WO2017160069A1 - Novel benzenesulfonamide derivative and use thereof - Google Patents

Novel benzenesulfonamide derivative and use thereof Download PDF

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WO2017160069A1
WO2017160069A1 PCT/KR2017/002765 KR2017002765W WO2017160069A1 WO 2017160069 A1 WO2017160069 A1 WO 2017160069A1 KR 2017002765 W KR2017002765 W KR 2017002765W WO 2017160069 A1 WO2017160069 A1 WO 2017160069A1
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Prior art keywords
dimethyl
oxo
isopropyl
pyrazol
benzenesulfonamide
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PCT/KR2017/002765
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French (fr)
Korean (ko)
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김성훈
한균희
양지선
이철호
김재현
정길수
한정민
김종현
Original Assignee
재단법인 의약바이오컨버젼스연구단
연세대학교 산학협력단
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Publication of WO2017160069A1 publication Critical patent/WO2017160069A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C07D231/42—Benzene-sulfonamido pyrazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone

Definitions

  • the present invention relates to a novel benzenesulfonamide derivative or a pharmaceutically acceptable salt thereof and its use, and more particularly, to a novel benzenesulfonamide derivative having an inhibitory effect of mTORCl (Mammal i an target of rapamycin complex 1) and Its active ingredients include cancer, epilepsy, inflammatory diseases, immune diseases, diabetes, obesity, respiratory obstructive diseases, fibrosis, Pompe disease, lysosomal storage di sease, Alzheimer's disease, Parkinson's disease and Huntington's disease. It relates to a pharmaceutical composition for the prevention or treatment of any one disease selected from the group consisting of neurodegenerative diseases such as, cardiovascular diseases and parasitic infections.
  • neurodegenerative diseases such as, cardiovascular diseases and parasitic infections.
  • Amino acids not only serve as raw materials for protein synthesis, but also act as nutrients that regulate protein metabolism.
  • the activity of amino acids available intracellularly is mediated by mTORCl (mechani st ic target of rapamycin com lex 1).
  • MTORCl regulates various cellular reactions such as protein synthesis, autophagy, and cell growth, as well as cancer. It is also closely related to various human diseases such as obesity, diabetes, neurodegeneration (Guert in and Sabat ini, 2005; Zoncu et al., 2011; Lap 1 ante and Sabat ini, 2012; Oddo, 2012).
  • MTOR also known as FRAP (FKBP12 and rapamycin related proteins)
  • FRAP FKBP12 and rapamycin related proteins
  • This protein consists of C—terminal kinase domain, FKBP12-rapamycin binding domain, 20 N-terminal HEAT repeats involved in protein-protein interactions, FAT (FRAP— ATM-TRRAP) domain, and Several domains, including C-terminal FAT domains, also present in other PIKKs (Wul l schleger et al. (2006) Cel l, 124, 471-484).
  • mTOR kinases are central regulators of cell growth and proliferation and play an important role in cell metabolism and angiogenesis. mTOR is activated by the PI3K / Akt axis, which in turn is the downstream effector of the PI3K / Akt signaling pathway, especially cellular proteins. It phosphorylates two major regulators of the translation machinery, ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein (4E-BP1) (mTOR signaling pathways are described in Zoncu et al. (2011) Nature Rev. MoL Cel l Biol. 12, 21-35).
  • S6K1 ribosomal protein S6 kinase
  • 4E-BP1 eukaryotic initiation factor 4E binding protein
  • mTOR signaling pathways are mutated and degenerated in various human cancers, protein kinase Akt, mutation of lipid kinase PI3K and / or inactivation of tumor suppressor PTEN and TSC2 and proliferation and / or mutations affecting growth factor receptors are several events in the upstream of mTOR that result in constitutive inactivation of the PI3K / Akt / mT0R pathway and unregulated cell proliferation. (For a review of the role of protein mTOR in cancer, see Guert in and Sabat lni ( 2007) See Cancer Cel l 12, 9-22).
  • mTOR pathway Genetic mutations and amplifications affecting the mTOR pathway include glioblastoma, prostate cancer, nodular carcinoma, lung cancer (NSCLC), breast cancer, ovarian cancer, endometrial cancer, colon cancer, pancreatic cancer, head and neck cancer, skin cancer and hepatocellular carcinoma. Yuan and Cant ley (2008) Oncogene 27, 5497-5510; Whit taker et al. (2010) Oncogene 29, ' 4989-5005). mTOR employs several collaborators to form two multi-protein complexes essential for tumor growth.
  • the mTORCl complex makes a link between tumor gene signaling and protein synthesis, glycolysis, and lipid biosynthesis (Yecies and Ma ⁇ ing (2011) J ⁇ Mol. Med. 89, 221-228 .
  • the mT0RC2 complex has recently been identified as a kinase that phosphorylates Akt on the Ser-473 residue, acting as an essential activator of the kinase Akt.
  • the role of the complex mT0RC2 has recently been found to be particularly linked to cellular changes (Sparks and Guert in (2010) Oncogene 29, 3733-3744).
  • RCC renal cell carcinoma
  • the efficacy of rapalog in the treatment of cancer is less than expected, despite certain promising results. This restriction is due to the fact that the rapalog does not interact with the mT0RC2 complex and that certain aspects of mTORCl complex activity and in particular the phosphorylation of 4E-BP1 is resistant to rapamycin and its analogs. Benjamin et al, (2011) Nature Reviews Drug Discovery 10, 868-880.
  • inhibitors of mTOR kinase sites are devoid of these drawbacks (Feldman et al. (2009) PLoS Biology 7, 371-383), and are recognized as new generation mTOR pathway modulators, which have the potential to increase anticancer activity and broader therapeutic potential. . this has coverage though some of the dogs are currently being clinically tested (Garcia-Echeverria (2011) Biochem Soc Trans 39, 451-455; Richard et al (2010) Curr Drug Opinion Disc Dev. 13, 428—440. Other potential therapeutic indications have been proposed for mTOR inhibitors (Tsang et al. (2007) Drug Discovery Today 12, 112-124).
  • mTOR inhibitors may have neuroprotective effects in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease (Bov'e et al. (2011) Nature Reviews Neuroscience 12, 437-452).
  • mTOR overactivity is associated with age-related diseases (Harrison et al. (2009) Nature 460, 392), and other tropisms are renal, lung and liver fibrosis (Mehrad et al. (2009) Int. J. Biochem Cell Biol. 41, 1708-1718; Lieberthal and Levi ne (2009); Shouval (2011)), inflammatory and autoimmune diseases (Bhonde et al. (2008) Am. J. Physiol. Gastrointest. Liver Physiol.
  • mTOR inhibition also activates autophagy and causes certain diseases, especially metabolic and renal Mildly degenerative white-, bacterial and viral infections and cancers are sensitive to their inhibition (review in Rubinsztein et al. (2007) Nature 6, 304-312).
  • mTORCl regulates various upstream signals such as cell growth, protein synthesis, and growth factor regulation.
  • Tuberous Scleros is Complex (TSC) which transfers growth factors and energy signals to mTORCl, is a GTPase-activating protein (GAP) for Ras ike smal l GTPase, Rheb, and Rheb Negatively regulate mTORCl by promoting GTP hydrolysis of
  • Rheb can migrate to late endosomes / lysosomes and is required for mTORCl activation induced by amino acids.
  • Rag GTPases and Ragul ator compl ex act as amino acid inducible docking sites for mTORCl.
  • Mammals express four Rag GTPases (RagA, RagB, RagC, RagD).
  • Rag GTPases essentially form heterodimers of RagA / C or RagB / D to mediate amino acid-induced mTORCl activation.
  • everol imus an allosteric inhibitor of mTOR
  • has the effect of treating a carcinoma with a change in mTOR signal its resistance is shown.
  • Acquireable resistance due to activation of the mTOR mutation inhibits everol imus binding to mTOR.
  • the FRB domain, S2035, in mTOR is essential for FKBP12—rapamycin to bind, and mutations in this position result in rapamycin resistance.
  • a clear understanding of the mechanism of achievable resistance could be used in the development of new therapeutics to combat mutations that are resistant to mTOR inhibitors.
  • aminoacyl-tRNA-synthetases ARSs
  • ARSs aminoacyl-tRNA-synthetases
  • ARS promotes the binding of amino acids to the tRNA being treated. To maintain protein homeostasis, ARS must sensitize amino acid availability.
  • Leucine-tRNA-synthetase functions as a leucine sensor for mTORCl activation by interacting with RagD GTPase and acting as a GAP for RagD GTPase. Therefore, if LRS detects a substance that inhibits its function as a leucine sensor without affecting the original function of binding leucine to tRNA, it inhibits the binding of LRS and RagD to inhibit the activation of mTORCl. Inhibition and consequently will have an effect on potential therapeutic sympathy for mTOR inhibitors.
  • an object of the present invention is to provide a compound represented by the following Chemical Formula 1 To provide acceptable salts: [Formula 1]
  • R 1 is substituted or unsubstituted phenyl; Halo; Or when straight or branched d—C 6 alkyl and R 1 is substituted phenyl the substituents are straight or substituted with a halogen atom, unsubstituted straight or branched d—C 6 alkyl and one or more halogen atoms or Branch type
  • C Ce alkyl is hydrogen; Or straight or branched d-Cs alkyl,
  • R 3 is hydrogen; Substituted or unsubstituted d-Cs straight or branched alkyl; C 5 -C 10 cycloalkyl; Substituted or unsubstituted C 5 -C 20 aryl; Dioxoanthracenyl; Or a heterocyclic ring or heteroaryl ring having one or more heteroatoms in the ring, where these substituents are linear or branched C 6C 6 alkyl; - (: 6 alkyloxy; d- C 6 alkyl, d- C 6 alkyloxy optionally substituted with amino group; substituted by morpholinyl d- C 6 alkyloxy; d- C 6 alkyloxy carbonyl Brassica; hydroxy-carbonyl d- C 6 alkyl; d-Cs alkyl substituted with one or more fluoro atoms; CrCs alkylamino; phenyl; straight or branched dC 6 alkyl,
  • R 2 and R 3 combine with each other to form a C 5 ⁇ C 20 hetero ring or heteroaryl ring containing one or more hetero atoms in the ring.
  • Another object of the present invention to provide a method for preparing a benzenesulfonamide derivative represented by the formula (1), another object of the present invention comprises a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient
  • a pharmaceutical composition for the prevention or treatment of cancer another object of the present invention by administering to a subject in need of an effective amount to a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof cancer-related diseases
  • Another object of the present invention to provide a use of the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for the manufacture of an anticancer agent.
  • the present invention provides a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
  • R 1 is substituted or unsubstituted phenyl; Halo; Or when straight or branched Ci-Cg alkyl and R 1 is substituted phenyl the substituents are straight or branched, substituted by halogen atoms, unsubstituted straight or branched d-Ce alkyl and one or more halogen atoms
  • R 2 is hydrogen; Or straight or branched dC 6 alkyl,
  • R 3 is hydrogen; Substituted or unsubstituted d— C 6 straight or branched alkyl; C 5 — C 10 cycloalkyl; Substituted or unsubstituted C 5 — C 20 aryl; Dioxoanthracenyl; Or a heterocyclic ring or heteroaryl ring having one or more heteroatoms in the ring, where these substituents are linear or branched dC 6 alkyl; dC 6 alkyloxy; d— C 6 alkyloxy substituted with d-alkyl amino group; DC 6 alkyloxy substituted with morpholine; d— C 6 alkyloxycarbonyl; Hydroxycarbonyl Cr ′′ C 6 alkyl; CrCs alkyl substituted with one or more fluoro atoms; d_C 6 alkylamino; phenyl; straight or branched d—C 6 alkyl, straight or branched Ci— C 6 Pheny
  • the present invention provides a method for preparing a benzenesulfonamide derivative represented by Formula 1.
  • the present invention provides a compound represented by Formula 1 or It provides a pharmaceutical composition for the prevention or treatment of cancer comprising a pharmaceutically acceptable salt as an active ingredient.
  • the present invention provides a method for treating cancer-related diseases by administering to a subject in need thereof an effective amount of a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof.
  • the present invention provides a use of the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for the manufacture of an anticancer agent.
  • the present invention will be described in detail.
  • the present invention provides a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
  • R 1 is substituted or unsubstituted phenyl; Halo; Or when straight or branched d—C 6 alkyl and R 1 is substituted phenyl the substituents are straight or substituted with a halogen atom, unsubstituted straight or branched d—C 6 alkyl and one or more halogen atoms or Branch type One or more selected from the group consisting of Ci-C 6 alkyl, R 2 is hydrogen; Or straight or branched d—C 6 alkyl,
  • R 3 is hydrogen; Substituted or unsubstituted dC 6 straight or branched alkyl; rC 10 cycloalkyl; Substituted or unsubstituted C 5 -C 20 aryl; Dioxoanthracenyl; Or a heterocyclic ring or heteroaryl ring having one or more heteroatoms in the ring, where these substituents are linear or branched dC 6 alkyl; dC 6 alkyloxy; d- C 6 a d- C 6 alkyloxy optionally substituted with an alkyl group; C— C 6 alkyloxy substituted with morpholine; d— C 6 alkyloxycarbonyl; Hydroxycarbonyl d—C 6 alkyl; D—C 6 alkyl substituted with one or more fluoro atoms; C 6 alkylamino; Phenyl; Group consisting of straight or branched C r -C 6 alkyl, straight or
  • the sing-groups R 2 and R 3 combine with each other to form a C 5 — C 20 hetero ring or heteroaryl ring containing one or more hetero atoms in the ring.
  • Alkyl 'means an aliphatic hydrocarbon group that may be straight or branched, containing from about 1 to about 20 carbon atoms in the chain. Preferred alkyl groups include from about 1 to about 12 carbon atoms in the chain. More preferred alkyl groups include about 1, 2, 3, 4, 5 or 6 carbon atoms in the chain, the side chains comprising one or more lower alkyl groups such as methyl, Ethyl or propyl linear alkyl chain It means attached to. "Loweralkyl”'means a group having from about 1 to about 6 carbon atoms in the chain, which may be straight or branched, "alkyl” means one or more, which may be unsubstituted, or may be the same or different.
  • each substituent may be halogen, alkyl, aryl, cycloalkyl, cyano, hydroxy, alkoxy, alkylthio, amino, carboxy, etc.
  • alkyl is butyl or isobutyl Can be.
  • Aryl means an aromatic hydrocarbon ring system, examples of which include phenyl, indenyl, indanyl, naphthyl and fluorenyl, and may preferably be (6C) aryl,
  • Halogen may include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, preferably a fluorine atom, a chlorine atom or a brom atom.
  • Cycloalkyl 'otherwise means a saturated hydrocarbon ring.
  • Heteroaryl is an aromatic cycloalkyl (also referred to as heteroaryl) in some embodiments of a compound of Formula (II) with a heteroatom, wherein one to four of the ring carbon atoms are selected from solvates consisting of 0, S and N Or non-aromatic cycloalkylide-, in some embodiments, the heterocyclyl group contains 3 to 10 ring members, while such other groups include 3 to 5, 3 6, or 3 to 8 ring members Hold them. Heterocyclyl may also be combined with other groups at any ring atom (ie, heterocarbon ring any carbon atom or heteroatom). Heterocycloalkyl groups can be substituted or unsubstituted.
  • Heterocyclyl groups include unsaturated, partially saturated and saturated ring systems such as midazolyl, imidazolinyl and imidazolidinyl groups.
  • the term hyterocyclyl includes fused ring species, eg, fused aromatic and non-aromatic groups, for example benzotriazolyl, 2, 3—dihydrobenzo [1,4] dioxynyl and Benzo [1, 3] dioxolyl.
  • the term also includes, but is not limited to, crosslinked polycyclic ring systems containing heteroatoms such as quinuclidyl.
  • heterocyclyl group examples include aziridinyl, azetidinyl, pyridyl, imidazolidinyl, pyrazole lidinyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydrofuranyl, dioxolyl, furanyl, thio Phenyl, pyrillyl, pylinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl, Isothiazolyl, thiadiazolyl, oxadiazolyl, pyreridyl, piperazinyl, morpholinyl, thiomorpholinyl tetrahydropyranyl (eg, tetrahydro-2H-pyranyl),
  • a "cycloalkylalkyl group” is a radical of the general formula -alkyl ⁇ cycloalkyl, wherein alkyl and cycloalkyl are as defined above.
  • the cycloalkylalkyl group is an alkyl, cyclo Alkyl, or both alkyl and cycloalkyl moieties .
  • Exemplary cycloalkylalkyl groups include, but are not limited to, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclonuxylethyl, and cyclonuxylpropyl No.
  • substituents include the exemplary compounds and embodiments disclosed herein. Examples of which can be found, and halogens (chloro, urethral, bromo or fluoro groups); alkyl; hydroxyl; alkoxy; al Sialic keel; amino; alkylamino; carboxy; nitro; cyano; thiol; thioether; imine; imide; amidine; guanidine; INC Min; aminocarbonyl; acylamino; phosphonate Nei Sat; PO Spin; Thiocarbonyl; Sulfonyl; Sulfone; Sulfonamides; Ketones; Aldehydes; ester; Urea; urethane; Oxime; Hydroxyl amines; Alkoxyamines; Aralcoxiamine; N-oxides; Hydrazine; Hydrazide; Hydr
  • straight or branched dC 6 alkyl d— C 6 alkyloxy; dC in 6 alkylamino group value hwandoen dC 6 alkyloxy; D-Cs alkyloxy substituted with morpholine; d— C 6 alkyloxycarbonyl; Hydroxycarbonyl d—C 6 alkyl; DC 6 alkyl substituted with one or more fluoro atoms; dC 6 alkylamino; Phenyl; Straight or branched dC 6 alkyl, straight or branched d—C 6 alkyloxy, straight or branched dC 6 alkyloxycarbonyl, halogen or alkyl substituted with one or more fluoro atoms Phenyl substituted with one or more substituents selected from; Phenoxy; Phenoxy substituted with one or more substituents selected from the group consisting of straight or branched d—C 6 alkyl, halogen atoms and straight
  • the compound of Formula 1 may be selected from the following.
  • N1-cyclonuclear chamber 4 ⁇ isopropyl -2,3-dimethyl- 5-oxo-pyrazol-l-yl) benzenesulfonami
  • NI (3, 5-dimethoxyphenyl) -4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) benzene sulfonamide;
  • N-cycloheptyl-4- (4—isopropyl-2, 3—dimethyl— 5—oxo—pyrazole— 1—yl) benzenesulfonami 4- (4 isopropyl— 2, 3—dimethyl-5—oxo-pyrazol— 1-yl) — N— [3- (trifluoromethyl) phenyl] benzenesulfonamide;
  • benzyl-4- (4—isopropyl-2, 3-dimethyl— 5-oxo-pyrazol-1—yl) benzenesulfonamide; methyl 2— [[4- (4-isopropyl-2, 3— dimethyl-5-oxo-pyrazol-1- yl) phenyl] sulfonyl amino furnace; - eu 2-phenyl-acetate;
  • N1 [2— (3, 5-dimethylphenoxy) ethyl] -4- (4-isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol one 1-yl) benzenesulfonamide; 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) - ⁇ 'propyl-benzenesulfonamide;
  • Methyl 6 (4- (4-isopropyl— 2, 3-dimethyl-5—oxo-2, 5-dihydro-1H-pyrazol-1-yl) phenylsulfonamido) -2 ⁇ naphthoate;
  • the benzosulfonamide derivatives of Formula 1 of the present invention may be used in the form of pharmaceutically acceptable salts.
  • Acid salts formed by various organic or inorganic acids that are pharmaceutically or physiologically acceptable are useful as such salts.
  • Suitable organic acids include, for example, carboxylic acid, phosphonic acid, sulfonic acid, acetic acid, propionic acid, octanoic acid, decanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, malic acid, tartaric acid, citric acid, glutamic acid, Aspartic acid, maleic acid, benzoic acid, salicylic acid, phthalic acid, phenylacetic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, methyl sulfuric acid, ethyl sulfuric acid, dodecyl sulfuric acid and the like can be used.
  • the benzosulfonamide derivatives of the general formula (I) of the present invention may include not only pharmaceutically acceptable leathers, but also all salts, hydrates, and solvates that can be prepared by conventional methods.
  • the present invention provides a method for preparing a benzosulfonamide derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof. Method for producing a derivative of formula 1 according to the present invention as shown in Scheme 1
  • R1, R2, and R3 are as defined in Chemical Formula 1. Since the benzosulfonamide derivatives or pharmaceutically acceptable salts thereof of the present invention exhibit the effect of inhibiting the activity of mTOR by inhibiting the binding between LRS and RagD, it is possible to prevent various diseases in which the therapeutic effect is achieved by inhibiting mTOR. Or can be treated.
  • Non-limiting examples of diseases in which the therapeutic effect is achieved by inhibiting the mTOR in the present invention is cancer, epilepsy, inflammatory diseases, immune diseases, diabetes, obesity, respiratory obstructive diseases, fibrosis, pamp disease, lysosomal accumulation disease (lysosomal storage di sease), neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, cardiovascular disease / and / or parasitic infections, preferably cancer or epilepsy.
  • the compounds of the present invention have a very good effect of inhibiting the activity of mTORCl, which is known to be highly active in cancer cells, and exhibit cytotoxicity against various cancer cells, while It was confirmed that no cytotoxicity was observed for the cells.
  • the present invention provides a pharmaceutical composition for preventing or treating cancer, comprising the benzosulfonamide derivative of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention is to treat a cancer-related disease by administering to a subject in need of a benzosulfonamide derivative of Formula 1 or a pharmaceutically acceptable salt thereof Provides a way to do it.
  • the cancer provides a method characterized in that the cancer showing rapamycin resistance, the present invention also provides a use for the production of an anticancer agent of the benzosulfonamide derivative of Formula 1 or a pharmaceutically acceptable salt thereof .
  • the cancer provides a use for the manufacture of a therapeutic agent, characterized in that the cancer showing rapamycin resistance,
  • LRSC leucyl tRNA synthetase functions as a key mediator of amino acid signaling to mTORCl. That is, LRS binds directly to Rag GTPase, an amino acid dependent signaling medium for mTORCl, and acts as a GTPase-act ivat mg protein (GAP) for Rag GTPase, thereby activating mTORCl.
  • GAP GTPase-act ivat mg protein
  • LRS Leucyl tRNA synthetase plays an important role in the activation of mTORCl derived from amino acids, so that LRS senses intracellular leucine concentrations and affects the activation of mTORCl derived from leucine.
  • Rag protein belongs to Rag subfami ly of Ras smal l GTPase and there are four kinds of RagA, RagB, RagC and RagD, of which A and B are orthologs of yeast Gtrlp GTPase and C and D are East's Gtr2p ortholog.
  • RagD combines with A or B to form a dimer and mediates mTORCl activity by amino acids. (Trends in Biochemi cal Sciences, 33: 565-568, 2008). Therefore, inhibiting the binding between LRS and RagD may inhibit the activation of mTORCl, which may have the effect of preventing or treating cancer. More specifically, the cancer is not limited thereto.
  • Melanoma leukemia, colorectal cancer, lung cancer, Liver cancer, stomach cancer, esophageal cancer, pancreatic cancer, gallbladder cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, cervical cancer, endometrial cancer, chorionic cancer, ovarian cancer, breast cancer, thyroid cancer, brain cancer, head and neck cancer, skin cancer, lymphoma, aplastic anemia And the like.
  • Lymphomas include both Hodgkin's lymphoma and non-Hodgkin's lymphoma and include B-cell neoplasms such as Precursor B cel l neoplasm, and B-cell tumors (Precursor Hodgkin lymphoma such as T-cell and ⁇ -cell neoplasia (T—Cell AND NK-CELL NEOPLASMS) and Hodgkin's lymphoma (Cl ass i cal Hodgkin lymphoma) lymphoma, Hodgkin di sease).
  • B-cell neoplasms such as Precursor B cel l neoplasm
  • B-cell tumors Precursor Hodgkin lymphoma such as T-cell and ⁇ -cell neoplasia (T—Cell AND NK-CELL NEOPLASMS) and Hodgkin's lymphoma (Cl ass i cal Hodgkin lymphom
  • the benzosulfonamide derivative of Formula 1 of the present invention may exhibit an effective therapeutic effect against cancer showing rapamycin resistance.
  • the benzosulfone amide derivatives of Formula 1 showed an effect of inhibiting leucine-sensitive activity of LRS without affecting the enzymatic activity of LRS.
  • the expression level of LRS was positively correlated with the activation of Rag GTPase and mTORCl in colorectal cancer tissues and cells.
  • the benzosulfonamide derivative of Formula 1 of the present invention specifically binds to a position interacting with RagD in LRS and specifically inhibits the position of LRS as a lysosome, thereby inhibiting the activity of RagD GTPase and mTORCl, resulting in cancer It showed the effect of inhibiting growth. This effect is the same in cancer cells that are resistant to rapamycin.
  • the benzosulfonamide derivative of Formula 1 of the present invention effectively prevents or treats cancers that exhibit resistance to rapamycin due to mTOR mutations.
  • treatment of the compound of the present invention in cells expressing mTOR mutations (L2427P) associated with epilepsy results in (i) hydrolysis of RagD GTP and lysosomal of LRS.
  • the translocat ion was inhibited, and the activity of (ii) mTORCl was also inhibited.
  • the compound of the present invention was administered to an interstitial animal model, the number of epileptic seizures was significantly reduced compared to the control group.
  • the compound of the present invention appears to have a very high blood-brain barrier (BBB) permeability and is highly likely to be developed as a prophylactic agent for brain diseases.
  • BBB blood-brain barrier
  • the pharmaceutical composition according to the present invention may be formulated in various ways depending on the route of administration by methods known in the art together with pharmaceutically acceptable carriers.
  • 'Pharmaceutically acceptable is a non-toxic composition that is physiologically acceptable and, when administered to humans, does not inhibit the action of the active ingredient and usually does not cause gastrointestinal disorders, allergic reactions such as dizziness or similar reactions.
  • the carriers include all kinds of solvents, dispersion media, oil-in-water or water-in-oil emulsions, aqueous compositions, liposomes, microbeads and hemp Microsomes are included.
  • the composition of the present invention may be formulated according to methods known in the art in the form of injections, transdermal and nasal inhalants with suitable parenteral carriers.
  • injectables must be sterilized and protected from contamination of microorganisms such as bacteria and fungi.
  • suitable carriers for injectables include, but are not limited to, solvents including water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycols), combinations thereof and / or vegetable oils. Or a dispersion medium. More preferably, suitable carriers include Hanks' solution, Ringer's solution, and triethane containing amines.
  • PBS phosphate buf fered sal ine
  • sterile water for injection 10% ethanol, 40% propylene glycol, and isotonic solutions such as 53 ⁇ 4 dextrose
  • Butane may further include various antibacterial and antifungal agents such as phenol, sorbic acid, thimerosal and the like.
  • the injection may in most cases further include an isotonic agent, such as sugar or sodium chloride.
  • ointments creams, lotions, gels, external preparations, pastas, liniments, Aerosols and the like.
  • 'transdermal administration means a topical administration of a composition of the present invention to the skin to deliver an effective amount of the active ingredient contained in the composition into the skin, for example, to prepare a composition of the present invention in an injectable formulation. This can be administered by lightly applying the skin directly to the skin with a 30-gauge thin needle.
  • the aerosol from a pressurized pack or nebulizer using a suitable propellant, for example ⁇ dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas It can be delivered conveniently in the form of a spray.
  • a suitable propellant for example ⁇ dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas
  • the dosage unit can be determined by providing a valve to deliver a metered amount.
  • gelatin capsules and cartridges used in inhalers or inhalers may be used as compounds and lactose or starch.
  • Formulations may be made to contain suitable powder based powder mixtures.
  • compositions according to the invention may also contain one or more buffers (eg saline or PBS), carbohydrates (eg glucose, mannose, sucrose or textane), antioxidants, bacteriostatic agents, chelating agents (eg For example, EDTA or glutathione), adjuvants (eg, aluminum hydroxide), suspending agents, thickening agents and / or preservatives may be further included.
  • buffers eg saline or PBS
  • carbohydrates eg glucose, mannose, sucrose or textane
  • antioxidants eg glucose, mannose, sucrose or textane
  • bacteriostatic agents eg For example, EDTA or glutathione
  • adjuvants eg, aluminum hydroxide
  • suspending agents eg, thickening agents and / or preservatives may be further included.
  • compositions of the present invention may be variously formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. It can be administered in combination with a known compound which is effective in preventing or treating cancer.
  • the term 'effective amount' of the present invention when administered to an individual, refers to an amount that exhibits an effect of improving, treating, preventing, detecting, or diagnosing cancer, and the term 'individual' includes an animal, preferably a mammal, particularly a human. It may be an animal, cells, tissues, organs, etc. derived from the animal. The subject may be a patient in need of treatment.
  • treatment is intended to inhibit the occurrence or recurrence of a disease, alleviate symptoms, reduce direct or indirect pathological consequences of a disease, Reduced, improved, improved, alleviated or improved prognosis. More specifically, the term "treatment” of the present invention refers generically to ameliorating symptoms of cancer, which may include curing, substantially preventing, or ameliorating such a disease, It may include, but is not limited to, alleviating, healing or preventing one symptom resulting from, or most of the symptoms resulting from.
  • Benzenesulfonamide derivatives of Formula 1 according to the present invention inhibit the binding between LRS and RagD and thus inhibit the mTORCl activation, thereby inhibiting mTOR Cancer, epilepsy, inflammatory disease, immune disease, diabetes, obesity, respiratory obstructive disease, fibrosis, pamp disease, lysosomal storage di sease, Alzheimer's disease, Parkinson's disease and Huntington Neurodegenerative diseases such as diseases, cardiovascular diseases and parasitic infections can be very useful in the development of a prophylactic or therapeutic agent for any disease selected from the group consisting of parasitic infections.
  • Figure 2 shows the EC50 of cytotoxicity of benzenesulfonamide derivatives against various cancer cells.
  • FIG. 3 shows the hydrolysis of RagD GTP and the lysosomal translocat of LRS when the LRS is deleted (FIG. 3A) or treated with a compound according to the invention (FIG. 3B) in NIH3T3 cells expressing an mTOR mutation associated with epilepsy (L2427P). Western blot confirmed that the ion is reduced.
  • Figure 4 shows that the NIH3T3 cells expressing mTOR mutations (L2427P) associated with epilepsy reduced the activity of niTORCl when treated with a compound according to the present invention by Western blot (FIG. 4A) and quantified it graphically (FIG. 4B).
  • Figure 5 is a result of measuring the number of expression of interstitial seizures after administering a compound, rapamycin or a control according to the invention in an epileptic animal model.
  • BBB blood-brain barrier
  • Example 1-13 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1 ⁇ yl) ⁇ > ⁇ [2- (2- hydroxyphenyl) ethyl] benzenesulfonamide Produce
  • Example 1_1 4 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl)-[2- (2-hydroxyphenoxy) ethyl] benzenesulfonamide
  • the target compound was obtained by reaction in the same manner as in Example 1-1 using 2- (2-methoxyphenoxy) ethanamine as a starting material. (Yield 92.4%)
  • the reaction mixture was reacted in the same manner as in Example 1-1, using 4-phenylbutanyl 1-amine as a starting material to obtain a target compound.
  • the reaction product was reacted in the same manner as in Example 1-1 using 2 ⁇ (4-chlorophenyl) ethanamine as a starting material to obtain the target compound.
  • Example 1-1 The same method as Example 1-1, using thiophene-2-ylmethanamine as starting material. Reaction to give the desired compound.
  • Example 1-30 The preparation of 4— (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) —N— (2-naphthylmethyl) benzenesulfonamide The reaction compound was reacted in the same manner as in Example 1-1 using naphthalene # 2-ylmethanamine as a starting material to obtain a target compound.
  • the reaction mixture was prepared in the same manner as in Example 1-1, using 5 ilfluoropyridin ⁇ 2-amine as a starting material, to obtain the target compound.
  • N, N-dimethylbenzene—1,4-diamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
  • the desired compound was obtained by reaction in the same manner as in Example 1-1, using methyl 3-aminobenzoate as starting material.
  • Example 1 38 Preparation of ethyl 3 — [[4- (4-isopropyl—2,3—dimethyl-5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] benzoate
  • Example 1-1 4-isopropylaniline was used as a starting material and reacted in the same manner as in Example 1-1, to obtain a target compound.
  • 3-fluoroaniline was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
  • Naphthalene— 1-amine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
  • Example 1-46 N — [(3-fluorophenyl) methyl] —4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Produce (3-fluorophenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
  • the reaction mixture was reacted in the same manner as in Example 1-1 using mylruidine as a starting material to obtain a target compound.
  • the reaction mixture was reacted in the same manner as in Example 1-1, using 0-erluidine as a starting material, to obtain a target compound.
  • Example 1-62 N- (2, 4-dimethylphenyl) -4 - Preparation of (4-isopropyl-2, 3-dimethyl-5-oxo-1-yl) benzenesulfonamide 2,4—dimethylaniline was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound.
  • 3-ethylaniline was used as a starting material and reacted in the same manner as in Example 1-1, to obtain a target compound.
  • Example 1-78 Ethyl 4- [[4— (4-isopropyl— 2, 3 ⁇ dimethyl-5-oxo-pyrazol-1—yl) phenyl] sulfonylamino] piperidine-1- Preparation of Carboxylate Reaction was carried out in the same manner as in Example 1-1, using ethyl 4-aminopiperidine— 1—carboxylate as starting material, to obtain the target compound.
  • 2-chloropyridin-4-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
  • Biphenyl] -2-2-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
  • 2-methylnaphthalene-l-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
  • the desired compound was obtained by reaction in the same manner as in Example 1-1-1 using 2- (5-methoxy-lH-indole-3-yl) ethanamine as starting material.
  • the target compound was obtained in the same manner as in Example 1-1, using 2methyl-1H ⁇ indole-5-amine as a starting material.
  • 6-Methoxybenzo [d] thiazole-2-amine was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound.
  • Example 1-106 Preparation of N- (3,5-dichlorophenyl) '4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-l-yl) benzenesulfonamide 3, 5-dichloroaniline was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
  • the reaction product was reacted in the same manner as in Example 1-1 using 4yethynylaniline as a starting material, to obtain the target compound (yield 79 bend43 ⁇ 4).
  • the target compound was obtained in the same manner as in Example 1-1, using 2 '(3—chlorophenyl) ethanamine as a starting material. (Yield 73.1)
  • the target compound was obtained in the same manner as in Example 1-1, using (2 ⁇ (trifluoromethyl) phenyl) methanamine as a starting material. (Yield 77.3)
  • Example 1-124 Preparation of ⁇ (3-chlorophenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Reaction was carried out in the same manner as in Example 1-1, using ternary chloroaniline as a starting material, to obtain the target compound. (Yield 88.8%)
  • the desired compound was obtained in the same manner as in Example 1-1, using 2 (2-bromophenyl) ethanamine as a starting material.
  • Example 1-135 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) -N- [2- [4- (trifluoromethyl) phenyl] ethyl ] Preparation of Benzenesulfonamide
  • the desired compound was obtained by reaction in the same manner as in Example 1-1, using 2 [[4] (trifluoromethyl) phenyl] ethanamine as starting material.
  • Example 1-136 4- (4—Isopropyl ⁇ 2, 3-dimethyl-5-oxo-pyrazol-1—yl) — N— [4— (trifluoromethyl) phenyl] benzenesulfonamide Manufacture
  • Example 1-138 Preparation of 4- (4 ⁇ chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N '(2-phenoxytyl) benzenesulfonamide Preparation of 1, 4— (4 ⁇ chloro-2,3—dimethyl—5—oxo-pyrazol-iyl) benzenesulfonyl chloride
  • Example 1-1 Preparation of 4 -— (4-chloro-2, 3-dimethyl-5-oxo-pyrazol-1xyl) -N-[(4-fluorophenyl) methyl] benzenesulfonamide
  • 2,3—dihydro—1,4-benzodioxin-6-amine was used as a starting material to react the same method as in Examples 1-127 to obtain the target compound.
  • Example 1-162 4- (4-Bromo-2,3-dimethyl-5-oxo-pyrazol-1xyl) — of N- (5-chloro-2—fluoro-phenyl) benzenesulfonamide Produce
  • the reaction product was reacted in the same manner as in Example 1-127, using dibasic aminophenol as a starting material, to obtain a target compound.

Abstract

The present invention relates to a novel benzenesulfonamide derivative or a pharmaceutically acceptable salt thereof and a use thereof and, more specifically, to a novel benzenesulfonamide derivative having a mammalian target of rapamycin complex 1 (mTORC1) inhibitory effect and to a pharmaceutical composition containing the same as an active ingredient. The benzenesulfonamide derivative of chemical formula 1 according to the present invention is very highly effective in inhibiting the activation of mTORC1 through the inhibition of the binding between LRS and RagD, and thus the benzenesulfonamide derivative is very favorably utilized in the development of a prophylactic or therapeutic agent for any one disease selected from the group consisting of cancer, epilepsy, inflammatory diseases, immune diseases, diabetes, obesity, respiratory obstructive diseases, fibrosis, Pompe's disease, lysosomal storage disease, neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease, and Huntington's disease), cardiovascular diseases, and parasitic infections, for which therapeutic effects can be attained by inhibiting mTOR.

Description

【명세서】  【Specification】
【발명의 명칭】  [Name of invention]
신규한 벤젠설폰아미드 유도체 및 이의 용도  Novel benzenesulfonamide derivatives and uses thereof
【기술분야】 Technical Field
본 출원은 2016년 3월 15일에 출원된 대한민국 특허출원 제 10-2016-0030845 호를 우선권으로 주장하고, 상기 명세서 전체는 본 출원의 참고문헌이다. 본 발명은 신규한 벤젠설폰아미드 유도체 또는 이의 약학적으로 허용가능한 염 및 이의 용도에 관한 것으로, 보다 상세하게는 mTORCl (Mammal i an target of rapamycin complex 1) 저해 효과를 갖는 신규한 벤젠설폰아미드 유도체 및 이를 유 효성분으로 포함하는 암, 간질, 염증질환， 면역질환， 당뇨, 비만， 호흡기계 폐쇄성 질환, 섬유증， 폼페병, 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질흰ᅳ， 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행성 질환, 심혈관계질환 및 기생 충 감염증으로 이루어진 군에서 선택된 어느 한 질환의 예방 또는 치료용 약학적 조성물에 관한 것이다.  This application claims the priority of Korean Patent Application No. 10-2016-0030845, filed March 15, 2016, the entirety of which is a reference of the present application. The present invention relates to a novel benzenesulfonamide derivative or a pharmaceutically acceptable salt thereof and its use, and more particularly, to a novel benzenesulfonamide derivative having an inhibitory effect of mTORCl (Mammal i an target of rapamycin complex 1) and Its active ingredients include cancer, epilepsy, inflammatory diseases, immune diseases, diabetes, obesity, respiratory obstructive diseases, fibrosis, Pompe disease, lysosomal storage di sease, Alzheimer's disease, Parkinson's disease and Huntington's disease. It relates to a pharmaceutical composition for the prevention or treatment of any one disease selected from the group consisting of neurodegenerative diseases such as, cardiovascular diseases and parasitic infections.
【배경기슬】 Background
아미노산은 단백질 합성의 원료로 사용될 뿐만 아니라 단백질 대사를 조절하 는 영양소로서 작용한다. 세포내에서 사용 가능한 아미노산의 작동은 mTORCl (mechani st i c target of rapamycin com lex 1)에 의해 매개가 되며, mTORCl 은 단백질 합성, 자가소화작용， 세포 성장과 같은 다양한 세포 내 반웅을 조절할 뿐만 아니라， 암, 비만， 당뇨 및 신경퇴행 등 다양한 인간 질환과도 밀접하게 관련 이 되어 있다 (Guert in and Sabat ini , 2005； Zoncu et al . , 2011； Lap 1 ante and Sabat ini , 2012； Oddo , 2012) .  Amino acids not only serve as raw materials for protein synthesis, but also act as nutrients that regulate protein metabolism. The activity of amino acids available intracellularly is mediated by mTORCl (mechani st ic target of rapamycin com lex 1). MTORCl regulates various cellular reactions such as protein synthesis, autophagy, and cell growth, as well as cancer. It is also closely related to various human diseases such as obesity, diabetes, neurodegeneration (Guert in and Sabat ini, 2005; Zoncu et al., 2011; Lap 1 ante and Sabat ini, 2012; Oddo, 2012).
FRAP(FKBP12 및 라파마이신 관련 단백질)로도 알려져 있는 mTOR (라파마이신 의 포유류 타깃)은 비록 인지질을 인산화하지는 않지만, PIKK (포스포이노시타이드 3一키나제 -유사 키나제) 패밀리의 289-kDa 세린 /트레오닌 키나제이다ᅳ 이 단백질은 C—말단 키나제 도메인, FKBP12-라파마이신 결합 도메인, 단백질 -단백질 상호작용에 관련된 20 N-말단 HEAT 반복， FAT(FRAP— ATM-TRRAP) 도메인 및 다른 PIKK에도 존재하는 C-말단 FAT 도메인을 포함하는 수개의 도메인을 포함한다 (Wul l schleger et al . (2006) Cel l , 124 , 471-484) . mTOR 키나제는 세포 성장 및 증식의 중심적인 조절자이며， 세포 대사 및 혈 관형성에도 중요한 역할을 한다, mTOR는 PI3K/Akt 축에 의해 활성화되며 차례로 PI3K/Akt 신호 경로의 다운스트림 이펙터, 특히 세포 단백질 번역 기구의 두개의 주 조절자인 리보좀 단백질 S6 키나제 (S6K1) 및 진핵 개시 인자 4E 결합 단백질 (4E-BP1)을 인산화한다 (mTOR 신호 경로는 Zoncu et al . (2011) Nature Rev. MoL Cel l Biol . 12， 21— 35에 기재되어 있다) . mTOR신호 경로는 다양한 인간 암에서 돌연변이되고 해제된다 (deregulated) , 단백질 키나제 Akt , 지질 키나제 PI3K의 돌연변이 및 /또는 종양 억제자 PTEN 및 TSC2의 불활성화와 성장 인자 수용체에 영향을 주는 증식 및 /또는 돌연변이는 PI3K/Akt/mT0R 경로의 구성적 불활성화 및 미조절 세포 증식을 초래하는 mTOR의 업 스트림에서의 몇 개의 이밴트이다 (암에서의 단백질 mTOR의 역할에 관한 리뷰를 위 해서는 Guert in and Sabat lni (2007) Cancer Cel l 12 , 9—22 참조) . mTOR 경로에 영향을 미치는 유전적 돌연변이 및 증폭은 교아종, 전립선암, 결절 경희-， 폐암 (NSCLC)ᅳ 유방암, 난소암, 자궁내막암, 대장암, 췌장암, 두경부암, 피부암 및 간세포암의 형성에서 확인된 바 있다 (Yuan and Cant ley (2008) Oncogene 27 , 5497-5510； Whi t taker et al . (2010) Oncogene 29 , ' 4989-5005) . mTOR는 수개의 협력자를 채용하여 종양 성장에 필수적인 두개의 복수-단백질 복합체를 형성한다. 단백질 s6K 및 4E— BP1를 인산화함으로써， mTORCl 복합체는 종 양 유전자 신호와 단백질 합성, 해당 및 지질생합성과의 연결을 만든다 (Yecies and Ma皿 ing (2011) Jᅳ Mol . Med . 89 , 221-228) . mT0RC2 복합체는 최근 Ser-473 잔기상 에서 Akt를 인산화하여, 키나제 Akt의 필수적인 활성자로서 역할하는 키나제로 확 인되었다. 복합체 mT0RC2의 역할은 최근 특히 세포 변화에 연결된 것으로 밝혀졌다 (Sparks and Guert in (2010) Oncogene 29 , 3733-3744) . 라파마이신 및 그 아날로그, 라팔로그 (rapalogues)는 단백질 FKBP12와 결합 하여 mTORCl 복합체의 알로스테릭 저해제로 작용한다. 이들 중 수개는 특정 암의 치료를 위해 임상적으로 개발되고 있다. 에버를리무스 (Novartis) 및 템시를리무스 (Wyeth)는 최근 신장임- (신장 세포암 또는 RCC)의 치료를 위해 승인되었다。 그러나 암 치료에 있어 라팔로그의 효능은 특정 유망한 결과에도 불구하고 기대 이하이며 하위세트 암에 제한되는 것으로 보인다, 이러한 제한은 라팔로그가 mT0RC2 복합체 와 상호작용하지 않고， mTORCl 복합체 활성의 특정 측면 및 특히 4E-BP1의 인산화 가 라파마이신 및 그 아날로그에 저항적인 사실에 기인한다 (Benjamin et al , (2011) Nature Reviews Drug Discovery 10， 868—880). 한편， mTOR 키나제 부위의 저해제는 이러한 결점이 없고 (Feldman et al . (2009) PLoS Biology 7, 371-383), 신세대 mTOR 경로 조절자로 인식되고 있으며， 이점으로서 항암활성의 잠재적 상승 및 더 넓은 치료적 적용범위를 갖는다。 이 :들 중 몇 개는 현재 임상시험 중이다 (Garcia-Echeverria (2011) Biochem. Soc. Trans. 39, 451-455； Richard et al . (2010) Curr . Drug Opinion Disc. Dev. 13， 428— 440). 다른 잠재적 치료적 적응증이 mTOR 저해제에 대해 제안되었다 (Tsang et al . (2007) Drug Discovery Today 12, 112—124). mTOR 저해제는 알쯔하이머 질환， 파킨 슨 질환 및 헌팅톤 질환과 같은 신경퇴행성 질환에서 신경보호작용을 가질 수 있다 (Bov'e et al . (2011) Nature Reviews Neuroscience 12， 437-452) . 게다가, mTOR 과잉활성은 연령—관련 질병과 관련된다 (Harrison et al . (2009) Nature 460, 392), 다른 적웅증은 신장, 폐 및 간 섬유증 (Mehrad et al . (2009) Int. J. Biochem. Cell Biol. 41, 1708-1718； Lieberthal and Levi ne (2009)； Shouval (2011)), 염증 및 자가면역 질환 (Bhonde et al . (2008) Am. J. Physiol . Gastrointest . Liver Physiol. 295, G1237-G1245; Young and Nicker son— Nutter (2005) Curr. Opinion Pharmacol . 5, 418-423) , 당뇨, 비만 (Dann et al . (2007) Trends Mol . Medicine 13, 252—259), 품페병 (Ashe et al. (2010) Molecular Genetics and Metabolism 100, 309-315), 심혈관계질환 (Hagenmueller et al. (2010). FEBS Lett. 584, 74- 80), 안질환 (Blumenkranz (2007) Retina Today 24-26) , 간질 (Huang et al. (2010) Neurobiology of Disease 40， 193-199), 및 기생층 질환 (Wang et al. (2010) 240th ACS National Meeting Boston, MED I -152)을 포함한다. mTOR 저해는 또한 자가포식을 활성화하고, 특정 질환들, 특히 대사질환, 신 경퇴행성질흰-， 박테리아 및 바이러스 감염 및 암은 그 저해에 민감하다 (review in Rubinsztein et al . (2007) Nature 6， 304-312) . 한편, mTORCl은 세포 성장， 단백질 합성, 성장인자의 조절 등과 같은 여러 가지의 upstream 신호를 조절한다. mTORCl에 성장인자와 에너지 신호를 전송하는 결절성경화증복합체 (Tuberous Scleros i s Complex , TSC)는 Rasᅳ l ike smal l GTPase , Rheb에 대한 GTPase-활성화 단백질 (GTPase-act ivat ing protein, GAP)이고, Rheb의 GTP 가수분해를 촉진함으로써 mTORCl을 음성조절 (negat ively regulate)한다, MTOR, also known as FRAP (FKBP12 and rapamycin related proteins), does not phosphorylate phospholipids, but does not phosphorylate phospholipids, but the 289-kDa serine / threonine kinase of the PIKK family This protein consists of C—terminal kinase domain, FKBP12-rapamycin binding domain, 20 N-terminal HEAT repeats involved in protein-protein interactions, FAT (FRAP— ATM-TRRAP) domain, and Several domains, including C-terminal FAT domains, also present in other PIKKs (Wul l schleger et al. (2006) Cel l, 124, 471-484). mTOR kinases are central regulators of cell growth and proliferation and play an important role in cell metabolism and angiogenesis. mTOR is activated by the PI3K / Akt axis, which in turn is the downstream effector of the PI3K / Akt signaling pathway, especially cellular proteins. It phosphorylates two major regulators of the translation machinery, ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein (4E-BP1) (mTOR signaling pathways are described in Zoncu et al. (2011) Nature Rev. MoL Cel l Biol. 12, 21-35). mTOR signaling pathways are mutated and degenerated in various human cancers, protein kinase Akt, mutation of lipid kinase PI3K and / or inactivation of tumor suppressor PTEN and TSC2 and proliferation and / or mutations affecting growth factor receptors Are several events in the upstream of mTOR that result in constitutive inactivation of the PI3K / Akt / mT0R pathway and unregulated cell proliferation. (For a review of the role of protein mTOR in cancer, see Guert in and Sabat lni ( 2007) See Cancer Cel l 12, 9-22). Genetic mutations and amplifications affecting the mTOR pathway include glioblastoma, prostate cancer, nodular carcinoma, lung cancer (NSCLC), breast cancer, ovarian cancer, endometrial cancer, colon cancer, pancreatic cancer, head and neck cancer, skin cancer and hepatocellular carcinoma. Yuan and Cant ley (2008) Oncogene 27, 5497-5510; Whit taker et al. (2010) Oncogene 29, ' 4989-5005). mTOR employs several collaborators to form two multi-protein complexes essential for tumor growth. By phosphorylating proteins s6K and 4E—BP1, the mTORCl complex makes a link between tumor gene signaling and protein synthesis, glycolysis, and lipid biosynthesis (Yecies and Ma 皿 ing (2011) J ᅳ Mol. Med. 89, 221-228 . The mT0RC2 complex has recently been identified as a kinase that phosphorylates Akt on the Ser-473 residue, acting as an essential activator of the kinase Akt. The role of the complex mT0RC2 has recently been found to be particularly linked to cellular changes (Sparks and Guert in (2010) Oncogene 29, 3733-3744). Rapamycin and its analogs, rapalogues, bind to protein FKBP12 and act as allosteric inhibitors of the mTORCl complex. Several of these are specific cancers It is being developed clinically for treatment. Evervarus and Wyeth have recently been approved for the treatment of kidneys (renal cell carcinoma or RCC). However, the efficacy of rapalog in the treatment of cancer is less than expected, despite certain promising results. This restriction is due to the fact that the rapalog does not interact with the mT0RC2 complex and that certain aspects of mTORCl complex activity and in particular the phosphorylation of 4E-BP1 is resistant to rapamycin and its analogs. Benjamin et al, (2011) Nature Reviews Drug Discovery 10, 868-880. On the other hand, inhibitors of mTOR kinase sites are devoid of these drawbacks (Feldman et al. (2009) PLoS Biology 7, 371-383), and are recognized as new generation mTOR pathway modulators, which have the potential to increase anticancer activity and broader therapeutic potential. . this has coverage..... some of the dogs are currently being clinically tested (Garcia-Echeverria (2011) Biochem Soc Trans 39, 451-455; Richard et al (2010) Curr Drug Opinion Disc Dev. 13, 428—440. Other potential therapeutic indications have been proposed for mTOR inhibitors (Tsang et al. (2007) Drug Discovery Today 12, 112-124). mTOR inhibitors may have neuroprotective effects in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease (Bov'e et al. (2011) Nature Reviews Neuroscience 12, 437-452). In addition, mTOR overactivity is associated with age-related diseases (Harrison et al. (2009) Nature 460, 392), and other tropisms are renal, lung and liver fibrosis (Mehrad et al. (2009) Int. J. Biochem Cell Biol. 41, 1708-1718; Lieberthal and Levi ne (2009); Shouval (2011)), inflammatory and autoimmune diseases (Bhonde et al. (2008) Am. J. Physiol. Gastrointest. Liver Physiol. 295, G1237-G1245; Young and Nicker son—Nutter (2005) Curr.Opinion Pharmacol. 5, 418-423), diabetes, obesity (Dann et al. (2007) Trends Mol. Medicine 13, 252—259), Pumpe disease ( Ashe et al. (2010) Molecular Genetics and Metabolism 100, 309-315), cardiovascular disease (Hagenmueller et al. (2010) .FEBS Lett. 584, 74- 80), eye disease (Blumenkranz (2007) Retina Today 24 -26), epilepsy (Huang et al. (2010) Neurobiology of Disease 40, 193-199), and parasitic disease (Wang et al. (2010) 240th ACS National Meeting Boston, MED I-152). mTOR inhibition also activates autophagy and causes certain diseases, especially metabolic and renal Mildly degenerative white-, bacterial and viral infections and cancers are sensitive to their inhibition (review in Rubinsztein et al. (2007) Nature 6, 304-312). On the other hand, mTORCl regulates various upstream signals such as cell growth, protein synthesis, and growth factor regulation. Tuberous Scleros is Complex (TSC), which transfers growth factors and energy signals to mTORCl, is a GTPase-activating protein (GAP) for Ras ike smal l GTPase, Rheb, and Rheb Negatively regulate mTORCl by promoting GTP hydrolysis of
Rheb은 후기 엔도좀 /라이소좀으로 이동할 수 있으며， 아미노산에 의해 유도 되는 mTORCl 활성화에 필요하다. 라이소좀막에서, Rag GTPases와 Ragul ator compl ex(MAP SPl , R0BLD3 및 cllorf59)는 mTORCl에 대한 아미노산 유도성 도킹 사 이트로서 작용한다. 포유류는 네 가지의 Rag GTPases (RagA, RagB, RagC , RagD)를 발현한다, Rag GTPases는 필수적으로 RagA/C 또는 RagB/D의 헤테로 다이머를 형성하여 아미노산 유도성 mTORCl 활성화를 매개한다, 아미노산은 mTORCl을 라이소좀으로 이동하도록 유도하며， 라이소좀에서는 GTP가 결합된 RagB를 포함하고 있는 Rag 헤테로 다이머 가 mTOR 과 상호작용한다. 류신과 글루타민은 각각 Rag GTPase-의존성 및 비의존성 기작에 의해 mTORCl 을 활성화 할 수 있다. RagA/B가 결손된 세포에서 글루타민은 ADP r ibosyl at i on factor l(ARFl) GTPase를 통해 mTORCl을 여전히 활성화할 수 있다. 그러므로, mTORCl은 글루타민과 류신에 의해 다르게 조절될 수 있다, 그러나， Rag GTPase-의 존성 류신 신호의 기능적 중요성은 잘 알려져 있지 않다。 mTORCl은 대부분의 인간 암에서 과활성화되어 세포 성장과 대사 과정을 조절 한다. 비록， mTOR의 알로스테릭 저해제인 everol imus가 mTOR 신호에 변화를 갖는 암종을 치료하는 효과를 나타낸다고 하더라도, 이의 저항성 (resi stance)이 나타난 다. mTOR 돌연변이를 활성화하기 때문에 나타나는 획득성 저항성은 everol imus가 mTOR에 결합하는 것을 저해한다. mTOR 내에서 S2035인 FRB 도메인은 FKBP12—라파마 이신이 결합하는데 필수적이며, 이 위치에 돌연변이가 생기면 라파마이신 저항성이 나타난다。 획득성 저항성의 기전을 명확히 이해할 수 있다면, mTOR 저해제에 저항 성을 나타내는 돌연변이에 대항하기 위한 새로운 치료제의 개발에 활용할 수 있을 것이다。 한편, 아미노아실 -tRNA—합성효소 (ARSs )는 단백질 합성에 필요할 뿐만 아니라 다양한 세포의 생리학적 반웅에도 또한 관련되어 있다. ARS는 대웅되는 tRNA에 아 미노산이 결합하는 것을 촉진한다. 단백질 항상성을 유지하기 위하여， ARS는 아미 노산 유용성을 감작시켜야 한다. 류신— tRNA—합성효소 (LRS)는 RagD GTPase와 상호작 용하고 RagD GTPase에 대한 GAP로써 작용함으로써 mTORCl 활성화를 위한 류신 센서 로서 기능한다. 따라서 , LRS가 tRNA에 류신을 결합시키는 본래의 기능에는 아무런 영향을 미 치지 않으면서, 류신 센서로서의 기능을 저해하는 물질을 탐색해낸다면, 이 물질은 LRS와 RagD와의 결합을 저해하여 mTORCl의 활성화를 저해하고, 결과적으로 mTOR 저 해제에 대한 잠재적 치료 적웅증에 효과를 나타낼 것이다ᅳ Rheb can migrate to late endosomes / lysosomes and is required for mTORCl activation induced by amino acids. In lysosome membranes, Rag GTPases and Ragul ator compl ex (MAP SPl, R0BLD3 and cllorf59) act as amino acid inducible docking sites for mTORCl. Mammals express four Rag GTPases (RagA, RagB, RagC, RagD). Rag GTPases essentially form heterodimers of RagA / C or RagB / D to mediate amino acid-induced mTORCl activation. It is induced to move to the lysosome, Rag heterodimer containing RagB with GTP in the lysosome interacts with mTOR. Leucine and glutamine can activate mTORCl by Rag GTPase-dependent and independent mechanisms, respectively. In RagA / B deficient cells, glutamine can still activate mTORCl via ADP r ibosyl at i on factor l (ARFl) GTPase. Therefore, mTORCl can be regulated differently by glutamine and leucine, but the functional significance of Rag GTPase-dependent leucine signaling is not well known. MTORCl is overactivated in most human cancers to regulate cell growth and metabolic processes do. Although everol imus, an allosteric inhibitor of mTOR, has the effect of treating a carcinoma with a change in mTOR signal, its resistance is shown. Acquireable resistance due to activation of the mTOR mutation inhibits everol imus binding to mTOR. The FRB domain, S2035, in mTOR is essential for FKBP12—rapamycin to bind, and mutations in this position result in rapamycin resistance. A clear understanding of the mechanism of achievable resistance could be used in the development of new therapeutics to combat mutations that are resistant to mTOR inhibitors. On the other hand, aminoacyl-tRNA-synthetases (ARSs) can be used for protein synthesis. In addition to the necessity, the physiological response of various cells is also involved. ARS promotes the binding of amino acids to the tRNA being treated. To maintain protein homeostasis, ARS must sensitize amino acid availability. Leucine-tRNA-synthetase (LRS) functions as a leucine sensor for mTORCl activation by interacting with RagD GTPase and acting as a GAP for RagD GTPase. Therefore, if LRS detects a substance that inhibits its function as a leucine sensor without affecting the original function of binding leucine to tRNA, it inhibits the binding of LRS and RagD to inhibit the activation of mTORCl. Inhibition and consequently will have an effect on potential therapeutic sympathy for mTOR inhibitors.
【발명의 상세한 설명】 [Detailed Description of the Invention]
【기술적 과제】  [Technical problem]
이에， 본 발명자들은 LRS와 RagD의 결합을 저해함으로써 mTOR를 저해하는 화 합물을 발견하기 위해 예의 노력을 기을인 결과, 본 명세서에서 화학식 1로 정의되 는 벤젠설폰아미드 유도체가 LRS와 RagD의 결합을 저해하여 암, 간질， 염증 질환， 면역 질환, 당뇨, 비만， 호흡기계 폐쇄성 질환， 섬유증, 품페병, 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질환, 파킨슨 질환 및 헌팅턴 질환과 같 은 신경퇴행성 질환, 심혈관계질환， 연령—관련질환 또는 기생충 감염증과 같은 질 환을 예방 또는 치료할 수 있음을 발견하고 본 발명을 완성하게 되었다, 따라서 , 본 발명의 목적은 하기 화학식 1로 표시되는 화합물 또는 이의 약학 적으로 허용 가능한 염을 제공하는 것이다: [화학식 1] Accordingly, the present inventors have made a diligent effort to find a compound that inhibits mTOR by inhibiting the binding of LRS and RagD, and as a result, the benzenesulfonamide derivatives defined in Formula 1 herein binds LRS and RagD. Neurodegenerative diseases such as cancer, epilepsy, inflammatory diseases, immune diseases, diabetes, obesity, respiratory obstructive diseases, fibrosis, bovine disease, lysosomal storage di sease, Alzheimer's disease, Parkinson's disease and Huntington's disease The present invention has been accomplished by discovering that it can prevent or treat diseases such as cardiovascular diseases, age-related diseases, or parasitic infections. Accordingly, an object of the present invention is to provide a compound represented by the following Chemical Formula 1 To provide acceptable salts: [Formula 1]
Figure imgf000008_0001
Figure imgf000008_0001
상기 화학식 1에서，  In Chemical Formula 1,
R1은 치환 또는 비치환 페닐; 할로; 또는 직선형 또는 분지형 d— C6 알킬이 고, 상기 R1이 치환된 페닐인 경우 그 치환기는 할로겐 원자, 치환되지 않은 직선형 또는 분지형 d— C6 알킬 및 1개 이상의 할로겐 원자로 치환된 직선형 또는 분지형 R 1 is substituted or unsubstituted phenyl; Halo; Or when straight or branched d—C 6 alkyl and R 1 is substituted phenyl the substituents are straight or substituted with a halogen atom, unsubstituted straight or branched d—C 6 alkyl and one or more halogen atoms or Branch type
C Ce 알킬로 이루어진 군에서 1개 이상 선택될 수 있으며， R2는 수소; 또는 직선형 또는 분지형 d-Cs 알킬이고, One or more selected from the group consisting of C Ce alkyl, R 2 is hydrogen; Or straight or branched d-Cs alkyl,
R3은 수소; 치환 또는 비치환 d-Cs 직선형 또는 분지형 알킬; C5-C10 시클로 알킬; 치환 또는 비치환 C5-C20 아릴; 디옥소안트라세닐; 또는 고리 내에 1개 이상 의 헤테로 원자를 포함하는 헤테로 고리 또는 헤테로아릴 고리로서, 이들이 치환되 는 경우 그 치환기는 직선형 또는 분지형의 C厂 C6 알킬; -(：6 알킬옥시 ; d— C6알킬 아미노기로 치환된 d— C6알킬옥시 ; 모폴린으로 치환된 d— C6알킬옥시 ; d— C6알킬옥 시카보닐 ; 히드록시카보닐 d— C6알킬 ; 플루오로 원자 1개 이상으로 치환된 d-Cs알 킬; CrCs알킬아미노; 페닐; 직선형 또는 분지형의 d-C6 알킬, 직선형 또는 분지형 의 C -Ce 알킬옥시， 직선형 또는 분지형의 d— C6 알킬옥시카보닐， 할로겐 원자 및 ,플 루오로 원자 1개 이상으로 치환된 알킬로 이루어진 군에서 선택되는 1개 이상의 치 환기로 치환된 페닐; 페녹시; 직선형 또는 분지형의 C :6 알킬， 할로겐 원자 및 직 선형 또는 분지형의 C6 알킬옥시로 이루어진 군에서 선택되는 1개 이상의 치환기 로 치환된 페녹시 ; 아미노설포닐; 할로; 시아노; 아세틸; 니트로; 에티닐; 히드록 시; 모폴리노; 나프틸; 테에닐; 피리딜; 테트라히드로퓨라닐; 카르복실; 티오페 닐; C— C10 사이클로알킬; 벤조디옥소릴; 직선형 또는 분지형의 d-C6 알킬옥시로 치 환된 인돌릴; 디히드로벤조옥시닐; 및 퓨릴메틸설파닐로 이루어진 군에서 1개 이상 선택되는 것이고, 싱-기 아릴， 헤테로 고리 및 헤테로아릴 고리는 각각 2개 이상의 고리가 융합된 복소환 구조일 수 있고， 또한 고리 내에 카보닐기를 포함할 수 있는 것이거나， R 3 is hydrogen; Substituted or unsubstituted d-Cs straight or branched alkyl; C 5 -C 10 cycloalkyl; Substituted or unsubstituted C 5 -C 20 aryl; Dioxoanthracenyl; Or a heterocyclic ring or heteroaryl ring having one or more heteroatoms in the ring, where these substituents are linear or branched C 6C 6 alkyl; - (: 6 alkyloxy; d- C 6 alkyl, d- C 6 alkyloxy optionally substituted with amino group; substituted by morpholinyl d- C 6 alkyloxy; d- C 6 alkyloxy carbonyl Brassica; hydroxy-carbonyl d- C 6 alkyl; d-Cs alkyl substituted with one or more fluoro atoms; CrCs alkylamino; phenyl; straight or branched dC 6 alkyl, straight or branched C-Ce alkyloxy, straight or branched d— C 6 alkyloxycarbonyl, phenyl substituted by one or more substituents selected from the group consisting of halogen atoms and alkyl substituted with one or more fluoro atoms; phenoxy; straight or branched C: Phenoxy; aminosulfonyl; halo; cyano; acetyl; nitro; ethynyl; hydroxy substituted with one or more substituents selected from the group consisting of 6 alkyl, a halogen atom and a linear or branched C 6 alkyloxy C; morpholino; naphthyl; teenyl; pyridyl; tetrahydrofue Group; carboxyl; thiophenoxy group; talking benzo-dioxide;; C- C 10 cycloalkyl value dC in 6 alkyloxy linear or branched Cyclized indolyl; Dihydrobenzooxyyl; And at least one selected from the group consisting of furylmethylsulfanyl, and the sing-group aryl, hetero ring and heteroaryl ring may each be a heterocyclic structure in which two or more rings are fused, and also include a carbonyl group in the ring. You can do it,
상기 R2와 R3은 서로 결합하여 고리 내에 1개 이상의 헤테로 원자를 포함하 는 C5ᅳ C20 헤테로 고리 또는 헤테로아릴 고리를 형성함. 본 발명의 다른 목적은 상기 화학식 1으로 표시되는 벤젠설폰아미드 유도체 의 제조방법을 제공하는 것이다, 본 발명의 다른 목적은 상기 화학식 1으로 표시되는 화합물 또는 이의 약학 적으로 허용가능한 염을 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조 성물을 제공하는 것이다, 본 발명의 다른 목적은 상기 화학식 1으로 표시되는 화합물 또는 이의 약학 적으로 허용가능한 염을 필요로 하는 개체에 유효량으로 투여하여 암 관련 질환을 치료하는 방법을 제공하는 것이다. 본 발명의 다른 목적은 상기 화학식 1으로 표시되는 화합물 또는 이의 약학 적으로 허용가능한 염의 항암제 제조를 위한 용도를 제공하는 것이다. R 2 and R 3 combine with each other to form a C 5 ᅳ C 20 hetero ring or heteroaryl ring containing one or more hetero atoms in the ring. Another object of the present invention to provide a method for preparing a benzenesulfonamide derivative represented by the formula (1), another object of the present invention comprises a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient To provide a pharmaceutical composition for the prevention or treatment of cancer, another object of the present invention by administering to a subject in need of an effective amount to a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof cancer-related diseases To provide a way to treat it. Another object of the present invention to provide a use of the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for the manufacture of an anticancer agent.
