Pd/C (0.004 g, 3.76 μmol) was added, and the mixture was stirred under hydrogen gas at room temperature for 3 hours. After the reaction was completed, 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.

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

After dissolving the compound prepared in step 2 (0.041 g, 0.197 mmol) in pyridine (1 ml), the compound prepared in step 1 of Example 31 (0.068 g, 0.217 mmol) was added at 0° C. , and stirred at room temperature for 3 hours. After the reaction was completed, it was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to give the desired compound (0.047 g, 49%, yellow solid).

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

A target compound was prepared in a manner similar to step 3 of Example 31.

<Example 90> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-1-yl)butyl)benzenesulfonamide

Step 1: Preparation of 4-(4-bromobutyl)benzene-1-sulfonyl chloride

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

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

After dissolving 4-(4-bromobutyl)benzene-1-sulfonyl chloride (300 mg, 0.963 mmol) prepared in step 1 in dichloromethane (5 ml), 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. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC to obtain the target compound (330 mg, 71%, white solid).

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

4-(4-bromobutyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonylamide (30 mg, 0.062 mmol) prepared in step 2 above and piper Dean (15.9 mg, 0.186 mmol) and potassium carbonate (12.9 mg, 0.093 mmol) were used to obtain the target compound (16 mg, 53%, white solid) in a manner similar to step 3 of Example 31.

Example 91 was prepared in a manner similar to Example 90 above.

<Example 92> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide manufacturing

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

4-Hydroxybenzene-1-sulfonyl chloride (0.5 g, 2.60 mmol) was dissolved in dichloromethane (8.7 ml) followed by 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, followed by stirring at room temperature for 3 hours. After the reaction was completed, it was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to give the desired compound (0.19 g, 21%, white solid).

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

After dissolving the compound prepared in step 1 (0.05 g, 0.137 mmol) in tetrahydrofuran (1.5 ml) under nitrogen gas at 0° C., 3-(1-methylpiperidin-4-yl)propane-1- Ol (0.026 g, 0.164 mmol), PPh ₃ (0.054 g, 0.206 mmol), DEAD (0.093 ml, 0.206 mmol) were added and stirred for 1 h. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by the addition of aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.004 g, 7%, white solid).

<Example 93> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide

The compound (0.035 g, 0.061 mmol) prepared in a similar manner to Example 92 was dissolved in dichloromethane (2 ml), and trifluoroacetic acid (1 ml, 12.98 mmol) was added thereto, and at room temperature for 1 hour. stirred. After completion of the reaction, the reaction solution was concentrated under reduced pressure, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.01 g, 37%, white solid).

Example 94 was prepared in a manner similar to that of Example 93.

Examples 95 and 96 were prepared in a manner similar to that of Example 94.

Example 97 was prepared in a manner similar to Example 31 above.

<Example 98> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzene sulfonamide manufacture of

After dissolving the compound (0.05 g, 0.136 mmol) prepared in a similar manner to step 2 of Example 47 in dimethylformamide (1 ml), 3-(4-methylpiperazin-1-yl)propane-1 -Amine (0.043 g, 0.273 mmol) and potassium carbonate (0.021 g, 0.150 mmol) were added, and the mixture was stirred at 100° C. for 3 days. After completion of the reaction, the reaction solution was concentrated under reduced pressure, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.01 g, 16%, white solid).

<Example 99> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-4-yl)butyl)benzenesulfonamide

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

Methyltriphenylphosphonium bromide (1.184 g, 3.32 mmol) was dissolved in anhydrous tetrahydrofuran (2 ml), and then lithium bistrimethylsilylamide (3.32 ml, 3.32 mmol) was slowly added at 0°C. Then, 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). After that, it was slowly added dropwise at 0°C. After stirring at 0° C. for 30 minutes, the mixture was stirred at room temperature for 20 hours. After completion of the reaction, the 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 obtain the target compound (0.2 g, 50%, clear oil).

Step 2: tert-Butyl 4-(4-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenyl)butyl)piperidine-1-carboxylate manufacture of

After dissolving tert-butyl 4-(but-3-en-1-yl)piperidine-1-carboxylate (50 mg, 0.209 mmol) prepared in step 2 in anhydrous tetrahydrofuran (1.5 ml) , 9-borabicyclo[3.3.1]nonane (0.796 ml, 0.398 mmol) was added at room temperature. The reaction mixture was then gradually heated and stirred at reflux for 1 hour. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. After dissolving the obtained residue in 1,4-dioxane (1.5 ml), 4-bromo-N-(3-(5-chloro-1H-indole-3) prepared in a method similar to step 2 of Example 90 above -yl)propyl)benzenesulfonamide (85 mg, 0.199 mmol) and 1M aqueous sodium carbonate solution (0.597 ml, 0.597 mmol) were added. To the reaction mixture was added Pd(PPh ₃ ) ₄ (23 mg, 0.02 mmol), heated gradually and stirred at 90° C. for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, filtered through Celite, concentrated under reduced pressure, and purified by prep HPLC to obtain the target compound (15 mg, 13%, yellow solid).

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

Tert-butyl 4-(4-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenyl)butyl)piperidine-1 prepared in step 2 -Carboxylate (15 mg, 0.013 mmol) was dissolved in dichloromethane (2 ml), and then trifluoroacetic acid (1 ml, 13.1 mmol) was added at room temperature and stirred for 1 hour. After completion of the reaction, the residue obtained by concentrating the mixture was neutralized with a supersaturated aqueous sodium hydrogen carbonate solution, and then extracted with ethyl acetate. The extracted organic layer was washed with distilled water, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure to obtain the target compound (5 mg, 56% white solid).

Examples 100 to 102 were prepared in a manner similar to Example 31 above.

<Example 103> N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy) Preparation of benzenesulfonamide

Step 1: Preparation of 1-(3-bromopropoxy)-2-fluorobenzene

After dissolving 2-fluorophenol (5 g, 44.6 mmol) in acetonitrile (74 ml), 1,3-dibromopropane (90 g, 446 mmol) and potassium carbonate (6.16 g, 44.6 mmol) were added was added and stirred at 80° C. for 16 hours. After completion of the reaction, the reaction solution was filtered, concentrated under reduced pressure, and used in the next step without further purification.

Step 2: Preparation of 4-(3-bromopropoxy)-3-fluorobenzenesulfonyl chloride

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

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

After dissolving the compound (1 g, 3.02 mmol) prepared in step 2 in dichloromethane (6 ml), 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, and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (1.1 g, 77%, white solid).

Step 4: N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfone Preparation of amides

After dissolving the compound prepared in step 3 (0.05 g, 0.099 mmol) in ethanol (1 ml), potassium carbonate (0.021 g, 0.149 mmol) and 1-methylpiperazine (0.020 g, 0.198 mmol) were added. , and stirred at 70 °C for 16 hours. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution, to obtain the desired compound (0.011 g, 22%, white solid).

Examples 104 to 106 were prepared in a manner similar to that of Example 103.

<Example 107> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide

Tert-Butyl4-(3-(4-(N-(3-(5-chloro-1H-indol-3-yl)propyl)sulfamoyl)phenoxy)propyl)- In a similar manner to step 4 of Example 99 using 2-methylpiperazine-1-carboxylate (25 mg, 0.041 mmol) and trifluoroacetic acid (1 ml, 13.1 mmol), the target compound as a pale yellow solid (15 mg, 72%) was obtained.

Examples 108 to 111 were prepared in a manner similar to that of Example 107.

Example 112 was prepared in a manner similar to Example 90 above.

<Example 113> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)propyl)amino)benzenesulfonamide

The compound (0.0142 g, 0.024 mmol) prepared in a similar manner to Example 98 was dissolved in dichloromethane (2 ml), and trifluoroacetic acid (1 ml, 12.98 mmol) was added thereto, and at room temperature for 1 hour. stirred. After completion of the reaction, the reaction solution was concentrated under reduced pressure, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.005 g, 50%, white solid).

Example 114 was prepared in a manner similar to Example 98 above.

Example 115 was prepared in a manner similar to steps 1 to 3 of Example 99 above.

<Example 116> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)me Preparation of oxy)benzenesulfonamide

Step 1. Preparation of (1-(((tert-butyldimethylsilyl)oxy)methyl)cyclopropyl)methanol

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

Step 2. Preparation of ((1-(bromomethyl)cyclopropyl)methoxy)(tert-butyl)dimethylsilane

(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 then at 0 ° C. Bromide (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. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC to obtain the target compound (1 g, 70%, clear oil).

Step 3. Preparation of (1-(bromomethyl)cyclopropyl)methanol

((1-(bromomethyl)cyclopropyl)methoxy)(tert-butyl)dimethylsilane (1 g, 3.58 mmol) prepared in step 2 above was mixed with acetic acid/tetrahydrofuran/distilled water (12 ml/4 ml / 4 ml), followed by stirring at room temperature for 3 hours. After completion of the reaction, it was neutralized with a supersaturated aqueous sodium hydrogen carbonate solution 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 obtained reaction mixture was purified by MPLC to obtain the target compound (0.3 g, 51%, yellow oil).

Step 4. Preparation of 4-((1-(bromomethyl)cyclopropyl)methoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide

(1-(bromomethyl)cyclopropyl)methanol (30 mg, 0.182 mmol) prepared in step 3 and N-(3-(5-chloro-1H-) obtained in a similar manner to step 2 of Example 90 Indol-3-yl) propyl) -4-hydroxybenzenesulfonamide (66 mg, 0.182 mmol) with triphenylphosphine (72 mg, 0.273 mmol), diethyl azodicarboxylate (0.124 ml, 0.273 mmol) was used to obtain the target compound (45 mg, 48%, yellow solid) in a similar manner to step 2 of Example 92.

Step 5. N-(3-(5-Chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)methoxy) Preparation of benzenesulfonamide

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

Example 117 was prepared in a manner similar to that of Example 116.

<Example 118> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide

Step 1: Preparation of 4-(3-bromophenoxy)benzenesulfonic acid

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

Step 2: Preparation of 4-(3-bromophenoxy)benzenesulfonyl chloride

At 0° C., 4-(3-bromophenoxy)benzenesulfonic acid (395 mg, 1.20 mmol) prepared in step 1 was dissolved in SnCl ₂ ·H ₂ O (3ml, 41.4 mmol) and stirred. Then, two drops of diformamide were added at 0° C., and the reaction mixture was gradually heated and stirred under reflux for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, concentrated under reduced pressure, and purified by MPLC to obtain the target compound (380 mg, 91%, yellow oil).

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

4-(3-bromophenoxy)benzenesulfonyl chloride (150 mg, 0.432 mmol) prepared in step 2 above and 3-(5-chloro-1H-indol-3-yl)propan-1-amine (90 mg, 0.432 mmol) and triethylamine (0.090 ml, 0.647 mmol) to obtain the target compound (170 mg, 76%, yellow solid) in a similar manner to step 2 of Example 90.

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

4-(3-bromophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide (90 mg, 0.173 mmol) prepared in step 3 above was mixed with 1, After dissolving in 4-dioxane (1.5 ml), t-BuOK (29.1 mg, 0.260 mmol) and 1-methylpiperazine (0.03 ml, 0.260 mmol) were added at room temperature. After the reaction mixture was degassed for 5 minutes using a nitrogen balloon while heating and stirring at 70° C., Pd(t-Bu ₃ P) ₂ (8 mg, 0.016 mmol) was added, and the mixture was stirred under reflux for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, filtered through Celite, concentrated, and purified by prpe HPLC. The obtained trifluoroacetate compound was neutralized by adding a supersaturated aqueous sodium hydrogen carbonate solution, followed by extraction with a 10% methanol/dichloromethane solution. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target compound (6.5 mg, 53%, white solid).

Example 119 was prepared in a manner similar to steps 1 to 3 of Example 118.

Examples 120 to 122 were prepared in a manner similar to that of Example 118.

<Example 123> N-(3-(5-chloro1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide manufacturing

After dissolving the compound (0.05 g, 0.117 mmol) prepared in a similar manner to step 2 of Example 47 in 2-butanol (1.5 ml), 3-(4-methylpiperazin-1-yl)aniline (0.02 g, 0.117 mmol) and potassium carbonate (0.08 g, 0.584 mmol) were added and degassed for 1 minute. _{Thereafter, Pd 2} (dba) ₃ (0.01 g, 0.012 mmol) and Xphos (0.005 g, 0.012 mmol) were added at 80° C., followed by stirring at 100° C. for 1 hour. After the reaction was completed, the reaction solution was filtered through celite and washed with ethyl acetate and dichloromethane. The filtrate was concentrated under reduced pressure, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.023 g, 37%, yellow solid).

Examples 124 to 127 were prepared in a manner similar to that of Example 123.

Examples 128 and 129 were prepared in a manner similar to that of Example 119.

<Example 130> 4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfone Preparation of amides

Step 1: Preparation of 1,3-dibromo-5-phenoxybenzene

After dissolving phenol (100 mg, 1.06 mmol) in N-methyl-2-pyrrolidinone (2 ml), cesium carbonate (173 mg, 0.531 mmol), 1,3-dibromo-5-fluoro at room temperature Robenzene (0.201 ml, 1.59 mmol), TMHDA (0.057 ml, 0.266 mmol) and CuCl (52.6 mg, 0.531 mmol) were added. After degassing the reaction mixture at room temperature using a nitrogen balloon, the mixture was stirred for 20 minutes. The reaction mixture was gradually heated and stirred at 120° C. for 16 hours. After completion of the reaction, the mixture was cooled to room temperature, filtered through celite using ethyl acetate, and then concentrated under reduced pressure. The obtained reaction mixture was purified by MPLC to obtain the target compound (220 mg, 63%, yellow solid).

Step 2: Preparation of 4-(3,5-dibromophenoxy)benzenesulfonic acid

Using 1.3-dibromo-5-phenoxybenzene (220 mg, 0.671 mmol) and chlorosulfonic acid (0.049 ml, 0.738 mmol) prepared in step 1 above, in a similar manner to step 1 of Example 118. The compound (274 mg, 100%, yellow oil) was obtained.

Step 3: Preparation of 4-(3,5-dibromophenoxy)benzenesulfonyl chloride

Using 4-(3,5-dibromophenoxy)benzenesulfonic acid (274 mg, 0.671 mmol) and thionyl chloride (4ml, 55.1 mmol) prepared in step 2 above, step 2 of Example 118 and In a similar manner, the target compound (230 mg, 80%, yellow oil) was obtained.

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

4-(3,5-dibromophenoxy)benzenesulfonyl chloride (230 mg, 0.539 mmol) prepared in step 3 and 3-(5-chloro-1H-indol-3-yl)propane-1- An amine (118 mg, 0.566 mmol) and triethylamine (0.113 ml, 0.809 mmol) were used to obtain the target compound (300 mg, 93%, white solid) in a similar manner to step 2 of Example 90.

Step 5: 4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide manufacturing

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3,5-dibromophenoxy)benzenesulfonamide prepared in step 4 (50 mg, 0.084 mmol) Example 118 using 1-methylpiperazine (0.037 ml, 0.334 mmol), potassium tert-butoxide (37.5 mg, 0.334 mmol), Pd(t-Bu ₃ P) ₂ (8.54 mg, 0.017 mmol) The target compound (5 mg, 9%, yellow solid) was obtained in a manner similar to step 4 of

Examples 131 to 134 were prepared in a manner similar to that of Example 123.

Examples 135 and 136 were prepared in a manner similar to that of Example 118 above.

Example 137 was prepared in a manner similar to Example 138 below.

<Example 138> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy) Preparation of benzenesulfonamide

Step 1: Preparation of 1-bromo-3-fluoro-5-phenoxybenzene

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) with CuCl (0.263 mg, 2.66 mmol) was used to obtain the target compound (0.45 g, 32%, clear oil) in a similar manner to step 1 of Example 130.

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

Using 1-bromo-3-fluoro-5-phenoxybenzene (0.45 g, 1.685 mmol) and chlorosulfonic acid (0.123 ml, 1.853 mmol) prepared in step 1 above, step 1 and In a similar manner, the target compound (0.44 g, 71%, yellow oil) was obtained.

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

4-(3-bromo-5-fluorophenoxy)benzene-1-sulfonyl chloride (200 mg, 0.547 mmol) prepared in step 2 and 3-(5-chloro-1H-indol-3-yl) ) The target compound (300 mg, 93% yellow solid) was prepared in a manner similar to step 2 of Example 90 above using propan-1-amine (115 mg, 0.553 mmol) and triethylamine (0.114 ml, 0.821 mmol). got it

Step 4: 4-(3-Bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfone Preparation of amides

4-(3-bromo5-fluorophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide prepared in step 3 (30 mg, 0.056 mmol ) was dissolved in dimethyl sulfoxide (1 ml), and then 1-methylpiperazine (0.025 ml, 0.223 mmol) and potassium carbonate (30.8 mg, 0.223 mmol) were added at room temperature. Thereafter, the reaction mixture was heated to 120° C. and stirred for 16 hours. After 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 prep HPLC. The obtained trifluoroacetate compound was neutralized by adding a supersaturated aqueous sodium hydrogen carbonate solution, followed by extraction with a 10% methanol/dichloromethane solution. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target compound (6.2 mg, 22%, ivory solid).

Examples 139 to 142 were prepared in a manner similar to that of Example 123.

<Example 143> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzamide

Step 1: Preparation of methyl 4-(3-bromopropoxy)benzoate

After dissolving methyl 4-hydroxybenzoate (0.5 g, 3.29 mmol) in acetonitrile (10 ml), 1,3-dibromopropane (0.995 g, 4.93 mmol) and potassium carbonate (0.681 g, 4.93 mmol) was added. The reaction mixture was heated to 80° C. and stirred for 5 hours. After completion of the reaction, the mixture was cooled to room temperature, filtered through celite, and concentrated under reduced pressure. The obtained residue was purified by MPLC to obtain the target compound (0.7 g, 78%, clear oil).

Step 2: Preparation of 4-(3-bromopropoxy)benzoic acid

After dissolving methyl 4-(3-bromopropoxy)benzoate (0.7 g, 2.56 mmol) prepared in step 1 in tetrahydrofuran/methanol/distilled water (6.0 ml/3 ml/3 ml), room temperature LiOH?H2O (0.323 g, 7.69 mmol) was added. Thereafter, the reaction mixture was heated to 50° C. and stirred for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, and 1N aqueous hydrochloric acid solution was slowly added dropwise to adjust the pH to 2, and the resulting solid was washed with distilled water and then vacuum dried to obtain the target compound (0.35 g, 53% white solid).

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

After dissolving 4-(3-bromopropoxy)benzoic acid (0.1 g, 0.386 mmol) prepared in step 2 in dichloromethane (2 ml), 3-(5-chloro-1H-indole-3) at room temperature -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. Then the reaction mixture was stirred at room temperature for 16 hours. After 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 obtain the target compound (0.1 g, 58%, ivory solid).

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

4-(3-bromopropoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzamide (20 mg, 0.044 mmol) prepared in step 3 above and 1-methyl The target compound (8 mg, 38%, ivory solid) was obtained in a manner similar to step 3 of Example 31 using piperazine (0.02 ml, 0.178 mmol) and potassium carbonate (12.3 mg, 0.089 mmol).

Example 144 was prepared in a manner similar to that of Example 143.

Example 145 was prepared in a manner similar to that of Example 92.

<Example 146> N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfone Preparation of amides

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

A target compound was prepared in a manner similar to that of Example 31-Step 2.

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

The compound 2-chloro-N-(3-(5-chloro-1H-indol-3-yl)propyl)thiazole-5-sulfonamide (30 mg, 0.077 mmol) prepared in step 1 was dissolved in dimethylformamide. After dissolution, 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. After completion of the reaction, the solvent was removed under reduced pressure, and then separated and purified by MPLC to obtain the target compound (37 mg, 81%, yellow solid).

Step 3: of N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfonamide manufacturing

The target compound (30 mg, 97%, light yellow solid) was obtained in a manner similar to Example 99-Step 3 above.

<Example 147> N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methyl piperazin-1-yl)propoxy)benzene Preparation of sulfonamides

Step 1: Preparation of 3-(5-chloro-2-methyl-1H-indol-3-yl)propan-1-amine hydrochloride salt

Chlorophenyl hydrazine (1.40 g, 9.81 mmol) and 6-chlorohexen-2-one (1.10 g, 8.17 mmol) were dissolved in ethanol (30 ml) and stirred under reflux for 20 hours. After completion of the reaction, the mixture was cooled to room temperature and the solvent was removed under reduced pressure. Without further purification, 3-(5-chloro-2-methyl-1H-indol-3-yl)propan-1-amine hydrochloride (2.114 g, quantatitive) , a pale yellow solid) was obtained.

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

Compound 3-(5-chloro-2-methyl-1H-indol-3-yl)propan-1-amine hydrochloride (0.413 g, 1.59 mmol) prepared in step 1 was dissolved in ethylene chloride (6 ml). Then, triethylamine (0.444 ml, 3.19 mmol) was added dropwise and stirred for 5 minutes. 4-(3-bromopropoxy)benzene-1-sulfonyl chloride (0.200 g, 0.638 mmol) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. After completion of the reaction by adding water dropwise, the mixture was extracted with dichloromethane. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. Then, the mixture was separated and purified by MPLC to obtain the target compound (177 mg, 56%, brown solid).

Step 3: N-(3-(5-Chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methyl piperazin-1-yl)propoxy)benzenesulfonamide manufacture of

The target compound (19.8 mg, 64%, light yellow solid) was obtained in a manner similar to step 3 of Example 31.

<Example 148> N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methyl piperazin-1-yl)propoxy)benzene Preparation of sulfonamides

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

<Example 149> N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfone Preparation of amides

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

After dissolving 5-chloro-1H-indole (1 g, 6.60 mmol) and (2-aminophenyl)methanol (0.812 g, 6.60 mmol) in 1,2-dichloroethane (20 mL), trifluoroacetic acid ( 0.151 mL, 1.979 mmol) was added at room temperature. The reaction mixture was stirred at 50° C. for 16 h. After the mixture was cooled to room temperature, a supersaturated aqueous sodium carbonate solution was added dropwise to complete the reaction, and the mixture was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and separated and purified by MPLC to obtain the target compound (0.55 g, 33%, yellow solid).

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

A target compound was prepared in a manner similar to that of Example 31-Step 2.

Step 3: N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide manufacturing

The target compound (13.2 mg, 64%, light yellow solid) was obtained in a similar manner to Example 148.

Example 150 was prepared in a manner similar to Example 149 above.

<Example 151> N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfone Preparation of amides

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

After dissolving 5-chloro-1H-indole (1 g, 6.60 mmol) in distilled water (20 mL), 3-buten-2-one (1.387 g, 19.79 mmol) and trifluoromethanesulfonic acid (10 mg, 0.066 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 16 hours. After 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 separated and purified by MPLC to obtain the target compound (0.64 g, 44%, pale yellow solid).

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

After dissolving 4-((5-chloro-1H-indol-3-yl)butan-2-one (200 mg, 0.902 mmol) prepared in step 1 in methanol (8 mL), 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.After completion of the reaction, the mixture was washed with supersaturated aqueous sodium carbonate solution and then ethyl acetate The extracted organic layer was dried over anhydrous sodium sulfate, filtered, and separated and purified by MPLC to obtain the target compound (0.2 g, 100%, pale yellow oil).

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

A target compound was prepared in a manner similar to that of Example 31-Step 2.

Step 4: N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide manufacturing

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

Example 152 was prepared in a manner similar to that of Example 151.

<Example 153> N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide

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

(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, followed by 3,4- at 100 °C. Dihydro-2H-pyran (0.40 ml, 4.47 mmol) was added slowly over 2 min and stirred at 100° C. for 2 h. After the reaction was completed, it was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.61 g, 54%).

Step 2: Preparation of 5-bromo-3-(3-bromopropyl)-1H-indole

The compound prepared in step 1 (0.31 g, 1.231 mmol) was dissolved in dichloromethane (2 ml), and then carbon tetrabromide (0.49 g, 1.477 mmol) and triphenylphosphine 0.38 g, 1.477 mmol) were added at 0° C. After addition, the mixture was stirred for 30 minutes. Thereafter, the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by MPLC to prepare the desired compound (0.29 g, 77%).

Step 3: Preparation of 3-(3-azidopropyl)-5-bromo-1H-indole

The compound prepared in step 2 (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. After the reaction was completed, it was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.54 g, 62%).

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

The compound prepared in step 3 (0.1 g, 0.358 mmol) was dissolved in tetrahydrofuran (3 ml and water (0.2 ml), and triphenylphosphine (0.47 g, 1.791 mmol) was added thereto, followed by 16 at room temperature. After completion of the reaction, the mixture was diluted with dichloromethane and washed with water and brine.The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.075 g). , 83%) was prepared.

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

After dissolving the compound (0.094 g, 0.299 mmol) prepared in step 1 of Example 31 in dichloromethane (1 ml), the compound prepared in step 4 (0.075 g, 0.299 mmol) and potassium carbonate (0.124 g) , 0.896 mmol) was added, followed by stirring at room temperature for 1 hour. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.12 g, 80 %).

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

After dissolving the compound prepared in step 5 (0.06 g, 0.113 mmol) in ethanol (1.5 ml), potassium carbonate (0.031 g, 0.226 mmol) and piperazine (0.02 g, 0.339 mmol) were added, and 70 It was stirred at ℃ for 16 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, diluted with dichloromethane, and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by the addition of aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.032 g, 53% yellow solid).

Examples 154 to 156 were prepared in a manner similar to that of Example 153.

Example 157 was prepared in a manner similar to that of Example 147.

Examples 158 and 159 were prepared in a manner similar to that of Example 31 above.

Examples 160 and 161 were prepared in a manner similar to that of Example 148.

Examples 162 and 163 were prepared in a manner similar to Example 31 above.

Examples 164 and 165 were prepared in a manner similar to that of Example 153.

Example 166 was prepared in a manner similar to that of Example 148.

<Example 167> N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzene sulfonamide manufacturing

Step 1: Preparation of (cyanomethyl)triphenylphosphonium

After dissolving 2-bromoacetonitrile (1.328 mL, 19.06 mmol) in dichloromethane (80 mL), triphenylphosphine (5 g, 19.06 mmol) was added at room temperature, and the reaction mixture was stirred for 6 hours. did. After completion of the reaction, the mixture was washed with diethyl ether without further purification to obtain the target compound (7 g, 96%, white solid).

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

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

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

After dissolving the compound (E)-3-(5-chloro-1H-indazol-3-yl)acrylonitrile (300 mg, 1.473 mmol) prepared in step 2 in ether (5 mL), -78 LAH (168 mg, 4.42 mmol) was added at °C. The temperature of the reaction mixture was slowly raised to room temperature and stirred for 2 hours. LAH (112 mg, 2.95 mmol) was additionally added to quench the reaction. After completion of the reaction, the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure, and then separated and purified by MPLC to obtain the target compound (200 mg, 65%, yellow oil).

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

The target compound (75 mg, 18%, white solid) was obtained in a manner similar to Example 31-Step 2 above.

Step 5: Preparation of N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzene sulfonamide

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

Examples 168 to 170 were prepared in a manner similar to that of Example 167.

<Example 171> (R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl) ) propoxy) benzenesulfonamide

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

After dissolving the compound (0.41 g, 1.026 mmol) prepared in step 1 of Example 92 in dimethylformamide (3.4 ml), (R)-2-(chloromethyl)oxirane (0.095 g, 1.026 mmol) After adding potassium percarbonate (0.21 g, 1.539 mmol), the mixture was stirred at 60° C. for 16 hours. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.16 g, 37 %).

Step 2: (R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)pro Poxy) Preparation of benzenesulfonamide

The compound prepared in step 1 (0.083 g, 0.198 mmol) was dissolved in acetone (1 ml), and 1-methylpiperazine (0.19 g, 1.981 mmol) and potassium carbonate (0.274 g, 1.981 mmol) were added. Then, the mixture was stirred at 80 °C for 16 hours. After the reaction was completed, it was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by addition of an aqueous sodium hydrogen carbonate solution to prepare the desired compound (0.030 g, 30% yellow solid).

Examples 172 to 174 were prepared in a manner similar to that of Example 171.

Examples 175 and 176 were prepared in a manner similar to that of Example 148 above.

<Example 177> N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl) 4- (3- (4-methylpiperazin-1-yl) ) Preparation of propoxy)benzene sulfonamide

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

Using the compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methanamine prepared in a similar manner to the reference [WO2006/89053], Example 31- The target compound was obtained in a manner similar to step 2.

Step 2: N-((6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)4-(3-(4-methylpiperazin-1-yl)pro Preparation of oxy)benzene sulfonamide

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

Example 178 was prepared in a manner similar to that of Example 177.

Examples 179 and 180 were prepared in a manner similar to Example 85 above.

<Example 181> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl) ) Preparation of propoxy)benzene sulfonamide

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

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 mixed with 1, After dissolving in 2-dichloroethane (40 ml), PdCl ₂ ·(CH ₃ CN) ₂ (0.0340 g, 0.132 mmol) was added, followed by stirring under reflux for 3 hours under a nitrogen stream. After completion of the reaction, the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and separated and purified by MPLC to obtain the target compound (1.02 g, 88%, white solid).

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

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

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

The target compound was obtained in a manner similar to that of Example 31-Step 2

Step 4: N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)prop Preparation of oxy)benzene sulfonamide

The target compound (17.2 mg, 33%, light yellow solid) was obtained in a similar manner to Example 148.

Example 182 was prepared in a manner similar to that of Example 181.

Examples 183 and 184 were prepared in a manner similar to that of Example 153.

<Example 185> Preparation of N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyridin-4-yloxy)propyl)benzenesulfonamide

Example 90 - Compound 4-(3-bromopropyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide prepared in a similar manner to Step 1 and Step 2 was used to obtain the target compound (18.5 mg, 60%, white solid) in a similar manner to Example 148.

Example 186 was prepared in a manner similar to that of Example 185.

Examples 187 to 190 were prepared in a manner similar to that of Example 177.

The compound names, chemical structural formulas, ¹ H NMR analysis results and MS analysis results of Examples 1 to 190 are summarized in Table 1 below.

Example rescue compound name ¹ H NMR, MS One

N-(3-([1,1'-biphenyl]-4-yl)propyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.78 - 7.74 (m, 2H), 7.59 - 7.54 (m, 2H), 7.50 - 7.46 (m, 2H), 7.46 - 7.39 (m, 2H), 7.36 - 7.30 (m, 1H), 7.16 (d, J = 8.2 Hz, 2H), 6.98 - 6.92 (m, 2H), 4.24 (t, J = 6.3 Hz, 1H), 4.00 (t, J = 6.5 Hz, 2H) ), 2.99 (dd, J = 13.4, 6.8 Hz, 2H), 2.69 - 2.62 (m, 2H), 1.80 (ddt, J = 14.4, 12.7, 6.8 Hz, 4H), 1.47 (dd, J = 14.8, 7.5) Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H); 424 [M+H] ⁺ 2

4-Butoxy-N-(3-(4-isopropylpiperazin-1-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.77 (d, J = 8.9 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 4.02 (t, J = 6.5 Hz, 2H), 3.04 ( t, J = 5.6 Hz, 2H), 2.65-2.40 (m, 9H), 2.39 (t, J = 5.8 Hz, 2H), 1.81-1.77 (m, 2H), 1.63-1.61 (m, 2H), 1.51 -1.48 (m, 2H), 1.06 (d, J = 6.5 Hz, 6H), 0.99 (t, J = 7.4 Hz, 3H); 398.3[M+H] ⁺ 3

4-Butoxy-N-(3-(4-chlorophenyl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.75 (d, J = 8.9 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.95 ( d, J = 8.9 Hz, 2H), 4.02 (t, J = 6.5 Hz, 2H), 2.93 (t, J = 6.8 Hz, 2H), 2.58 (t, J = 7.4 Hz, 2H), 1.82-1.74 ( m, 4H), 1.53-1.48 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H); 382.2[M+H] ⁺ 4

4-Butoxy-N-(3-cyclohexylpropyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.77 (d, J = 9.0 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 4.18 (t, J = 6.2 Hz, 1H, NH), 4.02 (t, J = 6.5 Hz, 2H), 2.93-2.88 (m, 2H), 1.79-1.77 (m, 2H), 1.64-1.46 (m, 11H), 1.13-1.10 (m, 6H), 0.99 ( t, J = 7.4 Hz, 3H); 354.3[M+H] ⁺ 5

4-Butoxy-N-(3-(pyridin-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.44 (d, J = 3.7 Hz, 1H), 8.38 (s, 1H), 7.76 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 7.8) Hz, 1H), 7.20 (dd, J = 7.6, 4.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 4.41 (t, J = 6.2 Hz, 1H, NH), 4.02 (t, J) = 6.5 Hz, 2H), 2.96 (dd, J = 13.4, 6.8 Hz, 2H), 2.63 (t, J = 7.5 Hz, 2H), 1.82-1.77 (m, 4H), 1.53-1.47 (m, 2H) , 0.98 (t, J = 7.4 Hz, 3H); 349[M+H] ⁺ 6

4-Butoxy-N-(3-morpholinopropyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.76 (d, J = 8.9 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 4.01 (t, J = 6.5 Hz, 2H), 3.71 ( t, J = 4.6 Hz, 4H), 3.06 (t, J = 5.8 Hz, 2H), 2.41 (t, J = 5.7 Hz, 4H), 1.81-1.77 (m, 2H), 1.66-1.61 (m, 2H) ), 1.56-1.47 (m, 4H), 0.99 (t, J = 7.4 Hz, 3H); 357[M+H] ⁺ 7

4-Butoxy-N-(4-morpholinophenethyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.74 - 7.69 (m, 2H), 7.02 - 6.96 (m, 2H), 6.96 - 6.91 (m, 2H), 6.84 - 6.80 (m, 2H), 4.24 - 4.14 (m, 1H), 4.01 (t, J = 6.5 Hz, 2H), 3.92 - 3.80 (m, 4H), 3.16 (dd, J = 13.4, 6.9 Hz, 2H), 3.14 - 3.09 (m, 4H) , 2.68 (t, J = 6.8 Hz, 2H), 1.84 - 1.74 (m, 2H), 1.48 (dd, J = 15.0, 7.5 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 419.16 [M+H] ⁺ 8

4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoic acid ¹ H NMR (400 MHz, CDCl ₃ ) δ7.95 (d, J = 7.9 Hz, 2H), 7.73 (d, J = 8.6 Hz, 2H), 7.20 (d, J = 7.5 Hz, 2H), 6.94 ( d, J = 8.8 Hz, 2H), 4.61 (s, 1H), 4.01 (t, J = 6.5 Hz, 2H), 3.25 (dd, J = 12.4, 5.9 Hz, 2H), 2.86 (t, J = 6.4) Hz, 2H), 1.78 (dd, J = 14.5, 6.7 Hz, 2H), 1.50 (dt, J = 22.4, 7.6 Hz, 2H), 0.98 (t, J = 7.3 Hz, 3H); 378[M+H] ⁺ 9

methyl 4-(2-(4-butoxyphenylsulfonamido)ethyl)benzoate ¹ H NMR (400 MHz, CDCl ₃ ) δ7.94 (d, J = 8.2 Hz, 2H), 7.77 - 7.66 (m, 2H), 7.16 (d, J = 8.2 Hz, 2H), 6.97 - 6.88 (m) , 2H), 4.22 (t, J = 6.3 Hz, 1H), 4.01 (t, J = 6.5 Hz, 2H), 3.91 (s, 3H), 3.24 (dd, J = 13.4, 6.8 Hz, 2H), 2.83 (t, J = 6.9 Hz, 2H), 1.84 - 1.75 (m, 2H), 1.48 (dd, J = 14.8, 7.4 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 392[M+H] ⁺ 10

N-(2-(4-benzylpiperidin-1-yl)ethyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.77 (d, J = 8.9 Hz, 2H), 7.28 (d, J = 7.1 Hz, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.12 ( d, J = 7.0 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 5.20 (s, 1H), 4.00 (t, J = 6.5 Hz, 2H), 2.94 (d, J = 5.6 Hz, 2H), 2.53 (dd, J = 16.1, 9.2 Hz, 4H), 2.33 (t, J = 5.7 Hz, 2H), 1.88 - 1.74 (m, 4H), 1.57 - 1.44 (m, 5H), 1.21 - 1.08 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H); 431[M+H] ⁺ 11

4-Butoxy-N-(3-hydroxy-3-phenylpropyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.83 - 7.75 (m, 2H), 7.32 (dt, J = 12.9, 4.4 Hz, 2H), 7.28 - 7.23 (m, 3H), 7.00 - 6.91 (m, 2H), 5.05 - 4.99 (m, 2H), 4.81 (td, J = 6.3, 3.2 Hz, 2H), 4.02 (t, J = 6.5 Hz, 2H), 3.27 - 2.98 (m, 2H), 1.86 (dt) , J = 9.5, 4.7 Hz, 2H), 1.83 - 1.73 (m, 2H), 1.54 - 1.46 (m, 3H), 0.99 (t, J = 7.4 Hz, 3H); 364[M+H] ⁺ 12

4-Butoxy-N-(3-oxo-3-phenylpropyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.88 (d, J = 7.2 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 ( t, J = 7.7 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 5.15 (t, J = 6.8 Hz, 1H), 4.00 (t, J = 6.5 Hz, 2H), 3.34 (dd, J = 11.9, 5.8 Hz, 2H), 3.25 - 3.16 (m, 2H), 1.85 - 1.72 (m, 2H), 1.53 - 1.45 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H); 362[M+H] ⁺ 13

4-Butoxy-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.81 - 7.72 (m, 2H), 6.97 - 6.89 (m, 2H), 5.75 (t, J = 6.8 Hz, 1H), 4.01 (t, J = 6.5 Hz) , 2H), 3.33 (dd, J = 9.1, 5.1 Hz, 4H), 2.86 (dd, J = 12.4, 6.6 Hz, 2H), 2.34 (t, J = 8.1 Hz, 2H), 2.05 - 1.95 (m, 2H), 1.83 - 1.75 (m, 2H), 1.69 (dt, J = 12.2, 6.2 Hz, 2H), 1.49 (dt, J = 14.7, 7.5 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H) ); 355[M+H] ⁺ 14

4-(3-(dimethylamino)propoxy)-N-phenethylbenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.76 - 7.67 (m, 2H), 7.31 - 7.19 (m, 3H), 7.10 - 7.01 (m, 2H), 6.99 - 6.90 (m, 2H), 4.27 ( t, J = 6.3 Hz, 1H), 4.08 (t, J = 6.4 Hz, 2H), 3.21 (q, J = 6.8 Hz, 2H), 2.76 (t, J = 6.9 Hz, 2H), 2.48 (t, J = 7.1 Hz, 2H), 2.28 (s, 6H), 2.05 - 1.92 (m, 2H); 363[M+H] ⁺ 15

4-(3-(dimethylamino)propoxy)-N-(3-phenylpropyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.78 - 7.73 (m, 2H), 7.29 - 7.21 (m, 2H), 7.21 - 7.15 (m, 1H), 7.11 - 7.05 (m, 2H), 6.99 - 6.93 (m, 2H), 4.31 (t, J = 6.2 Hz, 1H), 4.08 (t, J = 6.4 Hz, 2H), 2.96 (dd, J = 13.4, 6.8 Hz, 2H), 2.65 - 2.57 (m) , 2H), 2.49 (t, J = 7.1 Hz, 2H), 2.28 (s, 6H), 2.04 - 1.95 (m, 2H), 1.79 (dt, J = 14.2, 7.0 Hz, 2H); 377[M+H] ⁺ 16

methyl 4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoate ¹ H NMR (400 MHz, CDCl ₃ ) δ7.96 - 7.92 (m, 2H), 7.75 - 7.67 (m, 2H), 7.16 (d, J = 8.3 Hz, 2H), 6.99 - 6.89 (m, 2H) , 4.27 (t, J = 6.2 Hz, 1H), 4.08 (t, J = 6.4 Hz, 2H), 3.91 (s, 3H), 3.23 (q, J = 6.8 Hz, 2H), 2.83 (t, J = 6.9 Hz, 2H), 2.48 (t, J = 7.1 Hz, 2H), 2.28 (s, 6H), 2.03 - 1.94 (m, 2H); 421[M+H] ⁺ 17

4-(2-(4-(3-(dimethylamino)propoxy)phenylsulfonamido)ethyl)benzoic acid ¹ H NMR (400 MHz, CDCl ₃ ) δ7.56 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.9 Hz, 2H), 6.87 (d, J = 8.1 Hz, 2H), 6.58 ( d, J = 8.9 Hz, 2H), 4.28 (dd, J = 12.3, 4.9 Hz, 1H), 4.11 - 4.00 (m, 2H), 3.56 - 3.49 (m, 2H), 3.06 - 2.97 (m, 2H) , 2.68 (s, 2H), 2.66 (s, 6H), 2.13 - 2.07 (m, 2H); 407[M+H] ⁺ 18

4-(3-(dimethylamino)propoxy)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.82 - 7.73 (m, 2H), 6.98 - 6.93 (m, 2 H), 5.77 (t, J = 6.8 Hz, 1H), 4.07 (t, J = 6.4) Hz, 2H), 3.33 (dd, J = 9.4, 4.9 Hz, 4H), 2.85 (dd, J = 12.4, 6.6 Hz, 2H), 2.45 (t, J = 7.1 Hz, 2H), 2.35 (d, J) = 7.9 Hz, 2H), 2.25 (s, 6H), 2.05 - 1.91 (m, 4H), 1.69 (dt, J = 12.3, 6.1 Hz, 2H) ; 384[M+H] ⁺ 19

4-Butoxy-N-(3-(naphthalen-1-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92-7.83 (m, 2H), 7.74 (d, J = 38.9 Hz, 2H), 7.71 (d, J = 8.5 Hz, 1H), 7.50-7.46 (m, 2H), 7.35 (dd, J = 8.1, 7.0 Hz, 1H), 7.22 (d, J = 6.8 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 4.27 (t, J = 6.1 Hz, 1H, NH), 4.01 (t, J = 6.5 Hz, 2H), 3.09-3.02 (m, 4H), 1.95-1.88 (m, 2H), 1.83-1.76 (m, 2H), 1.52-1.48 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H); 398[M+H] ⁺ 20

N-(3-(1H-indol-3-yl)propyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.92 (s, 1H), 7.75 - 7.69 (m, 2H), 7.49 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H) ), 7.22 - 7.15 (m, 1H), 7.12 - 7.05 (m, 1H), 6.95 - 6.90 (m, 3H), 4.25 - 4.18 (m, 1H), 4.00 (t, J = 6.5 Hz, 2H), 3.01 (dd, J = 13.3, 6.8 Hz, 2H), 2.77 (t, J = 7.2 Hz, 2H), 1.91 - 1.83 (m, 2H), 1.83 - 1.72 (m, 2H), 1.48 (dd, J = 14.8, 7.5 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 387.01[M+H] ⁺ 21

N-(3-(1H-indol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.08 (s, 1H), 7.75 - 7.69 (m, 2H), 7.49 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H) ), 7.22 - 7.15 (m, 1H), 7.12 - 7.05 (m, 1H), 6.95 - 6.90 (m, 3H), 4.25 - 4.18 (m, 1H), 4.00 (t, J = 6.5 Hz, 2H), 3.01 (dd, J = 13.3, 6.8 Hz, 2H), 2.77 (t, J = 7.2 Hz, 2H), 1.91 - 1.83 (m, 2H), 1.83 - 1.72 (m, 2H), 1.48 (dd, J = 14.8, 7.5 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 387.01[M+H] ⁺ 22

N-(3-(1H-indol-3-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (s, 1H), 7.74 - 7.69 (m, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H) , 7.21 - 7.16 (m, 1H), 7.11 - 7.06 (m, 1H), 6.95 - 6.90 (m, 2H), 6.80 (d, J = 2.3 Hz, 1H), 4.25 - 4.18 (m, 1H), 4.09 (t, J = 6.3 Hz, 2H), 2.99 (dd, J = 13.1, 6.7 Hz, 2H), 2.74 (t, J = 7.1 Hz, 2H), 2.48 (t, J = 7.0 Hz, 2H), 2.28 (s, 6H), 1.99 (dt, J = 13.4, 6.7 Hz, 2H), 1.85 (dt, J = 14.1, 7.0 Hz, 2H); 416[M+H] ⁺ 23

N-(2-(1H-benzo[d]imidazol-2-yl)ethyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.74 - 7.68 (m, 2H), 7.48 (s, 2H), 7.24 - 7.18 (m, 2H), 6.97 - 6.90 (m, 2H), 4.03 (t, J = 6.4 Hz, 2H), 3.38 - 3.34 (m, 2H), 3.05 (d, J = 7.1 Hz, 2H), 1.78 (dd, J = 14.8, 6.7 Hz, 2H), 1.54 (dq, J = 14.8, 7.4 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H); 374[M+H] ⁺ 24

N-(2-(1H-indol-3-yl)ethyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.00 (s, 1H), 7.69 - 7.64 (m, 2H), 7.42 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 8.2 Hz, 1H) ), 7.19 (t, J = 7.2 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.99 (d, J = 2.3 Hz, 1H), 6.90 - 6.84 (m, 2H), 4.28 (t) , J = 6.1 Hz, 1H), 3.99 (t, J = 6.5 Hz, 2H), 3.28 (q, J = 6.5 Hz, 2H), 2.94 (t, J = 6.6 Hz, 2H), 1.84 - 1.73 (m) , 2H), 1.48 (dd, J = 14.8, 7.4 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 373[M+H] ⁺ 25

N-(2-(1H-indol-2-yl)ethyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.00 (s, 1H), 7.75 - 7.67 (m, 2H), 7.51 (d, J = 7.7 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H) ), 7.14 (dd, J = 11.0, 4.1 Hz, 1H), 7.09 (dd, J = 10.9, 4.0 Hz, 1H), 6.96 - 6.88 (m, 2H), 6.21 (s, 1H), 4.43 (t, J = 6.3 Hz, 1H), 4.01 (t, J = 6.5 Hz, 2H), 3.28 (q, J = 6.4 Hz, 2H), 2.96 (t, J = 6.4 Hz, 2H), 1.84 - 1.75 (m, 2H), 1.57 - 1.44 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H); 373[M+H] ⁺ 26

N-(3-(1H-indol-3-yl)propyl)-4-(isopentyloxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.92 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.35 (d, J = 8.2) Hz, 1H), 7.19 (t, J = 7.1 Hz, 1H), 7.09 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 2.1 Hz, 1H), 6.92 (d, J = 8.9 Hz, 2H), 4.22 (t, J = 6.2 Hz, 1H), 4.03 (t, J = 6.6 Hz, 2H), 3.01 (dd, J = 13.3, 6.7 Hz, 2H), 2.77 (t, J = 7.2 Hz, 2H), 1.91 - 1.79 (m, 3H), 1.70 (q, J = 6.7 Hz, 2H), 0.98 (s, 3H), 0.97 (s, 3H); 401[M+H] ⁺ 27