【기술적 해결방법】 Technical Solution
상기 목적을 달성하기 위하여 본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 제공한다:  In order to achieve the above object, the present invention provides a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
[화학식 13  [Formula 13]
Figure imgf000009_0001
상기 화학식 1에서,
Figure imgf000009_0001
In Chemical Formula 1,
R1은 치환 또는 비치환 페닐; 할로; 또는 직선형 또는 분지형 Ci-Cg 알킬이 고, 상기 R1이 치환된 페닐인 경우 그 치환기는 할로겐 원자， 치환되지 않은 직선형 또는 분지형 d-Ce 알킬 및 1개 이상의 할로겐 원자로 치환된 직선형 또는 분지형 R 1 is substituted or unsubstituted phenyl; Halo; Or when straight or branched Ci-Cg alkyl and R 1 is substituted phenyl the substituents are straight or branched, substituted by halogen atoms, unsubstituted straight or branched d-Ce alkyl and one or more halogen atoms
Cx-C6 알킬로 이루어진 군에서 1개 이상 선택될 수 있으며， R2는 수소; 또는 직선형 또는 분지형 d-C6 알킬이고， One or more selected from the group consisting of Cx-C 6 alkyl, R 2 is hydrogen; Or straight or branched dC 6 alkyl,
R3은 수소; 치환 또는 비치환 d— C6 직선형 또는 분지형 알킬; C5— C10 시클로 알킬; 치환 또는 비치환 C5— C20 아릴; 디옥소안트라세닐; 또는 고리 내에 1개 이상 의 헤테로 원자를 포함하는 헤테로 고리 또는 헤테로아릴 고리로서， 이들이 치환되 는 경우 그 치환기는 직선형 또는 분지형의 d-C6 알킬; d-C6 알킬옥시 ; d- 알킬 아미노기로 치환된 d— C6알킬옥시 ; 모폴린으로 치환된 d-C6알킬옥시 ; d— C6알킬옥 시카보닐 ; 히드록시카보닐 Cr"C6알킬 ; 플루오로 원자 1개 이상으로 치환된 CrCs알 킬; d_C6알킬아미노; 페닐; 직선형 또는 분지형의 d— C6 알킬， 직선형 또는 분지형 의 Ci— C6 알킬옥시， 직선형 또는 분지형의 C6 알킬옥시카보닐, 할로겐 원자 및;플 루오로 원자 1개 이상으로 치환된 알킬로 이루어진 군에서 선택되는 1개 이상의 치 환기로 치환된 페닐; 페녹시; 직선형 또는 분지형의 d-C6 알킬, 할로겐 원자 및 직 선형 또는 분지형의 d-c6 알킬옥시로 이루어진 군에서 선택되는 1개 이상의 치환기 로 치환된 페녹시 ; 아미노설포닐; 할로; 시아노; 아세틸; 니트로; 에티닐; 히드록 시; 모폴리노; 나프틸; 테에닐; 피리딜; 테트라히드로퓨라닐; 카르복실; 티오페 닐; d-c10 사이클로알킬; 벤조디옥소릴; 직선형 또는 분지형의 d-C6 알킬옥시로 치 환된 인돌릴; 디히드로벤조옥시닐; 및 퓨릴메틸설파닐로 이루어진 군에서 1개 이상 선택되는 것이고， 상기 아릴， 헤테로 고리 및 헤테로아릴 고리는 각각 2개 이상의 고리가 융합된 복소환 구조일 수 있고， 또한 고리 내에 카보닐기를 포함할 수 있는 것이거나 R 3 is hydrogen; Substituted or unsubstituted d— C 6 straight or branched alkyl; C 5 — C 10 cycloalkyl; Substituted or unsubstituted C 5 — C 20 aryl; Dioxoanthracenyl; Or a heterocyclic ring or heteroaryl ring having one or more heteroatoms in the ring, where these substituents are linear or branched dC 6 alkyl; dC 6 alkyloxy; d— C 6 alkyloxy substituted with d-alkyl amino group; DC 6 alkyloxy substituted with morpholine; d— C 6 alkyloxycarbonyl; Hydroxycarbonyl Cr ″ C 6 alkyl; CrCs alkyl substituted with one or more fluoro atoms; d_C 6 alkylamino; phenyl; straight or branched d—C 6 alkyl, straight or branched Ci— C 6 Phenyl substituted by one or more substituents selected from the group consisting of alkyloxy, straight or branched C 6 alkyloxycarbonyl, halogen atoms and alkyl substituted with one or more fluoro atoms; phenoxy; straight Or phenoxy substituted with one or more substituents selected from the group consisting of branched dC 6 alkyl, halogen atoms and linear or branched dc 6 alkyloxy; aminosulfonyl; halo; cyano; acetyl; nitro; Ethynyl; hydroxy; morpholino; naphthyl; teenyl; pyridyl; tetrahydrofuranyl; carboxyl; thiophenyl; dc 10 cycloalkyl; benzodioxolyl; straight or branched dC 6 alkyl Indolyl substituted with oxy; dihydrobenzo Cynyl; and one or more selected from the group consisting of furylmethylsulfanyl, and the aryl, hetero ring, and heteroaryl ring may each be a heterocyclic structure in which two or more rings are fused, and also include a carbonyl group in the ring. I can do it
, 싱-기 R2와 R3은 서로 결합하여 고리 내에 1개 이상의 헤테로 원자를 포함하 는 c5— c20 헤테로 고리 또는 헤테로아릴 고리를 형성함. 본 발명의 다른 목적을 달성하기 위하여 본 발명은 상기 화학식 1으로 표시 되는 벤젠설폰아미드 유도체의 제조방법을 제공한다。 본 발명의 다른 목적을 달성하기 위하여 본 발명은 상기 화학식 1으로 표시 되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조성물을 제공한다. 본 발명의 다른 목적을 달성하기 위하여 본 발명은 상기 화학식 1으로 표시 되는 화합물 또는 이의 약학적으로 허용가능한 염을 필요로 하는 개체에 유효량으 로 투여하여 암 관련 질환을 치료하는 방법을 제공한다. 본 발명의 다른 목적을 달성하기 위하여 본 발명은 상기 화학식 1으로 표시 되는 화합물 또는 이의 약학적으로 허용가능한 염의 항암제 제조를 위한 용도를 제 공한다. 이하 본 발명에 대해 상세히 설명한디- . 본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가 능한 염을 제공한다: And the sing-groups R 2 and R 3 combine with each other to form a c 5 — c 20 hetero ring or heteroaryl ring containing one or more hetero atoms in the ring. In order to achieve another object of the present invention, the present invention provides a method for preparing a benzenesulfonamide derivative represented by Formula 1. To achieve another object of the present invention, the present invention provides a compound represented by Formula 1 or It provides a pharmaceutical composition for the prevention or treatment of cancer comprising a pharmaceutically acceptable salt as an active ingredient. In order to achieve another object of the present invention, the present invention provides a method for treating cancer-related diseases by administering to a subject in need thereof an effective amount of a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof. In order to achieve another object of the present invention, the present invention provides a use of the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for the manufacture of an anticancer agent. Hereinafter, the present invention will be described in detail. The present invention provides a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
[화학식 1]  [Formula 1]
Figure imgf000011_0001
Figure imgf000011_0001
상기 화학식 1에서，  In Chemical Formula 1,
R1은 치환 또는 비치환 페닐; 할로; 또는 직선형 또는 분지형 d— C6 알킬이 고, 상기 R1이 치환된 페닐인 경우 그 치환기는 할로겐 원자, 치환되지 않은 직선형 또는 분지형 d— C6 알킬 및 1개 이상의 할로겐 원자로 치환된 직선형 또는 분지형 Ci-C6 알킬로 이루어진 군에서 1개 이상 선택될 수 있으며, R2는 수소; 또는 직선형 또는 분지형 d— C6 알킬이고， R 1 is substituted or unsubstituted phenyl; Halo; Or when straight or branched d—C 6 alkyl and R 1 is substituted phenyl the substituents are straight or substituted with a halogen atom, unsubstituted straight or branched d—C 6 alkyl and one or more halogen atoms or Branch type One or more selected from the group consisting of Ci-C 6 alkyl, R 2 is hydrogen; Or straight or branched d—C 6 alkyl,
R3은 수소; 치환 또는 비치환 d-C6 직선형 또는 분지형 알킬; rC10 시클로 알킬; 치환 또는 비치환 C5-C20 아릴; 디옥소안트라세닐; 또는 고리 내에 1개 이상 의 헤테로 원자를 포함하는 헤테로 고리 또는 헤테로아릴 고리로서， 이들이 치환되 는 경우 그 치환기는 직선형 또는 분지형의 d-C6 알킬; d-C6 알킬옥시 ; d— C6알킬 아미노기로 치환된 d— C6알킬옥시 ; 모폴린으로 치환된 C— C6알킬옥시 ; d— C6알킬옥 시카보닐 ; 히드록시카보닐 d— C6알킬 ; 플루오로 원자 1개 이상으로 치환된 d—C6알 킬; ― C6알킬아미노; 페닐; 직선형 또는 분지형의 Cr- C6 알킬, 직선형 또는 분지형 의 CrCs 알킬옥시， 직선형 또는 분지형의 d-C6 알킬옥시카보닐, 할로겐 원자 및 플 루오로 원자 1개 이상으로 치환된 알킬로 이루어진 군에서 선택되는 1개 이상의 치 환기로 치환된 페닐; 페녹시; 직선형 또는 분지형의 d— C6 알킬， 할로겐 원자 및 직 선형 또는 분지형의 Ci-C6 알킬옥시로 이루어진 군에서 선택되는 1개 이상의 치환기 로 치환된 페녹시 ; 아미노설포닐; 할로; 시아노; 아세틸; 니트로; 에티닐; 히드록 시; 모폴리노; 나프틸; 테에닐; 피리딜; 테트라히드로퓨라닐; 카르복실; 티오페 닐; d-C10 사이클로알킬; 벤조디옥소릴; 직선형 또는 분지형의 d- 알킬옥시로 치 환된 인돌릴; 디히드로벤조옥시닐; 및 퓨릴메틸설파닐로 이루어진 군에서 1개 이상 선택되는 것이고， 상기 아릴， 헤테로 고리 및 헤테로아릴 고리는 각각 2개 이상의 고리가 융합된 복소환 구조일 수 있고, 또한 고리 내에 카보닐기를 포함할 수 있는 것이거나, R 3 is hydrogen; Substituted or unsubstituted dC 6 straight or branched alkyl; rC 10 cycloalkyl; Substituted or unsubstituted C 5 -C 20 aryl; Dioxoanthracenyl; Or a heterocyclic ring or heteroaryl ring having one or more heteroatoms in the ring, where these substituents are linear or branched dC 6 alkyl; dC 6 alkyloxy; d- C 6 a d- C 6 alkyloxy optionally substituted with an alkyl group; C— C 6 alkyloxy substituted with morpholine; d— C 6 alkyloxycarbonyl; Hydroxycarbonyl d—C 6 alkyl; D—C 6 alkyl substituted with one or more fluoro atoms; C 6 alkylamino; Phenyl; Group consisting of straight or branched C r -C 6 alkyl, straight or branched CrCs alkyloxy, straight or branched dC 6 alkyloxycarbonyl, halogen atom and alkyl substituted with one or more atoms with fluoro Phenyl substituted with one or more substituents selected from; Phenoxy; Phenoxy substituted with one or more substituents selected from the group consisting of linear or branched d—C 6 alkyl, halogen atoms and linear or branched Ci-C 6 alkyloxy; Aminosulfonyl; Halo; Cyano; Acetyl; Nitro; Ethynyl; Hydroxyl; Morpholino; Naphthyl; Teenyl; Pyridyl; Tetrahydrofuranyl; Carboxyl; Thiophenyl; dC 10 cycloalkyl; Benzodioxolyl; Indolyl substituted with linear or branched d-alkyloxy; Dihydrobenzooxyyl; And at least one selected from the group consisting of furylmethylsulfanyl, and the aryl, hetero ring, and heteroaryl ring may each be a heterocyclic structure in which two or more rings are fused, and also include a carbonyl group in the ring. Is there, or
싱-기 R2와 R3은 서로 결합하여 고리 내에 1개 이상의 헤테로 원자를 포함하 는 C5— C20 헤테로 고리 또는 헤테로아릴 고리를 형성함。 The sing-groups R 2 and R 3 combine with each other to form a C 5 — C 20 hetero ring or heteroaryl ring containing one or more hetero atoms in the ring.
"알킬' '은 쇄 내에 약 1개 내지 약 20개의 탄소 원자를 포함하는, 직쇄 또는 측쇄일 수 있는 지방족 탄화수소 그룹을 의미한다. 바람직한 알킬 그룹은 상기 쇄 내에 약 1개 내지 약 12개의 탄소 원자를 포함한다. 보다 바람직한 알킬 그룹은 상 기 쇄 내에 약 1개 , 2개 , 3개， 4개 , 5개 또는 6개의 탄소 원자를 포함한다. 측쇄는 하나 이상의 저급 알킬 그룹， 예를 들면， 메틸， 에틸 또는 프로필이 선형 알킬 쇄 에 부착되어 있는 것을 의미한다. "저급알킬' '은 직쇄 또는 측쇄일 수 있는 쇄 내에 약 1개 내지 약 6개의 탄소 원자를 갖는 그룹을 의미한다, "알킬 "은 치환되지 않을 수 있거나 또는, 동일하거나 또는 상이할 수 있는 하나 이상의 치환체에 의해 임의 로 치환될 수 있고,각 치환체는 할로겐, 알킬, 아릴， 사이클로알킬， 시아노， 하아 드록시, 알콕시, 알킬티오， 아미노， 카르복시 등일 수 있다. 바람직하게 알킬은 부 틸 또는 이소부틸일 수 있다. "Alkyl"'means an aliphatic hydrocarbon group that may be straight or branched, containing from about 1 to about 20 carbon atoms in the chain. Preferred alkyl groups include from about 1 to about 12 carbon atoms in the chain. More preferred alkyl groups include about 1, 2, 3, 4, 5 or 6 carbon atoms in the chain, the side chains comprising one or more lower alkyl groups such as methyl, Ethyl or propyl linear alkyl chain It means attached to. "Loweralkyl"'means a group having from about 1 to about 6 carbon atoms in the chain, which may be straight or branched, "alkyl" means one or more, which may be unsubstituted, or may be the same or different. Optionally substituted by substituents, each substituent may be halogen, alkyl, aryl, cycloalkyl, cyano, hydroxy, alkoxy, alkylthio, amino, carboxy, etc. Preferably alkyl is butyl or isobutyl Can be.
"아릴''은 방향족 탄화수소 고리계를 의미하며， 이의 예로는 페닐, 인데닐， 인다닐, 나프틸 및 플루오레닐 등이 있으며， 바람직하게는 (6C)아릴일 수 있다, "Aryl" means an aromatic hydrocarbon ring system, examples of which include phenyl, indenyl, indanyl, naphthyl and fluorenyl, and may preferably be (6C) aryl,
"할로겐' '은 불소 원자， 염소 원자， 브롬 원자 및 요오드 원자를 포함할 수 있고, 바람직하게는 불소 원자, 염소 원자또는 브름 원자일 수 있다. "Halogen" 'may include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, preferably a fluorine atom, a chlorine atom or a brom atom.
"사이클로알킬' '은 달리 포화된 탄화수소환을 의미한다. "Cycloalkyl" 'otherwise means a saturated hydrocarbon ring.
"헤테로아릴 "은 고리 탄소 원자들 중 1~4개가 0, S 및 N으로 이루어진 용매 화물으로부터 선택되는 이종 원자로 화학식 ( I I )의 화합물의 몇몇 구체예에서된 방 향족 시클로알킬 (헤테로아릴이라고도 칭함) 또는 비 방향족 시클로알킬이디- , 몇몇 구체예에서, 헤테로시클릴 기는 3~10개의 고리 원들을 포함하는 반면에, 이와 같은 기타 기들은 3~5개， 3 6개， 또는 3~8개의 고리 원들을 보유한다. 헤테로시클릴은 또한 임의의 고리 원자 (즉， 헤테로시클릭 고리 증 임의의 탄소 원자 또는 이종 원 자)에서 다른 기들과 결합될 수도 있다. 헤테로시클로알킬 기는 치환 또는 비 치환 될 수 있다. 헤테로시클릴 기는 불포화, 부분 포화 및 포화 고리 계 예를 들어， 이 미다졸릴, 이미다졸리닐 및 이미다졸리디닐기를 포함한다. 혜테로시클릴이란 용어 는 융합된 고리 종, 예를 들어, 융합된 방향족 및 비 방향족 기를 포함하는 것 예 를 들어， 벤조트리아졸릴， 2 , 3—디하이드로벤조 [1 , 4]디옥시닐 및 벤조 [1 , 3]디옥솔 릴을 포함한다. 상기 용어는 또한 이종 원자를 함유하는 가교 폴리시클릭 고리 계 예를 들어, 퀴뉴클리딜도 포함하나, 이에 한정되는 것은 아니다. 헤테로시클릴 기 의 대표적인 예로서는 아지리디닐， 아제티디닐， 피를리딜, 이미다졸리디닐, 피라졸 리디닐, 티아졸리디닐, 테트라하이드로티오페닐, 테트라하이드로푸라닐, 디옥솔릴, 푸라닐， 티오페닐, 피를릴, 피를리닐， 이미다졸릴， 이미다졸리닐， 피라졸릴， 피라 졸리닐， 트리아졸릴, 테트라졸릴， 옥사졸릴， 이속사졸릴， 티아졸릴， 티아졸리닐, 이소티아졸릴, 티아디아졸릴, 옥사디아졸릴, 피레리딜， 피페라지닐， 모폴리닐， 티 오모폴리닐 테트라하이드로피라닐 (예를 들어, 테트라하이드로— 2H—피라닐)， 테트라 하이드로티오피라닐, 옥사티아닌, 디옥실， 디티아닐， 피라닐, 피리딜, 피리미디닐， 피리다지닐， 피라지닐， 트리아지닐， 디하이드로피리딜 , 디하이드로디티이닐 , 디하 이드로디티오닐, 호모피페라지닐, 퀴뉴클리딜， 인돌릴， 인돌리닐, 이소인돌릴, 아 자인돌릴 (피를로피리딜) , 인다졸릴， 인돌리지닐， 벤조트리아졸릴， 벤즈이미다졸릴, 벤조푸라닐, 벤조티오페닐， 벤즈티아졸릴, 벤족사디아졸릴, 벤족사지닐, 벤조디티 이닐， 벤족사티이닐, 벤조티아지닐， 벤족사졸릴, 벤조티아졸릴， 벤조티아디아졸릴, 벤조 [ 1，3]디옥솔릴， 피라졸로피리딜， 이미다조피리딜 (아자벤즈이미다졸릴; 예를 들 어， 1H—이미다조 [4 , 5-b]피리딜 또는 1H-이미다조 [4 , 5— b]피리딘ᅳ 2(3H)—오닐)ᅳ 트리 아졸로피리딜， 이속사졸로피리딜， 퓨리닐, 잔티닐, 아데니닐， 구아니닐, 퀴놀리닐, 이소퀴놀리닐， 퀴놀리지닐， 퀴녹살리닐， 퀴나졸리닐， 신놀리닐， 프탈라지닐， 나프 티리디닐, 프테리디닐, 티아나프탈레닐, 디하이드로벤조티아지닐, 디하이드로벤조 푸라닐， 디하이드로인돌릴, 디하이드로벤조디옥시닐, 테트라하이드로인돌릴, 테트 라하이드로인다졸릴, 테트라하이드로벤즈이미다졸릴, 테트라하이드로벤조트리아졸 릴, 테트라하이드로피를로피리딜， 테트라하이드로피라졸로피리딜, 테트라하이드로 이미다조피리딜， 테트라하이드로트리아졸로피리딜, 및 테트라하이드로퀴놀리닐 기 를 포함하나, 이에 한정되는 것은 아니다. "Heteroaryl" is an aromatic cycloalkyl (also referred to as heteroaryl) in some embodiments of a compound of Formula (II) with a heteroatom, wherein one to four of the ring carbon atoms are selected from solvates consisting of 0, S and N Or non-aromatic cycloalkylide-, in some embodiments, the heterocyclyl group contains 3 to 10 ring members, while such other groups include 3 to 5, 3 6, or 3 to 8 ring members Hold them. Heterocyclyl may also be combined with other groups at any ring atom (ie, heterocarbon ring any carbon atom or heteroatom). Heterocycloalkyl groups can be substituted or unsubstituted. Heterocyclyl groups include unsaturated, partially saturated and saturated ring systems such as midazolyl, imidazolinyl and imidazolidinyl groups. The term hyterocyclyl includes fused ring species, eg, fused aromatic and non-aromatic groups, for example benzotriazolyl, 2, 3—dihydrobenzo [1,4] dioxynyl and Benzo [1, 3] dioxolyl. The term also includes, but is not limited to, crosslinked polycyclic ring systems containing heteroatoms such as quinuclidyl. Representative examples of the heterocyclyl group include aziridinyl, azetidinyl, pyridyl, imidazolidinyl, pyrazole lidinyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydrofuranyl, dioxolyl, furanyl, thio Phenyl, pyrillyl, pylinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl, Isothiazolyl, thiadiazolyl, oxadiazolyl, pyreridyl, piperazinyl, morpholinyl, thiomorpholinyl tetrahydropyranyl (eg, tetrahydro-2H-pyranyl), tetra hydrothiopyra Neil, oxathinine, dioxyl, ditianyl, pyranyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, dihydropyridyl, dihydrodithiinyl, dihydrodithionyl, homopipera Geniyl, quinuclidyl, indolyl, indolinyl, isoindoleyl, azaindolyl (pyrropyridyl), indazolyl, indolizinyl, benzotriazolyl, benzimidazolyl, benzofuranyl, benzothiophenyl, benz Thiazolyl, benzoxadiazolyl, benzoxazinyl, benzodithiinyl, benzoxathiinyl, benzothiazinyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo [1,3] dioxolyl, pyrazolopyridyl ， Imidazo Dill (azabenzimidazolyl; for example, 1H—imidazo [4,5-b] pyridyl or 1H-imidazo [4,5—b] pyridin ᅳ 2 (3H) -onyl) ᅳ triazole Ropyridyl, isoxazolopyridyl, furinyl, xanthinyl, adeninyl, guanyl, quinolinyl, isoquinolinyl, quinolininyl, quinoxalinyl, quinazolinyl, cinnolinyl, fr Talazinyl, naphthyridinyl, putridinyl, thianaphthalenyl, dihydrobenzothiazinyl, dihydrobenzo furanyl, dihydroindolyl, dihydrobenzodioxynyl, tetrahydroindolyl, tetrahydroinda Zolyl, tetrahydrobenzimidazolyl, tetrahydrobenzotriazolyl, tetrahydropyrropyridyl, tetrahydropyrazolopyridyl, tetrahydro imidazopyridyl, tetrahydrotriazolopyridyl, and tetrahydroquinolinyl groups Including but not limited to It is not.
"시클로알킬알킬기' '는 일반식 -알킬ᅳ시클로알킬인 라디칼로서, 알킬 및 시클 로알킬은 상기 정의한 바외- 같다. 화학식 ( I I )의 화합물의 몇몇 구체예에서 시클로 알킬알킬 기는 기의 알킬， 시클로알킬， 또는 알킬 및 시클로알킬 부 모두에서 치환 될 수 있다. 대표적인 시클로알킬알킬 기로서 시클로펜틸메틸， 시클로펜틸에틸， 시 클로핵실메틸, 시클로핵실에틸, 및 시클로핵실프로필을 포함하나 이에 한정되는 것 은 아니다. 본 발명에 개시된 기들이 "치환된"이라고 표현될 때, 이 기들은 임의의 적당 한 치환기 또는 치환기들로 치환될 수 있는 것이다, 치환기의 예시적인 예로서는 본 발명에에 개시된 예시적인 화합물과 구체예에서 살펴볼 수 있는 것들, 그리고 할로겐 (클로로, 요도， 브로모 또는 플루오로 기) ; 알킬; 하이드록실; 알콕시; 알콕 시알킬; 아미노; 알킬아미노; 카복시; 니트로; 시아노; 티올; 티오에테르; 이민; 이미드; 아미딘; 구아니딘; 에나민; 아미노카보닐; 아실아미노; 포스포네이토; 포 스핀; 티오카보닐; 설포닐; 설폰; 설폰아미드; 케톤; 알데히드; 에스테르; 우레아; 우레탄; 옥심 ; 하이드록실 아민; 알콕시아민; 아랄콕시아민; N-옥시드; 히드라진; 히드라지드; 히드라존; 아지드; 이소시아네이트; 이소티오시아네이트; 시아네이트; 티오시아네이트; 산소 (=0) ; B(0H)2 , 0(알킬)아미노카보닐; 모노시클릭이거나 융합 또는 비 융합 폴리시클릭일 수 있는 시클로알킬 (예를 들어， 시클로프로필, 시클로 부틸, 시클로펜틸 또는 시클로핵실)， 또는 모노시클릭이거나 융합 또는 비 융합 폴 리시클릭일 수 있는 헤테로시클릴 (예를 들어, 피를리딜, 피페리딜, 피페라지닐， 모 폴리닐 또는 티아지닐) ; 모노시클릭이거나 융합 또는 비 융합 폴리시클릭 아릴 또 는 헤테로아릴 (예를 들어， 페닐, 나프틸， 피를릴， 인돌릴， 푸라닐, 티오페닐, 이미 다졸릴， 옥사졸릴， 이속사졸릴， 티아졸릴, 트리아졸릴, 테트라졸릴, 피라졸릴, 피 리딜, 퀴놀리닐， 이소퀴놀리닐, 아크리디닐, 피라지닐， 피리다지닐， 피리미디닐, 벤즈이미다졸릴， 벤조티오페닐 또는 벤조푸라닐) 아릴옥시; 아랄킬옥시; 헤테로시 클릴옥시; 및 헤테로시클릴 알콕시가 있으나, 이에 제한되는 것은 아니다. 바람직 하게는， 직선형 또는 분지형의 d-C6 알킬; d— C6 알킬옥시 ; d-C6알킬아미노기로 치 환된 d— C6알킬옥시 ; 모폴린으로 치환된 d-Cs알킬옥시 ; d— C6알킬옥시카보닐 ; 히드 록시카보닐 d—C6알킬; 플루오로 원자 1개 이상으로 치환된 d-C6알킬; d-C6알킬아 미노; 페닐; 직선형 또는 분지형의 d-C6 알킬， 직선형 또는 분지형의 d— C6 알킬옥 시, 직선형 또는 분지형의 d-C6 알킬옥시카보닐, 할로겐 원자 및 플루오로 원자 1 개 이상으로 치환된 알킬로 이루어진 군에서 선택되는 1개 이상의 치환기로 치환된 페닐; 페녹시; 직선형 또는 분지형의 d— C6 알킬, 할로겐 원자 및 직선형 또는 분지 형의 C6 알킬옥시로 이루어진 군에서 선택되는 1개 이상의 치환기로 치환된 페녹 시 ; 아미노설포닐; 할로; 시아노; 아세틸; 니트로; 에티닐; 히드록시 ; 모폴리노; 나프틸; 테에닐; 피리딜; 테트라히드로퓨라닐; 카르복실; 티오페닐; d-C10 사이클 로알킬; 벤조디옥소릴; 직선형 또는 분지형의 d— C6 알킬옥시로 치환된 인돌릴; 디 히드로벤조옥시닐; 및 퓨릴메틸설파닐로 이루어진 군에서 1개 이상 선택될 수 있 다. 더욱 바람직하게는 상기 화학식 1의 화합물은 다음 중에서 선택될 수 있다. N一시클로핵실 4ᅳ이소프로필 -2 ,3-디메틸— 5-옥소—피라졸 -1—일 )벤젠설폰아미 에틸 4- [ [4-(4—이소프로필 -2 , 3-디메틸 -5—옥소ᅳ피라졸— 1—일)페닐 ]설포닐아미 노]벤조에이트; A "cycloalkylalkyl group" is a radical of the general formula -alkyl ᅳ cycloalkyl, wherein alkyl and cycloalkyl are as defined above. In some embodiments of the compound of formula (II) the cycloalkylalkyl group is an alkyl, cyclo Alkyl, or both alkyl and cycloalkyl moieties .. Exemplary cycloalkylalkyl groups include, but are not limited to, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclonuxylethyl, and cyclonuxylpropyl No. When the groups disclosed herein are expressed as "substituted," these groups may be substituted with any suitable substituent or substituents. Exemplary examples of substituents include the exemplary compounds and embodiments disclosed herein. Examples of which can be found, and halogens (chloro, urethral, bromo or fluoro groups); alkyl; hydroxyl; alkoxy; al Sialic keel; amino; alkylamino; carboxy; nitro; cyano; thiol; thioether; imine; imide; amidine; guanidine; INC Min; aminocarbonyl; acylamino; phosphonate Nei Sat; PO Spin; Thiocarbonyl; Sulfonyl; Sulfone; Sulfonamides; Ketones; Aldehydes; ester; Urea; urethane; Oxime; Hydroxyl amines; Alkoxyamines; Aralcoxiamine; N-oxides; Hydrazine; Hydrazide; Hydrazone; Azide; Isocyanates; Isothiocyanate; Cyanate; Thiocyanate; Oxygen (= 0); B (0H) 2, 0 (alkyl) aminocarbonyl; Cycloalkyl which may be monocyclic or fused or unfused polycyclic (eg cyclopropyl, cyclo butyl, cyclopentyl or cyclonuxyl), or heterocyclic which may be monocyclic or fused or unfused polycyclic Reels (eg, pyridyl, piperidyl, piperazinyl, morpholinyl or thiazinyl); Monocyclic or fused or unfused polycyclic aryl or heteroaryl (e.g., phenyl, naphthyl, pyryl, indolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thia Zolyl, triazolyl, tetrazolyl, pyrazolyl, pyridyl, quinolinyl, isoquinolinyl, acridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, benzimidazolyl, benzothiophenyl or benzofuranyl Aryloxy; Aralkyloxy; Heterocyclyloxy; And heterocyclyl alkoxy, but are not limited thereto. Preferably, straight or branched dC 6 alkyl; d— C 6 alkyloxy; dC in 6 alkylamino group value hwandoen dC 6 alkyloxy; D-Cs alkyloxy substituted with morpholine; d— C 6 alkyloxycarbonyl; Hydroxycarbonyl d—C 6 alkyl; DC 6 alkyl substituted with one or more fluoro atoms; dC 6 alkylamino; Phenyl; Straight or branched dC 6 alkyl, straight or branched d—C 6 alkyloxy, straight or branched dC 6 alkyloxycarbonyl, halogen or alkyl substituted with one or more fluoro atoms Phenyl substituted with one or more substituents selected from; Phenoxy; Phenoxy substituted with one or more substituents selected from the group consisting of straight or branched d—C 6 alkyl, halogen atoms and straight or branched C 6 alkyloxy; Aminosulfonyl; Halo; Cyano; Acetyl; Nitro; Ethynyl; Hydroxy; Morpholino; Naphthyl; Teenyl; Pyridyl; Tetrahydrofuranyl; Carboxyl; Thiophenyl; dC 10 cycloalkyl; Benzodioxolyl; Indolyl substituted with straight or branched d—C 6 alkyloxy; Di hydrobenzooxynyl; And furylmethylsulfanyl may be selected from one or more. More preferably, the compound of Formula 1 may be selected from the following. N1-cyclonuclear chamber 4 ᅳ isopropyl -2,3-dimethyl- 5-oxo-pyrazol-l-yl) benzenesulfonami Ethyl 4- [[4- (4—isopropyl-2, 3-dimethyl-5—oxo-pyrazol- 1-yl) phenyl] sulfonylamino] benzoate;
4-(4—이소프로필— 2 , 3-디메틸 -5-옥소-피라졸 -1ᅳ일) -N—페닐-벤젠설폰아미드； Nᅳ시클로핵실 -4— (4-이소프로필一 2， 3-디메틸— 5-옥소—피라졸 -1—일 )— N-메틸 -벤젠 설폰아미드;  4- (4—Isopropyl— 2, 3-dimethyl-5-oxo-pyrazol-1xyl) -N—phenyl-benzenesulfonamide; N-cyclocyclohexyl-4— (4-isopropyl one 2 ， 3- Dimethyl— 5-oxo-pyrazol-1—yl) —N-methyl-benzene sulfonamide;
Nᅳ (4—터트—부틸페닐) -4-(4-이소프로필— 2， 3—디메틸 -5—옥소—피라졸 -1—일 )벤젠 설폰아미드;  N '(4—tert-butylphenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzene sulfonamide;
4ᅳ (4-이소프로필 -2， 3—디메틸 -5—옥소—피라졸 -1—일) -N— (4-메록시페닐)벤젠설폰 아미드；  4 '(4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N— (4-methoxyphenyl) benzenesulfon amide;
4ᅳ(4-이소프로필ᅳ 2 , 3-디메틸ᅳ5-옥소—피라졸-1-일)—^(4-모폴리노페닐)벤젠설 폰아미드;  4 '(4-isopropyl'2, 3-dimethyl'5-oxo-pyrazol-1-yl) — ^ (4-morpholinophenyl) benzenesulfonamide;
Nᅳ [ (3 , 4—디메록시페닐)메틸]ᅳ 4-(4ᅳ이소프로필— 2， 3—디메틸— 5-옥소ᅳ피라졸— 1- 일)벤젠설폰아미드;  N '[(3,4-dimethoxyphenyl) methyl]' 4- (4'isopropyl- 2,3-dimethyl- 5-oxo-pyrazol- 1-yl) benzenesulfonamide;
Nᅳ [2- (3 , 4-디메록시페닐)에틸] -4- (4-이소프로필— 2 ' 3一디메틸 -5ᅳ옥소—피라졸- 1—일)벤젠설폰아미드;  N '[2- (3,4-dimethoxyphenyl) ethyl] -4- (4-isopropyl—2' 3 dimethyl-5 boxo-pyrazol-1-yl) benzenesulfonamide;
4一(4-이소프로필ᅳ 2 , 3—디메틸— 5—옥소—피라졸 -1-일 )-N— [ (2—메특시페닐)메틸]벤 젠설폰아미드;  4 一 (4-isopropyl ᅳ 2, 3-dimethyl— 5—oxo-pyrazol-1-yl) -N— [(2—mesotphenyl) methyl] benzensulfonamide;
4-(4—이소프로필— 2，3ᅳ디메틸 -5—옥소—피라졸 -1—일 )— N-(p-를릴)벤젠설폰아미 N-(4ᅳ클로로페닐) -4— (4—이소프로필 -2，3-디메틸 -5-옥소—피라졸— 1-일 )벤젠설폰 아미드;  4- (4—Isopropyl— 2,3 ᅳ dimethyl-5—oxo—pyrazol-1—yl) —N- (p-ryll) benzenesulfonami N- (4 ᅳ chlorophenyl) -4— (4— Isopropyl-2,3-dimethyl-5-oxo-pyrazol- 1-yl) benzenesulfon amide;
4- ( 4-이소프로필 -2 , 3—디메틸 -5—옥소-피라졸— 1-일)— N— [ 2ᅳ ( 2-메특시페닐)에틸] 벤젠설폰아미드;  4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol— 1-yl) — N— [2 ′ (2-methoxyphenyl) ethyl] benzenesulfonamide;
4ᅳ(4-이소프로필 -2 , 3—디메틸 -5—옥소-피라졸—1-일) -N— [2ᅳ (2—메특시페녹시)에 틸]벤젠설폰아미드;  4 '(4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N— [2' (2-methoxyphenoxy) ethyl] benzenesulfonamide;
4ᅳ(4—이소프로필— 2， 3—디메틸ᅳ 5-옥소ᅳ피라졸— 1-일 )-N-(3—메톡시페닐)벤젠설폰 아미드;  4 ′ (4—isopropyl— 2, 3—dimethyl ᅳ 5-oxo-pyrazol— 1-yl) -N- (3-methoxyphenyl) benzenesulfon amide;
4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1-일) -N-(2ᅳ메록시페닐)벤젠설폰 아미드；  4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N- (2'methoxyphenyl) benzenesulfon amide;
4-(4—이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1ᅳ일) -N— (3ᅳ페닐프로필)벤젠설폰 아미드； 4-(4ᅳ이소프로필 -2 , 3ᅳ디메틸 -5-옥소-피라졸 -1-일) -N-(3—니트로페닐)벤젠설폰 아미드; 4- (4—isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1xyl) -N— (3′phenylpropyl) benzenesulfon amide; 4- (4'isopropyl-2,3'dimethyl-5-oxo-pyrazol-1-yl) -N- (3-nitrophenyl) benzenesulfon amide;
4一 (4ᅳ이소프로필—2， 3-디메틸—5-옥소—피라졸 -1—일) -N-(4-니트로페닐)벤젠설폰 아미드；  4 one (4 ᅳ isopropyl—2, 3-dimethyl-5-oxo-pyrazol-1—yl) -N- (4-nitrophenyl) benzenesulfon amide;
4-(4ᅳ이소프로필 -2 , 3—디메틸 -5-옥소—피라졸 -1-일)ᅳ N-(2-페닐에틸 )벤젠설폰아 미드;  4- (4'isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) 'N- (2-phenylethyl) benzenesulfonamide;
4— (4-이소프로필— 2， 3—디메틸 -5—옥소—피라졸 -1—일)— N-(4-페닐부틸)벤젠설폰아 미드;  4— (4-isopropyl— 2, 3—dimethyl-5—oxo—pyrazol-1—yl) —N- (4-phenylbutyl) benzenesulfonamide;
4一 (4-이소프로필— 2 , 3-디메틸ᅳ 5-옥소-피라졸 -1—일 )-Nᅳ (5—퀴놀릴)벤젠설폰아미 4-(4ᅳ이소프로필— 2， 3-디메틸— 5-옥소-피라졸 -1-일 )—N-(3-퀴놀릴 )벤젠설폰아미  4 一 (4-isopropyl— 2, 3-dimethyl ᅳ 5-oxo-pyrazol-1—yl) -N ᅳ (5—quinolyl) benzenesulfonami 4- (4 ᅳ isopropyl— 2, 3-dimethyl — 5-oxo-pyrazol-1-yl) —N- (3-quinolyl) benzenesulfonami
N- ( 4-플루오로페닐 )—4- ( 4—이소프로필 -2， 3-디메틸—5-옥소-피라졸— 1—일)벤젠설 폰아미드; N- (4-fluorophenyl) —4- (4—isopropyl-2, 3-dimethyl-5-oxo-pyrazole-1-yl) benzenesulfonamide;
터트ᅳ부틸 4— [ [4-(4ᅳ이소프로필— 2 , 3—디메틸 -5-옥소—피라졸 -1ᅳ일)페닐]설포닐 아미노]피페리딘 -1-카르복실레아트；  Tert-butyl 4 -— [[4- (4'isopropyl-2,3-dimethyl-5-oxo-pyrazol-1xyl) phenyl] sulfonyl amino] piperidine-1-carboxylate;
N- [ 2ᅳ ( 4—클로로페닐)에틸] -4— ( 4-이소프로필 -2 , 3-디메틸 -5-옥소—피라졸 - 1-일) 벤젠설폰아미드;  N- [2 ′ (4—chlorophenyl) ethyl] -4— (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
4- ( 4-이소프로필 -2 , 3—디메틸 -5—옥소-피라졸 - 1—일)— Nᅳ ( 2-티에닐메틸)벤젠설폰 아미드;  4- (4-isopropyl -2, 3 -dimethyl-5-oxo-pyrazol-1 -yl)-N '(2-thienylmethyl) benzenesulfon amide;
4- (4-이소프로필 -2 , 3-디메틸— 5—옥소—피라졸 -1-일 )— N-(3—피리딜메틸)벤젠설폰 아미드;  4- (4-isopropyl-2, 3-dimethyl— 5—oxo-pyrazol-1-yl) —N- (3—pyridylmethyl) benzenesulfon amide;
4- ( 4—이소프로필 -2 , 3-디메틸—5—옥소-피라졸— 1—일) -N- [ 2— ( 2—피리딜)에틸]벤젠 설폰아미드;  4- (4—isopropyl-2, 3-dimethyl—5—oxo-pyrazol— 1—yl) -N- [2— (2—pyridyl) ethyl] benzene sulfonamide;
4-(4—이소프로필— 2 , 3-디메틸— 5—옥소-피라졸 -1—일)— N-(2—나프틸메틸)벤젠설폰 아미드;  4- (4—Isopropyl— 2, 3-dimethyl— 5—oxo-pyrazol-1—yl) —N- (2—naphthylmethyl) benzenesulfon amide;
N— [2-(3-플루오로페닐 )에틸]— 4-(4-이소프로필— 2， 3-디메틸 -5—옥소-피라졸 -1— 일)벤젠설폰아미드;  N— [2- (3-fluorophenyl) ethyl] — 4- (4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazol-1—yl) benzenesulfonamide;
Nᅳ (5-플루오로— 2—피리딜) -4-(4-이소프로필ᅳ 2， 3—디메틸— 5—옥소-피라졸— 1—일 ) 벤젠설폰아미드;  N '(5-fluoro- 2-pyridyl) -4- (4-isopropyl ᅳ 2, 3-dimethyl- 5-oxo-pyrazole- 1-yl) benzenesulfonamide;
4— (4-이소프로필— 2， 3-디메틸— 5-옥소-피라졸 -1ᅳ일 )— Nᅳ [ (4—메록시페닐)메틸]벤 젠설폰아미드; 4-(4-이소프로필— 2 , 3-디메틸ᅳ 5—옥소—피라졸 -1-일 )-Ν-(6—퀴놀릴)벤젠설폰아미 4— (4-isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol-1xyl) — N ′ [(4—methoxyphenyl) methyl] benzensulfonamide; 4- (4-isopropyl— 2, 3-dimethyl ᅳ 5—oxo-pyrazol-1-yl) -Ν- (6-quinolyl) benzenesulfonami
Ν-(2 , 3—디히드로 -1 , 4ᅳ벤조디옥신 -6—일) -4-(4-이소프로필— 2 , 3-디메틸 -5-옥소ᅳ 피라졸 -1—일)벤젠설폰아미드; Ν- (2, 3—dihydro-1, 4 ᅳ benzodioxin-6-yl) -4- (4-isopropyl— 2, 3-dimethyl-5-oxopy pyrazol-1—yl) benzenesulfon amides;
Ν一 [4ᅳ (디메틸아미노)페닐] -4- (4-이소프로필 -2 ,3-디메틸 -5—옥소—피라졸— 1-일) 벤젠설폰아미드; Ν 一 [ 4 ᅳ (dimethylamino) phenyl] -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol- 1-yl) benzenesulfonamide;
메틸 3- [ [4-(4—이소프로필 -2 , 3—디메틸— 5—옥소'—피라졸 -1—일)페닐]설포닐아미 노]벤조에이트 ;  Methyl 3-[[4- (4—isopropyl-2,3—dimethyl-5—oxo'—pyrazol-1—yl) phenyl] sulfonylamino] benzoate;
에틸 3- [ [4-(4一이소프로필ᅳ 2 , 3-디메틸— 5-옥소—피라졸 - 1-일 )페닐]설포닐아미 노]벤조에이트;  Ethyl 3- [[4- (4yisopropyl ᅳ 2, 3-dimethyl- 5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] benzoate;
4一 (4ᅳ이소프로필— 2 , 3-디메틸— 5-옥소—피라졸— 1—일)— Ν— [3— (트리플루오로메틸 ) 페닐]벤젠설폰아미드;  4 one (4 ᅳ isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol— 1—yl) — N— [3— (trifluoromethyl) phenyl] benzenesulfonamide;
Ν- [2-(4-플루오로페닐)에틸]— 4-(4-이소프로필 -2， 3-디메틸— 5—옥소-피라졸 -1— 일. )벤젠설폰아미드;  N- [2- (4-fluorophenyl) ethyl] —4- (4-isopropyl-2, 3-dimethyl--5-oxo-pyrazole-1-yl.) Benzenesulfonamide;
4— (4ᅳ이소프로필— 2， 3-디메틸 -5-옥소—피라졸— 1-일) -Ν-(4-이소프로필페닐 )벤젠 설폰아미드;  4— (4 ᅳ isopropyl— 2, 3-dimethyl-5-oxo-pyrazol— 1-yl) -Ν- (4-isopropylphenyl) benzene sulfonamide;
Ν-(3ᅳ플루오로페닐)— 4-(4-이소프로필 -2， 3-디메틸ᅳ 5-옥소—피라졸— 1—일 )벤젠설 폰아미드;  Ν- (3 ᅳ fluorophenyl) —4- (4-isopropyl-2, 3-dimethyl ᅳ 5-oxo-pyrazol-1-yl) benzenesulfonamide;
Ν— (3-플루오로페닐) -4-(4-이소프로필— 2 , 3—디메틸ᅳ 5-옥소-피라졸— 1—일)— Νᅳ메 틸—벤젠설폰아미드;  Ν— (3-fluorophenyl) -4- (4-isopropyl— 2, 3—dimethyl ᅳ 5-oxo-pyrazol— 1—yl) —N—methyl-benzenesulfonamide;
4— (4-이소프로필 -2 , 3—디메틸ᅳ 5—옥소—피라졸 -1-일) -Νᅳ ( 1—나프틸)벤젠설폰아미  4— (4-isopropyl-2, 3—dimethyl ᅳ 5—oxo-pyrazol-1-yl) -Ν ᅳ (1—naphthyl) benzenesulfonami
4-(4-이소프로필— 2 , 3—디메틸— 5-옥소—피라졸— 1-일 )— Ν- [ (3-메록시페닐)메틸]벤 젠설폰아미드; 4- (4-isopropyl— 2, 3—dimethyl— 5-oxo-pyrazol— 1-yl) — Ν- [(3-methoxyphenyl) methyl] benzensulfonamide;
Ν- [ (3—플루오로페닐 )메틸] -4— (4-이소프로필 -2 ,3—디메틸— 5—옥소—피라졸 -1—일 ) 벤젠설폰아미드;  Ν- [(3—fluorophenyl) methyl] -4— (4-isopropyl-2,3—dimethyl— 5—oxo-pyrazol-1-yl) benzenesulfonamide;
4一 (4-이소프로필— 2， 3-디메틸 -5-옥소—피라졸 -1—일 )— Ν- (테트라히드로퓨란 -2—일 메틸)벤젠설폰아미드;  4 one (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazol-1—yl) —N— (tetrahydrofuran-2—yl methyl) benzenesulfonamide;
Ν- [2-(2—퓨릴메틸설파닐)에틸] -4ᅳ (4—이소프로필 -2，3-디메틸— 5—옥소 -피라졸- 1-일)벤젠설폰아미드;  N- [2- (2-furylmethylsulfanyl) ethyl] -4 '(4—isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
4-(4-이소프로필 -2 , 3—디메틸—5-옥소-피라졸 -1-일) -Ν— [2— (ρᅳ를릴)에틸]벤젠설 폰아미드; 4— (4-이소프로필 -2 , 3—디메틸— 5-옥소—피라졸 -1—일 )— N-(4-메특시페닐)— N-메틸一 벤젠설폰아미드; 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -Ν— [2— (ρ ᅳ aryl) ethyl] benzenesulfonamide; 4— (4-isopropyl-2, 3—dimethyl— 5-oxo-pyrazol-1—yl) — N- (4-methoxyphenyl) —N-methylone benzenesulfonamide;
4- (4—이소프로필— 2， 3-디메틸 -5—옥소—피라졸— 1-일 )-N— [2— (4-메록시페닐)에틸] 벤젠설폰아미드;  4- (4—Isopropyl— 2, 3-dimethyl-5—oxo-pyrazol— 1-yl) -N— [2— (4-methoxyphenyl) ethyl] benzenesulfonamide;
N- [ (2-클로로페닐)메틸]—4— (4ᅳ이소프로필 -2 , 3—디메틸 -5-옥소-피라졸ᅳ 1-일 )벤 젠설폰아미드;  N-[(2-chlorophenyl) methyl] —4— (4 ᅳ isopropyl-2, 3-dimethyl-5-oxo-pyrazolyl 1-yl) benzensulfonamide;
N-(2-플루오로페닐)— 4-(4—이소프로필 -2， 3一디메틸 -5-옥소-피라졸ᅳ 1—일 )벤젠설 폰아미드;  N- (2-fluorophenyl) —4- (4-isopropyl-2,3 dimethyl-5-oxo-pyrazolyl 1-yl) benzenesulfonamide;
N- [ (2-플루오로페닐)메틸] -4— (4-이소프로필— 2，3-디메틸— 5-옥소—피라졸 -1—일) 벤젠설폰아미드;  N-[(2-fluorophenyl) methyl] -4— (4-isopropyl—2,3-dimethyl—5-oxo-pyrazol-1—yl) benzenesulfonamide;
4一 (4-이소프로필 -2ᅳ 3-디메틸 -5—옥소-피라졸 -1-일 )—N-(p-롤릴메틸)벤젠설 ^아 미드;  4 one (4-isopropyl-2 ′ 3-dimethyl-5—oxo-pyrazol-1-yl) —N- (p-rollylmethyl) benzenesul ^ amide;
4— (4—이소프로필ᅳ 2， 3-디메틸 -5ᅳ옥소-피라졸 -1-일) -N-(m—를릴메틸 )벤젠설폰아 미드;  4— (4—isopropyl ᅳ 2, 3-dimethyl-5 ”oxo-pyrazol-1-yl) -N- (m- rylmethyl) benzenesulfonamide;
N-( 2 , 5-디메틸페닐)—4- (4-이소프로필 -2 , 3—디메틸 -5—옥소—피라졸— 1—일 )벤젠설 폰아미드;  N- (2, 5-dimethylphenyl) —4- (4-isopropyl-2, 3—dimethyl-5—oxo-pyrazol-1—yl) benzenesulfonamide;
4-(4-이소프로필 -2 , 3-디메틸— 5—옥소-피라졸 -1-일 )-N- (m—를릴 )벤젠설폰아미 4-(4—이소프로필 -2 , 3-디메틸 -5-옥소-피라졸— 1-일) -N- (으를릴 )벤젠설폰아미 드 * 4- (4-isopropyl-2, 3-dimethyl— 5—oxo-pyrazol-1-yl) -N- (m—lryl) benzenesulfonami 4- (4—isopropyl-2, 3-dimethyl- 5-oxo-pyrazole— 1-yl) -N- (neryl) benzenesulfonamide *
N-(4—시아노페닐) -4-(4-이소프로필— 2，3—디메틸— 5—옥소-피라졸 -1—일)벤젠설폰 아미드；  N- (4—cyanophenyl) -4- (4-isopropyl— 2,3—dimethyl— 5—oxo-pyrazol-1—yl) benzenesulfon amide;
4-(4-이소프로필— 2， 3—디메틸— 5-옥소—피라졸— 1-일 )-N— [2- (트리플루오로메틸 ) 페닐]벤젠설폰아미드;  4- (4-isopropyl— 2, 3—dimethyl— 5-oxo-pyrazol— 1-yl) -N— [2- (trifluoromethyl) phenyl] benzenesulfonamide;
N— (2 , 4-디메틸페닐)— 4- (4-이소프로필 -2， 3—디메틸 -5-옥소-피라졸 -1-일 )벤젠설 폰아미드;  N— (2, 4-dimethylphenyl) — 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
4-(4-이소프로필 -2， 3—디메틸 -5-옥소—피라졸 -1-일)— N-(6—메톡시—3—피리딜)벤 젠설폰아미드;  4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl)-N- (6-methoxy- 3-pyridyl) benzensulfonamide;
4-(4-이소프로필 -2， 3-디메틸 -5-옥소—피라졸 -1—일 )— N— (p—를릴)벤젠설폰아미  4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1—yl) — N— (p—lryl) benzenesulfonami
N-(2 , 2-디메틸프로필 )-4— (4-이소프로필 -2 , 3-디메틸—5—옥소ᅳ피라졸—1—일)벤젠 설폰아미드; 4- (4—이소프로필— 2 , 3—디메틸 -5ᅳ옥소ᅳ피라졸ᅳ 1-일 )-N— (2ᅳ피리딜메틸)벤젠설폰 이-미드； N- (2, 2-dimethylpropyl) -4— (4-isopropyl-2, 3-dimethyl—5—oxo-pyrazol-l-yl) benzene sulfonamide; 4- (4—Isopropyl— 2, 3—dimethyl-5 ”oxo” pyrazolyl 1-yl) -N— (2 ”pyridylmethyl) benzenesulfon i-mid;
4-(4—이소프로필— 2， 3-디메틸ᅳ 5—옥소-피라졸—1-일) -N— (2ᅳ피리딜)벤젠설폰아미 Ν-(3-브로모페닐) -4— (4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸 -1ᅳ일)벤젠설폰 아미드；  4- (4—Isopropyl— 2, 3-dimethyl ᅳ 5—oxo-pyrazol—1-yl) -N— (2 ᅳ pyridyl) benzenesulfonami Ν- (3-bromophenyl) -4— ( 4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1xyl) benzenesulfon amide;
Ν— (2-브로모페닐)— 4ᅳ (4-이소프로필— 2 , 3—디메틸— 5-옥소-피라졸 -1ᅳ일)벤젠설폰 아미드;  Ν— (2-bromophenyl) — 4 ′ (4-isopropyl— 2, 3—dimethyl— 5-oxo-pyrazol-1xyl) benzenesulfon amide;
Ν-(2 , 4—디브로모페닐 )ᅳ4— (4—이소프로필— 2， 3-디메틸 -5-옥소-피라졸— 1—일 )벤젠 설폰아미드;  Ν- (2, 4—dibromophenyl) ᅳ 4— (4—isopropyl— 2, 3-dimethyl-5-oxo-pyrazol— 1—yl) benzene sulfonamide;
Ν一 (2， 5—디브로모페닐)— 4— (4-이소프로필 -2 , 3-디메틸— 5-옥소—피라졸 -1—일 )벤젠 설폰아미드;  Ν 一 (2, 5—dibromophenyl) — 4— (4-isopropyl-2, 3-dimethyl— 5-oxo-pyrazol-1—yl) benzene sulfonamide;
Ν-(3—에틸페닐) -4— (4-이소프로필— 2 , 3-디메틸 -5—옥소-피라졸— 1ᅳ일)벤젠설폰아 미드;  Ν- (3—ethylphenyl) -4— (4-isopropyl—2, 3-dimethyl-5—oxo-pyrazol—1 ᅳ yl) benzenesulfonamide;
Ν—α， 1ᅳ디메틸프로필)—4— (4—이소프로필— 2 , 3-디메틸— 5—옥소—피라졸 -1—일 )벤젠 설폰아미드;  Ν—α ， 1 ᅳ dimethylpropyl) —4— (4—isopropyl— 2, 3-dimethyl— 5—oxo-pyrazol-1—yl) benzene sulfonamide;
Ν一 (3， 5-디메특시페닐 )-4— (4-이소프로필 -2， 3—디메틸 -5—옥소-피라졸— 1-일 )벤젠 설폰아미드;  NI (3, 5-dimethoxyphenyl) -4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) benzene sulfonamide;
Ν-시클로펜틸 -4— (4-이소프로필— 2， 3-디메틸— 5—옥소—피라졸 -1-일 )벤젠설폰아미  Ν-cyclopentyl-4— (4-isopropyl— 2, 3-dimethyl— 5—oxo-pyrazol-1-yl) benzenesulfonami
4一이소프로필— 2- [4- [4-(4-메록시페닐)피페라진— 1—일]설포닐페닐] -1 , 5-디메틸 ᅳ피라졸 -3—온; 4 one isopropyl— 2- [4- [4- (4-methoxyphenyl) piperazine— 1—yl] sulfonylphenyl] -1, 5-dimethyl cappyrazol-3-one;
4-(4—이소프로필— 2，3-디메틸-5-옥소—피라졸-1—일) -(4-36(ᅩ부틸페닐)벤젠설 폰아미드; 4- (4—Isopropyl— 2,3-dimethyl-5-oxo-pyrazol-1—yl)-(4-36 ( ᅩ butylphenyl) benzenesulfonamide;
에틸 4— [ [4— (4-이소프로필— 2，3-디메틸ᅳ 5-옥소-피라졸ᅳ 1—일)페닐]설포닐아미 노]피페리딘— 1-카르복실레이트；  Ethyl 4— [[4— (4-isopropyl— 2,3-dimethyl ᅳ 5-oxo-pyrazol ᅳ 1-yl) phenyl] sulfonylamino] piperidine— 1-carboxylate;
Ν-인단 -5-일— 4- ( 4-이소프로필 -2 , 3—디메틸—5—옥소-피라졸— 1ᅳ일)벤젠설폰아미  Ν-indane-5-yl— 4- (4-isopropyl-2,3-dimethyl--5-oxo-pyrazole- 1 ᅳ yl) benzenesulfonami
N一인단— 2-일 -4- -이소프로필 -2，3-디메틸 -5-옥소—피라졸— 1—일)벤젠설폰아미 N-indane- 2-yl-4--isopropyl-2,3-dimethyl-5-oxo-pyrazole- 1-yl) benzenesulfonami
N-시클로헵틸 -4-(4—이소프로필 -2 , 3—디메틸— 5—옥소—피라졸— 1—일 )벤젠설폰아미 4-(4 이소프로필— 2， 3—디메틸 -5—옥소-피라졸— 1-일 )— N— [3- (트리플루오로메틸 ) 페닐]벤젠설폰아미드; N-cycloheptyl-4- (4—isopropyl-2, 3—dimethyl— 5—oxo—pyrazole— 1—yl) benzenesulfonami 4- (4 isopropyl— 2, 3—dimethyl-5—oxo-pyrazol— 1-yl) — N— [3- (trifluoromethyl) phenyl] benzenesulfonamide;
N一 (4-아세틸페닐)— 4-(4-이소프로필— 2，3-디메틸 -5—옥소—피라졸— 1-일)벤젠설폰 아미드；  N 一 (4-acetylphenyl) — 4- (4-isopropyl— 2,3-dimethyl-5—oxo-pyrazol— 1-yl) benzenesulfon amide;
메틸 4- [ [4-(4—이소프로필 -2， 3-디메틸 -5—옥소—피라졸 -1-일)페닐]설포닐아미 노]벤조에이트;  Methyl 4- [[4- (4—isopropyl-2, 3-dimethyl-5—oxo-pyrazol-1-yl) phenyl] sulfonylamino] benzoate;
4一 (4—이소프로필— 2， 3-디메틸 -5—옥소-피라졸 -1—일 )-N—피리미딘— 2-일ᅳ벤젠설폰 아미드；  4 一 (4—isopropyl— 2, 3-dimethyl-5—oxo-pyrazol-1—yl) -N—pyrimidine— 2-yl ᅳ benzenesulfon amide;
N [ (2 , 4—디메록시페닐)메틸] -4— (4ᅳ이소프로필— 2 , 3-디메틸 -5ᅳ옥소-피라졸 -1- 일)벤젠설폰아미드;  N [(2, 4—dimethoxyphenyl) methyl] -4— (4 ᅳ isopropyl— 2, 3-dimethyl-5oxo-pyrazol-1-yl) benzenesulfonamide;
N—(2-클로로 -4-피리딜)— 4— (4-이소프로필ᅳ2 , 3ᅳ디메틸— 5-옥소—피라졸ᅳ 1-일)벤 젠설폰아미드;  N— (2-chloro-4-pyridyl) — 4— (4-isopropyl ᅳ 2, 3 ᅳ dimethyl— 5-oxo-pyrazolyl 1-yl) benzensulfonamide;
2- [4-(4—에틸피페라진ᅳ 1—일)설포닐페닐] -4—이소프로필 -1 , 5-디메틸―피라졸— 3ᅳ 은;  2- [4- (4-ethylpiperazin ᅳ 1-yl) sulfonylphenyl] -4-isopropyl-1, 5-dimethyl-pyrazole- 3 'silver;
N— [3， 5—비스 (트리플루오로메틸)페닐] -4— (4-이소프로필 -2 , 3-디메틸 -5ᅳ옥소—피 라졸— 1-일)벤젠설폰아미드;  N— [3, 5-bis (trifluoromethyl) phenyl] -4— (4-isopropyl-2,3-dimethyl-5oxoo-pyrazol- 1-yl) benzenesulfonamide;
4-(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸 -1-일) -N— (4-피리딜메틸)벤젠설폰 아미드；  4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N— (4-pyridylmethyl) benzenesulfon amide;
N-(9—에틸카르바졸— 3—일)— 4— (4—이소프로필 -2， 3-디메틸ᅳ 5—옥소-피라졸— 1—일) 벤젠설폰아미드;  N- (9—ethylcarbazole— 3—yl) — 4— (4—isopropyl-2, 3-dimethyl ᅳ 5—oxo-pyrazole— 1—yl) benzenesulfonamide;
N-(4—브로모— 1-나프틸 )— 4-(4—이소프로필 -2 , 3-디메틸 -5—옥소—피라졸 -1—일, )벤 젠설폰아미드;  N- (4—bromo— 1-naphthyl) — 4- (4—isopropyl-2, 3-dimethyl-5—oxo-pyrazol-1—yl,) benzensulfonamide;
4一( 4—이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1—일 )— N-(2-페닐페닐)벤젠설폰아 미드;  4 one (4—isopropyl-2, 3—dimethyl-5-oxo-pyrazol—1—yl) —N- (2-phenylphenyl) benzenesulfonamide;