N-(3-(1H-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.92 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.35 (d, J = 8.1) Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 6.95 (s, 1H), 6.92 (d, J = 8.9 Hz, 2H), 4.21 ( t, J = 6.2 Hz, 1H), 3.99 (t, J = 6.5 Hz, 2H), 3.01 (dd, J = 13.3, 6.8 Hz, 2H), 2.77 (t, J = 7.1 Hz, 2H), 1.88 ( dd, J = 14.2, 7.1 Hz, 2H), 1.80 (dd, J = 14.6, 6.7 Hz, 2H), 1.49 - 1.34 (m, 4H), 0.94 (t, J = 7.1 Hz, 3H); 401[M+H] ⁺ 28

N-(3-(1H-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.75 - 7.66 (m, 2H), 7.50 (s, 2H), 7.27 - 7.17 (m, 2H), 7.00 (d, J = 8.9 Hz, 2H), 4.03 ( t, J = 6.4 Hz, 2H), 2.92 (t, J = 7.0 Hz, 4H), 2.06 - 1.96 (m, 2H), 1.83 - 1.69 (m, 2H), 1.52 (dt, J = 14.7, 7.5 Hz) , 2H), 1.01 (t, J = 7.4 Hz, 3H); 388[M+H] ⁺ 29

4-Butoxy-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.88 (s, 1H), 7.70 - 7.63 (m, 2H), 7.23 - 7.18 (m, 1H), 6.97 (d, J = 2.4 Hz, 1H), 6.91 - 6.86 (m, 1H), 6.80 - 6.71 (m, 2H), 4.45 (s, 1H), 4.27 (t, J = 6.3 Hz, 1H), 4.00 (t, J = 6.5 Hz, 2H), 3.24 ( dd, J = 12.9, 6.5 Hz, 2H), 2.87 (t, J = 6.6 Hz, 2H), 1.80 (dd, J = 14.4, 7.2 Hz, 2H), 1.48 (dd, J = 14.8, 7.5 Hz, 2H) ), 0.99 (t, J = 7.4 Hz, 3H); 389[M+H] ⁺ 30

N-(3-(1H-indol-3-yl)propyl)-4-(3-morpholinopropoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.02 (s, 1H), 7.75 - 7.69 (m, 2H), 7.49 (d, J = 7.1 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H) ), 7.19 (t, J = 7.0 Hz, 1H), 7.12 - 7.06 (m, 1H), 6.96 - 6.88 (m, 3H), 4.23 (t, J = 6.3 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.79 - 3.66 (m, 4H), 3.01 (dd, J = 13.3, 6.8 Hz, 2H), 2.77 (t, J = 7.1 Hz, 2H), 2.58 - 2.50 (m, 2H), 2.48 - 2.46 (m, 4H), 2.00 (dd, J = 13.6, 6.6 Hz, 2H), 1.87 (dt, J = 14.2, 7.0 Hz, 2H); 458[M+H] ⁺ 31

N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.10 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.1) Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 8.8 Hz, 3H), 4.24 (t, J = 6.3 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.01 (dd, J = 13.3, 6.7 Hz, 2H), 2.76 (t, J = 7.3 Hz, 2H), 2.69 - 2.36 (m, 10H), 2.31 (s, 3H), 2.05 - 1.93 (m, 2H), 1.90 - 1.80 (m, 2H); 471[M+H] ⁺ 32

N-(3-(1H-indol-1-yl)propyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.72 - 7.64 (m, 2H), 7.62 (d, J = 7.9 Hz, 1H), 7.28 - 7.26 (m, 1H), 7.23 - 7.15 (m, 1H) , 7.13 - 7.07 (m, 1H), 7.05 (d, J = 3.1 Hz, 1H), 6.95 - 6.86 (m, 2H), 6.53 - 6.47 (m, 1H), 4.24 - 4.13 (m, 3H), 4.00 (t, J = 6.5 Hz, 2H), 2.88 (dd, J = 12.9, 6.4 Hz, 2H), 2.10 - 1.95 (m, 2H), 1.84 - 1.74 (m, 2H), 1.54 - 1.40 (m, 2H) ), 0.99 (t, J = 7.4 Hz, 3H); 387[M+H] ⁺ 33

N-(3-(1H-Benzo[d]imidazol-1-yl)propyl)-4-butoxybenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.92 (s, 1H), 7.83 - 7.78 (m, 1H), 7.75 - 7.71 (m, 2H), 7.39 - 7.34 (m, 1H), 7.29 (dt, J = 5.3, 3.5 Hz, 2H), 6.96 - 6.90 (m, 2H), 4.44 (dd, J = 8.1, 7.2 Hz, 1H), 4.31 (t, J = 6.7 Hz, 2H), 4.00 (t, J) = 6.5 Hz, 2H), 2.91 (dd, J = 12.8, 6.4 Hz, 2H), 2.13 - 2.04 (m, 2H), 1.79 (dt, J = 14.3, 6.4 Hz, 2H), 1.49 (dt, J =) 14.7, 7.5 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H); 388[M+H] ⁺ 34

N-(3-(1H-indol-3-yl)propyl)-4-(2-(piperidin-1-yl)ethoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.05 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 8.2) Hz, 1H), 7.21 - 7.15 (m, 1H), 7.12 - 7.07 (m, 1H), 6.92 (d, J = 8.9 Hz, 3H), 4.22 (d, J = 6.4 Hz, 1H), 4.17 - 4.08 (m, 2H), 3.00 (dd, J = 13.3, 6.8 Hz, 2H), 2.83 - 2.72 (m, 4H), 2.53 - 2.50 (m, 4H), 1.86 (dt, J = 14.4, 7.1 Hz, 2H) ), 1.61 (d, J = 5.4 Hz, 4H), 1.45 (s, 2H);442[M+H] ⁺ 35

N-(3-(1H-indol-3-yl)propyl)-4-(3-(diethylamino)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.22 (s, 1H), 7.76 - 7.68 (m, 2H), 7.49 (d, J = 7.7 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H) ), 7.21 - 7.15 (m, 1H), 7.11 - 7.06 (m, 1H), 6.96 - 6.89 (m, 2H), 6.87 (d, J = 2.2 Hz, 1H), 4.28 (t, J = 6.2 Hz, 1H), 4.08 (t, J = 6.2 Hz, 2H), 3.00 (q, J = 6.7 Hz, 2H), 2.75 (t, J = 7.2 Hz, 2H), 2.71 - 2.46 (m, 6H), 2.05 - 1.94 (m, 2H), 1.89 - 1.80 (m, 2H), 1.08 (t, J = 7.1 Hz, 6H); 444[M+H] ⁺ 36

N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-ethylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.12 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.7 Hz, 1H), 7.35 (d, J = 8.1) Hz, 1H), 7.19 (t, J = 7.1 Hz, 1H), 7.09 (t, J = 7.0 Hz, 1H), 6.92 (d, J = 8.8 Hz, 3H), 4.24 (t, J = 6.4 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.3, 6.7 Hz, 2H), 2.76 (t, J = 7.2 Hz, 2H), 2.53 - 2.44 (m, 12H), 2.00 (dt, J = 13.3, 6.5 Hz, 2H), 1.90 - 1.78 (m, 2H), 1.11 (t, J = 7.0 Hz, 3H); 485[M+H] ⁺ 37

N-(2-(1H-Benzo[d]imidazol-2-yl)ethyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.77 (d, J = 8.9 Hz, 2H), 7.26 - 7.22 (m, 4H), 6.93 (d, J = 8.9 Hz, 2H), 5.73 - 5.67 (m) , 1H), 4.08 (t, J = 6.4 Hz, 2H), 3.47 (dd, J = 11.9, 6.0 Hz, 2H), 3.07 - 3.01 (m, 2H), 2.50 - 2.44 (m, 2H), 2.27 ( s, 6H), 1.99 (dd, J = 13.7, 6.7 Hz, 2H); 403 [M+H] ⁺ 38

N-(2-(1H-indol-2-yl)ethyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.06 (s, 1H), 7.75 - 7.68 (m, 2H), 7.51 (d, J = 7.7 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H) ), 7.17 - 7.11 (m, 1H), 7.11 - 7.05 (m, 1H), 6.97 - 6.90 (m, 2H), 6.20 (d, J = 1.2 Hz, 1H), 4.48 (s, 1H), 4.07 ( t, J = 6.4 Hz, 2H), 3.27 (dd, J = 12.6, 6.3 Hz, 2H), 2.95 (t, J = 6.4 Hz, 2H), 2.47 (t, J = 7.1 Hz, 2H), 2.27 ( s, 6H), 2.05 - 1.94 (m, 2H); 402[M+H] ⁺ 39

N-(3-(1H-indol-1-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.70 - 7.64 (m, 2H), 7.62 (d, J = 7.9 Hz, 1H), 7.28 - 7.26 (m, 1H), 7.21 - 7.15 (m, 1H) , 7.13 - 7.06 (m, 1H), 7.05 (d, J = 3.2 Hz, 1H), 6.96 - 6.88 (m, 2H), 6.50 - 6.45 (m, 1H), 4.27 - 4.15 (m, 3H), 4.06 (t, J = 6.4 Hz, 2H), 2.88 (dd, J = 13.0, 6.5 Hz, 2H), 2.46 (t, J = 6.9 Hz, 2H), 2.26 (s, 6H), 2.00 (td, J = 13.4, 6.8 Hz, 4H); 416[M+H] ⁺ 40

N-(3-(1H-Benzo[d]imidazol-1-yl)propyl)-4-(3-(dimethylamino)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92 (s, 1H), 7.84 - 7.79 (m, 1H), 7.76 - 7.71 (m, 2H), 7.39 - 7.34 (m, 1H), 7.30 (dt, J) = 5.4, 3.5 Hz, 2H), 6.97 - 6.92 (m, 2H), 4.55 (d, J = 6.1 Hz, 1H), 4.31 (t, J = 6.7 Hz, 2H), 4.07 (t, J = 6.4 Hz) , 2H), 2.90 (dd, J = 12.7, 6.4 Hz, 2H), 2.46 (t, J = 7.0 Hz, 2H), 2.27 (s, 6H), 2.13 - 2.03 (m, 2H), 1.98 (dt, J = 13.5, 6.7 Hz, 2H); 417[M+H] ⁺ 41

N-(3-(1H-indol-1-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.71 - 7.65 (m, 2H), 7.62 (d, J = 7.9 Hz, 1H), 7.30 - 7.27 (m, 1H), 7.19 (dd, J = 8.1, 7.1 Hz, 1H), 7.11 (dd, J = 10.9, 4.0 Hz, 1H), 7.05 (d, J = 3.1 Hz, 1H), 6.94 - 6.89 (m, 2H), 6.48 (d, J = 3.1 Hz, 1H), 4.20 (t, J = 6.6 Hz, 2H), 4.16 (t, J = 6.5 Hz, 1H), 4.06 (t, J = 6.3 Hz, 2H), 2.88 (dd, J = 12.9, 6.5 Hz, 2H), 2.69 - 2.35 (m, 10H), 2.29 (s, 3H), 2.00 (tt, J = 9.9, 6.5 Hz, 4H); 471[M+H] ⁺ 42

N-(3-(1H-Benzo[d]imidazol-1-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.92 (s, 1H), 7.83 - 7.78 (m, 1H), 7.73 (d, J = 8.9 Hz, 2H), 7.38 - 7.34 (m, 1H), 7.32 - 7.28 (m, 2H), 6.95 (d, J = 8.9 Hz, 2H), 4.36 - 4.28 (m, 3H), 4.06 (t, J = 6.3 Hz, 2H), 2.91 (dd, J = 12.8, 6.4) Hz, 2H), 2.59 - 2.35 (m, 10H), 2.29 (s, 3H), 2.07 (dd, J = 13.1, 6.6 Hz, 2H), 2.02 - 1.94 (m, 2H); 472[M+H] ⁺ 43

N-(3-(1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl3) δ8.23 (s, 1H), 7.73 - 7.66 (m, 2H), 7.49 (d, J = 7.7 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H) , 7.19 (t, J = 7.0 Hz, 1H), 7.09 (t, J = 7.0 Hz, 1H), 6.94 - 6.89 (m, 2H), 6.88 (t, J = 2.6 Hz, 1H), 4.23 (t, J = 6.1 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.3, 6.7 Hz, 2H), 2.75 (t, J = 7.1 Hz, 2H), 2.62 - 2.32 ( m, 6H), 2.07 - 1.94 (m, 2H), 1.90 - 1.79 (m, 2H), 1.69 - 1.60 (m, 4H), 1.47 (dd, J = 16.1, 10.0 Hz, 2H); 456[M+H] ⁺ 44

N-(3-(1H-indol-3-yl)propyl)-4-(3-(2-oxopyrrolidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.70 (s, 1H), 7.74 - 7.67 (m, 2H), 7.49 (d, J = 7.5 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H) ), 7.19 - 7.13 (m, 1H), 7.11 - 7.05 (m, 1H), 6.91 (d, J = 7.1 Hz, 2H), 6.64 (s, 1H), 4.25 - 4.18 (m, 1H), 4.04 ( t, J = 5.1 Hz, 2H), 3.54 (t, J = 6.4 Hz, 2H), 3.46 (t, J = 6.9 Hz, 2H), 2.98 (dd, J = 12.2, 5.8 Hz, 2H), 2.74 ( t, J = 6.9 Hz, 2H), 2.40 (t, J = 8.0 Hz, 2H), 2.12 - 1.98 (m, 4H), 1.91 - 1.82 (m, 2H); 456[M+H] ⁺ 45

N-(3-(1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.13 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.7 Hz, 1H), 7.35 (d, J = 8.1) Hz, 1H), 7.19 (t, J = 7.1 Hz, 1H), 7.09 (t, J = 7.1 Hz, 1H), 6.92 (d, J = 8.9 Hz, 2H), 4.26 (t, J = 6.4 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.2, 6.7 Hz, 2H), 2.90 (t, J = 4.9 Hz, 4H), 2.76 (t, J = 7.2 Hz, 2H), 2.55 - 2.48 (m, 2H), 2.45 (br, 4H), 2.07 - 1.93 (m, 2H), 1.91 - 1.79 (m, 2H); 457[M+H] ⁺ 46

4-(3-(dimethylamino)propoxy)-N-(3-(1-methyl-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.75 - 7.69 (m, 2H), 7.47 (d, J = 7.9 Hz, 1H), 7.28 - 7.26 (m, 1H), 7.21 (t, J = 7.6 Hz) , 1H), 7.08 (dd, J = 10.9, 4.0 Hz, 1H), 6.97 - 6.90 (m, 2H), 6.77 (s, 1H), 4.22 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.4 Hz, 2H), 3.72 (s, 3H), 3.00 (dd, J = 13.3, 6.7 Hz, 2H), 2.75 (t, J = 7.3 Hz, 2H), 2.46 (t, J = 7.2 Hz, 2H), 2.26 (s, 6H), 1.98 (dt, J = 13.4, 6.7 Hz, 2H), 1.89 - 1.81 (m, 2H); 430[M+H] ⁺ 47

N-(3-(1H-indol-3-yl)propyl)-4-bromobenzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.95 (s, 1H), 7.66 - 7.56 (m, 4H), 7.48 (d, J = 7.8 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H) ), 7.21 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.1 Hz, 1H), 6.95 (d, J = 2.2 Hz, 1H), 4.32 (t, J = 5.9 Hz, 1H), 3.04 (dd, J = 13.3, 6.7 Hz, 2H), 2.78 (t, J = 7.1 Hz, 2H), 1.88 (p, J = 7.1 Hz, 2H); 394[M+H] ⁺ 48

N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-isopropylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.10 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.2) Hz, 1H), 7.20 - 7.16 (m, 1H), 7.11 - 7.06 (m, 1H), 6.94 - 6.88 (m, 3H), 4.26 - 4.21 (m,1H), 4.07 (t, J = 6.3 Hz, 2H), 3.01 (dd, J = 13.4, 6.8 Hz, 2H), 2.76 (t, J = 7.4 Hz, 2H), 2.71 - 2.46 (m, 10H), 2.26 - 2.17 (m, 1H), 1.99 (dd , J = 12.5, 5.8 Hz, 2H), 1.87 (dd, J = 14.2, 7.2 Hz, 2H), 1.06 (d, J = 5.5 Hz, 6H); 499[M+H] ⁺ 49

N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.96 (s, 1H), 7.64 (d, J = 8.9 Hz, 2H), 7.29 - 7.21 (m, 1H), 6.94 (d, J = 2.1 Hz, 1H) ), 6.86 (dd, J = 7.6, 5.4 Hz, 3H), 4.32 - 4.24 (m, 1H), 4.05 (t, J = 6.2 Hz, 2H), 3.80 (s, 3H), 3.26 (dd, J = 12.8, 6.5 Hz, 2H), 2.91 (t, J = 6.5 Hz, 2H), 2.73 - 2.34 (m, 10H), 2.29 (s, 3H), 2.04 - 1.93 (m, 2H); 487[M+H] ⁺ 50

N-(2-(1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.10 (s, 1H), 7.65 (d, J = 8.9 Hz, 2H), 7.43 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 8.1) Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.88 (d, J = 8.9 Hz, 2H), 4.29 (t, J = 6.1 Hz, 1H), 4.06 (t, J = 6.3 Hz, 2H), 3.28 (dd, J = 12.8, 6.4 Hz, 2H), 2.94 (t, J = 6.6 Hz, 2H), 2.67 - 2.33 (m, 10H), 2.30 (s, 3H), 2.04 - 1.95 (m, 2H); 457[M+H] ⁺ 51

N-(2-(1H-indol-3-yl)ethyl)-4-(3-(4-isopropylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.10 (s, 1H), 7.65 (d, J = 8.9 Hz, 2H), 7.43 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 8.2) Hz, 1H), 7.23 - 7.16 (m, 1H), 7.07 (t, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.88 (d, J = 8.9 Hz, 2H), 4.29 (t, J) = 6.2 Hz, 1H), 4.06 (t, J = 6.3 Hz, 2H), 3.28 (dd, J = 12.9, 6.5 Hz, 2H), 2.94 (t, J = 6.5 Hz, 2H), 2.78 - 2.37 (m) , 10H), 2.07 - 1.95 (m, 2H), 1.16 - 0.97 (m, 6H); 485[M+H] ⁺ 52

N-(3-(1H-indol-3-yl)propyl)-4-(2-(4-methylpiperazin-1-yl)ethoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.31 (s, 1H), 7.73 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 8.1) Hz, 1H), 7.18 (t, J = 7.1 Hz, 1H), 7.09 (t, J = 7.0 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 6.87 (d, J = 2.3 Hz, 1H), 4.26 (t, J = 6.2 Hz, 1H), 4.15 (t, J = 5.6 Hz, 2H), 3.02 (dd, J = 13.3, 6.8 Hz, 2H), 2.88 (t, J = 5.6 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 2.69 - 2.39 (m, 8H), 2.32 (s, 2H), 1.83 (dd, J = 14.2, 7.1 Hz, 2H); 457[M+H] ⁺ 53

N-(3-(1H-indol-3-yl)propyl)-4-(2-(4-isopropylpiperazin-1-yl)ethoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.20 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.0) Hz, 1H), 7.22 - 7.15 (m, 1H), 7.12 - 7.06 (m, 1H), 6.92 (d, J = 8.9 Hz, 2H), 6.89 (d, J = 2.2 Hz, 1H), 4.27 - 4.20 (m, 1H), 4.15 (t, J = 5.7 Hz, 2H), 3.01 (dd, J = 13.2, 6.6 Hz, 2H), 2.86 (t, J = 5.7 Hz, 2H), 2.75 (t, J = 7.3 Hz, 2H), 2.72 - 2.39 (m, 8H), 2.25 - 2.19 (m, 1H), 1.84 (dt, J = 14.3, 7.2 Hz, 2H), 1.06 (d, J = 5.9 Hz, 6H); 485[M+H] ⁺ 54

N-(2-(2-methyl-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.96 (s, 1H), 7.61 (d, J = 8.9 Hz, 2H), 7.31 (d, J = 7.9 Hz, 1H), 7.25 (d, J = 7.5) Hz, 1H), 7.11 (t, J = 7.0 Hz, 1H), 7.02 (t, J = 7.9 Hz, 1H), 6.85 (d, J = 8.9 Hz, 2H), 4.24 (t, J = 6.2 Hz, 1H), 4.06 (t, J = 6.3 Hz, 2H), 3.21 (q, J = 6.5 Hz, 2H), 2.89 (t, J = 6.6 Hz, 2H), 2.73 - 2.37 (m, 10H), 2.34 ( s, 3H), 2.29 (s, 3H), 1.99 (dt, J = 13.4, 6.5 Hz, 2H); 471[M+H] ⁺ 55

N-(3-(1H-indol-3-yl)propyl)-4-(2-(1-methylpiperidin-4-yl)ethoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.22 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.1) Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 4.27 (t, J = 6.2 Hz, 1H), 4.05 (t, J = 6.4 Hz, 2H), 3.02 (q, J = 6.7 Hz, 2H), 2.89 (d, J = 11.7 Hz, 2H), 2.75 (t, J = 7.3 Hz, 2H) , 2.30 (s, 3H), 1.97 (t, J = 11.6 Hz, 2H), 1.85 (dd, J = 14.3, 7.1 Hz, 2H), 1.76 (dt, J = 13.4, 6.7 Hz, 4H), 1.45 - 1.34 (m, 2H); 456[M+H] ⁺ 56

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.10 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.28 - 7.23 (m, 2H), 7.10 (dd, J = 9.6, 2.4 Hz) , 1H), 6.99 - 6.88 (m, 4H), 4.25 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.3, 6.8 Hz, 2H) , 2.70 (t, J = 7.3 Hz, 2H), 2.65 - 2.35 (m, 10H), 2.30 (s, 3H), 2.04 - 1.95 (m, 2H), 1.90 - 1.77 (m, 2H); 489[M+H] ⁺ 57

3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole ¹ H NMR (400 MHz, CDCl ₃ ) δ8.03 (s, 1H), 7.74 (d, J = 8.9 Hz, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.1) Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.08 (t, J = 7.1 Hz, 1H), 7.01 (t, J = 7.1 Hz, 2H), 6.94 (d, J = 2.2 Hz, 1H), 4.11 (t, J = 6.3 Hz, 2H), 3.91 (d, J = 11.3 Hz, 2H), 2.82 - 2.72 (m, 1H), 2.68 - 2.32 (m, 12H), 2.31 (s, 3H) ), 2.09 (dd, J = 18.5, 7.0 Hz, 2H), 2.01 (dd, J = 13.8, 6.9 Hz, 2H), 1.88 (ddd, J = 25.3, 12.5, 3.8 Hz, 2H); 497[M+H] ⁺ 58

N-(3-(2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.87 (s, 1H), 7.66 (d, J = 8.9 Hz, 2H), 7.36 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 1.1) Hz, 1H), 7.10 (t, J = 6.9 Hz, 1H), 7.04 (dd, J = 10.8, 4.0 Hz, 1H), 6.90 (d, J = 8.9 Hz, 2H), 4.17 (t, J = 6.1) Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 2.95 (dd, J = 13.3, 6.8 Hz, 2H), 2.69 (t, J = 7.2 Hz, 2H), 2.55 - 2.37 (m, 10H) ), 2.32 (s, 3H), 2.29 (s, 3H), 1.99 (dt, J = 13.4, 6.6 Hz, 2H), 1.78 (p, J = 7.0 Hz, 2H); 485[M+H] ⁺ 59

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.06 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.28 - 7.23 (m, 1H), 7.10 (dd, J = 9.6, 2.4 Hz) , 1H), 7.00 (s, 1H), 6.92 (d, J = 8.9 Hz, 2H), 4.25 (t, J = 6.1 Hz, 1H), 3.99 (t, J = 6.5 Hz, 2H), 3.01 (dd) , J = 13.3, 6.7 Hz, 2H), 2.88 (d, J = 11.0 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.28 (s, 3H), 1.93 (t, J = 10.4 Hz) , 2H), 1.88 - 1.78 (m, 4H), 1.72 (d, J = 9.8 Hz, 2H), 1.44 - 1.36 (m, 2H), 1.36 - 1.24 (m, 3H); 488[M+H] ⁺ 60

N-(3-(1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.04 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.1) Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.09 (t, J = 7.1 Hz, 1H), 6.94 (d, J = 2.1 Hz, 1H), 6.91 (d, J = 8.9 Hz, 2H), 4.27 (t, J = 6.1 Hz, 1H), 3.99 (t, J = 6.5 Hz, 2H), 3.01 (dd, J = 13.3, 6.7 Hz, 2H), 2.87 (d, J = 11.3 Hz, 2H), 2.77 (t, J = 7.3 Hz, 2H), 2.27 (s, 3H), 1.98 - 1.88 (m, 2H), 1.88 - 1.84 (m, 2H), 1.84 - 1.77 (m, 2H), 1.71 (d, J = 9.3 Hz, 2H), 1.45 - 1.35 (m, 2H), 1.31 - 1.20 (m, 2H); 470[M+H] ⁺ 61

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.13 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.24 (s, 1H), 7.10 (dd, J = 9.6, 2.4 Hz, 1H) ), 6.97 (s, 1H), 6.96 - 6.89 (m, 3H), 4.26 (s, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 12.7, 6.5 Hz, 2H) , 2.91 (t, J = 4.9 Hz, 4H), 2.70 (t, J = 7.3 Hz, 2H), 2.56 - 2.49 (m, 2H), 2.46 (s, 4H), 2.05 - 1.92 (m, 2H), 1.87 - 1.76 (m, 2H); 475[M+H] ⁺
62

N-(3-(1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.11 (s, 1H), 7.53 - 7.47 (m, 2H), 7.36 (d, J = 8.1 Hz, 1H), 7.28 (s, 1H), 7.22 - 7.15 (m, 1H), 7.12 - 7.05 (m, 1H), 7.00 - 6.91 (m, 2H), 4.29 - 4.21 (m, 1H), 4.15 (t, J = 6.3 Hz, 2H), 3.02 (dd, J = 13.3, 6.8 Hz, 2H), 2.77 (t, J = 7.1 Hz, 2H), 2.69 - 2.39 (m, 8H), 2.31 (s, 3H), 2.25 - 2.17 (m, 2H), 2.06 - 1.95 ( m, 2H), 1.88 (dt, J = 14.1, 6.9 Hz, 2H); 489[M+H] ⁺ 63

4-(3-(4-ethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.11 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.24 (s, 1H), 7.10 (dd, J = 9.6, 2.3 Hz, 1H) ), 6.98 - 6.88 (m, 4H), 4.22 (t, J = 6.2 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.3, 6.8 Hz, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.56 - 2.39 (m, 10H), 2.03 - 1.96 (m, 2H), 1.86 - 1.77 (m, 2H), 1.10 (t, J = 6.9 Hz, 3H); 503[M+H] ⁺ 64

5-Methoxy-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole ¹ H NMR (400 MHz, CDCl ₃ ) δ7.91 (s, 1H), 7.74 (d, J = 8.9 Hz, 2H), 7.24 (s, 1H), 7.01 (t, J = 6.8 Hz, 2H), 6.93 (dd, J = 7.2, 2.3 Hz, 2H), 6.85 (dd, J = 8.8, 2.3 Hz, 1H), 4.10 (t, J = 6.3 Hz, 2H), 3.91 (d, J = 11.8 Hz, 2H) ), 3.83 (s, 3H), 2.71 (t, J = 11.7 Hz, 1H), 2.66 - 2.37 (m, 12H), 2.31 (s, 3H), 2.07 (t, J = 11.1 Hz, 2H), 2.04 - 1.95 (m, 2H), 1.86 (ddd, J = 25.6, 12.6, 3.8 Hz, 2H); 527[M+H] ⁺ 65

5-methyl-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole ¹ H NMR (400 MHz, CDCl ₃ ) δ7.91 (s, 1H), 7.74 (d, J = 8.9 Hz, 2H), 7.32 - 7.21 (m, 3H), 7.01 (dd, J = 7.6, 5.5 Hz) , 2H), 6.90 (d, J = 2.2 Hz, 1H), 4.10 (t, J = 6.3 Hz, 2H), 3.91 (d, J = 11.9 Hz, 2H), 2.78 - 2.67 (m, 1H), 2.65 - 2.44 (m, 10H), 2.47 - 2.39 (m, 5H), 2.32 (s, 3H), 2.08 (dd, J = 15.6, 4.1 Hz, 2H), 2.01 (dd, J = 13.8, 6.9 Hz, 2H) ), 1.88 (ddd, J = 25.2, 12.5, 3.7 Hz, 2H); 511[M+H] ⁺ 66

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.16 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 1.6 Hz, 1H), 7.28 (s, 1H), 7.13 (dd, J = 8.7, 1.7 Hz, 1H), 6.97 - 6.89 (m, 3H), 4.22 (t, J = 6.1 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.00 (dd , J = 13.4, 6.8 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.63 - 2.40 (m, 10H), 2.30 (s, 3H), 1.99 (dt, J = 13.3, 6.5 Hz, 2H), 1.83 (dt, J = 14.0, 7.0 Hz, 2H); 505[M+H] ⁺ 67

N-(3-(5-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.99 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.32 - 7.22 (m, 2H), 7.01 (d, J = 8.1 Hz, 1H) ), 6.92 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 1.8 Hz, 1H), 4.23 (t, J = 6.1 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.1, 6.6 Hz, 2H), 2.73 (t, J = 7.2 Hz, 2H), 2.50 (ddd, J = 14.0, 10.9, 5.9 Hz, 10H), 2.45 (s, 3H), 2.30 (s, 3H), 2.00 (dd, J = 13.8, 6.8 Hz, 2H), 1.84 (dd, J = 14.2, 7.0 Hz, 2H); 485[M+H] ⁺ 68

N-(3-(5-methoxy-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.99 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.23 (s, 1H), 6.97 - 6.88 (m, 4H), 6.85 (dd , J = 8.8, 2.3 Hz, 1H), 4.23 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.85 (s, 3H), 3.01 (dd, J = 13.2, 6.8 Hz, 2H), 2.73 (t, J = 7.2 Hz, 2H), 2.68 - 2.36 (m, 10H), 2.30 (s, 3H), 1.99 (dt, J = 13.4, 6.7 Hz, 2H), 1.86 ( dt, J = 14.0, 7.1 Hz, 2H); 501[M+H] ⁺ 69

N-(3-(1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.12 (s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.1) Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.09 (t, J = 7.1 Hz, 1H), 6.92 (d, J = 8.8 Hz, 3H), 4.25 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.73 (s, 1H), 3.00 (dd, J = 13.3, 6.8 Hz, 2H), 2.80 (ddd, J = 23.9, 12.3, 5.4 Hz, 4H) ), 2.52 (t, J = 7.1 Hz, 2H), 2.24 - 2.11 (m, 2H), 2.04 - 1.96 (m, 2H), 1.95 - 1.80 (m, 4H), 1.66 - 1.59 (m, 2H) ; 472[M+H] ⁺ 70

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.21 (s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.44 (d, J = 1.3 Hz, 1H), 7.28 (s, 1H), 7.13 (dd, J = 8.5, 1.7 Hz, 1H), 6.94 (d, J = 8.9 Hz, 3H), 4.24 (t, J = 6.0 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 2.99 (dd, J = 13.4, 6.8 Hz, 2H), 2.91 (t, J = 4.8 Hz, 4H), 2.71 (t, J = 7.2 Hz, 2H), 2.56 - 2.49 (m, 2H), 2.49 - 2.36 (m, 4H), 2.04 - 1.94 (m, 2H), 1.83 (dt, J = 13.9, 7.0 Hz, 2H); 491 [M] 71

5-fluoro-3-(1-((4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-indole ¹ H NMR (400 MHz, CDCl ₃ ) δ8.03 (s, 1H), 7.74 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.7 Hz, 1H), 7.13 (dd, J = 9.7) , 2.0 Hz, 1H), 7.02 (t, J = 7.4 Hz, 2H), 6.99 (t, J = 3.1 Hz, 1H), 6.93 (td, J = 9.1, 2.2 Hz, 1H), 4.11 (t, J) = 6.3 Hz, 2H), 3.91 (d, J = 11.3 Hz, 2H), 2.73 - 2.65 (m, 1H), 2.63 - 2.34 (m, 12H), 2.31 (s, 3H), 2.03 (dt, J = 14.1, 9.8 Hz, 4H), 1.84 (ddd, J = 25.4, 12.5, 3.9 Hz, 2H); 502[M+H] ⁺ 72

4-(3-((3S,5R)-3,5-dimethylpiperazin-1-yl)propoxy)-N-(3-(5-fluoro-1H-indol-3-yl)propyl)benzene sulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.15 (s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.30 - 7.22 (m, 1H), 7.10 (dd, J = 9.6, 2.1 Hz) , 1H), 6.94 (dt, J = 12.5, 3.0 Hz, 4H), 4.24 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.2 Hz, 2H), 3.00 (dd, J = 13.2, 6.6 Hz, 2H), 2.98 - 2.88 (m, 2H), 2.83 (d, J = 10.7 Hz, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.3 Hz, 2H) , 2.01 (dt, J = 12.6, 6.4 Hz, 2H), 1.82 (dt, J = 13.8, 7.0 Hz, 2H), 1.07 (s, 3H), 1.06 (s, 3H); 502[M] 73

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-isobutyrylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.05 (s, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.30 - 7.24 (m, 1H), 7.09 (dd, J = 9.6, 2.2 Hz) , 1H), 7.00 (s, 1H), 6.97 - 6.89 (m, 3H), 4.25 (t, J = 6.4 Hz, 1H), 4.09 (t, J = 6.2 Hz, 2H), 3.71 - 3.60 (m, 2H), 3.57 - 3.50 (m, 2H), 3.01 (dd, J = 13.4, 6.7 Hz, 2H), 2.79 (dt, J = 13.6, 6.9 Hz, 1H), 2.70 (d, J = 7.2 Hz, 2H) ), 2.55 (t, J = 7.1 Hz, 2H), 2.51 - 2.38 (m, 4H), 2.05 - 1.93 (m, 2H), 1.87 - 1.77 (m, 2H), 1.14 (s, 3H), 1.12 ( s, 3H); 545[M+H] ⁺ 74

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)prop Foxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.04 (s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.30 - 7.22 (m, 1H), 7.10 (dd, J = 9.6, 2.2 Hz) , 1H), 6.99 (t, J = 2.8 Hz, 1H), 6.94 (dd, J = 11.7, 5.5 Hz, 3H), 4.24 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.3 Hz) , 2H), 3.06 - 2.92 (m, 4H), 2.71 (t, J = 7.1 Hz, 6H), 2.53 (t, J = 7.1 Hz, 6H), 2.04 - 1.95 (m, 2H), 1.88 - 1.76 ( m, 2H); 557[M+H] ⁺ 75

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.19 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 1.5 Hz, 1H), 7.28 (s, 1H), 7.13 (dd, J = 8.6, 1.8 Hz, 1H), 6.97 - 6.90 (m, 3H), 4.28 - 4.19 (m, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.78 - 3.67 (m, 1H), 3.49 (s, 1H), 2.99 (dd, J = 13.3, 6.7 Hz, 2H), 2.85 - 2.76 (m, 2H), 2.71 (t, J = 7.3 Hz, 2H), 2.57 - 2.47 (m) , 2H), 2.21 - 2.10 (m, 2H), 1.99 (dt, J = 13.1, 6.5 Hz, 2H), 1.95 - 1.87 (m, 2H), 1.87 - 1.76 (m, 2H), 1.65 - 1.59 (m) , 2H); 506[M] 76

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)propoxy ) Benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.10 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.44 (s, 1H), 7.28 (s, 1H), 7.14 (d, J) = 8.6 Hz, 1H), 6.97 (s, 1H), 6.93 (d, J = 8.7 Hz, 2H), 4.25 - 4.21 (m, 1H), 4.07 (t, J = 6.2 Hz, 2H), 3.06 - 2.91 (m, 4H), 2.71 (t, J = 7.1 Hz, 6H), 2.53 (s, 6H), 2.06 - 1.93 (m, 4H), 1.83 (dt, J = 14.1, 7.1 Hz, 2H); 573 [M] 77

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-(methylamino)azetidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.67 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.44 (s, 1H), 7.25 (s, 1H), 7.13 (d, J = 7.3 Hz, 1H), 6.92 (d, J = 8.7 Hz, 2H), 6.82 (s, 1H), 4.23 (t, J = 6.4 Hz, 1H), 4.07 (t, J = 6.2 Hz, 2H), 3.61 (t, J = 6.8 Hz, 2H), 3.42 - 3.33 (m, 1H), 2.98 (dd, J = 13.2, 6.6 Hz, 2H), 2.78 (t, J = 6.5 Hz, 2H), 2.68 (t) , J = 7.0 Hz, 2H), 2.64 (t, J = 7.0 Hz, 2H), 2.37 (s,3H), 1.90 - 1.83 (m, 2H), 1.79 (dd, J = 14.1, 7.0 Hz, 2H) ; 491 [M] 78

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-chloropiperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.11 (s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.44 (s, 1H), 7.28 (s, 1H), 7.14 (d, J = 8.8 Hz, 1H), 6.97 (s, 1H), 6.93 (d, J = 8.7 Hz, 2H), 4.24 (t, J = 6.5 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.00 (dd, J = 13.2, 6.6 Hz, 2H), 2.78 (s, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.53 (t, J = 7.2 Hz, 2H), 2.36 - 2.16 (m) , 3H), 2.14 - 2.09 (s,2H), 2.03 - 1.94 (m, 2H), 1.94 - 1.87 (m, 2H), 1.87 - 1.78 (m, 2H); 524 [M] 79

N-(3-(5-chloro-1H-indol-3-yl)propyl)-6-(3-(piperazin-1-yl)propoxy)pyridine-3-sulfonamide ¹ H NMR (400 MHz, MeOD) δ8.56 (d, J = 1.9 Hz, 1H), 8.01 (dd, J = 8.7, 2.3 Hz, 1H), 7.42 (s, 1H), 7.29 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 8.8 Hz, 1H), 4.48 (t, J = 5.9 Hz, 2H), 3.50 (d, J = 4.4 Hz) , 4H), 3.38 (s, 4H), 3.25 - 3.14 (m, 2H), 2.95 (t, J = 6.9 Hz, 2H), 2.71 (t, J = 7.4 Hz, 2H), 2.22 (dd, J = 12.8, 6.7 Hz, 2H), 2.05 (d, J = 5.5 Hz, 1H), 1.87 - 1.74 (m, 2H), 0.92 (t, J = 6.6 Hz, 1H); 492.06[M] 80

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-fluoropiperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.72 (d, J = 8.7 Hz, 2H), 7.42 (s, 1H), 7.29 (d, J = 8.6 Hz, 1H), 7.03 (dd, J = 10.2, 8.0 Hz, 4H), 4.75 (s, 1H), 4.62 (s, 1H), 4.11 (t, J = 6.1 Hz, 2H), 2.90 (t, J = 7.0 Hz, 2H), 2.69 (t, J = 7.3 Hz, 4H), 2.62 - 2.56 (m, 2H), 2.50 (s, 2H), 2.07 - 1.94 (m, 4H), 1.92 - 1.83 (m, 2H), 1.78 (dt, J = 14.3, 7.2 Hz) , 2H); 508[M] 81

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-(trifluoromethyl)piperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.04 (s, 1H), 7.72 (d, J = 8.7 Hz, 2H), 7.44 (s, 1H), 7.27 (d, J = 7.9 Hz, 2H), 7.14 (d, J = 8.7 Hz, 1H), 6.99 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 4.24 (t, J = 6.3 Hz, 1H), 4.07 (t, J = 6.3) Hz, 2H), 3.00 (dd, J = 13.4, 6.6 Hz, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.58 (t, J = 6.9 Hz, 6H), 2.07 - 1.94 (m, 6H) ), 1.85 - 1.78 (m, 2H); 558 [M] 82

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,4-difluoropiperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.73 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.29 (d, J = 8.6 Hz, 1H), 7.04 (dd, J = 10.0, 7.3 Hz, 4H), 4.12 (t, J = 6.2 Hz, 2H), 2.91 (t, J = 6.9 Hz, 2H), 2.73 - 2.66 (m, 2H), 2.63 (t, J = 7.3 Hz, 6H) , 2.20 (dd, J = 15.5, 7.0 Hz, 1H), 2.10 - 1.94 (m, 6H), 1.84 - 1.73 (m, 2H); 526 [M] 83

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.37 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 1.6 Hz, 1H), 7.29 - 7.22 (m, 1H) ), 7.13 (dd, J = 8.6, 1.8 Hz, 1H), 6.96 - 6.88 (m, 2H), 4.33 (t, J = 5.9 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.00 (q, J = 6.5 Hz, 2H), 2.80 - 2.73 (m, 4H), 2.69 (dd, J = 14.4, 7.3 Hz, 4H), 2.66 - 2.59 (m, 4H), 2.37 (s, 3H), 1.95 (dt, J = 13.3, 6.5 Hz, 2H), 1.87 - 1.78 (m, 4H); 519 [M] 84

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.27 (br s, 1H), 7.70 (d, J = 8.7 Hz, 2H), 7.29 - 7.21 (m, 1H), 7.10 (dd, J = 9.6, 2.0) Hz, 1H), 6.97 - 6.88 (m, 4H), 4.29 (t, J = 6.2 Hz, 1H), 4.08 (t, J = 6.3 Hz, 2H), 2.99 (q, J = 6.6 Hz, 2H), 2.69 (t, J = 7.2 Hz, 2H), 2.56 - 2.49 (m, 2H), 2.49 - 2.35 (m, 4H), 2.02 (p, J = 13.3, 7.0 Hz, 2H), 1.82 (p, J = 13.3, 7.0 Hz, 2H), 1.64 - 1.60 (m, 4H), 1.46 (s, 2H); 474[M+H] ⁺ 85

N-(3-(1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.14 (br s, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.17 (t, J = 7.6 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 6.86 - 6.82 (m, 1H) , 4.68 (d, J = 6.9 Hz, 1H), 4.03 (t, J = 6.3 Hz, 2H), 3.73 - 3.65 (m, 1H), 3.08 - 2.98 (m, 1H), 2.58 - 2.49 (m, 5H) ), 2.31 (s, 3H), 2.06 - 1.92 (m, 4H), 1.74 - 1.63 (m, 4H), 1.62 - 1.51 (m, 2H); 511[M+H] ⁺ 86

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)naphthalene-1-sulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.55 (d, J = 8.5 Hz, 1H), 8.37 (d, J = 8.3 Hz, 1H), 8.14 (d, J = 8.2 Hz, 2H), 7.66 (t, J = 7.7 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.31 (s, 1H), 7.21 (d, J = 8.5 Hz, 1H), 7.10-7.08 (m, 1H), 6.76 ( d, J = 8.4 Hz, 1H), 6.70 (s, 1H), 4.52 (t, J = 6.2 Hz, 1H), 4.27 (t, J = 6.2 Hz, 2H), 2.91 (q, J = 6.5 Hz, 2H), 2.64 (t, J = 7.2 Hz, 2H), 2.56-2.48 (m, 10H), 2.30 (s, 3H), 2.15 (p, J = 6.4 Hz, 2H), 1.72 (p, J = 7.0) Hz, 2H); 556[M+H] ⁺ 87

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.33 (br s, 1H), 7.70 (d, J = 8.7 Hz, 2H), 7.44 (s, 1H), 7.26-7.24 (m, 1H), 7.13-7.11 ( m, 1H), 6.9 (d, J = 8.8 Hz, 3H), 4.28 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 2.98 (q, J = 6.6 Hz, 2H), 2.69 (t, J = 7.2 Hz, 2H), 2.49 (t, J = 7.2 Hz, 2H), 2.42 (br s, 4H), 1.99 (p, J = 6.5 Hz, 2H), 1.83 (p , J = 7.0 Hz, 2H), 1.62-1.57 (m, 4H), 1.46-1.45 (m, 2H); 491[M+H] ⁺ 88

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-4-yl)propyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, DMSO δ10.97 (s, 1H), 7.50 (s, 1H), 7.43 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 8.6 Hz, 1H), 7.15-7.13 (m, 2H), 7.05-7.03 (m, 1H), 6.59 (d, J = 8.7 Hz, 2H), 6.44 (t, J = 5.0 Hz, 1H), 3.02 (q, J = 5.9 Hz, 2H) , 2.92 (d, J = 11.7 Hz, 2H), 2.71-2.68 (m, 2H), 2.60 (t, J = 7.4 Hz, 2H), 2.45-2.42 (m, 1H), 1.67 (p, J = 7.1) Hz, 2H), 1.60-1.50 (m, 4H), 1.28-1.23 (m, 4H), 1.03-0.95 (m, 2H); 490[M+H] ⁺ 89

N-(3-(1H-indol-3-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.57 (br s, 1H), 7.73-7.71 (m, 3H), 7.42-7.40 (m, 2H), 7.33-7.28 (m, 4H), 7.26-7.21 (m , 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 8.1 Hz, 1H), 6.88 (d, J = 8.8 Hz, 2H), 4.01 (t, J = 6.3 Hz, 2H) ), 2.51-2.47 (m, 10H), 2.29 (s, 3H), 1.94 (p, J = 6.9 Hz, 2H); 505[M+H] ⁺ 90

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-1-yl)butyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ9.44 (br s, 1H), 7.66 (d, J = 8.1 Hz, 2H), 7.48 - 7.43 (m, 1H), 7.23 (d, J = 8.4 Hz, 3H), 7.26 - 7.20 (m, 1H), 6.79 - 6.72 (m, 1H), 4.29 (t, J = 6.1 Hz, 1H), 2.95 (q, J = 6.6 Hz, 2H), 2.69 (t, J) = 7.0 Hz, 4H), 2.58 - 2.39 (m, 4H), 2.39 - 2.31 (m, 2H), 1.85 - 1.76 (m, 2H), 1.68 - 1.58 (m, 6H), 1.54 - 1.40 (m, 4H) ); 488[M+H] ⁺ 91

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperazin-1-yl)butyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.83 (br s, 1H), 7.69 (d, J = 8.1 Hz, 2H), 7.47 - 7.42 (m, 1H), 7.25 - 7.20 (m, 2H), 7.12 (dd, J = 8.7, 1.6 Hz, 1H), 6.89 - 6.83 (m, 1H), 4.39 (br s, 1H), 2.98 (t, J = 6.7 Hz, 2H), 2.92 (t, J = 4.8) Hz, 4H), 2.70 (t, J = 6.7 Hz, 4H), 2.57 - 2.40 (m, 4H), 2.40 - 2.32 (m, 2H), 1.99 - 1.84 (m, 4H), 1.84 - 1.76 (m, 2H), 1.70 - 1.58 (m, 2H), 1.55 - 1.42 (m, 2H); 489[M+H] ⁺ 92

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(1-methylpiperidin-4-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.16 (br s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.44 (s, 1H), 7.28-7.26 (m, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.99 (s, 1H), 6.92 (d, J = 8.7 Hz, 2H), 4.29 (t, J = 5.8 Hz, 1H), 3.99 (t, J = 6.4 Hz, 2H) , 2.99 (q, J = 6.6 Hz, 2H), 2.91 (t, J = 10.8 Hz, 2H), 2.30 (s, 3H), 2.05-1.93 (m, 4H), 1.86-1.78 (m, 4H), 1.72 (d, J = 9.4 Hz, 2H), 1.42-1.40 (m, 1H); 505 [M+H] ⁺ 93