4一(4—이소프로필— 2， 3-디메틸— 5-옥소—피라졸— 1-일 )— N-(2ᅳ메틸 -1—나프틸 )벤젠 설폰아미드; : 4 one (4—isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol— 1-yl) —N- (2 ᅳ methyl-1—naphthyl) benzene sulfonamide; :
N- [2— (4—브로모페닐)에틸] -4— (4—이소프로필 -2 , 3-디메틸ᅳ 5—옥소-피라졸—1—일) 벤젠설폰아미드;  N- [2— (4—bromophenyl) ethyl] -4— (4—isopropyl-2, 3-dimethyl ᅳ 5—oxo-pyrazol—1—yl) benzenesulfonamide;
4-(4-이소프로필— 2， 3—디메틸 -5—옥소-피라졸 -1—일 )-N- [2ᅳ (5-메록시— 1H—인돌- 3一일)에틸]벤젠설폰아미드;  4- (4-isopropyl— 2, 3—dimethyl-5—oxo-pyrazol-1—yl) -N- [2 ′ (5-methoxy- 1H—indole-3 ilyl) ethyl] benzenesulfonamide ;
4- (4-이소프로필— 2， 3—디메틸— 5—옥소-피라졸 -1—일)— N-(2-메틸 -1Hᅳ인돌—5-일 ) 벤젠설폰아미드; N-( 1H—인돌— 5—일메틸)— 4-(4—이소프로필— 2 , 3—디메틸— 5-옥소—피라졸ᅳ 1-일 )벤젠 설폰아미드; 4- (4-isopropyl— 2, 3—dimethyl— 5—oxo-pyrazol-1—yl) —N- (2-methyl-1H ᅳ indole—5-yl) benzenesulfonamide; N- (1H—indole— 5—ylmethyl) — 4- (4—isopropyl— 2, 3—dimethyl— 5-oxo-pyrazolyl 1-yl) benzene sulfonamide;
4-(4—이소프로필— 2 , 3-디메틸— 5-옥소-피라졸 -1-일) -N— (6—메록시 1，3—벤조티아 졸 -2—일)벤젠설폰아미드;  4- (4—isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol-1-yl) -N— (6—methoxy 1,3—benzothiazol-2—yl) benzenesulfonamide;
Ν—[2-( 1Η-인돌— 3—일)에틸]— 4— (4—이소프로필— 2， 3-디메틸 -5-옥소—피라졸 1—일) 벤젠설폰아미드;  Ν— [2- (1Η-indole— 3—yl) ethyl] — 4— (4—isopropyl— 2, 3-dimethyl-5-oxo-pyrazol 1—yl) benzenesulfonamide;
4- (4-이소프로필 -2， 3-디메틸 -5—옥소—피라졸— 1—일 )— N— (2-메틸 -8—퀴놀릴)벤젠 설폰아미드;  4- (4-isopropyl-2, 3-dimethyl-5—oxo-pyrazol— 1—yl) — N— (2-methyl-8—quinolyl) benzene sulfonamide;
N-(4—에록시 -2-니트로—페닐) -4— (4—이소프로필— 2， 3—디메틸— 5-옥소—피라졸ᅳ 1- 일)벤젠설폰아미드;  N- (4—hydroxy-2-nitro-phenyl) -4— (4—isopropyl— 2, 3—dimethyl— 5-oxo-pyrazolyl 1-yl) benzenesulfonamide;
N— (3， 4-디클로로페닐) -4-(4—이소프로필 -2 , 3—디메틸 -5—옥소-피라졸 -1—일 )벤젠 설폰아미드;  N— (3, 4-dichlorophenyl) -4- (4—isopropyl-2, 3—dimethyl-5—oxo-pyrazol-1-yl) benzene sulfonamide;
N— [2— (2-클로로페닐)에틸] -4-(4-이소프로필— 2 , 3-디메틸— 5—옥소ᅳ피라졸ᅳ 1-일 ) 벤젠설폰아미드;  N— [2— (2-chlorophenyl) ethyl] -4- (4-isopropyl— 2, 3-dimethyl— 5—oxo-pyrazolyl 1-yl) benzenesulfonamide;
N— [ (4-클로로페닐)메틸] -4-(4一이소프로필 -2 , 3-디메틸 -5—옥소-피라졸ᅳ 1—일 )벤 젠설폰아미드;  N— [(4-chlorophenyl) methyl] -4- (4iisopropyl-2, 3-dimethyl-5-oxo-pyrazolyl 1-yl) benzensulfonamide;
Nᅳ (3， 5-디클로로페닐) -4ᅳ (4ᅳ이소프로필 -2 , 3—디메틸— 5—옥소—피라졸— 1ᅳ일 )벤젠 설폰아미드;  N '(3, 5-dichlorophenyl) -4' (4 'isopropyl -2, 3-dimethyl-5-oxo-pyrazol-1) yl) benzene sulfonamide;
N— ( 1， 2-디메록시프로필 )ᅳ4— (4-이소프로필 -2， 3-디메틸ᅳ 5ᅳ옥소-피라졸— —일 )벤 젠설폰아미드;  N— (1, 2-dimethoxypropyl) ᅳ 4— (4-isopropyl-2, 3-dimethyl ᅳ 5 ᅳ oxo-pyrazol— —yl) benzensulfonamide;
N- ( 5-클로로 -2-플루오로-페닐) -4— ( 4-이소프로필 -2 , 3-디메틸—5-옥소—피라졸— 1一일)벤젠설폰아미드;  N- (5-chloro-2-fluoro-phenyl) -4— (4-isopropyl-2, 3-dimethyl- 5-oxo-pyrazole- 1 day) benzenesulfonamide;
Nᅳ (4-에티닐페닐) -4-(4—이소프로필 -2 , 3—디메틸 -5—옥소-피라졸 -1-일 )벤젠설폰 아미드；  N '(4-ethynylphenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfon amide;
N- [ (4—플루오로페닐)메틸] -4-(4—이소프로필 -2 , 3-디메틸 -5-옥소—피라졸— 1-일 ) 벤젠설폰아미드;  N- [(4—fluorophenyl) methyl] -4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) benzenesulfonamide;
N-(2 , 4-디메틸— 6—니트로ᅳ페닐)— 4-(4—이소프로필— 2， 3—디메틸 -5—옥소—피라졸— 1—일)벤젠설폰아미드;  N- (2, 4-dimethyl-6-nitrosphenyl)-4- (4-isopropyl- 2, 3-dimethyl-5-oxo-pyrazole- 1-yl) benzenesulfonamide;
N-(2， 5-디클로로 -4-니트로—페닐) -4— (4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1-일)벤젠설폰아미드;  N- (2, 5-dichloro-4-nitro-phenyl) -4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
N-(4-클로로 -3-니트로-페닐) -4— (4-이소프로필— 2 , 3—디메틸— 5-옥소-피라졸 -1 일)벤젠설폰아미드; N-(2 , 3-디메틸 -6—니트로—페닐 )-4-(4-이소프로필 -2 , 3-디메틸 5—옥소—피라졸一 1-일)벤젠설폰아미드; N- (4-chloro-3-nitro-phenyl) -4— (4-isopropyl— 2, 3—dimethyl— 5-oxo-pyrazol-1 yl) benzenesulfonamide; N- (2, 3-dimethyl-6-nitro-phenyl) -4- (4-isopropyl-2, 3-dimethyl 5-oxo-pyrazolyl 1-yl) benzenesulfonamide;
4一(4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸— 1ᅳ일 )-Ν— ( 1—나프틸메틸 )벤젠설폰 아미드;  4 one (4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazole—monoyl) -Ν— (1—naphthylmethyl) benzenesulfon amide;
Ν-[ (3—브로모페닐)메틸] -4-(4-이소프로필 -2， 3-디메털 -5—옥소—피라졸 -1-일 )벤 젠설폰아미드;  Ν- [(3—bromophenyl) methyl] -4- (4-isopropyl-2, 3-dimetal-5-oxo-pyrazol-1-yl) benzensulfonamide;
Ν- [2— (3-브로모페닐)에틸]—4— (4—이소프로필— 2 , 3—디메틸 _5-옥소—피라졸 -1—일) 벤젠설폰아미드;  Ν- [2— (3-bromophenyl) ethyl] —4— (4—isopropyl— 2, 3—dimethyl _5-oxo-pyrazol-1—yl) benzenesulfonamide;
Ν- [ (2—브로모페닐 )메틸 4-(4—이소프로필ᅳ 2 , 3 메틸 -5-옥소—피라졸— 1-일 )벤 젠설폰아미드;  Ν- [(2—bromophenyl) methyl 4- (4—isopropyl ᅳ 2, 3 methyl-5-oxo-pyrazol— 1-yl) benzensulfonamide;
Ν- [2— (3ᅳ클로로페닐)에틸] -4— (4-이소프로필— 2 , 3-디메틸 -5-옥소—피라졸 -1—일 ) 벤젠설폰아미드;  Ν- [2— (3 ᅳ chlorophenyl) ethyl] -4— (4-isopropyl—2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
4-(4—이소프로필— 2 , 3 메틸 -5-옥소—피라졸— 1—일 )-Ν— [ [3— (트리플루오로메틸 ) 페닐]메틸]벤젠설폰아미드;  4- (4—Isopropyl— 2, 3 methyl-5-oxo-pyrazol— 1—yl) -Ν— [[3— (trifluoromethyl) phenyl] methyl] benzenesulfonamide;
4ᅳ (4—이소프로필 -2 3-디메틸— 5—옥소-피라졸 -1ᅳ일)—Ν—[ [2— (트리플루오로메틸 ) 페닐]메틸]벤젠설폰아미드;  4 '(4—isopropyl-2 3-dimethyl— 5—oxo-pyrazol-1xyl) —Ν— [[2— (trifluoromethyl) phenyl] methyl] benzenesulfonamide;
4-(4—이소프로필 -2， 3—디메틸— 5—옥소-피라졸— 1-일)— Ν- [ [4- (트리플루오로메틸 ) 페닐]메틸]벤젠설폰아미드;  4- (4—Isopropyl-2, 3—dimethyl— 5—oxo-pyrazol— 1-yl) —N— [[4- (trifluoromethyl) phenyl] methyl] benzenesulfonamide;
4-(4ᅳ이소프로필— 2 , 3—디메틸 -5-옥소—피라졸 -1-일) -Ν— ( 0—를릴메틸)벤젠설폰아 미드；  4- (4 ᅳ isopropyl— 2, 3—dimethyl-5-oxo-pyrazol-1-yl) -Ν— (0— rylmethyl) benzenesulfonamide;
Ν— (3-클로로페닐 )-4— (4-이소프로필 -2 , 3—디메틸 -5-옥소-피라졸 -1-일)벤젠설폰 아미드；  Ν— (3-chlorophenyl) -4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfon amide;
Ν-(2-클로로페닐 )—4— (4—이소프로필— 2 , 3-디메틸— 5—옥소—피라졸 -1—일)벤젠설폰 아미드;  Ν- (2-chlorophenyl) —4— (4—isopropyl— 2, 3-dimethyl— 5—oxo—pyrazol-1—yl) benzenesulfon amide;
Ν- [ (3-클로로페닐)메틸] -4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1 )벤 젠설폰아미드;  Ν-[(3-chlorophenyl) methyl] -4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazole-1) benzensulfonamide;
4-(4—브로모—2 , 3-디메틸 -5-옥소-피라졸 -1-일)ᅳ Ν— (2-페녹시에틸)벤젠설폰아미  4- (4—Bromo—2, 3-dimethyl-5-oxo-pyrazol-1-yl) ᅳ Ν— (2-phenoxyethyl) benzenesulfonami
N- [2ᅳ (2-플루오로페닐)에틸]— 4-(4—이소프로필 -2 , 3—디메틸 -5-옥소-피라졸 -1- 일)벤젠설폰아미드; N- [2 '(2-fluorophenyl) ethyl] —4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
N- [ (4—브로모페닐 )메틸] -4-(4-이소프로필 -2， 3—디메틸 -5—옥소-피라졸— 1-일 )벤 젠설폰아미드; N- [2— (2ᅳ브로모페닐 )에틸]— 4-(4—이소프로필 -2 , 3—디메틸 -5—옥소—피라졸ᅳ 1-일 ) 벤젠설폰아미드; N- [(4—bromophenyl) methyl] -4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) benzensulfonamide; N- [2— (2′bromophenyl) ethyl] —4- (4—isopropyl-2,3—dimethyl-5—oxo-pyrazolyl 1-yl) benzenesulfonamide;
4ᅳ(4—이소프로필— 2 , 3一디메틸— 5-옥소-피라졸 -1—일 )— N- [2-(o—를릴 )에틸]벤젠설 폰아미드;  4 '(4—isopropyl—2,3 dimethyl—5-oxo-pyrazol-1—yl) —N- [2- (o-lryl) ethyl] benzenesulfonamide;
4— ( 4-이소프로필 -2 , 3—디메틸 -5—옥소ᅳ피라졸 - 1—일)— N- [ 2- ( 3—메특시페닐)에틸] 벤젠설폰아미드;  4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) — N- [2- (3-methoxyphenyl) ethyl] benzenesulfonamide;
4-(4-이소프로필 -2 , 3—디메틸— 5-옥소—피라졸— 1—일)— N- [2— [2- (트리플루오로메 틸)페닐]에틸]벤젠설폰아미드;  4- (4-isopropyl-2, 3—dimethyl— 5-oxo-pyrazol— 1—yl) — N- [2— [2- (trifluoromethyl) phenyl] ethyl] benzenesulfonamide;
4ᅳ (4—이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1—일 )— N- [2— [3ᅳ (트리플루오로메 틸)페닐]에틸]벤젠설폰아미드;  4 '(4—isopropyl-2, 3—dimethyl-5-oxo-pyrazol—1—yl) —N— [2— [3 ′ (trifluoromethyl) phenyl] ethyl] benzenesulfonamide;
4-(4-이소프로필— 2 , 3—디메틸 -5-옥소-피라졸 -1-일) -N- [2- [4— (트리플루오로메 틸)페닐]에틸]벤젠설폰아미드;  4- (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N- [2- [4— (trifluoromethyl) phenyl] ethyl] benzenesulfonamide;
4一 (4—이소프로필 -2， 3—디메틸—5-옥소-피라졸—1—일)— N— [4— (트리플루오로메틸) 페닐]벤젠설폰아미드;  4 one (4—isopropyl-2, 3—dimethyl—5-oxo-pyrazol—1—yl) — N— [4— (trifluoromethyl) phenyl] benzenesulfonamide;
N一 (2， 3—디히드로ᅳ 1 , 4—벤조디옥신— 6-일메틸)— 4— (4-이소프로필 -2， 3ᅳ디메틸 -5— 옥소—피라졸 -1-일 )벤젠설폰아미드；  N 一 (2 ， 3—dihydro ᅳ 1, 4—benzodioxine — 6-ylmethyl) — 4— (4-isopropyl-2, 3 ᅳ dimethyl-5 — oxo-pyrazol-1-yl) benzene Sulfonamide;
4-(4-클로로 -2， 3—디메틸—5-옥소—피라졸ᅳ1-일) -N— (2—페녹시에틸)벤젠설폰아미 드 '  4- (4-Chloro-2, 3—dimethyl-5-oxo-pyrazolyl-yl) -N— (2—phenoxyethyl) benzenesulfonamide ''
4-(4-클로로— 2ᅳ 3-디메틸 -5ᅳ옥소—피라졸 -1-일 )— N- [ (2ᅳ플루오로페닐)메틸]벤젠 설폰아미드;  4- (4-Chloro—2 ′ 3-dimethyl-5 ”oxo-pyrazol-1-yl) —N-[(2′fluorophenyl) methyl] benzene sulfonamide;
4- (4-클로로—2 , 3-디메틸 -5ᅳ옥소—피라졸 -1—일 )— N— [ (3ᅳ플루오로페닐)메틸]벤젠 설폰아미드;  4- (4-Chloro-2, 3-dimethyl-5oxo-pyrazol-1-yl) —N— [(3 ᅳ fluorophenyl) methyl] benzene sulfonamide;
4— (4—클로로 -2 , 3-디메틸 -5ᅳ옥소-피라졸 -1—일 )-N- [ (4ᅳ플루오로페닐)메틸]벤젠 설폰아미드;  4— (4—chloro-2, 3-dimethyl-5 디메틸 oxo-pyrazol-1—yl) -N-[(4 ᅳ fluorophenyl) methyl] benzene sulfonamide;
4- (4-클로로—2 , 3—디메틸— 5-옥소ᅳ피라졸ᅳ 1—일 )— N-(3，4—디클로로페닐)벤젠설폰 아미드;  4- (4-Chloro-2, 3-dimethyl- 5-oxo-pyrazolyl 1-yl)-N- (3,4-dichlorophenyl) benzenesulfon amide;
4- -클로로ᅳ 2， 3-디메틸 -5ᅳ옥소—피라졸— 1-일 )-N— (5-클로로—2-플루오로-페닐 ) 벤젠설폰아미드;  4- -chloro-2-, 3-dimethyl-5-oxo-pyrazol- 1-yl) -N- (5-chloro- 2-fluoro-phenyl) benzenesulfonamide;
4一 (4—클로로—2 , 3-디메틸—5-옥소-피라졸 -1-일) -N— [4- (디메틸아미노)페닐]벤젠 설폰아미드;  4 one (4—chloro-2, 3-dimethyl—5-oxo-pyrazol-1-yl) -N— [4- (dimethylamino) phenyl] benzene sulfonamide;
4-(4ᅳ클로로 -2， 3—디메틸ᅳ 5-옥소-피라졸ᅳ 1—일 )— N-(2—피리딜메틸 )벤젠설폰아미 메틸 3— [ [4-(4—클로로 -2 , 3-디메틸 -5-옥소-피라졸—1—일)페닐]설포닐아미노]벤 조에이트; 4- (4 ᅳ chloro-2, 3—dimethyl ᅳ 5-oxo-pyrazolyl 1-yl)-N- (2-pyridylmethyl) benzenesulfonami Methyl 3— [[4- (4—chloro-2, 3-dimethyl-5-oxo-pyrazol—1—yl) phenyl] sulfonylamino] benzoate;
4ᅳ (4-클로로 -2 , 3-디메틸—5-옥소—피라졸—1-일) -N—( 1H—인돌 -5-일메틸)벤젠설폰 아미드；  4 '(4-chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N— (1H-indol-5-ylmethyl) benzenesulfon amide;
4ᅳ(4—클로로ᅳ2 , 3—디메틸— 5-옥소-피라졸— 1—일 )— N- ( l—나프틸메틸 )벤젠설폰아미  4 ᅳ (4—chloro ᅳ 2, 3—dimethyl— 5-oxo-pyrazole— 1—yl) — N- (l—naphthylmethyl) benzenesulfonami
4— (4ᅳ클로로— 2 , 3-디메틸 -5—옥소-피라졸 - 1-일 )— Ν- [ (3 , 4一디메록시페닐)메틸]벤 젠설폰아미드; 4— (4 ᅳ chloro— 2, 3-dimethyl-5—oxo-pyrazol-1-yl) — Ν- [(3,4idimethoxyphenyl) methyl] benzensulfonamide;
4-(4—클로로ᅳ 2， 3—디메틸 -5—옥소—피라졸— 1-일) -Ν- (5—퀴놀릴)벤젠설폰아미드； 4-(4—클로로 -2， 3—디메틸 -5—옥소-피라졸 -1—일) -Ν— [ (2 , 4-디메특시페닐)메틸]벤 젠설폰아미드; ' 4- (4—Chloro-2-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) -Ν- (5-quinolyl) benzenesulfonamide; 4- (4-chloro-2, 3-dimethyl- 5—oxo-pyrazol-1—yl) -Ν— [(2,4-dimethoxyphenyl) methyl] benzensulfonamide; '
4- (4—브로모 -2， 3—디메틸 -5—옥소ᅳ피라졸— 1—일) -Ν- [ (3， 4—디메특시페닐)메틸]벤 젠설폰아미드;  4- (4—Bromo-2, 3—dimethyl-5—oxo-pyrazol—1—yl) -Ν- [(3, 4-dimethoxyphenyl) methyl] benzensulfonamide;
4- ( 4-브로모 -2 , 3ᅳ디메틸—5—옥소-피라졸— 1-일)— Ν- ( 5-퀴놀릴)벤젠설폰아미드; 4- ( 4—브로모—2， 3—디메틸— 5—옥소-피라졸— 1-일) -Ν- [4— (디메틸아미노)페닐]벤젠 설폰아미드;  4- (4-bromo-2, 3 ᅳ dimethyl—5—oxo-pyrazol— 1-yl) — Ν- (5-quinolyl) benzenesulfonamide; 4- (4—Bromo—2, 3—dimethyl— 5—oxo-pyrazol— 1-yl) -Ν- [4— (dimethylamino) phenyl] benzene sulfonamide;
메틸 3— [ [4— (4—브로모 -2， 3-디메틸— 5—옥소-피라졸 -1—일)페닐 ]설포닐아미노]벤 조에이트;  Methyl 3— [[4— (4—bromo-2, 3-dimethyl— 5—oxo-pyrazol-1—yl) phenyl] sulfonylamino] benzoate;
4一 (4-브로모 -2 , 3—디메틸 -5—옥소—피라졸 -1—일 )— Ν- [ (3-플루오로페닐)메틸]벤젠 설폰아미드;  4 one (4-bromo-2,3—dimethyl-5—oxo-pyrazol-1—yl) —N — [(3-fluorophenyl) methyl] benzene sulfonamide;
4- (4—브로모 -2 , 3—디메틸 -5—옥소-피라졸 -1—일 )— Ν— [ (2-플루오로페닐)메틸]벤젠 설폰아미드;  4- (4—Bromo-2, 3—dimethyl-5—oxo-pyrazol-1—yl) —N — [(2-fluorophenyl) methyl] benzene sulfonamide;
4-(4—브로모 -2， 3-디메틸— 5-옥소-피라졸 -1-일)— Ν-(2—피리딜메틸)벤젠설폰아미  4- (4—Bromo-2, 3-dimethyl— 5-oxo-pyrazol-1-yl) — Ν- (2—pyridylmethyl) benzenesulfonami
4— -브로모 -2 , 3-디메틸 -5—옥소ᅳ피라졸— 1-일 )— Ν— (2， 3-디히드로ᅳ 1 , 4-벤조디옥 신 -6-일)벤젠설폰아미드; 4—-bromo-2, 3-dimethyl-5—oxo-pyrazol- 1-yl) —N— (2, 3-dihydrox 1, 4-benzodioxine-6-yl) benzenesulfonamide;
Ν— [3， 5—비스 (트리플루오로메틸)페닐] -4- (4-브로모—2， 3-디메틸— 5—옥소—피라졸 —1-일)벤젠설폰아미드;  Ν— [3, 5-bis (trifluoromethyl) phenyl] -4- (4-bromo-2, 3-dimethyl-5-oxo-pyrazol —1-yl) benzenesulfonamide;
4- (4—브로모 -2 , 3-디메틸— 5-옥소—피라졸 -1-일) -Ν— (3， 4-디클로로페닐 )벤젠설폰 아미드;  4- (4—Bromo-2, 3-dimethyl— 5-oxo-pyrazol-1-yl) -Ν— (3, 4-dichlorophenyl) benzenesulfon amide;
4一 (4-브로모ᅳ2 , 3-디메틸 -5—옥소—피라졸— 1-일 )— Ν- (5—클로로— 2—플루오로-페닐 ) 벤젠설폰아미드; N— [3 , 5-비스 (트리플루오로메틸)페닐]—4— (4-클로로—2， 3-디메틸— 5—옥소-피라졸4 one (4-bromopropyl 2, 3-dimethyl-5—oxo-pyrazol— 1-yl) —N— (5—chloro— 2—fluoro-phenyl) benzenesulfonamide; N— [3, 5-bis (trifluoromethyl) phenyl] —4— (4-chloro—2, 3-dimethyl— 5—oxo-pyrazole
■—1一일)벤젠설폰아미드; ■ —one day) benzenesulfonamide;
4- (4—클로로 -2 , 3—디메틸— 5-옥소—피라졸— 1-일 )-Ν-(2 , 3-디히드로.— 1 , 4—벤조디옥 신 -6ᅳ일)벤젠설폰아미드; 4- (4—Chloro-2, 3-dimethyl— 5-oxo-pyrazol— 1-yl) -Ν- (2, 3-dihydro . — 1, 4-benzodioxin-6 hexayl) benzenesulfonamide ;
4-(4—브로모 -2 , 3-디메틸 -5—옥소-피라졸 -1—일 )-N-시클로펜틸-벤젠설폰아미드； 4-(4-브로모— 2 , 3-디메틸 -5—옥소—피라졸— 1—일 )-N—시클로헵틸-벤젠설폰아미드； 4— (4—브로모 -2， 3-디메틸 -5—옥소—피라졸 -1-일 )— N—페닐ᅳ벤젠설폰아미드； 4- ( 2 , 3-디메틸— 5-옥소— 4-페닐-피라졸 -1-일 )-N-(2—페녹시에틸 )벤젠설폰아미  4- (4—Bromo-2, 3-dimethyl-5—oxo-pyrazol-1—yl) -N-cyclopentyl-benzenesulfonamide; 4- (4-bromo— 2, 3-dimethyl-5 —Oxo—pyrazole— 1—yl) -N—cycloheptyl-benzenesulfonamide; 4— (4—bromo-2, 3-dimethyl-5—oxo-pyrazol-1-yl) — N—phenyl ᅳ Benzenesulfonamide; 4- (2, 3-dimethyl— 5-oxo— 4-phenyl-pyrazol-1-yl) -N- (2-phenoxyethyl) benzenesulfonami
4- [4- (4—클로로페닐) -2 , 3—디메틸ᅳ 5-옥소—피라졸 -1—일 ] -Ν— ( 2-페녹시에틸)벤젠 설폰아미드; 4- [4- (4—chlorophenyl) -2, 3-dimethyl ᅳ 5-oxo-pyrazol-1-yl] -Ν— (2-phenoxyethyl) benzene sulfonamide;
2- [3- [ [4— (4-이소프로필 -2 , 3-디메틸 -5—옥소—피라졸 -1-일)페닐]설포닐아미노] 페닐]아세트산;  2- [3- [[4— (4-isopropyl-2, 3-dimethyl-5—oxo-pyrazol-1-yl) phenyl] sulfonylamino] phenyl] acetic acid;
Ν- (2—히드록시페닐) -4- (4-이소프로필ᅳ 2 , 3-디메틸— 5-옥소—피라졸 -1—일)벤젠설 돈아미드；  Ν- (2—hydroxyphenyl) -4- (4-isopropyl ᅳ 2, 3-dimethyl- 5-oxo-pyrazol-1-yl) benzenesuldonamide;
Ν- (4—히드록시페닐 )-4- (4-이소프로필— 2 , 3-디메틸-5—옥소-피라졸-1-일)벤젠설 폰아미드;  Ν- (4—hydroxyphenyl) -4- (4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazol-1-yl) benzenesulfonamide;
4— [ 2 , 3-디메틸 -5—옥소— 4— [ 4— (트리플루오로메틸)페닐]피라졸 - 1—일]— Ν- ( 2-페녹 시에틸)벤젠설폰아미드;  4— [2, 3-dimethyl-5—oxo— 4— [4— (trifluoromethyl) phenyl] pyrazol-1—yl] — Ν- (2-phenoxyethyl) benzenesulfonamide;
Ν— [3- (히드록시메틸)페닐]—4- (4—이소프로필 -2， 3-디메틸— 5-옥소ᅳ피라졸— 1—일 ) 벤젠설폰아미드;  Ν— [3- (hydroxymethyl) phenyl] —4- (4—isopropyl-2, 3-dimethyl— 5-oxo-pyrazol— 1—yl) benzenesulfonamide;
Ν- (6-히드록시 -1—나프틸 )— 4- (4—이소프로필— 2 , 3-디메틸— 5—옥소—피라졸— 1—일) 벤젠설폰아미드;  N- (6-hydroxy-l-naphthyl)-4- (4-isopropyl- 2, 3-dimethyl- 5-oxo-pyrazole- 1-yl) benzenesulfonamide;
4ᅳ (4-이소프로필— 2， 3—디메틸 -5-옥소—피라졸 -1—일 )-Ν— (2-페녹시프로필 )벤젠설 폰아미드;  4 ′ (4-isopropyl— 2, 3—dimethyl-5-oxo-pyrazol-1—yl) -Ν— (2-phenoxypropyl) benzenesulfonamide;
Ν- [2— (2-플루오로페녹시 )에틸] -4ᅳ (4—이소프로필 -2， 3—디메틸— 5-옥소—피라졸- 1-일)벤젠설폰아미드;  Ν- [2— (2-fluorophenoxy) ethyl] -4 ′ (4—isopropyl-2,3—dimethyl—5-oxo-pyrazol-1-yl) benzenesulfonamide;
Ν一 [4— [2- (디메틸아미노)에록시]페닐]—4— (4—이소프로필 -2， 3-디메틸— 5ᅳ옥소-피 라졸— 1-일)벤젠설폰아미드;  Ν 一 [4— [2- (dimethylamino) ethoxy] phenyl] —4— (4—isopropyl-2, 3-dimethyl-5oxo-pyrazole- 1-yl) benzenesulfonamide;
메틸 3- [ [4— (4-이소프로필 -2， 3—디메틸— 5—옥소-피라졸 -1—일)페닐 ]설포닐아미 노]프로파노에이트 ;  Methyl 3- [[4— (4-isopropyl-2, 3-dimethyl-5] oxo-pyrazol-1-yl) phenyl] sulfonylamino] propanoate;
Ν- (4—히드록시 -3-메틸―페닐) -4-(4-이소프로필— 2， 3-디메틸 -5—옥소—피라졸 -1- 일)벤젠설폰아미드; Ν- (4—hydroxy-3-methyl-phenyl) -4- (4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazole-1- (1) benzenesulfonamide;
Nᅳ (6-아세틸 -1 , 3ᅳ벤조디옥소 1-5-일 )— 4-(4ᅳ이소프로필— 2 , 3—디메틸— 5-옥소-피 라졸 -1—일)벤젠설폰아미드;  N '(6-Acetyl-l, 3'benzodioxoxo 1-5-yl) — 4- (4'isopropyl- 2,3-dimethyl- 5-oxo-pyrazol-l-yl) benzenesulfonamide;
4- ( 4-이소프로필 -2 , 3-디메틸 -5—옥소-피라졸— 1—일 ) -N— ( 1， 3 , 5ᅳ트리메틸피라졸一 4ᅳ일)벤젠설폰아미드;  4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol— 1—yl) -N— (1, 3,5 ᅳ trimethylpyrazoll 4 ᅳ yl) benzenesulfonamide;
2-(4-인돌린— 1-일설포닐페닐 ) -4-이소프로필— 1， 5—디메틸ᅳ피라졸 -3—온； 2- (4-indoline— 1-ylsulfonylphenyl) -4-isopropyl— 1, 5-dimethyldimethylpyrazole-3-one;
4ᅳ (4—이소프로필 -2， 3—디메틸ᅳ5—옥소-피라졸 -1-일)— N-테트랄린 -1—일―벤젠설폰 아미드； 4 ′ (4—isopropyl-2, 3—dimethyl ᅳ 5—oxo-pyrazol-1-yl) —N-tetralin-1—yl-benzenesulfon amide;
Ν , Ν—디에틸— 4— (4ᅳ이소프로필 -2 , 3-디메틸— 5-옥소-피라졸— 1—일)벤젠설폰아미  Ν, Ν—diethyl— 4— (4 ᅳ isopropyl-2, 3-dimethyl— 5-oxo-pyrazole— 1—yl) benzenesulfonami
4-(4—이소프로필ᅳ2 , 3—디메틸 -5-옥소—피라졸— 1—일)벤젠설폰아미드； 4- (4—isopropyl ᅳ 2, 3—dimethyl-5-oxo-pyrazole— 1-yl) benzenesulfonamide;
4— (4—이소프로필ᅳ 2 , 3—디메틸— 5-옥소-피라졸 -1-일) -Ν-메틸 -Ν-페닐—벤젠설폰아 미드;  4— (4—isopropyl ᅳ 2, 3—dimethyl— 5-oxo-pyrazol-1-yl) -Ν-methyl-Ν-phenyl-benzenesulfonamide;
Ν一벤질 -4-(4—이소프로필 -2， 3-디메틸— 5-옥소-피라졸 -1—일)벤젠설폰아미드； 메틸 2— [ [ 4- ( 4-이소프로필 -2 , 3—디메틸 -5—옥소—피라졸— 1—일)페닐]설포닐아미 노]— 2ᅳ페닐—아세테이트; Ν 一 benzyl-4- (4—isopropyl-2, 3-dimethyl— 5-oxo-pyrazol-1—yl) benzenesulfonamide; methyl 2— [[4- (4-isopropyl-2, 3— dimethyl-5-oxo-pyrazol-1- yl) phenyl] sulfonyl amino furnace; - eu 2-phenyl-acetate;
Ν一 (2-에록시에틸)— 4— (4—이소프로필 -2， 3—디메틸— 5-옥소—피라졸ᅳ 1-일 )벤젠설폰 아미드；  Ν 一 (2-hydroxyethyl) — 4— (4—isopropyl-2, 3-dimethyl— 5-oxo-pyrazolyl 1-yl) benzenesulfon amide;
Ν-(2 , 6—디메틸페닐) -4— (4—이소프로필— 2 , 3-디메틸 -5-옥소—피라졸—1 일)벤젠설 폰아미드;  Ν- (2, 6-dimethylphenyl) -4— (4—isopropyl— 2, 3-dimethyl-5-oxo-pyrazole—one day) benzenesulfonamide;
4一 (4—이소프로필 -2 , 3—디메틸ᅳ 5—옥소-피라졸 -1-일) -Ν-(9-옥소티옥산텐ᅳ2-일) 벤젠설폰아미드;  4 one (4—isopropyl-2, 3—dimethyl ᅳ 5—oxo-pyrazol-1-yl) -Ν- (9-oxothioxanthen-2-yl) benzenesulfonamide;
4一 (4—이소프로필 -2 , 3-디메틸— 5—옥소—피라졸 -1-일 )-Νᅳ (4—메특시—3 , 5-디메틸- 페닐)벤젠설폰아미드;  4 one (4—isopropyl-2, 3-dimethyl— 5—oxo-pyrazol-1-yl) -Ν ᅳ (4—methoxy-3, 5-dimethyl-phenyl) benzenesulfonamide;
Ν-( 1 , 3—디메틸 -2ᅳ옥소 -벤지미다졸— 5—일)— 4-(4-이소프로필 -2， 3-디메틸— 5ᅳ옥소 —피라졸— 1-일 )벤젠설폰아미드；  Ν- (1, 3—Dimethyl-2oxo-benzimidazole— 5—yl) — 4- (4-isopropyl-2, 3-dimethyl— 5oxo-pyrazole— 1-yl) benzenesulfonamide ;
에틸 5— [ [4— (4-이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1—일 )페닐]설포닐아미 노]벤조티오펜 -2-카르복실레이트；  Ethyl 5— [[4— (4-isopropyl-2, 3—dimethyl-5-oxo-pyrazole— 1—yl) phenyl] sulfonylamino] benzothiophene-2-carboxylate;
4- [4-(4-이소프로필 -2，3-디메틸— 5-옥소-피라졸 -1—일)페닐]설포닐 -1 , 3-디히드 로퀴녹살린— 2-온;  4- [4- (4-isopropyl-2,3-dimethyl- 5-oxo-pyrazol-1-yl) phenyl] sulfonyl-1, 3-dihydroquinoxaline—2-one;
Νᅳ터트—부틸— 4— (4-이소프로필 -2， 3—디메틸 -5-옥소ᅳ피라졸 -1-일 )벤젠설폰아미 N— (3-플루오로 -2—메틸-페닐)— 4— (4—이소프로필ᅳ 2， 3ᅳ디메틸 -5—옥소-피라졸 - 1 - 일)벤젠설폰아미드; N-tert-butyl- 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonami N— (3-fluoro-2—methyl-phenyl) — 4— (4—isopropyl ᅳ 2, 3 ”dimethyl-5—oxo-pyrazol 1-yl) benzenesulfonamide;
4— [ [4-(4-이소프로필ᅳ 2， 3ᅳ디메틸— 5ᅳ옥소-피라졸— 1—일 )페닐]설포닐아미노]벤 젠설폰아미드;  4— [[4- (4-isopropyl ᅳ 2, 3'dimethyl— 5 ”oxo-pyrazol— 1—yl) phenyl] sulfonylamino] benzensulfonamide;
4—이소프로필— 1 , 5-디메틸 -2- [4- [4-(3-페닐퀴녹살린ᅳ 2-일)피페라진— 1-일 ]설포 닐페닐]피라졸 -3—온;  4—isopropyl— 1, 5-dimethyl-2- [4- [4- (3-phenylquinoxalinyl 2-yl) piperazin— 1-yl] sulfonylphenyl] pyrazole-3—one;
4-이소프로필 -2- [4—[ [4— [4— (4-이소프로필 -2 , 3ᅳ디메틸 -5—옥소-피라졸—1-일)페 닐]설포닐 -1， 4—디아제판— 1-일 ]설포닐]페닐] -1 , 5-디메틸―피라졸 -3—온；  4-isopropyl-2- [4— [[4— [4— (4-isopropyl-2,3 ᅳ dimethyl-5—oxo-pyrazol—1-yl) phenyl] sulfonyl-1, 4— Diazepan— 1-yl] sulfonyl] phenyl] -1, 5-dimethyl-pyrazole-3-one;
4-이소프로필 -1， 5ᅳ디메틸 -2— [4- [4— [4- (모폴린ᅳ 4-카르보닐) -2-니트로-페닐 ]피 페라진— 1—일]설포닐페닐]피라졸— 3-온；  4-isopropyl-1,5 ᅳ dimethyl-2— [4- [4— [4- (morpholinyl 4-carbonyl) -2-nitro-phenyl] piperazine— 1—yl] sulfonylphenyl] Pyrazole—3-one;
4-이소프로필— 1 , 5-디메틸 -2— [4- [4-(2-피리딜)피페라진— 1—일 ]설포닐페닐]피라  4-isopropyl— 1, 5-dimethyl-2— [4- [4- (2-pyridyl) piperazin— 1—yl] sulfonylphenyl] pyra
N— (2， 2一디메틸프로필 )— 4— (4-이소프로필— 2， 3—디메틸 -5-옥소—피라졸 -1—일 )벤젠 설폰아미드; N— (2, 2 一 dimethylpropyl) — 4— (4-isopropyl— 2, 3—dimethyl-5-oxo-pyrazol-1—yl) benzene sulfonamide;
4—이소프로필 -2- [4- [4-(4—메록시페닐)피페라진— 1-일]설포닐페닐] -1 , 5-디메틸 一피라졸— 3—은;  4—isopropyl-2- [4- [4- (4—methoxyphenyl) piperazin— 1-yl] sulfonylphenyl] -1, 5-dimethyl one pyrazole-3;
N- [2— (3 , 4-디메록시페닐)에틸] -2- [ [4一 (4-이소프로필— 2 , 3_디메틸—5—옥소ᅳ피라 졸 -1-일)페닐]설포닐아미노]벤자미드;  N- [2— (3,4-dimethoxyphenyl) ethyl] -2-[[4 一 (4-isopropyl—2,3_dimethyl—5—oxotoppyrazol-1-yl) phenyl] sulfonyl Amino] benzamide;
에틸 2- [ [4— (4-이소프로필 -2 , 3-디메틸— 5—옥소—피라졸— 1—일)페닐 ]설포닐아미 노] -4， 5 , 6， 7-테트라히드로벤조티오펜— 3—카르복실레이트;  Ethyl 2- [[4— (4-isopropyl-2, 3-dimethyl— 5—oxo-pyrazol— 1—yl) phenyl] sulfonylamino]]-4, 5, 6, 7-tetrahydrobenzoti Offen—3—carboxylate;
2- [4- [4— (7-클로로 -4-퀴놀릴)피페라진 -1-일]설포닐페닐]—4-이소프로필— 1 , 5- 디메틸-피라졸 -3—온;  2- [4- [4— (7-chloro-4-quinolyl) piperazin-1-yl] sulfonylphenyl] —4-isopropyl— 1, 5- dimethyl-pyrazole-3—one;
4-이소프로필— 1， 5—디메틸— 2— [4-( 1-피페리딜설포닐)페닐]피라졸 -3—온； 4-isopropyl— 1, 5—dimethyl— 2— [4- (1-piperidylsulfonyl) phenyl] pyrazole-3—one;
N-이소프로필 -4— (4-이소프로필 -2 , 3-디메틸 -5—옥소-피라졸ᅳ1-일)벤젠설폰아미 N-isopropyl-4— (4-isopropyl-2,3-dimethyl-5—oxo-pyrazol ᅳ 1-yl) benzenesulfonami
N-시클로프로필—4— (4-이소프로필 -2， 3ᅳ디메틸—5—옥소-피라졸 -1—일)벤젠설폰아 미드; N-cyclopropyl-4 (4-isopropyl-2,32dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide;
4—이소프로필— 1， 5-디메틸— 2-(4-모폴리노설포닐페닐)피라졸 -3—은；  4—isopropyl— 1, 5-dimethyl— 2- (4-morpholinosulfonylphenyl) pyrazole-3—silver;
4-(4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸 -1—일)— N-(2—페녹시에틸)벤젠설폰 아미드;  4- (4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazol-1—yl) —N- (2—phenoxyethyl) benzenesulfon amide;
N一 [2— (3， 5-디메틸페녹시 )에틸] -4-(4-이소프로필— 2 , 3-디메틸— 5-옥소—피라졸一 1-일)벤젠설폰아미드; 4-(4—이소프로필 -2 , 3—디메틸 -5-옥소-피라졸 -1—일 )-Νᅳ프로필—벤젠설폰아미드；N1 [2— (3, 5-dimethylphenoxy) ethyl] -4- (4-isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol one 1-yl) benzenesulfonamide; 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -Ν'propyl-benzenesulfonamide;
Ν-(4-히드록시— [ 1 , 1 '—바이페닐] -3—일) -4— (4-이소프로필 -2，3—디메틸 -5-옥소ᅳ 2， 5-디히드로ᅳ 1H-피라졸ᅳ 1—일)벤젠설폰아미드； Ν- (4-hydroxy— [1, 1 '—biphenyl] -3 -yl) -4-(4-isopropyl -2,3-dimethyl -5-oxo ᅳ 2, 5-dihydro ᅳ 1H- Pyrazolyl 1-yl) benzenesulfonamide;
Ν—(2—히드록시페닐)— 4— (4—이소프로필 -2 , 3-디메틸 -5—옥소— 2， 5-디히드로 -1Η-피 라졸ᅳ 1—일)벤젠설폰아미드;  Ν— (2—hydroxyphenyl) — 4— (4—isopropyl-2, 3-dimethyl-5—oxo— 2, 5-dihydro-l-pyrazolyl 1-yl) benzenesulfonamide;
Ν— (5-히드록시나프탈렌ᅳ 2—일 )-4-(4—이소프로필 -2， 3-디메틸— 5-옥소— 2 ' 5-디히 드로ᅳ 1H—피라졸- 1-일)벤젠설폰아미드;  Ν— (5-hydroxynaphthalene) 2 —yl) -4- (4—isopropyl-2, 3-dimethyl— 5-oxo— 2 '5-dihydroprene 1H—pyrazole-1-yl) benzenesulfon amides;
4一 (4-브로모 -2 , 3-디메틸— 5-옥소ᅳ 2， 5-디히드로— 1H—피라졸 -1ᅳ일 )— Ν— (2， 4-디메 틸페닐)벤젠설폰아미드;  4 one (4-bromo-2, 3-dimethyl— 5-oxo benzyl 2, 5-dihydro— 1 H—pyrazol-1-hexyl) — N— (2, 4- dimethylphenyl) benzenesulfonamide;
4— (4-이소프로필 -2， 3—디메틸 -5-옥소ᅳ 2 , 5-디히드로— 1H-피라졸— 1—일) -Ν— (4— (2ᅳ 몰포리노에특시)페닐)밴젠설폰아미드;  4— (4-Isopropyl-2, 3—dimethyl-5-oxoxo 2, 5-dihydro— 1H-pyrazole— 1—yl) -Ν— (4— (2 ′ morpholino-specific) phenyl ) Bansensulfonamide;
Ν-(2，4—디히드록시페닐) -4-(4—이소프로필 -2 , 3-디메틸 -5—옥소 _2 , 5—디히드로- 1Hᅳ피라졸 -1—일 )벤젠설폰아미드；  N- (2,4-dihydroxyphenyl) -4- (4-isopropyl-2, 3-dimethyl-5-oxo _2, 5-dihydro-1H ᅳ pyrazol-1-yl) benzenesulfonamide;
4一(4-브로모 -2， 3—디메틸— 5-옥소 -2 , 5—디히드로— 1H—피라졸— 1—일 )-Ν-(4— (트리플 루오로메틸)페닐)벤젠설폰아미드；  4 一 (4-Bromo-2, 3—dimethyl— 5-oxo-2, 5—dihydro— 1H—pyrazole— 1—yl) -Ν- (4— (trifluoromethyl) phenyl) benzenesulfon amides;
Ν— (3-플루오로—4-히드록시페닐) -4-(4—이소프로필 -2， 3-디메틸 -5-옥소 -2 , 5-디 히드로— 1H-피라졸— 1ᅳ일 )밴젠설폰아미드；  Ν— (3-fluoro—4-hydroxyphenyl) -4- (4—isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro— 1H-pyrazole— 1 ᅳ yl) banzensulfone amides;
4- (4-이소프로필ᅳ 2 , 3—디메틸 -5-옥소— 2， 5-디히드로 -1Η-피라졸 -1—일)— Ν— (2-메 록시— 4-니트로페닐)벤젠설폰아미드;  4- (4-Isopropyl ᅳ 2, 3—dimethyl-5-oxo— 2, 5-dihydro-l-pyrazol-l—yl) — Ν— (2-hydroxy- 4-nitrophenyl) benzenesulfon amides;
3- (4— (4—이소프로필— 2， 3-디메틸— 5-옥소 -2 , 5—디히드로ᅳ 1H-피라졸 -1-일 )페닐설 폰아미도)벤조산;  3- (4— (4—Isopropyl— 2, 3-dimethyl— 5-oxo-2, 5—dihydroxy 1H-pyrazol-1-yl) phenylsulfonamido) benzoic acid;
4- (4-이소프로필ᅳ 2， 3—디메틸 -5—옥소— 2， 5—디히드로ᅳ 1H—피라졸— 1—일)— Ν-(2-메 록시 -5-니트로페닐 )벤젠설폰아미드；  4- (4-isopropyl ᅳ 2 ， 3—dimethyl-5—oxo— 2 ， 5—dihydro ᅳ 1H—pyrazole— 1—yl) — Ν- (2-methoxy-5-nitrophenyl) benzenesulfon amides;
4一(4—이소프로필ᅳ 2， 3—디메틸 -5—옥소— 2 , 5—디히드로— 1H—피라졸— 1—일)— Ν-(2-메 틸벤조퓨란 -5-일)벤젠설폰아미드;  4 一 (4—Isopropyl ᅳ 2 ， 3—dimethyl-5—oxo— 2, 5—dihydro— 1H—pyrazole— 1—yl) —N— (2-methylbenzofuran-5-yl) benzene Sulfonamides;
Ν一 (벤조 [b]티오펜—5-일 )-4— (4—이소프로필— 2， 3-디메틸ᅳ 5-옥소 -2 , 5—디히드로- 1H-피라졸— 1-일)벤젠설폰아미드;  Ν 一 (Benzo [b] thiophene—5-yl) -4— (4—isopropyl— 2, 3-dimethyl ᅳ 5-oxo-2, 5—dihydro-1H-pyrazole— 1-yl) benzene Sulfonamides;
Nᅳ (벤조퓨란— 5-일 )-4— (4-이소프로필— 2 , 3—디메틸 -5—옥소— 2， 5-디히드로— 1H-피 라졸— 1—일 )벤젠설폰아미드；  N '(benzofuran— 5-yl) -4— (4-isopropyl— 2, 3—dimethyl-5—oxo— 2, 5-dihydro— 1H-pyrazole— 1—yl) benzenesulfonamide;
N— (밴조퓨란— 5-일메틸 )—4- ( 4—이소프로필 -2， 3—디메틸 -5-옥소 -2 , 5—디히드로一 1H-피라졸— 1-일)벤젠설폰아미드;  N— (banjofuran— 5-ylmethyl) —4- (4—isopropyl-2, 3—dimethyl-5-oxo-2, 5—dihydrol 1H-pyrazol— 1-yl) benzenesulfonamide;
메틸 5- (4- (4-이소프로필 -2， 3-디메틸 -5-옥소— 2， 5—디히드로ᅳ 1H-피라졸 -1—일 ) 페닐설폰아미도)벤조 [b]티오펜 -2-카르복실레이트; Methyl 5- (4- (4-isopropyl-2, 3-dimethyl-5-oxo- 2, 5-dihydrosyl 1H-pyrazol-1-yl) Phenylsulfonamido) benzo [b] thiophene-2-carboxylate;
메틸 4-( (4— (4-이소프로필 -2， 3一디메틸 -5-옥소 -2， 5-디히드로— 1H-피라졸— 1ᅳ일 ) 페닐설폰아미도)메틸)벤조에이트;  Methyl 4- ((4— (4-isopropyl-2, 3ldimethyl-5-oxo-2, 5-dihydro—1H-pyrazol-1xyl) phenylsulfonamido) methyl) benzoate;
메틸 6— (4-(4-이소프로필— 2， 3-디메틸 -5—옥소 -2 , 5-디히드로 -1H-피라졸 -1-일) 페닐설폰아미도 )-2ᅳ나프토에이트；  Methyl 6— (4- (4-isopropyl— 2, 3-dimethyl-5—oxo-2, 5-dihydro-1H-pyrazol-1-yl) phenylsulfonamido) -2 ᅳ naphthoate;
4- (4-이소프로필— 2 , 3ᅳ디메틸— 5-옥소— 2， 5-디히드로— 1H-피라졸 -1—일)— Nᅳ메시틸 벤젠설폰아미드;  4- (4-isopropyl— 2, 3 ᅳ dimethyl— 5-oxo— 2, 5-dihydro— 1H-pyrazol-1—yl) —N ᅳ mesityl benzenesulfonamide;
N-(9 , 1으디옥소ᅳ 9， 1으디히드로안트라센 -2—일 )—4- (4-이소프로필— 2， 3—디메틸- 5-옥소— 2 , 5一디히드로 -1H-피라졸 -1—일 )벤젠설폰아미드；  N- (9,1 dioxoxo9,1, didihydroanthracene-2—yl) —4- (4-isopropyl— 2, 3—dimethyl-5 oxo— 2, 5 一 dihydro-1H-pyrazole -1—yl) benzenesulfonamide;
4-(4—이소프로필 -2， 3-디메틸 -5-옥소— 2 , 5ᅳ디히드로ᅳ 1H-피라졸 -1-일 )-N- (이소 퀴놀린 -5-일)벤젠설폰아미드;  4- (4—Isopropyl-2, 3-dimethyl-5-oxo— 2,5'dihydro ᅳ 1H-pyrazol-1-yl) -N- (isoquinolin-5 yl) benzenesulfonamide;
N- (벤조 [d] [ 1， 3]디옥실 -5—일 )—4— (4-이소프로필 -2 , 3—디메틸 -5-옥소ᅳ 2 , 5-디히 드로— 1H-피라졸 -1—일)벤젠설폰아미드;  N- (benzo [d] [1,3] dioxyl-5—yl) —4— (4-isopropyl-2,3—dimethyl-5-oxophot 2, 5-dihydro— 1H-pyrazole- 1-yl) benzenesulfonamide;
N- (벤조 [d] [ lᅳ 3]디옥실—5—일메틸 )-4— (4—이소프로필 -2 , 3-디메틸 -5ᅳ옥소 -2 , 5— 디히드로— 1H-피라졸— 1ᅳ일 )벤젠설폰아미드；  N- (benzo [d] [l ᅳ 3] dioxyl—5—ylmethyl) -4— (4—isopropyl-2,3-dimethyl-5oxoo-2,5—dihydro—1H-pyrazole — 1 day) benzenesulfonamide;
4- -이소프로필 -2， 3-디메틸— 5-옥소 -2 , 5-디히드로 -1H-피라졸 -1—일 )-N-(2ᅳ옥 소인돌린 -5—일)벤젠설폰아미드;  4--isopropyl-2, 3-dimethyl- 5-oxo-2, 5-dihydro-1H-pyrazol-1-yl) -N- (2-ioxoindolin-5-yl) benzenesulfonamide;
4— (4-브로모 -2， 3-디메틸 -5—옥소 -2 , 5-디히드로 -1H-피라졸— 1-일 )— N— (4- (트리플 루오로메틸)페닐)벤젠설폰아미드;  4— (4-Bromo-2, 3-dimethyl-5—oxo-2, 5-dihydro-1H-pyrazol— 1-yl) — N— (4- (trifluoromethyl) phenyl) benzenesulfon amides;
4- (4—이소프로필— 2 , 3ᅳ디메틸— 5-옥소 -2， 5—디히드로 -1H-피라졸 -1-일)— N- (2— (티 오펜 -2-일)에틸)벤젠설폰아미드;  4- (4—Isopropyl— 2, 3 ᅳ dimethyl— 5-oxo-2, 5—dihydro-1H-pyrazol-1-yl) — N- (2— (thiophen-2-yl) ethyl) Benzenesulfonamide;
4-(4ᅳ이소프로필 -2， 3-디메틸— 5-옥소— 2， 5-디히드로— 1H-피라졸 -1-일 )-N- (3， 4 , 5—트리메록시페닐 )벤젠설폰아미드；  4- (4 ᅳ isopropyl-2, 3-dimethyl— 5-oxo— 2, 5-dihydro— 1H-pyrazol-1-yl) -N- (3, 4, 5—trimethoxyphenyl) benzene Sulfonamide;
N- (시클로핵실메틸)ᅳ 4-(4-이소프로필— 2， 3—디메틸— 5—옥소— 2 , 5—디히드로ᅳ 1Hᅳ피 라졸 -1—일 )벤젠설폰아미드；  N- (cyclonucleomethylmethyl) ᅳ 4- (4-isopropyl—2, 3—dimethyl— 5—oxo— 2, 5-dihydro ᅳ 1Hpipyrazol-1—yl) benzenesulfonamide;
N- (시클로헵틸메틸) -4-(4-이소프로필 -2 , 3-디메틸— 5—옥소 -2 , 5-디히드로— 1H-피 라졸 - 1-일)벤젠설폰아미드;  N- (cycloheptylmethyl) -4- (4-isopropyl-2, 3-dimethyl— 5—oxo-2, 5-dihydro—1H-pyrazol-1-yl) benzenesulfonamide;
N-(2—시클로핵실에틸) -4-(4-이소프로필— 2 , 3-디메틸 -5-옥소 -2 , 5—디히드로— 1H— 피라졸— 1—일 )벤젠설폰아미드；  N- (2—cyclonucleoethylethyl) -4- (4-isopropyl— 2, 3-dimethyl-5-oxo-2, 5—dihydro— 1H—pyrazole— 1—yl) benzenesulfonamide;
Ν-(3 , 4-디메록시페닐) -4-(4-이소프로필 -2， 3-디메틸 -5—옥소ᅳ 2 , 5-디히드로— 1H— 피라졸 -1-일 )벤젠설폰아미드 . 본 발명의 상기 화합물의 구조식을 하기 표 1에 정리하여 나타내었다. [표 1] Ν- (3,4-dimethoxyphenyl) -4- (4-isopropyl-2, 3-dimethyl-5—oxo ᅳ 2, 5-dihydro— 1H—pyrazol-1-yl) benzenesulfonamide. The structural formulas of the compounds of the present invention are shown in Table 1 below. TABLE 1
Ν—시클로핵실 -4— (4一 Ν—cyclonuclear chamber -4— (4 一
이소프로필 -2 , 3-디메틸— 5-옥소-피 라졸 -1-일)벤젠설폰아미드 에틸 4- [ [4-(4—이소프로필— 2 , 3- 디메틸一 5—옥소-피라졸 -1-일 )페닐] 설포닐아미노]밴조에이트  Isopropyl-2, 3-dimethyl— 5-oxo-pyrazol-1-yl) benzenesulfonamide ethyl 4- [[4- (4—isopropyl— 2, 3- dimethyl one 5—oxo-pyrazole-1 -Yl) phenyl] sulfonylamino] banjoate
4一 (4—이소프로필— 2， 3-디메틸 -5-옥 소一피라졸 -1-일 ) -Ν-페닐―벤젠설폰 이-미드 4 one (4—isopropyl— 2, 3-dimethyl-5-oxo one pyrazol-1-yl) -Ν-phenyl-benzenesulfon imide
Ν-시클로핵실— 4-(4ᅳ 이소프로필— 2 , 3-디메틸— 5—옥소-피 라졸 -1—일)— Ν-메틸-벤젠설폰아미 Ν-cyclonuclear chamber- 4- (4 'isopropyl- 2, 3-dimethyl- 5-oxo-pyrazole-1-yl)-Ν-methyl- benzenesulfonami
N一 (4-터트—부틸페닐)— 4— (4—이소프 로필— 2， 3-디메틸 -5-옥소ᅳ 피라졸 -1ᅳ일)벤젠설폰아미드 N 一 (4-tert-butylphenyl) — 4— (4—isopropyl— 2, 3-dimethyl-5-oxo benzyl pyrazol-1-hexyl) benzenesulfonamide
4- (4-이소프로필 -2 , 3-디메틸— 5-옥 소—피라졸— 1-일) -Nᅳ (4- 메특시페닐)벤젠설폰아미드
Figure imgf000032_0001
4- (4-Isopropyl-2, 3-dimethyl— 5-oxo-pyrazol— 1-yl) -N '(4-methoxyphenyl) benzenesulfonamide
Figure imgf000032_0001
4- (4-이소프로필 -2， 3—디메틸 -5-옥 ''ᅳ' 、 ' 소-피라졸— 1—일 )— N— (4—모폴리노페 닐)벤젠설폰아미드 4- (4-isopropyl-2, 3-dimethyl-5-octa '' ᅳ '', 'so -pyrazole- 1-yl)-N— (4-morpholinophenyl) benzenesulfonamide
N- [ (3 , 4- 디메록시페닐)메틸] -4- ( 4—이소프 로필 -2， 3—디메틸—5-옥소ᅳN-[(3,4-dimethoxyphenyl) methyl] -4- (4—isopropyl-2,3—dimethyl-5-oxo ᅳ
： ᅳ 피라졸 -1-일 )벤젠설폰아미드 N- [2-(3 , 4- 디메록시페닐)에틸]ᅳ 4-(4-이소프 셔 로필 -2 , 3-디메틸—5—옥소-： Pyrazol-1-yl) benzenesulfonamide N- [2- (3,4-dimethoxyphenyl) ethyl] ᅳ 4- (4-isosorber lofil-2, 3-dimethyl--5-oxo-
/ 피라졸— 1ᅳ일)벤젠설폰아미드 / Pyrazole- 1-yl) benzenesulfonamide
4-(4-이소프로필— 2， 3—디메틸 -5ᅳ옥 소-피라졸 -1-일 )— N一 [ (2—메록시페 닐)메틸]벤젠설폰아미드  4- (4-isopropyl— 2, 3-dimethyl-5oxo-pyrazol-1-yl) — N 一 [(2—methoxyphenyl) methyl] benzenesulfonamide
4-(4-이소프로필— 2， 3-디메틸 -5-옥 소―피라졸 -1-일 )-N— (p—를릴 )벤젠 설폰아미드 4- (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N— (p—lryl) benzene sulfonamide
N-( 4-클로로페닐)—4- (4-이소프로 필— 2， 3一디메틸 -5-옥소-피라졸一 1— 일)벤젠설폰아미드N- (4-chlorophenyl) —4- (4-isopropyl- 2,3 dimethyl -5-oxo-pyrazol 一 1-yl) benzenesulfonamide
Figure imgf000033_0001
Figure imgf000033_0001
4-(4—이소프로필ᅳ 2 , 3ᅳ디메틸— 5-옥 소-피라졸ᅳ 1—일) -N- [2-(2—메록시 페닐)에틸]벤젠설폰아미드  4- (4—Isopropyl ᅳ 2, 3 ᅳ dimethyl— 5-oxo-pyrazol ᅳ 1-yl) -N- [2- (2-methoxy phenyl) ethyl] benzenesulfonamide
ᅵ,:^ 4-(4—이소프로필ᅳ2 , 3—디메틸 -5—옥 소一피라졸 -1—일) -N- [2— (2-메록시 페녹시)에틸]밴젠설폰아미드ᅵ,: ^ 4- (4—isopropyl ᅳ 2, 3—dimethyl-5—oxo one pyrazole-1—yl) -N- [2— (2-methoxy phenoxy) ethyl] banzensulfonamide
/ 녜 / 녜
4-(4-이소프로필 -2， 3-디메틸 -5-옥 소—피라졸— 1-일)— N-(3— 메록시페닐)벤젠설폰아미드4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol— 1-yl) — N- (3— methoxyphenyl) benzenesulfonamide
'!' ^^气 . ' ! '^^ 气.
4-(4—이소프로필— 2 , 3-디메틸 -5-옥 소-피라졸 -1-일) -N— (2— 메특시페닐)벤젠설폰아미드4- (4—Isopropyl— 2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N— (2— mesophenyl) benzenesulfonamide
' " :! ' \ 4ᅳ (4—이소프로필ᅳ2， 3ᅳ디메틸ᅳ 5-옥 소一피라졸 -1-일) -N-(3— 페닐프로필)벤젠설폰아미드
Figure imgf000034_0001
'":!' \ 4 '(4—isopropyl ᅳ 2,3'dimethyl ᅳ 5-oxoonepyrazol-1-yl) -N- (3—phenylpropyl) benzenesulfonamide
Figure imgf000034_0001
4- (4-이소프로필 -2 , 3-디메틸 -5—옥 소-피라졸— 1-일)— N-(3- ᅵ W 니트로페닐)벤젠설폰아미드  4- (4-isopropyl-2, 3-dimethyl-5—oxo-pyrazol— 1-yl) — N- (3- ᅵ W nitrophenyl) benzenesulfonamide
4-(4-이소프로필 -2 , 3—디메틸一 5—옥 소—피라졸—1-일)— N— (4- 니트로페닐)벤젠설폰아미드 4- (4-Isopropyl-2, 3—dimethyl one 5—oxo—pyrazol—1-yl) — N— (4-nitrophenyl) benzenesulfonamide
4一 (4-이소프로필— 2 , 3—디메틸 -5—옥 소-피라졸ᅳ —일) -N-(2—페닐에틸) 벤젠설폰아미드 4一(4- isopropyl-2, 3-dimethyl-octanoic small-pyrazol-eu-yl) - N - (2-phenylethyl) benzenesulfonamide
4-(4-이소프로필— 2 , 3—디메틸— 5-옥 소一피라졸 -1-일) -N— (4-페닐부틸 ) 벤젠설폰아미드 4- ( 4 -Isopropyl— 2, 3—dimethyl— 5-oxo one pyrazol-1-yl) -N— (4-phenylbutyl) benzenesulfonamide
4一 (4-이소프로필— 2 3—디메틸 -5—옥 소-피라졸 -1-일)— N-(5—퀴놀릴)벤 젠설폰아미드 4 一 (4-isopropyl— 2 3—dimethyl-5—oxo-pyrazol-1-yl) — N- (5—quinolyl) benzensulfonamide
4一 (4-이소프로필 -2 , 3ᅳ디메틸— 5-옥 소-피라졸 -1-일)— N— (3—퀴놀릴)벤 젠설폰아미드4 一 (4-isopropyl-2,3 ᅳ dimethyl— 5-oxo-pyrazol-1-yl) — N— (3—quinolyl) benzensulfonamide
Figure imgf000034_0002
Figure imgf000034_0002
N一 (4ᅳ플루오로페닐)— 4- (4ᅳ이소프 로필 -2 , 3—디메틸—5—옥소- 피라졸 -1-일 )벤젠설폰아미드
Figure imgf000035_0001
4ᅳ (4-이소프로필 -2， 3-디메틸 -5-옥N 一 (4 ᅳ fluorophenyl) — 4- (4 ᅳ isopropyl-2, 3-dimethyl--5-oxo-pyrazol-1-yl) benzenesulfonamide
Figure imgf000035_0001
4 '(4-isopropyl-2, 3-dimethyl-5-jade
、'". 소-피라졸 -1—일)ᅳ N- [ (4-메록시페 、. ^ 닐)메틸]벤젠설폰아미드 지ᅳ.. '' '. Bovine-pyrazole-1-yl) ᅳ N- [(4-methoxyphen ,. ^ nil) methyl] benzenesulfonamide
4-(4-이소프로필 -2， 3ᅳ디메틸— 5-옥 쯰\ < 소—피라졸 -1-일)ᅳ N— (6-퀴놀릴)벤 i 젠설폰아미드 r N— (2,3—디히드로 -1,4— 4- (4-isopropyl-2,3 ᅳ dimethyl— 5-octane \ < small—pyrazol-1-yl) ᅳ N— (6-quinolyl) benizensulfonamide r N— (2,3 —Dehydro-1,4—
벤조디옥신— 6—일 )-4-(4-이소프로 필— 2, 3-디메틸 -5ᅳ옥소—피라졸—1-
Figure imgf000036_0001
일)벤젠설폰아미드 Benzodioxine — 6—yl) -4- (4-isopropyl— 2, 3-dimethyl-5oxoxo-pyrazole—1-
Figure imgf000036_0001
Benzenesulfonamide
N— [4- (디메틸아미노)페닐 ]— 4ᅳ(4— 이소프로필 -2， 3—디메틸— 5-옥소-피 라졸— 1—일)벤젠설폰아미드 f '， ., 메틸 3-[ [4— (4—이소프로필ᅳ 2,3— 디메틸ᅳ 5—옥소—피라졸— 1ᅳ일 )페닐] 설포닐아미노]벤조에이트 N— [ 4- (dimethylamino) phenyl] — 4 ᅳ (4— isopropyl-2, 3—dimethyl— 5-oxo-pyrazole— 1—yl) benzenesulfonamide f ',., Methyl 3- [[ 4— (4—Isopropyl ᅳ 2,3—Dimethyl ᅳ 5—oxo—pyrazole— 1 ᅳ yl) phenyl] sulfonylamino] benzoate
에틸 3-[ [4— (4—이소프로필ᅳ 2,3- 디메틸 -5-옥소-피라졸— 1-일 )페닐] 설포닐아미노]벤조에이트
Figure imgf000036_0002
Ethyl 3- [[4— (4—isopropyl ᅳ 2,3-dimethyl- 5 -oxo-pyrazol— 1-yl) phenyl] sulfonylamino] benzoate
Figure imgf000036_0002
4— (4-이소프로필 -2 , 3-디메틸— 5ᅳ옥 소一피라졸— 1一일 )-N— [3- (트리플루 오로메틸)페닐]벤젠설폰아미드  4— (4-isopropyl-2, 3-dimethyl— 5-pentoxyisopyrazole— 1-day) -N— [3- (trifluoromethyl) phenyl] benzenesulfonamide
N-[2-(4- 플루오로페닐)에틸]—4— (4-이소프 로필— 2, 3-디메틸—5—옥소- 피라졸 -1-일 )벤젠설폰아미드 4- (4-이소프로필— 2 3-디메틸 -5-옥 소一피라졸 -1—일)ᅳ N-(4-이소프로필 페닐)벤젠설폰아미드 N- [2- (4-fluorophenyl) ethyl] —4— (4-isopropyl— 2, 3-dimethyl—5—oxo-pyrazol-1-yl) benzenesulfonamide 4- (4-Isopropyl— 2 3-dimethyl-5-oxo one pyrazol-1—yl) ᅳ N- (4-isopropyl phenyl) benzenesulfonamide
N-(3—플루오로페닐)— 4-(4—이소프 로필 -2 3-디메틸 -5-옥소- 피라졸ᅳ 1—일 )벤젠설폰아미드 N- (3—fluorophenyl) — 4- (4—isoprop-2-2 3-dimethyl-5-oxo-pyrazolyl 1-yl) benzenesulfonamide
N-(3ᅳ플루오로페닐 )—4一 (4-이소프 로필 -2 , 3—디메틸—5-옥소ᅳ 피라졸 -1—일 )-N-메틸 -벤젠설폰아 미드N- (3 ᅳ fluorophenyl) —4 one (4-isopropyl-2,3—dimethyl-5-oxo ᅳ pyrazol-1-yl) -N-methyl-benzenesulfonamide
Figure imgf000037_0001
Figure imgf000037_0001
4-(4—이소프로필— 2 , 3—디메틸 -5—옥 소―피라졸— 1—일)— N- ( 1-나프틸)벤 젠설폰아미드  4- (4—Isopropyl— 2, 3—dimethyl-5—oxo-pyrazole— 1—yl) — N- (1-naphthyl) benzensulfonamide
4— (4—이소프로필— 2 , 3-디메틸ᅳ 5-옥 소-피라졸 -1-일 )-N- [ (3—메록시페 닐)메틸]벤젠설폰아미드 4— (4—Isopropyl— 2, 3-dimethyl ᅳ 5-oxo-pyrazol-1-yl) -N- [(3—methoxyphenyl) methyl] benzenesulfonamide
N- [ ( 3-플루오로페닐)메틸]—4ᅳ (4- 이소프로필— 2 , 3-디메틸— 5—옥소一피 라졸ᅳ 1—일)벤젠설폰아미드N- [(3-fluorophenyl) methyl] —4 ᅳ (4-isopropyl— 2, 3-dimethyl— 5—oxo one pyrazolyl 1—yl) benzenesulfonamide
/ . /.
4-(4—이소프로필ᅳ 2 , 3—디메틸 -5—옥 소一피라졸— 일)— Nᅳ (테트라히드로 퓨란 -2ᅳ일메틸)벤젠설폰아미드
Figure imgf000037_0002
4- (4—Isopropyl ᅳ 2, 3—dimethyl-5—oxo one pyrazol— one) — N ' (tetrahydrofuran-2xylmethyl) benzenesulfonamide
Figure imgf000037_0002
N— [2— (2—  N— [2— (2—
퓨릴메틸설파닐)에틸] -4-(4'-이소 프로필—2 3-디메틸 -5-옥소- 피라졸— 1-일 )벤젠설폰아미드 4- (4-o]소프로필— 2， 3-디메틸 -5—옥Furylmethylsulfanyl) ethyl] -4- (4'-isopropyl—2 3-dimethyl-5-oxo-pyrazol— 1-yl) benzenesulfonamide 4- (4-o] sopropyl— 2, 3-dimethyl-5—jade
. 소-피라졸 -1ᅳ일) N— [2-(p-를릴)에 틸]벤젠설폰아미드 . Bovine-pyrazol-1-hexyl) N— [2- (p-lryl) ethyl] benzenesulfonamide
4 (4-이소프로필— 2 , 3-디메틸— 5—옥4 (4-isopropyl— 2, 3-dimethyl— 5—jade
； 소ᅳ피라졸— 1-일) -N— (4— 气' . Sopypyrazole — 1-day —N— (4— 气'.