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.13 (br s, 1H), 7.72 (d, J = 8.7 Hz, 2H), 7.45 (s, 1H), 7.28-7.26 (m, 1H), 7.14 (d, J = 8.6 Hz, 1H), 6.99 (s, 1H), 6.93 (d, J = 8.7 Hz, 2H), 4.31 (br s, 1H), 3.99 (t, J = 6.4 Hz, 2H), 3.09 (d) , J = 12.1 Hz, 2H), 3.00 (t, J = 6.6 Hz, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.60 (t, J = 11.8 Hz, 2H), 1.85-1.81 (m) , 4H), 1.71 (d, J = 12.5 Hz, 4H), 1.41-1.38 (m, 3H), 1.19-1.10 (m, 1H); 491[M+H] ⁺ 94

N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperidin-4-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.21 (br s, 1H), 7.44 (s, 1H), 7.39-7.37 (m, 2H), 7.32 (s, 1H), 7.28-7.26 (m, 1H), 7.13 (d, J = 8.4 Hz, 1H), 7.08-7.07 (m, 1H), 6.99 (s, 1H), 4.40 (br s, 1H), 3.96 (t, J = 6.4 Hz, 2H), 3.09 ( d, J = 12.1 Hz, 2H), 3.03 (t, J = 6.8 Hz, 2H), 2.73 (t, J = 7.2 Hz, 2H), 2.60 (t, J = 11.4 Hz, 2H), 1.88-1.77 ( m, 4H), 1.72-1.69 (m, 4H), 1.40-1.37 (m, 3H), 1.19-1.10 (m, 1H); 491[M+H] ⁺ 95

N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.97 (br s, 1H), 7.42 - 7.39 (m, 1H), 7.36 - 7.28 (m, 2H), 7.25 - 7.22 (m, 2H), 7.14 - 7.09 (m, 1H), 7.01 - 6.96 (m, 1H), 6.94 - 6.91 (m, 1H), 4.36 (t, J = 6.0 Hz, 1H), 4.01 (t, J = 6.2 Hz, 2H), 2.98 ( dd, J = 13.2, 6.7 Hz, 2H), 2.71 (t, J = 7.0 Hz, 2H), 2.66 - 2.59 (m, 2H), 2.59 - 2.44 (m, 4H), 2.10 - 2.00 (m, 2H) , 1.87 - 1.80 (m, 2H), 1.71 - 1.56 (m, 4H), 1.54 - 1.42 (m, 2H).; 490[M+H] ⁺ 96

N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.53 (br s, 1H), 7.44 - 7.40 (m, 1H), 7.38 - 7.31 (m, 2H), 7.28 (s, 1H), 7.26 - 7.22 (m) , 1H), 7.15 - 7.10 (m, 1H), 7.07 - 7.00 (m, 1H), 6.98 - 6.94 (m, 1H), 4.40 - 4.28 (m, 1H), 4.03 (t, J = 6.2 Hz, 2H) ), 3.06 - 2.95 (m, 2H), 2.92 (t, J = 4.8 Hz, 4H), 2.72 (t, J = 7.1 Hz, 2H), 2.53 (t, J = 7.2 Hz, 2H), 2.51 - 2.40 (m, 4H), 1.99 (p, J = 13.4, 6.7 Hz, 2H), 1.84 (p, J = 13.7, 6.8 Hz, 2H); 491[M+H] ⁺ 97

N-(3-(5-fluoro-1H-indol-3-yl)propyl)-4-(3-(piperidin-4-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.19 (br s, 1H), 7.72 (d, J = 8.7 Hz, 2H), 7.26 - 7.22 (m, 1H), 7.09 (dd, J = 9.6, 2.2) Hz, 1H), 6.99 (s, 1H), 6.95 - 6.88 (m, 3H), 3.98 (t, J = 6.4 Hz, 2H), 3.09 (d, J = 12.1 Hz, 2H), 2.99 (t, J) = 6.9 Hz, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.60 (t, J = 11.5 Hz, 2H), 1.86 - 1.75 (m, 4H), 1.75 - 1.63 (m, 3H), 1.45 - 1.30 (m, 2H), 1.30 - 1.20 (m, 1H), 1.19 - 1.05 (m, 2H); 474[M+H] ⁺ 98

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.31 (br s, 1H), 7.57 (d, J = 8.7 Hz, 2H), 7.44 (d, J = 1.7 Hz, 1H), 7.26-7.24 (m, 1H) , 7.11 (dd, J = 8.6, 1.9 Hz, 1H), 6.95 (d, J = 1.9 Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 5.74 (br s, 1H), 4.39 (t) , J = 6.2 Hz, 1H), 3.23 (t, J = 6.2 Hz, 2H), 2.96 (q, J = 6.5 Hz, 2H), 2.69 (t, J = 7.2 Hz, 2H), 2.53-2.50 (m) , 10H), 2.32 (s, 3H), 1.83-1.76 (m, 4H); 505[M+H] ⁺ 99

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(piperidin-4-yl)butyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.25 (br s, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 1.9 Hz, 1H), 7.28 (d, J = 4.5 Hz, 2H), 7.26 - 7.24 (m, 1H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 6.98 (s, 1H), 3.10 - 3.03 (m, 2H), 3.01 (t, J) = 6.9 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.69 - 2.62 (m, 2H), 2.61 - 2.52 (m, 2H), 2.06 - 2.00 (m, 1H), 1.87 - 1.78 ( m, 4H), 1.66 - 1.56 (m, 2H), 1.36 - 1.18 (m, 4H), 1.14 - 1.02 (m, 2H); 488[M+H] ⁺ 100

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyrrolidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, DMSO δ10.94 (br s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.48-7.44 (m, 2H), 7.32 (d, J = 8.6 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 7.07-7.02 (m, 3H), 4.07 (t, J = 6.4 Hz, 2H), 2.75 (br s, 2H), 2.60 (t, J = 7.4 Hz, 2H), 2.40 (br s, 4H), 1.89 (p, J = 6.7 Hz, 2H), 1.71-1.63 (m, 6H); 477[M+H] ⁺ 101

4-(3-(azepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.53 (br s, 1H), 7.70 (d, J = 8.9 Hz, 2H), 7.42 (d, J = 1.8 Hz, 1H), 7.26 (d, J = 2.1 Hz, 1H), 7.10 (dd, J = 8.6, 1.9 Hz, 1H), 6.89 (d, J = 8.8 Hz, 3H), 4.72 - 4.58 (m, 1H), 4.05 (t, J = 6.2 Hz, 2H), 3.00 - 2.91 (m, 2H), 2.80 - 2.71 (m, 6H), 2.67 (t, J = 7.2 Hz, 2H), 2.06 - 1.97 (m, 2H), 1.79 (p, J = 7.0 Hz) , 2H), 1.74 - 1.65 (m, 4H), 1.65 - 1.56 (m, 4H); 504[M+H] ⁺ 102

4-(3-(1,4-diazepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.72 (d, J = 8.9 Hz, 2H), 7.41 - 7.38 (m, 1H), 7.28 (d, J = 8.6 Hz, 1H), 7.07 - 6.98 (m, 4H), 4.12 (t, J = 6.1 Hz, 2H), 3.30 - 3.20 (m, 4H), 2.96 - 2.86 (m, 4H), 2.84 - 2.73 (m, 4H), 2.67 (t, J = 7.4 Hz) , 2H), 2.02 - 1.93 (m, 4H), 1.77 (p, J = 14.4, 7.2 Hz, 2H); 505[M+H] ⁺ 103

N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.20 (br s, 1H), 7.51-7.47 (m, 2H), 7.43 (d, J = 1.6 Hz, 1H), 7.26-7.25 (m, 1H), 7.12 ( dd, J = 8.6, 1.9 Hz, 1H), 7.00 (d, J = 8.2 Hz, 1H), 6.96-6.95 (m, 1H), 4.34 (t, J = 6.2 Hz, 1H), 4.14 (t, J) = 6.3 Hz, 2H), 2.99 (q, J = 6.5 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.56-2.47 (m, 10H), 2.28 (s, 3H), 2.02 (p , J = 6.6 Hz, 2H), 1.84 (p, J = 7.0 Hz, 2H); 524[M+H] ⁺ 104

N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.23 (br s, 1H), 7.52-7.48 (m, 2H), 7.44 (d, J = 1.7 Hz, 1H), 7.27-7.24 (m, 1H), 7.12 ( dd, J = 8.6, 1.8 Hz, 1H), 7.01-6.95 (m, 2H), 4.33 (br s, 1H), 4.15 (t, J = 6.3 Hz, 2H), 3.00 (br s, 1H), 2.89 (t, J = 4.8 Hz, 4H), 2.72 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.1 Hz, 2H), 2.44 (br s, 4H), 2.02 (p, J = 6.6) Hz, 2H), 1.84 (p, J = 7.0 Hz, 2H); 510[M+H] ⁺ 105

N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluoro-4-(3-(4-hydroxypiperidin-1-yl)propoxy)benzenesulfonamide ¹ H NMR 400 MHz, DMSO δ 10.95 (br s, 1H), 7.59-7.53 (m, 3H), 7.47 (d, J = 1.9 Hz, 1H), 7.34-7.29 (m, 2H), 7.12 (d, J = 2.1 Hz, 1H), 7.03 (dd, J = 8.6, 2.0 Hz, 1H), 4.52 (d, J = 6.9 Hz, 1H), 4.14 (t, J = 6.4 Hz, 2H), 3.45-3.38 ( m, 1H), 2.77 (q, J = 6.3 Hz, 2H), 2.70-2.67 (m, 2H), 2.60 (t, J = 7.4 Hz, 2H), 2.37 (t, J = 7.0 Hz, 2H), 1.98 (t, J = 10.1 Hz, 2H), 1.88 (p, J = 6.5 Hz, 2H), 1.71-7.64 (m, 4H), 1.40-1.31 (m, 2H); 525[M+H] ⁺ 106

4-(3-(1,4-diazepan-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-3-fluorobenzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ10.95 (br s, 1H), 7.56-753 (m, 2H), 7.47 (d, J = 1.7 Hz, 1H), 7.34-7.30 (m, 2H), 7.12 ( d, J = 1.7 Hz, 1H), 7.03 (dd, J = 8.6, 1.9 Hz, 1H), 4.16 (t, J = 6.3 Hz, 2H), 2.79-2.70 (m, 6H), 2.63-2.54 (m) , 9H), 1.86 (p, J = 6.4 Hz, 2H), 1.71-1.59 (m, 4H); 524[M+H] ⁺ 107

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.23 (br s, 1H), 7.75 - 7.66 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.30 - 7.23 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 6.96 - 6.87 (m, 3H), 4.35 - 4.27 (m, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.04 - 2.79 (m, 7H), 2.71 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.3 Hz, 2H), 2.10 - 1.93 (m, 4H), 1.82 (p, J = 14.1, 7.1 Hz, 2H), 1.06 (d, J = 6.3 Hz, 3H); 505[M+H] ⁺ 108

(R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.23 (br s, 1H), 7.75 - 7.68 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.31 - 7.23 (m, 1H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 6.97 - 6.90 (m, 3H), 4.35 - 4.26 (m, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.05 - 2.78 (m, 7H), 2.71 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.3 Hz, 2H), 2.08 - 1.95 (m, 3H), 1.82 (p, J = 14.1, 7.1 Hz, 2H), 1.75 - 1.70 (m, 2H), 1.06 (d, J = 6.3 Hz, 3H); 505[M+H] ⁺ 109

(S)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.23 (br s, 1H), 7.74 - 7.67 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.28 - 7.23 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 6.97 - 6.90 (m, 3H), 4.37 - 4.26 (m, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.03 - 2.79 (m, 7H), 2.71 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.3 Hz, 2H), 2.09 - 1.94 (m, 3H), 1.82 (p, J = 7.0 Hz, 2H), 1.06 ( d, J = 6.3 Hz, 3H); 505[M+H] ⁺ 110

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-((3S, 5R)-3,5-dimethylpiperazin-1-yl)propoxy)benzenesulfone amides ¹ H NMR (400 MHz, CDCl ₃ ) δ8.26 (br s, 1H), 7.75 - 7.68 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.27 - 7.24 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 6.98 - 6.89 (m, 3H), 4.35 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.03 - 2.89 (m, 4H), 2.85 - 2.78 (m, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.56 - 2.46 (m, 2H), 2.07 - 1.95 (m, 2H), 1.82 (p, J) = 7.1 Hz, 2H), 1.66 - 1.59 (m, 2H), 1.06 (d, J = 6.4 Hz, 6H); 520[M+H] ⁺ 111

(S)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3,4-dimethylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.53 - 8.32 (m, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 1.3 Hz, 1H), 7.25 (d, J) = 8.4 Hz, 1H), 7.10 (dd, J = 8.6, 1.8 Hz, 1H), 6.96 - 6.86 (m, 3H), 4.76 - 4.54 (m, 1H), 4.04 (t, J = 6.1 Hz, 2H) , 3.03 - 2.92 (m, 3H), 2.92 - 2.78 (m, 2H), 2.68 (t, J = 7.2 Hz, 2H), 2.61 - 2.34 (m, 8H), 2.10 (t, J = 10.7 Hz, 1H) ), 1.98 (p, J = 13.3, 7.0 Hz, 2H), 1.81 (p, J = 14.7, 7.0 Hz, 2H), 1.15 (d, J = 6.3 Hz, 3H); 520[M+H] ⁺ 112

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(4-methylpiperazin-1-yl)butyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.73 (br s, 1H), 7.68 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 1.9 Hz, 1H), 7.26 - 7.23 (m, 2H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 6.86 (d, J = 2.2 Hz, 1H), 4.34 - 4.24 (m, 1H), 2.99 (q, J = 6.7 Hz, 2H), 2.74 - 2.66 (m, 4H), 2.66 - 2.40 (m, 8H), 2.41 - 2.35 (m, 2H), 2.29 (s, 3H), 1.83 (q, J = 14.7, 7.0 Hz, 2H), 1.69 - 1.60 (m, 2H), 1.54 - 1.45 (m, 2H); 505[M+H] ⁺ 113

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)propyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.24 (br s, 1H), 7.57-7.55 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.25-7.23 (m, 2H), 7.11 ( dd, J = 8.6, 2.0 Hz, 1H), 6.95 (s, 1H), 6.54-6.50 (m, 2H), 5.76 (br s, 1H), 4.33 (br s, 1H), 3.22 (t, J = 6.2 Hz, 2H), 2.98-2.91 (m, 6H), 2.69 (t, J = 7.3 Hz, 2H), 2.50-2.45 (m, 6H), 1.84-1.71 (m, 4H); 491[M+H] ⁺ 114

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperidin-1-yl)propyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.22 (br s, 1H), 7.57-7.55 (m, 2H), 7.45 (dd, J = 1.9 Hz, 1H), 7.25-7.23 (m, 2H), 7.11 ( dd, J = 8.6, 2.0 Hz, 1H), 6.93 (d, J = 2.1 Hz, 1H), 6.51 (d, J = 8.8 Hz, 2H), 4.24 (t, J = 6.3 Hz, 1H), 3.21 ( t, J = 6.2 Hz, 2H), 2.96 (d, J = 6.6 Hz, 2H), 2.69 (t, J = 7.3 Hz, 2H), 2.49-2.44 (m, 6H), 1.83-1.75 (m, 4H) ), 1.62 (p, J = 5.6 Hz, 4H), 1.49-1.48 (m, 2H); 490[M+H] ⁺ 115

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(4-(1-methylpiperidin-4-yl)butyl)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.70 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 1.8 Hz, 1H), 7.33 (d, J = 8.2 Hz, 2H), 7.27 (d) , J = 8.6 Hz, 1H), 7.02 (dd, J = 8.6, 2.0 Hz, 1H), 6.99 (s, 1H), 2.92 (t, J = 7.0 Hz, 2H), 2.87 - 2.77 (m, 2H) , 2.72 - 2.59 (m, 4H), 2.23 (s, 3H), 2.00 - 1.90 (m, 2H), 1.78 - 1.70 (m, 2H), 1.68 - 1.58 (m, 4H), 1.37 - 1.14 (m, 7H); 502[M+H] ⁺ 116

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-((4-methylpiperazin-1-yl)methyl)cyclopropyl)methoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.25 (br s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.47 - 7.41 (m, 1H), 7.26 - 7.22 (m, 1H), 7.16 - 7.10 (m, 1H), 7.00 - 6.88 (m, 3H), 4.30 - 4.21 (m, 1H), 3.94 (s, 2H), 2.99 (q, J = 6.7 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.63 - 2.38 (m, 8H), 2.38 (s, 2H), 2.27 (s, 3H), 1.88 - 1.78 (m, 2H), 0.65 (t, J = 5.1 Hz, 2H) ), 0.48 (t, J = 5.2 Hz, 2H); 531[M+H] ⁺ 117

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((1-(piperazin-1-ylmethyl)cyclopropyl)methoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.45 (br s, 1H), 7.72 - 7.65 (m, 2H), 7.44 (d, J = 1.8 Hz, 1H), 7.26 - 7.22 (m, 1H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 6.97 - 6.93 (m, 2H), 6.91 (s, 1H), 4.45 - 4.21 (m, 1H), 3.94 (s, 2H), 2.98 (t, J = 6.9 Hz, 2H), 2.85 (t, J = 4.8 Hz, 4H), 2.70 (t, J = 7.1 Hz, 2H), 2.52 - 2.39 (m, 4H), 2.36 (s, 2H), 1.89 - 1.78 (m, 3H), 0.65 (t, J = 5.3 Hz, 2H), 0.47 (t, J = 5.4 Hz, 2H); 517[M+H] ⁺ 118

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.15 (br s, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 1.7 Hz, 1H), 7.29 - 7.22 (m, 4H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 7.04 - 6.97 (m, 3H), 6.77 (dd, J = 8.3, 2.1 Hz, 1H), 6.60 (t, J = 2.2 Hz, 1H) ), 6.51 (dd, J = 7.9, 1.8 Hz, 1H), 4.36 (t, J = 6.2 Hz, 1H), 3.27 - 3.14 (m, 4H), 3.01 (q, J = 6.7 Hz, 2H), 2.73 (t, J = 7.2 Hz, 2H), 2.60 - 2.51 (m, 2H), 2.35 (s, 3H), 1.91 - 1.80 (m, 2H),; 540[M+H] ⁺ 119

4-(3-Bromophenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.01 (br s, 1H), 7.81 - 7.74 (m, 2H), 7.46 (d, J = 1.8 Hz, 1H), 7.37 - 7.32 (m, 1H), 7.30 - 7.23 (m, 3H), 7.21 (t, J = 2.0 Hz, 1H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 7.06 - 6.96 (m, 4H), 4.40 (t, J = 6.0 Hz, 1H), 3.03 (q, J = 6.7 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 1.87 (p, J = 7.1 Hz, 2H); 521[M+H] ⁺ 120

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperidin-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.06 (br s, 1H), 7.77 - 7.69 (m, 2H), 7.46 (d, J = 1.8 Hz, 1H), 7.26 - 7.21 (m, 2H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 7.05 - 6.96 (m, 3H), 6.78 (dd, J = 8.3, 2.1 Hz, 1H), 6.61 (t, J = 2.2 Hz, 1H), 6.46 (dd, J = 7.9, 1.8 Hz, 1H), 4.36 (t, J = 6.3 Hz, 1H), 3.21 - 3.11 (m, 4H), 3.01 (q, J = 6.7 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 1.86 (p, J = 14.1, 7.1 Hz, 2H), 1.72 - 1.64 (m, 4H), 1.64 - 1.52 (m, 4H); 524[M+H] ⁺ 121

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.78 - 7.70 (m, 2H), 7.42 (d, J = 1.8 Hz, 1H), 7.30 - 7.23 (m, 2H), 7.02 (d, J = 8.7 Hz, 4H), 6.83 (dd, J = 8.3, 2.2 Hz, 1H), 6.64 (t, J = 2.2 Hz, 1H), 6.49 (dd, J = 7.8, 1.8 Hz, 1H), 3.16 - 3.09 (m, 4H) ), 3.00 - 2.88 (m, 6H), 2.68 (t, J = 7.4 Hz, 2H), 1.78 (p, J = 14.4, 7.2 Hz, 2H); 525[M+H] ⁺ 122

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.78 - 7.70 (m, 2H), 7.42 (d, J = 1.8 Hz, 1H), 7.27 (d, J = 8.6 Hz, 1H), 7.19 (t, J = 8.2 Hz, 1H), 7.05 - 6.99 (m, 4H), 6.59 (dd, J = 8.4, 2.2 Hz, 1H), 6.38 (t, J = 2.2 Hz, 1H), 6.29 (dd, J = 7.9, 1.7) Hz, 1H), 3.55 - 3.48 (m, 2H), 3.43 (t, J = 6.3 Hz, 2H), 2.92 (t, J = 7.0 Hz, 2H), 2.71 - 2.63 (m, 4H), 2.60 - 2.53 (m, 2H), 2.34 (s, 3H), 2.00 - 1.92 (m, 2H), 1.78 (p, J = 14.5, 7.2 Hz, 2H); 553[M+H] ⁺ 123

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.09 (br s, 1H), 7.61 (d, J = 8.6 Hz, 2H), 7.44 (s, 1H), 7.23-7.19 (m, 2H), 7.11 (d, J = 8.0 Hz, 1H), 6.97-6.95 (m, 3H), 6.68-6.63 (m, 3H), 6.01 (s, 1H), 4.29 (t, J = 6.2 Hz, 1H), 3.20-3.18 (m) , 4H), 3.00 (q, J = 6.0 Hz, 2H), 2.71 (t, J = 7.3 Hz, 2H), 2.57-2.55 (m, 4H), 2.34 (s, 3H), 1.82 (p, J = 7.1 Hz, 2H); 539[M+H] ⁺ 124

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(piperazin-1-yl)phenyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.05 (br s, 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 1.7 Hz, 1H), 7.23-7.20 (m, 3H) , 7.11 (dd, J = 8.6, 1.9 Hz, 1H), 6.97-6.95 (m, 3H), 6.68-6.64 (m, 3H), 6.00 (s, 1H), 4.26 (t, J = 6.0 Hz, 1H) ), 3.14-3.12 (m, 4H), 3.03-2.98 (m, 6H), 2.71 (t, J = 7.2 Hz, 2H), 1.82 (p, J = 7.1 Hz, 2H); 525[M+H] ⁺ 125

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)pyrimidin-2-yl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.30 (br s, 1H), 8.01 (br s, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.66 (d, J = 8.9 Hz, 2H), 7.43 (d, J = 1.8 Hz, 1H), 7.37 (br s, 1H), 7.21 (d, J = 8.6 Hz, 1H), 7.09 (dd, J = 8.6, 1.9 Hz, 1H), 6.81 (d, J = 1.7 Hz, 1H), 6.11 (d, J = 5.8 Hz, 1H), 4.65 (br s, 1H), 3.67-3.64 (m, 4H), 2.99-2.94 (m, 2H), 2.69 (t, J = 7.1 Hz, 2H), 2.49-2.47 (m, 4H), 2.34 (s, 3H), 1.82 (p, J = 6.9 Hz, 2H); 541[M+H] ⁺ 126

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-morpholinophenyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.00 (br s, 1H), 7.63-7.61 (m, 2H), 7.44 (d, J = 2.0 Hz, 1H), 7.26-7.21 (m, 2H), 7.12 ( dd, J = 8.6, 2.0 Hz, 1H), 6.98-6.95 (m, 3H), 6.68-6.64 (m, 3H), 6.01 (s, 1H), 4.26 (t, J = 6.3 Hz, 1H), 3.85 -3.83 (m, 4H), 3.15-3.13 (m, 4H), 3.01 (q, J = 5.5 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 1.83 (p, J = 7.0 Hz, 2H); 526 [M+H] ⁺ 127

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(piperazin-1-yl)pyrimidin-2-yl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.26 (br s, 1H), 8.02 (d, J = 6.2 Hz, 1H), 7.72-7.70 (m, 2H), 7.67-7.65 (m, 2H), 7.44 ( d, J = 1.8 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.13-7.09 (m, 2H), 6.81 (d, J = 2.2 Hz, 1H), 6.11 (d, J = 6.2) Hz, 1H), 4.32 (br s, 1H), 3.62 (t, J = 4.8 Hz, 4H), 3.00-2.94 (m, 6H), 2.71 (t, J = 7.1 Hz, 2H), 1.83 (p J = 7.0 Hz, 2H); 540[M+H] ⁺ 128

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-morpholinophenoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.01 (br s, 1H), 7.77 - 7.71 (m, 2H), 7.46 (d, J = 1.9 Hz, 1H), 7.30 - 7.24 (m, 2H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 7.07 - 6.97 (m, 3H), 6.75 (dd, J = 8.3, 1.9 Hz, 1H), 6.59 (t, J = 2.3 Hz, 1H), 6.56 - 6.50 (m, 1H), 4.38 - 4.28 (m, 1H), 3.92 - 3.80 (m, 4H), 3.19 - 3.11 (m, 4H), 3.02 (q, J = 6.7 Hz, 2H), 2.74 (t) , J = 7.3 Hz, 2H), 1.86 (p, J = 7.1 Hz, 2H); 526[M+H] ⁺ 129

4-(3-(1,4-diazepan-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.11 (br s, 1H), 7.77 - 7.68 (m, 2H), 7.46 (d, J = 1.9 Hz, 1H), 7.27 - 7.24 (m, 2H), 7.20 (t, J = 8.2 Hz, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 7.05 - 7.00 (m, 2H), 7.00 - 6.97 (m, 1H), 6.54 (dd, J = 8.4, 2.4 Hz, 1H), 6.37 (t, J = 2.3 Hz, 1H), 6.32 (dd, J = 7.9, 1.7 Hz, 1H), 4.93 - 4.81 (m, 1H), 4.38 - 4.26 (m, 1H) ), 3.61 - 3.46 (m, 4H), 3.06 - 2.98 (m, 4H), 2.91 - 2.82 (m, 2H), 2.74 (t, J = 7.3 Hz, 2H), 1.94 - 1.82 (m, 4H); 539[M+H] ⁺ 130

4-(3,5-bis(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.29 (br s, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 1.6 Hz, 1H), 7.24 (d, J = 8.7 Hz, 1H), 7.12 (dd, J = 8.6, 1.9 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H), 6.96 (s, 1H), 6.30 (s, 1H), 6.13 (d, J = 1.9 Hz, 2H), 4.36 - 4.28 (m, 1H), 3.23 - 3.14 (m, 8H), 3.06 - 2.98 (m, 2H), 2.73 (t, J = 7.2 Hz, 2H), 2.60 - 2.51 (m, 8H), 2.34 (s, 6H), 1.89 - 1.81 (m, 2H); 637[M+H] ⁺ 131

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.15 (br s, 1H), 7.70-7.68 (m, 2H), 7.48-7.39 (m, 4H), 7.22 (d, J = 8.6 Hz, 1H), 7.10 ( dd, J = 6.7 Hz, 1H), 6.90 (d, J = 2.1 Hz, 1H), 6.58 (s, 1H), 6.21 (dd, J = 12.1, 8.2 Hz, 2H), 4.41 (t, J = 6.2) Hz, 1H), 3.57-3.54 (m, 4H), 3.00 (q, J = 6.5 Hz, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.54-2.51 (m, 4H), 2.35 (s) , 3H), 1.82 (p, J = 7.0 Hz, 2H); 540[M+H] ⁺ 132

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-(piperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.07 (br s, 1H), 7.71-7.69 (m, 2H), 7.50-7.40 (m, 4H), 7.25-7.23 (m, 1H), 7.12 (dd, J = 8.6, 2.0 Hz, 1H), 6.92 (d, J = 2.1 Hz, 1H), 6.53 (s, 1H), 6.21 (dd, J = 11.6, 8.2 Hz, 2H), 4.25 (t, J = 6.1 Hz) , 1H), 3.52-3.49 (m, 4H), 3.02-2.98 (m, 6H), 2.72 (t, J = 14.3 Hz, 2H), 2.04-2.02 (m, 1H), 1.84 (p, J = 7.0) Hz, 2H); 526[M+H] ⁺ 133

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.86 (br s, 1H), 8.01 (d, J = 5.9 Hz, 1H), 7.68-7.65 (m, 2H), 7.43-7.37 (m, 3H), 7.20 ( d, J = 8.6 Hz, 1H), 7.08 (dd, J = 8.6, 2.0 Hz, 1H), 6.70 (br s, 1H), 6.61 (d, J = 2.0 Hz, 2H), 6.41 (dd, J = 6.0, 2.0 Hz, 1H), 6.21 (s, 1H), 4.37 (br s, 1H), 3.35-3.32 (m, 4H), 2.93 (t, J = 6.1 Hz, 2H), 2.68 (t, J = 7.0 Hz, 2H), 2.54-2.51 (m, 4H), 2.35 (s, 3H), 1.83 (p, J = 6.8 Hz, 2H); 540[M+H] ⁺ 134

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(piperazin-1-yl)pyridin-2-yl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.86 (br s, 1H), 8.02 (d, J = 5.9 Hz, 1H), 7.68-7.66 (m, 2H), 7.43-7.37 (m, 3H), 7.20 ( d, J = 8.6 Hz, 1H), 7.09 (dd, J = 8.6, 1.9 Hz, 1H), 6.66 (br s, 1H), 6.61 (d, J = 1.9 Hz, 1H), 6.41 (dd, J = 6.1, 2.0 Hz, 1H), 6.21 (s, 1H), 4.27 (br s, 1H), 3.30-3.28 (m, 4H), 3.01-2.99 (m, 4H), 2.94 (br s, 2H), 2.69 (t, J = 7.0 Hz, 2H), 1.83 (p, J = 6.8 Hz, 2H); 526[M+H] ⁺ 135

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyrrolidin-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.00 (br s, 1H), 7.77 - 7.68 (m, 2H), 7.47 (d, J = 1.9 Hz, 1H), 7.28 - 7.24 (m, 1H), 7.21 (t, J = 8.1 Hz, 1H), 7.13 (dd, J = 8.6, 1.9 Hz, 1H), 7.07 - 7.01 (m, 2H), 6.99 (d, J = 2.2 Hz, 1H), 6.41 (dd) , J = 8.1, 2.0 Hz, 1H), 6.31 (dd, J = 8.0, 1.7 Hz, 1H), 6.24 (t, J = 2.3 Hz, 1H), 4.32 - 4.25 (m, 1H), 3.26 (t, J = 6.6 Hz, 4H), 3.02 (q, J = 6.7 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 2.03 - 1.96 (m, 4H), 1.87 (p, J = 13.3, 7.0) Hz, 2H); 510[M+H] ⁺ 136

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-hydroxypiperidin-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.04 (br s, 1H), 7.76 - 7.70 (m, 2H), 7.46 (d, J = 2.0 Hz, 1H), 7.28 - 7.21 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 7.05 - 6.97 (m, 3H), 6.78 (dd, J = 8.2, 2.1 Hz, 1H), 6.61 (t, J = 2.3 Hz, 1H), 6.48 (dd, J = 8.0, 1.6 Hz, 1H), 4.30 (t, J = 6.3 Hz, 1H), 3.91 - 3.84 (m, 1H), 3.59 - 3.51 (m, 2H), 3.02 (q, J = 6.7 Hz, 2H), 2.96 (ddd, J = 12.8, 9.8, 3.2 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 2.03 - 1.95 (m, 2H), 1.86 (p, J = 7.1 Hz) , 2H), 1.72 - 1.61 (m, 2H); 540[M+H] ⁺ 137

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-fluoro-5-(4-methylpiperazin-1-yl)phenoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.05 (br s, 1H), 7.79 - 7.73 (m, 2H), 7.46 (d, J = 1.8 Hz, 1H), 7.30 - 7.23 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 7.07 - 7.01 (m, 2H), 6.99 (d, J = 2.1 Hz, 1H), 6.43 (td, J = 12.0, 2.0 Hz, 1H), 6.37 - 6.34 (m, 1H), 6.19 (td, J = 10.7, 2.0 Hz, 1H), 4.29 (t, J = 6.3 Hz, 2H), 3.24 - 3.13 (m, 4H), 3.03 (q, J = 8.0) Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 2.58 - 2.47 (m, 4H), 2.34 (s, 2H), 1.87 (p, J = 14.7, 7.0 Hz, 2H); 557[M+H] ⁺ 138

4-(3-Bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.09 (br s, 1H), 7.78 - 7.72 (m, 2H), 7.46 (d, J = 1.9 Hz, 1H), 7.28 - 7.23 (m, 1H), 7.15 - 7.10 (m, 1H), 7.05 - 7.00 (m, 2H), 6.99 (d, J = 2.1 Hz, 1H), 6.88 - 6.85 (m, 1H), 6.62 (t, J = 1.8 Hz, 1H) , 6.50 (t, J = 2.1 Hz, 1H), 4.44 - 4.33 (m, 1H), 3.24 - 3.17 (m, 4H), 3.03 (q, J = 6.7 Hz, 2H), 2.74 (t, J = 7.2) Hz, 2H), 2.58 - 2.50 (m, 4H), 2.35 (s, 3H), 1.91 - 1.82 (m, 2H); 619[M+H] ⁺ 139

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((3-(4-hydroxypiperidin-1-yl)phenyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.09 (br s, 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 1.4 Hz, 1H), 7.24-7.18 (m, 2H) , 7.10 (dd, J = 8.6, 1.8 Hz, 1H), 6.96-6.94 (m, 3H), 6.69-6.67 (m, 2H), 6.62 (d, J = 7.3 Hz, 1H), 6.03 (s, 1H) ), 4.36 (t, J = 6.2 Hz, 1H), 4.07-3.97 (m, 1H), 3.89-3.83 (m, 1H), 3.56- 3.50 (m, 2H), 3.02-2.89 (m, 4H), 2.70 (t, J = 7.2 Hz, 2H), 2.00-1.96 (m, 2H), 1.81 (p, J = 7.0 Hz, 2H), 1.71-1.54 (m, 2H); 540[M+H] ⁺ 140

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((6-chloro-4-(4-methylpiperazin-1-yl)pyridin-2-yl)amino) Benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.31 (br s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 1.8 Hz, 1H), 7.37 (d, J = 8.8 Hz) , 2H), 7.25-7.23 (m, 1H), 7.09 (dd, J = 6.6 Hz, 1H), 6.74 (d, J = 2.1 Hz, 1H), 6.69 (s, 1H), 6.37 (d, J = 1.8 Hz, 1H), 6.11 (d, J = 1.8 Hz, 1H), 5.29 (s, 1H), 4.40 (t, J = 6.1 Hz, 1H), 3.33-3.31 (m, 4H), 2.97 (p, J = 6.4 Hz, 2H), 2.69 (t, J = 7.0 Hz, 2H), 2.52-2.49 (m, 4H), 2.34 (s, 3H), 1.83 (p, J = 6.8 Hz, 2H); 574[M+H] ⁺ 141

4-((4,6-bis(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzene sulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ8.24 (br s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.43-7.40 (m, 3H), 7.21 (d, J = 8.6 Hz, 1H) , 7.09 (dd, J = 8.6, 2.0 Hz, 1H), 6.81 (d, J = 2.0 Hz, 1H), 6.47 (br s, 1H), 5.75-5.67 (m, 2H), 4.34 (t, J = 6.2 Hz, 1H), 3.52-3.49 (m, 4H), 3.30-3.27 (m, 4H), 2.98 (q, J = 6.4 Hz, 2H), 2.69 (t, J = 7.1 Hz, 2H), 2.50 ( br s, 8H), 2.33 (s, 6H), 1.81 (p, J = 6.9 Hz, 2H); 638[M+H] ⁺ 142

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)benzenesulfonamide ¹ H NMR 400 MHz, CDCl ₃ δ10.93 (br s, 1H), 8.39 (br s, 1H), 7.50-7.48 (m, 3H), 7.31 (d, J = 8.6 Hz, 1H), 7.22 (t) , J = 5.8 Hz, 1H), 7.13 (d, J = 1.8 Hz, 1H), 7.04-7.02 (m, 3H), 6.91-6.87 (m, 4H), 3.09-3.06 (m, 4H), 2.73 ( q, J = 6.4 Hz, 2H), 2.61 (t, J = 7.4 Hz, 2H), 2.45-2.43 (m, 4H), 2.21 (s, 3H), 1.68 (p, J = 7.4 Hz, 2H); 539[M+H] ⁺ 143

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.06 (br s, 1H), 7.60 - 7.53 (m, 3H), 7.31 - 7.27 (m, 1H), 7.17 - 7.12 (m, 1H), 7.08 (s) , 1H), 6.87 (d, J = 8.7 Hz, 2H), 6.01 - 5.93 (m, 1H), 4.04 (t, J = 6.3 Hz, 2H), 3.52 (q, J = 6.6 Hz, 2H), 2.83 (t, J = 7.2 Hz, 2H), 2.70 - 2.40 (m, 10H), 2.33 (s, 3H), 2.05 - 1.96 (m, 4H); 469[M+H] ⁺ 144

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzamide ¹ H NMR (400 MHz, MeOD) δ7.79 - 7.70 (m, 2H), 7.54 - 7.46 (m, 1H), 7.28 (d, J = 8.6 Hz, 1H), 7.12 (s, 1H), 7.03 ( dd, J = 8.6, 1.9 Hz, 1H), 6.99 - 6.91 (m, 2H), 4.54 (br s, 2H), 4.11 (t, J = 6.1 Hz, 2H), 3.44 (t, J = 7.1 Hz, 2H), 3.19 - 3.09 (m, 4H), 2.80 (t, J = 7.3 Hz, 2H), 2.73 - 2.66 (m, 4H), 2.64 (t, J = 7.2 Hz, 2H), 2.06 - 1.94 (m) , 4H); 455[M+H] ⁺ 145

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(methylsulfonyl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.14 (br s, 1H), 7.75 - 7.68 (m, 2H), 7.42 (d, J = 2.0 Hz, 1H), 7.30 - 7.26 (m, 1H), 7.12 (dd, J = 8.6, 2.1 Hz, 1H), 6.96 - 6.87 (m, 3H), 4.43 (t, J = 6.2 Hz, 1H), 4.17 (t, J = 5.8 Hz, 2H), 3.32 - 3.23 (m, 2H), 3.03 - 2.95 (m, 5H), 2.69 (t, J = 7.2 Hz, 2H), 2.44 - 2.34 (m, 2H), 1.81 (p, J = 7.1 Hz, 2H); 486[M+H] ⁺ 146

N-(3-(5-chloro-1H-indol-3-yl)propyl)-2-((3-(piperazin-1-yl)propyl)amino)thiazole-5-sulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.17 (br s, 1H), 8.11 (br s, 1H), 7.57 (s, 1H), 7.50 (s, 1H), 7.13 (d, J = 7.7 Hz) , 1H), 7.01 (s, 1H), 4.49 (br s, 1H), 3.45 - 3.31 (m, 2H), 3.15 - 3.02 (m, 2H), 2.77 (t, J = 7.2 Hz, 2H), 2.67 - 2.21 (m, 6H), 2.02 - 1.86 (m, 2H), 1.86 - 1.73 (m, 2H), 1.68 - 1.44 (m, 4H); 497[M+H] ⁺ 147

N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.93 (s, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.31 (s, 1H), 7.16 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H), 4.15 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.2 Hz, 2H), 2.93 ( dd, J = 13.3, 6.6 Hz, 2H), 2.70 - 2.36 (m, 8H), 2.32 (s, 3H), 2.30 (s, 3H), 2.05 - 1.95 (m, 2H), 1.79 - 1.70 (m, 2H), 1.70 - 1.50 (m, 4H); 519[M+H] ⁺ 148

4-(4-(1H-imidazol-1-yl)butyl)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, DMSO) δ10.95 (s, 1H), 7.67 (d, J = 8.3 Hz, 2H), 7.59 (s, 1H), 7.55 (br s, 1H), 7.47 (d, J) = 2.0 Hz, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.6 Hz, 1H), 7.12 (s, 1H), 7.11 (d, J = 2.1 Hz, 1H), 7.04 (dd, J = 8.6, 2.0 Hz, 1H), 6.86 (s, 1H), 3.96 (t, J = 7.0 Hz, 2H), 2.78 (t, J = 6.5 Hz, 2H), 2.69 - 2.62 (m) , 2H), 2.59 (t, J = 7.5 Hz, 2H), 1.75 - 1.60 (m, 4H), 1.56 - 1.43 (m, 2H); 471[M+H] ⁺ 149

N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.17 (br s, 1H), 8.11 (br s, 1H), 7.57 (s, 1H), 7.50 (s, 1H), 7.13 (d, J = 7.7 Hz) , 1H), 7.01 (s, 1H), 4.49 (br s, 1H), 3.45 - 3.31 (m, 2H), 3.15 - 3.02 (m, 2H), 2.77 (t, J = 7.2 Hz, 2H), 2.67 - 2.21 (m, 6H), 2.02 - 1.86 (m, 2H), 1.86 - 1.73 (m, 2H), 1.68 - 1.44 (m, 4H); 497[M+H] ⁺ 150

N-(2-((5-chloro-1H-indol-3-yl)methyl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.93 (s, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.31 (s, 1H), 7.16 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H), 4.15 (t, J = 6.2 Hz, 1H), 4.07 (t, J = 6.2 Hz, 2H), 2.93 ( dd, J = 13.3, 6.6 Hz, 2H), 2.70 - 2.36 (m, 8H), 2.32 (s, 3H), 2.30 (s, 3H), 2.05 - 1.95 (m, 2H), 1.79 - 1.70 (m, 2H), 1.70 - 1.50 (m, 4H); 519[M+H] ⁺ 151

N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, DMSO) δ10.95 (s, 1H), 7.67 (d, J = 8.3 Hz, 2H), 7.59 (s, 1H), 7.55 (br s, 1H), 7.47 (d, J) = 2.0 Hz, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.6 Hz, 1H), 7.12 (s, 1H), 7.11 (d, J = 2.1 Hz, 1H), 7.04 (dd, J = 8.6, 2.0 Hz, 1H), 6.86 (s, 1H), 3.96 (t, J = 7.0 Hz, 2H), 2.78 (t, J = 6.5 Hz, 2H), 2.69 - 2.62 (m) , 2H), 2.59 (t, J = 7.5 Hz, 2H), 1.75 - 1.60 (m, 4H), 1.56 - 1.43 (m, 2H); 471[M+H] ⁺ 152

N-(4-(5-chloro-1H-indol-3-yl)butan-2-yl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.28 (br s, 1H), 7.50 - 7.42 (m, 3H), 7.29 (d, J = 8.6 Hz, 1H), 7.24 (dd, J = 7.9, 1.7) Hz, 1H), 7.21 - 7.11 (m, 4H), 6.83 - 6.76 (m, 2H), 6.75 (d, J = 2.3 Hz, 1H), 6.45 (br s, 1H), 4.05 (t, J = 6.3) Hz, 2H), 3.67 (s, 2H), 2.77 - 2.33 (m, 10H), 2.30 (s, 3H), 2.03 - 1.95 (m, 2H); 553[M+H] ⁺ 153

N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.44 (br s, 1H), 7.80 - 7.66 (m, 2H), 7.64 - 7.54 (m, 1H), 7.26 - 7.18 (m, 2H), 6.96 - 6.88 (m, 3H), 4.64 (br s, 1H), 4.06 (t, J = 6.3 Hz, 2H), 2.97 (t, J = 6.9 Hz, 2H), 2.90 (t, J = 4.9 Hz, 4H), 2.69 (t, J = 7.2 Hz, 2H), 2.59 - 2.35 (m, 6H), 2.05 - 1.93 (m, 2H), 1.90 - 1.78 (m, 3H); 536[M+H] ⁺ 154

N-(3-(5-bromo-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.48 (br s, 1H), 7.75 - 7.67 (m, 2H), 7.63 - 7.56 (m, 1H), 7.25 - 7.18 (m, 2H), 6.95 - 6.88 ( m, 3H), 4.67 (t, J = 6.2 Hz, 1H), 4.05 (t, J = 6.3 Hz, 2H), 2.96 (q, J = 6.5 Hz, 2H), 2.68 (t, J = 7.2 Hz, 2H), 2.60 - 2.41 (m, 8H), 2.29 (s, 3H), 2.08 (br s, 1H), 2.04 - 1.91 (m, 3H), 1.80 (p, J = 7.1 Hz, 2H); 550[M+H] ⁺ 155

N-(3-(5-phenyl-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 (br s, 1H), 7.71 - 7.66 (m, 3H), 7.66 - 7.61 (m, 2H), 7.47 - 7.39 (m, 4H), 7.34 - 7.28 ( m, 1H), 6.96 (s, 1H), 6.88 - 6.83 (m, 2H), 4.36 (br s, 1H), 3.99 (t, J = 6.2 Hz, 2H), 3.05 - 2.99 (m, 2H), 2.96 (t, J = 4.9 Hz, 4H), 2.80 (t, J = 7.2 Hz, 2H), 2.57 - 2.44 (m, 6H), 1.99 - 1.91 (m, 3H), 1.90 - 1.83 (m, 2H) ; 533[M+H] ⁺ 156

4-(3-(4-methylpiperazin-1-yl)propoxy)-N-(3-(5-phenyl-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 (br s, 1H), 7.72 - 7.66 (m, 3H), 7.66 - 7.61 (m, 2H), 7.48 - 7.39 (m, 4H), 7.32 (t, J = 7.4 Hz, 1H), 6.98 - 6.94 (m, 1H), 6.90 - 6.83 (m, 2H), 4.32 (t, J = 6.3 Hz, 1H), 4.00 (t, J = 6.4 Hz, 2H), 3.02 (q, J = 6.6 Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 2.69 - 2.34 (m, 10H), 2.30 (s, 3H), 1.96 (p, J = 6.7 Hz, 2H) ), 1.88 (p, J = 7.0 Hz, 2H); 547[M+H] ⁺ 157

N-(3-(5-chloro-2-methyl-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.99 (br s, 1H), 7.70 - 7.62 (m, 2H), 7.30 (d, J = 1.9 Hz, 1H), 7.16 (d, J = 8.5 Hz, 1H), 7.04 (dd, J = 8.5, 2.0 Hz, 1H), 6.96 - 6.88 (m, 2H), 4.23 (br s, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.00 - 2.79 ( m, 6H), 2.64 (t, J = 7.2 Hz, 2H), 2.56 - 2.37 (m, 6H), 2.32 (s, 3H), 2.06 - 1.94 (m, 2H), 1.80 - 1.67 (m, 6H) ; 505[M+H] ⁺ 158

N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.17 (s, 1H), 7.68 - 7.60 (m, 2H), 7.32 (d, J = 1.9 Hz, 1H), 7.28 - 7.25 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 7.01 (d, J = 2.3 Hz, 1H), 6.92 - 6.84 (m, 2H), 4.27 (t, J = 6.1 Hz, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.25 (q, J = 6.5 Hz, 2H), 2.88 (t, J = 6.6 Hz, 2H), 2.69 - 2.32 (m, 10H), 2.29 (s, 3H), 2.05 - 1.93 (m, 2H); 491[M+H] ⁺ 159

N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.22 (br s, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 1.7 Hz, 1H), 7.28 - 7.24 (m, 1H), 7.13 (dd, J = 8.6, 1.8 Hz, 1H), 7.01 (s, 1H), 6.88 (d, J = 8.8 Hz, 2H), 4.30 (br s, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.25 (t, J = 6.4 Hz, 2H), 3.01 - 2.80 (m, 6H), 2.55 - 2.42 (m, 6H), 2.00 (dt, J = 13.3, 6.5 Hz, 2H); 477[M+H] ⁺ 160