메톡시페닐) -N-메틸—벤젠설폰아미  Methoxyphenyl) -N-methyl-benzenesulfonami
4-(4-이소프로필 -2ᅳ 3ᅳ디메틸ᅳ 5-옥4- (4-isopropyl-2 -3 ᅳ dimethyl ᅳ 5-jade
1 소-피라졸 -1—일) -IH2— -메특시 1 bovine-pyrazole -1-day) -IH2--Special
페닐)에틸]벤젠설픈아미드  Phenyl) ethyl] benzenesulfenamide
N— [ (2—클로로페닐)메틸]—4— (4-이 소프로필 -2， 3-디메틸ᅳ 5—옥소—피라 졸 -1-일)벤젠설폰아미드
Figure imgf000038_0001
N— [(2—chlorophenyl) methyl] —4— (4-isopropyl-2, 3-dimethyl ᅳ 5—oxo-pyrazol-1-yl) benzenesulfonamide
Figure imgf000038_0001
N-(2-플루오로페닐)ᅳ 4— (4—이소프 소' 로필— 2 , 3-디메틸ᅳ 5-옥소— 피라졸— 1-일)벤젠설폰아미드 ζ } "'、 N- (2-fluorophenyl) ᅳ 4— (4—Isopso 'Lophyl— 2, 3-dimethyl ᅳ 5-oxo— pyrazol— 1-yl) benzenesulfonamide ζ } " ',
N— [ (2—플루오로페닐)메틸] -4ᅳ (4- 이소프로필 -2， 3—디메틸— 5-옥소-피 라졸 -1—일)벤젠설폰아미드  N— [(2—fluorophenyl) methyl] -4 '(4-isopropyl-2, 3-dimethyl- 5-oxo-pyrazol-1-yl) benzenesulfonamide
4 (4—이소프로필— 2 , 3-디메틸ᅳ 5-옥 소-피라졸— 1-일 )-N— (p—를릴메틸 )4 (4—Isopropyl— 2, 3-dimethyl ᅳ 5-oxo-pyrazol— 1-yl) -N— (p—lylmethyl)
■,, ¾ h ¾t 벤젠설폰아미드 ■,, ¾ h ¾t benzenesulfonamide
^쮀  ^ 쮀
'ᅵ ; 4 (4—이소프로필 -2， 3-디메틸— 5-옥 소ᅳ피라졸— 1一일 )— N-(m—를릴메틸 ) 벤젠설폰아미드 Ν-(2 , 5-디메틸페닐) -4— (4-이소프 로필 -2， 3-디메틸 -5—옥소- ' ᅵ; 4 (4—Isopropyl-2, 3-dimethyl— 5-oxopypyrazole— 1 one day) — N- (m—lylmethyl) benzenesulfonamide Ν- (2, 5-dimethylphenyl) -4— (4-isopropyl-2, 3-dimethyl-5—oxo-
! 피라졸- 1-일)벤젠설폰아미드 ! Pyrazol-1-yl) benzenesulfonamide
4-(4-이소프로필 -2， 3—디메틸— 5-옥 소ᅳ피라졸 -1-일)— Νᅳ (m-를릴)벤젠 설폰아미드 4- (4-isopropyl-2, 3—dimethyl— 5-oxo-pyrazol-1-yl)-Ν ᅳ (m-lryl) benzene sulfonamide
4-(4-이소프로필ᅳ2，3-디메틸-5一옥 소-피라졸— 1-일) -N— ( 0-를릴 )벤젠 설폰아미드
Figure imgf000039_0001
4- (4-isopropyl ᅳ 2,3-dimethyl-5-oxo-pyrazol— 1-yl) -N— (0-lryl) benzene sulfonamide
Figure imgf000039_0001
Nᅳ (4—시아노페닐) -4— (4—이소프로 필 -2， 3-디메틸 -5—옥소-피라졸一 1ᅳ 일)벤젠설폰아미드  N '(4—cyanophenyl) -4— (4—isopropyl-2,3-dimethyl-5—oxo-pyrazolyl 1-yl) benzenesulfonamide
4一 (4—이소프로필— 2 , 3-디메틸ᅳ 5—옥 소一피라졸— 1-일) -N— [2ᅳ (트리플루 오로메틸)페닐]벤젠설폰아미드 4 一 (4—Isopropyl— 2, 3-dimethyl ᅳ 5—oxo one pyrazol— 1-yl) -N— [2 ᅳ (trifluoromethyl) phenyl] benzenesulfonamide
N-(2， 4-디메틸페닐)— 4-(4-이소프 로필 -2 , 3—디메틸—5-옥소— 피라졸— 1—일 )벤젠설폰아미드
Figure imgf000039_0002
N- (2, 4-dimethylphenyl) — 4- (4-isopropyl-2, 3-dimethyl-5-oxo- pyrazole- 1-yl) benzenesulfonamide
Figure imgf000039_0002
4ᅳ (4—이소프로필 -2， 3—디메틸— 5一옥 :- 소—피라졸 -1ᅳ일)— N-(6—메톡시一 3一 4 ᅳ (4—Isopropyl-2, 3—dimethyl— 5 jade:-small—pyrazole-1 ᅳ yl) — N- (6—methoxy 一 3 一
/ 피리딜)벤젠설폰아미드 Pyridyl) benzenesulfonamide
、： 、 V 4-(4-이소프로필 -2 , 3—디메틸— 5-옥 소一피라졸— 1-일) -N-(p—를릴)벤젠 、 ： 、 V 4- (4-isopropyl-2,3—dimethyl- 5-oxo-pyrazol- 1-yl) -N- (p-lryl) benzene
、 % 、%
설폰아미드  Sulfonamide
ᅳ Ν一 (2， 2-디메틸프로필) -4-(4—이소 프로필ᅳ2 , 3-디메틸— 5-옥소ᅳ 피라졸 -1—일 )벤젠설폰아미드ᅳ Ν 一 (2 ， 2-dimethylpropyl) -4- (4—isopropyl ᅳ 2, 3-dimethyl— 5-oxo ᅳ pyrazol-1—yl) benzenesulfonamide
/시 / / Hour /
/ \一  / \ 一
4-(4-이소프로필— 2 , 3-디메틸— 5—옥 4- (4-isopropyl— 2, 3-dimethyl— 5—jade
" , .-·.-·%기 ,,、^ . 소一피라졸 -1-일) -Ν-(2- 피리딜메틸)벤젠설폰아미드 갸세 " , .- · .- · % group ,,、 ^. Soypyrazol-1-yl) -Ν- (2-pyridylmethyl) benzenesulfonamide Gyase
4-(4—이소프로필— 2 , 3-디메틸ᅳ 5-옥 소一피라졸 -1一일 )— Νᅳ (2一피리딜)벤 젠설폰아미드4- (4—Isopropyl— 2, 3-dimethyl ᅳ 5-oxo one pyrazole -1 one day) — Ν ᅳ (2 one pyridyl) benzensulfonamide
Figure imgf000040_0001
Figure imgf000040_0001
Ν-(3—브로모페닐)— 4— (4-이소프로 필— 2 , 3一디메틸— 5-옥소—피라졸 -1一 일)벤젠설폰아미드  Ν- (3—bromophenyl) — 4— (4-isopropyl— 2, 3 一 dimethyl— 5-oxo-pyrazole -1 one day) benzenesulfonamide
Ν-(2-브로모페닐)— 4-(4-이소프로 필ᅳ 2 , 3—디메틸 -5—옥소—피라졸 -1— 일)벤젠설폰아미드 Ν- (2-bromophenyl) — 4- (4-isopropylpropyl 2, 3—dimethyl-5-oxo-pyrazole-1-yl) benzenesulfonamide
Ν一 (2 , 4ᅳ디브로모페닐)— 4-(4一이소 프로필 -2， 3—디메틸— 5—옥소- 피라졸 -1-일)벤젠설폰아미드
Figure imgf000040_0002
Ν 一 (2,4 ᅳ dibromophenyl) — 4- (4 一 isopropyl-2,3—dimethyl- 5—oxo-pyrazol-1-yl) benzenesulfonamide
Figure imgf000040_0002
Νᅳ (2 ' 5—디브로모페닐) -4— (4-이소 프로필 -2 , 3-디메틸— 5—옥소- 피라졸—1-일)벤젠설폰아미드  Ν ᅳ (2 '5—dibromophenyl) -4— (4-isopropyl-2, 3-dimethyl— 5—oxo-pyrazol—1-yl) benzenesulfonamide
Ν—(3-에틸페닐)— 4— (4- 이소프로필 -2 , 3-디메틸— 5—옥소一피 라졸— 1—일)밴젠설폰아미드
Figure imgf000040_0003
N一 ( 1， 1-디메틸프로필) -4— (4—이소 프로필—2 , 3一디메틸— 5-옥소- 피라졸ᅳ 1-일)벤젠설폰아미드 Ν— (3-ethylphenyl) — 4— (4- isopropyl-2, 3-dimethyl— 5—oxo one pyrazole— 1—yl) banzensulfonamide
Figure imgf000040_0003
N 一 (1 ， 1-dimethylpropyl) -4— (4—isopropyl—2, 3 一 dimethyl— 5-oxo-pyrazolyl 1-yl) benzenesulfonamide
N-(3， 5—디메톡시페닐) -4ᅳ (4-이소 프로필 -2， 3—디메틸—5—옥소- 피라졸ᅳ 1—일)벤젠설폰아미드 N- (3, 5-dimethoxyphenyl) -4 '(4-isopropyl-2, 3-dimethyl--5-oxo-pyrazolyl 1-yl) benzenesulfonamide
N-시클로펜틸— 4- (4- 이소프로필ᅳ 2 , 3—디메틸 -5-옥소—피 라졸 -1—일)벤젠설폰아미드 N-cyclopentyl— 4- (4-isopropyl ᅳ 2, 3—dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
4-이소프로필 -2— [4- [4ᅳ (4ᅳ메특시 페닐)피페라진ᅳ 1一4-isopropyl-2— [4- [4 '(4'mephenyl) piperazine ᅳ 1 一
Figure imgf000041_0001
일]설포닐페닐]—1 , 5-디메틸 -피라
Figure imgf000041_0001
General] sulfonylphenyl] —1, 5-dimethyl-pyra
졸 -3-온  Sol-3-one
4-(4-이소프로필 -2 , 3-디메틸 -5-옥 소ᅳ피라졸— 1—일 )— Nᅳ (4— sec-부틸페 닐)벤젠설폰아미드 에틸 4- [ [4— (4ᅳ이소프로필 -2 , 3- 디메틸 -5ᅳ옥소—피라졸 -1—일 )페닐] 설포닐아미노]피페리딘— 1-카르복 실레이트  4- (4-isopropyl-2, 3-dimethyl-5-oxoxopenpyrazole— 1—yl) — N ᅳ (4— sec-butylphenyl) benzenesulfonamide ethyl 4- [[4— (4 Isopropyl-2, 3-dimethyl-5oxoo-pyrazol-1-yl) phenyl] sulfonylamino] piperidine- 1-carboxylate
^ᅳ인단— 5-일— 4— (4- 이소프로필ᅳ 2 , 3—디메틸— 5—옥소-피 라졸— 1-일)벤젠설폰아미드  ^ ᅳ Indan— 5-yl— 4— (4-isopropyl ᅳ 2, 3—dimethyl— 5—oxo-pyrazole— 1-yl) benzenesulfonamide
N-인단 -2—일— 4- (4— 이소프로필 -2 , 3-디메틸— 5—옥소一피 라졸 -1-일)벤젠설폰아미드
Figure imgf000041_0002
Ν—시클로헵틸— 4-(4— N-indane-2-yl- 4- (4-isopropyl-2, 3-dimethyl- 5-oxo-pyrazol-1-yl) benzenesulfonamide
Figure imgf000041_0002
Ν—cycloheptyl— 4- (4—
이소프로필ᅳ 2 ,3-디메틸 -5ᅳ옥소-피 라졸ᅳ 1-일)벤젠설폰아미드 f "、 -" Isopropyl ᅳ 2,3-dimethyl-5oxo-pyrazolyl 1-yl) benzenesulfonamide f " ,-"
4ᅳ (4—이소프로필 -2 , 3-디메틸 -5—옥 소-피라졸— 1-일)— Ν— [3- (트리플루 오로메틸)페닐]벤젠설폰아미드 '》'人  4 ᅳ (4—Isopropyl-2, 3-dimethyl-5—oxo-pyrazol— 1-yl) — N— [3- (trifluoromethyl) phenyl] benzenesulfonamide '》' 人
Ν- (4-아세틸페닐)— 4- ( 4-이소프로 필 -2， 3—디메틸一 5-옥소-피라졸— ·1- 일)벤젠설폰아미드 Ν- (4-acetylphenyl) — 4- (4-isopropyl -2, 3-dimethyl one 5-oxo-pyrazole- -1-yl) benzenesulfonamide
Figure imgf000042_0001
Figure imgf000042_0001
메틸 4-[[4-(4—이소프로필 -2,3- 디메틸 -5—옥소—피라졸— 1-일 )페닐] 설포닐아미노]벤조에이트 Methyl 4-[[4- (4—isopropyl-2,3-dimethyl- 5 —oxo-pyrazol— 1-yl) phenyl] sulfonylamino] benzoate
4ᅳ (4-이소프로필ᅳ 2 , 3ᅳ디메틸— 5ᅳ옥 소-피라졸 -1—일 )-Ν—피리미딘 -2 일一벤젠설폰아미드
Figure imgf000042_0002
4 '(4-isopropyl ᅳ 2,3'dimethyl- 5oxo-pyrazole-1-yl) -Ν-pyrimidine-2 days benzenesulfonamide
Figure imgf000042_0002
Ν-[(2,4ᅳ  Ν-[(2,4 ᅳ
디메록시페닐)메틸]—4— (4—이소프 로필ᅳ 2 ,3-디메틸—5-옥소ᅳ Dimethoxyphenyl) methyl] —4— (4—isopropione 2,3-dimethyl-5-oxo)
/ N< 피라졸 -1ᅳ일 )벤젠설폰아미드 / N < pyrazole-1-hexyl) benzenesulfonamide
Ν-(2-클로로 -4—피리딜)— 4ᅳ (4-이소 프로필 -2 , 3—디메틸 -5ᅳ옥소一 피라졸 -1—일 )벤젠설폰아미드
Figure imgf000042_0003
Ν- (2-chloro-4—pyridyl) —4— (4-isopropyl-2,3—dimethyl-5 ᅳ oxo 1 pyrazol-1—yl) benzenesulfonamide
Figure imgf000042_0003
2-[4— (4ᅳ에틸피페라진— 1ᅳ—일)설포 2- [4— (4 ᅳ ethylpiperazine—1 ᅳ —yl) sulfo
Ά. 기 닐페닐 ]-4—이소프로필— 1,5- 디메틸—피라졸— 3-온 Ν一 [3 , 5ᅳ비스 (트리플루오로메틸)페 닐]— 4ᅳ (4ᅳ이소프로필 -2 , 3- 디메틸 -5—옥소-피라졸 -1-일 )벤젠 설폰아미드 Ά. Nylphenyl] -4—isopropyl— 1,5-dimethyl-pyrazole— 3-one Ν 一 [3,5 ᅳ bis (trifluoromethyl) phenyl] —4 '(4 ᅳ isopropyl-2,3-dimethyl- 5 —oxo-pyrazol-1-yl) benzene sulfonamide
4-(4—이소프로필 -2 , 3—디메틸 -5-옥 소-피라졸— 1-일)— Ν-(4- 피리딜메틸)벤젠설폰아미드 4- (4—Isopropyl-2, 3—dimethyl-5-oxo-pyrazol— 1-yl) — Ν- (4-pyridylmethyl) benzenesulfonamide
Ν- ( 9-에틸카르바졸— 3ᅳ일)—4- ( 4一이 소프로필ᅳ 2 , 3—디메틸— 5—옥소—피라 졸 -1—일)벤젠설폰아미드
Figure imgf000043_0001
Ν- (9-ethylcarbazol— 3 ᅳ yl) —4- (4-Isopropyl ᅳ 2, 3—dimethyl— 5—oxo-pyrazole-1—yl) benzenesulfonamide
Figure imgf000043_0001
Ν- ( 4-브로모 -1—나프틸) -4- ( 4-이소 프로필 -2 , 3—디메틸— 5—옥소ᅳ 피라졸 -1—일 )벤젠설폰아미드 Ν- (4-bromo-1-naphthyl) -4- (4-isopropyl-2,3-dimethyl- 5-oxo-pyrazol-l-yl) benzenesulfonamide
4- (4-이소프로필— 2 , 3-디메틸— 5-옥 소―피라졸— ^일 )— Ν— (2ᅳ페닐페닐 ) 벤젠설폰아미드
Figure imgf000043_0002
4- (4-isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol— ^ yl) — Ν— (2 phenylphenyl) benzenesulfonamide
Figure imgf000043_0002
4一 (4—이소프로필 -2 , 3—디메틸 -5-옥 소一피라졸 _ 일)— Ν— ( 2ᅩ메틸- -나 프틸)벤젠설폰아미드4 一 (4—Isopropyl-2,3—dimethyl-5-oxo-pyrazol _yl) — Ν — (2 ᅩ methyl--naphthyl) benzenesulfonamide
N- [2— (4ᅳ브로모페닐)에틸] -4-(4一 이소프로필 -2 , 3—디메틸 -5-옥소-피 라졸ᅳ 1-일)벤젠설폰아미드 N- [2— (4 ᅳ bromophenyl) ethyl] -4- (4 one isopropyl-2,3—dimethyl-5-oxo-pyrazolyl 1-yl) benzenesulfonamide
4-(4—이소프로필-2 , 3-디메틸—5一옥 소-피라졸— 1—일) -N- [2— (5— 메록시—1H-인돌ᅳ 3ᅳ일)에틸]벤젠설 폰아미드 4- (4—Isopropyl-2, 3-dimethyl—5 ioxo-pyrazole— 1—yl) -N- [2— (5— methoxy-1H-indolexylxyl) ethyl] benzenesulfon amides
4ᅳ (4—이소프로필 -2， 3-디메틸— 5-옥 소-피라졸 -1—일 )— N— (2-메틸ᅳ 1H-인 돌— 5—일)벤젠설폰아미드
Figure imgf000044_0001
Figure imgf000045_0001
4-(4—이소프로필— 2 , 3-디메틸 -5ᅳ옥 4 ᅳ (4—Isopropyl-2, 3-dimethyl— 5-oxo-pyrazol-1—yl) — N— (2-methyl ᅳ 1H-phosphorine— 5—yl) benzenesulfonamide
Figure imgf000044_0001
Figure imgf000045_0001
4- (4—Isopropyl— 2, 3-dimethyl-5 jade
소-피라졸— 1—일)— N— ( 1- 나프틸메틸)벤젠설폰아미드  Bovine-pyrazole— 1—yl) — N— (1-naphthylmethyl) benzenesulfonamide
N- [ (3ᅳ브로모페닐)메틸]—4— (4—이 소프로필 -2 , 3-디메틸 -5—옥소-피라 졸 -1—일)벤젠설폰아미드
Figure imgf000046_0001
N- [(3vbromophenyl) methyl] —4— (4—isopropyl-2, 3-dimethyl-5—oxo-pyrazole-1—yl) benzenesulfonamide
Figure imgf000046_0001
N- [2-(3—브로모페닐)에틸]— 4-(4- 이소프로필— 2 , 3—디메틸 -5—옥소ᅳ피 N- [2- (3—bromophenyl) ethyl] — 4- (4-isopropyl— 2, 3—dimethyl-5—oxopypi
/ , 라졸— 1—일)벤젠설폰아미드 /, Razol— 1—yl) benzenesulfonamide
N— [ (2-브로모페닐)메틸]— 4ᅳ(4ᅳ이 X.... 소프로필 -2 3-디메틸 -5—옥소-피라N— [(2-bromophenyl) methyl] — 4 ᅳ (4-V X .... Sopropyl-2 3-dimethyl-5—oxo-pyra
.". '、\ . "," \
졸 -1-일)벤젠설폰아미드  Sol-1-yl) benzenesulfonamide
N- [2— (3-클로로페닐)에틸]— 4-(4一 이소프로필— 2 , 3-디메틸 -5-옥소ᅳ피 라졸— 1-일)벤젠설폰아미드N- [2— (3-chlorophenyl) ethyl] — 4- (4 一 isopropyl— 2, 3-dimethyl-5-oxo-pyrazol- 1-yl) benzenesulfonamide
' , ' ,
4一(4-이소프로필— 2 , 3—디메틸 -5ᅳ옥 소-피라졸ᅳ 1—일 )— N-[ [3— (트리플루 오로메틸)페닐]메틸]벤젠설폰아미 4 一 (4-isopropyl— 2, 3—dimethyl-5oxo-pyrazolyl 1-yl) — N -[[ 3 — (trifluoromethyl) phenyl] methyl] benzenesulfonami
4-(4—이소프로필 -2 , 3—디메틸— 5-옥 소-피라졸ᅳ 1—일)— N—[ [2— (트리플루4- (4—Isopropyl-2, 3—dimethyl— 5-oxo-pyrazolyl 1—yl) — N— [[2— (Triflu
% '"Y'% 人 % '" Y ' % 人
오로메틸)페닐]메틸]벤젠설폰아미  Oromethyl) phenyl] methyl] benzenesulfonami
4-(4—이소프로필-2 , 3-디메틸—5—옥 소-피라졸ᅳ 1—일 )— N-[ [4- (트리폴루 오로메틸)페닐]메틸]벤젠설폰아미
Figure imgf000047_0001
4— (4-이소프로필 -2， 3-디메틸— 5—옥 소-피라졸ᅳ1—일) -Ν- [2- (으를릴)에 ¾ j β ' ' 4- (4—Isopropyl-2, 3-dimethyl—5—oxo-pyrazolyl 1-yl) — N -[[4- (trifluoromethyl) phenyl] methyl] benzenesulfonami
Figure imgf000047_0001
4— (4-isopropyl-2, 3-dimethyl— 5—oxo-pyrazol ᅳ 1—yl) -Ν- [2- (aryl) to ¾ j β ''
틸]벤젠설폰아미드  Til] benzenesulfonamide
4一 (4-이소프로필— 2 , 3-디메틸 -5-옥 소-피라졸— 1-일) -Ν- [2-(3—메록시 페닐)에틸]벤젠설폰아미드
Figure imgf000048_0001
4 一 (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazol— 1-yl) -Ν- [2- (3—methoxy phenyl) ethyl] benzenesulfonamide
Figure imgf000048_0001
4ᅳ (4-이소프로필 -2 , 3-디메틸 -5-옥 소-피라졸— 1—일) -Ν- [2- [2- (트리플 4 ′ (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazole— 1—yl) -Ν- [2- [2- (triple
」 루오로메틸)페닐]에틸]벤젠설폰아Roomethyl) phenyl] ethyl] benzenesulfona
- 세; -Three ;
/ X 미드  Mid X
4— (4—이소프로필 -2 , 3-디메틸— 5一옥 소ᅳ피라졸— 1-일 )— Ν— [2- [3ᅳ (트리플 루오로메틸)페닐]에틸]벤젠설폰아 미드  4— (4—Isopropyl-2, 3-dimethyl—5 octasoxopyrazol— 1-yl) — Ν— [2- [3 ᅳ (trifluoromethyl) phenyl] ethyl] benzenesulfonamide
4— (4-이소프로필— 2 , 3-디메틸— 5—옥 소-피라졸 -1—일 )-Ν- [2— [4— (트리플 루오로메틸)페닐]에틸]벤젠설폰아 미드 4— (4-isopropyl— 2, 3-dimethyl— 5—oxo-pyrazol-1—yl) -Ν- [2— [4— (trifluoromethyl) phenyl] ethyl] benzenesulfonamide
4-(4—이소프로필 -2 , 3—디메틸ᅳ 5-옥 소-피라졸 -1-일 )-Ν- [4— (트리플루 오로메틸)페닐]벤젠설폰아미드
Figure imgf000048_0002
4- (4—Isopropyl-2, 3—dimethyl ᅳ 5-oxo-pyrazol-1-yl) -Ν- [4— (trifluoromethyl) phenyl] benzenesulfonamide
Figure imgf000048_0002
Ν-(2 , 3-디히드로 -1 , 4一 벤조디옥신 -6-일메틸)— 4— (4—이소 프로필 -2 , 3—디메틸ᅳ 5-옥소一 피라졸—1-일)벤젠설폰아미드  Ν- (2, 3-dihydro-1,4 benzodioxine-6-ylmethyl) — 4— (4—isopropyl-2, 3—dimethyl ᅳ 5-oxo- 1 pyrazol- 1-yl) benzene Sulfonamide
4-(4-클로로— 2， 3-디메틸— 5-옥소— 피라졸 -1—일 )— Νᅳ (2一페녹시에틸)벤 젠설폰아미드 139 4-(4—클로로 2 , 3-디메틸 -5—옥소一 피라졸 -1—일)— N- [ (2- 플루오로페닐)메틸]벤젠설폰아미 시.^ 4- (4-chloro- 2, 3-dimethyl- 5-oxo- pyrazol-1-yl)-Ν ᅳ (2 phenoxyethyl) benzensulfonamide 139 4- (4—chloro 2, 3-dimethyl-5—oxo one pyrazol-1—yl) — N- [(2-fluorophenyl) methyl] benzenesulfonamici. ^
140 4-(4—클로로 2， 3-디메틸 -5—옥소- 피라졸 -1—일) -Nᅳ [ (3- 플루오로페닐)메틸]벤젠설폰아미140 4- (4—chloro 2, 3-dimethyl-5—oxo-pyrazol-1—yl) -N ᅳ [(3-fluorophenyl) methyl] benzenesulfonami
！ ！
141 4-(4—클로로 -2 , 3—디메틸—5-옥소— 피라졸 -1-일)— Ν- [ (4— 플루오로페닐)메틸]벤젠설폰아미 仁 141 4- (4—Chloro-2, 3—dimethyl-5-oxo- pyrazol-1-yl) — Ν- [(4— fluorophenyl) methyl] benzenesulfonami 仁
142 4ᅳ(4—클로로 -2 , 3—디메틸 -5—옥소— 피라졸 -1-일 ΗΗ3, 4—디클로로페 닐)벤젠설폰아미드 142 4 ᅳ (4—chloro-2, 3—dimethyl-5—oxo—pyrazol-1-yl ΗΗ3, 4—dichlorophenyl) benzenesulfonamide
143 4-(4-클로로 2， 3—디메틸 -5 옥소一 피라졸— 1—일) -Ν-( 5—클로로 -2—플루 오로ᅳ페닐)벤젠설폰아미드 143 4- (4-Chloro 2, 3-dimethyl-5 oxo one pyrazole— 1—yl) -Ν- (5—chloro-2—fluorophenyl) benzenesulfonamide
144 4-(4—클로로ᅳ2， 3—디메틸— 5-옥소— 피라졸 1-일)— Ν— [4-( 디메틸아미노)페닐]벤젠설폰아미 144 4- (4—chloro ᅳ 2 ， 3—dimethyl— 5-oxo- pyrazol 1-yl) — Ν— [4- (dimethylamino) phenyl] benzenesulfonami
145 4 (4-클로로一 2， 3-디메틸— 5ᅳ옥소一 피라졸 -1-일) -Ν-(2—피리딜메틸)벤 젠설폰아미드 145 4 (4-Chloro-I2, 3-dimethyl- 5oxo-isopyrazol-1-yl) -Ν- (2-pyridylmethyl) benzensulfonamide
146 메틸 3 [ [4— (4-클로로—2 , 3-디메 틸一 5-옥소-피라졸 -1—일)페닐]설포 닐아미노]벤조에이트 4— (4-클로로 -2 , 3-디메틸一 5-옥소— 피라졸— 1ᅳ일)ᅳ N— ( 1H—인돌— 5-일메 틸)벤젠설폰아미드
Figure imgf000050_0001
146 Methyl 3 [[4— (4-chloro—2, 3-dimethylyl 5-oxo-pyrazol-1—yl) phenyl] sulfonylamino] benzoate 4— (4-Chloro-2, 3-dimethyl-l 5-oxo- pyrazol— 1 ᅳ yl) ᅳ N— (1H—indol— 5-ylmethyl) benzenesulfonamide
Figure imgf000050_0001
시 4— (4-클로로 -2 ' 3-디메틸— 5—옥소一 피라졸— 1-일) -Ν- ( 1—나프틸메틸)벤 젠설폰아미드  Hour 4— (4-Chloro-2 '3-dimethyl— 5—oxo one pyrazol— 1-yl) -Ν- (1—naphthylmethyl) benzensulfonamide
4-(4—클로로— 2， 3—디메틸— 5-옥소- 피라졸 -1—일) -Ν- [ (3 , 4-디메록시페 닐)메틸]벤젠설폰아미드 4- (4—chloro— 2, 3—dimethyl— 5-oxo-pyrazol-1—yl) -Ν- [(3,4-dimethoxyphenyl) methyl] benzenesulfonamide
4-(4—클로로— 2 , 3—디메틸— 5-옥소ᅳ 피라졸 -1-일)— Ν— ( 5ᅳ퀴놀릴)벤젠설 폰아미드 4- (4—Chloro— 2, 3—dimethyl— 5-oxo ᅳ pyrazol-1-yl) —Ν— (5 ᅳ quinolyl) benzenesulfonamide
4一(4-클로로— 2， 3ᅳ디메틸— 5—옥소 피라졸 -1-일 )-Ν- [ (2 , 4ᅳ디메특시페 닐)메틸]벤젠설폰아미드4 一 (4-Chloro-2,3 ᅳ dimethyl-5-oxopyrazol-1-yl) -Ν-[(2,4'dimethoxyphenyl) methyl] benzenesulfonamide
. "、"^. . " 、" ^.
4一(4-브로모— 2 , 3-디메틸 -5-옥소— 피라졸— 1-일 )— Ν— [ (3， 4—디메록시페 닐)메틸]벤젠설폰아미드
Figure imgf000050_0002
4 一 (4-bromo— 2, 3-dimethyl-5-oxo- pyrazol— 1-yl) — Ν— [(3, 4—dimethoxyphenyl) methyl] benzenesulfonamide
Figure imgf000050_0002
4-(4—브로모 -2 , 3-디메틸一 5—옥소— 피라졸— 1-일)— Ν-(5-퀴놀릴)벤젠설  4- (4—Bromo-2, 3-dimethyl 一 5—oxo—pyrazol— 1-yl) — Ν- (5-quinolyl) benzenesulfur
폰아미드  Ponamide
4-(4—브로모 -2 , 3-디메틸— 5—옥소一 피라졸 -1-일) -Ν- [4—( 디메틸아미노)페닐]벤젠설폰아미
Figure imgf000050_0003
메틸 3-[[4ᅳ(4—브로모.—2,3ᅳ디메 틸一 5-옥소-피라졸 -1-일 )페닐]설포 닐아미노]벤조에이트 飞 4- (4—Bromo-2, 3-dimethyl— 5—oxo one pyrazol-1-yl) -Ν- [4— (dimethylamino) phenyl] benzenesulfonami
Figure imgf000050_0003
Methyl 3-[[4 '(4—bromo . —2,3'dimethyl-l 5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] benzoate
4— (4-브로모 -2 ' 3—디메틸 -5-옥소ᅳ 피라졸 -1-일)— N-[(3- 플루오로페닐)메틸]벤젠설폰아미
Figure imgf000051_0001
4— (4-Bromo-2 '3—dimethyl-5-oxoxetpyrazol-1-yl) — N-[(3-fluorophenyl) methyl] benzenesulfonami
Figure imgf000051_0001
4— (4—브로모ᅳ2 , 3—디메틸 -5—옥소- 피라졸— 1ᅳ일)— N-[(2- 플루오로페닐)메틸]벤젠설폰아미：  4— (4—Bromodium 2, 3—Dimethyl-5—oxo-pyrazole—1) yl—N-[(2-fluorophenyl) methyl] benzenesulfonami ：
4ᅳ (4—브로모 -2 , 3-디메틸—5—옥소ᅳ 피라졸—1—일)— Ν— (2-피리딜메틸)벤 젠설폰아미드 4 '(4—bromo-2, 3-dimethyl—5—oxoxet pyrazol—1—yl) —Ν— (2-pyridylmethyl) benzensulfonamide
4-(4-브로모— 2 , 3-디메틸ᅳ 5—옥소ᅳ 피라졸 -1-일)— Ν-(2,3— 디히드로— 1 , 4-벤조디옥신 -6—일 )벤 젠설폰아미드 4- (4-Bromo— 2, 3-dimethyl ᅳ 5—oxozepyrazol-1-yl) — Ν- (2,3— dihydro— 1, 4-benzodioxin-6-yl) benzen Sulfonamide
Ν-[3, 5-비스 (트리플루오로메틸)페 닐 ]— 4-(4—브로모 -2 , 3ᅳ디메틸— 5-옥 Ν- [3,5-bis (trifluoromethyl) phenyl] — 4- (4—bromo-2,3 ᅳ dimethyl— 5-jade
¾ .-4 、、 소ᅳ피라졸— 1—일)벤젠설폰아미드 、 ¾ .-4 、、 Sopypyrazole— 1—yl) benzenesulfonamide 、
4-(4-브로모 -2 , 3—디메틸一 5—옥소- 피라졸— 1-일) -Ν-(3 , 4—디클로로페 닐)벤젠설폰아미드
Figure imgf000051_0002
4- (4-Bromo-2,3—dimethyl- 1 5—oxo-pyrazol— 1-yl) -Ν- (3, 4-dichlorophenyl) benzenesulfonamide
Figure imgf000051_0002
4一 (4-브로모 -2， 3-디메틸一 5—옥소- 피라졸 - 1-일 ) -Ν- ( 5-클로로 -2—플루 . 오로-페닐)벤젠설폰아미드 N- [3 , 5-비스 (트리플루오로메틸)페 닐 ] -4— (4-클로로—2， 3-디메틸 -5-옥 i f 소-피라졸— 1—일 )벤젠설폰아미드 4 one (4-bromo-2,3-dimethyl one 5—oxo-pyrazol-1-yl) -Ν- (5-chloro-2—flu. Oro-phenyl) benzenesulfonamide N- [3,5-bis (trifluoromethyl) phenyl] -4— (4-chloro-2,3-dimethyl-5-oxi f so -pyrazol— 1—yl) benzenesulfonamide
4— (4-클로로—2， 3-디메틸—5-옥소- 피라졸 -1—일)ᅳ N-(2 , 3一 디히드로— 1， 4-벤조디옥신 -6-일 )벤 젠설폰아미드 4— (4-Chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) ᅳ N- (2, 3 디 dihydro— 1, 4-benzodioxin-6-yl) benzensulfon amides
4-(4—브로모 -2， 3-디메틸—5—옥소一 피라졸—1—일)— N-시클로펜틸—벤젠 'V 、 설폰아미드  4- (4—Bromo-2, 3-dimethyl—5—oxo one pyrazole—1—yl) —N-cyclopentyl—benzene 'V, sulfonamide
ί " .、'\ ί " . 、 '\
4ᅳ (4—브로모 -2 , 3一디메틸ᅳ 5—옥소- 피라졸 -1-일)— N-시클로헵틸ᅳ벤젠 설폰아미드 4 '(4—Bromo-2, 3 dimethyl ᅳ 5—oxo-pyrazol-1-yl) — N-cycloheptyl ᅳ benzene sulfonamide
4-(4-브로모— 2， 3—디메틸 -5-옥소- 피라졸 -1-일 )— N-페닐 -밴젠설폰아 미드 4- (4-Bromo— 2, 3—dimethyl-5-oxo-pyrazol-1-yl) — N-phenyl-banzensulfonamide
4— (2， 3一디메틸 -5—옥소 -4-페닐-피 라졸— 1ᅳ일)ᅳ N-(2-페녹시에틸)벤젠 설폰아미드4— (2 ， 3 一 dimethyl-5—oxo-4-phenyl-pyrazole— 1 ᅳ yl) ᅳ N- (2-phenoxyethyl) benzene sulfonamide
Figure imgf000052_0001
Figure imgf000052_0001
4- [4— (4-클로로페닐) -2 , 3- 디메틸 -5-옥소—피라졸 -1ᅳ- 일 ] -N- ( 2-페녹시에틸)벤젠설폰아 미드  4- [4— (4-chlorophenyl) -2, 3-dimethyl-5-oxo-pyrazol-1 졸 -yl] -N- (2-phenoxyethyl) benzenesulfonamide
2- [3- [ [4-(4-이소프로필 -2 , 3ᅳ디메 틸ᅳ 5—옥소-피라졸 -1-일)페닐 ]설포 닐아미노]페닐]아세트산 N— (2—히드록시페닐 )— 4— (4-이소프 로필 -2, 3—디메틸 -5ᅳ옥소—2- [3- [[4- (4-isopropyl-2,3'dimethylyl-5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] phenyl] acetic acid N— (2—hydroxyphenyl) — 4— (4-isopropyl-2, 3—dimethyl-5oxo-—
1One
피라졸—1ᅳ일)벤젠설폰아미드  Pyrazol--1-hexyl) benzenesulfonamide
N-(4-히드록시페닐 )-4— (4-이소프 로필— 2, 3-디메틸 -5-옥소— 피라졸 -1-일)벤젠설폰아미드 N- (4-hydroxyphenyl) -4— (4-isopropyl— 2, 3-dimethyl-5-oxo— pyrazol-1-yl) benzenesulfonamide
4-[2，3-디메틸 -5—옥소 -4— [4— (트리 플루오로메틸)페닐]피라졸 -1- 일] -N-(2-페녹시에틸)벤젠설폰아 미드 4- [2,3-dimethyl-5—oxo-4— [4— (trifluoromethyl) phenyl] pyrazol-1-yl] -N- (2-phenoxyethyl) benzenesulfonamide
N- [3- (히드록시메틸)페닐] -4— (4- 이소프로필— 2 , 3-디메틸ᅳ 5-옥소-피 라졸ᅳ1-일)벤젠설폰아미드
Figure imgf000053_0001
N- [3- (hydroxymethyl) phenyl] -4— (4-isopropyl— 2, 3-dimethyl ᅳ 5-oxo-pyrazol ᅳ 1-yl) benzenesulfonamide
Figure imgf000053_0001
N一 (6—히드록시— 1—나프틸 )-4— (4—이 소프로필 -2 , 3-디메틸— 5-옥소—피라 졸 -1—일)벤젠설폰아미드  N 一 (6—hydroxy— 1—naphthyl) -4— (4—isopropyl-2, 3-dimethyl— 5-oxo-pyrazole-1—yl) benzenesulfonamide
4一 (4—이소프로필 -2 , 3—디메틸— 5—옥 소ᅳ피라졸— 1—일) -Nᅳ (2-페녹시프로 필)벤젠설폰아미드
Figure imgf000053_0002
4 一 (4—Isopropyl-2, 3—dimethyl— 5—oxoxypyrazole— 1—yl) -N ᅳ (2-phenoxypropyl) benzenesulfonamide
Figure imgf000053_0002
N-[2-(2- 교 씨 c 、 ' ᅳ 플루오로페녹시)에틸] -4— (4一이소 프로필 -2,3ᅳ디메틸—5—옥소- 피라좀 -1ᅳ임 )벤젠설폰아미드N- [2- (2-gyocyc c '′ ᅳ fluorophenoxy) ethyl] -4— (4-one isopropyl-2,3 ᅳ dimethyl—5—oxo-pyrasome-1 ′) benzenesulfonamide
N-[4-[2— (디메틸아미노)에톡시]페 닐]— 4-(4—이소프로필— 2,3- 디메틸—5—옥소—피라졸 -1-일 )벤젠
Figure imgf000053_0003
설폰아미드 N- [4- [2— (dimethylamino) ethoxy] phenyl] — 4- (4—isopropyl— 2,3-dimethyl— 5 —oxo-pyrazol-1-yl) benzene
Figure imgf000053_0003
Sulfonamide
Figure imgf000054_0001
N-벤질 -4— (4-이소프로필 -2 , 3—디메 틸 -5-옥소-피라졸 -1—일)벤젠설폰
Figure imgf000055_0001
아미드
Figure imgf000054_0001
N-benzyl-4— (4-isopropyl-2,3—dimethyl-5-oxo-pyrazole-1—yl) benzenesulfon
Figure imgf000055_0001
amides
메틸 2-[ [4— (4ᅳ이소프로필 -2 , 3- 디메틸 -5—옥소—피라졸 -1一일 )페닐] 설포닐아미노] -2-페닐—아세테이트 Methyl 2- [[4— (4 ᅳ isopropyl-2, 3-dimethyl- 5 —oxo-pyrazole-1 yl) phenyl] sulfonylamino] -2-phenyl-acetate
N-(2—에록시에틸) -4— (4-이소프로N- (2—hydroxyethyl) -4— (4-isopro
- 一 필 -2 , 3-디메틸 -5—옥소一피라졸 -1— -One-pill-2, 3-dimethyl-5-oxo-one pyrazole-1
일)벤젠설폰아미드  Benzenesulfonamide
N-(2， 6-디메틸페닐 )— 4-(4-이소프 로필— 2 , 3—디메틸—5-옥소— N- (2, 6-dimethylphenyl) — 4- (4-isopropyl— 2, 3—dimethyl-5-oxo—
¾ 피라졸 -1ᅳ일)벤젠설폰아미드 ¾ pyrazol-1-hexyl) benzenesulfonamide
4一 (4-이소프로필 -2， 3—디메틸ᅳ 5ᅳ옥 소-피라졸— 1—일) -N— (9—옥소티옥산 텐 -2—일)벤젠설폰아미드 4 一 ( 4 -isopropyl-2,3—dimethyl ᅳ 5oxo-pyrazole— 1—yl) -N— (9—oxothioxanthene-2-2-yl) benzenesulfonamide
ύ ^ 4-(4-이소프로필 -2 , 3-디메틸— 5ᅳ옥 ύ ^ 4- (4-isopropyl-2, 3-dimethyl— 5 jade
소一피라졸ᅳ 1-일)— N-(4- 메록시—3 , 5—디메틸-페닐)벤젠설폰 Sodium pyrazolyl 1-yl) — N- (4-methoxy-3, 5-dimethyl-phenyl) benzenesulfon
「、、 아미드 `` 、 Amide
N-( l , 3—디메틸ᅳ 2-옥소一 벤지미다졸— 5-일)— 4-(4-이소프로 필 -2 , 3ᅳ디메틸 -5-옥소—피라졸ᅳ 1一
Figure imgf000055_0002
일)벤젠설폰아미드 N- (l, 3—dimethyl ᅳ 2-oxo one benzimidazole— 5-yl) — 4- (4-isopropyl-2, 3 ᅳ dimethyl-5-oxo-pyrazole ᅳ 1 一
Figure imgf000055_0002
Benzenesulfonamide
에틸 5ᅳ[ [4-(4-이소프로필-2 , 3— 디메틸—5—옥소-피라졸—工—일)페닐 ] 설포닐아미노]벤조티오펜— 2-카르 복실레이트 Ethyl 5 '[[4- (4-isopropyl-2,3—dimethyl— 5 —oxo-pyrazol— 工 —yl) phenyl] sulfonylamino] benzothiophene— 2-carboxylate
4一 [4-(4_이소프로필ᅳ 2 , 3一 디메틸—5-옥소—피라졸ᅳ i_일)페닐 ] 설포닐 -1，3ᅳ디히드로퀴녹살린一 2—
Figure imgf000055_0003
요 198 N-터트-부틸— 4— (4— 4 一 [4- (4_Isopropyl ᅳ 2, 3 一 dimethyl— 5 -oxo-pyrazol ᅳ i_yl) phenyl] sulfonyl-1,3 ᅳ dihydroquinoxaline 一 2—
Figure imgf000055_0003
Yo 198 N-tert-butyl- 4— (4—
이소프로필— 2， 3ᅳ디메틸 -5-옥소-피 라졸— 1-일)벤젠설폰아미드 Isopropyl — 2, 3 ᅳ dimethyl-5-oxo-pyrazol— 1-yl) benzenesulfonamide
199 N-(3—플루오로 -2—메틸— 199 N- (3—Fluoro-2—methyl—
페닐) -4— (4—이소프로필ᅳ 2 , 3-디메 틸' -5—옥소-피라졸— 1—일 )벤젠설폰
Figure imgf000056_0001
Phenyl) -4— (4—isopropyl ᅳ 2,3-dimethyl'-5—oxo-pyrazole— 1—yl) benzenesulfon
Figure imgf000056_0001
아미드  amides
200 4- [ [4-(4-이소프로필— 2，3一 디메틸 -5—옥소—피라졸— iᅳ일)페닐 ] 설포닐아미노]벤젠설폰아미드 200 4- [[4- (4-isopropyl— 2,3 dimethyl- 5 —oxo-pyrazol- i ᅳ yl) phenyl] sulfonylamino] benzenesulfonamide
201 4-이소프로필— 1， 5— 201 4-isopropyl— 1 ， 5—
디메틸— 2- [4— [4-(3— 페닐퀴녹살린 -2ᅳ일 )피페라진— 1- 일]설포닐페닐]피라졸—3-온  Dimethyl— 2- [4— [4- (3—phenylquinoxaline-2-hexyl) piperazin— 1-yl] sulfonylphenyl] pyrazole-3-one
202 4-이소프로필— 2- [4- [ [4- [4-(4ᅳ이 202 4-isopropyl— 2- [4- [[4- [4- (4
소프로필 -2， 3-디메틸 -5—옥소—피라 졸 -1ᅳ일 )페닐]설포닐一 1， 4-디아제 판— 1-일]설포닐]페닐] -1 , 5— 디메틸-피라졸 -3ᅳ온  Sopropyl-2, 3-dimethyl-5-oxo-pyrazol-1xyl) phenyl] sulfonyl one 1, 4-diazepan— 1-yl] sulfonyl] phenyl] -1, 5- dimethyl-pyrazole -3 degrees
203 4一이소프로필—1， 5一 203 4 一 Isopropyl—1 ， 5 一
디메틸 -2- [4- [4— [4- (모폴린 -4-카 르보닐 )-2-니트로— 페닐]피페라진 -4一일 ]설포닐페닐] 피라졸— 3—온  Dimethyl-2- [4- [4— [4- (morpholine-4-carbonyl) -2-nitro- phenyl] piperazin-4 yl] sulfonylphenyl] pyrazole— 3-one
204 4—이소프로필 -1 , 5- 디메틸 -2- [4— [4— (2—피리딜)피페라 진一 1—일 ]설포닐페닐]피라졸— 3-온204 4—Isopropyl-1, 5-dimethyl-2- [4— [4— (4— (2—pyridyl) piperazin 一 1-yl] sulfonylphenyl] pyrazole— 3-one
205 N-(2， 2-디메틸프로필)— 4-(4ᅳ이소 프로필—2， 3-디메틸 -5—옥소一 피라졸 -1-일)벤젠설폰아미드
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
245 N—(시클로헵틸메틸) -4-(4ᅳ이소프 入 - o H I ) 로필— 2 , 3-디메틸— 5—옥소 -2 , 5—디히 드로ᅳ 1Hᅳ피라졸 -1-일)벤젠설폰아 미드 205 N- (2, 2-dimethylpropyl) — 4- (4 ᅳ isopropyl—2, 3-dimethyl-5—oxo one pyrazol-1-yl) benzenesulfonamide
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
245 N— (Cycloheptylmethyl) -4- (4isosorbent-o HI) Lofil— 2, 3-dimethyl— 5—oxo-2, 5—dihydrodrop 1H ᅳ pyrazol-1-yl) benzene Sulfonamide
气 _  气 _
/ 、、  / 、、
246 N-(2—시클로핵실에틸)— 4— (4—이소  246 N- (2—cyclonucleoethylethyl) 4 — (4—iso
프로필 -2 , 3-디메틸 -5—옥소 -2 , 5-디 히드로 -1H-피라졸— 1—일)벤젠설폰
Figure imgf000062_0001
아미드 Propyl-2, 3-dimethyl-5—oxo-2, 5-dihydro-1H-pyrazole— 1—yl) benzenesulfon
Figure imgf000062_0001
amides
247 N一 (3 , 4-디메록시페닐 )—4— (4—이소  247 N 一 (3, 4-dimethoxyphenyl) —4— (4—iso
프로필ᅳ 2 , 3—디메틸— 5-옥소 -2 , 5-디 히드로— 1H-피라졸 -1-일 )벤젠설폰 아미드  Propyl ᅳ 2, 3—dimethyl— 5-oxo-2, 5-dihydro— 1H-pyrazol-1-yl) benzenesulfon amide
본 발명의 화학식 1의 벤조설폰아미드 유도체는 약학적으로 허용가능한 염의 형태로 사용할 수 있다。 상기 염으로는 약학적으로나 생리학적으로 허용되는 다양 한 유기산 또는 무기산에 의해 형성된 산부가염이 유용하다. 적합한 유기산으로는， 예를 들면 카르복실산, 포스폰산, 술폰산, 아세트산, 프로피온산， 옥탄산, 데칸산, 글리콜산, 락트산， 푸마르산, 숙신산, 아디프산, 말산, 타르타르산, 시트르산， 글 루탐산, 아스파르트산， 말레산， 벤조산， 살리실산, 프탈산， 페닐아세트산, 벤젠술 폰산， 2-나프탈렌술폰산， 메틸황산, 에틸황산， 도데실황산 등을 사용할 수 있고， 적합한무기산으로는, 예를 들면 염산， 황산 또는 인산 등을 사용할 수 있다。 본 발명의 화학식 1의 벤조설폰아미드 유도체는 약학적으로 허용가능한 혁뿐 만 아니라, 통상의 방법에 의해 제조될 수 있는 모든 염, 수화물 및 용매화물을 모 두 포함할 수 있다。 본 발명은 상기 화학식 1로 표시되는 벤조설폰아미드 유도체 또는 이의 약학 적으로 허용가능한 염의 제조방법을 제공한다. 본 발명에 따른 화학식 1의 유도체의 제조방법은 반응식 1로 나타낸 바와 같 이 The benzosulfonamide derivatives of Formula 1 of the present invention may be used in the form of pharmaceutically acceptable salts. Acid salts formed by various organic or inorganic acids that are pharmaceutically or physiologically acceptable are useful as such salts. Suitable organic acids include, for example, carboxylic acid, phosphonic acid, sulfonic acid, acetic acid, propionic acid, octanoic acid, decanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, malic acid, tartaric acid, citric acid, glutamic acid, Aspartic acid, maleic acid, benzoic acid, salicylic acid, phthalic acid, phenylacetic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, methyl sulfuric acid, ethyl sulfuric acid, dodecyl sulfuric acid and the like can be used. Examples of suitable inorganic acids include hydrochloric acid and sulfuric acid. Or phosphoric acid, etc. The benzosulfonamide derivatives of the general formula (I) of the present invention may include not only pharmaceutically acceptable leathers, but also all salts, hydrates, and solvates that can be prepared by conventional methods. The present invention provides a method for preparing a benzosulfonamide derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof. Method for producing a derivative of formula 1 according to the present invention as shown in Scheme 1
1) 화학식 2의 피라졸론 화합물을 클로로설폰산과 방웅하여 화학식 3의 화합 물을 제조하는 단계， 2) 상기 1)단계에서 제조환 화학식 2의 화합물과 2차 아민을 반응시켜 화학 식 1의 화합물을 제조하는 단계를 포함하여 이루어지며, 하기 반웅식 1로 표시되는 벤젠설폰아미드 유도체의 제조 방법을 제공한다. 1) preparing a compound of the formula (3) by leaving the pyrazolone compound of the formula (2) with chlorosulfonic acid, 2) preparing a compound of Chemical Formula 1 by reacting a compound of Formula 2 with a secondary amine in step 1), and preparing a benzenesulfonamide derivative represented by Formula 1 below. to provide.
[반옹식 1]  Rebellion 1
Figure imgf000063_0001
Figure imgf000063_0001
상기 반웅식 1에서 In the reaction 1
Rl , R2 , R3는 상기 화학식 1에서 정의한 바와 같다. 본 발명의 벤조설폰아미드 유도체 또는 이의 약학적으로 허용가능한 염은 LRS와 RagD 간의 결합을 저해하여 mTOR의 활성을 저해하는 효과를 나타내기 때문 에 , mTOR를 저해함으로써 치료효과가 달성되는 다양한 질환들을 예방 또는 치료할 수 있다. 본 발명에서 상기 mTOR를 저해함으로써 치료효과가 달성되는 질환들의 비 제한적인 예시는 암， 간질, 염증질환， 면역질환, 당뇨， 비만， 호흡기계 폐쇄성 질 환, 섬유증, 품페병， 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질 환， 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행성 질환， 심혈관계질환 / \또는 기생 충 감염증을 들 수 있으며， 바람직하게는 암 또는 간질일 수 있다. 구체적으로, 본 발명의 일실시예에 따르면 본 발명의 화합물들은 암세포에서 활성이 높은 것으로 알려져 있는 mTORCl의 활성을 억제하는 효과가 매우 우수하며 , 다양한 암 세포에 대해 세포독성을 나타내는 반면, 정상세포주에 대해서는 세포득 성을 전혀 나타내지 않는 것으로 확인되었다. 따라서 , 본 발명은 상기 화학식 1의 벤조설폰아미드 유도체 또는 이의 약학 적으로 허용가능한 염을 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조 성물을 제공한다. 또한 본 발명은 상기 화학식 1의 벤조설폰아미드 유도체 또는 이의 약학적으 로 허용가능한 염을 필요로 하는 개체에 유효량으로 투여하여 암 관련 질환을 치료 하는 방법을 제공한다。 R1, R2, and R3 are as defined in Chemical Formula 1. Since the benzosulfonamide derivatives or pharmaceutically acceptable salts thereof of the present invention exhibit the effect of inhibiting the activity of mTOR by inhibiting the binding between LRS and RagD, it is possible to prevent various diseases in which the therapeutic effect is achieved by inhibiting mTOR. Or can be treated. Non-limiting examples of diseases in which the therapeutic effect is achieved by inhibiting the mTOR in the present invention is cancer, epilepsy, inflammatory diseases, immune diseases, diabetes, obesity, respiratory obstructive diseases, fibrosis, pamp disease, lysosomal accumulation disease (lysosomal storage di sease), neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, cardiovascular disease / and / or parasitic infections, preferably cancer or epilepsy. Specifically, according to one embodiment of the present invention, the compounds of the present invention have a very good effect of inhibiting the activity of mTORCl, which is known to be highly active in cancer cells, and exhibit cytotoxicity against various cancer cells, while It was confirmed that no cytotoxicity was observed for the cells. Accordingly, the present invention provides a pharmaceutical composition for preventing or treating cancer, comprising the benzosulfonamide derivative of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. In another aspect, the present invention is to treat a cancer-related disease by administering to a subject in need of a benzosulfonamide derivative of Formula 1 or a pharmaceutically acceptable salt thereof Provides a way to do it.
상기 암은 라파마이신 (rapamycin) 저항성을 나타내는 암인 것을 특징으로 하 는 방법을 제공한다, 또한 본 발명은 상기 화학식 1의 벤조설폰아미드 유도체 또는 이의 약학적으 로 허용가능한 염의 항암제 제조를 위한 용도를 제공한다。  The cancer provides a method characterized in that the cancer showing rapamycin resistance, the present invention also provides a use for the production of an anticancer agent of the benzosulfonamide derivative of Formula 1 or a pharmaceutically acceptable salt thereof .
상기 암은 라파마이신 (rapamycin) 저항성을 나타내는 암인 것을 특징으로 하 는 치료제 제조를 위한 용도를 제공한다,  The cancer provides a use for the manufacture of a therapeutic agent, characterized in that the cancer showing rapamycin resistance,
LRSC leucyl tRNA synthetase)는 mTORCl로의 아미노산 신호전달의 핵심매개체 로 기능한다. 즉, LRS가 아미노산 의존적으로, mTORCl으로의 신호전달 매개체인 Rag GTPase에 직접적으로 결합하고， Rag GTPase에 대한 GTPase-act ivat mg protein(GAP)의 역할을 하여 Rag GTPase가 mTORCl을 활성화한다, 또한， 류실— tRNA 합성효소 ( leucyl tRNA synthetase , LRS)가 아미노산으로부터 유도되는 mTORCl의 활성화에 있어 중요한 역할을 수행하여, LRS가 세포내의 류신 농도를 감지하고 류 신에서 유도되는 mTORCl의 활성화에 영향을 미친다. Rag 단백질은 Ras smal l GTPase 중 Rag subfami ly 에 속하고 RagA, RagB , RagC , RagD의 네 가지 종류가 존 재한다, 이중 A와 B는 이스트의 Gtrlp GTPase의 오솔로그 (ortholog)이고 C와 D는 이스트의 Gtr2p 의 오솔로그이다. RagD는 A 혹은 B와 함께 결합하여 이합체 (dimer )를 이루며 아미노산에 의한 mTORCl 활성을 매개한다. (Trends in Biochemi cal Sci ences , 33 : 565-568 , 2008) . 따라서 , LRS와 RagD 간의 결합을 저해 하면 mTORCl의 활성화가 저해되어 암을 예방 또는 치료하는 효과가 나타날 수 있 다 보다 구체적으로 상기 암은 이에 제한되지는 않으나， 흑색종， 백혈병, 대장 암, 폐암, 간암， 위암， 식도암, 췌장암， 담낭암, 신장암, 방광암, 전립선암, 고환 암， 자궁경부암, 자궁내막암, 융모암, 난소암, 유방암， 갑상선암, 뇌암, 두경부암， 피부암， 림프종, 재생불량성 빈혈 등을 포함한다. 상기에서 림프종은 호지킨씨 림 프종 및 비호지킨씨 림프종을 모두 포함하며, 전구 B세포종양 (Precursor Bᅳ cel l neoplasm)과 같은 B세포신생물 (B— CELL NEOPLASMS) , 전구 Τ세포종양 (Precursor T一 cel l neoplasm)과 같은 T세포와 ΝΚ세포 신생물 (T— CELL AND NK-CELL NEOPLASMS) 및 전형적호지킨병 (Cl ass i cal Hodgkin lymphoma)와 같은 호지킨림프종 (Hodgkin lymphoma , Hodgkin di sease)을 포함한다. 본 발명의 일실시예에 따르면， 본 발명의 상기 화학식 1의 벤조설폰 아미드 유도체는 라파마이신 (rapamycin) 저항성을 나타내는 암에 대해서도 유효한 치료효 과를 나타낼 수 있음을 확인하였다。 즉, 본 발명의 상기 화학식 1의 벤조설폰 아미드 유도체는 LRS의 효소적 활 성에는 영향을 미치지 않으면서 LRS의 류신—센성 활성을 저해하는 효과를 나타내었 다. LRS의 발현수준은 대장암 조직 및 세포에서 Rag GTPase 및 mTORCl의 활성화와 긍정적인 상관관계를 나타내었으며， 세포의 이주 경향성이 영향을 미치는 것으로 확인되었다. 본 발명의 상기 화학식 1의 벤조설폰아미드 유도체는 LRS에서 RagD와 상호작용하는 위치에 결합하여 LRS가 라이소좀으로 위치하는 것을 특이적으로 저해 하며， RagD GTPase 및 mTORCl의 활성을 저해하여 결과적으로 암의 성장을 억제하는 효과를 나타내었다. 이러한 효과는 라파마이신에 대해 저항성을 나타내는 암 세포 에서도 동일하게 나타낸 바， 본 발명의 상기 화학식 1의 벤조설폰아미드 유도체는 mTOR 돌연변이가 나타나 라파마이신에 대해 저항성을 나타내는 암을 효과적으로 예 방 또는 치료하는 효과를 나타낼 수 있다는 특징이 있다, 본 발명의 다른 일실시예에 따르면 간질과 연관된 mTOR돌연변이 (L2427P)를 발현하는 세포에 본 발명의 화합물을 처리한 결과 ( i ) RagD GTP의 가수분해와 LRS 의 lysosomal translocat ion이 저해되었고， ( i i ) mTORCl의 활성 또한 저해되었으 며， 본 발명의 화합물을 간질 동물모델에 투여한 결과， 간질성 발작의 흿수가 대조 군과 비교하여 현저하게 감소하는 것을 확인할 수 있었다. 특히， 본 발명의 상기 화합물은 혈액—뇌 장벽 (blood-brain barr ier , BBB) 투과성이 매우 높은 것으로 나 타나 뇌 질환의 예방 치료제로 개발될 가능성이 우수하다. 본 발명에 따른 약학적 조성물은 약학적으로 허용되는 담체외— 함께 당업계에 공지된 방법으로 투여경로에 따라 다양하게 제형화될 수 있다. '약학적으로 허용되 는'이란 생리학적으로 허용되고 인간에게 투여될 때， 활성 성분의 작용을 저해하지 않으며 통상적으로 위장 장애, 현기증과 같은 알레르기 반옹 또는 이와 유사한 반 웅을 일으키지 않는 비독성의 조성물을 말한다. 상기 담체로는 모든 종류의 용미] , 분산매질， 수중유 또는 유중수 에멀견， 수성 조성물, 리포좀, 마이크로비드 및 마 이크로좀이 포함된다. 본 발명의 조성물을 비경구적으로 투여하는 경우， 본 발명의 조성물은 적합 한 비경구용 담체와 함께 주사제, 경피투여제 및 비강흡입제의 형태로 당해 기술 분야에 공지된 방법에 따라 제형화될 수 있다。 상기 주사제의 경우에는 반드시 멸 균되어야 하며 박테리아， 진균과 같은 미생물의 오염으로부터 보호되어야 한다. 주 사제의 경우 적합한 담체의 예로는' 이에 한정되지는 않으나， 물， 에탄올, 폴리올 ( 예를 들어, 글리세를， 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜 등) , 이들의 흔 합물 및 /또는 식물유를 포함하는 용매 또는 분산매질일 수 있다。 보다 바람직하게 는 적합한 담체로는 행크스 용액, 링거 용액, 트리에탄을 아민이 함유된LRSC leucyl tRNA synthetase) functions as a key mediator of amino acid signaling to mTORCl. That is, LRS binds directly to Rag GTPase, an amino acid dependent signaling medium for mTORCl, and acts as a GTPase-act ivat mg protein (GAP) for Rag GTPase, thereby activating mTORCl. Leucyl tRNA synthetase (LRS) plays an important role in the activation of mTORCl derived from amino acids, so that LRS senses intracellular leucine concentrations and affects the activation of mTORCl derived from leucine. Rag protein belongs to Rag subfami ly of Ras smal l GTPase and there are four kinds of RagA, RagB, RagC and RagD, of which A and B are orthologs of yeast Gtrlp GTPase and C and D are East's Gtr2p ortholog. RagD combines with A or B to form a dimer and mediates mTORCl activity by amino acids. (Trends in Biochemi cal Sciences, 33: 565-568, 2008). Therefore, inhibiting the binding between LRS and RagD may inhibit the activation of mTORCl, which may have the effect of preventing or treating cancer. More specifically, the cancer is not limited thereto. Melanoma, leukemia, colorectal cancer, lung cancer, Liver cancer, stomach cancer, esophageal cancer, pancreatic cancer, gallbladder cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, cervical cancer, endometrial cancer, chorionic cancer, ovarian cancer, breast cancer, thyroid cancer, brain cancer, head and neck cancer, skin cancer, lymphoma, aplastic anemia And the like. Lymphomas include both Hodgkin's lymphoma and non-Hodgkin's lymphoma and include B-cell neoplasms such as Precursor B cel l neoplasm, and B-cell tumors (Precursor Hodgkin lymphoma such as T-cell and ΝΚ-cell neoplasia (T—Cell AND NK-CELL NEOPLASMS) and Hodgkin's lymphoma (Cl ass i cal Hodgkin lymphoma) lymphoma, Hodgkin di sease). According to one embodiment of the present invention, it was confirmed that the benzosulfonamide derivative of Formula 1 of the present invention may exhibit an effective therapeutic effect against cancer showing rapamycin resistance. The benzosulfone amide derivatives of Formula 1 showed an effect of inhibiting leucine-sensitive activity of LRS without affecting the enzymatic activity of LRS. The expression level of LRS was positively correlated with the activation of Rag GTPase and mTORCl in colorectal cancer tissues and cells. The benzosulfonamide derivative of Formula 1 of the present invention specifically binds to a position interacting with RagD in LRS and specifically inhibits the position of LRS as a lysosome, thereby inhibiting the activity of RagD GTPase and mTORCl, resulting in cancer It showed the effect of inhibiting growth. This effect is the same in cancer cells that are resistant to rapamycin. The benzosulfonamide derivative of Formula 1 of the present invention effectively prevents or treats cancers that exhibit resistance to rapamycin due to mTOR mutations. According to another embodiment of the present invention, treatment of the compound of the present invention in cells expressing mTOR mutations (L2427P) associated with epilepsy results in (i) hydrolysis of RagD GTP and lysosomal of LRS. The translocat ion was inhibited, and the activity of (ii) mTORCl was also inhibited. When the compound of the present invention was administered to an interstitial animal model, the number of epileptic seizures was significantly reduced compared to the control group. In particular, the compound of the present invention appears to have a very high blood-brain barrier (BBB) permeability and is highly likely to be developed as a prophylactic agent for brain diseases. The pharmaceutical composition according to the present invention may be formulated in various ways depending on the route of administration by methods known in the art together with pharmaceutically acceptable carriers. 'Pharmaceutically acceptable' is a non-toxic composition that is physiologically acceptable and, when administered to humans, does not inhibit the action of the active ingredient and usually does not cause gastrointestinal disorders, allergic reactions such as dizziness or similar reactions. Say The carriers include all kinds of solvents, dispersion media, oil-in-water or water-in-oil emulsions, aqueous compositions, liposomes, microbeads and hemp Microsomes are included. When parenterally administering a composition of the present invention, the composition of the present invention may be formulated according to methods known in the art in the form of injections, transdermal and nasal inhalants with suitable parenteral carriers. Injectables must be sterilized and protected from contamination of microorganisms such as bacteria and fungi. Examples of suitable carriers for injectables include, but are not limited to, solvents including water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycols), combinations thereof and / or vegetable oils. Or a dispersion medium. More preferably, suitable carriers include Hanks' solution, Ringer's solution, and triethane containing amines.
PBS(phosphate buf fered sal ine) 또는 주사용 멸균수, 10% 에탄올, 40% 프로필렌 글리콜 및 5¾ 덱스트로즈와 같은 등장 용액 등을 사용할 수 있다ᅳ 상기 주사제를 미생물 오염으로부터 보호하기 위해서는 파라밴， 클로로부탄을， 페놀， 소르빈산, 티메로살 등과 같은 다양한 항균제 및 항진균제를 추가로 포함할 수 있다. 또한, 상기 주사제는 대부분의 경우 당 또는 나트륨 클로라이드와 같은 등장화제를 추가 로 포함할 수 있다ᅳ 경피투여제의 경우 연고제， 크림제, 로션제， 겔제, 외용액제， 파스타제, 리 니멘트제, 에어를제 등의 형태가 포함된다. 상기에서 '경피투여'는 본 발명의 조성 물을 국소적으로 피부에 투여하여 조성물에 함유된 유효한 양의 활성성분이 피부 내로 전달되는 것을 의미한다, 예컨대, 본 발명의 조성물을 주사형 제형으로 제조 하여 이를 30 게이지의 가는 주사 바늘로 피부를 가볍게 단지 -(pr i ck)하거나 피부에 직접적으로 도포하는 방법으로 투여될 수 있다. 이들 제형은 제약 화학에 일반적으 로 공지된 처방서인 문헌 (Remington ' s Pharmaceut i cal Science , 15th Edi t ion , 1975 , Mack Publ i shing Company , East on, Pennsylvani a)에 기술되어 있다, 흡입투여제의 경우, 본 발명에 따른 조성물은 적합한 추진제, 예를 들면ᅳ 디 클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산 화탄소 또는 다른 적합한 기체를 사용하여， 가압 팩 또는 연무기로부터 에어로졸 스프레이 형태로 편리하게 전달할 수 있다. 가압 에어로졸의 경우， 투약 단위는 계 량된 양을 전달하는 밸브를 제공하여 결정할 수 있다. 예를 들면, 흡입기 또는 취 입기에 사용되는 젤라틴 캡슐 및 카트리지는 화합물 및 락토오즈 또는 전분과 같은 적합한 분말 기제의 분말 흔합물을 함유하도록 제형화할 수 있다, 그 밖의 약학적으로 허용되는 담체로는 다음의 문헌에 기재되어 있는 것을 참고로 할 수 있다 (Remington' s Pharmaceut i cal Sci ences , 19th ed,， Mack Publ i shing Company, Easton, PA, 1995) . 또한 본 발명에 따른 조성물은 하나 이상의 완충제 (예를 들어, 식염수 또는 PBS) , 카보하이트레이트 (예를 들어, 글루코스, 만노즈, 수크로즈 또는 텍스트란)， 항산화제 , 정균제 , 킬레이트화제 (예를 들어 , EDTA 또는 글루타치온)， 아쥬반트 (예 를 들어, 알루미늄 하이드록사이드)， 현탁제, 농후제 및 /또는 보존제를 추가로 포 함할 수 있다. 또한 본 발명의 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또 는 지연된 방출을 제공할 수 있도록 당업계에 공지된 방법을 사용하여 다양하게 제 형화될 수 있다ᅳ 본 발명의 조성물은 또한 암을 예방 또는 치료하는 효과가 있는 공지의 화합물과 병용하여 투여할 수 있다. 본 발명의 상기 '유효량'이란 개체에게 투여하였을 때， 암의 개선, 치료, 예 방, 검출 또는 진단 효과를 나타내는 양을 말하며， 상기'개체'란 동물, 바람직하게 는 포유동물, 특히 인간을 포함하는 동물일 수 있으며 , 동물에서 유래한 세포， 조 직， 기관 등일 수도 있다. 상기 개체는 치료가 필요한 환자 (pat ient ) 일 수 있다ᅳ 본 발명의 상기'치료'는 질환의 발생 또는 재발 억제, 증상의 완화, 질병의 직접 또는 간접적인 병리학적 결과의 감소, 질병 진행 속도의 감소， 질병 상태의 개선, 호전， 완화 또는 개선된 예후를 의미한다. 보다 구체적으로는， 본 발명의 상 기 '치료 '는 암의 증상을 개선시키는 것을 포괄적으로 지칭하고, 이는 이러한 질환 을 치유하거나， 실질적으로 예방하거나, 또는 상태를 개선시키는 것을 포함할 수 있으며， 암으로부터 비롯된 한 가지 증상 또는 대부분의 증상을 완화시키거나， 치 유하거나 예방하는 것을 포함하나， 이에 제한되는 것은 아니다. PBS (phosphate buf fered sal ine) or sterile water for injection, 10% ethanol, 40% propylene glycol, and isotonic solutions such as 5¾ dextrose can be used. Butane may further include various antibacterial and antifungal agents such as phenol, sorbic acid, thimerosal and the like. In addition, the injection may in most cases further include an isotonic agent, such as sugar or sodium chloride. ᅳ For transdermal administration, ointments, creams, lotions, gels, external preparations, pastas, liniments, Aerosols and the like. As used herein, 'transdermal administration' means a topical administration of a composition of the present invention to the skin to deliver an effective amount of the active ingredient contained in the composition into the skin, for example, to prepare a composition of the present invention in an injectable formulation. This can be administered by lightly applying the skin directly to the skin with a 30-gauge thin needle. These formulations are described in Remington's Pharmaceut i cal Science, 15th Edion, 1975, Mack Publ i Shing Company, East on, Pennsylvani a, a prescription commonly known in pharmaceutical chemistry. In the case of the composition according to the invention the aerosol from a pressurized pack or nebulizer, using a suitable propellant, for example ᅳ dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas It can be delivered conveniently in the form of a spray. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. For example, gelatin capsules and cartridges used in inhalers or inhalers may be used as compounds and lactose or starch. Formulations may be made to contain suitable powder based powder mixtures. Other pharmaceutically acceptable carriers may be referred to those described in Remington's Pharmaceut i cal Sciences, 19 th ed. ,, Mack Publ i shing Company, Easton, PA, 1995). The compositions according to the invention may also contain one or more buffers (eg saline or PBS), carbohydrates (eg glucose, mannose, sucrose or textane), antioxidants, bacteriostatic agents, chelating agents (eg For example, EDTA or glutathione), adjuvants (eg, aluminum hydroxide), suspending agents, thickening agents and / or preservatives may be further included. In addition, the compositions of the present invention may be variously formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. It can be administered in combination with a known compound which is effective in preventing or treating cancer. The term 'effective amount' of the present invention, when administered to an individual, refers to an amount that exhibits an effect of improving, treating, preventing, detecting, or diagnosing cancer, and the term 'individual' includes an animal, preferably a mammal, particularly a human. It may be an animal, cells, tissues, organs, etc. derived from the animal. The subject may be a patient in need of treatment. The 'treatment' of the present invention is intended to inhibit the occurrence or recurrence of a disease, alleviate symptoms, reduce direct or indirect pathological consequences of a disease, Reduced, improved, improved, alleviated or improved prognosis. More specifically, the term "treatment" of the present invention refers generically to ameliorating symptoms of cancer, which may include curing, substantially preventing, or ameliorating such a disease, It may include, but is not limited to, alleviating, healing or preventing one symptom resulting from, or most of the symptoms resulting from.