4-(3-(1H-1,2,4-triazol-1-yl)propoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.44 (br s, 1H), 8.01 (d, J = 18.3 Hz, 2H), 7.77 - 7.68 (m, 2H), 7.44 (d, J = 2.0 Hz, 1H), 7.27 - 7.24 (m, 1H), 7.12 (dd, J = 8.6, 2.0 Hz, 1H), 6.92 - 6.86 (m, 3H), 4.44 (t, J = 6.5 Hz, 2H), 4.32 (t) , J = 6.1 Hz, 1H), 3.95 (t, J = 5.7 Hz, 2H), 3.03 - 2.94 (m, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.44 - 2.37 (m, 2H) , 1.82 (p, J = 7.0 Hz, 2H); 474[M+H] ⁺ 161

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(2-methyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.71 (d, J = 1.9 Hz, 2H), 7.39 (d, J = 2.0 Hz, 1H), 7.34 (s, 1H), 7.27 (d, J = 8.6 Hz) , 1H), 7.21 (br s, 1H), 7.06 - 6.95 (m, 4H), 4.29 (t, J = 6.8 Hz, 2H), 4.07 (t, J = 5.5 Hz, 2H), 2.90 (t, J) = 7.0 Hz, 2H), 2.67 (t, J = 7.4 Hz, 2H), 2.50 (s, 3H), 2.31 (p, J = 12.3, 6.2 Hz, 2H), 1.76 (p, J = 14.4, 7.2 Hz) , 2H); 487[M+H] ⁺ 162

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4 methyl-3-oxopiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.26 (br s, 1H), 7.74 - 7.68 (m, 2H), 7.46 - 7.42 (m, 1H), 7.28 - 7.26 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 6.97 - 6.88 (m, 3H), 4.29 (t, J = 6.3 Hz, 1H), 4.08 (t, J = 6.1 Hz, 2H), 3.35 - 3.30 (m, 2H) ), 3.15 (s, 2H), 3.04 - 2.93 (m, 5H), 2.74 - 2.67 (m, 4H), 2.58 (t, J = 6.9 Hz, 2H), 1.98 (p, J = 6.5 Hz, 2H) , 1.82 (p, J = 7.1 Hz, 2H); 520[M+H] ⁺ 163

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(3-oxopiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (br s, 1H), 7.76 - 7.68 (m, 2H), 7.46 - 7.42 (m, 1H), 7.29 - 7.26 (m, 1H), 7.16 - 7.10 ( m, 1H), 6.97 - 6.90 (m, 3H), 5.77 (s, 1H), 4.29 (t, J = 6.3 Hz, 1H), 4.09 (t, J = 6.2 Hz, 2H), 3.41 - 3.35 (m) , 2H), 3.17 (s, 2H), 3.00 (q, J = 6.7 Hz, 2H), 2.74 - 2.67 (m, 4H), 2.62 (t, J = 6.9 Hz, 2H), 1.99 (p, J = 6.5 Hz, 2H), 1.82 (p, J = 7.1 Hz, 2H); 506[M+H] ⁺ 164

N-(3-(5,7-dichloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.45 (br s, 1H), 7.76 - 7.67 (m, 2H), 7.39 - 7.33 (m, 1H), 7.21 - 7.15 (m, 1H), 7.02 (s, 1H), 6.96 - 6.89 (m, 2H), 4.43 (s, 1H), 4.06 (t, J = 6.3 Hz, 2H), 3.48 (s, 1H), 2.97 (t, J = 6.9 Hz, 2H), 2.90 (t, J = 4.9 Hz, 4H), 2.70 (m, J = 7.3, 0.9 Hz, 2H), 2.54 - 2.34 (m, 6H), 2.05 - 1.93 (m, 2H), 1.82 (p, J = 7.1 Hz, 2H); 526[M+H] ⁺ 165

N-(3-(5,7-dichloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.30 (br s, 1H), 7.76 - 7.68 (m, 2H), 7.40 - 7.34 (m, 1H), 7.21 - 7.16 (m, 1H), 7.05 - 7.01 ( m, 1H), 6.97 - 6.89 (m, 2H), 4.31 (t, J = 6.3 Hz, 1H), 4.07 (t, J = 6.4 Hz, 2H), 2.98 (q, J = 6.7 Hz, 2H), 2.75 - 2.67 (m, 2H), 2.64 - 2.33 (m, 10H), 2.29 (s, 3H), 2.06 - 1.93 (m, 2H), 1.83 (p, J = 7.1 Hz, 2H); 540[M+H] ⁺ 166

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dichloro-1H-imidazol-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.60 (br s, 1H), 7.78 - 7.69 (m, 2H), 7.44 (d, J = 2.0 Hz, 1H), 7.29 (d, J = 5.6 Hz, 1H), 7.12 (dd, J = 8.6, 2.0 Hz, 1H), 6.94 - 6.87 (m, 2H), 6.85 (d, J = 2.3 Hz, 1H), 4.30 (t, J = 6.2 Hz, 1H), 4.20 (t, J = 6.5 Hz, 2H), 3.93 (t, J = 5.6 Hz, 2H), 3.00 (q, J = 6.8 Hz, 2H), 2.70 (t, J = 7.1 Hz, 2H), 2.33 - 2.22 (m, 2H), 1.82 (p, J = 7.0 Hz, 2H); 541[M+H] ⁺ 167

N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.74 - 7.67 (m, 2H), 7.57 (dd, J = 1.8, 0.6 Hz, 1H), 7.37 (dd, J = 8.8, 0.6 Hz, 1H), 7.32 (dd, J = 8.8, 1.8 Hz, 1H), 6.92 - 6.84 (m, 2H), 5.22 - 5.13 (m, 1H), 4.05 (t, J = 6.3 Hz, 2H), 3.05 (q, J = 6.5) Hz, 2H), 2.93 (t, J = 7.1 Hz, 2H), 2.67 - 2.38 (m, 10H), 2.32 (s, 3H), 2.04 - 1.90 (m, 4H); 506[M+H] ⁺ 168

N-(3-(5-chloro-1H-indazol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.74 - 7.66 (m, 2H), 7.57 (d, J = 1.1 Hz, 1H), 7.40 - 7.30 (m, 2H), 6.93 - 6.84 (m, 2H) , 4.06 (t, J = 6.3 Hz, 2H), 3.05 (t, J = 6.7 Hz, 2H), 2.96 - 2.88 (m, 6H), 2.55 - 2.40 (m, 6H), 2.03 - 1.98 (m, 4H) ); 492[M+H] ⁺ 169

N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzene sulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ9.02 (br s, 1H), 8.21 (d, J = 2.2 Hz, 1H), 7.76 (d, J = 2.2 Hz, 1H), 7.75 - 7.68 (m, 2H), 7.00 (d, J = 1.9 Hz, 1H), 6.95 - 6.86 (m, 2H), 4.42 (t, J = 6.2 Hz, 1H), 4.08 (t, J = 6.2 Hz, 2H), 2.98 ( dd, J = 13.1, 6.7 Hz, 2H), 2.76 - 2.57 (m, 10H), 2.43 (s, 3H), 2.06 - 1.97 (m, 2H), 1.87 - 1.79 (m, 2H); 506[M+H] ⁺ 170

N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.21 (d, J = 2.2 Hz, 1H), 7.77 (d, J = 2.2 Hz, 1H), 7.75 - 7.68 (m, 2H), 7.02 (s, 1H) ), 6.94 - 6.86 (m, 2H), 4.42 (br s, 1H), 4.08 (t, J = 6.2 Hz, 2H), 3.03 - 2.94 (m, 4H), 2.70 (t, J = 7.3 Hz, 2H) ), 2.60 - 2.53 (m, 4H), 2.06 - 1.95 (m, 2H), 1.90 - 1.75 (m, 6H); 492[M+H] ⁺ 171

(R)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzene sulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (s, 1H), 7.76 - 7.68 (m, 2H), 7.47 - 7.40 (m, 1H), 7.27 - 7.24 (m, 1H), 7.12 (dd, J) = 8.6, 2.0 Hz, 1H), 6.99 - 6.93 (m, 2H), 6.93 - 6.88 (m, 1H), 4.38 (t, J = 6.0 Hz, 1H), 4.16 - 4.08 (m, 1H), 4.08 - 3.98 (m, 2H), 2.98 (q, J = 6.5 Hz, 2H), 2.81 - 2.65 (m, 4H), 2.64 - 2.37 (m, 8H), 2.32 (s, 3H), 1.81 (p, J = 7.0 Hz, 2H); 522[M+H] ⁺ 172

(R)-N-(3-(5-chloro-1H-yn-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.12 (br s, 1H), 7.76 - 7.67 (m, 2H), 7.46 - 7.42 (m, 1H), 7.28 - 7.24 (m, 1H), 7.13 (dd , J = 8.6, 2.0 Hz, 1H), 7.00 - 6.94 (m, 2H), 6.93 - 6.89 (m, 1H), 4.26 (br s, 1H), 4.16 - 4.09 (m, 1H), 4.09 - 3.99 ( m, 2H), 3.04 - 2.96 (m, 2H), 2.96 - 2.87 (m, 4H), 2.74 - 2.62 (m, 4H), 2.59 - 2.51 (m, 2H), 2.49 - 2.39 (m, 2H), 1.82 (p, J = 7.0 Hz, 2H); 508[M+H] ⁺ 173

(S)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)benzene sulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (br s, 1H), 7.76 - 7.67 (m, 2H), 7.47 - 7.40 (m, 1H), 7.28 - 7.23 (m, 1H), 7.12 (dd, J = 8.6, 2.0 Hz, 1H), 6.99 - 6.92 (m, 2H), 6.91 (d, J = 2.4 Hz, 1H), 4.36 (t, J = 6.3 Hz, 1H), 4.16 - 4.07 (m, 1H) ), 4.07 - 3.98 (m, 2H), 2.98 (q, J = 6.6 Hz, 2H), 2.81 - 2.66 (m, 4H), 2.64 - 2.38 (m, 8H), 2.32 (s, 3H), 1.81 ( p, J = 7.0 Hz, 2H); 522[M+H] ⁺ 174

(S)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.15 (br s, 1H), 7.75 - 7.68 (m, 2H), 7.46 - 7.41 (m, 1H), 7.27 - 7.24 (m, 1H), 7.13 (dd, J = 8.6, 2.0 Hz, 1H), 6.99 - 6.93 (m, 2H), 6.92 - 6.89 (m, 1H), 4.32 (br s, 1H), 4.17 - 4.09 (m, 1H), 4.08 - 3.99 (m) , 2H), 3.03 - 2.90 (m, 6H), 2.73 - 2.63 (m, 4H), 2.56 - 2.51 (m, 2H), 2.48 - 2.39 (m, 2H), 1.82 (p, J = 7.0 Hz, 2H) ); 508[M+H] ⁺ 175

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dimethyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ9.97 (br s, 1H), 7.75 - 7.68 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.26 - 7.21 (m, 2H), 7.08 (dd, J = 8.6, 2.0 Hz, 1H), 6.90 - 6.82 (m, 2H), 6.70 (d, J = 1.7 Hz, 1H), 4.38 (br s, 1H), 4.10 (t, J = 6.4) Hz, 2H), 3.84 (t, J = 5.5 Hz, 2H), 3.01 - 2.91 (m, 2H), 2.69 (t, J = 7.0 Hz, 2H), 2.23 - 2.10 (m, 8H), 1.80 - 1.77 (m, 2H); 501[M+H] ⁺ 176

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(2,4,5-trimethyl-1H-imidazol-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ9.31 (br s, 1H), 7.75 - 7.67 (m, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.24 - 7.21 (m, 1H), 7.10 (dd, J = 8.6, 2.0 Hz, 1H), 6.88 - 6.81 (m, 3H), 4.29 (t, J = 6.2 Hz, 1H), 4.00 (t, J = 6.7 Hz, 2H), 3.87 (t) , J = 5.5 Hz, 2H), 2.97 (q, J = 6.7 Hz, 2H), 2.69 (t, J = 7.1 Hz, 2H), 2.21 (s, 3H), 2.18 - 2.07 (m, 8H), 1.84 - 1.74 (m, 2H); 515[M+H] ⁺ 177

N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(4-methylpiperazin-1-yl)propoxy) Benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.86 - 7.76 (m, 3H), 7.32 (d, J = 1.9 Hz, 1H), 7.16 (d, J = 8.5 Hz, 1H), 7.05 (dd, J) = 8.5, 2.0 Hz, 1H), 7.01 - 6.94 (m, 2H), 4.54 - 4.46 (m, 1H), 4.07 (t, J = 6.3 Hz, 2H), 3.09 - 2.94 (m, 2H), 2.79 - 2.68 (m, 3H), 2.64 - 2.33 (m, 9H), 2.29 (s, 3H), 2.27 - 2.14 (m, 1H), 2.07 - 1.91 (m, 4H).; 531[M+H] ⁺ 178

N-((6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ7.88 - 7.76 (m, 3H), 7.32 (d, J = 1.9 Hz, 1H), 7.16 (d, J = 8.5 Hz, 1H), 7.05 (dd, J) = 8.5, 2.0 Hz, 1H), 7.01 - 6.94 (m, J = 8.9 Hz, 2H), 4.49 (br s, 1H), 4.08 (t, J = 6.3 Hz, 2H), 3.06 - 2.97 (m, 2H) ), 2.90 (t, J = 4.9 Hz, 4H), 2.78 - 2.68 (m, 3H), 2.54 - 2.37 (m, 6H), 2.26 - 2.18 (m, 1H), 2.07 - 1.93 (m, 4H); 517[M+H] ⁺ 179

N-(3-(5-chloro-1H-indol-3-yl)cyclohexyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.81 - 7.74 (m, 2H), 7.46 (d, J = 1.9 Hz, 1H), 7.27 (d, J = 8.6 Hz, 1H), 7.02 (dd, J = 8.6, 2.0 Hz, 1H), 7.00 - 6.93 (m, 3H), 4.03 (t, J = 6.1 Hz, 2H), 3.57 - 3.47 (m, 1H), 3.16 - 3.06 (m, 1H), 2.74 - 2.50 (m, 8H), 2.39 (s, 3H), 2.02 - 1.91 (m, 4H), 1.87 - 1.80 (m, 1H), 1.78 - 1.68 (m, 1H), 1.67 - 1.52 (m, 5H); 545[M+H] ⁺ 180

N-(3-(5-chloro-1H-indol-3-yl)cyclohexyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.78 (d, J = 8.9 Hz, 2H), 7.46 (d, J = 1.9 Hz, 1H), 7.27 (d, J = 8.6 Hz, 1H), 7.02 (dd , J = 8.6, 2.0 Hz, 1H), 7.00 - 6.92 (m, 3H), 4.04 (t, J = 6.1 Hz, 2H), 3.53 - 3.48 (m, 1H), 3.15 - 3.10 (m, 1H), 2.97 (t, J = 5.0 Hz, 4H), 2.63 - 2.44 (m, 6H), 2.01 - 1.91 (m, 3H), 1.87 - 1.80 (m, 1H), 1.77 - 1.69 (m, 1H), 1.67 - 1.53 (m, 5H).; 531[M+H] ⁺ 181

N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzene sulfonamide ¹ H NMR (400 MHz, MeOD) δ7.69 - 7.63 (m, 1H), 7.56 (s, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.28 - 7.22 (m, 1H), 7.18 - 7.07 (m, 3H), 6.82 - 6.76 (m, 2H), 6.63 - 6.55 (m, 2H), 6.49 (d, J = 1.9 Hz, 1H), 4.02 (t, J = 6.1 Hz, 2H), 2.86 - 2.35 (m, 10H), 2.31 (s, 3H), 2.02 - 1.92 (m, 2H); 583[M+H] ⁺ 182

N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.68 - 7.62 (m, 1H), 7.56 (s, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.28 - 7.21 (m, 1H), 7.18 - 7.07 (m, 3H), 6.82 - 6.75 (m, 2H), 6.63 - 6.56 (m, 2H), 6.49 (d, J = 1.9 Hz, 1H), 4.03 (t, J = 6.1 Hz, 2H), 3.01 (t, J = 5.0 Hz, 4H), 2.66 - 2.46 (m, 6H), 2.03 - 1.92 (m, 2H), 1.73 (s, 6H); 567[M+H] ⁺ 183

N-(3-(5,6-dichloro-1H-indol-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.45 (br s, 1H), 7.75 - 7.65 (m, 2H), 7.53 (s, 1H), 7.43 (s, 1H), 6.96 - 6.87 (m, 3H) , 4.52 (br s, 1H), 4.06 (t, J = 6.3 Hz, 2H), 2.97 (t, J = 6.8 Hz, 2H), 2.90 (t, J = 4.9 Hz, 4H), 2.68 (t, J) = 7.2 Hz, 2H), 2.55 - 2.37 (m, 6H), 2.05 - 1.96 (m, 2H), 1.85 - 1.75 (m, 2H); 526[M+H] ⁺ 184

N-(3-(5,6-dichloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propoxy)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.54 (br s, 1H), 7.75 - 7.66 (m, 2H), 7.52 (s, 1H), 7.42 (s, 1H), 6.96 - 6.86 (m, 3H) , 4.65 (t, J = 6.3 Hz, 1H), 4.05 (t, J = 6.3 Hz, 2H), 2.96 (q, J = 6.6 Hz, 2H), 2.67 (t, J = 7.3 Hz, 2H), 2.62 - 2.34 (m, 9H), 2.29 (s, 3H), 2.07 - 1.93 (m, 3H), 1.79 (p, J = 7.1 Hz, 2H); 540[M+H] ⁺ 185

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(pyridin-4-yloxy)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.11 (br s, 1H), 7.75 - 7.70 (m, 2H), 7.40 (d, J = 1.9 Hz, 1H), 7.28 - 7.22 (m, 3H), 7.18 - 7.10 (m, 3H), 7.01 (d, J = 2.2 Hz, 1H), 6.37 - 6.32 (m, 2H), 4.47 (t, J = 5.8 Hz, 1H), 3.74 (t, J = 7.1 Hz) , 2H), 3.07 (q, J = 6.7 Hz, 2H), 2.71 (q, J = 7.5 Hz, 2H), 2.12 (p, J = 14.8, 7.4 Hz, 2H), 1.81 (p, J = 14.2, 7.1 Hz, 2H); 489[M+H] ⁺ 186

N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methylpiperazin-1-yl)propyl)benzenesulfonamide ¹ H NMR (400 MHz, CDCl ₃ ) δ8.62 (br s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 1.9 Hz, 1H), 7.32 - 7.21 (m, 2H), 7.12 (dd, J = 8.6, 2.0 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 4.33 (t, J = 6.2 Hz, 1H), 3.01 (q, J = 6.7 Hz, 2H), 2.70 (t, J = 7.3 Hz, 4H), 2.66 - 2.24 (m, 13H), 1.88 - 1.75 (m, 4H); 484[M+H] ⁺ 187

N-((6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(4-methylpiperazin-1-yl)propoxy ) Benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.84 - 7.75 (m, 2H), 7.14 (dd, J = 8.7, 4.4 Hz, 1H), 7.11 - 7.02 (m, 2H), 6.92 (dd, J = 9.8 , 2.5 Hz, 1H), 6.77 - 6.69 (m, 1H), 4.10 (t, J = 6.1 Hz, 2H), 2.98 - 2.85 (m, 2H), 2.82 - 2.34 (m, 12H), 2.31 (s, 3H), 2.19 - 2.11 (m, 1H), 2.07 - 1.96 (m, 3H), 1.96 - 1.87 (m, 1H), 1.59 - 1.47 (m, 1H); 515[M+H] ⁺ 188

N-((6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)-4-(3-(piperazin-1-yl)propoxy)benzenesulfone amides ¹ H NMR (400 MHz, MeOD) δ7.83 - 7.76 (m, 2H), 7.14 (dd, J = 8.7, 4.4 Hz, 1H), 7.10 - 7.04 (m, 2H), 6.92 (dd, J = 9.8 , 2.5 Hz, 1H), 6.77 - 6.68 (m, 1H), 4.11 (t, J = 6.1 Hz, 2H), 2.97 - 2.84 (m, 6H), 2.78 - 2.63 (m, 3H), 2.63 - 2.43 ( m, 6H), 2.20 - 2.08 (m, 1H), 2.08 - 1.86 (m, 4H), 1.59 - 1.47 (m, 1H); 501[M+H] ⁺ 189

4-(3-(4-methylpiperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.83 - 7.76 (m, 2H), 7.29 (d, J = 7.6 Hz, 1H), 7.20 (d, J = 7.9 Hz, 1H), 7.09 - 7.03 (m, 2H), 7.01 - 6.95 (m, 1H), 6.95 - 6.89 (m, 1H), 4.14 - 4.06 (m, 2H), 2.96 - 2.87 (m, 2H), 2.84 - 2.34 (m, 12H), 2.30 ( s, 3H), 2.24 - 2.15 (m, 1H), 2.08 - 1.86 (m, 5H), 160 - 1.48 (m, 1H); 497[M+H] ⁺ 190

4-(3-(piperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide ¹ H NMR (400 MHz, MeOD) δ7.84 - 7.74 (m, 2H), 7.29 (d, J = 7.7 Hz, 1H), 7.20 (d, J = 7.9 Hz, 1H), 7.10 - 7.03 (m, 2H), 7.01 - 6.95 (m, 1H), 6.95 - 6.89 (m, 1H), 4.10 (t, J = 6.1 Hz, 2H), 2.95 - 2.86 (m, 6H), 2.80 - 2.67 (m, 3H) , 2.62 - 2.40 (m, 6H), 2.24 - 2.15 (m, 1H), 2.07 - 1.88 (m, 4H), 1.59 - 1.49 (m, 1H); 484[M+H] ⁺

<Analysis and purification conditions>

[LC-MS analysis conditions]

Device name: Shimadzu LCMS-2020

Column: ACE Excel2 C18, 75x2.1 mm

Mobile phase: acetonitrile/H ₂ O + 0.1% TFA

Flow rate: 0.5 mL/min

UV detector: 254 nm

[MPLC Purification Conditions]

Device Name: CombiFlash®Rf+

UV detector: 254 nm

[Prep-HPLC purification conditions]

Device name: Gilson GX-281, 321 pump, UV/VIS-155

Column: Luna® 10 νM C18 (2) 100 Å, 250x21.2 mm

Mobile phase: acetonitrile/0.1% TFA H ₂ O

Flow rate: 18 mL/min

UV detector: 254 nm

[ ¹ H NMR]

Device Name: Bruker Avance (400 MHz)

<Experimental Example 1> Pin1 enzyme inhibitory ability evaluation

The following experiment was performed to evaluate the Pin1 enzyme inhibitory activity of the compound represented by Formula 1 according to the present invention, and the results are shown in Table 2 below.

The enzymatic activity of Pin1 protein was measured using Anaspec's sensolyte Green Pin1 assay kit. The substrate was diluted in a buffer at a ratio of 1:100 to prepare a concentration of 1 μM, and the protein was diluted in a buffer at a ratio of 1:20 to prepare a concentration of 50 μg/ml. In addition, the developer was prepared by diluting the buffer in a ratio of 1:100.

The compounds prepared in each Example were prepared at a concentration of 100 μM by diluting with DMSO, and 10 μM, 1 μM, or 0.1 μM using a buffer thereto. In a black 96-well plate, 10 μl of the compound prepared in each Example, 10 μl of Pin1 protein, and 30 μl of the developer diluted in each concentration according to the above method were sequentially added, and finally, 50 μl of the substrate was added and 10 The enzymatic reaction was performed by shaking for a second.

Thereafter, the cells were incubated for 2 hours at room temperature in an environment without light, and fluorescence values of 490 nm/520 nm wavelength were measured using Synergy Neo (Tecan) equipment. The results are shown in Table 2 below by dividing the grades from A to D by the concentration (μM) at which the Pin1 enzyme is inhibited.