【유리한 효과】 Advantageous Effects
본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는 LRS와 RagD 간의 결합 을 저해하여 mTORCl의 활성화를 억제하는 효과가 매우 우수하므로, mTOR를 저해함 으로써 치료효과가 달성될 수 있는 암, 간질 , 염증질환， 면역질환, 당뇨, 비만， 호 흡기계 폐쇄성 질환, 섬유증， 품페병， 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질환, 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행성 질환, 심혈관계질환 및 기생충 감염증으로 이루어진 군에서 선택된 어느 한 질환의 예방 또는 치료제 개발에 매우 유용하게 활용될 수 있다. Benzenesulfonamide derivatives of Formula 1 according to the present invention inhibit the binding between LRS and RagD and thus inhibit the mTORCl activation, thereby inhibiting mTOR Cancer, epilepsy, inflammatory disease, immune disease, diabetes, obesity, respiratory obstructive disease, fibrosis, pamp disease, lysosomal storage di sease, Alzheimer's disease, Parkinson's disease and Huntington Neurodegenerative diseases such as diseases, cardiovascular diseases and parasitic infections can be very useful in the development of a prophylactic or therapeutic agent for any disease selected from the group consisting of parasitic infections.
【도면의 간단한 설명】 [Brief Description of Drawings]
도 1은 정상 세포주 FHC (colon normal epi thel i al cel l )에 대한 벤젠설폰아 미드 유도체의 세포독성을 농도별로 평가한 결과이다 (Rap : rapamycin, 5-FU: 5ᅳ f luoro uraci 1 ) .  1 shows the results of evaluating the cytotoxicity of benzenesulfonamide derivatives against concentration of the normal cell line FHC (colon normal epithel alcel) by concentration (Rap: rapamycin, 5-FU: 5 ᅳ f luoro uraci 1).
도 2는 여러 가지 암 세포에 대한 벤젠설폰아미드 유도체의 세포독성의 EC50 을 나타낸 도면이다.  Figure 2 shows the EC50 of cytotoxicity of benzenesulfonamide derivatives against various cancer cells.
도 3은 간질과 연관된 mTOR 돌연변이 (L2427P)를 발현하는 NIH3T3 세포에서 LRS를 결손시키거나 (도 3A) 또는 본 발명에 따른 화합물을 처리하였을 때 (도 3B) RagD GTP의 가수분해 및 LRS의 lysosomal translocat ion이 감소되는 것을 웨스턴 블롯을 통해 확인한 결과이다.  FIG. 3 shows the hydrolysis of RagD GTP and the lysosomal translocat of LRS when the LRS is deleted (FIG. 3A) or treated with a compound according to the invention (FIG. 3B) in NIH3T3 cells expressing an mTOR mutation associated with epilepsy (L2427P). Western blot confirmed that the ion is reduced.
도 4는 간질과 연관된 mTOR 돌연변이 (L2427P)를 발현하는 NIH3T3 세포에 본 발명에 따른 화합물을 처리하였을 때 niTORCl의 활성이 감소되는 것을 웨스턴 블롯 을 통해 확인한 결과 (도 4A)와 이를 정량화하여 그래프로 나타낸 것이다 (도 4B) . 도 5는 간질 동물모델에 본 발명에 따른 화합물, 라파마이신 또는 대조물질 을 투여한 후 간질성 발작의 발현 횟수를 측정한 결과이다.  Figure 4 shows that the NIH3T3 cells expressing mTOR mutations (L2427P) associated with epilepsy reduced the activity of niTORCl when treated with a compound according to the present invention by Western blot (FIG. 4A) and quantified it graphically (FIG. 4B). Figure 5 is a result of measuring the number of expression of interstitial seizures after administering a compound, rapamycin or a control according to the invention in an epileptic animal model.
도 6은 본 발명에 따른 화합물의 혈액-뇌 장벽 (BBB) 투과성을 in vitro Pion BBB-PAMPA assay ki t를 이용하여 분석한 결과이다.  6 is a result of analyzing the blood-brain barrier (BBB) permeability of the compound according to the present invention using an in vitro Pion BBB-PAMPA assay kit.
【발명의 실시를 위한 형태】 [Form for implementation of invention]
이하 본 발명을 상세히 설명한다,  Hereinafter, the present invention will be described in detail.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐， 본 발명의 내용이 하기 실 시예에 한정되는 것은 아니다.  However, the following examples are merely to illustrate the present invention, the content of the present invention is not limited to the following embodiments.
<실시예 1> <Example 1>
본 발명의 화합물의 제조 <실시예 1-1> N—시클로핵실 -4— (4ᅳ이소프로필 -2, 3-디메틸 -5-옥소—피라졸 -1- 일)벤젠설폰아미드의 제조 Preparation of Compounds of the Invention Example 1-1 Preparation of N—cyclonucleosil-4— (4 ᅳ isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
1. 4— (4-이소프로필— 2, 3-디메틸—5—옥소—피라졸 -1일)벤젠설포닐 클로라이드의 제조 1. Preparation of 4— (4-isopropyl— 2, 3-dimethyl—5—oxo-pyrazole-1day) benzenesulfonyl chloride
250ml 등근바닥 플라스크에 0°C에서 클로로설폰산 (43.3 mL, 651匪 ol)의 존 재 하에 4-이소프로필— 1,5—디메틸 -2—페닐피라졸론 (15 g, 65.1 瞧 ol)을 첨가한 후 72시간 동안 40°C에서 교반한다. 상온으로 식힌 후 생성물은 얼음물에 천천히 부어 주고 디클로로메탄 (100ml)를 첨가하여 추출하고 무수황산마그네슘을 사용하여 건 조시킨다, 상기와 같이 얻어진 1차 화합물을 실리카겔 컬럼 크로마토그래피 (100% 디클로로메탄)를 사용해 정제하면 53%의 수율로 노란색 고체인 4-(4—이소프로필- 2,3ᅳ디메틸— 5—옥소-피라졸—1일)벤젠설포닐 클로라이드 (ll„3g)를 얻을 수 있다„ To a 250 ml isometric flask add 4-isopropyl—1,5—dimethyl-2—phenylpyrazolone (15 g, 65.1 瞧 ol) in the presence of chlorosulfonic acid (43.3 mL, 651 μl) at 0 ° C. Then stirred at 40 ° C for 72 h. After cooling to room temperature, the product is slowly poured into iced water, extracted by adding dichloromethane (100 ml) and dried using anhydrous magnesium sulfate. The primary compound obtained as described above is subjected to silica gel column chromatography (100% dichloromethane). Purification using this yields 4- (4—isopropyl-2,3 ᅳ dimethyl—5—oxo-pyrazole—daily) benzenesulfonyl chloride (ll „3g) as a yellow solid in 53% yield.
2. N—시클로핵실— 4-(4—이소프로필— 2，3—디메틸 -5-옥소-피라졸ᅳ 1-일)벤젠설폰 아미드의 제조  2. Preparation of N—cyclonucleus—4- (4—isopropyl—2,3—dimethyl-5-oxo-pyrazolyl 1-yl) benzenesulfonamide
10ml 등근바닥 풀라스크에 디클로로메탄 (2ml) 중에서 피리딘 (216.50 nig, 2.737醒 ol) 존재 하에 시클로핵산아민 (91.53 mg, 0.547 mmol)과 상기 1의 결과물 4-(4—이소프로필 -2,3—디메틸 -5—옥소-피라졸—1일)벤젠설포닐 클로라이드 (150 mg, 0.456 mmol) 을 상온의 온도에서 약 3시간 반응시킨다. TLC (EA/HX=1) 를 이용하여 반응의 종결을 확인하고 진공펌프를 이용해 용매를 제거한 후 실리카겔 컬럼크로 마토그래피 (EA/HX=1)를 이용하여 정제한다ᅳ 추가적으로 디클로로메탄과 핵산 혹은 에틸에테르와 핵산을 사용하여 재결정해주면 50.66%의 수율로 밝은 하얀색 고체인 N-시클로핵실 -4-(4—이소프로필— 2,3—디메틸—5-옥소—피라졸 -1—일)벤젠설폰아미드 (209 .64 mg)를 수득하였다.  Cyclonucleic acid amine (91.53 mg, 0.547 mmol) and the resultant of 1 above 4- (4—isopropyl-2,3— in the presence of pyridine (216.50 nig, 2.737 μl) in dichloromethane (2 ml) in a 10 ml isometric bottom fulasque. Dimethyl-5-oxo-pyrazole-yl) benzenesulfonyl chloride (150 mg, 0.456 mmol) is reacted at room temperature for about 3 hours. Confirm the end of the reaction using TLC (EA / HX = 1), remove the solvent using a vacuum pump, and purify using silica gel column chromatography (EA / HX = 1). Recrystallization using ether and nucleic acid yields 50.66% yield of N-cyclonucleosil-4- (4—isopropyl— 2,3—dimethyl-5-oxo-pyrazole-1-yl) benzenesulfonamide as a light white solid. (209 .64 mg) was obtained.
ESI (m/z) 392 (MH+) 390 (MH-)  ESI (m / z) 392 (MH +) 390 (MH-)
<실시예 1-2> 에틸 4-[[4-(4-이소프로필— 2,3ᅳ디메틸— 5-옥소ᅳ피라졸 1-일)페 닐 ]설포닐아미노]벤조에이트의 제조 Example 1-2 Preparation of Ethyl 4-[[4- (4-isopropyl—2,3 ᅳ dimethyl—5-oxo-pyrazol 1-yl) phenyl] sulfonylamino] benzoate
에틸 4-아미노벤조에이트를 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다。  Using the ethyl 4-aminobenzoate as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 458 (MH+) 480 (MNa+) 456 (MH-)  ESI (m / z) 458 (MH +) 480 (MNa +) 456 (MH-)
<실시예 1-3> 4-(4-이소프로필ᅳ2 , 3-디메틸ᅳ 5-옥소-피라졸 -1-일) -N-페닐 -벤젠 설폰아미드의 제조 <Example 1-3> 4- (4-isopropyl'2, 3-dimethyl '5-oxo-pyrazol-1-yl) -N-phenyl-benzene Preparation of Sulfonamide
아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Aniline was used as the starting material and reacted in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 386 (MH+) 408 (MNa+) 384 (MH-)  ESI (m / z) 386 (MH +) 408 (MNa +) 384 (MH-)
<실시예 1-4> N-시클로핵실 -4— (4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1一 일) -N-메틸ᅳ벤젠설폰아미드의 제조 Example 1-4 Preparation of N-cyclonuxyl-4— (4-isopropyl-2,3-dimethyl-5-oxo-pyrazole-1 one day) —N-methyl ᅳ benzenesulfonamide
N-메틸시클로핵산아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다。  Using N-methylcyclonucleic acid amine as starting material, reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 406 (MH+) 428 (MNa+)  ESI (m / z) 406 (MH +) 428 (MNa +)
<실시예 1-5> N-(4-터트-부틸페닐) -4-(4—이소프로필 -2 , 3-디메틸— 5-옥소-피라 졸一 1-일)벤젠설폰아미드의 제조 Example 1-5 Preparation of N- (4-tert-butylphenyl) -4- (4—isopropyl-2,3-dimethyl—5-oxo-pyrazolyl 1-yl) benzenesulfonamide
4一 (터트—부틸)아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  4I (tert-butyl) aniline was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 442 (MH+) 440 (MH-)  ESI (m / z) 442 (MH +) 440 (MH-)
<실시예 1— 6> 4-(4—이소프로필— 2， 3-디메틸 -5—옥소-피라졸—1-일 ) -N-(4—메특시 페닐)벤젠설폰아미드의 제조 Example 1-6 Preparation of 4- (4—Isopropyl—2, 3-dimethyl-5—oxo-pyrazol—1-yl) -N- (4-methoxyphenyl) benzenesulfonamide
4-메특시아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다, (수율 81.3%)  Reaction was carried out in the same manner as in Example 1-1, using 4-methoxaniline as a starting material, to obtain the target compound (yield 81.3%).
ESI (m/z) 416 (MH+) 438 (MNa+) 414 (MH-); IH NMR (400 MHz, DMS0-d6) δ 9.95 (s, IH), 7.76 (d, 2H, J = 8.8 Hz), 7.52 (cl, 2H, 8.4 Hz), 그 01 (d, 2H, J = 8.8 Hz), 6.82 (d, 2H, J = 8.8 Hz), 3.67 (s, 3H), 2.93 (s, 3H), 2.79-2.68 (m, IH), 2.19 (s, 3H) , 1.17 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165.1, 156.9， 155.6, 139.3, 135.8, 130.5, 128.1， 123.7, 122.0, 144.7, 144.6, 55.5， 37.2, 23.9， 21.2, 11.2  ESI (m / z) 416 (MH <+>) 438 (MNa <+>) 414 (MH <+>); IH NMR (400 MHz, DMS0-d6) δ 9.95 (s, IH), 7.76 (d, 2H, J = 8.8 Hz), 7.52 (cl, 2H, 8.4 Hz), its 01 (d, 2H, J = 8.8 Hz), 6.82 (d, 2H, J = 8.8 Hz), 3.67 (s, 3H), 2.93 (s, 3H), 2.79-2.68 (m, IH), 2.19 (s, 3H), 1.17 (d, 6H , J = 6.8 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165.1, 156.9, 155.6, 139.3, 135.8, 130.5, 128.1, 123.7, 122.0, 144.7, 144.6, 55.5, 37.2, 23.9, 21.2, 11.2
<실시예 l-7> 4- (4-이소프로필 -2， 3—디메틸 -5-옥소-피라졸— 1-일) -N-(4—모폴리 노페닐)벤젠설폰아미드의 제조 Example l-7 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N- (4-morpholinophenyl) benzenesulfonamide
4-몰포리노아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 84.5%) ESI (m/z) 471 (MH+) 493 (MNa+) 469 (MH-)； 1H NMR (400 MHz, DMSO— d6) δ 9.94 (s, 1H), 7.78 (d, 2H, J = 8.4 Hz), 7.52 (d, 2H, J = 8.4 Hz), 6.98 (d, 2H, J = 8.4 Hz), 6.86 (d, 2H, J = 8.4 Hz), 3.70 (t, 4H, J = 4,2 Hz), 3.03 (s, 4H), 2。93 (s, 3H), 2.77-2.70 (m, IH) , 2.19 (s, 3H) , 1.17 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz , DMSO— d6) δ peak 165.1, 155.6, 148.1， 139.2, 136.0, 129.7, 128.1, 123.2, 122.0, 116.3, 114.6, 66.3, 49.1, 37.2, 23,9, 21.3, 11.3 Using the 4-morpholino aniline as a starting material was reacted in the same manner as in Example 1-1 to obtain the target compound. (Yield 84.5%) ESI (m / z) 471 (MH +) 493 (MNa +) 469 (MH −); 1 H NMR (400 MHz, DMSO—d 6) δ 9.94 (s, 1H), 7.78 (d, 2H, J = 8.4 Hz), 7.52 (d, 2H, J = 8.4 Hz), 6.98 (d, 2H, J = 8.4 Hz), 6.86 (d, 2H, J = 8.4 Hz), 3.70 (t, 4H, J = 4,2 Hz), 3.03 (s, 4H), 2 .93 (s, 3H), 2.77-2.70 (m, IH), 2.19 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO— d6) δ peak 165.1, 155.6, 148.1, 139.2, 136.0, 129.7, 128.1, 123.2, 122.0, 116.3, 114.6, 66.3, 49.1, 37.2, 23,9, 21.3, 11.3
<실시예 l-8> N- [ (3， 4-디메특시페닐)메틸] -4-(4-이소프로필 -2 , 3—디메틸 -5-옥 소-피라졸ᅳ 1-일)벤젠설폰아미드의 제조 Example l-8 N-[(3,4-dimethoxyphenyl) methyl] -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazolyl 1-yl) benzene Preparation of Sulfonamide
(3,4—디메특시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다, (수율 75.9%)  (3,4-dimethoxyphenyl) methanamine was used as a starting material to react with the same method as in Example 1-1 to obtain the target compound, (yield 75.9%).
ESI (m/z) 460 (MH+) 482 (MNa+) 458 (MH-); IH NMR (400 MHz, DMS0-d6) δ 8.10 (t, IH, J = 6.8 Hz), 7.83 (d, 2H, J = 8.4 Hz), 7.51 (d, 2H, J = 8.4 Hz), 6.81-6.72 (m, 3H) , 3.96 (d, 2H, J = 6.0Hz), 3.68 (s, 3H), 3ᅳ 65 (s, 3H), 2.96 (s, 3H), 2.81-2.70 (m, IH) , 2.22 (s, 3H) , 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165,1, 155.5, 148.8, 148,3, 138.9, 137,2, 130.0, 127.9, 122.0, 120.2, 114.5, 111,8, 111.7, 55.8, 55.7, 49.0, 46,5, 37.1, 23.9, 21.3, 11.2  ESI (m / z) 460 (MH <+>) 482 (MNa <+>) 458 (MH <+>); IH NMR (400 MHz, DMS0-d6) δ 8.10 (t, IH, J = 6.8 Hz), 7.83 (d, 2H, J = 8.4 Hz), 7.51 (d, 2H, J = 8.4 Hz), 6.81-6.72 (m, 3H), 3.96 (d, 2H, J = 6.0 Hz), 3.68 (s, 3H), 3 ° 65 (s, 3H), 2.96 (s, 3H), 2.81-2.70 (m, IH), 2.22 (s, 3 H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165,1, 155.5, 148.8, 148,3, 138.9, 137,2, 130.0, 127.9, 122.0, 120.2, 114.5, 111,8, 111.7, 55.8, 55.7, 49.0, 46,5, 37.1, 23.9, 21.3, 11.2
<실시예 l-9> N— [ 2_ ( 3 , 4-디메록시페닐)에틸]ᅳ 4- ( 4-이소프로필 -2， 3—디메틸— 5一 옥소-피라졸—1—일)벤젠설폰아미드의 제조 Example l-9 N— [2_ (3, 4-dimethoxyphenyl) ethyl] ᅳ 4- (4-isopropyl-2, 3—dimethyl— 5 one oxo-pyrazole—1-yl) benzenesulfon Preparation of Amides
2-(3，4-디메틸메록시페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1-1 과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。 (수율 94,7%)  Reaction was carried out in the same manner as in Example 1-1, using 2- (3,4-dimethylmethoxyphenyl) ethanamine as a starting material to obtain the target compound. (Yield 94,7%)
ESI (m/z) 474 (MH+) 496 (MNa+) 472 (MH-); IH NMR (400 MHz, DMS0-d6) δ 7.85 (d, 2H, J = 8.4 Hz), 7.70 (t, IH, J = 5.4 Hz), 7.56 (d, 2H, J = 8.4 Hz), 6.82 (d, IH, J = 8.0 Hz), 6.81 (s, IH) , 6.65 (d, IH, J = 8.4 Hz), 3,70 (cl, 6H, J = 5.6 Hz), 3.00-2.95 (m, 5H), 2.79-2.70 (m, IH), 2.62 (t, 2H, J = 7.4 Hz), 2.21 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO— d6) δ peak 165.2， 155.5, 148.9, 147.7, 139.0, 136.8, 131.4, 127.9, 122.2, 120.9, 114.5, 112.9， 112.2, 55.8, 55.7, 44.6, 37.1， 35.3, 23.9, 21.3, 11.2  ESI (m / z) 474 (MH <+>) 496 (MNa <+>) 472 (MH <->); IH NMR (400 MHz, DMS0-d6) δ 7.85 (d, 2H, J = 8.4 Hz), 7.70 (t, IH, J = 5.4 Hz), 7.56 (d, 2H, J = 8.4 Hz), 6.82 (d , IH, J = 8.0 Hz), 6.81 (s, IH), 6.65 (d, IH, J = 8.4 Hz), 3,70 (cl, 6H, J = 5.6 Hz), 3.00-2.95 (m, 5H) , 2.79-2.70 (m, IH), 2.62 (t, 2H, J = 7.4 Hz), 2.21 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO— d6) δ peak 165.2, 155.5, 148.9, 147.7, 139.0, 136.8, 131.4, 127.9, 122.2, 120.9, 114.5, 112.9, 112.2, 55.8, 55.7, 44.6, 37.1, 35.3, 23.9, 21.3, 11.2
<실시예 l-lO 4-(4-이소프로필 -2， 3-디메틸— 5-옥소-피라졸— 1—일) -N-[ (2-메록 시페닐)메틸]벤젠설폰아미드의 제조 <Example l-lO 4- (4-isopropyl-2, 3-dimethyl- 5-oxo-pyrazol- 1-yl) -N- [(2-merox Preparation of Ciphenyl) methyl] benzenesulfonamide
(2-메록시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다. (수율 86.9«  (2-Methoxyphenyl) methanamine was used as a starting material and reacted in the same manner as in Example 1-1, to obtain the target compound. (Yield 86.9 «
ESI (m/z) 430 (MH+) 452 (MNa+) 428 (MH-); 1H NMR (400 MHz, DMS0-d6) δ 7.99 (t, 1H, J = 6.2 Hz), 7.84 (d, 2H, J = 8.4 Hz), 7.52 (d, 2H, J = 8„4 Hz), 7.25-7.17 (m, 2H) , 6.89—6.84 (m, 2H), 3.97 (d, 2H, J = 6.0 Hz), 3.70 (s, 3H) , 2.97 (s, 3H), 2.81-2.71 (m, 1H) , 2.22 (s, 3H) , 1,20 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMS0_d6) δ peak 165.1, 156.8, 155.4, 138.9, 137.1 , 128.9, 128,98， 127.84, 125.4, 122.1, 120.3, 114.5, 110.7, 55.5, 49.0, 41.4, 37.1, 23.9, 21.3， 11.2  ESI (m / z) 430 (MH <+>) 452 (MNa <+>) 428 (MH <->); 1 H NMR (400 MHz, DMS0-d6) δ 7.99 (t, 1H, J = 6.2 Hz), 7.84 (d, 2H, J = 8.4 Hz), 7.52 (d, 2H, J = 8 „4 Hz), 7.25 -7.17 (m, 2H), 6.89-6.84 (m, 2H), 3.97 (d, 2H, J = 6.0 Hz), 3.70 (s, 3H), 2.97 (s, 3H), 2.81-2.71 (m, 1H ), 2.22 (s, 3H), 1,20 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMS0_d6) δ peak 165.1, 156.8, 155.4, 138.9, 137.1, 128.9, 128,98, 127.84, 125.4, 122.1, 120.3, 114.5, 110.7, 55.5, 49.0, 41.4, 37.1, 23.9, 21.3, 11.2
<실시예 1~11> 4-(4-이소프로필 -2 ,3-디메틸 -5ᅳ옥소-피라졸 -1-일) -N-(p-를릴 ) 벤젠설폰아미드의 제조 Examples 1 to 11 Preparation of 4- (4-isopropyl-2,3-dimethyl-53-oxo-pyrazol-1-yl) -N- (p-lryl) benzenesulfonamide
pᅳ를루이딘을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시 켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1 using pVerluidine as a starting material to obtain the target compound.
1H NMR (400 MHz, DMS0-d6) δ 7.83(d, 2H, J = 7.6 Hz), 7.62 (s, 1H) , 7.51 (d, 2H, J = 7.2 Hz), 6.99 (s, 4H), 2.93 (s, 3H) , 2.80-2.77 (m, 1H) , 2.25 (s, 3H), 2.19 (s, 3H), 1.27 (d, 6H, J = 6.4 Hz)  1 H NMR (400 MHz, DMS0-d6) δ 7.83 (d, 2H, J = 7.6 Hz), 7.62 (s, 1H), 7.51 (d, 2H, J = 7.2 Hz), 6.99 (s, 4H), 2.93 (s, 3H), 2.80-2.77 (m, 1H), 2.25 (s, 3H), 2.19 (s, 3H), 1.27 (d, 6H, J = 6.4 Hz)
<실시예 1-12> Nᅳ (4-클로로페닐 ) -4一(4-이소프로필 -2 , 3—디메틸 -5-옥소—피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-12 Preparation of N '(4-Chlorophenyl) -4i (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
4-클로로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다.  Using 4-chloroaniline as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
<실시예 1-13> 4-(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸-1ᅳ일 )ᅳ>卜[2-(2-메 록시페닐)에틸]벤젠설폰아미드의 제조 <Example 1-13> 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1 ᅳ yl) ᅳ> 卜 [2- (2- hydroxyphenyl) ethyl] benzenesulfonamide Produce
2-(2—메록시페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 55.5%)  Reaction was carried out in the same manner as in Example 1-1, using 2- (2-methoxyphenyl) ethanamine as a starting material, to obtain the target compound. (Yield 55.5%)
ESI (m/z) 444 (MH+) 466 (顾 a+) 442 (MH— )  ESI (m / z) 444 (MH +) 466 (顾 a +) 442 (MH—)
<실시예 1_14>4-(4-이소프로필 -2，3-디메틸-5-옥소ᅳ피라졸-1—일) -[2-(2-메 록시페녹시)에틸]벤젠설폰아미드의 제조 2- (2—메록시페녹시 )에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 92.4%) Example 1_1 4 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl)-[2- (2-hydroxyphenoxy) ethyl] benzenesulfonamide The target compound was obtained by reaction in the same manner as in Example 1-1 using 2- (2-methoxyphenoxy) ethanamine as a starting material. (Yield 92.4%)
ESI (m/z) 460 (MH+) 482 (MNa+)  ESI (m / z) 460 (MH +) 482 (MNa +)
<실시예 1-15> 4— (4-이소프로필 -2， 3ᅳ디메틸— 5—옥소-피라졸 -1-일)— N-(3-메특 시페닐)벤젠설폰아미드의 제조 Example 1-15 Preparation of 4— (4-isopropyl-2,3 ᅳ dimethyl—5—oxo-pyrazol-1-yl) —N- (3-methoxyphenyl) benzenesulfonamide
3—메록시아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다. (수율 86ᅳ9¾  3—Meroxyaniline was used as a starting material and reacted in the same manner as in Example 1-1, to obtain the target compound. (Yield 86 ᅳ 9¾
ESI (m/z) 416 (MH+) 438 (MNa+) 414 (MH-)  ESI (m / z) 416 (MH +) 438 (MNa +) 414 (MH-)
<실시예 1-16> 4ᅳ (4—이소프로필— 2， 3-디메틸 -5ᅳ옥소-피리-졸— 1_일)— N-(2-메톡 시페닐)벤젠설폰아미드의 제조 Example 1-16 Preparation of 4 '(4—Isopropyl— 2, 3-dimethyl-5 ᅳ oxo-pyri-sol—1_yl) —N- (2-methoxycyphenyl) benzenesulfonamide
2-메록시아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다. (수율 83ᅳ 3«  The reaction was carried out in the same manner as in Example 1-1, using 2-methoxyaniline as a starting material, to obtain the target compound. (Yield 83 ᅳ 3 «
ESI (m/z) 416 (MH+) 438 (MNa+) 414 (MH-)  ESI (m / z) 416 (MH +) 438 (MNa +) 414 (MH-)
<실시예 1-17> 4-(4-이소프로필 -2， 3—디메틸 -5—옥소-피라졸 -1-일 )-N— (3—페닐 프로필)벤젠설폰아미드의 제조 Example 1-17 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N— (3-phenylpropyl) benzenesulfonamide
3-페닐프로판 -1—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다。 (수율 62 , 6%)  Reaction was carried out in the same manner as in Example 1-1 using 3-phenylpropane-1-amine as a starting material to obtain the target compound. (Yield 62, 6%)
ESI (m/z) 428 (MH+) 450 (MNa+) 426 (MH-)  ESI (m / z) 428 (MH +) 450 (MNa +) 426 (MH-)
<실시예 1-18> 4— (4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1—일)— Nᅳ (3-니트 로페닐)벤젠설폰아미드의 제조 Example 1-18 4— (4-Isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1—yl) — Preparation of N ′ (3-nitrophenyl) benzenesulfonamide
3-니트로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다, (수율 73.0%)  Using 3-nitroaniline as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound (yield 73.0%).
ESI (m/z) 431 (MH+) 453 (MNa+) 429 (MH-)  ESI (m / z) 431 (MH +) 453 (MNa +) 429 (MH-)
<실시예 1_19> 4-(4-이소프로필 -2，3-디메틸—5-옥소-피라졸—1ᅳ일)—^(4-니트 로페닐)벤젠설폰아미드의 제조 <Example 1_19> Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-l ᅳ yl)-^ (4-nitrophenyl) benzenesulfonamide
4-니트로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다. (수율 72.9%) ESI (m/z) 431 (MH+) 453 (丽 a+) 429 (MH-) The reaction was carried out in the same manner as in Example 1-1, using 4-nitroaniline as a starting material, to obtain the target compound. (Yield 72.9%) ESI (m / z) 431 (MH +) 453 (丽 a +) 429 (MH-)
<실시예 l-20> 4-(4ᅳ이소프로필— 2， 3-디메틸 -5-옥소—피라졸 -1—일 )— N-(2-페닐 에틸)벤젠설폰아미드의 제조 Example l-20 Preparation of 4- (4 ᅳ isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N- (2-phenylethyl) benzenesulfonamide
2-페닐에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2-phenylethanamine as a starting material, to obtain the target compound.
ESI (m/z) 414 (MH+) 436 (MNa+) 412 (MH-)  ESI (m / z) 414 (MH +) 436 (MNa +) 412 (MH-)
<실시예 1-21> 4-(4ᅳ이소프로필—2， 3-디메틸ᅳ 5-옥소ᅳ피라졸 -1-일) -Nᅳ (4-페닐 부털)벤젠설폰아미드의 제조 Example 1-21 Preparation of 4- (4'isopropyl—2,3-dimethyl'5-oxo'pyrazol-1-yl) -N '(4-phenylbutyrate) benzenesulfonamide
4-페닐부탄ᅳ 1-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  The reaction mixture was reacted in the same manner as in Example 1-1, using 4-phenylbutanyl 1-amine as a starting material to obtain a target compound.
ESI (m/z) 442 (MH+) 464 (MNa+) 440 (MH— )  ESI (m / z) 442 (MH +) 464 (MNa +) 440 (MH—)
<실시예 1-22> 4-(4ᅳ이소프로필 -2， 3-디메틸—5ᅳ옥소-피라졸 -1-일) (5-퀴놀 릴)벤젠설폰아미드의 제조 Example 1-22 Preparation of 4- (4 ᅳ isopropyl-2, 3-dimethyl--5 ᅳ oxo-pyrazol-1-yl) (5-quinolyl) benzenesulfonamide
퀴놀린—5—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1 using quinolin-5-amine as a starting material to obtain the target compound.
ESI (m/z) 437 (MH+) 459 (MNa+) 435 (MH— )  ESI (m / z) 437 (MH +) 459 (MNa +) 435 (MH—)
<실시예 1-23> 4-(4-이소프로필 -2 , 3-디메틸-5-옥소-피라졸—1—일)—11-(3—퀴놀 릴)벤젠설폰아미드의 제조 Example 1-23 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol—1—yl) —11- (3-quinolyl) benzenesulfonamide
퀴놀린 -3-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다ᅳ  Reaction was carried out in the same manner as in Example 1-1 using quinolin-3-amine as a starting material to obtain the target compound.
ESI (m/z) 437 (MH+) 459 (丽 a+) 435 (MH-)  ESI (m / z) 437 (MH +) 459 (丽 a +) 435 (MH-)
<실시예 1-24> N— (4-플루오로페닐)— 4- (4-이소프로필 -2， 3-디메틸ᅳ 5-옥소-피라 졸 -1—일)벤젠설폰아미드의 제조 Example 1-24 Preparation of N— (4-fluorophenyl) —4- (4-isopropyl-2,3-dimethyl ᅳ 5-oxo-pyrazol-1-yl) benzenesulfonamide
4-플루오로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다, Using 4-fluoroaniline as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound .
ESI (m/z) 404 (MH+) 402 (MH-) <실시예 l-25>터트-부틸 4- [ [4-(4-이소프로필— 2 , 3-디메틸 -5-옥소—피라졸 -1ᅳ 일 )페닐]설포닐아미노]피페리딘 -1-카르복실레이트의 제조 ESI (m / z) 404 (MH +) 402 (MH-) Example l-25 Tert-Butyl 4- [[4- (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazol-1xyl) phenyl] sulfonylamino] piperidine-1 Preparation of Carboxylate
터트 -부틸 4—아미노피페리딘— 1-카르복실레이트를 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Tert-Butyl 4-Aminopiperidine— Using 1-carboxylate as a starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 493 (MH+) 491 (MH-)  ESI (m / z) 493 (MH +) 491 (MH-)
<실시예 1-26> N- [2-(4-클로로페닐)에틸 ] -4-(4—이소프로필ᅳ 2，3_디메틸 -5—옥 소-피라졸— 1-일)벤젠설폰아미드의 제조 Example 1-26 N- [2- (4-chlorophenyl) ethyl] -4- (4—isopropyl 이 2,3_dimethyl-5—oxo-pyrazol— 1-yl) benzenesulfonamide Manufacture
2一 (4-클로로페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  The reaction product was reacted in the same manner as in Example 1-1 using 2 一 (4-chlorophenyl) ethanamine as a starting material to obtain the target compound.
ESI (m/z) 448 (MH+) 446 (MH-)  ESI (m / z) 448 (MH +) 446 (MH-)
<실시예 1-27〉 4-(4-이소프로필 -2 , 3-디메틸ᅳ 5-옥소ᅳ피라졸 -1—일)— N— (2-티에 닐메틸)벤젠설폰아미드의 제조 Example 1-27 Preparation of 4- (4-isopropyl-2,3-dimethyl ᅳ 5-oxo-pyrazol-1-yl) —N— (2-thienylmethyl) benzenesulfonamide
티오펜—2-일메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법 . 로 반웅시켜 목적 화합물을 수득하였다.  The same method as Example 1-1, using thiophene-2-ylmethanamine as starting material. Reaction to give the desired compound.
ESI (m/z) 406 (MH+) 428 (MNa+) 404 (MH-)  ESI (m / z) 406 (MH +) 428 (MNa +) 404 (MH-)
<실시예 1-28〉 4-(4-이소프로필 -2， 3-디메틸 -5—옥소-피라졸— 1-일 )-N— (3-피리 딜메틸)벤젠설폰아미드의 제조 Example 1-28 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol— 1-yl) -N— (3-pyridylmethyl) benzenesulfonamide
피리딘—3—일메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  Using pyridine-3 ylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 401 (MH+) 423 (MNa+) 399 (MH-)  ESI (m / z) 401 (MH +) 423 (MNa +) 399 (MH-)
<실시예 1-29> 4— ( 4-이소프로필 -2 , 3-디메틸 -5—옥소-피라졸- 1-일) -N— [ 2- ( 2-피 리딜)에틸]벤젠설폰아미드의 제조 Example 1-29 4— (4-Isopropyl-2, 3-dimethyl-5—oxo-pyrazol-1-yl) -N— [2- (2-pyridyl) ethyl] benzenesulfonamide Produce
2- (피리딘 -2-일)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  Using the 2- (pyridin-2-yl) ethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 415 (MH+) 437 (丽 a+) 413 (MH— )  ESI (m / z) 415 (MH +) 437 (丽 a +) 413 (MH—)
<실시예 1ᅳ30> 4— (4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸 -1-일)— N— (2-나프 틸메틸)벤젠설폰아미드의 제조 나프탈렌ᅳ 2-일메탄아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법 으로 반응시켜 목적 화합물을 수득하였다. Example 1-30 The preparation of 4— (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) —N— (2-naphthylmethyl) benzenesulfonamide The reaction compound was reacted in the same manner as in Example 1-1 using naphthalene # 2-ylmethanamine as a starting material to obtain a target compound.
ESI (m/z) 450 (MH+) 472 (MNa+) 448 (MH-)  ESI (m / z) 450 (MH +) 472 (MNa +) 448 (MH-)
<실시예 1-31> N— [2-(3-플루오로페닐)에틸 ] -4— (4-이소프로필 -2， :3-디메틸 -5- 옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-31 N— [2- (3-fluorophenyl) ethyl] -4— (4-isopropyl-2,: 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfon Preparation of Amides
2-(3—플루오로페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2- (3-fluorophenyl) ethanamine as a starting material to obtain the target compound.
ESI (m/z) 432 (MH+) 454 (MNa+) 430 (MH-)  ESI (m / z) 432 (MH +) 454 (MNa +) 430 (MH-)
<실시예 1-32> N-(5-플루오로— 2-피리딜)— 4-(4-이소프로필 -2 , 3-디메틸ᅳ 5-옥소 -피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1-32 Preparation of N- (5-fluoro- 2-pyridyl)-4- (4-isopropyl-2, 3-dimethyl 3- 5-oxo-pyrazol-1xyl) benzenesulfonamide
5一플루오로피리딘ᅳ 2—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다.  The reaction mixture was prepared in the same manner as in Example 1-1, using 5 ilfluoropyridin ᅳ 2-amine as a starting material, to obtain the target compound.
ESI (m/z) 405 (MH+) 427 (MNa+) 403 (MH— )  ESI (m / z) 405 (MH +) 427 (MNa +) 403 (MH—)
<실시예 1-33> 4-(4-이소프로필— 2 , 3-디메틸 -5—옥소-피라졸— 1-일 )—Nᅳ [ (4—메록 시페닐)메틸]벤젠설폰아미드의 제조 Example 1-33 Preparation of 4- (4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazol— 1-yl) —N ′ [(4—methoxyphenyl) methyl] benzenesulfonamide
(4-메록시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다.  (4-Methoxyphenyl) methanamine was used as a starting material to react in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 430 (MH+) 452 (MNa+) 428 (MH-)  ESI (m / z) 430 (MH +) 452 (MNa +) 428 (MH-)
<실시예 1ᅳ 34> 4-(4-이소프로필ᅳ2， 3-디메 ¾ -5—옥소-피라졸 -1—일)— N— (6—퀴놀 릴)벤젠설폰아미드의 제조 Example 1-34 Preparation of 4- (4-isopropyl ᅳ 2, 3-dimethy-3--5-oxo-pyrazol-1-yl) -N— (6-quinolyl) benzenesulfonamide
퀴놀린ᅳ 6-아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다.  The reaction was carried out in the same manner as in Example 1-1, using Quinolin ᅳ 6-amine as a starting material, to obtain the target compound.
ESI (m/z) 437 (MH+) 459 (MNa+) 435 (MH-)  ESI (m / z) 437 (MH +) 459 (MNa +) 435 (MH-)
<실시예 1-35> N-(2 , 3-디히드로 -1 , 4ᅳ벤조디옥신 -6—일) -4ᅳ (4-이소프로필 -2， 3- 디메틸 -5-옥소-피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1-35 N- (2, 3-dihydro-1, 4'benzodioxine-6-yl) -4 '(4-isopropyl-2, 3-dimethyl-5-oxo-pyrazole -1 ᅳ yl) benzenesulfonamide
2 , 3-디히드로— 1 , 4-벤조디옥신 -6ᅳ아민을 출발물질로 사용하여 상기 실시예 1- 1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다, ESI (m/z) 444 (MH+) 466 (MNa+) 442 (MHᅳ) 2, 3-dihydro— 1, 4-benzodioxine-6 ᅳ amine was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound. ESI (m / z) 444 (MH +) 466 (MNa +) 442 (MH ᅳ)
<실시예 l-36> N- - (디메틸아미노)페닐 ] -4-(4-이소프로필 -2， 3—디메릴ᅳ 5-옥 소-피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example l-36 Preparation of N--(dimethylamino) phenyl] -4- (4-isopropyl-2,3-dimeryl ᅳ 5-oxo-pyrazol-1xyl) benzenesulfonamide
N , N-디메틸벤젠— 1， 4-디아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  N, N-dimethylbenzene—1,4-diamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 429 (MH+) 451 (MNa+) 427 (MH-)  ESI (m / z) 429 (MH +) 451 (MNa +) 427 (MH-)
<실시예 1-37>메틸 3-[ [4-(4-이소프로필 -2，3-디메틸 -5-옥소-피라졸 -1-일)페 닐 ]설포닐아미노]벤조에이트의 제조 Example 1-37 Preparation of Methyl 3- [[4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] benzoate
메틸 3—아미노벤조에이트를 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  The desired compound was obtained by reaction in the same manner as in Example 1-1, using methyl 3-aminobenzoate as starting material.
ESI (m/z) 444 (MH+) 466 (MNa+) 442 (MH-)  ESI (m / z) 444 (MH +) 466 (MNa +) 442 (MH-)
<실시예 1— 38>에틸 3— [ [4-(4-이소프로필— 2，3—디메틸 -5-옥소-피라졸 -1—일)페 닐]설포닐아미노]벤조에이트의 제조 Example 1 38 Preparation of ethyl 3 — [[4- (4-isopropyl—2,3—dimethyl-5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] benzoate
에틸 3-아미노벤조에이트를 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다.  Using ethyl 3-aminobenzoate as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 458 (MH+) 480 (MNa+) 456 (MH— )  ESI (m / z) 458 (MH +) 480 (MNa +) 456 (MH—)
<실시예 1—39> 4- ( 4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸 -1-일)— N- [ 3— (트리 풀루오로메틸)페닐]벤젠설폰아미드의 제조 Example 1—39 4- (4-isopropyl—2,3-dimethyl-5—oxo—pyrazol-1-yl) —N— [3— (tri pullouromethyl) phenyl] benzenesulfonamide Manufacture
3- (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1ᅳ1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  3- (trifluoromethyl) aniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 454 (MH+) 476 (MNa+) 452 (MH-)  ESI (m / z) 454 (MH +) 476 (MNa +) 452 (MH-)
<실시예 1-40> N- [2ᅳ (4-플루오로페닐)에틸] -4-(4-이소프로필 -2 , 3-디메틸 -5- 옥소—피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-40 N- [2 ′ (4-fluorophenyl) ethyl] -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Manufacture
2-(4-플루오로페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2- (4-fluorophenyl) ethanamine as a starting material, to obtain the target compound.
ESI (m/z) 432 (MH+) 454 (MNa+) 430 (MH-) <실시예 1-41> 4-(4-이소프로필 -2，3-디메틸-5-옥소—피라졸-1ᅳ일>ᅦ-(4-이소 프로필페닐)벤젠설폰아미드의 제조 ESI (m / z) 432 (MH +) 454 (MNa +) 430 (MH-) Example 1-41 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1xyl>-(4-isopropylphenyl) benzenesulfonamide
4-이소프로필아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으 로 반응시켜 목적 화합물을 수득하였다.  4-isopropylaniline was used as a starting material and reacted in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 428 (MH+) 450 (MNa+) 426 (MHᅳ)  ESI (m / z) 428 (MH +) 450 (MNa +) 426 (MH ᅳ)
<실시예 1-42> N-(3ᅳ플루오로페닐 ) -4- (4-이소프로필 -2， 3-디메틸 -5—옥소-피라 졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1-42 Preparation of N- (3'fluorophenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1xyl) benzenesulfonamide
3-플루오로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  3-fluoroaniline was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 404 (MH+) 426 (丽 a+) 402 (MH-)  ESI (m / z) 404 (MH +) 426 (丽 a +) 402 (MH-)
<실시예 1- 3> Nᅳ (3—플루오로페닐 )ᅳ 4- (4-이소프로필 -2 , 3—디메틸 -5—옥소-피라 졸 -1—일) -N-메틸 -벤젠설폰아미드의 제조 Example 1-3 N '(3—Fluorophenyl)' 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N-methyl-benzenesulfonamide Manufacture
3-플루오로 -N-메틸아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  3-fluoro-N-methylaniline was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 418 (MH+)  ESI (m / z) 418 (MH +)
<실시예 1-44> 4— (4-이소프로필 -2 , 3-디메틸—5-옥소-피라졸 -1-일) -N—( lᅳ나프 틸)벤젠설폰아미드의 제조 Example 1-44 Preparation of 4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N— (l-naphthyl) benzenesulfonamide
나프탈렌— 1-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Naphthalene— 1-amine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 436 (MH+) 458 (MNa+) 434 (MH—)  ESI (m / z) 436 (MH +) 458 (MNa +) 434 (MH—)
<실시예 1-45> 4-(4-이소프로필— 2 , 3-디메틸 -5-옥소-피라졸ᅳ1ᅳ일) -N- [ (3-메특 시페닐)메틸]벤젠설폰아미드의 제조 Example 1-45 Preparation of 4- (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazol ᅳ ylyl) -N-[(3-methoxyphenyl) methyl] benzenesulfonamide
(3一메록시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다,  Using (3 methoxyphenyl) methanamine as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 430 (MH+) 452 (丽 a+) 428 (MH— )  ESI (m / z) 430 (MH +) 452 (丽 a +) 428 (MH—)
<실시예 1-46> N— [ (3-플루오로페닐)메틸]—4-(4-이소프로필 -2 , 3—디메틸 -5-옥 소-피라졸 -1-일)벤젠설폰아미드의 제조 (3-플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. Example 1-46 N — [(3-fluorophenyl) methyl] —4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Produce (3-fluorophenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 418 (MH+) 440 (MNa+) 416 (MH-)  ESI (m / z) 418 (MH +) 440 (MNa +) 416 (MH-)
<실시예 1-47> 4-(4-이소프로필— 2， 3—디메틸ᅳ 5-옥소-피라졸ᅳ 1ᅳ일) -N- (테트라 히드로퓨란 -2-일메틸)벤젠설폰아미드의 제조 Example 1-47 Preparation of 4- (4-isopropyl-2,3-dimethyl-3-5-oxo-pyrazol-1-yl) yl-N- (tetra hydrofuran-2-ylmethyl) benzenesulfonamide
(테트라히드로퓨란 -2-일)메탄아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  (Tetrahydrofuran-2-yl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 394 (MH+) 416 (MNa+) 392 (MH-)  ESI (m / z) 394 (MH +) 416 (MNa +) 392 (MH-)
<실시예 1-48> N- [2-(2-퓨릴메틸설파닐)에틸] -4ᅳ (4—이소프로필 -2，3-디메틸- 5-옥소—피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-48 N- [2- (2-furylmethylsulfanyl) ethyl] -4 '(4—isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfon Preparation of Amides
2- ( (퓨란 -2-일메틸)티오)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  Reaction was carried out in the same manner as in Example 1-1, using 2-((furan-2-ylmethyl) thio) ethanamine as a starting material to obtain the target compound.
ESI (m/z) 450 (MH+) 472 (MNa+) 448 (MH— )  ESI (m / z) 450 (MH +) 472 (MNa +) 448 (MH—)
<실시예 1-49> 4— (4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸 일 )— N— 1.2_(Pᅳ틀 릴)에틸]벤젠설폰아미드의 제조 Example 1-49 4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazolyl) —N— 1 . Preparation of 2_ ( P phenyl) ethyl] benzenesulfonamide
2-(p-를릴)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2- (p-lryl) ethanamine as a starting material to obtain a target compound.
ESI (m/z) 428 (MH+) 450 (丽 a+) 426 (MH-)  ESI (m / z) 428 (MH +) 450 (丽 a +) 426 (MH-)
<실시예 1-50> 4-(4-이소프로필 -2 , 3-디메틸-5—옥소—피라졸ᅳ1ᅳ일)ᅳ1^-(4—메톡 시페닐)— N-메틸—벤젠설폰아미드의 제조 <Example 1-50> 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol ᅳ 1-yl) ᅳ 1 ^-(4- methoxy ciphenyl)-N-methyl- benzenesulfonamide Manufacture
4ᅳ메록시 메틸아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  4′Methoxy methylaniline was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 430 (MH+) 452 (MNa+)  ESI (m / z) 430 (MH +) 452 (MNa +)
<실시예 1-51> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소—피라졸 -1—일) [2— (4-메 톡시페닐)에틸]벤젠설폰아미드의 제조 Example 1-51 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) [2— (4-methoxyphenyl) ethyl] benzenesulfonamide
2-(4—메록시페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. ESI (m/z) 444 (MH+) 466 (MNa+) 442 (MH-) Reaction was carried out in the same manner as in Example 1-1, using 2- (4-methoxyphenyl) ethanamine as a starting material, to obtain the target compound. ESI (m / z) 444 (MH +) 466 (MNa +) 442 (MH-)
<실시예 i-52> N- [ (2-클로로페닐 )메틸] -4-(4-이소프로필 -2 , 3-디메틸— 5-옥소— 피라졸 -1-일)벤젠설폰아미드의 제조 Example i-52 Preparation of N-[(2-chlorophenyl) methyl] -4- (4-isopropyl-2,3-dimethyl- 5-oxo-pyrazol-1-yl) benzenesulfonamide
(2-클로로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  (2-Chlorophenyl) methanamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 434 (MH+) 456 (MNa+) 432 (MH— )  ESI (m / z) 434 (MH +) 456 (MNa +) 432 (MH—)
<실시예 ι-53> N-(2-플루오로페닐 ) -4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라 졸 -1-일)벤젠설폰아미드의 제조 Example ι-53 Preparation of N- (2-fluorophenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
2-플루오로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2-fluoroaniline as a starting material, to obtain the desired compound.
ESI (m/z) 404 (MH+) 426 (MNa+) 402 (MHᅳ)  ESI (m / z) 404 (MH +) 426 (MNa +) 402 (MH ᅳ)
<실시예 1-54> N- [ (2-플루오로페닐 )메틸 ] -4ᅳ(4—이소프로필— 2， 3—디메털— 5—옥 소-피라졸— 1-일)벤젠설폰아미드의 제조 Example 1-54 N-[(2-fluorophenyl) methyl] -4 '(4—isopropyl— 2, 3—dimetallic— 5—oxo-pyrazole— 1-yl) benzenesulfonamide Manufacture
(2—플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다,  (2—fluorophenyl) methanamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 418 (MH+) 416 (MH-)  ESI (m / z) 418 (MH +) 416 (MH-)
<실시예 1-55> 4ᅳ (4-이소프로필— 2， 3-디메틸 -5—옥소-피라졸ᅳ1ᅳ일 )— N-(p—롤릴 메틸)벤젠설폰아미드의 제조 Example 1-55 Preparation of 4 '(4-isopropyl— 2, 3-dimethyl-5—oxo-pyrazol ᅳ 1-yl) — N- (p-rollyl methyl) benzenesulfonamide
P一를릴메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다, Reaction was carried out in the same manner as in Example 1-1 using Pylylmethanamine as a starting material to obtain a target compound .
ESI (m/z) 414 (MH+) 436 (MNa+) 412 (MH-)  ESI (m / z) 414 (MH +) 436 (MNa +) 412 (MH-)
<실시예 1_56> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소—피리ᅳ졸ᅳ 1_일) -N-(m-롤릴 메틸)벤젠설폰아미드의 제조 <Example 1_56> Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyridoxazol 1_yl) -N- (m-rollyl methyl) benzenesulfonamide
m—를릴메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다.  The reaction was carried out in the same manner as in Example 1-1, using m-rrylmethanamine as a starting material, to obtain a target compound.
ESI (m/z) 414 (MH+) 436 (MNa+) 412 (MH-) <실시예 1-57> Ν-(2 , 5-디메틸페닐 )— 4-(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라 졸 -1—일)벤젠설폰아미드의 제조 ESI (m / z) 414 (MH +) 436 (MNa +) 412 (MH-) Example 1-57 Preparation of N- (2,5-dimethylphenyl) —4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
2 , 5—디메틸아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다ᅳ  2, 5—dimethylaniline was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 414 (MH+) 436 (MNa+) 412 (MH— )  ESI (m / z) 414 (MH +) 436 (MNa +) 412 (MH—)
<실시예 1-58> 4-(4-이소프로필 -2 , 3ᅳ디메틸— 5-옥소-피라졸— 1-일 ) -Nᅳ (mᅳ를릴 ) 벤젠설폰아미드의 제조 Example 1-58 Preparation of 4- (4-isopropyl-2,3'dimethyl- 5-oxo-pyrazol- 1-yl) -N '(m'ryl) benzenesulfonamide
m一를루이딘을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시 켜 목적 화합물을 수득하였다.  The reaction mixture was reacted in the same manner as in Example 1-1 using mylruidine as a starting material to obtain a target compound.
ESI (m/z) 400 (MH+) 422 (MNa+) 398 (MH— )  ESI (m / z) 400 (MH +) 422 (MNa +) 398 (MH—)
<실시예 1-59> 4-(4—이소프로필 -2， 3ᅳ디메틸 -5ᅳ옥소-피라졸 -1—일 )— N- (으를릴 ) 벤젠설폰아미드의 제조 Example 1-59 Preparation of 4- (4—Isopropyl-2,3 ᅳ dimethyl-5 ᅳ oxo-pyrazol-1—yl) —N- (sallyl) benzenesulfonamide
0-를루이딘을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법으로 반웅시 켜 목적 화합물을 수득하였다.  The reaction mixture was reacted in the same manner as in Example 1-1, using 0-erluidine as a starting material, to obtain a target compound.
ESI (m/z) 400 (MH+) 422 (丽 a+) 398 (MH— )  ESI (m / z) 400 (MH +) 422 (丽 a +) 398 (MH—)
<실시예 1ᅳ 60> N-(4-시아노페닐 )— 4— (4-이소프로필 -2 , 3—디메틸 -5-옥소-피라졸 ᅳ 1-일)벤젠설폰아미드의 제조 Example 1-60 Preparation of N- (4-cyanophenyl)-4— (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol X 1-yl) benzenesulfonamide
4-아미노벤조니트릴을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법으 로 반응시켜 목적 화합물을 수득하였다。  Using 4-aminobenzonitrile as a starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 411 (MH+) 433 (MNa+) 409 (MH-)  ESI (m / z) 411 (MH +) 433 (MNa +) 409 (MH-)
<실시예 1-61> 4- (4—이소프로필 -2 , 3—디메틸 -5ᅳ옥소-피라졸 -1—일)— N— [2ᅳ (트리 플루오로메틸)페닐]벤젠설폰아미드의 제조 Example 1-61 4- (4—Isopropyl-2,3—dimethyl-5 ”oxo-pyrazol-1—yl) —N— of [2 ′ (trifluoromethyl) phenyl] benzenesulfonamide Produce
2- (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2- (trifluoromethyl) aniline as a starting material, to obtain the target compound.
ESI (m/z) 454 (MH+) 476 (丽 a+) 452 (MH-)  ESI (m / z) 454 (MH +) 476 (丽 a +) 452 (MH-)
<실시예 1-62> N- ( 2， 4-디메틸페닐) -4- ( 4-이소프로필 -2 , 3-디메틸 -5-옥소—피라 졸 -1-일)벤젠설폰아미드의 제조 2 ,4—디메틸아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. <Example 1-62> N- (2, 4-dimethylphenyl) -4 - Preparation of (4-isopropyl-2, 3-dimethyl-5-oxo-1-yl) benzenesulfonamide 2,4—dimethylaniline was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 414 (MH+) 436 (MNa+) 412 (MH-)  ESI (m / z) 414 (MH +) 436 (MNa +) 412 (MH-)
<실시예 1-63> 4-(4-이소프로필 -2 ,3-디메틸 -5—옥소-피라졸 -1—일 )_N-(6—메톡 시 -3-피리딜)벤젠설폰아미드의 제조 Example 1-63 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) _N- (6-methoxyoxy-3-pyridyl) benzenesulfonamide
6-메특시피리딘 -3—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다,  Using the 6-methoxypyridin-3-amine as a starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 417 (MH+) 439 (MNa+) 415 (MH-) .  ESI (m / z) 417 (MH <+>) 439 (MNa <+>) 415 (MH <->).
<실시예 1-64> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸— 1-일 ) -N— (p—를릴) 벤젠설폰아미드의 제조 Example 1-64 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) -N— (p-lryl) benzenesulfonamide
P-톨루이딘을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반응시 켜 목적 화합물을 수득하였다.  Using the P- toluidine as a starting material it was reacted in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 400 (MH+) 422 (MNa+) 398 (MH— )  ESI (m / z) 400 (MH +) 422 (MNa +) 398 (MH—)
<실시예 1— 65> N-C2 , 2-디메틸프로필) -4-(4ᅳ이소프로필— 2 , 3-디메틸 -5—옥소—피 라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1 65 Preparation of N-C2, 2-dimethylpropyl) -4- (4 ᅳ isopropyl-2, 3-dimethyl-5-oxo-pyrazole-1xyl) benzenesulfonamide
2 , 2-디메틸프로판 -1-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  2, 2-dimethylpropane-1-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 380 (MH+) 402 (MNa+) 378 (MHᅳ)  ESI (m / z) 380 (MH +) 402 (MNa +) 378 (MH ᅳ)
<실시예 1-66> 4ᅳ(4-이소프로필 -2 , 3—디메틸 -5-옥소-피라졸ᅳ1_일 ) -N-(2—피리 딜메틸)벤젠설폰아미드의 제조 Example 1-66 Preparation of 4 '(4-isopropyl-2,3-dimethyl-5-oxo-pyrazol_l_yl) -N- (2-pyridylmethyl) benzenesulfonamide
피리딘—2—일메탄아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  Using pyridine-2 ylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 401 (MH+) 423 (顧 a+) 399 (MH— )  ESI (m / z) 401 (MH +) 423 (顧 a +) 399 (MH—)
<실시예 1-67> 4ᅳ(4-이소프로필 -2 ,3-디메틸-5-옥소—피라졸-1-일)— (2-피리 딜)벤젠설폰아미드의 제조 Example 1-67 Preparation of 4 '(4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) — (2-pyridyl) benzenesulfonamide
피리딘 -2-아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다. ESI (m/z) 387 (MH+) 409 (MNa+) 385 (MH-) Using pyridine-2-amine as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound. ESI (m / z) 387 (MH +) 409 (MNa +) 385 (MH-)
<실시예 l-68> N-(3-브로모페닐 )-4-(4-이소프로필 -2， 3ᅳ디메틸 -5ᅳ옥소-피라졸 —1-일)벤젠설폰아미드의 제조 Example l-68 Preparation of N- (3-bromophenyl) -4- (4-isopropyl-2,3'dimethyl-5oxo-pyrazol —1-yl) benzenesulfonamide
3-브로모아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다。  The reaction was carried out in the same manner as in Example 1-1 using 3-bromoaniline as a starting material to obtain the target compound.
ESI (m/z) 464 (M+) 466 (M+2)  ESI (m / z) 464 (M +) 466 (M + 2)
<실시예 1-69> N-(2-브로모페닐 )-4-(4—이소프로필 -2， 3-디메틸 -5—옥소—피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-69 Preparation of N- (2-bromophenyl) -4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
2-브로모아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다.  The reaction was carried out in the same manner as in Example 1-1, using 2-bromoaniline as a starting material, to obtain the target compound.
ESI (m/z) 464 (M+) 466 (M+2)  ESI (m / z) 464 (M +) 466 (M + 2)
<실시예 1-70> Ν-(2 , 4-디브로모페닐 ) -4— (4-이소프로필 -2 , 3-디메틸— 5-옥소ᅳ피 라졸 -1-일)벤젠설폰아미드의 제조 Example 1-70 Preparation of N- (2,4-dibromophenyl) -4— (4-isopropyl-2,3-dimethyl—5-oxopypyrazol-1-yl) benzenesulfonamide
2.4-디브로모아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반응시켜 목적 화합물을 수득하였다.  2.4-Dibromoaniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 544 (MH+) 546 (M+2) 542 (MH— )  ESI (m / z) 544 (MH +) 546 (M + 2) 542 (MH—)
<실시예 1-71> Nᅳ (2 , 5-디브로모페닐)ᅳ 4ᅳ(4-이소프로필 -2 , 3—디메틸 -5—옥소—피 라졸 -1-일)벤젠설폰아미드의 제조 Example 1-71 Preparation of N '(2,5-dibromophenyl)' 4 '(4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
2.5—디브로모아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  2.5—Dibromoaniline was used as a starting material and reacted in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 544 (MH+) 546 (M+2) 542 (MH— )  ESI (m / z) 544 (MH +) 546 (M + 2) 542 (MH—)
<실시예 1ᅳ72> (3-에틸페닐)-4-(4-이소프로필—2，3-디메틸-5-옥소-피라졸- 1-일)벤젠설폰아미드의 제조 Example 1-72 Preparation of (3-ethylphenyl) -4- (4-isopropyl—2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
3-에틸아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반응 시켜 목적 화합물을 수득하였다.  3-ethylaniline was used as a starting material and reacted in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 414 (MH+) 436 (MNa+) 412 (MH— ) <실시예 l-73> N-( 1， 1ᅳ디메틸프로필 ) -4-(4-이소프로필 -2， 3_디메틸ᅳ5_옥소 -피 라졸— 1-일)벤젠설폰아미드의 제조 ESI (m / z) 414 (MH +) 436 (MNa +) 412 (MH—) Example l-73 Preparation of N- (1,1 ᅳ dimethylpropyl) -4- (4-isopropyl-2,3_dimethyl ᅳ 5_oxo-pyrazol-1-yl) benzenesulfonamide
2-메틸부탄ᅳ 2—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  2-methylbutanyl 2-amine was used as a starting material and reacted in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 380 (MH+)  ESI (m / z) 380 (MH +)
<실시예 1-74> N-(3， 5ᅳ디메록시페닐 ) -4- (4-이소프로필 -2， 3-디메틸— 5-옥소-피 라졸 -1-일)벤젠설폰아미드의 제조 Example 1-74 Preparation of N- (3,5′dimethoxyphenyl) -4- (4-isopropyl-2,3-dimethyl—5-oxo-pyrazol-1-yl) benzenesulfonamide
3 , 5—디메록시아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다。  3, 5—dimethoxyaniline was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 446 (MH+) 468 (丽 a+) 444 (丽― )  ESI (m / z) 446 (MH +) 468 (丽 a +) 444 (丽 ―)
<실시예 1-75> N-시클로펜틸 -4-(4-이소프로필— 2， 3-디메틸 -5-옥소-피라졸— 1— 일)벤젠설폰아미드의 제조 Example 1-75 Preparation of N-cyclopentyl-4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazole-1-yl) benzenesulfonamide
시클로펜탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다,  Using cyclopentanamine as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 378 (MH+) 376 (MH-)  ESI (m / z) 378 (MH +) 376 (MH-)
<실시예 1-76> 4-이소프로필 -2- [4— [4-(4—메특시페닐)피페라진— 1-일 ]설포닐페 닐 ] -1， 5—디메틸―피라졸 -3—은의 제조 Example 1-76 4-Isopropyl-2- [4— [4- (4-methoxyphenyl) piperazin— 1-yl] sulfonylphenyl] -1, 5-dimethyl-pyrazole-3 Manufacture of silver
1_(4-메특시페닐)피페라진을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  Using the 1_ (4-methoxyphenyl) piperazine as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 485 (MH+) 507 (MNa+)  ESI (m / z) 485 (MH +) 507 (MNa +)
<실시예 1-77> 4-(4-이소프로필 -2， 3-디메틸— 5-옥소ᅳ피라졸 -1-일) -N-(4 sec- 부틸페닐)벤젠설폰아미드의 제조 Example 1-77 Preparation of 4- (4-isopropyl-2,3-dimethyl—5-oxopypyrazol-1-yl) -N- (4 sec-butylphenyl) benzenesulfonamide
4-( sec-부틸)아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  4- (sec-butyl) aniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (ra/z) 442 (MH+) 464 (MNa+) 440 (MH-)  ESI (ra / z) 442 (MH +) 464 (MNa +) 440 (MH-)
<실시예 1-78>에틸 4- [ [4— (4-이소프로필— 2 , 3ᅳ디메틸 -5-옥소-피라졸 -1—일)페 닐 ]설포닐아미노]피페리딘 -1-카르복실레이트의 제조 에틸 4-아미노피페리딘— 1—카르복실레이트를 출발물질로 사용하여 상기 실시 예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. Example 1-78 Ethyl 4- [[4— (4-isopropyl— 2, 3 ᅳ dimethyl-5-oxo-pyrazol-1—yl) phenyl] sulfonylamino] piperidine-1- Preparation of Carboxylate Reaction was carried out in the same manner as in Example 1-1, using ethyl 4-aminopiperidine— 1—carboxylate as starting material, to obtain the target compound.
ESI (m/z) 465 (MH+) 487 (MNa+) 463 (MH— )  ESI (m / z) 465 (MH +) 487 (MNa +) 463 (MH—)
<실시예 1-79> N-인단 -5-일 -4-(4—이소프로필 -2， 3_디메틸ᅳ 5ᅳ옥소ᅳ피라졸 -1- 일)벤젠설폰아미드의 제조 Example 1-79 Preparation of N-Indan-5-yl-4- (4-isopropyl-2,3_dimethyl'5-pentoxopypyrazol-1-yl) benzenesulfonamide
2 , 3-디히드로 -1H—인덴 -5-아민을 출발물질로 사용하여 상기 실시예 1-1과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다.  2, 3-dihydro-1H—indene-5-amine was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 426 (MH+) 448 (MNa+) 424 (MH— )  ESI (m / z) 426 (MH +) 448 (MNa +) 424 (MH—)
<실시예 1-80> N—인단 -2-일 -4-(4-이소프로필 -2 , 3-디메틸-5-옥소—피라졸-1一 일)벤젠설폰아미드의 제조 Example 1-80 Preparation of N—Indan-2-yl-4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1 yl) benzenesulfonamide
2 , 3ᅳ디히드로 -1H—인덴— 2-아민을 출발물질로 사용하여 상기 실시예 1—1과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다.  2,3 ᅳ dihydro-lH-indene- 2-amine was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 426 (MH+) 424 (MH-)  ESI (m / z) 426 (MH +) 424 (MH-)
<실시예 1-81> N-시클로헵틸 -4-(4-이소프로필 -2 , 3-디메틸-5—옥소-피라졸-1— 일)벤젠설폰아미드의 제조 Example 1-81 Preparation of N-cycloheptyl-4- (4-isopropyl-2, 3-dimethyl-5—oxo-pyrazol-1—yl) benzenesulfonamide
시클로헵탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다.  Using cycloheptanamine as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 406 (MH+) 404(MH— )  ESI (m / z) 406 (MH +) 404 (MH—)
<실시예 1-82> 4-(4-이소프로필 -2 , 3-디메틸 -5-옥소—피라졸 -1-일 ) -N [3— (트리 플루오로메틸)페닐]벤젠설폰아미드의 제조 Example 1-82 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N [3— (trifluoromethyl) phenyl] benzenesulfonamide
3- (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  3- (trifluoromethyl) aniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 454 (MH+) 476 (MNa+) 452 (MH-)  ESI (m / z) 454 (MH +) 476 (MNa +) 452 (MH-)
<실시예 1-83> N— (4-아세틸페닐) -4-(4-이소프로필 -2 , 3-디메틸 -5—옥소-피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-83 Preparation of N— (4-acetylphenyl) -4- (4-isopropyl-2, 3-dimethyl-5—oxo-pyrazol-1—yl) benzenesulfonamide
1-(4-아미노페닐)에타논을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다. ESI (iii/z) 428 (MH+) 450 (MNa+) 426 (MH-) Using 1- (4-aminophenyl) ethanone as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound. ESI (iii / z) 428 (MH +) 450 (MNa +) 426 (MH-)
<실시예 l-84>메틸 4-[ [4-(4-이소프로필 -2 , 3-디메틸ᅳ5—옥소-피라졸ᅳ1-일)페 닐]설포닐아미노]벤조에이트의 제조 Example l-84 Preparation of methyl 4- [[4- (4-isopropyl-2, 3-dimethyl ᅳ 5—oxo-pyrazol ᅳ 1-yl) phenyl] sulfonylamino] benzoate
메틸 4-아미노벤조에이트을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다.  Using methyl 4-aminobenzoate as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 444 (丽 +) 466 (丽 a+) 442 (MH-)  ESI (m / z) 444 (丽 +) 466 (丽 a +) 442 (MH-)
<실시예 1-85> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸ᅳ 1-일 )— N—피리미딘 -2ᅳ일 -벤젠설폰아미드의 제조 Example 1-85 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazolyl 1-yl) —N—pyrimidin-2xyl-benzenesulfonamide
피리미딘 -2-아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Using pyrimidin-2-amine as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 388 (MH+) 386 (MH一)  ESI (m / z) 388 (MH +) 386 (MH 一)
<실시예 1-86> N-[ (2 , 4-디메록시페닐)메틸] -4-(4—이소프로필 -2，3-디메틸-5— 옥소-피라졸_l-일)벤젠설폰아미드의 제조 Example 1-86 N- [(2,4-dimethoxyphenyl) methyl] -4- (4—isopropyl-2,3-dimethyl-5—oxo-pyrazol_l-yl) benzenesulfonamide Manufacture
(2，4-디메록시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  (2,4-Dimethoxyphenyl) methanamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 460 (MH+)  ESI (m / z) 460 (MH +)
<실시예 1ᅳ87> (2-클로로-4-피리딜)-4-(4-이소프로필ᅳ2，3-디메틸-5ᅳ옥소— 피라졸—1—일)벤젠설폰아미드의 제조 Example 1-87 Preparation of (2-chloro-4-pyridyl) -4- (4-isopropyl 이 2,3-dimethyl-5 디메틸 oxo-pyrazol-1-yl) benzenesulfonamide
2-클로로피리딘 -4-아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  2-chloropyridin-4-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 421 (MH+) 443 (MNa+) 419 (MH— )  ESI (m / z) 421 (MH +) 443 (MNa +) 419 (MH—)
<실시예 1-88> 2- [4-(4-에틸피페라진 -1-일)설포닐페닐] -4-이소프로필 -1 , 5-디 메틸-피라졸 -3-온의 제조 Example 1-88 Preparation of 2- [4- (4-ethylpiperazin-1-yl) sulfonylphenyl] -4-isopropyl-1,5-dimethyl-pyrazol-3-one
1-에틸피페라진을 출발물질로 사용하여 상기 실시예 κ과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다.  Using 1-ethylpiperazine as starting material, the reaction was carried out in the same manner as in Example κ to obtain the target compound.
ESI (m/z) 407 (MH+) <실시예 1-89> Ν-[3 , 5-비스 (트리플루오로메틸)페닐] -4-(4-이소프로필ᅳ 2 ' 3—디 메틸— 5—옥소-피라졸 -1—일)벤젠설폰아미드의 제조 ESI (m / z) 407 (MH +) Example 1-89 N- [3,5-bis (trifluoromethyl) phenyl] -4- (4-isopropyl ᅳ 2 '3—dimethyl— 5—oxo-pyrazol-1—yl) Preparation of Benzenesulfonamide
3,5-비스 (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1一1 과 같은 방법으로 반응시켜 목적 화합물을 수득하였다,  Using the 3,5-bis (trifluoromethyl) aniline as a starting material it was reacted in the same manner as in Example 1 一 1 to obtain the target compound,
ESI (m/z) 522 (MH+) 520 (MH-)  ESI (m / z) 522 (MH +) 520 (MH-)
<실시예 1-90> 4-(4ᅳ이소프로필 -2， 3-디메틸—5-옥소—피라졸 -1-일) -N— (4-피리 딜메틸)벤젠설폰아미드의 제조 Example 1-90 Preparation of 4- (4 ᅳ isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N— (4-pyridylmethyl) benzenesulfonamide
피리딘ᅳ 4—일메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반응시켜 목적 화합물을 수득하였다.  Using pyridine ᅳ 4-ylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 420 (MH+) 423 (丽 a+) 399 (MH-)  ESI (m / z) 420 (MH +) 423 (丽 a +) 399 (MH-)
<실시예 1-91> N-(9-에틸카르바졸 -3-일 ) -4- (4-이소프로필— 2 , 3-디메털 -5ᅳ옥소 -피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1-91 of N- (9-ethylcarbazol-3-yl) -4- (4-isopropyl—2,3-dimetal-5 ”oxo-pyrazol-1xyl) benzenesulfonamide Produce
9-에틸— 9H—카르바졸ᅳ3-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  9-Ethyl-9H-carbazol-3-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 503 (MH+) 525 (MNa+) 501 (MH— )  ESI (m / z) 503 (MH +) 525 (MNa +) 501 (MH—)
<실시예 1-92> N-(4ᅳ브로모 -1-나프털 )-4-(4-이소프로필— 2,3—디메틸— 5—옥소— 피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-92 of N- (4vbromo-1-naphth) -4- (4-isopropyl—2,3—dimethyl-5—oxo-pyrazol-1-yl) benzenesulfonamide Produce
4一브로모나프텔렌—1-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다。  Reaction was carried out in the same manner as in Example 1-1, using 4 il bromonaphthylene-1-amine as starting material, to obtain the target compound.
ESI (m/z) 514 (M+) 516 (M+2)  ESI (m / z) 514 (M +) 516 (M + 2)
<실시예 1-93> 4-(4-이소프로필— 2,3-디메틸-5ᅳ옥소-피라졸-1-일>ᅦ-(2-페닐 페닐)벤젠설폰아미드의 제조 Example 1-93 Preparation of 4- (4-isopropyl—2,3-dimethyl-5 ᅳ oxo-pyrazol-1-yl> VII- (2-phenylphenyl) benzenesulfonamide
비페닐 ]— 2—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  Biphenyl] -2-2-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 462 (MH+) 460 (腿 -); 1H NMR (400 腿 z, DMSO— d6) δ 8,27 (s, 1H), 8.04 (t, 1H, J = 2.0 Hz) 8.02—7.99 (m, 3H), 그 96 (t, 1H, J = 2.2 Hz), 7.94 (t, 1H, J = 2.0 Hz), 7.80 (td, 1H, Ja = 6.0 Hz, Jb = 1.6 Hz), 7。77 一 7.23 (in, 3H), 7.68 (td, 1H, Ja = 8.0 Hz, Jb = 1.2 Hz), 7.60 (dd, 1H, Ja = 8.0 Hz, Jb = 1.6 Hz), 3.45 (s, 3H) , 2.69 (s, 3H), 2.49 - 2,46 (m, 1H) , 1.67 (d,ESI (m / z) 462 (MH &lt; + &gt;) 460 (vi-); 1 H NMR (400 Hz z, DMSO—d6) δ 8,27 (s, 1H), 8.04 (t, 1H, J = 2.0 Hz) 8.02—7.99 (m, 3H), 96 (t, 1H, J = 2.2 Hz), 7.94 (t, 1H, J = 2.0 Hz), 7.80 (td, 1H, Ja = 6.0 Hz, Jb = 1.6 Hz), 7。77 one 7.23 (in, 3H), 7.68 (td, 1H, Ja = 8.0 Hz, Jb = 1.2 Hz, 7.60 (dd, 1H, Ja = 8.0 Hz, Jb = 1.6 Hz), 3.45 (s, 3H), 2.69 (s, 3H), 2.49-2,46 (m, 1H), 1.67 (d,
6H, J = 6ᅳ 8 Hz); 13C NMR (100 MHz, DMSO— d6) δ 205.6， 165.7, 155.9, 140.4,6H, J = 6 Hz 8 Hz); 13 C NMR (100 MHz, DMSO—d6) δ 205.6, 165.7, 155.9, 140.4,
138,4, 137.0, 136.1, 134.1, 131.0, 129.4, 128.9, 128.6， 128.1, 127.8, 126.2, 124.9, 121.7, 115,9, 37.2, 24.5， 20.7， 10.7 138,4, 137.0, 136.1, 134.1, 131.0, 129.4, 128.9, 128.6, 128.1, 127.8, 126.2, 124.9, 121.7, 115,9, 37.2, 24.5, 20.7, 10.7
<실시예 1ᅳ 94> 4-(4-이소프로필— 2 ,3-디메틸ᅳ 5-옥소-피라졸 -1-일 ) -N-(2-메틸- 1-나프틸)벤젠설폰아미드의 제조 Example 1 94. Preparation of 4- (4-isopropyl— 2,3-dimethyl ᅳ 5-oxo-pyrazol-1-yl) -N- (2-methyl-1-naphthyl) benzenesulfonamide
2-메틸나프탈렌—1-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  2-methylnaphthalene-l-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 450 (MH+) 448 (MH-); 1H NMR (400 MHz, DMS0-d6) δ 9.10 (s, 1Η), 8.25-8.20 (m, 3H) , 8.12 (d, 2H, J = 8.8 Hz), 7.96 (d, 2H, J = 8,8 Hz), 7.81 (d, 2H, J = 8.4 Hz), 7.77 (t, 1H, J = 7.4 Hz), 7.68 (t, 1H, J = 8.4 Hz), 3.41 (s, 3H), 3.23-3.21 (m, 1H) , 2.75 (s, 3H), 2.68 (s, 3H) , 1.67 (d, 6H, J = 6.8 Hz)  ESI (m / z) 450 (MH &lt; + &gt;) 448 (MH-); 1 H NMR (400 MHz, DMS0-d6) δ 9.10 (s, 1Η), 8.25-8.20 (m, 3H), 8.12 (d, 2H, J = 8.8 Hz), 7.96 (d, 2H, J = 8,8 Hz), 7.81 (d, 2H, J = 8.4 Hz), 7.77 (t, 1H, J = 7.4 Hz), 7.68 (t, 1H, J = 8.4 Hz), 3.41 (s, 3H), 3.23-3.21 ( m, 1H), 2.75 (s, 3H), 2.68 (s, 3H), 1.67 (d, 6H, J = 6.8 Hz)
<실시예 l-95> N— [2-(4-브로모페닐)에틸] -4-(4-이소프로필 -2，3-디메틸 -5-옥 소-피라졸ᅳ 1—일)벤젠설폰아미드의 제조 Example l-95 N— [2- (4-bromophenyl) ethyl] -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazolyl 1-yl) benzenesulfon Preparation of Amides
2ᅳ(4-브로모페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Using the 2 ′ (4-bromophenyl) ethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 492 (M+) 494 (M+2); 1H NMR (400 MHz, DMS0-d6) δ 8.30 (d, 2H, J = 8.8 Hz), 8.05 (d, 2H, J = 8.8 Hz), 7.82 (d, 2H, 8.4 Hz), 7.54 (d, 2H, J = 8.0 Hz), 7.03 (t, 1H, J - 5.8 Hz), 3.63-3.57 Cm, 2H) , 3.48 (s, 3H) , 3.28-3.18 (m, 3H), 2.69 (s, 3H) , 1,67 (d, 6H, J = 7.2 Hz)  ESI (m / z) 492 (M +) 494 (M + 2); 1 H NMR (400 MHz, DMS0-d6) δ 8.30 (d, 2H, J = 8.8 Hz), 8.05 (d, 2H, J = 8.8 Hz), 7.82 (d, 2H, 8.4 Hz), 7.54 (d, 2H , J = 8.0 Hz), 7.03 (t, 1H, J-5.8 Hz), 3.63-3.57 Cm, 2H), 3.48 (s, 3H), 3.28-3.18 (m, 3H), 2.69 (s, 3H), 1,67 (d, 6H, J = 7.2 Hz)
<실시예 l-96> 4-(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸 -1-일) -Ν-[2ᅳ (5ᅳ메 톡시— 1H-인돌ᅳ 3-일)에틸]벤젠설폰아미드의 제조 Example l-96 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N- [2 ′ (5′methoxy— 1H-indolex 3-yl ) Ethyl] benzenesulfonamide
2-(5—메록시— 1H-인돌 -3—일)에탄아민을 출발물질로 사용하여 상기 실시예 1一 1 과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  The desired compound was obtained by reaction in the same manner as in Example 1-1-1 using 2- (5-methoxy-lH-indole-3-yl) ethanamine as starting material.
ESI (m/z) 483 (MH+) 481 (MH-)； 1H NMR (400 MHz, DMSO— d6) δ 10.26 (s, 1Η), 8.27 (d, 2H, J = 8.8 Hz), 8.00 (d, 2H, 8.4 Hz), 7.63 (d, 1H, J = 8,8 Hz), 7.43-7.41 (m, 2H)， 7.14 (dd, 1H, Ja = 8.0 Hz, Jb = 2.4 Hz), 6.93 (t, 1H, J = 5.8 Hz), 4.19 (s, 3H), 3.70 - 3.65 (m, 2H) , 3.33 (t, 2H, J = 7.4 Hz) 3.27-3.19 (m, 1H), 2.69 (m, 3H) , 1.67 (d, 6H, J = 6.8 Hz) ESI (m / z) 483 (MH &lt; + &gt;) 481 (MH-); 1 H NMR (400 MHz, DMSO—d6) δ 10.26 (s, 1Η), 8.27 (d, 2H, J = 8.8 Hz), 8.00 (d, 2H, 8.4 Hz), 7.63 (d, 1H, J = 8,8 Hz), 7.43-7.41 (m, 2H), 7.14 (dd, 1H, Ja = 8.0 Hz, Jb = 2.4 Hz), 6.93 (t, 1H, J = 5.8 Hz), 4.19 (s, 3H), 3.70-3.65 (m, 2H), 3.33 (t, 2H, J = 7.4 Hz) 3.27-3.19 (m, 1H), 2.69 (m, 3H), 1.67 (d, 6H, J = 6.8 Hz)
<실시예 l-97> 4- (4-이소프로필ᅳ 2， 3-디메틸— 5-옥소-피라졸 -1-일 ) -N_(2-메틸- 1H-인돌— 5-일)벤젠설폰아미드의 제조 Example l-97 4- (4-Isopropyl ᅳ 2, 3-dimethyl— 5-oxo-pyrazol-1-yl) -N_ (2-methyl-1H-indole— 5-yl) benzenesulfonamide Manufacture
2ᅳ메틸 -1Hᅳ인돌—5-아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법 으로 반응시켜 목적 화합물을 수득하였다.  The target compound was obtained in the same manner as in Example 1-1, using 2methyl-1H ᅳ indole-5-amine as a starting material.
ESI (m/z) 439 (MH+) 437 (MH-); 1H 匪 R (400 丽 z, DMS0-d6) δ 10.40 (s, 1H), 9,04 (s, 1H), 8.18 (d, 2H, J = 8.8 Hz), 7.95 (d, 2H, J = 8.4 Hz), 7.69 (s, 1H), 7.55 (d, 2H, 8.8 Hz), 7.29 (dd, 1H, Ja = 12,0 Hz, Jb = 1,6 Hz), 6.48 (s, 1H)ᅳ 3.37 (s, 3H), 3.24—3.15 (m, 1H) , 2.78 (s, 3H) , 2.64 (s, 3H) , 1.63 (d, 6H, J = 7.2 Hz); 13C 匿 (100 MHz, DMS0-d6) δ 165.6, 155.7, 139.9, 137.1, 136.9, 136.3, 134.9， 129.7, 129.4, 128.4, 121.4, 117.3, 115.9, 114.5, 110.8, 100.0, 37.1, 24.4-， 20.7, 13.0， 10.7  ESI (m / z) 439 (MH &lt; + &gt;) 437 (MH-); 1H 匪 R (400 d z, DMS0-d6) δ 10.40 (s, 1H), 9,04 (s, 1H), 8.18 (d, 2H, J = 8.8 Hz), 7.95 (d, 2H, J = 8.4 Hz), 7.69 (s, 1H), 7.55 (d, 2H, 8.8 Hz), 7.29 (dd, 1H, Ja = 12,0 Hz, Jb = 1,6 Hz), 6.48 (s, 1H) ᅳ 3.37 ( s, 3H), 3.24—3.15 (m, 1H), 2.78 (s, 3H), 2.64 (s, 3H), 1.63 (d, 6H, J = 7.2 Hz); 13C 匿 (100 MHz, DMS0-d6) δ 165.6, 155.7, 139.9, 137.1, 136.9, 136.3, 134.9, 129.7, 129.4, 128.4, 121.4, 117.3, 115.9, 114.5, 110.8, 100.0, 37.1, 24.4-, 20.7, 13.0, 10.7
<실시예 1ᅳ98> Ν-(1Η-인돌— 5—일메틸) -4-(4—이소프로필 -2， 3—디메틸 -5ᅳ옥소—피 라졸— 1-일)벤젠설폰아미드의 제조 Example 1 98: Preparation of N- (1Η-indole-5-ylmethyl) -4- (4-isopropyl-2,3-dimethyl-5oxo-pyrazol-1-yl) benzenesulfonamide
(1H-인돌— 5-일)메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다ᅳ  (1H-indole-5-yl) methanamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 439 (MH+)  ESI (m / z) 439 (MH +)
<실시예 1-99> 4-(4-이소프로필— 2,3-디메틸—5—옥소-피라졸—1ᅳ일) -(6—메록 시 -1， 3-벤조티아졸 -2-일 )벤젠설폰아미드의 제조 Example 1-99 4- (4-isopropyl—2,3-dimethyl—5—oxo-pyrazol—1xyl)-(6-meroxy-1, 3-benzothiazol-2-yl) Preparation of Benzenesulfonamide
6-메특시벤조 [d]티아졸 -2—아민을 출발물질로 사용하여 상기 실시예 1-1과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다.  6-Methoxybenzo [d] thiazole-2-amine was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 473 (MH+) 495 (MNa+) 471 (MH一)  ESI (m / z) 473 (MH +) 495 (MNa +) 471 (MH 一)
<실시예 1-100〉 N- 2-( 1H-인돌 -3-일 )에틸 ] -4- (4ᅳ이소프로필ᅳ 2 ' 3-디메틸 -5一옥 소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-100 N-2- (1H-indol-3-yl) ethyl] -4- (4'isopropyl'2'3-dimethyl-5 iodine-pyrazol-1-yl) benzene Preparation of Sulfonamide
2-(1Η-인돌 -3—일)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2- (1Η-indole-3-3-yl) ethanamine as a starting material to obtain a target compound.
ESI (m/z) 453 (MH+) 475 (MNa+) 451 (MH-) <실시예 1ᅳ101> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1-일)— N-(2-메틸 -8-퀴놀릴)벤젠설폰아미드의 제조 ESI (m / z) 453 (MH +) 475 (MNa +) 451 (MH-) Example 1-101 Preparation of 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) —N- (2-methyl-8-quinolyl) benzenesulfonamide
2-메틸 -8-퀴놀릴아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반응시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2-methyl-8-quinolylamine as a starting material to obtain the target compound.
ESI (m/z) 451 (MH+) 473 (MNa+)  ESI (m / z) 451 (MH +) 473 (MNa +)
<실시예 1-102> N-(4-에톡시 -2-니트로-페닐 )-4-(4-이소프로필— 2， 3—디메틸 -5— 옥소-피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1-102 of N- (4-ethoxy-2-nitro-phenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-hexyl) benzenesulfonamide Produce
4ᅳ에특시 -2-니트로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  Using 4-2-nitroaniline as a starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 475 (MH+) 497 (丽 a+) 473 (MH一)  ESI (m / z) 475 (MH +) 497 (丽 a +) 473 (MH 一)
<실시예 1-103> N-(3 ,4-디클로로페닐 )-4-(4-이소프로필 -2 ,3-디메틸-5—옥소ᅳ 피라졸-l-일)벤젠설폰아미드의 제조 Example 1-103 Preparation of N- (3,4-dichlorophenyl) -4- (4-isopropyl-2,3-dimethyl-5—oxozepyrazol-l-yl) benzenesulfonamide
3 , 4-디클로로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다,  3, 4-dichloroaniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 454 (M+) 456 (M+2)  ESI (m / z) 454 (M +) 456 (M + 2)
<실시예 1-104> N-[2ᅳ (2-클로로페닐 )에틸] -4- (4-이소프로필 -2 , 3一디메틸 -5-옥 소-피라졸 -1-일)벤젠설폰아미드 Example 1-104 N- [2 ′ (2-chlorophenyl) ethyl] -4- (4-isopropyl-2,3ldimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
2-(2-클로로페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  Reaction was carried out in the same manner as in Example 1-1, using 2- (2-chlorophenyl) ethanamine as a starting material to obtain the target compound.
ESI (m/z) 448 (MH+) 446 (MH— )  ESI (m / z) 448 (MH +) 446 (MH—)
<실시예 1-10δ> Νᅳ [ (4ᅳ클로로페닐)메틸] -4- (4-이소프로필 -2， 3—디메틸 -5-옥소 -피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-10δ Preparation of N '[(4 ᅳ chlorophenyl) methyl] -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
(4—클로로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였디- .  (4—Chlorophenyl) methanamine was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 434 (MH+) 456 (MNa+) 432 (MH-)  ESI (m / z) 434 (MH +) 456 (MNa +) 432 (MH-)
<실시예 1-106> N-(3 , 5-디클로로페닐)ᅳ 4-(4-이소프로필 -2，3-디메틸-5-옥소- 피라졸-l—일)벤젠설폰아미드의 제조 3, 5-디클로로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다. Example 1-106 Preparation of N- (3,5-dichlorophenyl) '4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-l-yl) benzenesulfonamide 3, 5-dichloroaniline was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 454 (M+) 456 (M+2)  ESI (m / z) 454 (M +) 456 (M + 2)
<실시예 1—107> N-(l， 2-디메특시프로필 )-4-(4-이소프로필— 2， 3-디메틸 -5ᅳ옥소 -피라졸 -1—일)벤젠설폰아미드의 제조 Example 1—107 Preparation of N- (l, 2-dimethoxypropyl) -4- (4-isopropyl— 2, 3-dimethyl-5oxo-pyrazol-1-yl) benzenesulfonamide
1,2-디메록시프로판— 1-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  1,2-dimethoxypropane— Using 1-amine as starting material, reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 412 (MH+)  ESI (m / z) 412 (MH +)
<실시예 1-108> N-(5-클로로 -2-플루오로-페닐)ᅳ 4— (4-이소프로필— 2 , 3-디메틸— 5—옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-108 N- (5-chloro-2-fluoro-phenyl) 페닐 4— (4-isopropyl— 2, 3-dimethyl— 5—oxo-pyrazol-1-yl) benzenesulfonamide Manufacture
5-클로로 -2-플루오로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다,  5-chloro-2-fluoroaniline was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound.
ESI (m/z) 438 (MH+) 436 (MH-)  ESI (m / z) 438 (MH +) 436 (MH-)
<실시예 1-109〉 N— (4-에티닐페닐 )-4-(4—이소프로필 -2，3-디메틸 -5-옥소-피라 졸 -1-일)벤젠설폰아미드의 제조 Example 1-109 Preparation of N— (4-ethynylphenyl) -4- (4—isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
4一에티닐아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다, (수율 79„4¾)  The reaction product was reacted in the same manner as in Example 1-1 using 4yethynylaniline as a starting material, to obtain the target compound (yield 79 „4¾).
ESI (m/z) 410 (MH+) 408 (MH-)； 1H NMR (400 MHz, DMS0—d6) δ 10.57 (s, 1H), 7.82 (d, 2H, J = 8.4 Hz), 7.51 (d, 2H, J = 8.0 Hz), 7.32 (d, 2H, J = 8。4 Hz), 7.09 (d, 2H, J = 8.8 Hz), 4.04 (s, 1H), 2.88(s, 3H) , 2.74 ᅳ 2.63 (m, IH), 2.14 (s,3H), 1.12 (d, 6H, J = 7.2 Hz) ； 13C NMR (100 MHz, DMS0~d6) δ peak 165.1, 155.8, 139.6, 138.7, 135.5, 133.2, 128.1, 122.1, 119.6, 117.2, 114.6, 83.4, 80.7, 37.2, 23.9, 21.2, 11.2 ESI (m / z) 410 (MH &lt; + &gt;) 408 (MH-); 1 H NMR (400 MHz, DMS0-d6) δ 10.57 (s, 1H), 7.82 (d, 2H, J = 8.4 Hz), 7.51 (d, 2H, J = 8.0 Hz), 7.32 (d, 2H, J = 8。4 Hz), 7.09 (d, 2H, J = 8.8 Hz), 4.04 (s, 1H), 2.88 (s, 3H), 2.74 ᅳ 2.63 (m, IH), 2.14 (s, 3H), 1.12 (d, 6H, J = 7.2 Hz); 13C NMR (100 MHz, DMS0 to d6) δ peak 165.1, 155.8, 139.6, 138.7, 135.5, 133.2, 128.1, 122.1, 119.6, 117.2, 114.6, 83.4, 80.7, 37.2, 23.9, 21.2, 11.2
<실시예 l-llO N-[ (4-플루오로페닐)메틸] -4-(4-이소프로필 -2， 3-디메틸 -5-옥 소-피라졸 -1-일)벤젠설폰아미드의 제조 Example l Preparation of l-llO N-[(4-fluorophenyl) methyl] -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
(4-플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다, (수율 67.9W  Using (4-fluorophenyl) methanamine as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound, (yield 67.9 W).
ESI (m/z) 418 (MH+) 416 (丽一) <실시예 1-111> N-C2, 4-디메틸— 6—니트로-페닐 )— 4-(4-이소프로필 -2， 3-디메틸- 5-옥소-피라졸 -1ᅳ일)벤젠설폰아미드의 제조 ESI (m / z) 418 (MH +) 416 (丽 一) Example 1-111 N-C2, 4-dimethyl-6-nitro-phenyl)-4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1xyl) benzenesulfonamide Produce
2ᅳ 4—디메틸—6-니트로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 38.0%)  The reaction was carried out in the same manner as in Example 1-1, using 2 ′ 4—dimethyl-6-nitroaniline as a starting material to obtain the target compound. (Yield 38.0%)
ESI (m/z) 459 (MH+) 457 (MH-)； 1H NMR (400 MHz, DMS0—d6) δ 10.02 (s, 1H), 7.59 (d, 2H, J = 8.8 Hz), 7.50-7.47 (m, 3H) , 7.29 (s, 1H)， 2.91 (s, 3H) , 2.77 - 2.66 (m, 1H), 2.28 (s, 3H) , 2.17 (s, 3H) , 1.77 (s,3H), 1,15 (d, 6H, J = 그 2 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165.0, 155.7, 149.4, 139.57, 139.52, 138.7, 136.8, 135.8, 127.8, 124.4, 123.4, 122.3, 114.7, 37.2, 12.9, 21.3, 20.5, 17.6, 11.3  ESI (m / z) 459 (MH &lt; + &gt;) 457 (MH-); 1 H NMR (400 MHz, DMS0—d6) δ 10.02 (s, 1H), 7.59 (d, 2H, J = 8.8 Hz), 7.50-7.47 ( m, 3H), 7.29 (s, 1H), 2.91 (s, 3H), 2.77-2.66 (m, 1H), 2.28 (s, 3H), 2.17 (s, 3H), 1.77 (s, 3H), 1 , 15 (d, 6H, J = 2 Hz thereof); 13C NMR (100 MHz, DMS0-d6) δ peak 165.0, 155.7, 149.4, 139.57, 139.52, 138.7, 136.8, 135.8, 127.8, 124.4, 123.4, 122.3, 114.7, 37.2, 12.9, 21.3, 20.5, 17.6, 11.3
<실시예 1-112> ^(2,5-디클로로ᅳ4-니트로-페닐)-4-(4-이소프로필-2,3—디메 털 -5—옥소ᅳ피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-112 ^ (2,5-dichloro ᅳ 4-nitro-phenyl) -4- (4-isopropyl-2,3—dimetal-5—oxo-pyrazole-1-yl) benzenesulfon Preparation of Amides
2,5—디클로로— 4—니트로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 42„6¾  2,5—Dichloro-4—nitroaniline was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain a target compound. (Yield 42 „6¾
ESI (m/z) 499 (M)  ESI (m / z) 499 (M)
<실시예 1_113> N— (4-클로로—3—니트로—페닐) -4— (4-이소프로필— 2 , 3ᅳ디메틸ᅳ 5ᅳ 옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1_113 Preparation of N— (4-Chloro—3—nitro—phenyl) -4— (4-isopropyl— 2, 3'dimethyl ᅳ 5 ′ oxo-pyrazol-1-yl) benzenesulfonamide
4-클로로—3—니트로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다. (수율 86,0%)  Using 4-chloro-3 nitroaniline as starting material, the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound. (Yield 86,0%)
1H 丽 R (400 MHz, DMSO— d6) δ 11.01 (s, 1H)， 7.87 (d, 2H, J = 8.8 Hz), 7.73 (d, 1H, J = 2.4 Hz), 7.62 (d, 1H, J = 8.8 Hz), 7.54 (d, 2H, J = 8.4 Hz), 7.38 (dd, 1H, Ja = 12.0 Hz, Jb = 2.4 Hz), 2.89 (s, 3H) , 2.74 - 2.63 (m, 1H), 2.15 (s, 3H), 1.12 (d, 6H, J = 7.2 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165.1, 156.0, 147.9， 140.0， 138.2, 134.8, 133.1， 128.2, 124.4, 122.2, 120,0, 116.0, 114.6, 37.3, 23.9, 21.2, 11.3  1 H δ R (400 MHz, DMSO—d6) δ 11.01 (s, 1H), 7.87 (d, 2H, J = 8.8 Hz), 7.73 (d, 1H, J = 2.4 Hz), 7.62 (d, 1H, J = 8.8 Hz), 7.54 (d, 2H, J = 8.4 Hz), 7.38 (dd, 1H, Ja = 12.0 Hz, Jb = 2.4 Hz), 2.89 (s, 3H), 2.74-2.63 (m, 1H), 2.15 (s, 3 H), 1.12 (d, 6 H, J = 7.2 Hz); 13C NMR (100 MHz, DMS0-d6) δ peak 165.1, 156.0, 147.9, 140.0, 138.2, 134.8, 133.1, 128.2, 124.4, 122.2, 120,0, 116.0, 114.6, 37.3, 23.9, 21.2, 11.3
<실시예 1— 114> N-(2 , 3—디메틸— 6-니트로-페닐) -4-(4—이소프로필ᅳ 2， 3—디메틸- 5-옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1 114 N- (2, 3-dimethyl-6-nitro-phenyl) -4- (4-isopropyl ᅳ 2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfon Preparation of Amides
2，3—디메틸 6-니트로아닐린을 출발물질로 사용하여 상기 실시예 1ᅳ1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 35„9%) 2,3-dimethyl-6-nitroaniline as a starting material as in Example 1-1 Reaction was carried out to obtain the target compound. (Yield 35 „9%)
ESI (m/z) 459 (MH+) 457 (MH-)； 1H NMR (400 MHz, DMS0-d6) δ 10.16 (s, 1H), 7.64 (d, 1H, J = 8.4 Hz), 7.60 (d, 2H, J = 8.8 Hz), 7.52 (d, 2H, J = 8.8 Hz), 7.33 (d, 1H, J = 8.4 Hz), 2.96 (s, 3H) , 2.97 ― 2.72 (m, 1H) , 2.22 (d, 6H, J = 8.4 Hz), 1.79 (s, 3H), 1.19 (d, 6H, J = 7.2 Hz); 13C 丽 R (100 MHz, DMS0-d6) δ peak 165.0， 155.7， 147.8， 143.9, 139.4, 138.9, 136.5, 129.5, 127.8, 126.8, 122.4, 122.3， 114.7, 37.1, 23.9, 21.3, 20.8, 14,7, 11.3  ESI (m / z) 459 (MH &lt; + &gt;) 457 (MH-); 1 H NMR (400 MHz, DMS0-d6) δ 10.16 (s, 1H), 7.64 (d, 1H, J = 8.4 Hz), 7.60 (d, 2H, J = 8.8 Hz), 7.52 (d, 2H, J = 8.8 Hz), 7.33 (d, 1H, J = 8.4 Hz), 2.96 (s, 3H), 2.97-2.72 (m, 1H), 2.22 ( d, 6H, J = 8.4 Hz), 1.79 (s, 3H), 1.19 (d, 6H, J = 7.2 Hz); 13C D R (100 MHz, DMS0-d6) δ peak 165.0, 155.7, 147.8, 143.9, 139.4, 138.9, 136.5, 129.5, 127.8, 126.8, 122.4, 122.3, 114.7, 37.1, 23.9, 21.3, 20.8, 14,7 , 11.3
<실시예 1-115> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1-일) -Nᅳ (1—나프 틸메틸)벤젠설폰아미드의 제조 Example 1-115 Preparation of 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N '(1-naphthylmethyl) benzenesulfonamide
나프탈렌— 1ᅳ일메탄아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다. (수율 9.21 %)  Naphthalene—1 ylylmethanamine was used as starting material, and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound. (Yield 9.21%)
ESI (m/z) 450 (MH+) 472 (MNa+) 448 (MH— )  ESI (m / z) 450 (MH +) 472 (MNa +) 448 (MH—)
<실시예 1_116> N-[ (3-브로모페닐 )메틸] -4-(4-이소프로필 -2， 3—디메틸ᅳ 5-옥소 —피라졸 -1-일)벤젠설폰아미드의 제조 Example 1_116 Preparation of N-[(3-bromophenyl) methyl] -4- (4-isopropyl-2,3-dimethyldimethyl 5-oxo-pyrazol-1-yl) benzenesulfonamide
(3-브로모페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다. (수율 76.7 )  (3-Bromophenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound. (Yield 76.7)
ESI (m/z) 478 (M+) 480 (M+2)  ESI (m / z) 478 (M +) 480 (M + 2)
<실시예 1-117> Nᅳ [2-(3ᅳ브로모페닐)에틸] -4- (4-이소프로필 -2 , 3—디메틸ᅳ 5-옥 소-피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-117 N '[2- (3'bromophenyl) ethyl] -4- (4-isopropyl-2,3-dimethyl' 5-oxo-pyrazol-1-yl) benzenesulfon Preparation of Amides
2— (3—브로모페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 61,8 %)  2— (3—bromophenyl) ethanamine was used as a starting material and reacted in the same manner as in Example 1-1 to obtain the target compound. (Yield 61,8%)
ESI (m/z) 492 (M+) 494 (M+2)  ESI (m / z) 492 (M +) 494 (M + 2)
<실시예 1-118> N- [ (2-브로모페닐 )메틸] -4-(4-이소프로필 -2， 3 디메틸 -5-옥소 -피라졸— 1-일)벤젠설폰아미드의 제조 Example 1-118 Preparation of N-[(2-bromophenyl) methyl] -4- (4-isopropyl-2,3 dimethyl-5-oxo-pyrazol- 1-yl) benzenesulfonamide
(2-브로모페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다. (수율 95.8 )  (2-bromophenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound. (Yield 95.8)
ESI (m/z) 478 (M+) 480 (M+2) <실시예 1-119> N- [2-(3-클로로페닐 )에틸] -4-(4-이소프로필 -2 , 3-디메틸 -5ᅳ옥 소-피라졸 L-일)벤젠설폰아미드의 제조 ESI (m / z) 478 (M +) 480 (M + 2) Example 1-119 Preparation of N- [2- (3-chlorophenyl) ethyl] -4- (4-isopropyl-2,3-dimethyl-5ioxo-pyrazol L-yl) benzenesulfonamide
2ᅳ (3—클로로페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 73.1 )  The target compound was obtained in the same manner as in Example 1-1, using 2 '(3—chlorophenyl) ethanamine as a starting material. (Yield 73.1)
ESI (m/z) 448 (丽+) 470 (爾 a+) 446 (腿― )  ESI (m / z) 448 (丽 +) 470 (爾 a +) 446 (腿 ―)
<실시예 1-120> 4-(4—이소프로필 -2 ,3-디메틸 -5-옥소—피라졸— 1-일) _N-[ [3- (트 리플루오로메틸)페닐]메틸]벤젠설폰아미드의 제조 Example 1-120 4- (4—Isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) _N-[[3- (trifluoromethyl) phenyl] methyl] benzene Preparation of Sulfonamide
(3一 (트리플루오로메틸)페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1一 1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 78.9 %)  The reaction product was reacted in the same manner as in Example 1-1-1 using (3 一 (trifluoromethyl) phenyl) methanamine as a starting material to obtain the target compound. (Yield 78.9%)
ESI (m/z) 468 (MH+) 490 (MNa+) 466 (MH-)  ESI (m / z) 468 (MH +) 490 (MNa +) 466 (MH-)
<실시예 1-121> 4- (4-이소프로필 -2， 3-디메틸 -5-옥소—피라졸— 1—일) -N-[ [2— (트 리플루오로메틸)페닐]메틸]벤젠설폰아미드의 제조 Example 1-121 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol- 1-yl) -N-[[2— (trifluoromethyl) phenyl] methyl] Preparation of Benzenesulfonamide
(2一 (트리플루오로메틸)페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1— 1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 77.3 )  The target compound was obtained in the same manner as in Example 1-1, using (2 一 (trifluoromethyl) phenyl) methanamine as a starting material. (Yield 77.3)
ESI (m/z) 468 (MH+) 490 (MNa+) 466 (腿ᅳ)  ESI (m / z) 468 (MH +) 490 (MNa +) 466 (腿 ᅳ)
<실시예 1ᅳ122> 4-(4-이소프로필 -2 , 3-디메틸— 5-옥소ᅳ피라졸 -1-일 )— N— [ [4- (트 리플루오로메틸)페닐]메틸]벤젠설폰아미드의 제조 Example 1-122 4- (4-isopropyl-2,3-dimethyl- 5-oxopypyrazol-1-yl)-N— [[4- (trifluoromethyl) phenyl] methyl] Preparation of Benzenesulfonamide
(4— (트리플루오로메틸)페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1一 1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 74.6 %)  (4— (trifluoromethyl) phenyl) methanamine was used as a starting material and reacted in the same manner as in Example 1-1-1 to obtain the target compound. (Yield 74.6%)
ESI (m/z) 468 (MH+) 490 (MNa+) 466 (MH-)  ESI (m / z) 468 (MH +) 490 (MNa +) 466 (MH-)
<실시예 1-123> 4— (4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸 -1-일)— N-(o-를릴 메틸)벤젠설폰아미드의 제조 Example 1-123 4— (4-Isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl) —Preparation of N- (o-lryl methyl) benzenesulfonamide
0一를릴메탄아민을 출발물질로 사용하여 상기 실시예 1— 과 같은 방법으로 반 옹시켜 목적 화합물을 수득하였다, (수율 84.2 %)  Reaction was carried out in the same manner as in Example 1— above using 0-l lylmethaneamine as a starting material to obtain the target compound (yield 84.2%)
ESI (m/z) 414 (MH+) 436 (丽 a+) 412 (MH-)  ESI (m / z) 414 (MH +) 436 (丽 a +) 412 (MH-)
<실시예 1-124> ^(3-클로로페닐)-4-(4-이소프로필-2，3-디메틸-5-옥소-피라 졸 -1—일)벤젠설폰아미드의 제조 3一클로로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다. (수율 88.8 %) Example 1-124 Preparation of ^ (3-chlorophenyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Reaction was carried out in the same manner as in Example 1-1, using ternary chloroaniline as a starting material, to obtain the target compound. (Yield 88.8%)
ESI (m/z) 420 (MH+) 418 (MH-)  ESI (m / z) 420 (MH +) 418 (MH-)
<실시예 1-125> N-(2-클로로페닐) -4-(4-이소프로필 -2， 3_디메틸— 5-옥소-피라 졸 -1—일)벤젠설폰아미드의 제조 Example 1-125 Preparation of N- (2-chlorophenyl) -4- (4-isopropyl-2,3_dimethyl- 5-oxo-pyrazol-1-yl) benzenesulfonamide
2-클로로아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다. (수율 80.6 )  Reaction was carried out in the same manner as in Example 1-1 using 2-chloroaniline as a starting material to obtain the target compound. (Yield 80.6)
ESI (m/z) 420 (MH+) 418 (MH-)  ESI (m / z) 420 (MH +) 418 (MH-)
<실시예 1-126> N— [ (3-클로로페닐 )메틸] -4- (4-이소프로필— 2 , 3—디메틸 -5-옥소 ᅳ피라졸—1-일)벤젠설폰아미드의 제조 Example 1-126 Preparation of N — [(3-chlorophenyl) methyl] -4- (4-isopropyl—2,3—dimethyl-5-oxo cappyrazol—1-yl) benzenesulfonamide
3一클로로페닐메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다. (수율 96.4 %) The reaction mixture was reacted in the same manner as in Example 1-1, using tribasic chloromethanamine as a starting material, to obtain a target compound. (Yield 96.4%)
ESI (m/z) 434 (MH+) 456 (MNa+) 432 (MH-)  ESI (m / z) 434 (MH +) 456 (MNa +) 432 (MH-)
<실시예 1-127> 4- (4-브로모 -2 , 3-디메틸 -5—옥소-피라졸 -1-일 ) _N-(2—페녹시에 틸)벤젠설폰아미드의 제조 Example 1-127 Preparation of 4- (4-bromo-2,3-dimethyl-5-oxo-pyrazol-1-yl) _N- (2-phenoxytyl) benzenesulfonamide
1. 4ᅳ(4-브로모—2， 3-디메틸 -5-옥소—피라졸—1일)벤젠설포닐 클로라이드의 제 조 , 1. Preparation of 4 '(4-bromo—2, 3-dimethyl-5-oxo-pyrazole—daily) benzenesulfonyl chloride,
4-이소프로필 -1， 5-디메틸 -2—페닐피라졸론을 출발물질로 사용하여 상기 실시 예 1—1의 1과 같은 방법으로 반웅시켜 목적 화합물을 연한 노란색 고체로 수득하였 다。 Reaction was carried out in the same manner as in Example 1-1, using 4-isopropyl-1,5-dimethyl-2-phenylpyrazolone as a starting material to obtain the target compound as a pale yellow solid.
2. 4— (4—브로모 -2， 3—디메틸 -5—옥소-피라졸— 1ᅳ일)— N— (2-페녹시에틸)밴젠설폰 아미드의 제조  2. Preparation of 4— (4—bromo-2, 3—dimethyl-5—oxo-pyrazol—1syl) —N— (2-phenoxyethyl) banzensulfonamide
2-페녹시에탄아민을 출발물질로 사용하여 상기 실시예 1-1의 2와 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다ᅳ (수율 80.6%)  Reaction was carried out in the same manner as in Example 1-1, using 2-phenoxyethanamine as a starting material, to obtain the target compound (yield 80.6%).
ESI (m/z) 466 (M+) 468 (M+2)； 1H NMR (400 MHz, DMS0-d6) δ 8,03 (s, 1H), 7.95 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8.8 Hz), 7.25 (t, 2H, J = 8.8 Hz), 6.91 (t, 1H, J = 8.8 Hz), 6.83 (d, 2H, J = 8.0 Hz), 3.94 (t, 2H, J = 8.0 Hz), 3.19 (t, 2H, J = 8.0 Hz), 3.13 (s, 3H) , 2.33 (s, 3H)； 13C NMR (100 MHz, DMS0-d6) δ peak 161.9， 158.4, 157.3, 138.4, 138.3, 129.87, 129.84, 28.0， 123.6 , 121. 1， 114.79 , 114.77， 88.4 , 66 , 6， 42.4 , 37. 1 , 12.7 ESI (m / z) 466 (M +) 468 (M + 2); 1 H NMR (400 MHz, DMS0-d6) δ 8,03 (s, 1H), 7.95 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8.8 Hz), 7.25 (t, 2H, J = 8.8 Hz), 6.91 (t, 1H, J = 8.8 Hz), 6.83 (d, 2H, J = 8.0 Hz), 3.94 (t , 2H, J = 8.0 Hz), 3.19 (t, 2H, J = 8.0 Hz), 3.13 (s, 3H), 2.33 (s, 3H); 13 C NMR (100 MHz, DMS0-d6) δ peak 161.9, 158.4 , 157.3, 138.4, 138.3, 129.87, 129.84, 28.0 123.6, 121. 1, 114.79, 114.77, 88.4, 66, 6, 42.4, 37. 1, 12.7
<실시예 1-128> N- [2-(2—플루오로페닐 )에틸] -4-(4ᅳ이소프로필 -2 , 3-디메틸— 5- 옥소-피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-128 N- [2- (2—fluorophenyl) ethyl] -4- (4 (isopropyl-2, 3-dimethyl- 5-oxo-pyrazol-1-yl) benzenesulfonamide Manufacture
2— (2—풀루오로페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다,  2— (2—Pluorophenyl) ethanamine was used as a starting material to react in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 432 (MH+) 454 (MNa+) 430 (MH— )  ESI (m / z) 432 (MH +) 454 (MNa +) 430 (MH—)
<실시예 1-129> Nᅳ [ (4-브로모페닐 )메틸] -4-(4-이소프로필ᅳ 2 , 3-디메틸— 5—옥소 —피라졸— 1—일)벤젠설폰아미드의 제조 Example 1-129 Preparation of N '[(4-Bromophenyl) methyl] -4- (4-isopropyl'2, 3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide
(4ᅳ브로모페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  (4V bromophenyl) methanamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 478 (M+) 480 (M+2)  ESI (m / z) 478 (M +) 480 (M + 2)
<실시예 1-130> Ν-[2-(2-브로모페닐)에틸] -4-(4-이소프로필 -2 , 3-디메틸 -5-옥 소-피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-130 N- [2- (2-bromophenyl) ethyl] -4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazole-1-yl) benzenesulfon Preparation of Amides
2一 (2-브로모페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  The desired compound was obtained in the same manner as in Example 1-1, using 2 (2-bromophenyl) ethanamine as a starting material.
ESI (m/z) 492 (M+) 494 (M+2)  ESI (m / z) 492 (M +) 494 (M + 2)
<실시예 1— 131> 4-(4-이소프로필 -2 , 3-디메틸 5-옥소-피라졸-1-일) -[2-(으 를릴)에털]벤젠설폰아미드의 제조 Example 1 131 Preparation of 4- (4-isopropyl-2,3-dimethyl 5-oxo-pyrazol-1-yl)-[2- (erryl) ether] benzenesulfonamide
2一 (으를릴)에탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으 로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2 il (aryl) ethanamine as a starting material, to obtain the target compound.
ESI (m/z) 428 (MH+) 450 (MNa+)  ESI (m / z) 428 (MH +) 450 (MNa +)
<실시예 1-132> 4-(4-이소프로필 -2 , 3-디메틸-5-옥소-피라졸-l-일)-N-[2-(3- 메톡시페닐)에틸]벤젠설폰아미드의 제조 Example 1-132 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol-l-yl) -N- [2- (3-methoxyphenyl) ethyl] benzenesulfonamide Manufacture
2-(3—메록시페닐)에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using 2- (3-methoxyphenyl) ethanamine as a starting material, to obtain the target compound.
ESI (m/z) 444 (MH+) 466 (MNa+) <실시예 1— 133> 4- (4-이소프로필— 2， 3-디메틸 -5-옥소-피라졸— 1-일)ᅳ N_[2ᅳ [2-( 트리플루오로메틸)페닐]에틸]벤젠설폰아미드의 제조 ESI (m / z) 444 (MH +) 466 (MNa +) Example 1-133 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) ᅳ N_ [2 ′ [2- (trifluoromethyl) phenyl] ethyl] Preparation of Benzenesulfonamide
2-[2ᅳ (트리플루오로메틸)페닐]에탄아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  Reaction was carried out in the same manner as in Example 1- 1 using 2- [2 '(trifluoromethyl) phenyl] ethanamine as a starting material to obtain the target compound.
ESI (m/z) 482 (MH+) 504 (MNa+) 480 (MH-)  ESI (m / z) 482 (MH +) 504 (MNa +) 480 (MH-)
<실시예 1-134> 4- (4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1-일 ) -N— [ 2- [ 3- ( 트리플루오로메틸)페닐]에틸]벤젠설폰아미드의 제조 Example 1-134 4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) -N— [2- [3- (trifluoromethyl) phenyl] ethyl ] Preparation of Benzenesulfonamide
2— [3- (트리플루오로메틸)페닐]에탄아민을 출발물질로 사용하여 상기 실시예 工—丄과 같은 방법으로 반응시켜 목적 화합물을 수득하였다。  2— [3- (trifluoromethyl) phenyl] ethanamine was used as a starting material, and the reaction was carried out in the same manner as in Example.
ESI (m/z) 482 (MH+) 504 (MNa+) 480 (MH-)  ESI (m / z) 482 (MH +) 504 (MNa +) 480 (MH-)
<실시예 1-135> 4-(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸— 1-일 ) -N-[2- [4-( 트리플루오로메틸)페닐]에틸]벤젠설폰아미드의 제조 Example 1-135 4- (4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol- 1-yl) -N- [2- [4- (trifluoromethyl) phenyl] ethyl ] Preparation of Benzenesulfonamide
2一 [4ᅳ (트리플루오로메틸)페닐]에탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。  The desired compound was obtained by reaction in the same manner as in Example 1-1, using 2 [[4] (trifluoromethyl) phenyl] ethanamine as starting material.
ESI (m/z) 482 (MH+) 504 (MNa+) 480 (MH-)  ESI (m / z) 482 (MH +) 504 (MNa +) 480 (MH-)
<실시예 1-136> 4-(4—이소프로필ᅳ 2, 3-디메틸 -5-옥소ᅳ피라졸 -1—일)— N— [4— (트 리플루오로메틸)페닐]벤젠설폰아미드의 제조 Example 1-136 4- (4—Isopropyl ᅳ 2, 3-dimethyl-5-oxo-pyrazol-1—yl) — N— [4— (trifluoromethyl) phenyl] benzenesulfonamide Manufacture
4一 (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다,  The reaction was carried out in the same manner as in Example 1-1, using 4 一 (trifluoromethyl) aniline as a starting material, to obtain the target compound.
ESI (m/z) 454 (MH+) 476 (丽 a+) 452 (MH-)  ESI (m / z) 454 (MH +) 476 (丽 a +) 452 (MH-)
<실시예 1_137> N-(2，3-디히드로 -1 ,4-벤조디옥신 -6-일메털 )-4-(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸ᅳ 1-일 )벤젠설폰아미드의 제조 Example 1_137 N- (2,3-dihydro-1,4-benzodioxine-6-ylmetal) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazolyl Preparation of 1-yl) benzenesulfonamide
(2 , 3-디히드로벤조 [b] [ l , 4]디옥신 -6-일)메탄아민을 출발물질로 사용하여 상 기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  (2,3-Dihydrobenzo [b] [l, 4] dioxin-6-yl) methanamine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 458 (MH+) 480 (MNa+) 456 (MH-)  ESI (m / z) 458 (MH +) 480 (MNa +) 456 (MH-)
<실시예 1-138> 4-(4ᅳ클로로-2 , 3-디메틸 -5-옥소—피라졸 -1-일) -Nᅳ (2—페녹시에 틸)벤젠설폰아미드의 제조 1, 4— (4ᅳ클로로 -2 ,3—디메틸—5—옥소-피라졸 -i일)벤젠설포닐 클로라이드의 제 조 Example 1-138 Preparation of 4- (4 ᅳ chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N '(2-phenoxytyl) benzenesulfonamide Preparation of 1, 4— (4 ᅳ chloro-2,3—dimethyl—5—oxo-pyrazol-iyl) benzenesulfonyl chloride
4—클로로—1， 5-디메틸—2—페닐피라졸론을 출발물질로 사용하여 상기 실시예 1- 1의 1과 같은 방법으로 반웅시켜 목적 화합물을 연한 노란색 고체로 수득하였다, ( 수율 40.5%)  4—Chloro-1, 5-dimethyl-2, phenylpyrazolone was used as a starting material, and reaction was carried out in the same manner as in Example 1-1 to obtain the target compound as a pale yellow solid, (yield 40.5%).
2. 4— (4-클로로 2，3-디메틸 -5-옥소—피라졸 -1-일) -N-(2-페녹시에틸)벤젠설폰 아미드의 제조  2. Preparation of 4— (4-chloro 2,3-dimethyl-5-oxo-pyrazol-1-yl) -N- (2-phenoxyethyl) benzenesulfonamide
2-페녹시에탄아민을 출발물질로 사용하여 상기 실시예 1-1의 2와 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다. (수율 51,94%)  2-Phenoxyethanamine was used as a starting material, and reaction was carried out in the same manner as in Example 1-1, to obtain the target compound. (Yield 51,94%)
ESI (m/z) 422 (MH+) 444 (丽 a+) 420 (MH— ); 1H NMR (400MHz, DMS0-d6) 8.04 (t, 1H, J = 5.8 Hz), 7.95 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8.8 Hz), 7.25 (t, 2H, J = 8.0 Hz), 6.91 (t, 1H, J = 7.4 Hz), 6.83 (d, 2H, J = 8.0 Hz), 3.94 (t, 2H, J = 5.4 Hz), 3.19 (q, 2H, J = 5.6 Hz), 3.11 (s, 3H) , 2.32 (s, 3H); 13C NMR (100MHz, DMSO— d6) δ 161.1， 158.4， 155.3, 138.5, 138.1, 129.8, 128.0, 123.6, 121.1, 114.7, 100.6, 66.6, 42.4, 37.0, 11.5  ESI (m / z) 422 (MH &lt; + &gt;) 444 (丽 a +) 420 (MH—); 1 H NMR (400 MHz, DMS0-d6) 8.04 (t, 1H, J = 5.8 Hz), 7.95 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8.8 Hz), 7.25 (t, 2H , J = 8.0 Hz), 6.91 (t, 1H, J = 7.4 Hz), 6.83 (d, 2H, J = 8.0 Hz), 3.94 (t, 2H, J = 5.4 Hz), 3.19 (q, 2H, J = 5.6 Hz), 3.11 (s, 3H), 2.32 (s, 3H); 13C NMR (100MHz, DMSO— d6) δ 161.1, 158.4, 155.3, 138.5, 138.1, 129.8, 128.0, 123.6, 121.1, 114.7, 100.6, 66.6, 42.4, 37.0, 11.5
<실시예 -139> 4-(4-클로로 2,3ᅳ디메틸 -5—옥소-피라졸 -1ᅳ일) -N-[(2-플루오 로페닐)메틸]벤젠설폰아미드의 제조 Example -139 Preparation of 4- (4-Chloro 2,3 -dimethyl-5-oxo-pyrazol-1xyl) -N-[(2-fluorophenyl) methyl] benzenesulfonamide
(2一플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다。 (수율 50。8«  The reaction product was reacted in the same manner as in Example 1-138 using (2 fluorophenyl) methanamine as starting material to obtain the target compound. (Yield 50。8 «
ESI (m/z) 410 (MH+) 432 (MNa+) 408 (MH-) ； 1H NMR (400MHz, DMS0-d6) 8.29 (t, 1H, J 二 6.2 Hz), 7.90 (d, 2Hᅳ J - 8.4 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.34 (t, 1H, J = 7.6 Hz), 7.30 ― 7.25 (m, 1H) , 7.13 - 그 07 (m, 2H) , 4,09 (d, 2H, J = 6.0 Hz), 3.13 (s, 3H)， 2.33 (s, 3H)  ESI (m / z) 410 (MH +) 432 (MNa +) 408 (MH-); 1 H NMR (400 MHz, DMS0-d6) 8.29 (t, 1H, J 2 6.2 Hz), 7.90 (d, 2H ᅳ J-8.4 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.34 (t, 1H, J = 7.6 Hz), 7.30-7.25 (m, 1H), 7.13-07 (m, 2H), 4,09 ( d, 2H, J = 6.0 Hz), 3.13 (s, 3H), 2.33 (s, 3H)
<실시예 1-140> 4-(4ᅳ클로로 -2， 3-디메틸— 5-옥소—피리-졸ᅳ1_일 )— N— [ (3—플루오 로페닐)메틸]벤젠설폰아미드의 제조 Example 1-140 Preparation of 4- (4 ᅳ Chloro-2,3-dimethyl—5-oxo-pyri-zol ᅳ 1_yl) —N — [(3—fluorophenyl) methyl] benzenesulfonamide
(3-플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 17.3%)  (3-fluorophenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Examples 1 to 138 to obtain the target compound. (Yield 17.3%)
ESI (m/z) 410 (MH+) 432 (MNa+) 408 (MH-)； 1H NMR (400MHz, DMS0-d6) δ 8.34 (t, 1H, J = 6.0 Hz), 7.90 (d, 2H, J = 8.4 Hz), 7.54 (d, 2H, J = 8.4 Hz), 7.31 (q, 1H, J = 7.2 Hz), 7.10 ― 7,01 (m, 3H)， 4.08 (d, 2H, J = 6.4 Hz), 3.13 (s, 3H), 2.33 (s, 3H) ESI (m / z) 410 (MH &lt; + &gt;) 432 (MNa &lt; + &gt;) 408 (MH-); 1H NMR (400 MHz, DMS0-d6) δ 8.34 (t, 1H, J = 6.0 Hz), 7.90 (d, 2H, J = 8.4 Hz), 7.54 (d, 2H, J = 8.4 Hz), 7.31 (q, 1H, J = 7.2 Hz), 7.10-7,01 (m, 3H), 4.08 (d, 2H, J = 6.4 Hz) , 3.13 (s, 3H), 2.33 (s, 3H)
<실시예 1-1 1> 4— (4-클로로 -2, 3-디메틸—5—옥소-피라졸 -1ᅳ일) -N-[(4-플루오 로페닐)메틸]벤젠설폰아미드의 제조 Example 1-1 1 Preparation of 4 -— (4-chloro-2, 3-dimethyl-5-oxo-pyrazol-1xyl) -N-[(4-fluorophenyl) methyl] benzenesulfonamide
(4-플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 40.9«  (4-fluorophenyl) methanamine was used as a starting material to react the same method as in Examples 1 to 138 to obtain the target compound. (Yield 40.9 «
ESI (m/z) 410 (MH+) 432 (MNa+) 408 (MH— ); IH NMR (400MHz, DMS0-d6) 8.29 (t, IH, J = 6.4 Hz), 7.89 (d, 2H, J = 8.4 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.28 ― 7.25 (m, 2H), 7.08 (t, 2H, J = 8.8 Hz), 4.04 (d, 2H, J = 6.4 Hz), 3.13 (s, 3H), 2.33 (s, 3H); 13C NMR (100MHz, DMS0-d6) δ 162.9, 161.1, 160.5, 155.3, 138.7, 138.1, 134.2, 134.1， 130.1, 130.0, 128.1， 123.6， 115.5, 115.2, 100.6, 45.8, 37.0, 11.5,  ESI (m / z) 410 (MH +) 432 (MNa +) 408 (MH—); IH NMR (400 MHz, DMS0-d6) 8.29 (t, IH, J = 6.4 Hz), 7.89 (d, 2H, J = 8.4 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.28-7.25 (m , 2H), 7.08 (t, 2H, J = 8.8 Hz), 4.04 (d, 2H, J = 6.4 Hz), 3.13 (s, 3H), 2.33 (s, 3H); 13C NMR (100MHz, DMS0-d6) δ 162.9, 161.1, 160.5, 155.3, 138.7, 138.1, 134.2, 134.1, 130.1, 130.0, 128.1, 123.6, 115.5, 115.2, 100.6, 45.8, 37.0, 11.5,
<실시예 1-142> 4-(4-클로로ᅳ 2 , 3-디메틸 -5-옥소-피라졸ᅳ 1—일 )-Ν— (3 , 4—디클로 로페닐)벤젠설폰아미드의 제조 Example 1-142 Preparation of 4- (4-chloro-2-, 3-dimethyl-5-oxo-pyrazol-1-1-yl) -N— (3,4-dichlorophenyl) benzenesulfonamide
3,4—디클로로아닐린을 출발물질로 사용하여 상기 실시예 1-138과 같은 방법 으로 반응시켜 목적 화합물을 수득하였다. (수율 91.4 %)  3,4—Dichloroaniline was used as a starting material and reacted in the same manner as in Example 1-138, to obtain the target compound. (Yield 91.4%)
ESI (m/z) 447 (MH+) 489 (顧 a+) 445 (MH— ); 1H匪 R (400MHz, DMSO— d6) 7.85 (d, 2H, J = 8.8Hz), 7.51 (d, 2H, J = 8.8Hz), 7.45 (d, IH, J = 8.8Hz), 7.24 (d, IH, J = 2.4Hz)， 7.06 (dd, IH, J = 2.6Hz), 3.03 (s, 3H) , 2.23 (s, 3H); 13C NMR (100MHz, DMSO— d6) δ 161.1, 155.8， 138.9, 138.2, 136.4, 131.9, 131.7, 128.3, 126.5, 123.5, 121.3, 120.0， 100.7, 37.2， 11.5  ESI (m / z) 447 (MH &lt; + &gt;) 489 (VII a +) 445 (MH—); 1H 匪 R (400MHz, DMSO— d6) 7.85 (d, 2H, J = 8.8Hz), 7.51 (d, 2H, J = 8.8Hz), 7.45 (d, IH, J = 8.8Hz), 7.24 (d, IH, J = 2.4 Hz), 7.06 (dd, IH, J = 2.6 Hz), 3.03 (s, 3H), 2.23 (s, 3H); 13C NMR (100MHz, DMSO— d6) δ 161.1, 155.8, 138.9, 138.2, 136.4, 131.9, 131.7, 128.3, 126.5, 123.5, 121.3, 120.0, 100.7, 37.2, 11.5
<실시예 1-143> 4— (4-클로로 -2, 3-디메틸 -5-옥소-피라졸 -1-일)— N— (5-클로로— 2—플루오로-페닐)벤젠설폰아미드의 제조 Example 1-143 4— (4-Chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) — N— (5-chloro-2 —fluoro-phenyl) benzenesulfonamide Produce
5-클로로 -2ᅳ플루오로아닐린을 출발물질로 사용하여 상기 실시예 1—138과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 88.2 )  Reaction was carried out in the same manner as in Examples 1 to 138 using 5-chloro-2- ᅳ fluoroaniline as a starting material to obtain the target compound. (Yield 88.2)
ESI (m/z) 431 (MH+) 453 (MNa+) 429 (MH-); IH NMR (400MHz, DMS0-d6) 7.82 (d, 2H, J = 8.8Hz), 7.51 (d, 2H, J = 8.8Hz), 7.25 - 7.15 (m, 3H) , 3.04 (s, 3H), 2.24 (s, 3H); ' ESI (m / z) 431 (MH <+>) 453 (MNa <+>) 429 (MH <+>); IH NMR (400 MHz, DMS0-d6) 7.82 (d, 2H, J = 8.8 Hz), 7.51 (d, 2H, J = 8.8 Hz), 7.25-7.15 (m, 3H), 3.04 (s, 3H), 2.24 (s, 3H); '
<실시예 1-144> 4-(4-클로로ᅳ2,3-디메틸-5-옥소ᅳ피라졸ᅳ1-일) -[4-(디메틸 아미노)페닐]벤젠설폰아미드의 제조 Example 1-144 4- (4-Chloro-2-2,3-dimethyl-5-oxo-pyrazol-yl-yl)-[4- (dimethyl Preparation of Amino) phenyl] benzenesulfonamide
Ν,Ν-디메틸벤젠— 1,4—디아민을 출발물질로 사용하여 상기 실시예 1—138과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 13,7 )  The desired compound was obtained by reaction in the same manner as in Example 1-138 using Ν, Ν-dimethylbenzene-1,4-diamine as starting material. (Yield 13,7)
ESI (m/z) 421 (MH+) 443 (MNa+) 419 (MH-); IH NMR (400MHz, DMS0-d6) 9.69 (s, IH), 7.74 (d, 2H, J = 8.8 Hz), 7.48 (d, 2H, J = 8.4 Hz), 6.84 (d, 2H, J = 8,8 Hz), 6.54 (d, 2H, J = 9.2 Hz), 3.06 (s, 3H), 2.76 (s, 6H), 2.26 (s, 3H)； 13C NMR (100MHz, DMS0-d6) δ 161.0, 155.4, 148.6, 138.2, 137.5, 128.3, 126.1, 124.5, 123.3, 113, 100.6, 37.1, 11.4  ESI (m / z) 421 (MH <+>) 443 (MNa <+>) 419 (MH <+>); IH NMR (400 MHz, DMS0-d6) 9.69 (s, IH), 7.74 (d, 2H, J = 8.8 Hz), 7.48 (d, 2H, J = 8.4 Hz), 6.84 (d, 2H, J = 8, 8 Hz), 6.54 (d, 2H, J = 9.2 Hz), 3.06 (s, 3H), 2.76 (s, 6H), 2.26 (s, 3H); 13 C NMR (100 MHz, DMS0-d6) δ 161.0, 155.4 , 148.6, 138.2, 137.5, 128.3, 126.1, 124.5, 123.3, 113, 100.6, 37.1, 11.4
<실시예 1-145> 4- (4—클로로 -2， 3-디메틸 -5-옥소-피라졸 -1-일)— N—(2—피리딜메 틸)벤젠설폰아미드의 제조 Example 1-145 Preparation of 4- (4—Chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) —N— (2—pyridylmethyl) benzenesulfonamide
피리딘 2—일메탄아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방법 으로 반응시켜 목적 화합물을 수득하였다. (수율 64.9 %)  Using pyridine 2—ylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-138, to obtain the target compound. (Yield 64.9%)
ESI (m/z) 393 (MH+) 415 (丽 a+) 491 (MH-)； IH NMR (400MHz, DMS0-cl6) 8.35 (d, IH, J = 4.4 Hz), 8,31 (t, IH, J = 6.4 Hz), 7.83 (d, 2H, J = 8.8 Hz), 7.64 (t, IH, J - 7.8 Hz), 7.46 (d, 2H, J = 8.8 Hz), 7.27 (d, IH, J = 8.9 Hz), 7.15 (q, IH, J = 4.8 Hz), 4.07 (d, 2H, J = 6.0 Hz), 4.07 (d, 2H, J = 6.0 Hz), 3.06 (s, 3H), 2.25 (s, 3H) ； 13C NMR (100MHz, DMS0— d6) 161.0, 157.3, 155.3, 149.1, 138.4, 138.1, 137.0, 128.1, 123.6, 122.8, 122.0, 100.6, 48.3, 37.0， 11.5  ESI (m / z) 393 (MH +) 415 (丽 a +) 491 (MH-); IH NMR (400 MHz, DMS0-cl6) 8.35 (d, IH, J = 4.4 Hz), 8,31 (t, IH, J = 6.4 Hz), 7.83 (d, 2H, J = 8.8 Hz), 7.64 (t, IH, J-7.8 Hz), 7.46 (d, 2H, J = 8.8 Hz), 7.27 (d, IH, J = 8.9 Hz), 7.15 (q, IH, J = 4.8 Hz), 4.07 (d, 2H, J = 6.0 Hz), 4.07 (d, 2H, J = 6.0 Hz), 3.06 (s, 3H), 2.25 (s , 3H); 13C NMR (100MHz, DMS0—d6) 161.0, 157.3, 155.3, 149.1, 138.4, 138.1, 137.0, 128.1, 123.6, 122.8, 122.0, 100.6, 48.3, 37.0, 11.5
<실시예 1-146>메틸 3-[[4-(4-클로로 -2，3-디메틸-5-옥소-피라졸—1-일)페닐] 설포닐아미노]벤조에이트의 제조 Example 1-146 Preparation of Methyl 3-[[4- (4-chloro-2,3-dimethyl-5-oxo-pyrazol-l-yl) phenyl] sulfonylamino] benzoate
메틸— 3-아미노벤조에이트를 출발물질로 사용하여 상기 실시예 1—138과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다, (수율 27„2 )  Reaction was carried out in the same manner as in Example 1-138 using methyl—3-aminobenzoate as starting material, to obtain the target compound (yield 27′2).