Example Pin1 inhibitory activity Example Pin1 inhibitory activity Example Pin1 inhibitory activity One D 65 C 128 B 2 D 66 A 129 B 3 D 67 B 130 A 4 D 68 B 131 B 5 D 69 B 132 B 6 D 70 A 133 A 7 D 71 C 134 A 8 D 72 C 135 B 9 D 73 C 136 B 10 D 74 B 137 A 11 C 75 A 138 A 12 C 76 B 139 B 13 D 77 A 140 A 14 D 78 B 141 A 15 D 79 A 142 B 16 D 80 B 143 A 17 D 81 B 144 B 18 D 82 B 145 A 19 D 83 A 146 A 20 C 84 B 147 A 21 C 85 C 148 A 22 C 86 A 149 A 23 D 87 A 150 A 24 D 88 A 151 A 25 D 89 C 152 A 26 C 90 A 153 A 27 C 91 A 154 A 28 D 92 A 155 B 29 D 93 A 156 B 30 D 94 B 157 B 31 B 95 B 158 A 32 D 96 B 159 A 33 D 97 B 160 A 34 C 98 A 161 A 35 C 99 A 162 B 36 B 100 A 163 B 37 D 101 A 164 A 38 D 102 A 165 A 39 D 103 A 166 A 40 D 104 A 167 A 41 D 105 A 168 A 42 D 106 A 169 A 43 C 107 A 170 A 44 D 108 A 171 A 45 B 109 A 172 A 46 D 110 B 173 A 47 D 111 B 174 A 48 C 112 A 175 A 49 C 113 A 176 A 50 C 114 A 177 A 51 D 115 A 178 A 52 C 116 A 179 B 53 C 117 A 180 B 54 C 118 A 181 B 55 C 119 B 182 B 56 A 120 B 183 A 57 C 121 A 184 A 58 B 122 B 185 A 59 B 123 A 186 A 60 B 124 A 187 A 61 A 125 A 188 A 62 B 126 B 189 A 63 B 127 A 190 A 64 C 128 B

* A < 1 μM, 1 μM < B < 10 μM, 10 μM < C < 100 μM, 100 μM < D.

Looking at Table 2, Example compounds 56, 61, 66, 70, 75, 77, 79, 83, 86, 87, 88, 90, 91, 92, 93, 98, 99, 100, 101, 102, 103 , 104, 105, 106, 107, 108, 109, 112, 113, 114, 115, 116, 117, 118, 121, 123, 124, 125, 127, 130, 133, 134, 137, 138, 140, 141 , 143, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 158, 159, 160, 161, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173 , 174, 175, 176, 177, 178, 183, 184, 185, 186, 187, 188, 189 or 190 treatment showed Pin1 inhibitory activity at less than 1 μM.

The above results indicate that the compounds of the above examples have excellent ability to inhibit the Pin1 enzyme, and through this, it can be seen that the benzenesulfonamide derivative compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention or treatment of cancer.

<Experimental Example 2> MDA-MB 231 triple-negative breast cancer cell line protein expression inhibition evaluation

In order to confirm the ability of the compound represented by 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 performed, and the results are shown in Table 3 below.

MDA-MB-231 cells were cultured in an RPMI medium supplemented with 10% FBS and 1% penicillin/streptomycin at 37° C., 5% CO ₂ incubator. Cells were washed with PBS once daily and replaced with fresh medium, and cells grown to a density of at least 90% were detached using Trypsin / EDTA one day before the experiment, and then plated at a density of 100,000 per well in a 6-well plate. .

The next day of culture, the compound prepared in each Example was treated at a concentration of 10 μM, and DMSO was treated at a concentration of 0.1% of the total as a control, and cultured for 72 hours. After 72 hours, the cells were washed twice with PBS, scraped and harvested, and centrifuged at 13,000 rpm for 3 minutes to remove all of the supernatant and only the cells were collected.

To the prepared cells, 80 μl of RIPA buffer (containing 1x protease inhibitor and dephosphorylation enzyme inhibitor) was added and shaken once every 5 minutes to disrupt the cells for a total of 15 minutes. The disrupted cells were centrifuged at 13,000 rpm for 15 minutes to collect only the supernatant protein, and the obtained protein was quantified using a BCA protein quantification kit (Pierece, MA, USA), and a total of 10 μg of protein was collected. Western blot was used.

Protein samples were separated using SDS-PAGE at a concentration of 10%, transferred to PVDF membrane, combined with anti-human cycline D1 antibody (Cell signal) and anti-Vinculin antibody, and protein expression was monitored by using ECL reagent and LAS4000 equipment. measured. The measurement results were digitized and generalized using ImageJ. The results are shown in Table 3 below by dividing the grades from A to D according to the amount of protein compared to the control group treated with DMSO.

Example MBA-MB-231 Example MBA-MB-231 Example MBA-MB-231 22 D 66 A 92 A 31 C 70 A 93 A 34 D 75 A 98 A 35 A 77 A 99 A 36 D 78 A 103 B 44 D 79 A 104 D 45 D 80 B 105 D 55 D 81 A 106 C 56 B 82 D 118 C 57 D 83 A 121 A 58 D 86 D 123 D 59 B 88 C 60 C 90 B 61 A 91 A

* 0 < A < 35%, 35% < B < 50%, 50% < C < 70%, 70% < D < 100%.

Looking at Table 3, in the case of treating Example compounds 35, 61, 66, 70, 75, 77, 78, 79, 81, 83, 91, 92, 93, 98, 99 or 121, MDA-MB 231 triple It was found that the protein expression level of the negative breast cancer cell line was less than 35% compared to the control group treated with DMSO.

The above results indicate that the compounds of the Examples have excellent ability to inhibit MDA-MB 231 triple-negative breast cancer cell line protein expression, through which the benzenesulfonamide derivative compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention or treatment of cancer. it can be seen that

<Experimental Example 3> Evaluation of cell viability of MCF7 cells, MCF7-SP cells, A2780 cells or A2780-SP cells

In order to confirm the growth inhibitory effect of the compound represented by Formula 1 according to the present invention on MCF7 cells, MCF7-SP cells, A2780 cells or A2780-SP cells, the following experiments were performed, and the results are shown in Table 4 and Tables below 5 is shown.

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

The next day, cells were treated with the compounds of Example 71 or Examples 76, 80, 84, 92, 99, 100, and 119, and cultured for 3 days. Cell viability was evaluated by Cell-titer Glo (Promega, WC, USA), and luciferase activity was detected using a Tecan plate reader (Biocompare, USA).

Meanwhile, MCF7-SP cells (breast cancer stem cells) were plated at a density of 1,500 viable cells per well in an Ultra-Low Attachment round bottom 96-well plate (corning) and cultured in a cancer stem cell medium. The cancer stem cell medium consists of a neurobasal medium supplemented with bFGF 20 ng/ml, EGF 10 ng/ml, Amphotericin B 2.5 ng/ml, HEPES, Glutamax and B27.

The next day, cells were treated with the compounds of Example 71 or Examples 76, 80, 84, 92, 99, 100, and 119 and cultured for 8 days. Media containing the compound was added once again on day 4. Spherical cell viability was evaluated by Cell-titer Glo (Promega, WC, USA), and luciferase activity was detected using a Tecan plate reader (Biocompare, USA).

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

On the next day of culture, cells were treated with the compounds of Example 57 or other Examples 69 to 144 and cultured for 3 days. Cell viability was evaluated by Cell-titer Glo (Promega, WC, USA), and luciferase activity was detected using a Tecan plate reader (Biocompare, USA).

In addition, A2780-SP cells (ovarian cancer stem cells) were plated at a density of 1,500 viable cells per well in an Ultra-Low Attachment round bottom 96-well plate (corning) and cultured in a cancer stem cell medium. The cancer stem cell medium consists of a neurobasal medium supplemented with bFGF 20 ng/ml, EGF 10 ng/ml, Amphotericin B 2.5 ng/ml, HEPES, Glutamax and B27.

On the next day of culture, cells were treated with the compounds of Example 57 or other Examples 69 to 144 and cultured for 8 days. Media containing the compound was added once again on day 4. Spherical cell viability was evaluated by Cell-titer Glo (Promega, WC, USA), and luciferase activity was detected using a Tecan plate reader (Biocompare, USA).

Example MCF7 MCF7-SP 70 B B 75 B C 79 C C 83 B B 91 B B 98 C C 99 B B 118 B B

* A < 1 μM, 1 μM < B < 10 μM, 10 μM < C.

Example A2780 A2780-SP Example A2780 A2780-SP Example A2780 A2780-SP 56 B A 114 - B 158 C A 59 B A 115 - A 159 C A 61 B A 117 - B 160 C C 66 B A 118 C A 161 C A 70 B A 121 B A 164 B A 75 B B 123 B B 165 B A 77 C B 124 B B 166 C B 79 C A 125 C B 167 B A 83 B A 127 C B 168 C A 88 C A 130 B B 169 B A 90 C A 133 C B 170 B A 91 C A 134 C A 171 C A 92 C A 137 C B 172 C A 93 B A 138 C B 173 B A 95 C B 140 - B 174 C A 98 B B 141 - B 175 B A 99 B A 143 - B 176 B A 100 B A 145 C C 177 B A 103 C A 146 C B 178 B A 104 C A 147 C C 183 C A 105 C A 148 C B 184 C A 106 B A 149 C C 185 C C 108 B A 150 C A 186 C A 109 B A 151 C A 187 C A 110 C A 152 C A 188 C A 111 C A 153 B A 189 C A 112 C A 154 B A 190 C A 113 - B 157 C A

* A < 1 μM, 1 μM < B < 10 μM, 10 μM < C, - : Not tested.

Looking at Table 4, it was found that when treating Examples 70, 75, 83, 91, 99 or 118, the MCF7 cell concentration was less than 10 μM, and when treating Examples 70, 83, 91, 99 or 118 showed that the MCF7-SP cell concentration was less than 10 μM.

Looking at Table 5, Examples 56, 59, 61, 66, 70, 75, 83, 93, 98, 99, 100, 106, 108, 109, 121, 123, 124, 130, 153, 154, 164, When treated with 165, 167, 169, 170, 173, 175, 176, 177 or 178, the A2780 cell concentration was found to be less than 10 μM, Examples 56, 59, 61, 66, 70, 79, 83, 88 , 90, 91, 92, 93, 99, 100, 103, 104, 105, 106, 108, 109, 110, 111, 112, 115, 118, 121, 134, 150, 151, 152, 153, 154, 157 , 158, 159, 161, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 183, 184, 186, 187, 188, 189 or 190 In this case, the A2780-SP cell concentration was found to be less than 1 μM.

The above results indicate that the compounds of the Examples have excellent growth inhibitory effects on MCF7 cells, MCF7-SP cells, A2780 cells or A2780-SP cells, through which the benzenesulfonamide derivative compound according to the present invention is used for the prevention or treatment of cancer It can be seen that it can be usefully used as a pharmaceutical composition.

Claims (12)

A compound represented by the following formula (1), an isomer thereof, or a pharmaceutically acceptable salt thereof:
[Formula 1]

In Formula 1,
Ar is 6-10 membered aryl or 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O;
R ¹ and R ² are each independently hydrogen, halogen or 5 to 8 membered heterocycloalkyl C _1-5 alkoxy comprising at least one N;
R ³ is hydrogen, halogen, unsubstituted or substituted straight or branched C _1-8 alkoxy, unsubstituted or substituted straight or branched C _1-8 alkyl, NR ^a1 R ^a2 , OR ^a3 , wherein R ^a1 , R ^a2 and R ^a3 are each independently hydrogen, unsubstituted or substituted straight or branched chain C _1-8 alkyl, unsubstituted or substituted phenyl, or at least one selected from the group consisting of N, S and O 5 to 8 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,
In this case, the substituted alkoxy, substituted alkyl, substituted phenyl, and substituted heteroaryl are each independently 4 to 8 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 4 to 8 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 6 substituted with one or more substituents selected from the group consisting of atom cycloalkyl, halogen, hydroxy and sulfonyl, wherein the substituted alkoxy and substituted alkyl are each independently 3 to 6 membered cycloalkyl together with the carbon being substituted can be further substituted to form
Said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-5 alkyl unsubstituted or substituted with one or more halogen, straight or branched C _1-5 alkylcarbonyl, NR ^b1 R ^b2 , halogen , substituted with one or more substituents selected from the group consisting of hydroxy and oxo,
wherein R ^b1 and R ^b2 are each independently hydrogen, straight-chain or branched C _1-6 alkyl;
L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form a 5 to 8 membered heterocycloalkylene comprising N;
L ² is a single bond, unsubstituted or straight or branched C _1-8 alkylene, C _3-8 cycloalkylene or phenylene substituted with one of hydroxy and oxo;
Z is unsubstituted or substituted C _6-10 aryl, unsubstituted or 5 to 9 membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S and O this fused C _3-8 cycloalkyl, 4 to 8 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 5 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 5 to 5 containing at least one heteroatom selected from the group consisting of N, S and O to 9 membered unsubstituted or substituted heteroaryl C _1-5 alkyl,
The substituted aryl is an unsubstituted or substituted heterocycloalkyl of 4 to 8 members or straight or branched chain containing one or more heteroatoms selected from the group consisting of halogen, phenyl, carboxy, N, S and O. substituted with C _{1-8 alkoxycarbonyl,}
In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently linear or branched C _1-5 alkyl, straight or branched C _1-8 alkoxy, phenyl, benzyl, halogen, hydride It is substituted with one or more substituents selected from the group consisting of hydroxy or oxo.
According to claim 1,
Ar is 6-10 membered aryl or 5-6 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O;
R ¹ and R ² are each independently hydrogen or fluorine;
R ³ is hydrogen, bromine, unsubstituted or substituted straight or branched C _1-6 alkoxy, unsubstituted or substituted straight or branched C _1-6 alkyl, NR ^a1 R ^a2 , OR ^ac , wherein R ^a1 , R ^a2 and R ^a3 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted straight or branched chain C _1-6 alkyl, unsubstituted or substituted phenyl, or N, S and O 5 to 7 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,
In this case, the substituted alkoxy, substituted alkyl, substituted phenyl and substituted heteroaryl are each independently 4 to 7 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 4 to 7 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 5 atom is substituted with one or more substituents selected from the group consisting of cycloalkyl, fluorine, bromine, hydroxy and sulfonyl, or wherein said substituted alkoxy and substituted alkyl are each independently 3 to 5 together with the carbon being substituted may be further substituted to form a cycloalkyl of atoms;
wherein said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-4 alkyl unsubstituted or substituted with one or more halogen, straight or branched C _1-4 alkylcarbonyl, NR ^b1 R ^b2 , chlorine , substituted with one or more substituents selected from the group consisting of fluorine, bromine, hydroxy and oxo,
wherein R ^b1 and R ^b2 are each independently hydrogen, straight-chain or branched C _1-3 alkyl;
L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form piperidinylene;
L ² is a single bond, unsubstituted or straight or branched C _1-6 alkylene, C _4-6 cycloalkylene or phenylene substituted with one of hydroxy and oxo;
Z is unsubstituted or substituted C _6-9 aryl, unsubstituted or 5 to 9 membered unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, S and O This fused C _4-7 cycloalkyl, 5 to 6 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 6 to 9-membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 6 to 6 containing at least one heteroatom selected from the group consisting of N, S and O to 9 membered unsubstituted or substituted heteroaryl C _1-4 alkyl;
said substituted aryl is substituted with chlorine, phenyl, carboxy, morpholinyl or straight or branched C _1-3 alkoxycarbonyl,
In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently straight or branched C _1-4 alkyl, straight or branched C _1-4 alkoxy, benzyl, phenyl, fluorine, chlorine , bromine, a compound substituted with one or more substituents selected from the group consisting of hydroxy or oxo, an isomer thereof, or a pharmaceutically acceptable salt thereof.
According to claim 1,
Ar is phenyl, naphthyl, pyridine or thiazole;
R ¹ and R ² are each independently hydrogen or fluorine;
R ³ is hydrogen, bromine, unsubstituted or substituted straight or branched C _1-5 alkoxy, unsubstituted or substituted straight or branched C _1-5 alkyl, NR ^a1 R ^a2 , OR ^a3 , wherein R ^a1 , R ^a2 and R ^a3 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted straight or branched C _1-5 alkyl, unsubstituted or substituted phenyl, or N, S and O 5 to 6 membered unsubstituted or substituted heteroaryl containing at least one heteroatom,
In this case, the substituted alkoxy, substituted alkyl, substituted phenyl and substituted heteroaryl are each independently 4 to 7 membered unsubstituted containing one or more heteroatoms selected from the group consisting of N, S and O. substituted or substituted heterocycloalkyl, 5 to 7 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of N, S and O, NR ^b1 R ^b2 , 3 to 4 atom is substituted with one or more substituents selected from the group consisting of cycloalkyl, fluorine, bromine, hydroxy and sulfonyl, wherein said substituted alkoxy and substituted alkyl are each independently taken together with the carbon being substituted to form a cyclopropyl; can be further substituted,
wherein said substituted heterocycloalkyl and substituted heteroaryl are straight or branched C _1-3 alkyl unsubstituted or substituted with one or more fluorine, straight or branched C _1-4 alkylcarbonyl, NR ^b1 R ^b2 , chlorine , substituted with one or more substituents selected from the group consisting of fluorine, bromine, hydroxy and oxo,
wherein R ^b1 and R ^b2 are each independently hydrogen, methyl or ethyl;
L ¹ is

or

wherein R ^c is hydrogen or ^{together with L 2} and the nitrogen to which they are attached form piperidinylene;
L ² is a single bond, unsubstituted or straight or branched C _1-4 alkylene, cyclohexylene or phenylene substituted with one of hydroxy and oxo;
Z is an unsubstituted or substituted 5 to 9 membered unsubstituted or substituted heteroaryl containing at least one hetero atom selected from the group consisting of unsubstituted or substituted phenyl, cyclohexyl, naphthyl, N, S and O; fused C _5-6 cycloalkyl, 5 to 6 membered unsubstituted or substituted heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, S and O, N, S and O 6 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 6 to 9 membered unsubstituted or substituted heteroaryl containing at least one heteroatom selected from the group consisting of 6 to 9 membered unsubstituted or substituted heteroaryl C _1-3 alkyl;
wherein said substituted phenyl is substituted with chlorine, phenyl, carboxy, morpholinyl or methoxycarbonyl,
In this case, the substituted heterocycloalkyl, substituted heteroaryl and substituted heteroarylalkyl are each independently linear or branched C _1-3 alkyl, methoxy, benzyl, phenyl, fluorine, chlorine, bromine, hydroxy or oxo. A compound substituted with one or more substituents selected from the group consisting of, an isomer thereof, or a pharmaceutically acceptable salt thereof.
According to claim 1,
Ar is phenyl, naphthyl, pyridine or thiazole;
R ¹ and R ² are each independently hydrogen or fluorine;
R ³ is hydrogen, bromine,

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ego;
L ¹ is

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ego;
L ² is a single bond,

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ego;
Z is

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A phosphorus compound, an isomer thereof, or a pharmaceutically acceptable salt thereof.
According to claim 1,
The compound represented by Formula 1 is any one selected from the group of 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)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-indol-3-yl)propyl)-4-(pentyloxy)benzenesulfonamide;
<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-indol-3-yl)propyl)-4-(2-(piperidin-1-yl)ethoxy)benzenesulfonamide;
<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)piperazine-1- 1) 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)benzene sulfonamides;
<82> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,4-difluoropiperidin-1-yl)propoxy)benzenesulfone amides;
<83> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4-methyl-1,4-diazepan-1-yl)propoxy)benzenesulfone amides;
<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 amides;
<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-fluorobenzene sulfonamides;
<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)benzene sulfonamides;
<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)benzenesulfone amides;
<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)benzene sulfonamides;
<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)benzene sulfonamides;
<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)benzenesulfone amides;
<138> 4-(3-bromo-5-(4-methylpiperazin-1-yl)phenoxy)-N-(3-(5-chloro-1H-indol-3-yl)propyl)benzenesulfone amides;
<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)benzenesulfone amides;
<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)benzenesulfone amides;
<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) pro oxy)benzenesulfonamide;
<170> N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)propyl)-4-(3-(piperazin-1-yl)propoxy)benzene sulfonamides;
<171> (R) -N- (3- (5-chloro-1H-indol-3-yl) propyl) -4- (2-hydroxy-3- (4-methylpiperazin-1-yl) pro oxy)benzenesulfonamide;
<172> (R)-N-(3-(5-chloro-1H-yn-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzene sulfonamides;
<173> (S) -N- (3- (5-chloro-1H-indol-3-yl) propyl) -4- (2-hydroxy-3- (4-methylpiperazin-1-yl) pro oxy)benzenesulfonamide;
<174> (S)-N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(2-hydroxy-3-(piperazin-1-yl)propoxy)benzene sulfonamides;
<175> N-(3-(5-chloro-1H-indol-3-yl)propyl)-4-(3-(4,5-dimethyl-1H-imidazol-1-yl)propoxy)benzenesulfone amides;
<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)prop oxy)benzenesulfonamide;
<182> N-(2-(2-(5-chloro-1H-indol-3-yl)propan-2-yl)phenyl)-4-(3-(piperazin-1-yl)propoxy)benzene sulfonamides;
<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)benzene sulfonamides;
<190>4-(3-(piperazin-1-yl)propoxy)-N-((2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl)benzenesulfonamide;
As shown in Scheme 1 below,
A method for preparing a compound represented by Formula 1 of claim 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.
[Scheme 1]

In 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; and
J ² is amine or piperidine.
A pharmaceutical composition for the prevention or treatment of cancer, inflammatory disease or metabolic disease, comprising the compound represented by Formula 1 of claim 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
8. The method of claim 7,
The compound is a pharmaceutical composition that inhibits Pin1 (Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1).
8. The method of claim 7,
The cancer is pseudomyxoma, intrahepatic biliary tract cancer, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, labial cancer, mycosis fungoides, acute myeloid leukemia, acute lymphoblastic 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 myelogenous leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, ampulla Barter cancer, bladder cancer, peritoneal cancer , parathyroid cancer, adrenal cancer, nasal sinus cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, juvenile brain cancer, juvenile lymphoma, juvenile leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, renal pelvic cancer, kidney cancer, heart cancer, Duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureter cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoma, gastrointestinal stromal cancer, Wilm Breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational chorionic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoma, vaginal cancer, spinal cord cancer, acoustic 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 thymus cancer A pharmaceutical composition, characterized in that at least one selected from the group consisting of.
8. The method of claim 7,
The inflammatory diseases include arthritis, encephalomyelitis, meningitis, peritonitis, osteomyelitis, encephalitis, ankylosing spondylitis, vasculitis, uveitis, ileitis, atherosclerosis, myopathy, leukocyte damage, inflammatory bowel disease, ulcerative colitis, retinal detachment, retinitis pigmentosa. , macular degeneration, pancreatitis, atopic dermatitis, gout, vasculitis, non-alcoholic steatohepatitis, primary sclerosing cholangitis, nephritis, celiac disease, sepsis, systemic inflammatory response syndrome, myocardial infarction, allergic disease, asthma, atopic dermatitis, Wegener A pharmaceutical composition, characterized in that at least one inflammatory disease selected from the group consisting of granulomatosis, pulmonary sarcoidosis, Behcet's disease, chronic obstructive pulmonary disease, and periodontitis.
8. The method of claim 7,
The metabolic disease is obesity, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, arteriosclerosis, fatty liver, gout, a pharmaceutical composition, characterized in that at least one metabolic disease selected from the group consisting of stroke and heart disease.
A health functional food for the prevention or improvement of cancer, inflammatory disease or metabolic disease, comprising the compound represented by Formula 1 of claim 1, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.