ESI (m/z) 436 (MH+) 458 (MNa+) 434 (丽― ); IH NMR (400MHz, DMS0— d6) 10.58 (s, IH), 7.82 (d, 2H, J = 8.8 Hz), 7.66 一 7.62 (m, IH), 7.57 - 7.55 (m, IH), 7.48 (d, 2H, J - 8.4 Hz), 7.34 (d, 2H, J - 4.4 Hz), 3.74 (s, 3H) , 3.01 (s, 3H), 2.22 (s, 3H);  ESI (m / z) 436 (MH <+>) 458 (MNa <+>) 434 (丽-); IH NMR (400 MHz, DMS0—d6) 10.58 (s, IH), 7.82 (d, 2H, J = 8.8 Hz), 7.66 one 7.62 (m, IH), 7.57-7.55 (m, IH), 7.48 (d, 2H, J-8.4 Hz), 7.34 (d, 2H, J-4.4 Hz), 3.74 (s, 3H), 3.01 (s, 3H), 2.22 (s, 3H);
<실시예 1-147> 4-(4-클로로 2 , 3-디메틸 -5-옥소-피라졸 -1—일) N-( 1H-인돌 -5- 일메틸)벤젠설폰아미드의 제조 Example 1-147 Preparation of 4- (4-Chloro 2, 3-dimethyl-5-oxo-pyrazol-1-yl) N- (1H-indole-5 ylmethyl) benzenesulfonamide
1H—인돌 -5ᅳ일메탄아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다. (수율 15.2 %) 1H—Indol-5 1ylmethanamine as a starting material, and in the same manner as in Example 1-138. The reaction was carried out to obtain the target compound. (Yield 15.2%)
ESI (m/z) 431 (MH+) 453 (MNa+) 429 (MH— ); 1H NMR (400MHz, DMSO— d6) 10,95 (s, 1H), 8.07 (t, 3H, J = 4,4 Hz), 7.85 (d, 2H, J = 8.8 Hz), 7.45 (d, 2H, J = 8.8 Hz), 7.29 (s, 1H)， 7.21 (d, 2H, J = 8.8 Hz), 6.88 (d, 2H, J = 8.4 Hz), 6.28 (s, 1H), 4.00 (d, 2H, J = 6.4 Hz), 3.01 (s, 3H) , 2.25 (s, 3H)； 13C NMR (100MHz, DMS0-d6) 161.0, 155.2, 138.8, 137.9, 135.5, 128.0, 127.9, 127.8, 126.0, 123.6, 121.6, 119.7, 111.5, 101.3, 100.5, 47.3, 36.9, 11.4  ESI (m / z) 431 (MH +) 453 (MNa +) 429 (MH—); 1H NMR (400 MHz, DMSO— d6) 10,95 (s, 1H), 8.07 (t, 3H, J = 4,4 Hz), 7.85 (d, 2H, J = 8.8 Hz), 7.45 (d, 2H, J = 8.8 Hz), 7.29 (s, 1H), 7.21 (d, 2H, J = 8.8 Hz), 6.88 (d, 2H, J = 8.4 Hz), 6.28 (s, 1H), 4.00 (d, 2H, J = 6.4 Hz), 3.01 (s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz, DMS0-d6) 161.0, 155.2, 138.8, 137.9, 135.5, 128.0, 127.9, 127.8, 126.0, 123.6, 121.6 , 119.7, 111.5, 101.3, 100.5, 47.3, 36.9, 11.4
<실시예 1ᅳ 148>4-(4-클로로 -2,3-디메틸-5—옥소-피라졸-1-일) —(1-나프틸메 틸)벤젠설폰아미드의 제조 Example 1-148> Preparation of 4- (4-chloro-2,3-dimethyl-5—oxo-pyrazol-1-yl) — (1-naphthylmethyl) benzenesulfonamide
나프탈렌 -1—일메탄아민을 출발물질로 사용하여 상기 실시예 1ᅳ 138과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다。 (수율 5,6 %)  Reaction was carried out in the same manner as in Example 1-138 using naphthalene-1-ylmethanamine as starting material to obtain the target compound. (Yield 5,6%)
ESI (m/z) 442 (MH+) 464 (MNa+) 440 (MH一)  ESI (m / z) 442 (MH +) 464 (MNa +) 440 (MH 一)
<실시예 1-149> 4-(4-클로로 -2,3ᅳ디메틸 -5-옥소-피라졸 -1ᅳ일)— N-[(3,4-디메 록시페닐)메틸]벤젠설폰아미드의 제조 Example 1-149 Preparation of 4- (4-chloro-2,3, dimethyl-5-oxo-pyrazol-1xyl) —N-[(3,4-dimethoxyphenyl) methyl] benzenesulfonamide
(3,4—디메록시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—138과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다。 (수율 5,4 %)  (3,4—dimethoxyphenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Example 1-138, to obtain the target compound. (Yield 5,4%)
ESI (m/z) 452 (MH+) 474 (MNa+) 450 (MH— )  ESI (m / z) 452 (MH +) 474 (MNa +) 450 (MH—)
<실시예 1-1504— (4-클로로 -2, 3-디메틸 -5-옥소-피라졸ᅳ1—일)— N-(5ᅳ퀴놀릴) 벤젠설폰아미드의 제조 Example 1-1504— (4-Chloro-2, 3-dimethyl-5-oxo-pyrazolyl-1-yl) — Preparation of N- (5′quinolyl) benzenesulfonamide
퀴놀린—5—아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 38.5 %)  Quinoline-5-amine was used as a starting material and reacted in the same manner as in Example 1-138 to obtain the target compound. (38.5% yield)
ESI (m/z) 429 (MH+) 451 (MNa+) 427 (MH— ); 1H NMR (400MHz, DMS0-d6) 10.42 (s, 1H), 8.79 (t, 1H, J = 2.2 Hz), 8.30 (d, 1H, J = 8.8 Hz), 7.84 (d, 1H, J = 8.4 Hz), 7.71 (d, 2H, J = 8,4 Hz), 7.62 (t, 1H, J = 8.0 Hz), 7.42 (d, 2H, J = 8.4 Hz), 7.38 (t, 1H, J = 4.2 Hz), 7.21 (d, 1H, J = 7.6 Hz), 2.99 (s, 3H), 2.23 (s, 3H); 13C NMR (100MHz, DMSO— d6) 161.0, 155.6， 151.1, 148.6, 138.5, 137.0, 132.8， 131.9, 129.4, 128.3, 128.3, 125.1, 124.1, 123.4, 121.6, 100.7, 37.0, 11.4 <실시예 1-151> 4-(4-클로로 -2， 3-디메틸 -5-옥소-피라졸 -1-일)—N— (5-퀴놀릴 ) 벤젠설폰아미드의 제조 ESI (m / z) 429 (MH <+>) 451 (MNa <+>) 427 (MH <->); 1H NMR (400MHz, DMS0-d6) 10.42 (s, 1H), 8.79 (t, 1H, J = 2.2 Hz), 8.30 (d, 1H, J = 8.8 Hz), 7.84 (d, 1H, J = 8.4 Hz ), 7.71 (d, 2H, J = 8,4 Hz), 7.62 (t, 1H, J = 8.0 Hz), 7.42 (d, 2H, J = 8.4 Hz), 7.38 (t, 1H, J = 4.2 Hz ), 7.21 (d, 1H, J = 7.6 Hz), 2.99 (s, 3H), 2.23 (s, 3H); 13C NMR (100MHz, DMSO— d6) 161.0, 155.6, 151.1, 148.6, 138.5, 137.0, 132.8, 131.9, 129.4, 128.3, 128.3, 125.1, 124.1, 123.4, 121.6, 100.7, 37.0, 11.4 Example 1-151 Preparation of 4- (4-chloro-2, 3-dimethyl-5-oxo-pyrazol-1-yl) —N— (5-quinolyl) benzenesulfonamide
퀴놀린—5—아민을 출발물질로 사용하여 상기 실시예 1—138과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 7.3 %)  Quinoline-5-amine was used as a starting material and reacted in the same manner as in Example 1-138 to obtain the target compound. (Yield 7.3%)
ESI (m/z) 452 (MH+) 474 (MNa+) 450 (MH-)  ESI (m / z) 452 (MH +) 474 (MNa +) 450 (MH-)
<실시예 1-152> 4-(4-브로모 -2 , 3ᅳ디메틸 -5-옥소-피라졸ᅳ 1—일) -N— [ (3 , 4ᅳ디메 록시페닐)메틸]벤젠설폰아미드의 제조 Example 1-152 4- (4-Bromo-2,3'dimethyl-5-oxo-pyrazolyl 1-yl) -N — [(3,4'dihydroxyphenyl) methyl] benzenesulfonamide Manufacture
(3 , 4-디메록시페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1-138과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다.  (3, 4-dimethoxyphenyl) methanamine was used as a starting material to react with the same method as in Example 1-138 to obtain the target compound.
ESI (m/z) 496 (M+) 498 (M+2)  ESI (m / z) 496 (M +) 498 (M + 2)
<실시예 1-153> 4-(4-브로모 -2， 3-디메틸— 5-옥소-피라졸 -1—일 )— N— ( 5-퀴놀릴 ) 벤젠설폰아미드의 제조 Example 1-153 Preparation of 4- (4-bromo-2,3-dimethyl—5-oxo-pyrazol-1—yl) —N— (5-quinolyl) benzenesulfonamide
퀴놀린 -5-아민을 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  Quinoline-5-amine was used as a starting material and reacted in the same manner as in Examples 1-127, to obtain the target compound.
ESI (m/z) 473 (M+) 475 (M+2)  ESI (m / z) 473 (M +) 475 (M + 2)
<실시예 1-154> 4— (4—브로모 -2 , 3—디메틸ᅳ 5-옥소-피라졸—1-일)— N— [4- (디메틸 아미노)페닐]벤젠설폰아미드의 제조 Example 1-154 Preparation of 4— (4—Bromo-2, 3—dimethyl ᅳ 5-oxo-pyrazol—1-yl) — N— [4- (dimethyl amino) phenyl] benzenesulfonamide
Ν, Ν-디메틸벤젠 -1 , 4ᅳ디아민을 출발물질로 사용하여 상기 실시예 1—127과 같 은 방법으로 반응시켜 목적 화합물을 수득하였다,  By using Ν, Ν-dimethylbenzene-1,4 아민 diamine as starting materials, the reaction was carried out in the same manner as in Examples 1 to 127 to obtain the target compound.
ESI (m/z) 465 (M+) 467 (M+2)  ESI (m / z) 465 (M +) 467 (M + 2)
<실시예 1-155>메틸 3—[ [4-(4-브로모 -2 , 3-디메틸—5-옥소ᅳ피라졸-1-일)페닐] 설포닐아미노]벤조에이트의 제조 Example 1-155 Preparation of methyl 3— [[4- (4-bromo-2, 3-dimethyl-5-oxopypyrazol-1-yl) phenyl] sulfonylamino] benzoate
메틸 -3-아미노벤조에이트를 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. Using methyl- 3 -aminobenzoate as a starting material, the reaction was carried out in the same manner as in Examples 1-127, to obtain the target compound.
<실시예 1-156> 4-(4-브로모 -2 , 3-디메틸 -5-옥소-피라졸 -1-일 )_N- 1； (3—플루오 로페닐)메틸]벤젠설폰아미드의 제조 Example 1-156 Preparation of 4- (4-bromo-2, 3-dimethyl-5-oxo-pyrazol-1-yl) _N-1; (3—fluorophenyl) methyl] benzenesulfonamide
(3—플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (3—fluorophenyl) methanamine as starting material was used as in Examples 1-127. Reaction was carried out to obtain the target compound.
<실시예 1-157> 4ᅳ (4-브로모 -2 ,3-디메틸—5-옥소—피라졸 -1-일)— N-[ (2-플루오 로페닐)메틸]벤젠설폰아미드의 제조 Example 1-157 Preparation of 4 ′ (4-Bromo-2,3-dimethyl-5-oxo-pyrazol-1-yl) —N-[(2-fluorophenyl) methyl] benzenesulfonamide
(2-플루오로페닐)메탄아민을 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다,  (2-fluorophenyl) methanamine was used as a starting material and the reaction was carried out in the same manner as in Examples 1-127, to obtain the target compound.
<실시예 1-158> 4-(4-브로모ᅳ2 , 3-디메틸 -5-옥소-피라졸— 1—일) -N-(2-피리딜메 틸)벤젠설폰아미드의 제조 Example 1-158 Preparation of 4- (4-bromoxet 2, 3-dimethyl-5-oxo-pyrazol-1—yl) -N- (2-pyridylmethyl) benzenesulfonamide
피리딘—2-일메탄아민을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  Using pyridine-2-ylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-127, to obtain the target compound.
ESI (m/z) 437 (M+) 439 (M+2); 1H NMR (400 MHz, DMS0-d6) δ 8.38 (d, 1Η, J = 4.4 Hz), 8.34 (t, 1H, J = 6.2 Hz), 7.86 (d, 2H, J = 8.4 Hz), 7.67 (t, 1H, J = 7.6 Hz), 7.48 (d, 2H, J = 8.4 Hz), 7.31 (d, 1H, J = 7.6 Hz), 7.20-7.16 (m, 1H), 4.10 (d, 2H, J = 6.4 Hz), 3,1。 (d, 3H, J = 9.2 Hz), 2.29 (s, 3H)  ESI (m / z) 437 (M &lt; + &gt;) 439 (M + 2); 1 H NMR (400 MHz, DMS0-d6) δ 8.38 (d, 1Η, J = 4.4 Hz), 8.34 (t, 1H, J = 6.2 Hz), 7.86 (d, 2H, J = 8.4 Hz), 7.67 (t , 1H, J = 7.6 Hz), 7.48 (d, 2H, J = 8.4 Hz), 7.31 (d, 1H, J = 7.6 Hz), 7.20-7.16 (m, 1H), 4.10 (d, 2H, J = 6.4 Hz), 3,1。 (d, 3H, J = 9.2 Hz), 2.29 (s, 3H)
<실시예 1— 159> 4ᅳ(4-브로모 -2 , 3-디메틸 -5-옥소ᅳ피라졸 -1—일) -Ν_(2 , 3—디히드 로ᅳ , 4-벤조디옥신 -6-일)벤젠설폰아미드의 제조 Example 1—159 4 ′ (4-Bromo-2, 3-dimethyl-5-oxo-pyrazol-1—yl) -N— (2, 3—dihydrophane, 4-benzodioxine- Preparation of 6-yl) benzenesulfonamide
2,3—디히드로— 1,4-벤조디옥신 -6-아민을 출발물질로 사용하여 상기 실시예 1- 127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다ᅳ  2,3—dihydro—1,4-benzodioxin-6-amine was used as a starting material to react the same method as in Examples 1-127 to obtain the target compound.
ESI (m/z) 480 (M+) 482 (M+2)； 1H NMR (400 MHz, DMS0-d6) δ 10.05 (s, 1H), 7.83 (d, 2H, J = 8.4 Hz), 7.55-7.53 (m, 2H)， 6.72 (d, 1H, J = 8.8 Hz), 6.60 (d, 1H, J = 2.0 Hz), 6.56-6.54 (m, 1H), 4.16 (s, 4H) , 3.12 (d, 3H, J = 8.8 Hz), 2.31 (s, 3H)  ESI (m / z) 480 (M +) 482 (M + 2); 1 H NMR (400 MHz, DMS0-d6) δ 10.05 (s, 1H), 7.83 (d, 2H, J = 8.4 Hz), 7.55-7.53 (m, 2H), 6.72 (d, 1H, J = 8.8 Hz), 6.60 (d, 1H, J = 2.0 Hz), 6.56-6.54 (m, 1H), 4.16 (s, 4H), 3.12 (d, 3H, J = 8.8 Hz), 2.31 (s, 3H)
<실시예 1-160> N— [3, 5-비스 (트리풀루오로메틸)페닐] -4— (4-브로모 -2,3—디메 틸 -5-옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-160 N— [3, 5-bis (tripulouromethyl) phenyl] -4— (4-bromo-2,3—dimethyl-5-oxo-pyrazol-1-yl Preparation of Benzenesulfonamide
3， 5-비스 (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1一 127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  3, 5-bis (trifluoromethyl) aniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1-127 to obtain the target compound.
ESI (m/z) 558 (M+) 560 (M+2)； 1H NMR (400 MHz, DMSO— d6) δ 11,03 (s, 1H), 7.97 (d, 2H, J = 8.8 Hz), 7.79 (s, 1H), 7.70 (s, 2H), 7.61 (dd, 2H, Ja = 8.0 Hz, Jb = 2.0 Hz), 3.11 (d, 3H, J = 8.8 Hz), 2.32 (s, 3H) <실시예 1-161> 4-(4—브로모 -2 , 3—디메틸 -5-옥소ᅳ피라졸—1—일 ) -N— (3， 4—디클로 로페닐)벤젠설폰아미드의 제조 ESI (m / z) 558 (M +) 560 (M + 2); 1 H NMR (400 MHz, DMSO—d6) δ 11,03 (s, 1H), 7.97 (d, 2H, J = 8.8 Hz), 7.79 (s, 1H), 7.70 (s, 2H), 7.61 (dd, 2H, Ja = 8.0 Hz, Jb = 2.0 Hz), 3.11 (d, 3H, J = 8.8 Hz), 2.32 (s, 3H) Example 1-161 Preparation of 4- (4—Bromo-2,3—dimethyl-5-oxo-pyrazol-1-yl) -N— (3,4-dichlorophenyl) benzenesulfonamide
3.4-디클로로아닐린을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법 으로 반응시켜 목적 화합물을 수득하였다.  3.4-Dichloroaniline was used as a starting material and reacted in the same manner as in Example 1-127, to obtain the target compound.
ESI (m/z) 492 (MH+) 514 (丽 a+) 490 (MH— ); 1H NMR (400 MHz, DMS0-d6) δ 10.79 (s, 1Η), 7.92 (d, 2H, J = 8.8 Hz), 7.58 (d, 2H, 8.8 Hz), 7,53 (d, 1H, J = 8.8 Hz), 7.32 (d, 1H, J = 2.4 Hz), 7.13 (dd, 1H, Ja = 8.0 Hz, Jb = 2.4 Hz), ESI (m / z) 492 (MH &lt; + &gt;) 514 (丽 a +) 490 (MH—); 1 H NMR (400 MHz, DMS0-d6) δ 10.79 (s, 1Η), 7.92 (d, 2H, J = 8.8 Hz), 7.58 (d, 2H, 8.8 Hz), 7,53 (d, 1H, J = 8.8 Hz), 7.32 (d, 1H, J = 2.4 Hz), 7.13 (dd, 1H, Ja = 8.0 Hz, Jb = 2.4 Hz),
3.12 (d, 3H, J = 9.2 Hz), 2.31 (s, 3H) 3.12 (d, 3H, J = 9.2 Hz), 2.31 (s, 3H)
〈실시예 1-162〉 4-(4-브로모 -2,3-디메틸 -5-옥소-피라졸 -1ᅳ일)— N-(5-클로로- 2—플루오로-페닐)벤젠설폰아미드의 제조 Example 1-162 4- (4-Bromo-2,3-dimethyl-5-oxo-pyrazol-1xyl) — of N- (5-chloro-2—fluoro-phenyl) benzenesulfonamide Produce
5-클로로—2-플루오로아닐린을 출발물질로 사용하여 상기 실시예 1-127과 같 은 방법으로 반웅시켜 목적 화합물을 수득하였다.  5-chloro—2-fluoroaniline was used as a starting material, and reaction was carried out in the same manner as in Example 1-127, to obtain the target compound.
ESI (m/z) 474 (M+) 476 (M+2); 1H NMR (400 MHz, DMS0-d6) δ 10.56 (s, 1H), 7.85 (d, 2H, J = 8.4 Hz), 7.58 (d, 2H, J = 8.8 Hz), 7.32-7.26 (m, 3H)， ESI (m / z) 474 (M &lt; + &gt;) 476 (M + 2); 1 H NMR (400 MHz, DMS0-d6) δ 10.56 (s, 1H), 7.85 (d, 2H, J = 8.4 Hz), 7.58 (d, 2H, J = 8.8 Hz), 7.32-7.26 (m, 3H) ，
3.13 (d, 3H, J - 9.2 Hz), 2.32 (s, 3H) 3.13 (d, 3H, J-9.2 Hz), 2.32 (s, 3H)
<실시예 1-163> N-[3,5—비스 (트리플루오로메틸)페닐] _4-(4-클로로 -2,3—디메 틸ᅳ 5-옥소-피라졸 -1_일)벤젠설폰아미드의 제조 Example 1-163 N- [3,5—bis (trifluoromethyl) phenyl] _4- (4-chloro-2,3-dimethyl ᅳ 5-oxo-pyrazol-1_yl) benzenesulfon Preparation of Amides
3.5—비스 (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1- 138과 같은 방법으로 반응시켜 목적 화합물을 수득하였다ᅳ (수율 82ᅳ 4 %)  3.5—Bis (trifluoromethyl) aniline was used as a starting material and was reacted in the same manner as in Examples 1-138 to obtain the target compound. (Yield 82 ᅳ 4%)
ESI (m/z) 514 (MH+) 536 (MNa+) 512 (MH-)； 1H NMR (400MHz, DMSO— d6) δ 11.30 (s, 1H), 7.97 (d, 2H, J - 8.8 Hz), 7.79 (s, 1H)， 7.70 (s, 2H) , 7.62 (d, 2H, J = 8.4 Hz), 3.11 (s, 3H)， 2.32 (s, 3H)； 13C NMR (lOOfflz, DMSO— d6) 161.096, 155.964, 140.214, 139.225, 136.019, 131.914, 131.586, 128.378, 124.605, 123.636, 121.893, 119.325, 117.498, 100.842, 37.156, 31.077, 11.509  ESI (m / z) 514 (MH &lt; + &gt;) 536 (MNa &lt; + &gt;) 512 (MH-); 1 H NMR (400 MHz, DMSO—d6) δ 11.30 (s, 1H), 7.97 (d, 2H, J-8.8 Hz), 7.79 (s, 1H), 7.70 (s, 2H), 7.62 (d, 2H, J = 8.4 Hz), 3.11 (s, 3H), 2.32 (s, 3H); 13C NMR (lOOfflz, DMSO—d6) 161.096, 155.964, 140.214, 139.225, 136.019, 131.914, 131.586, 128.378, 124.605, 123.636, 121.893, 119.325, 117.498, 100.842, 37.156, 31.077, 11.509
<실시예 1-164> 4- (4-클로로 -2 , 3-디메틸 -5-옥소 _피라졸 -1—일 ) -Ν-(2ᅳ 3—디히드 로 -1,4-벤조디옥신 -6-일)벤젠설폰아미드의 제조 Example 1-164 4- (4-Chloro-2,3-dimethyl-5-oxo _pyrazol-1—yl) -N— (2 ′ 3—dihydro-1,4-benzodioxine Preparation of -6-yl) benzenesulfonamide
2,3—디히드로ᅳ 1,4—벤조디옥신 -6-아민을 출발물질로 사용하여 상기 실시예 1一 138과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 10.3 %) ESI (m/z) 436 (MH+) 458 (丽 a+) 434 (MH-) 2,3—Dihydrox 1,4—benzodioxin-6-amine was used as a starting material, and the reaction was carried out in the same manner as in Example 1-1-138 to obtain the target compound. (Yield 10.3%) ESI (m / z) 436 (MH +) 458 (丽 a +) 434 (MH-)
<실시예 1-165> 4- (4-브로모 -2 , 3-디메틸 -5-옥소-피라졸 -1ᅳ일 )-Ν_시클로펜틸- 벤젠설폰아미드의 제조 Example 1-165 Preparation of 4- (4-bromo-2,3-dimethyl-5-oxo-pyrazol-1xyl) -Ν_cyclopentyl-benzenesulfonamide
시클로펜탄아민을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 4.9 %) .  Using cyclopentanamine as a starting material, the reaction was carried out in the same manner as in Example 1-127, to obtain the target compound. (Yield 4.9%).
ESI (m/z) 414 (M+) 416 (M+2); 1H NMR (400MHz, DMSO— d6) δ 7.92 (d, 2H, J = 8.4 Hz), 7.71 (d, 1H, J = 7.2 Hz), 7.57 (q, 2H, J = 2.4 Hz), 3.15 (d, 3H, J = 9.2 Hz), 2.33 (s, 3H) , 1.66 ― 1.60 (m, 2H), 1.52 ― 1.36 (m, 8H), 1.25 一 1.21 (m, 2H)  ESI (m / z) 414 (M &lt; + &gt;) 416 (M + 2); 1 H NMR (400 MHz, DMSO— d6) δ 7.92 (d, 2H, J = 8.4 Hz), 7.71 (d, 1H, J = 7.2 Hz), 7.57 (q, 2H, J = 2.4 Hz), 3.15 (d, 3H, J = 9.2 Hz), 2.33 (s, 3H), 1.66-1.60 (m, 2H), 1.52-1.36 (m, 8H), 1.25 one 1.21 (m, 2H)
<실시예 1-166> 4— (4-브로모 -2， 3-디메틸— 5-옥소—피라졸 -1-일 ) N—시클로헵틸- 벤젠설폰아미드의 제조 Example 1-166 Preparation of 4— (4-Bromo-2,3-dimethyl—5-oxo-pyrazol-1-yl) N—cycloheptyl-benzenesulfonamide
시클로협탄아민을 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반응시켜 목적 화합물을 수득하였다. (수율 3,7 )  The reaction was carried out in the same manner as in Examples 1 to 127 using cyclocotantanamine as a starting material to obtain a target compound. (Yield 3,7)
ESI (m/z) 442 (M+) 444 (M+2); 1H 丽 R (400MHz , DMSO— d6) δ 10.39 (s, 1H), 7.91 一 7.89 (m, 2H) , 7.57 - 7.54 (m, 2H), 7.26 (t, 2H, J = 9.2 Hz), 7.14 (d, 2H, J = 8.0 Hz), 7.05 (t, 1H, J = 7.4 Hz), 3.12 (d, 3H, J = 8.8 Hz), 2.316 (s, 3H)  ESI (m / z) 442 (M &lt; + &gt;) 444 (M + 2); 1H δ R (400MHz, DMSO— d6) δ 10.39 (s, 1H), 7.91 7. 7.89 (m, 2H), 7.57-7.54 (m, 2H), 7.26 (t, 2H, J = 9.2 Hz), 7.14 ( d, 2H, J = 8.0 Hz), 7.05 (t, 1H, J = 7.4 Hz), 3.12 (d, 3H, J = 8.8 Hz), 2.316 (s, 3H)
<실시예 1-167> 4-(4-브로모 -2， 3-디메틸—5-옥소-피라졸— 1—일) -N-페닐-벤젠설 폰아미드의 제조 Example 1-167 Preparation of 4- (4-bromo-2, 3-dimethyl-5-oxo-pyrazol-1-yl) -N-phenyl-benzenesulfonamide
아닐린을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. (수율 4.4 %)  Aniline was used as the starting material and reacted in the same manner as in Example 1-127, to obtain the target compound. (Yield 4.4%)
ESI (m/z) 422 (M+) 424 (M+2)  ESI (m / z) 422 (M +) 424 (M + 2)
<실시예 1-168> 4-(2，3-디메틸—5-옥소 -4—페닐-피라졸 -1-일) -N— (2 페녹시에 틸)벤젠설폰아미드의 제조 Example 1-168 Preparation of 4- (2,3-dimethyl-5-oxo-4-phenyl-pyrazol-1-yl) -N— (2 phenoxytyl) benzenesulfonamide
2-5 ml 마이크로웨이브 반웅기 튜브에 1,2-디메록시에탄과 물의 흔합 용액 (1:1) 하에 상기 실시예 1-127의 결과물 4— (4-브로모— 2,3—디메틸 -5—옥소-피라졸 -1- 일) -N-(2—페녹시에틸)벤젠설폰아미드 (150 mg, 0.322 匪 ol)과 페닐보로닉산 (39.22 mg, 0.322 隱 ol), 디클로로비스 (트리페닐포스핀)팔라듐 (II) (11.29 mg, 0.016 隱 ol), 탄산나트룹 (68.18 mg, 0.643 腿 ol)을 첨가하여 마이크로웨이브 반응기를 이용하여 120°C, 40 분간 반웅시킨다. 반웅 확인 후， 물을 첨가하여 반웅을 종결하 고, 디클로로메탄을 이용하여 추출한다. 추출 용액은 진공펌프를 이용해 용매를 제 거하고, 실리카겔 컬럼크로마토그래피 (에틸아세테이트:핵산 = 1:3 ~ 1:1)으로 정 제한다。 추가적으로 디클로로메탄과 핵산을 사용하여 재결정하여 10.5 %의 수율로 하얀색 고체인 4— (2 , 3-디메틸 -5—옥소 -4-페닐—피라졸— 1-일) -N-(2-페녹시에틸 )벤젠설 폰아미드를 수득하였다. The resulting product 4— (4-bromo— 2,3—dimethyl-5 in Example 1-127 under a mixed solution of 1,2-dimethoxyethane and water (1: 1) in a 2-5 ml microwave reaction vessel. —Oxo-pyrazol-1-yl) -N- (2—phenoxyethyl) benzenesulfonamide (150 mg, 0.322 μl), phenylboronic acid (39.22 mg, 0.322 μl), dichlorobis (triphenyl Phosphine) Palladium (II) (11.29 mg, 0.016 隱 ol) and sodium carbonate (68.18 mg, 0.643 腿 ol) are added and reacted for 120 minutes at 120 ° C. using a microwave reactor. After confirming reaction, the reaction was terminated by adding water, and extracted with dichloromethane. The extraction solution is removed using a vacuum pump to remove the solvent, and purified by silica gel column chromatography (ethyl acetate: nucleic acid = 1: 3 to 1: 1). The yield is 10.5% by recrystallization using dichloromethane and nucleic acid. To a white solid, 4— (2, 3-dimethyl-5—oxo-4-phenyl-pyrazol— 1-yl) -N- (2-phenoxyethyl) benzenesulfonamide.
ESI (m/z) 464 (MH+) 462 (MH-)； 1H NMR (400 MHz, DMS0-d6) δ 8.01 (t, 1H, J = 7.2 Hz), 7。95 (d, 2H, J = 8.8 Hz), 7.62 (d, 2H, J = 8.4 Hz), 7,51 (d, 1H, J 二 8.0 Hz), 7.42 (t, 2H, J = 7.8 Hz), 7.31-7.23 (m, 3H) , 6.91 (t, 1H, J = 7.4 Hz), 6.84 (d, 2H, J = 8.0 Hz), 3.95 (t, 2H, J = 5.4 Hz), 3.21-3.15 (m, 5H), 2.40 (s, 3H)  ESI (m / z) 464 (MH <+>) 462 (MH <->); 1 H NMR (400 MHz, DMS0-d6) δ 8.01 (t, 1H, J = 7.2 Hz), 7。95 (d, 2H, J = 8.8 Hz), 7.62 (d, 2H, J = 8.4 Hz), 7,51 (d, 1H, J 2 8.0 Hz), 7.42 (t, 2H, J = 7.8 Hz), 7.31-7.23 (m, 3H), 6.91 (t, 1H, J = 7.4 Hz), 6.84 (d, 2H, J = 8.0 Hz), 3.95 (t, 2H, J = 5.4 Hz), 3.21-3.15 (m, 5H), 2.40 (s, 3H )
<실시예 1-169> 4- [4- (4-클로로페닐 ) -2, 3—디메틸 -5ᅳ옥소-피라졸 -1ᅳ일 ] -N— ( 2- 페녹시에틸)벤젠설폰아미드의 제조 Example 1-169 Preparation of 4- [4- (4-chlorophenyl) -2,3-dimethyl-5oxo-pyrazol-1xyl] -N— (2-phenoxyethyl) benzenesulfonamide
(4一클로로페닐)보로닉산을 출발물질로 사용하여 상기 실시예 1-168과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  Using (4 chlorochloro) boronic acid as a starting material, the reaction was carried out in the same manner as in Example 1-168 to obtain the target compound.
ESI (m/z) 498 (MH+) 497 (MH-)  ESI (m / z) 498 (MH +) 497 (MH-)
<실시예 1-170> 2-[3ᅳ [[4-(4-이소프로필 -2,3-디메틸ᅳ5-옥소 피라졸-1-일)페 닐]설포닐아미노]페닐]아세트산의 제조 Example 1-170 Preparation of 2- [3 ′ [[4- (4-isopropyl-2,3-dimethyl ᅳ 5-oxo pyrazol-1-yl) phenyl] sulfonylamino] phenyl] acetic acid
2-(3-아미노페닐)아세트산을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  2- (3-aminophenyl) acetic acid was used as a starting material and reacted in the same manner as in Example 1-127, to obtain the target compound.
ESI (m/z) 444 (MH+) 466 (MNa+) 442 (MH一)  ESI (m / z) 444 (MH +) 466 (MNa +) 442 (MH 一)
<실시예 1-171> N-(2-히드록시페닐) -4-(4-이소프로필 -2， 3-디메틸ᅳ 5-옥소—피 라졸 -1-일)벤젠설폰아미드의 제조 Example 1-171 Preparation of N- (2-hydroxyphenyl) -4- (4-isopropyl-2,3-dimethyl ᅳ 5-oxo-pyrazol-1-yl) benzenesulfonamide
2一아미노페놀을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법으로 반 웅시켜 목적 화합물을 수득하였다.  The reaction product was reacted in the same manner as in Example 1-127, using dibasic aminophenol as a starting material, to obtain a target compound.
ESI (m/z) 402 (MH+) 424 (MNa+) 400 (MH  ESI (m / z) 402 (MH +) 424 (MNa +) 400 (MH
<실시예 1-172> N-(4-히드록시페닐) -4-(4-이소프로필 -2， 3-디메틸ᅳ 5-옥소—피 라졸 -i-일)벤젠설폰아미드의 제조 Example 1-172 N- (4-hydroxyphenyl) -4- (4-isopropyl-2,3-dimethyl ᅳ 5-oxo-blood Preparation of Razol-i-yl) benzenesulfonamide
4-아미노페놀을 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다, Reaction was carried out in the same manner as in Example 1-127 using 4-aminophenol as a starting material, to obtain the desired compound .
ESI (m/z) 402 (MH+) 424 (MNa+) 400 (MH-)  ESI (m / z) 402 (MH +) 424 (MNa +) 400 (MH-)
<실시예 1-173> 4-[2, 3-디메틸 -5-옥소— 4-[4- (트리플루오로메틸)페닐]피라졸- 1ᅳ일] -N-(2-페녹시에틸)벤젠설폰아미드의 제조 Example 1-173 4- [2,3-dimethyl-5-oxo—4- [4- (trifluoromethyl) phenyl] pyrazol-1xyl] -N- (2-phenoxyethyl) benzene Preparation of Sulfonamide
(4— (트리플루오로메틸)페닐)보로닉산을 출발물질로 사용하여 상기 실시예 1- 168과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  (4— (trifluoromethyl) phenyl) boronic acid was used as a starting material and reacted in the same manner as in Examples 1-168, to obtain the target compound.
1H 丽 R (400MHz, DMSO— d6) δ 7.98 (d, 2H, J = 8.8 Hz), 7.67-7.58 (m, 6H), 7,24—7,21(m, 2H) ' 6.92 (t, 1H, J = 7.4 Hz), 6.78 (d, 2H, J = 8.0 Hz), 5.25 (t, 1H, J = 6ᅳ 2 Hz), 3.96 (t, 2H, J - 5.2 Hz), 3.35 (q, 2H, J = 5.6 Hz), 3.16 (s, 3H), 2.40 (s, 3H)  1H δ R (400MHz, DMSO— d6) δ 7.98 (d, 2H, J = 8.8 Hz), 7.67-7.58 (m, 6H), 7,24—7,21 (m, 2H) '6.92 (t, 1H , J = 7.4 Hz), 6.78 (d, 2H, J = 8.0 Hz), 5.25 (t, 1H, J = 6 ᅳ 2 Hz), 3.96 (t, 2H, J-5.2 Hz), 3.35 (q, 2H , J = 5.6 Hz), 3.16 (s, 3H), 2.40 (s, 3H)
<실시예 1-174> N-[3— (히드록시메틸)페닐] -4-(4-이소프로필—2， 3ᅳ디메틸 -5—옥 소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-174 of N- [3— (hydroxymethyl) phenyl] -4- (4-isopropyl-2,3'dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Produce
(3—아미노페닐)메탄올을 출발물질로 사용하여 상기 실시예 1-127과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다,  (3—Aminophenyl) methanol was used as a starting material and the reaction was carried out in the same manner as in Example 1-127, to obtain the target compound.
1H NMR (400MHz, DMS0-d6) d 10.30 (s, 1H) , 7.84 (d, 2H, J = 8.8 Hz), 7.52 (d, 2H, J = 8.4 Hz), 7.19 - 7.12 (m, 2H) , 7.01 - 6.94 (m, 2H) , 5.17 (t, 1H, J = 5.8 Hz), 4.39 (d, 2H, J = 4.0 Hz), 2.93 (s, 3H) , 2.78 - 2.68 (m, II— I) , 2.19 (s, 3H), 1.16 (d, 6H, J = 6.8 Hz)  1 H NMR (400 MHz, DMS0-d6) d 10.30 (s, 1H), 7.84 (d, 2H, J = 8.8 Hz), 7.52 (d, 2H, J = 8.4 Hz), 7.19-7.12 (m, 2H), 7.01-6.94 (m, 2H), 5.17 (t, 1H, J = 5.8 Hz), 4.39 (d, 2H, J = 4.0 Hz), 2.93 (s, 3H), 2.78-2.68 (m, II—I) , 2.19 (s, 3H), 1.16 (d, 6H, J = 6.8 Hz)
<실시예 1ᅳ175> (6-히드특시-1-나프틸)-4-(4-이소프로필-2,3-디메틸-5-옥 소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-175 Of (6-Hydroxy-1-naphthyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Produce
5-아미노나프탈렌 -2-올을 출발물질로 사용하여 상기 실시예 1—127과 같은 방 법으로 반웅시켜 목적 화합물을 수득하였다.  5-aminonaphthalene-2-ol was used as a starting material and the reaction was carried out in the same manner as in Examples 1-127, to obtain the target compound.
ESI (m/z) 452 (MH+) 450 (MH-); 1H NMR (400 MHz, DMSO— d6) δ 10.12 (s, 1H), 9.79 (s, 1H), 7.84 (d, 1H, J = 9.2 Hz), 7.73 (d, 2H, J = 8。4 Hz), 7.53 (d, 1H, J = 8.4 Hz), 7.47 (d, 2H, J = 8.4 Hz), 7.27 (t, 1H, J = 8.4 Hz), 7.07 (d, 1H, 1 = 2. Hz), 6.97 (dd, 1H, Ja = 12,0 Hz, Jb = 2.4 Hz), 6.92 (d, 1H, J = 7.6)， 2.90 (s, 3H), 2.78-2.68 (m, 1H), 2.19 (s, 3H)， 1.18 (d, 6H, J - 7.2) <실시예 1-176〉 4- (4—이소프로필ᅳ 2， 3—디메틸— 5-옥소ᅳ피라졸 -1-일)— Nᅳ (2—페녹 시프로필)벤젠설폰아미드의 제조 ESI (m / z) 452 (MH < + &gt;) 450 (MH-); 1 H NMR (400 MHz, DMSO— d6) δ 10.12 (s, 1H), 9.79 (s, 1H), 7.84 (d, 1H, J = 9.2 Hz), 7.73 (d, 2H, J = 8。4 Hz) , 7.53 (d, 1H, J = 8.4 Hz), 7.47 (d, 2H, J = 8.4 Hz), 7.27 (t, 1H, J = 8.4 Hz), 7.07 (d, 1H, 1 = 2. Hz), 6.97 (dd, 1H, Ja = 12,0 Hz, Jb = 2.4 Hz), 6.92 (d, 1H, J = 7.6), 2.90 (s, 3H), 2.78-2.68 (m, 1H), 2.19 (s, 3H), 1.18 (d, 6H, J-7.2) Example 1-176 Preparation of 4- (4—Isopropyl ᅳ 2, 3—dimethyl— 5-oxo-pyrazol-1-yl) —N ′ (2—phenoxypropyl) benzenesulfonamide
2-페녹시프로판 -1-아민을 출발물질로 사용하여 상기 실시예 1—127과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다.  2-Phenoxypropane-1-amine was used as a starting material and reacted in the same manner as in Example 1-127, to obtain the target compound.
ESI (m/z) 444 (MH+) 466 (MNa+) 442 (MH-)  ESI (m / z) 444 (MH +) 466 (MNa +) 442 (MH-)
<실시예 1-177> N-[2-(2-플루오로페녹시 )에틸 ] -4-(4-이소프로필ᅳ2， 3-디메틸— 5-옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-177 N- [2- (2-fluorophenoxy) ethyl] -4- (4-isopropyl 이 2, 3-dimethyl- 5-oxo-pyrazol-1-yl) benzenesulfon Preparation of Amides
2— (2—플루오로페녹시)에탄아민을 출발물질로 사용하여 상기 실시예 1-127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다,  2— (2—fluorophenoxy) ethanamine was used as a starting material to react the same method as in Example 1-127 to obtain the target compound.
ESI (m/z) 448 (MH+) 446 (MH-)； 1H NMR (400 MHz, DMS0—d6) δ 8.01 (t, 1H, J = 5.8 Hz), 7.91 (d, 2H, J = 8.8 Hz), 7.56 (d, 2H, 8.8 Hz), 7.22-7.17 (m, 1H), 7.10-7.08 (m, 2H) , 6.96-6.89 (m, 1H) , 4.05 (t, 2H, J = 5,6 Hz), 3.18 (q, 2H, J =: 5.6 Hz), 2.96 (s, 3H) , 2.79-2.72 (m, 1H), 2.22 (s, 3H) , 1.19 (d, 6H, J = 6.8 Hz) ESI (m / z) 448 (MH &lt; + &gt;) 446 (MH-); 1 H NMR (400 MHz, DMS0—d6) δ 8.01 (t, 1H, J = 5.8 Hz), 7.91 (d, 2H, J = 8.8 Hz) , 7.56 (d, 2H, 8.8 Hz), 7.22-7.17 (m, 1H), 7.10-7.08 (m, 2H), 6.96-6.89 (m, 1H), 4.05 (t, 2H, J = 5,6 Hz ), 3.18 (q, 2H, J = : 5.6 Hz), 2.96 (s, 3H), 2.79-2.72 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz)
<실시예 1-178> N-[4-[2- (디메틸아미노)에록시]페닐]—4— (4-이소프로필 -2,3- 디메틸 -5-옥소-피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example 1-178 N- [4- [2- (dimethylamino) ethoxy] phenyl] -4— (4-isopropyl-2,3-dimethyl-5-oxo-pyrazol-1xyl) benzene Preparation of Sulfonamide
4一 (2- (디메틸아미노)에록시)아닐린을 출발물질로 사용하여 상기 실시예 1— 127과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  4I (2- (dimethylamino) ethoxy) aniline was used as a starting material and reacted in the same manner as in Examples 1 to 127, to obtain the target compound.
ESI (m/z) 473 (MH+) 471 (MH— ); 1H NMR (400 MHz, DMSO— d6) δ 10.05 (s, 1H), 7.77 (d, 2H, J = 8,8 Hz), 7.51 (d, 2H, J = 8.8 Hz), 7.02 (d, 2H, J = 8.8 Hz), 6.84 (d, 2H, J = 8.8 Hz), 4,06 (t, 2H, J = 5.6 Hz), 2.93 (s, 3H), 2,89 (t, 2H, J = 9,2 Hz), 2.79-2.68 (ra, 1H), 2.42 (s, 6H), 2.19 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz)  ESI (m / z) 473 (MH &lt; + &gt;) 471 (MH—); 1 H NMR (400 MHz, DMSO—d6) δ 10.05 (s, 1H), 7.77 (d, 2H, J = 8,8 Hz), 7.51 (d, 2H, J = 8.8 Hz), 7.02 (d, 2H, J = 8.8 Hz), 6.84 (d, 2H, J = 8.8 Hz), 4,06 (t, 2H, J = 5.6 Hz), 2.93 (s, 3H), 2,89 (t, 2H, J = 9 , 2 Hz), 2.79-2.68 (ra, 1H), 2.42 (s, 6H), 2.19 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz)
<실시예 1-179> 메틸 3-[[4-(4-이소프로필 -2，3-디메틸_5-옥소-피라졸-1-일) 페닐]설포닐아미노]프로파노에이트의 제조 Example 1-179 Preparation of Methyl 3-[[4- (4-isopropyl-2,3-dimethyl_5-oxo-pyrazol-1-yl) phenyl] sulfonylamino] propanoate
메틸 3—아미노프로파노에이트를 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  The desired compound was obtained by reaction in the same manner as in Example 1-127 using methyl 3-aminopropanoate as a starting material.
ESI (m/z) 396 (MH+) 418 (MNa+)； 1H NMR (400 MHz, DMS0-d6) δ 7.87 (d, 2H, J = 6.6 Hz), 7.77 (t, 1H, J - 5.8 Hz), 7.58 (d, 2H, J = 8.8 Hz), 3.57 (s, 3H), 3.02-2.97 (m, 5H) , 2.81-2.72 (m, 1H), 2.47 (t, 2H, J = 6.8 Hz), 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz) ESI (m / z) 396 (MH &lt; + &gt;) 418 (MNa &lt; + &gt;); 1 H NMR (400 MHz, DMS0-d6) δ 7.87 (d, 2H, J = 6.6 Hz), 7.77 (t, 1H, J-5.8 Hz), 7.58 (d, 2H, J = 8.8 Hz), 3.57 (s, 3H), 3.02-2.97 (m, 5H), 2.81- 2.72 (m, 1H), 2.47 (t, 2H, J = 6.8 Hz), 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz)
<실시예 1-180> N— (4-히드록시 -3-메틸-페닐 )— 4- (4-이소프로필 -2 , 3一디메틸 -5- 옥소-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-180 N— (4-hydroxy-3-methyl-phenyl) — 4- (4-isopropyl-2, 3 dimethyl-5-oxo-pyrazol-1-yl) benzenesulfonamide Manufacture
4-아미노—2-메틸페놀을 출발물질로 사용하여 상기 실시예 1ᅳ 127과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  Using 4-amino-2-methylphenol as a starting material, the reaction was carried out in the same manner as in Example 1-127 to obtain the target compound.
1H NMR (400MHz, DMS0-d6) d 9.70 (s, 1H) , 9.21 (s, 1H), 7.73 (d, 2H, J = 8.8 Hz), 7.51 (d, 2H, J = 8.8 Hz), 6.78 - 6.60 (m, 3H) , 2.93 (s, 3H) , 2,79 ᅳ 2.69 (in, 1H), 2.19 (s, 3H) , 2.00 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz); 13C NMR (400MHz, DMS0-d6) d 165.13, 155.59, 153.35, 139.17, 136ᅳ 02， 128.60, 128.11 (2), 125.55, 124.76, 121.99 (2)， 121.43, 115.14, 114.59, 37.19, 23.92， 21.30 (2), 16.44， 11.29  1 H NMR (400 MHz, DMS0-d6) d 9.70 (s, 1H), 9.21 (s, 1H), 7.73 (d, 2H, J = 8.8 Hz), 7.51 (d, 2H, J = 8.8 Hz), 6.78- 6.60 (m, 3H), 2.93 (s, 3H), 2,79 ᅳ 2.69 (in, 1H), 2.19 (s, 3H), 2.00 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz) ; 13C NMR (400 MHz, DMS0-d6) d 165.13, 155.59, 153.35, 139.17, 136 ᅳ 02, 128.60, 128.11 (2), 125.55, 124.76, 121.99 (2), 121.43, 115.14, 114.59, 37.19, 23.92, 21.30 ( 2), 16.44 ， 11.29
<실시예 1-217> N-(4-히드록시 - [ 1 , 1 ' -바이페닐] -3-일 ) -4ᅳ (4-이소프로필— 2， 3- 디메틸ᅳ 5—옥소 -2， 5-디히드로 -1Η-피라졸 -1-일 )벤젠설폰아미드의 제조 Example 1-217 N- (4-hydroxy- [1,1′-biphenyl] -3-yl) -4 ′ (4-isopropyl—2, 3-dimethyl ᅳ 5—oxo-2, Preparation of 5-dihydro-1Η-pyrazol-1-yl) benzenesulfonamide
3-아미노 -[1，1、-바이페닐] -4-을을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 81.45%의 수율로 수득하였다.  3-amino- [1,1, -biphenyl] -4- was used as a starting material to react the same method as in Example 1-1, to obtain the target compound in a yield of 81.45%.
ESI (m/z) 478 (MH+); 1H NMR (400MHz, DMS0-d6) d 8.07 (d, 2H, J = 8.8 Hz), 7.65 (d, 2H, J = 8.8), 7.52 (d, 2H, J = 7.6 Hz), 7.42 (t, 2H, J = 7.6 Hz), 7.33 (t, 1H, J = 7.4), 7.02 - 6.99 (m, 2H) , 6.78 (dd, 1H, J = 8.4, 2.0 Hz), 5.24 (s, 1H), 2.97 (s, 3H) , 2.79 ― 2.73 (m, 1H) , 2.22 (s, 3H) , 1.19 (d, 6H, J = 8.0 Hz); 13C NMR (100MHz, DMSCK16) d 206.9, 165.2, 156.5, 141.6, 141.1, 140.0 (2)， 135.4, 130.7， 130.0, 129.2 (2), 127,8, 126.8 (2)， 123.6, 123.0, 121.7， 114.8， 73.9, 37.4, 31.1， 23.9, 21.2 (2), 11.3  ESI (m / z) 478 (MH &lt; + &gt;); 1 H NMR (400 MHz, DMS0-d6) d 8.07 (d, 2H, J = 8.8 Hz), 7.65 (d, 2H, J = 8.8), 7.52 (d, 2H, J = 7.6 Hz), 7.42 (t, 2H , J = 7.6 Hz), 7.33 (t, 1H, J = 7.4), 7.02-6.99 (m, 2H), 6.78 (dd, 1H, J = 8.4, 2.0 Hz), 5.24 (s, 1H), 2.97 ( s, 3H), 2.79-2.73 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 8.0 Hz); 13C NMR (100MHz, DMSCK16) d 206.9, 165.2, 156.5, 141.6, 141.1, 140.0 (2), 135.4, 130.7, 130.0, 129.2 (2), 127,8, 126.8 (2), 123.6, 123.0, 121.7, 114.8 , 73.9, 37.4, 31.1, 23.9, 21.2 (2), 11.3
<실시예 1-218> N-(2-히드록시페닐 )-4-(4-이소프로필— 2，3-디메틸-5-옥소- 2， 5-디히드로 -1H-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-218 N- (2-hydroxyphenyl) -4- (4-isopropyl— 2,3-dimethyl-5-oxo-2, 5-dihydro-1H-pyrazol-1-yl Preparation of Benzenesulfonamide
2一아미노페놀을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅 시켜 목적 화합물을 55.04<¾의 수율로 수득하였다, Using the 2-aminoaminophenol as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound in a yield of 55.04 < ¾,
ESI (m/z) 402 (MH+); 1H NMR (400MHz, DMS0-d6) d 8,02 (d, 2H, J = 8ᅳ 8 Hz), 7.62 (d, 2H, J = 8.8 Hz), 6.98 - 6.92 (m, 2H), 6.70 (dd, 1H, J = 8.0， 1,6 Hz), 6.51 ᅳ 6.47 (m, 1H) , 5.03 (s, 2H), 2.97 (s, 3H), 2.81 ᅳ 2.71 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 7.2 Hz); 13C NMR (100MHz, DMS0-d6) d 165.2, 156.4, 141.3, 141.0, 135.7, 130.7, 129.9 (2), 128.1, 122.6， 121.7 (2), 116.8, 116.1, 114.8, 37.4, 23.9, 21.2 (2), 11.3 ESI (m / z) 402 (MH &lt; + &gt;); 1 H NMR (400 MHz, DMS0-d6) d 8,02 (d, 2H, J = 8 ᅳ 8 Hz), 7.62 (d, 2H, J = 8.8 Hz), 6.98-6.92 (m, 2H), 6.70 (dd, 1H, J = 8.0, 1,6 Hz), 6.51 ᅳ 6.47 (m, 1H), 5.03 (s, 2H), 2.97 (s, 3H), 2.81 ᅳ 2.71 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 7.2 Hz); 13C NMR (100MHz, DMS0-d6) d 165.2, 156.4, 141.3, 141.0, 135.7, 130.7, 129.9 (2), 128.1, 122.6, 121.7 (2), 116.8, 116.1, 114.8, 37.4, 23.9, 21.2 (2) , 11.3
<실시예 1-219> N-(5-히드록시나프탈렌 -2—일) -4-(4-이소프로필 -2，3ᅳ디메틸— 5-옥소ᅳ 2， 5-디히드로 -1H—피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-219 N- (5-hydroxynaphthalene-2—yl) -4- (4-isopropyl-2,3'dimethyl—5-oxo 5- 2, 5-dihydro-1H—pyrazole -1-yl) benzenesulfonamide
6-아미노나프탈렌 -1—올을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법 으로 반웅시켜 목적 화합물을 5, 03%의 수율로 수득하였다.  6-aminonaphthalene-1—ol was used as a starting material and reacted in the same manner as in Example 1-1 to obtain the target compound in a yield of 5, 03%.
ESI (m/z) 452 (MH+) 450 (MH-)； 1H NMR (400MHz, DMS0-d6) d 7.98 (d, 2H, J = 8.4 Hz), 7.61 (d, 2H, J = 8.4 Hz), 7,50 (d, 1H, J = 8.8 Hz), 7.45 (d, 1H, J = 8.4 Hz), 7.23 (t, 1H, J = 7.8 Hz), 6.90 (d, 1H, J = 8.8 Hz), 6.81 ― 6.78 (ni, 2H), 5.58 (s, 2H), 2.93 (s, 3H), 2.79 - 2.72 (m, 1H) , 2.22 (s, 3H), 1.19 (d, 6H, J = 6,8 Hz); 13C NMR (100MHz, DMS0-d6) d 165.1, 156.4, 147.9, 145.8, 141.0, 137.1, 130.5, 129.7 (2), 125.8, 124.9, 122.3， 122.0 (2)， 119.5, 119,5' 114.8, 113.44, 105.8, 37.4, 23.9, 21.2 (2)， 11.3  ESI (m / z) 452 (MH &lt; + &gt;) 450 (MH-); 1 H NMR (400 MHz, DMS0-d6) d 7.98 (d, 2H, J = 8.4 Hz), 7.61 (d, 2H, J = 8.4 Hz), 7,50 (d, 1H, J = 8.8 Hz), 7.45 (d, 1H, J = 8.4 Hz), 7.23 (t, 1H, J = 7.8 Hz), 6.90 (d, 1H, J = 8.8 Hz), 6.81-6.78 (ni, 2H), 5.58 (s, 2H), 2.93 (s, 3H), 2.79-2.72 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 6,8 Hz); 13C NMR (100MHz, DMS0-d6) d 165.1, 156.4, 147.9, 145.8, 141.0, 137.1, 130.5, 129.7 (2), 125.8, 124.9, 122.3, 122.0 (2), 119.5, 119,5 '114.8, 113.44, 105.8, 37.4, 23.9, 21.2 (2), 11.3
<실시예 l-220> 4— (4-브로모 -2， 3—디메틸 -5—옥소— 2, 5ᅳ디히드로 -1H—피라졸—1— 일) -N-(2, 4-디메틸페닐)벤젠설폰아미드의 제조 Example l-220 4— (4-Bromo-2,3—dimethyl-5—oxo—2,5 ᅳ dihydro-1H—pyrazole—1—yl) -N- (2,4-dimethylphenyl Preparation of Benzenesulfonamide
2, 4ᅳ디메틸아닐린을 출발물질로 사용하여 상기 실시예 1—127과 같은 방법으 로 반웅시켜 목적 화합물을 29.13%의 수율로 수득하였다。  Using 2,4'dimethylaniline as starting material, the reaction was carried out in the same manner as in Examples 1 to 127 to obtain the target compound in a yield of 29.13%.
ESI (m/z) 451 (MH+) 449 (MH— ); 1H 丽 R (400MHz, DMS0-cl6) cl 9.54 (s, 1H), 7.76 (dd, 2H, J = 8.6， 1.4 Hz), 7.54 (dd, 2H, J = 8.8， 2.4 Hz), 6.95 (s, 1H), 6.90 (d, 1H, J = 8.4 Hz), 6,83 (d, 1H, J = 8.4 Hz), 3.13 (d, 3H, J = 8.8 Hz), 2.32 (s, 3H), 2.20 (s, 3H), 1.96 (s, 3H)； 13C NMR (100MHz, DMS0— d6) d 161.8， 161.1， 157.4, 155.5, 138.5， 136.3, 134.7, 132.3， 131.7, 128.1, 127.2, 123.5, 100.7, 88.5, 37.1, 20.8, 17,9， 12.7, 11.5  ESI (m / z) 451 (MH &lt; + &gt;) 449 (MH—); 1 H δ R (400 MHz, DMS0-cl6) cl 9.54 (s, 1H), 7.76 (dd, 2H, J = 8.6, 1.4 Hz), 7.54 (dd, 2H, J = 8.8, 2.4 Hz), 6.95 (s, 1H), 6.90 (d, 1H, J = 8.4 Hz), 6,83 (d, 1H, J = 8.4 Hz), 3.13 (d, 3H, J = 8.8 Hz), 2.32 (s, 3H), 2.20 ( s, 3H), 1.96 (s, 3H); 13 C NMR (100 MHz, DMS0—d6) d 161.8, 161.1, 157.4, 155.5, 138.5, 136.3, 134.7, 132.3, 131.7, 128.1, 127.2, 123.5, 100.7, 88.5, 37.1, 20.8, 17,9, 12.7, 11.5
<실시예 1-221> 4-(4—이소프로필 -2 , 3-디메틸 -5-옥소 -2， 5—디히드로 -1H—피라졸 -1-일 )-Ν-(4-(2-몰포리노에특시 )페닐 )벤젠설폰아미드의 제조 Example 1-221 4- (4—Isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro-1H—pyrazol-1-yl) -Ν- (4- (2- Preparation of morpholino-specific) phenyl) benzenesulfonamide
4-(2—몰포리노에록시)아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다. Using 4- (2—morpholinoethoxy) aniline as starting material, the same procedure as in Example 1-1 The reaction was carried out to obtain the desired compound.
<실시예 1-222> N-C2， 4-디히드록시페닐 ) -4-(4-이소프로필ᅳ 2 , 3-디메틸 -5-옥소 —2, 5ᅳ디히드로ᅳ 1H—피라졸 -1-일)벤젠설폰아미드의 제조 <Example 1-222> N-C2, 4-dihydroxyphenyl) -4- (4-isopropyl '2, 3-dimethyl-5-oxo —2, 5' dihydro ᅳ 1H—pyrazole-1- (1) Preparation of Benzenesulfonamide
4-아미노벤젠— 1,3-디을을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법 으로 반웅시켜 목적 화합물을 17.01%의 수율로 수득하였다ᅳ  Reaction was carried out in the same manner as in Example 1-1, using 4-aminobenzene-1,3-di as starting material to obtain the target compound in a yield of 17.01%.
ESI (m/z) 418 (MH+) 416 (MH-)； 1H NMR (400MHz, DMS0-d6) d 7.74 (d, 2H, J = 8.8 Hz), 7.48 (d, 2H, J = 8.8 Hz), 6.84 (d, 1H, J = 8.4 Hz), 6,18 (d, 1H, J = 2.8 Hz), 6.12 (dd, 1H, J = 8.4, 2.4 Hz), 2.94 (s, 3H) , 2.78 - 2.71 (m, 1H), 2.20 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100MHz, DMSO— d6) d 165.1, 157.0， 155.4, 153,2， 138.9, 137.3, 128.6, 128.1 (2), 121.6 (2)， 115.1, 114.6, 106.4， 103.0, 37.2, 23.9, 21.3 (2), 11.2  ESI (m / z) 418 (MH <+>) 416 (MH <->); 1 H NMR (400 MHz, DMS0-d6) d 7.74 (d, 2H, J = 8.8 Hz), 7.48 (d, 2H, J = 8.8 Hz), 6.84 (d, 1H, J = 8.4 Hz), 6,18 (d, 1H, J = 2.8 Hz), 6.12 (dd, 1H, J = 8.4, 2.4 Hz), 2.94 (s, 3H), 2.78-2.71 (m, 1 H), 2.20 (s, 3 H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100MHz, DMSO— d6) d 165.1, 157.0, 155.4, 153,2, 138.9, 137.3, 128.6, 128.1 (2), 121.6 (2), 115.1, 114.6, 106.4, 103.0, 37.2, 23.9, 21.3 ( 2), 11.2
<실시예 l-223> 4-(4-브로모 -2， 3-디메틸 -5—옥소 -2， 5-디히드로 - 1.H—피라졸 -1— 일)— N-(4— (트리플루오로메틸)페닐)벤젠설폰아미드의 제조 Example l-223 4- (4-Bromo-2, 3-dimethyl-5-oxo-2, 5-dihydro-1.H-pyrazole-1-yl) -N- (4— ( Preparation of Trifluoromethyl) phenyl) benzenesulfonamide
3- (트리플루오로메틸)아닐린을 출발물질로 사용하여 상기 실시예 1-127과 같 은 방법으로 반응시켜 목적 화합물을 32, 9%의 수율로 수득하였다.  3- (trifluoromethyl) aniline was used as a starting material and reacted in the same manner as in Example 1-127, to obtain the target compound in 32, 9% yield.
ESI (m/z) 490 (M)； 13C 丽 R (100MHz, DMS0-d6) d 161.9， 161.2, 158.5, 156.5, 140.4, 140.3, 135.1, 135.0, 132.8, 129.9 (2)， 123.2 (2), 101,0, 88.8, 37.5, 12.8, 11.6  ESI (m / z) 490 (M); 13 C D R (100 MHz, DMS0-d6) d 161.9, 161.2, 158.5, 156.5, 140.4, 140.3, 135.1, 135.0, 132.8, 129.9 (2), 123.2 (2), 101,0, 88.8, 37.5, 12.8, 11.6
<실시예 1-22 > N-(3-플루오로 -4-히드록시페닐 ) -4-(4-이소프로필 -2 , 3-디메틸 -5-옥소 -2， 5—디히드로 -1H-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-22 N- (3-fluoro-4-hydroxyphenyl) -4- (4-isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro-1H-pyra Preparation of sol-1-yl) benzenesulfonamide
4-아미노ᅳ2ᅳ플루오로페놀을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반응시켜 목적 화합물을 수득하였다.  Using 4-amino ᅳ 2 ᅳ fluorophenol as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
<실시예 1-225> 4-(4-이소프로필 -2， 3-디메틸 -5—옥소 -2 , 5-디히드로 -1H—피라졸 -1—일) -N— (2-메록시 -4-니트로페닐)벤젠설폰아미드의 제조 Example 1-225 4- (4-Isopropyl-2, 3-dimethyl-5—oxo-2, 5-dihydro-1H—pyrazole-1—yl) -N— (2-methoxy- Preparation of 4-nitrophenyl) benzenesulfonamide
2一메록시 -4-니트로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반응시켜 목적 화합물을 92.68%의 수율로 수득하였다.  The reaction product was reacted in the same manner as in Example 1-1 using 2-dimethoxy-4-nitroaniline as a starting material to obtain the target compound in a yield of 92.68%.
ESI (m/z) 461 (MH+) 459 (MH-)； 1H NMR (400MHz, DMSO— d6) d 10.34 (s, 1H), 7.97 (d, 2H, J = 8.8 Hz), 7.84 (dd, 1H, J = 8.8, 2.4 Hz), 7.73 (d, 1H, J = 2,4 Hz), 7.59 - 7.53 (m, 3H) , 3.83 (s, 3H) , 2.95 (s, 3H) , 2.79 - 2.69 (m, 1H), 2.21 (3H), 1.17 (d, 6H, J = 7,2 Hz); 13C NMR (100MHz, DMSO— d6) d 165.1, 155.8, 150.3, 144.1, 139.7, 135.9, 133.3, 128.2 (2)， 122.0 (2)， 120.1， 117.1, 114,5, 106.9， 56.8, 37.2, 23.9, 21.2 (2), 11.3 ESI (m / z) 461 (MH &lt; + &gt;) 459 (MH-); 1 H NMR (400 MHz, DMSO—d6) d 10.34 (s, 1 H), 7.97 (d, 2H, J = 8.8 Hz), 7.84 (dd, 1H) , J = 8.8, 2.4 Hz), 7.73 (d, 1H, J) = 2,4 Hz), 7.59-7.53 (m, 3H), 3.83 (s, 3H), 2.95 (s, 3H), 2.79-2.69 (m, 1H), 2.21 (3H), 1.17 (d, 6H, J = 7,2 Hz); 13C NMR (100MHz, DMSO— d6) d 165.1, 155.8, 150.3, 144.1, 139.7, 135.9, 133.3, 128.2 (2), 122.0 (2), 120.1, 117.1, 114,5, 106.9, 56.8, 37.2, 23.9, 21.2 (2), 11.3
<실시예 1-226〉 3-(4ᅳ(4-이소프로필 -2,3-디메틸—5-옥소-2ᅳ5-디히드로- -피 라졸 -1-일)페닐설폰아미도)벤조산의 제조 Example 1-226 of 3- (4 '(4-isopropyl-2,3-dimethyl-5-oxo-2'5-dihydro-pyrazol-1-yl) phenylsulfonamido) benzoic acid Produce
3ᅳ아미노벤조산을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 응시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1 using 3 'aminobenzoic acid as a starting material to obtain the target compound.
<실시예 1-227> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소 -2， 5-디히드로—1H-피라졸 — 1-일 )-N-(2-메특시—5-니트로페닐)벤젠설폰아미드의 제조 Example 1-227 4- (4-Isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro—1H-pyrazol — 1-yl) -N- (2-method— Preparation of 5-nitrophenyl) benzenesulfonamide
2—메톡시ᅳ 5—니트로아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반웅시켜 목적 화합물을 32, 04%의 수율로 수득하였다.  Using 2—methoxy 반 5—nitroaniline as a starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound in a yield of 32, 04%.
ESI (m/z) 461 (MH+) 459 (MH— ); 1H NMR (400MHz, DMS0-d6) d 10.14 (s, 1H), 8.12 (d, 1H, J = 2.4 Hz), 8.12 ᅳ 8.05 (m, 2H) , 7.85 (d, 2H, J = 8.8 Hz), 7.55 (d, 2H, J = 8.8 Hz), 7.16 (d, 1H, J = 9.2 Hz), 3.71 (s, 3H) , 2.95 (s, 3H), 2,78 - 2.71 (m, 1H), 2.21 (s, 3H) , 1.17 (d, 6H, J = 6.8 Hz); 13C NMR (100MHz, DMSO— d6) d 165. a, 157.5, 155.7, 140.7, 139.5, 136.1, 128.1 (2), 126.5, 122.9, 122.0 (2)， 119.3, 114.5, 112.2， 56.9, 37.1, 23.9, 21.2 (2)， 11.2  ESI (m / z) 461 (MH &lt; + &gt;) 459 (MH—); 1 H NMR (400 MHz, DMS0-d6) d 10.14 (s, 1H), 8.12 (d, 1H, J = 2.4 Hz), 8.12 ᅳ 8.05 (m, 2H), 7.85 (d, 2H, J = 8.8 Hz), 7.55 (d, 2H, J = 8.8 Hz), 7.16 (d, 1H, J = 9.2 Hz), 3.71 (s, 3H), 2.95 (s, 3H), 2,78-2.71 (m, 1H), 2.21 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO— d6) d 165.a, 157.5, 155.7, 140.7, 139.5, 136.1, 128.1 (2), 126.5, 122.9, 122.0 (2), 119.3, 114.5, 112.2, 56.9, 37.1, 23.9, 21.2 (2), 11.2
<실시예 l-228> 4-(4-이소프로필 -2， 3-디메틸 -5—옥소 -2， 5-디히드로— 1Hᅳ피라졸 -1ᅳ일) -N-(2-메틸벤조퓨란 -5-일)벤젠설폰아미드의 제조 Example l-228 4- (4-Isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro—1H ᅳ pyrazole-1xyl) -N- (2-methylbenzofuran- Preparation of 5-yl) benzenesulfonamide
2一메록시벤조퓨란— 5-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방 법으로 반옹시켜 목적 화합물을 수득하였다.  2 iloxybenzofuran—reflected in the same manner as in Example 1-1 using 5-amine as a starting material to obtain the target compound.
<실시예 1-229> N- 벤조 [b]티오펜 -5-일)— 4-(4-이소프로필ᅳ 2， 3-디메틸ᅳ 5-옥소 -2 , 5—디히드로 -1H-피라졸 1ᅳ일)벤젠설폰아미드의 제조 Example 1-229 N-Benzo [b] thiophen-5-yl) — 4- (4-isopropyl ᅳ 2, 3-dimethyl ᅳ 5-oxo-2, 5—dihydro-1H-pyrazole 1 day) Preparation of Benzenesulfonamide
벤조 [b]티오펜—5—아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반응시켜 목적 화합물을 수득하였다.  Using the benzo [b] thiophene-5 amine as a starting material it was reacted in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 442 (MH+) 440 (MH-) <실시예 1— 230 N- (벤조퓨란— 5-일) -4-(4-이소프로필 -2， 3-디메틸 -5-옥소— 2 , 5- 디히드로 -1H-피라졸 -1-일 )벤젠설폰아미드의 제조 ESI (m / z) 442 (MH +) 440 (MH-) Example 1 230 N- (benzofuran-5-yl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl Preparation of Benzenesulfonamide
벤조퓨란ᅳ 5-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  Benzofuranyl 5-amine was used as a starting material to react the same method as in Example 1-1 to obtain the target compound.
ESI (m/z) 426 (MH+) 424 (MH— )  ESI (m / z) 426 (MH +) 424 (MH—)
<실시예 1-231> N- (벤조퓨란 -5-일메틸 ) -4- ( 4-이소프로필 -2， 3-디메틸 -5-옥소- 2 , 5-디히드로 -1H-피라졸 -1—일)벤젠설폰아미드의 제조 Example 1-231 N- (benzofuran-5-ylmethyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazole-1 Preparation of benzenesulfonamide
벤조퓨란 -5-일메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법 으로 반웅시켜 목적 화합물을 수득하였다.  Using benzofuran-5-ylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound.
ESI (m/z) 440 (MH+) 438 (MH-)  ESI (m / z) 440 (MH +) 438 (MH-)
<실시예 1-232> 메틸 5-(4-(4-이소프로필 -2， 3-디메틸 -5-옥소 -2， 5-디히드로- 1H-피라졸— 1-일)페닐설폰아미도)벤조 [ b ]티오펜 -2-카르복실레이트의 제조 Example 1-232 Methyl 5- (4- (4-isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro-1H-pyrazol- 1-yl) phenylsulfonamido) Preparation of Benzo [b] thiophene-2-carboxylate
메틸 5-아미노벤조 [b]티오펜 -2-카볼실레이트을 출발물질로 사용하여 상기 실 시예 1-1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다.  Methyl 5-aminobenzo [b] thiophene-2-carbocylate was used as a starting material and reacted in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 500 (MH+) 498 (MH-)  ESI (m / z) 500 (MH +) 498 (MH-)
<실시예 1-233>메틸 4ᅳ ((4-(4ᅳ이소프로필— 2， 3-디메틸—5-옥소 -2 ,5—디히드로— 1Hᅳ피라졸 -1-일)페닐설폰아미도)메틸)벤조에이트의 제조 Example 1-233 Methyl 4 '((4- (4'isopropyl-2, 3-dimethyl-5-oxo-2,5-dihydro- 1 H ᅳ pyrazol-1-yl) phenylsulfonamido Preparation of Methyl) benzoate
메틸 4— (아미노메틸)벤조에이트을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 27.25«>의 수율로 수득하였다。  Reaction was carried out in the same manner as in Example 1-1, using methyl 4— (aminomethyl) benzoate as starting material, to obtain the target compound in a yield of 27.25 «>.
ESI (m/z) 458 (MH+) 480 (顧 a+) 456 (MH— ); 1H NMR (400MHz , DMS0-d6) d 8.33 (t, 1H, J = 6.2 Hz), 7.87 (d, 2H, J = 2.0 Hz), 7.85 (d, 2H, J = 2.0 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.40 (d, 2H, J = 8.4 Hz), 4.11 (d, 2H, J = 5.6 Hz), 3.83 (s, 3H), 2.95 (s, 3H) , 2.79 ᅳ 2.72 (m, 1H) , 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR ( XMHz, DMS으 d6) d 166.39, 165.18, 155.58, 143.72, 139.11, 136.96, 129.49 (2), 128.78, 128.18 (2)， 127.92 (2)， 122.15 (2), 114.56, 52.49, 46.15， 37.12, 23.95, 21.30, 11.29  ESI (m / z) 458 (MH &lt; + &gt;) 480 (VII a +) 456 (MH—); 1 H NMR (400 MHz, DMS0-d6) d 8.33 (t, 1H, J = 6.2 Hz), 7.87 (d, 2H, J = 2.0 Hz), 7.85 (d, 2H, J = 2.0 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.40 (d, 2H, J = 8.4 Hz), 4.11 (d, 2H, J = 5.6 Hz), 3.83 (s, 3H), 2.95 (s, 3H), 2.79 ᅳ 2.72 ( m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (d6 at XMHz, DMS) d 166.39, 165.18, 155.58, 143.72, 139.11, 136.96, 129.49 (2), 128.78, 128.18 (2), 127.92 (2), 122.15 (2), 114.56, 52.49, 46.15, 37.12, 23.95, 21.30, 11.29
<실시예 1— 234> 메틸 6-(4—(4-이소프로필-2，3-디메틸-5-옥소—2，5-디히드로- 1H-피라졸 -1-일)페닐설폰아미도) -2-나프토에이트의 제조 Example 1—234 Methyl 6- (4— (4-isopropyl-2,3-dimethyl-5-oxo—2,5-dihydro- Preparation of 1H-pyrazol-1-yl) phenylsulfonamido) -2-naphthoate
메틸 6—아미노 -2-나프토에이트을 출발물질로 사용하여 상기 실시예 1-1과 같 은 방법으로 반웅시켜 목적 화합물을 20, 03%의 수율로 수득하였다,  Using methyl 6-amino-2-naphthoate as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound in a yield of 20, 03%.
ESI (m/z) 494 (MH+) 492 (MH-)； 1H NMR (400MHz, DMS0-d6) d 10.86 (s, 1Η)' 8.51 (s, 1H), 8.05 (d, 1H, J = 8.8 Hz), 7.97 (d, 2H, J = 8.4 Hz), 7.91 (s, 2H), 7.70 (s, 1H), 7.55 (d, 2H, J = 8.4 Hz), 7.43 (d, 1H, J - 8.4 Hz), 3.89 (s, 3H), 2.90 (s, 3H), 2.74 - 2.67 (m, 1H) , 2.17 (s, 3H), 1.14 (d, 6H, J = 7.2 Hz); 13C 丽 R (100MHz, DMS0-d6) d 166.62, 165.14, 155.84, 139.69， 138.31, 136.03, 135.55, 131.31, 130.73, 129.14, 128.23 (2)， 128.10， 126.12, 125.95, 122.09 (2)， 120.91， 114.76， 114.59, 52ᅳ 57， 37.25, 23.88， 21.23 (2)， 11.26  ESI (m / z) 494 (MH &lt; + &gt;) 492 (MH-); 1 H NMR (400 MHz, DMS0-d6) d 10.86 (s, 1Η) '8.51 (s, 1H), 8.05 (d, 1H, J = 8.8 Hz ), 7.97 (d, 2H, J = 8.4 Hz), 7.91 (s, 2H), 7.70 (s, 1H), 7.55 (d, 2H, J = 8.4 Hz), 7.43 (d, 1H, J-8.4 Hz ), 3.89 (s, 3H), 2.90 (s, 3H), 2.74-2.67 (m, 1H), 2.17 (s, 3H), 1.14 (d, 6H, J = 7.2 Hz); 13C δ R (100MHz, DMS0-d6) d 166.62, 165.14, 155.84, 139.69, 138.31, 136.03, 135.55, 131.31, 130.73, 129.14, 128.23 (2), 128.10, 126.12, 125.95, 122.09 (2), 120.91, 11476 , 114.59, 52 ᅳ 57, 37.25, 23.88, 21.23 (2), 11.26
<실시예 l-235> 4-(4-이소프로필— 2 , 3-디메틸 -5-옥소— 2 , 5-디히드로 -1Hᅳ피라졸 ᅳ 1-일) -Ν-메시틸벤젠설폰아미드의 제조 Example l-235 of 4- (4-isopropyl—2, 3-dimethyl-5-oxo—2,5-dihydro-1H ᅳ pyrazol X 1-yl) -N-methylbenzenesulfonamide Produce
2,4,6—트리메틸아닐린을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법 으로 반웅시켜 목적 화합물을 60, 81%로 수득하였다.  2,4,6—trimethylaniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound at 60, 81%.
ESI (m/z) 428 (MH+) 426 (顧ᅳ); 1H NMR (400MHz, DMS0-d6) d 9.24 (s, 1H), 7.73 (d, 2H, J = 8.4 Hz), 7.55 (d, 2H, J = 8.8 Hz), 6.82 (s, 2H)， 2.95 (s, 3H), 2.95 - 2.73 (m, 1H) , 2.20 (d, 6H' J = 11.6 Hz), 1.92 (s, 6H) , 1.20 (d, 6H, J = 6.8 Hz); 13C NMR (100MHz, DMSO— d6) d 165.08, 155.57, 139.13, 138.29， 137.73 (2), 136.74, 131.04, 129.43 (2), 127.86 (2), 122.28 (2)， 114.71, 37.17, 23.94， 21.33 (2), 20,83, 18.74 (2), 11.30  ESI (m / z) 428 (MH &lt; + &gt;) 426 (iii); 1 H NMR (400 MHz, DMS0-d6) d 9.24 (s, 1H), 7.73 (d, 2H, J = 8.4 Hz), 7.55 (d, 2H, J = 8.8 Hz), 6.82 (s, 2H), 2.95 ( s, 3H), 2.95-2.73 (m, 1H), 2.20 (d, 6H 'J = 11.6 Hz), 1.92 (s, 6H), 1.20 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO— d6) d 165.08, 155.57, 139.13, 138.29, 137.73 (2), 136.74, 131.04, 129.43 (2), 127.86 (2), 122.28 (2), 114.71, 37.17, 23.94, 21.33 ( 2), 20,83, 18.74 (2), 11.30
〈실시예 1-236>N-(9,10-디옥소 -9，10-디히드로안트라센-2—일)—4-(4-이소프로 필 -2， 3-디메틸 -5—옥소 -2， 5—디히드로 -1H-피라졸 -1-일 )벤젠설폰아미드의 제조 Example 1-236 N- (9,10-dioxo-9,10-dihydroanthracene-2—yl) —4- (4-isopropyl-2, 3-dimethyl-5—oxo-2 , 5—dihydro-1H-pyrazol-1-yl) benzenesulfonamide
6-아미노 -4a, 9a—디히드로안트라센 -9,1으디온을 출발물질로 사용하여 상기 실 시예 1—1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  6-Amino-4a, 9a-dihydroanthracene-9,1 adione was used as a starting material and the reaction was carried out in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 516 (MH+) 514 (MH-)  ESI (m / z) 516 (MH +) 514 (MH-)
<실시예 1-237> 4- (4—이소프로필 -2 , 3-디메틸 -5-옥소 -2 , 5-디히드로 -1H—피라졸 —1-일) -N- (이소퀴놀린 -5-일)벤젠설폰아미드의 제조 Example 1-237 4- (4—Isopropyl-2, 3-dimethyl-5-oxo-2, 5-dihydro-1H—pyrazol —1-yl) -N- (isoquinoline-5- (1) Preparation of Benzenesulfonamide
이소퀴놀린— 5-아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반응시켜 목적 화합물을 수득하였다, Isoquinoline—In the same manner as in Example 1-1, using 5-amine as a starting material. Reaction to obtain the target compound,
ESI (m/z) 437 (MH+) 435 (MH— )  ESI (m / z) 437 (MH +) 435 (MH—)
<실시예 1-238> N-(벤조 [d] [ 1， 3]디옥실— 5-일 )— 4— (4—이소프로필— 2， 3-디메틸- 5-옥소 -2， 5-디히드로 -1H-피라졸 -1-일 )벤젠설폰아미드의 제조 Example 1-238 N- (benzo [d] [1,3] dioxyl—5-day) —4— (4—isopropyl—2, 3-dimethyl-5 oxo-2, 5-di Preparation of Hydro-1H-pyrazol-1-yl) benzenesulfonamide
벤조 [d] [ 1 , 3]디옥실ᅳ 5—아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반옹시켜 목적 화합물을 수득하였다.  Reaction was carried out in the same manner as in Example 1-1, using benzo [d] [1, 3] dioxyl ᅳ 5—amine as starting material to obtain the target compound.
ESI (m/z) 430 (MH+) 428 (MH-)  ESI (m / z) 430 (MH +) 428 (MH-)
<실시예 1-239> N- (벤조 [ d ] [ 1， 3 ]디옥실 -5-일메틸 ) -4ᅳ ( 4-이소프로필 -2， 3-디메 틸 -5-옥소 -2 , 5-디히드로 -1H-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1-239 N- (benzo [d] [1,3] dioxyl-5-ylmethyl) -4 ′ (4-isopropyl-2,3-dimethyl-5-oxo-2,5 Preparation of -dihydro-1H-pyrazol-1-yl) benzenesulfonamide
벤조 [d] [ 1 , 3]디옥실—5—일메탄아민을 출발물질로 사용하여 상기 실시예 1-1과 같은 방법으로 반웅시켜 목적 화합물을 수득하였다.  The desired compound was obtained by reaction in the same manner as in Example 1-1 using benzo [d] [1, 3] dioxyl-5-ylmethanamine as starting material.
ESI (m/z) 443 (MH+) 442 (MH-)  ESI (m / z) 443 (MH +) 442 (MH-)
<실시예 1-240> 4- (4ᅳ이소프로필 -2， 3-디메틸 -5-옥소ᅳ 2， 5-디히드로— 1H—피라졸 -1-일)— N-(2-옥소인돌린—5-일)벤젠설폰아미드의 제조 Example 1-240 4- (4 ᅳ isopropyl-2, 3-dimethyl-5-oxo ᅳ 2, 5-dihydro—1H—pyrazol-1-yl) —N- (2-oxoindolin —5-yl) benzenesulfonamide
5-아미노인돌린—2-온을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반응시켜 목적 화합물을 수득하였다.  5-Aminoindolin-2-2-one was used as a starting material and reacted in the same manner as in Example 1-1 to obtain the target compound.
ESI (m/z) 441 (MH+) 439 (MHᅳ)  ESI (m / z) 441 (MH +) 439 (MH ᅳ)
<실시예 1-241> 4-(4—브로모 -2，3-디메틸-5-옥소-2，5-디히드로-lH-피라졸—l- 일)-N-(4-(트리플루오로메틸)페닐)벤젠설폰아미드의 제조 Example 1-241 4- (4—Bromo-2,3-dimethyl-5-oxo-2,5-dihydro-lH-pyrazol-l-yl) -N- (4- (trifluoro Preparation of Rhomethyl) phenyl) benzenesulfonamide
4-트리플루오로아닐린을 출발물질로 사용하여 상기 실시예 1—127과 같은 방 법으로 반웅시켜 목적 화합물을 49.27%의 수율로 수득하였다.  4-trifluoroaniline was used as a starting material and reacted in the same manner as in Examples 1 to 127, to obtain the target compound in a yield of 49.27%.
ESI (m/z) 491 (MH+) 489 (MH— ) ; 1H NMR (400MHz , DMSO— d6) d 10.96 (s , 1H) , 7.96 (d, 2H , J = 7.6 Hz) , 7.63 - 7.56 (m , 4H) , 7.32 (d, 2H , J = 8.0 Hz) , 3.10 (d, 3H , J = 9.2 Hz) , 2.29 (s , 3H)；  ESI (m / z) 491 (MH &lt; + &gt;) 489 (MH—); 1 H NMR (400 MHz, DMSO— d6) d 10.96 (s, 1H), 7.96 (d, 2H, J = 7.6 Hz), 7.63-7.56 (m, 4H), 7.32 (d, 2H, J = 8.0 Hz), 3.10 (d, 3H, J = 9.2 Hz), 2.29 (s, 3H);
<실시예 l-242> 4-(4-이소프로필 -2， 3-디메틸 -5-옥소—2， 5ᅳ디히드로—1H-피라졸 — 1—일)— N-(2- (티오 ¾-2-일)에틸)벤젠설폰아미드의 제조 Example l-242 4- (4-isopropyl-2, 3-dimethyl-5-oxo—2, 5 ᅳ dihydro—1H-pyrazole — 1—yl) —N- (2- (thio ¾- Preparation of 2-yl) ethyl) benzenesulfonamide
2- (티오펜 -2—일)에탄 -1-아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반응시켜 목적 화합물을 25.13%의 수율로 수득하였다. Example 2- 1, using 2- (thiophene-2-yl) ethane-1-amine as starting material Reaction was carried out to give the desired compound in 25.13% yield.
ESI (m/z) 420 (MH+) 418 (MH— ); 1H丽 R (400MHz, DMS0-d6) d 7.88 - 7.81 (m, 3H), 7.57 (d, 2H, J = 8.4 Hz), 7.32 (d, 1H, J = 4.0 Hz), 6.93 ― 6.87 (m, 2H), 3.01 ― 2.93 (m, 7H), 2.79 ― 2.72 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100MHz, DMSO— d6) d 165.2, 155,5， 141.0, 139,1, 136.6, 127.9 (2)， 127.3, 125.9, 124.5, 122.2 (2), 114.5, 44.5. 37.2, 30.0, 23.9， 21.3 (2), 11.2  ESI (m / z) 420 (MH &lt; + &gt;) 418 (MH—); 1Heli R (400MHz, DMS0-d6) d 7.88-7.81 (m, 3H), 7.57 (d, 2H, J = 8.4 Hz), 7.32 (d, 1H, J = 4.0 Hz), 6.93-6.87 (m, 2H), 3.01-2.93 (m, 7H), 2.79-2.72 (m, 1H), 2.22 (s, 3H), 1.19 (d, 6H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO—d6) d 165.2, 155,5, 141.0, 139,1, 136.6, 127.9 (2), 127.3, 125.9, 124.5, 122.2 (2), 114.5, 44.5. 37.2, 30.0, 23.9, 21.3 (2), 11.2
<실시예 1— 243> 4-(4-이소프로필 -2 , 3-디메틸— 5_옥소 -2 , 5-디히드로 -1H—피라졸 —1-일) -Ν— (3,4,5—트리메록시페닐)벤젠설폰아미드의 제조 Example 1 243 4- (4-isopropyl-2,3-dimethyl-5_oxo-2,5-dihydro-1H—pyrazol —1-yl) -N— (3,4,5 Preparation of —trimethoxyphenyl) benzenesulfonamide
3, 4, 5-트리메록시아닐린을 출발물질로 사용하여 상기 실시예 1—1과 같은 방 법으로 반웅시켜 목적 화합물을 51.17%의 수율로 수득하였다ᅳ  3, 4, 5-trimethoxyaniline was used as a starting material and the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound in a yield of 51.17%.
ESI (m/z) 476 (MH+) 498 (MNa+) 474 (MH-)； 1H NMR (400MHz, DMS0~d6) d 10.13 (s, 1H), 7.86 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8,4 Hz), 6.40 (s, 2H), 3.65 (s, 6H), 3.56 (s, 3H), 2.93 (s, 3H) , 2,77 - 2.70 (m, IH) , 2.19 (s, 3H), 1.17 (d, 6H, J = 6.4 Hz); 13C NMR (100MHz, DMSO— d6) d 165.1, 155.7, 153.3 (2)， 139.5, 135.6, 134.6, 133.9, 128.3 (2)， 122.1 (2), 114,6， 98.4 (2), 60.4, 56.1 (2), 37.2, 23.9, 21,2 (2)， 11.2 ESI (m / z) 476 (MH <+>) 498 (MNa <+>) 474 (MH <->); 1 H NMR (400 MHz, DMS0 to d6) d 10.13 (s, 1H), 7.86 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8,4 Hz), 6.40 (s, 2H), 3.65 (s, 6H), 3.56 (s, 3H), 2.93 (s, 3H), 2,77-2.70 (m, IH ), 2.19 (s, 3 H), 1.17 (d, 6 H, J = 6.4 Hz); 13C NMR (100MHz, DMSO— d6) d 165.1, 155.7, 153.3 (2), 139.5, 135.6, 134.6, 133.9, 128.3 (2), 122.1 (2), 114,6, 98.4 (2), 60.4, 56.1 ( 2), 37.2, 23.9, 21,2 (2), 11.2
<실시예 l-244> N- (시클로핵실메틸) -4-(4-이소프로필ᅳ 2，3—디메털—5-옥소- 2， 5-디히드로 -1H-피라졸 -1-일 )벤젠설폰아미드의 제조 Example l-244 N- (cyclonuxylmethyl) -4- (4-isopropyl ᅳ 2,3-dimetal-5-oxo-2, 5-dihydro-1H-pyrazol-1-yl) Preparation of Benzenesulfonamide
시클로핵실메탄아민을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으 로 반웅시켜 목적 화합물을 45.59%의 수율로 수득하였다.  Using cyclonuxylmethanamine as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound in a yield of 45.59%.
ESI (m/z) 406 (MH+) 404 (MH-)； IH NMR (400MHz, DMS0-d6) d 7.86 (d, 2H, J = 8.4 Hz), 7.60 - 7.56 (m, 3H), 2.97 (s, 3H), 2.79 ― 2.74 (m, IH) , 2.58 (t, 2H, J = 6.0 Hz), 2.22 (s, 3H) , 1.66 - 1.59 (m, 5H) , 1.33 (br s, IH) , 1.19 (d, 6H, J = 6.8 Hz), 1.14 - 1.06 (m, 3H), 0.85 - 0.79 (m, 2H)； 13C NMR (100MHz, DMS0-d6) d 165.2, 155.4, 138.9, 137.1, 127.8 (2), 122.2 (2)， 114.5, 49,1, 37.7, 37.1, 30.5 (2)， 26.3, 25.6 (2), 23.9, 21.3 (2)， 11.2  ESI (m / z) 406 (MH &lt; + &gt;) 404 (MH-); IH NMR (400 MHz, DMS0-d6) d 7.86 (d, 2H, J = 8.4 Hz), 7.60-7.56 (m, 3H), 2.97 (s , 3H), 2.79-2.74 (m, IH), 2.58 (t, 2H, J = 6.0 Hz), 2.22 (s, 3H), 1.66-1.59 (m, 5H), 1.33 (br s, IH), 1.19 (d, 6H, J = 6.8 Hz), 1.14-1.06 (m, 3H), 0.85-0.79 (m, 2H); 13C NMR (100 MHz, DMS0-d6) d 165.2, 155.4, 138.9, 137.1, 127.8 (2 ), 122.2 (2), 114.5, 49,1, 37.7, 37.1, 30.5 (2), 26.3, 25.6 (2), 23.9, 21.3 (2), 11.2
<실시예 1-245〉 N- (시클로헵틸메틸) -4-(4-이소프로필— 2，3-디메틸 -5-옥소- 2， 5—디히드로 -1H—피라졸 -1-일)벤젠설폰아미드의 제조 시클로헵틸메틸을 출발물질로 사용하여 상기 실시예 1—1과 같은 방법으로 반 응시켜 목적 화합물을 53.50%의 수율로 수득하였다. Example 1-245 N- (Cycloheptylmethyl) -4- (4-isopropyl-2,3-dimethyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl) benzene Preparation of Sulfonamide Using cycloheptylmethyl as starting material, the reaction was carried out in the same manner as in Example 1-1, to obtain the target compound in a yield of 53.50%.
ESI (m/z) 420 (MH+) 418 (MHᅳ); 1H NMR (400MHz, DMS0-d6) d 7,86 (d, 2H, J = 8.8 Hz), 7.62 (t, 1H, J = 6.0 Hz), 7.57 (d, 2H, J = 8.4 Hz), 2.96 (s, 3H), 2,79 - 2.72 (m, 1H), 2.57 (t, 2H, J = 6.4 Hz), 2.22 (s, 3H)， 1.66 ― 1.61 (m, 2Η)' 1.54 - 1.36 (m, 7H) , 1.34 ᅳ 1.26 (m, 2H)， 1.19 (d, 6H, J = 6.8 Hz), 1.11 - 1.03 (m, 2H); 13C NMR (100MHz, DMSO— d6) d 162.2, 155.4, 138.9， 137.2, 127.8 (2), 122.2 (2)， 114.5， 49.3, 39.1， 37.1， 31.6 (2), 28.3 (2)， 26.1 (2), 23.9, 21.3 (2), 11.2  ESI (m / z) 420 (MH &lt; + &gt;) 418 (MH '); 1 H NMR (400 MHz, DMS0-d6) d 7,86 (d, 2H, J = 8.8 Hz), 7.62 (t, 1H, J = 6.0 Hz), 7.57 (d, 2H, J = 8.4 Hz), 2.96 ( s, 3H), 2,79-2.72 (m, 1H), 2.57 (t, 2H, J = 6.4 Hz), 2.22 (s, 3H), 1.66-1.61 (m, 2Η) '1.54-1.36 (m, 7H), 1.34 ᅳ 1.26 (m, 2H), 1.19 (d, 6H, J = 6.8 Hz), 1.11-1.03 (m, 2H); 13C NMR (100MHz, DMSO— d6) d 162.2, 155.4, 138.9, 137.2, 127.8 (2), 122.2 (2), 114.5, 49.3, 39.1, 37.1, 31.6 (2), 28.3 (2), 26.1 (2) , 23.9, 21.3 (2), 11.2
<실시예 l-246> N-(2—시클로핵실에틸) -4-(4-이소프로필 -2， 3-디메틸— 5—옥소一 2 ' 5-디히드로ᅳ 1H-피라졸 -1ᅳ일)벤젠설폰아미드의 제조 Example l-246 N- (2—cyclonucleoethylethyl) -4- (4-isopropyl-2, 3-dimethyl-5—oxo one 2 ′ 5-dihydro ᅳ 1H-pyrazol-1 ᅳ yl) Preparation of Benzenesulfonamide
2-시클로핵실에탄 -1-아민을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방 법으로 반웅시켜 목적 화합물을 50.31?¾의 수율로 수득하였다.  The reaction mixture was reacted in the same manner as in Example 1- 1 using 2-cyclonucleoethane-1-amine as a starting material, to obtain the target compound in a yield of 50.31? ¾.
ESI (m/z) 420 (腿 +) 418 (MH-)； 1H NMR (400MHz, DMS0~d6) d 7.86 (d, 2H, J = 8.4 Hz), 7.58 - 7.52 (m, 3H), 2.97 (s, 3H) , 2.78 - 2.75 (m, 3H), 2.22 (s, 3H), 1.57 (t, 5H, J = 11.8 Hz), 1.25 ― 1.24 (m, 3H) , 1.19 (d, 6H, J = 6.8 Hz), 1.14 - 1.04 (m, 3H) , 0.81 ― 0.76 (m, 2H)； 13C NMR (100MHz, DMS0-d6) d 165.2, 155.5, 139.0， 136.9, 127.8 (2)， 122.2 (2), 114.5, 40.6, 37,1， 36.8, 34,4, 32.8 (2)， 26.4, 26.0 (2), 23,9, 21,2 (2), 11.2 ESI (m / z) 420 (dl +) 418 (MH-); 1 H NMR (400 MHz, DMS0 to d6) d 7.86 (d, 2H, J = 8.4 Hz), 7.58-7.52 (m, 3H), 2.97 ( s, 3H), 2.78-2.75 (m, 3H), 2.22 (s, 3H), 1.57 (t, 5H, J = 11.8 Hz), 1.25-1.24 (m, 3H), 1.19 (d, 6H, J = 6.8 Hz), 1.14-1.04 (m, 3H), 0.81-0.76 (m, 2H); 13 C NMR (100 MHz, DMS0-d6) d 165.2, 155.5, 139.0, 136.9, 127.8 (2), 122.2 (2), 114.5, 40.6, 37,1, 36.8, 34,4, 32.8 (2), 26.4, 26.0 (2), 23,9, 21,2 (2), 11.2
<실시예 1ᅳ247> N-(3， 4-디메록시페닐 )-4ᅳ (4—이소프로필 -2, 3-디메틸—5—옥소- 2， 5ᅳ디히드로 -1H-피라졸 -1-일)벤젠설폰아미드의 제조 Example 1 # 247 N- (3,4-dimethoxyphenyl) -4 '(4—isopropyl-2, 3-dimethyl-5-oxo-2,5'dihydro-1H-pyrazole-1- (1) Preparation of Benzenesulfonamide
3,4—메록시아닐린을 출발물질로 사용하여 상기 실시예 1ᅳ 1과 같은 방법으로 반응시켜 목적 화합물을 18.06%의 수율로 수득하였다.  The reaction was carried out in the same manner as in Example 1-1 using 3,4—methoxy aniline as a starting material to obtain the target compound in a yield of 18.06%.
ESI (m/z) 446 (MH+) 468 (丽 a+) 444 (MH-); 1H NMR (400MHz , DMS0-d6) d 9.92 (s, 1H), 7.78 (d, 2H, J = 8.4 Hz), 7.52 (d, 2H, J = 8.8 Hz), 6.80 (d, 1H, J = 8.4 Hz), 6.68 (d, 1H, J = 1.6 Hz), 6.58 (d, 1H, J = 8.8 Hz), 3.64 (d, 6H, J = 14.0 Hz), 2.93 (s, 3H), 2.77 - 2.70 (m, 1H) , 2.19 (s, 3H) , 1.17 (d, 6H, J = 6.8 Hz)  ESI (m / z) 446 (MH &lt; + &gt;) 468 (丽 a +) 444 (MH &lt; + &gt;); 1H NMR (400MHz, DMS0-d6) d 9.92 (s, 1H), 7.78 (d, 2H, J = 8.4 Hz), 7.52 (d, 2H, J = 8.8 Hz), 6.80 (d, 1H, J = 8.4 Hz), 6.68 (d, 1H, J = 1.6 Hz), 6.58 (d, 1H, J = 8.8 Hz), 3.64 (d, 6H, J = 14.0 Hz), 2.93 (s, 3H), 2.77-2.70 ( m, 1H), 2.19 (s, 3H), 1.17 (d, 6H, J = 6.8 Hz)
<실시예 2> 벤젠설폰아미드 유도체의 mTORCl 억제 활성평가 <Example 2> Evaluation of mTORCl Inhibitory Activity of Benzenesulfonamide Derivatives
<2-1> 벤젠설폰아미드 유도체의 mTORCl 활성 억제효과 평가 <2-1> Evaluation of mTORCl Activity Inhibitory Effect of Benzenesulfonamide Derivatives
본 발명에 따른 벤젠설폰아미드 유도체의 mTORCl에 대한 활성 억제효과를 평 가하기 위하여 하기와 같은 방법으로 실험을 수행하였다. 대장암 세포주인 SW620은 Amer i can Type Cul ture Col lect ion (ATCC)에서 구 입하였다. 세포주를 24 웰 플레이트에 분주하여 24시간 배양 후, 류신 아미노산이 포함되어 있지 않은 배지에서 1시간 30분 처리하고 나서 다시 류신이 함유된 배지 에서 15분 배양하였다. 벤젠설폰아미드 유도체는 최종 농도 20uM로 류신이 함유된 배지에서 배양 시 첨가하였다. Cel l lysate 20ug을 전기영동하여 분리하고 mTORCl 활성을 보기 위하여 phospho-p70 S6 Kinase (Thr380) 항체 (#9206 , Cel l Signal ing Techno logy사)를 사용하여 웨스턴 블롯방법으로 분석하였다. 각 웰의 DMS0만 처리 한 음성대조군과 화합물을 처리한 군을 비교하여 mTORCl 활성 억제효과를 평가하였 다.  In order to evaluate the inhibitory effect of benzenesulfonamide derivatives on mTORCl of the present invention, the experiment was carried out as follows. Colon cancer cell line SW620 was purchased from Amer i can Type Culture Collect ion (ATCC). Cell lines were divided into 24 well plates and cultured for 24 hours, and then treated for 1 hour and 30 minutes in a medium containing no leucine amino acid, followed by further culture for 15 minutes in a medium containing leucine. Benzenesulfonamide derivatives were added upon incubation in a medium containing leucine at a final concentration of 20 uM. 20 ug of Cel llysate was isolated by electrophoresis and analyzed by Western blotting using phospho-p70 S6 Kinase (Thr380) antibody (# 9206, Cel l Signaling Technology) to see the mTORCl activity. Inhibition of mTORCl activity was evaluated by comparing the negative control group treated with DMS0 only and the compound treated group of each well.
[표 1] TABLE 1
mTORlCl 억제효과 ( 1) (%, 20 uM) mTORlCl inhibitory effect (1) (%, 20 uM)
실시예 억제효과 ( ) 실시예 억제효과 (%) 실시예 억제효과 (%) 실시예 1-1 66.15±12 실시예 1-63 55.01±0.64 실시예 1-125 13,91±8,66 실시예 1-2 42.67±17,1 실시예 1一 64 38.32±0.44 실시예 1-126 10.88±21.93 실시예 1-3 63.54±11.31 실시예 1-65 40.17±0.31 실시예 1—127 35.23±15.58 실시예 1-5 16·2±3·42 실시예 1-66 67.71±8.33 실시예 1-128 43.71±2.44 실시예 1-6 42.42±4.44 실시예 1-67 27.94±2.38 실시예 1-129 40.19±1.75 실시예 1-7 48.67±4.43 실시예 1-70 그 87±12.45 실시예 1-130 72 ,16±3,95 실시예 1—8 68.53±4.6 실시예 1-71 4.33±0.05 실시예 1-131 85.3±2.66 실시예 1一 9 39.68±4,56 실시예 1—73 2.85±3,25 실시예 1-132 69.83±1,49 실시예 1-10 33.18±2.42 실시예 1-74 22.7±2.72 실시예 1ᅳ 133 82.81±2.05 실시예 1-11 37土 7.07 실시예 1-79 37.78 실시예 1-134 70,67±3,21' 실시예 1一 16 10.12±2.98 실시예 1-83 3,87±0.98 실시예 1ᅳ 135 34,21±3.8 실시예 1-17 21.28±4.13 실시예 1-84 13.33±22.61 실시예 1-136 79,65±1,06 실시예 1-18 19,2±3.35 실시예 1ᅳ85 71.36士그 08 실시예 1ᅳ 137 80.38±1ᅳ 92 실시예 1—19 30.88±4.6 실시예 1-86 77,52±12.94 실시예 1ᅳ 138 89, 84± 12/77 실시예 1一 20 49.91±14.53 실시예 1—87 49.72±1.03 실시예 1-140 28.05±8.06 실시예 1-21 52.4±4.04 실시예 1ᅳ 88 64.85±11.63 실시예 1ᅳ 141138,95±12.55 실시예 1-22 64,57±12.67 실시예 1-89 79.89±11.32 실시예 1-142 19.27±7.93 실시예 1-24 63.55±3.96 실시예 1-90 45。3±22.87 실시예 1ᅳ 143 14,93±18.67 실시예 1-25 45.3±4.11 실시예 1-92 3.66±25.13 실시예 1一 146 45.64±5.64 실시예 1-26 23.43±12.06 실시예 1-93 44.28±4.74 실시예 1ᅳ 147 34.68±1,69 실시예 1-27 25.87土 11,42 실시예 1—94 45.13±6.44 실시예 1-148 35。71±1.79 실시예 1-28 61.52±13 실시예 1一 95 40,41±6.02 실시예 1ᅳ 149 17,98±그47 실시예 1-29 38.35±3.57 실시예 1-96 69ᅳ71±3,51 실시예 1-150 32.63土 3.34 실시예 1一 30 41.67±11.21 실시예 1-97 74.97±4,7 실시예 1-151 39 ,1±3。98 실시예 1一 31 48.37±10,19 실시예 1-98 70.31士 3.94 실시예 1-152 50,25±7。83 실시예 1-32 59.88±3.51 실시예 1-99 56.79士 4, 44 실시예 1-153 29.94±4,99 실시예 1-33 45.32±0.92 실시예 1-100 4-4.34±2.29 실시예 1ᅳ 154 37.11±5 실시예 1-34 60.37±0,72 실시예 1-101 59.73±0,65 실시예 1-155 52.15±4.24 실시예 1-35 78.06±1.35 실시예 1-102 14.33±6,63 실시예 1ᅳ156 63.84±3.52 실시예 1-36 78.59±3,49 실시예 1-103 85.54±4.67 실시예 1-157 63.67±2.64 실시예 1-37 77.08±3.26 실시예 1-104 56.93±9.67 실시예 1ᅳ158 89.52±6.14 실시예 1-38 76.97±0.37 실시예 1-105 21.5±7.22 실시예 1—159 79.39 ±'6.54 실시예 1-39 43.9±14.96 실시예 1-106 43.6±17.9 실시예 1-160 76,43±3.9'7 실시예 1-40 20.05±2.55 실시예 1—107 67.83±14.84 실시예 1—161 74.83±7,22 실시예 1-41 60.01±2,89 실시예 1—108 88.83±13.38 실시예 1—162 62.9土 2.4 실시예 1-42 33.24±5.93 실시예 1-109 60.49±0.3 실시예 1—163 59.29±6,2;9 실시예 1-43 13.53±0.35 실시예 1-110 49.46±0.36 실시예 1—164 82.82±0,69 실시예 1-44 10.24±6.14 실시예 1-111 35.54±0.24 실시예 1—165 52.12±4ᅳ43 실시예 1一 45 21.62±12.57 실시예 1-112 11.53±0.1 실시예 1-166 88.65±1.42 실시예 1—46 68.27±0.51 실시예 1-113 38,93±0.4 실시예 1-167 70.83土 1.96 실시예 1-49 26,93±2,78 실시예 1-114 21, 86土으 32 실시예 1-168 57,66±5.60 실시예 1-50 26.37±4.39 실시예 1-115 82„67±0,58 실시예 1-169 63,50±3,36 실시예 1一 52 35ᅳ 91±10.8 실시예 1—116 62.72±4.91 실시예 1— 170 66.31±2.09 실시예 1-54 67±3.94 실시예 1—117 51.9±5.7 실시예 1-171 14.67±10.20 실시예 1-55 25.11±7.03 실시예 1—118 26.28±10.7 실시예 1-172 33.62±10.11 실시예 1-56 33.86±8.99 실시예 1ᅳ 119 42±10.22 실시예 1-174 56.46±2.77 실시예 1一 58 32.08士그 76 실시예 1—120 47,78±4.06 실시예 1—175 49.13土 6, 17 실시예 1—59 55,36±8.67 실시예 1ᅳ 121 59ᅳ 15±8.4 실시예 1-176 62.50士그 37 실시예 1-60 65.58±0,87 실시예 1-122 62.34士 4.75 실시예 1-177 6으 29±2,10 실시예 1ᅳ 61 59, 76土 1.44 실시예 1—123 9,49±14ᅳ 28 실시예 1-178 2。15±8.38. 실시예 1-62 94.18±3.81 실시예 1-124 20.24±12.83 실시예 1—179 60.43±12.00 Example Inhibitory Effect () Example Inhibitory Effect (%) Example Inhibitory Effect (%) Example 1-1 66.15 ± 12 Example 1-63 55.01 ± 0.64 Example 1-125 13,91 ± 8,66 Example 1-2 42.67 ± 17,1 Example 1 One 64 38.32 ± 0.44 Example 1-126 10.88 ± 21.93 Example 1-3 63.54 ± 11.31 Example 1-65 40.17 ± 0.31 Example 1—127 35.23 ± 15.58 Example 1-5 16 · 2 ± 3 · 42 Example 1-66 67.71 ± 8.33 Example 1-128 43.71 ± 2.44 Example 1-6 42.42 ± 4.44 Example 1-67 27.94 ± 2.38 Example 1-129 40.19 ± 1.75 Example 1-7 48.67 ± 4.43 Example 1-70 Its 87 ± 12.45 Example 1-130 72, 16 ± 3,95 Example 1—8 68.53 ± 4.6 Example 1-71 4.33 ± 0.05 Example 1-131 85.3 ± 2.66 Example 1 1 9 39.68 ± 4,56 Example 1—73 2.85 ± 3,25 Example 1-132 69.83 ± 1,49 Example 1-10 33.18 ± 2.42 Example 1-74 22.7 ± 2.72 Example 1 133 82.81 ± 2.05 Example 1-11 37 土 7.07 Example 1-79 37.78 Example 1-134 70,67 ± 3,21 ' Example 1 一 16 10.12 ± 2.98 Example 1-83 3,87 ± 0.98 Example 1 ᅳ 135 34,21 ± 3.8 Example 1 -17 21.28 ± 4.13 Example 1-84 13.33 ± 22.61 Example 1-136 79,65 ± 1,06 Example 1-18 19,2 ± 3.35 Example 1 ᅳ 85 71.36 ᅳ 08 Example 1 ᅳ 137 80.38 ± 1 μA 92 Example 1—19 30.88 ± 4.6 Example 1-86 77,52 ± 12.94 Example 1 ᅳ 138 89, 84 ± 12/77 Example 1 1 20 49.91 ± 14.53 Example 1—87 49.72 ± 1.03 Examples 1-140 28.05 ± 8.06 Examples 1-21 52.4 ± 4.04 Examples 1 ᅳ 88 64.85 ± 11.63 Example 1 ᅳ 141138,95 ± 12.55 Example 1-22 64,57 ± 12.67 Example 1-89 79.89 ± 11.32 Example 1-142 19.27 ± 7.93 Example 1-24 63.55 ± 3.96 Example 1-90 45 ° 3 ± 22.87 Example 1 ᅳ 143 14,93 ± 18.67 Example 1-25 45.3 ± 4.11 Example 1-92 3.66 ± 25.13 Example 1 146 45.64 ± 5.64 Example 1-26 23.43 ± 12.06 Example 1-93 44.28 ± 4.74 Example 1 ᅳ 147 34.68 ± 1,69 Example 1-27 25.87 土 11,42 Example 1 —94 45.13 ± 6.44 Example 1-148 35 ° 71 ± 1.79 Example 1-28 61.52 ± 13 Example 1 One 95 40,41 ± 6.02 Example 1 ᅳ 149 17,98 ± 47 Example 1-29 38.35 ± 3.57 Example 1-96 69 ᅳ 71 ± 3,51 Example 1-150 32.63 土 3.34 Example 1 1 30 41.67 ± 11.21 Example 1-97 74.97 ± 4,7 Example 1-151 39, 1 ± 3.98 Example 1 1 31 48.37 ± 10, 19 Example 1-98 70.31 士 3.94 Example 1-152 50,25 ± 7。83 Example 1-32 59.88 ± 3.51 Example 1-99 56.79 士 4, 44 Example 1-153 29.94 ± 4,99 Example 1-33 45.32 ± 0.92 Example 1-100 4-4.34 ± 2.29 Example 1 ᅳ 154 37.11 ± 5 Example 1-34 60.37 ± 0,72 Example 1-101 59.73 ± 0,65 Example 1-155 52.15 ± 4.24 Examples 1-35 78.06 ± 1.35 Examples 1-102 14.33 ± 6,63 Examples 1 ᅳ 156 63.84 ± 3.52 Examples 1-36 78.59 ± 3,49 Examples 1-103 85.54 ± 4.67 Example 1 -157 63.67 ± 2.64 Examples 1-37 77.08 ± 3.26 Examples 1-104 56.93 ± 9.67 Examples 1 ᅳ 158 89.52 ± 6.14 Examples 1-38 76.97 ± 0.37 Examples 1-105 21.5 ± 7.22 Examples 1—159 79.39 ± ' 6.54 Examples 1-39 43.9 ± 14.96 Examples 1-106 43.6 ± 17.9 Examples 1-160 76,43 ± 3.9 ' 7 Examples 1-40 20.05 ± 2.55 Examples 1—107 67.83 ± 14.84 Examples 1—161 74.83 ± 7,22 Example 1-41 60.01 ± 2,89 Example 1—108 88.83 ± 13.38 Example 1—162 62.9 μs 2.4 Example 1-42 33.24 ± 5.93 Example 1-109 60.49 ± 0.3 Example 1—163 59.29 ± 6,2 ; 9 Example 1-43 13.53 ± 0.35 Example 1-110 49.46 ± 0.36 Example 1—164 82.82 ± 0,69 Example 1-44 10.24 ± 6.14 Example 1-111 35.54 ± 0.24 Example 1—165 52.12 ± 4 ᅳ 43 Example 1 One 45 21.62 ± 12.57 Example 1-112 11.53 ± 0.1 Example 1-166 88.65 ± 1.42 Example 1—46 68.27 ± 0.51 Example 1-113 38,93 ± 0.4 Example 1-167 70.83 土 1.96 Examples 1-49 26,93 ± 2,78 Examples 1-114 21, 86 Hz 32 Examples 1-168 57,66 ± 5.60 Examples 1-50 26.37 ± 4.39 Examples 1-115 82′67 ± 0,58 Example 1-169 63,50 ± 3,36 Example 1 One 52 35 ᅳ 91 ± 10.8 Example 1—116 62.72 ± 4.91 Example 1—170 66.31 ± 2.09 Example 1-54 67 ± 3.94 Example 1—117 51.9 ± 5.7 Example 1-171 14.67 ± 10.20 Example 1-55 25.11 ± 7.03 Example 1—118 26.28 ± 10.7 Example 1-172 33.62 ± 10.11 Example 1-56 33.86 ± 8.99 Example 1 ᅳ 119 42 ± 10.22 Example 1-174 56.46 ± 2.77 Example 1 1 58 32.08 그 76 Example 1—120 47,78 ± 4.06 Example 1—175 49.13 土 6, 17 Example 1—59 55,36 ± 8.67 Example 1 ᅳ 121 59 ᅳ 15 ± 8.4 Example 1-176 62.50 그 37 Example 1-60 65.58 ± 0,87 Example 1-122 62.34 4. 4.75 Example 1-177 6 29 29 ± 2, 10 Example 1 ᅳ 61 59, 76 土 1.44 Example 1—123 9,49 ± 14 ° 28 Example 1-178 2 ° 15 ± 8.38. Example 1-62 94.18 ± 3.81 Example 1-124 20.24 ± 12.83 Example 1—179 60.43 ± 12.00
[표. 2] [table. 2]
mTORlCl 억제효과 (2) (%, 20 uM)  mTORlCl inhibitory effect (2) (%, 20 uM)
Figure imgf000120_0001
Figure imgf000120_0001
표 3]  Table 3]
mTORlCl 억제효과 (¾， 100 uM)  mTORlCl inhibitory effect (¾ ， 100 uM)
실시예 억제효과 ( ) 실시예 억제효과 (%) 실시예 억제효과 (%) 실시예 1-181 99.98 실시예 1-191 0.69 실시예 1—211 11.19 실시예 1—182 100 실시예 1—192 79.23 실시예 1-212 98.7 실시예 1-185 79.91 실시예 1-193 84.3 실시예 1-213 100 실시예 1-186 87.68 실시예 1—200 20.55 실시예 1—214 74.91±1.61.. 실시예 1—188 14.58 실시예 1—201 44.43 실시예 1-215 99.87 실시예 1-189 89.98 실시예 1-204 100 실시예 1—216 99.98 실시예 1-190 84.25 실시예 1-210 21.92 상기 표 1 및 표 2 에 나타낸 바와 같이， 본 발명에 따른 벤젠설폰아미드 유 도체는 20uM에서 유의적으로 mTORCl의 활성을 억제하는 것을 알 수 있다, 실시예 1-35-38, 1-62, 1—85， 1—86， 1—89， 1-97, 1-98, 1-103, 1-108, 1—115, 1-130, 1- 131, 1-133, 1-134, 1-136-1-138, 1-158~1-161, 1-164, 1—166， 1-167, 1—220, 1— 229, 1-230, 1-239, 1—240의 화합물들은 70% 이상의 우수한 억제 효과를 나타내는 것을 알 수 있었다. 따라서, 본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는, 암세포에서 활성이 높은 것으로 알려져 있는 mTORCl의 활성을 억제하므로， 암의 치료에 유용하 게 사용될 수 있다. Example Inhibitory Effect () Example Inhibitory Effect (%) Example Inhibitory Effect (%) Example 1-181 99.98 Example 1-191 0.69 Example 1—211 11.19 Example 1—182 100 Example 1—192 79.23 Examples 1-212 98.7 Examples 1-185 79.91 Examples 1-193 84.3 Examples 1-213 100 Examples 1-186 87.68 Example 1—200 20.55 Example 1—214 74.91 ± 1.61. Example 1— 188 14.58 Example 1—201 44.43 Example 1-215 99.87 Example 1-189 89.98 Example 1-204 100 Example 1—216 99.98 Example 1-190 84.25 Example 1-210 21.92 As shown in Table 1 and Table 2, it can be seen that the benzenesulfonamide derivative according to the present invention significantly inhibits the activity of mTORCl at 20 uM, Examples 1-35-38, 1-62, 1 —85 ， 1—86 ， 1—89 ， 1-97, 1-98, 1-103, 1-108, 1-115, 1-130, 1-131, 1-133, 1-134, 1-136 -1-138, 1-158-1-161, 1-164, 1-166, 1-167, 1-220, 1-229, 1-230, 1-239, 1-240 It turned out that it shows the outstanding inhibitory effect. Therefore, the benzenesulfonamide derivative of Formula 1 according to the present invention can inhibit the activity of mTORCl, which is known to be highly active in cancer cells, and thus can be useful for the treatment of cancer.
<2-2> 벤젠설폰아미드 유도체의 mTORCl 활성 억제효과 (IC50) 평가 <2-2> Evaluation of mTORCl activity inhibitory effect (IC50) of benzenesulfonamide derivatives
본 발명에 따른 벤젠설폰아미드 유도체의 mTORCl에 대한 활성 억제효과 (IC50)를 평가하기 위하여 하기와 같은 방법으로 실험을 수행하였다. 대장암 세포주인 SW620은 American Type Culture Collection (ATCC)에서 구 입하였다. 세포주를 24 웰 플레이트에 분주하여 24시간 배양 후， 벤젠설폰아미드 유도체는 (최종 농도 0,1, 0.5, 1, 2, 5, 10, 20uM) 10% FBS가 포함된 배지에서 6 시간 동안 배양 시 첨가하였다, Cell lysate 20ug을 전기영동하여 분리하고 mTORCl 활성을 보기 위하여 phospho-p70 S6 Kinase (Thr380) 항체 (#9206, Cell Signaling Technology사)를 사용하여 웨스턴 블롯방법으로 분석하였다. 각 웰의 DMS0만 처리 한 음성대조군과 화합물을 처리한 군을 비교하여 mTORCl 활성 억제효과를 평가하였 다,  In order to evaluate the inhibitory effect (IC50) on mTORCl of the benzenesulfonamide derivatives according to the present invention, the experiment was carried out as follows. Colon cancer cell line SW620 was purchased from the American Type Culture Collection (ATCC). After culturing the cell line in a 24 well plate for 24 hours, the benzenesulfonamide derivative (final concentration 0,1, 0.5, 1, 2, 5, 10, 20 uM) was cultured for 6 hours in a medium containing 10% FBS. 20 ug of Cell lysate was isolated by electrophoresis and analyzed by Western blotting using phospho-p70 S6 Kinase (Thr380) antibody (# 9206, Cell Signaling Technology) to see mTORCl activity. Inhibition of mTORCl activity was evaluated by comparing the negative control group treated with DMS0 only and the compound treated group of each well.
[표 4] TABLE 4
mTORCl 활성 억제효과 (IC50) 평가 Evaluation of mTORCl activity inhibitory effect (IC50)
Figure imgf000122_0001
이상의 mTORCl 저해활성이 평가된 화합물 가운테, 우수한 저해활성 (저해활 성 이상)을 보였던 화합물을 선별하여 추가적으로 mTORCl의 저해활성을 평가하 였다. 싱-기 표 4에 나타낸 바와 같이, 본 발명에 따른 벤젠설폰아미드 유도체는 1 uM 이하에서 유의적으로 mTORCl의 활성을 억제하는 것을 알 수 있다. 특히， 실시예 1-62, 1ᅳ 166의 화합물들은 IC50 ΙΟΟηΜ 이하의 농도에서 우수한 효과를 나타내는 것 을 알 수 있었다. 따라서， 본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는， 암세포에서 활성이 높은 것으로 알려져 있는 mTORCl의 활성을 억제하므로， 암의 치료에 유용하 게 사용될 수 있음을 알 수 있다.
Figure imgf000122_0001
Compounds whose mTORCl inhibitory activity was evaluated above were selected, and compounds showing excellent inhibitory activity (inhibitory activity or higher) were selected to further evaluate the inhibitory activity of mTORCl. As shown in Singh-Table 4, it can be seen that the benzenesulfonamide derivative according to the present invention significantly inhibits the activity of mTORCl at 1 uM or less. In particular, Examples Compounds 1-62 and 1 ᅳ 166 showed good effects at concentrations below IC50 ΙΟΟηΜ. Therefore, the benzenesulfonamide derivative of Formula 1 according to the present invention, since it inhibits the activity of mTORCl known to be highly active in cancer cells, it can be seen that it can be useful for the treatment of cancer.
<실시예 3> <Example 3>
벤젠설폰아미드 유도체의 대장암 세포 (SW620)에 대한 성장 억제 효과 평가 <3-1> RFP 발현 세포주 제작  Evaluation of Growth Inhibitory Effect of Benzenesulfonamide Derivatives on Colon Cancer Cells (SW620) <3-1> Preparation of RFP Expressing Cell Line
본 발명의 벤젠설폰아미드 유도체가 대장암 세포 SW620의 성장을 억제하는 효과를 평가하기 위하여 RFP 형광표지된 세포주를 제작하였다。 대장암 세포주인 SW620은 American Type Culture Collection (ATCC)에서 구입하였다. RFP 형광 표지 된 SW620 세포주 제작을 위해서 NucLight Red Lent i virus Reagent (EFla, Puro) (#4476, Essen Bioscience사)를 구입하였다。 24시간 동안 SW620 세포주에 NucLight Red Lent i virus Reagent를 첨가하여 세포 내로 형질 주입시키고 10% FBS와 1% 페니 실린 /스트렙토마이신을 포함하는 RPMI 1640 배지에서 37°C, 5% C02 조건 하에 배양 하였다. 이후에 푸로마이신을 0,5 ug/ml의 농도로 배지에 첨가한 후 4일간 37°C, 5% C02 조건 하에 배양하였다. In order to evaluate the effect of benzenesulfonamide derivatives of the present invention on inhibiting the growth of colon cancer cell SW620, RFP fluorescent labeled cell lines were prepared. SW620, a colon cancer cell line, was purchased from the American Type Culture Collection (ATCC). NucLight Red Lent i Virus Reagent (EFla, Puro) (# 4476, Essen Bioscience) was purchased for the preparation of RFP fluorescently labeled SW620 cell lines. The cells were transfected into cells by adding NucLight Red Lent i Virus Reagent to SW620 cell line for 24 hours. Injected and incubated under 37 ° C, 5% C02 conditions in RPMI 1640 medium containing 10% FBS and 1% penicillin / streptomycin. Thereafter, puromycin was added to the medium at a concentration of 0,5 ug / ml, and then cultured at 37 ° C and 5% C02 for 4 days.
<3-2> 화합물에 의한 SW620 세포 성장 억제 효과 <3-2> SW620 cell growth inhibition effect by the compound
RFP 형광 표지된 SW620 세포주를 96 웰 플레이트에 분주하여 24시간 배양 후 , 10% FBS를 함유하는 배지에서 본 방명에 의한 벤젠설폰아미드 유도체를 24시간 동안 처리하였다 (최종농도 0.000282, 0.000847, 0.00254, 0.0076, 0.0229. 0.0686, 0.206, 0.617， 1.85， 5.56, 16.67, 50uM) . 화합물 처리 후 2시간 간격으로 세포 위상차 이미지 및 적색형광이미지를 Incucyte Zoom (Essen Bioscience사) 장 시간 세포관찰 분석 시스템을 이용하여 얻고 RFP 형광의 정량 분석은 Incucyte Zoom basic analyzer (Essen Bioscience사) 프로그램을 이용하여 실시하였다, 화합 물의 각 농도별 RFP 형광 수치를 GraphPad Prism tool 프로그램을 이용하여 GI50 (50% growth inhibition) 값을 계산하였다. 각 웰의 RFP 형광을 DMS0만 처리한 음 성대조군과 화합물을 처리한 군을 비교하여 SW620 세포 성장 억제효과를 평가하였 다. RFP fluorescently labeled SW620 cell lines were dispensed into 96 well plates for 24 hours, and then treated with benzenesulfonamide derivatives according to the present invention for 24 hours in a medium containing 10% FBS (final concentrations 0.000282, 0.000847, 0.00254, 0.0076). , 0.0229. 0.0686, 0.206, 0.617, 1.85, 5.56, 16.67, 50 uM). Cell phase contrast and red fluorescence images were obtained using the Incucyte Zoom (Essen Bioscience) long-term cell observation assay system at 2 hour intervals after compound treatment. The quantitative analysis of RFP fluorescence was performed using the Incucyte Zoom basic analyzer (Essen Bioscience) program. RFP fluorescence values for each concentration of the compound were calculated using the GraphPad Prism tool program to calculate the GI50 (50% growth inhibition) value. The SW620 cell growth inhibition effect was evaluated by comparing the negative control group treated with DMS0 and the compound treated group with RFP fluorescence in each well. All.
[표 5]  TABLE 5
SW620 세포 성장 억제효과 GI50 (i M)  SW620 cell growth inhibitory effect GI50 (i M)
Figure imgf000124_0001
Figure imgf000124_0001
상기 표 5에 나타낸 바와 같이， 본 발명에 따른 벤젠설폰아미드 유도체 의적으로 SW620 세포의 성장을 억제하는 것을 알 수 있다. 실시예 1-35, 1-62， 1-As shown in Table 5, the benzenesulfonamide derivative according to the present invention It can be seen that it inhibits the growth of SW620 cells intentionally. Examples 1-35, 1-62, 1-
89, 1-103, 1-108， 1-115， 1—131， 1-133, 1-136-1-138, 1—158， 1-159, 1-164, 1—89, 1-103, 1-108, 1-115, 1—131, 1-133, 1-136-1-138, 1—158, 1-159, 1-164, 1—
166, 1-174-1-177, 1-179, 1-204, 1—214， 1-220, 1-222, 1-229, 1-230, 1-231, 1—166, 1-174-1-177, 1-179, 1-204, 1—214, 1-220, 1-222, 1-229, 1-230, 1-231, 1—
239, 1—240, 1-243, 1—247의 화합물들은 GI50 100 nM이하의 우수한 억제 효과를 나 타내는 것을 알 수 있다. 따라서, 본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는， 암 세포의 성 장을 억제하는 효과가 우수하므로, 암의 치료에 유용하게 사용될 수 있다. The compounds of 239, 1-240, 1-243, and 1-247 show excellent inhibitory effects below GI50 100 nM. Therefore, the benzenesulfonamide derivative of Formula 1 according to the present invention is excellent in inhibiting the growth of cancer cells, and thus can be usefully used for the treatment of cancer.
<3-3> 벤젠설폰아미드 유도체의 대장암 세포 (SW620)에 대한 세포 독성평가 본 발명에 따른 벤젠설폰아미드 유도체의 대장암 세포에 대한 세포 독성 효 과를 평가하기 위하여 하기와 같은 방법으로 실험을 수행하였다. <3-3> Cytotoxicity Evaluation of Benzenesulfonamide Derivatives against Colorectal Cancer Cells (SW620) Experiments were performed by the following methods to evaluate the cytotoxic effects of colorectal cancer cells of benzenesulfonamide derivatives according to the present invention. Was performed.
RFP 형광 표지된 SW620 세포주를 96 웰 플레이트에 분주하여 24시간 배양 후 , 10% FBS를 함유하는 배지에서 본 방명에 의한 벤젠설폰아미드 유도체를 24시간 동안 처리하였다 (최종농도 으 000282, 0.000847, 0.00254, 0.0076， 0.0229. 0.0686, 0.206， 0.617, 1.85, 5.56, 16.67, 50uM) . 화합물 처리시에 세포 독성을 실시간 관찰하기 위하여 세포 사멸 시에 녹색형광을 띄는 CellTox Green (#G8741, Pr omega사)를 첨가하였다. 화합물 처리 후 2시간 간격으로 녹색형광이미지를 Incucyte Zoom (Essen Bioscience사) 장시간 세포관찰 분석 시스템을 이용하여 얻 고 녹색형광의 정량 분석은 Incucyte Zoom basic analyzer (Essen Bioscience사) 프로그램을 이용하여 실시하였다. 화합물의 각 농도별 녹색형광 수치를 GraphPacl Prism tool 프로그램을 이용하여 EC50 (50% cell death) 값을 계산하였다. 각 웰의 녹색형광을 DMS0만 처리한 음성대조군과 화합물을 처리한 군을 비교하여 SW620 세 포 성장 억제효과를 평가하였다.  RFP fluorescently labeled SW620 cell lines were dispensed into 96 well plates for 24 hours, and then treated with benzenesulfonamide derivatives according to the present invention for 24 hours in a medium containing 10% FBS (final concentration 000282, 0.000847, 0.00254, 0.0076, 0.0229. 0.0686, 0.206, 0.617, 1.85, 5.56, 16.67, 50 uM). CellTox Green (# G8741, Pr omega), which displays green fluorescence upon cell death, was added to observe the cytotoxicity during compound treatment. Green fluorescence images were obtained using Incucyte Zoom (Essen Bioscience) long-term cell observation analysis system at 2 hour intervals after compound treatment, and quantitative analysis of green fluorescence was performed using Incucyte Zoom basic analyzer (Essen Bioscience) program. The green fluorescence value of each concentration of the compound was calculated using the GraphPacl Prism tool program to calculate the EC50 (50% cell death) value. The green fluorescence of each well was compared with the negative control group treated with DMS0 and the compound treated group to evaluate the SW620 cell growth inhibition effect.
[표 6] TABLE 6
대장암 세포 (SW620)에 대한 세포 독성 EC50 (nM) •실시예 EC50(nM) 실시예 EC50(nM) Cytotoxic EC50 (nM) against colorectal cancer cells (SW620) Example EC50 (nM) Example EC50 (nM)
실시예 1 8 688.6±10.60 심시예 1—214 62. ±3.48  Example 1 8 688.6 ± 10.60 Trial example 1—214 62. ± 3.48
심시예 1-35 358,7±9,74 심시예 1—215 10198 ±2.18  Trial example 1-35 358,7 ± 9,74 Trial example 1—215 10198 ± 2.18
실시예 1-36 525.3±21.39 ᅳ실시예 1-216 13108 ±2.29  Examples 1-36 525.3 ± 21.39 Examples 1-216 13108 ± 2.29
실시예 1-37 423.1±6.59 심시예 1-217 159.80土 13.34  Examples 1-37 423.1 ± 6.59 Acute Example 1-217 159.80 ° 13.34
실시예 1-38 358ᅳ8±2.77 심시예 1-218 820.47±45.61  Example 1-38 358 ° 8 ± 2.77 Acute Example 1-218 820.47 ± 45.61
실시예 1-54 444.8±4.98 실시예 1-219 523.30±18.91  Example 1-54 444.8 ± 4.98 Examples 1-219 523.30 ± 18.91
실시예 1-62 204.4±6.22 심시예 1—220 76.58士 5.26  Example 1-62 204.4 ± 6.22 Trial example 1—220 76.58 士 5.26
심시예 1-66 614.9±10.31 •실시예 1-221 303.41±19.23 For simsi 1-66 614.9 ± 10.31 • Example 1-221 303.41 ± 19.23
실시예 1-85 576.2±9.51 심시예 1-222 106.29±5.84  Example 1-85 576.2 ± 9.51 Acute Example 1-222 106.29 ± 5.84
심시예 1-86 912.6±5.49 실시예 1—223 588.40 ±59ᅳ 43  Example 1-86 912.6 ± 5.49 Example 1—223 588.40 ± 59 ° 43
실시예 1-89 321.9±3.39 실시예 1-224 287.45±17,82  Examples 1-89 321.9 ± 3.39 Examples 1-224 287.45 ± 17,82
실시예 1—103 103,99±5.67 심시예 1—225 303.32±17.09  Example 1—103 103,99 ± 5.67 Trial example 1—225 303.32 ± 17.09
심시예 1-108 141.91±7,99 ᅳ실시예 1-226 676.06±62.14  Example 1-108 141.91 ± 7,99 Example 1-226 676.06 ± 62.14
심시예 1—115 120.23±11.06 심시예 1—227 222.02士 12.26  Trial example 1—115 120.23 ± 11.06 Trial example 1—227 222.02 士 12.26
실시예 1-131 108.64±15.24 심시예 1—228 460.57 ±46.26  Example 1-131 108.64 ± 15.24 Trial example 1—228 460.57 ± 46.26
실시예 1-133 103.75±4.98 실시예 1—229 103.63±1.59  Example 1-133 103.75 ± 4.98 Example 1—229 103.63 ± 1.59
실시예 1—136 158.85±4.16 심시예 1—230 78.98±2.32  Example 1—136 158.85 ± 4.16 Trial example 1—230 78.98 ± 2.32
실시예 1-137 13그 2±3.39 실시예 1-231 112,85±6.78  Example 1-137 13 g 2 ± 3.39 Example 1-231 112,85 ± 6.78
실시예 1—138 44.74土 1.75 심시예 1—232 404.82±21.35  Example 1—138 44.74 ° 1.75 Trial example 1—232 404.82 ± 21.35
실시예 1-158 68.6±1.14 심시예 1-233 333,64±37.69  Examples 1-158 68.6 ± 1.14 Acute Example 1-233 333,64 ± 37.69
심시예 1—159 161.43±7.38 심시예 1-234 717.71±62.72  Trial example 1—159 161.43 ± 7.38 Trial example 1-234 717.71 ± 62.72
실시예 1-164 80.15±3.74 실시예 1-235 798.31±35.26  Example 1-164 80.15 ± 3.74 Examples 1-235 798.31 ± 35.26
실시예 1—166 70.79±2.17 실시예 1—236 2415.98 ±385.33  Example 1—166 70.79 ± 2.17 Example 1—236 2415.98 ± 385.33
실시예 1-168 723.34±24.57 실시예 1-237 220.30土 15.46  Example 1-168 723.34 ± 24.57 Example 1-237 220.30 ° 15.46
심시예 1-169 540.53±8.72 심시예 1—238 252.44±16.43  Example 1-169 540.53 ± 8.72 Example 1-238 252.44 ± 16.43
심시예 1— 170 257.50±19.03 심시예 1—239 126.17±8.38  Example 1—170 257.50 ± 19.03 Example 1—239 126.17 ± 8.38
심시예 1-174 106.1士 11.06 실시예 1-240 73,81±3.68  Examination Example 1-174 106.1 士 11.06 Example 1-240 73,81 ± 3.68
실시예 1—175 205.0±18.35 •실시예 1—241 701.63±41.27 Example 1-175 205.0 ± 18.35 • Example 1-241 701.63 ± 41.27
실시예 1-176 198.8±12.8 실시예 1-242 331.89±22.64  Examples 1-176 198.8 ± 12.8 Examples 1-242 331.89 ± 22.64
심시예 1—177 150.8±11.91 실시예 1-243 123.10±6.56  Example 1—177 150.8 ± 11.91 Example 1-243 123.10 ± 6.56
실시예 1— Γ78 1443.4± 80.51 실시예 1-244 245.47±5,82  Example 1—Γ78 1443.4 ± 80.51 Examples 1-244 245.47 ± 5,82
^시예 1-179 94.0±4/78 실시예 1—245 701.63土 41.27  ^ Example 1-179 94.0 ± 4/78 Example 1—245 701.63 ° 41.27
섣시예 1—180 1526.5 ±132.75 실시예 1—246 331.89±22.64  Example 1—180 1526.5 ± 132.75 Example 1—246 331.89 ± 22.64
실시예 1-190 3789土 2.15 실시예 1-247 123.10±6.56  Example 1-190 3789 ° 2.15 Examples 1-247 123.10 ± 6.56
실시예 1-193 940.8±2.13  Example 1-193 940.8 ± 2.13
실시예 1-204 355.5± 1.24  Example 1-204 355.5 ± 1.24
실시예 1-212 8692±1.16  Example 1-212 8692 ± 1.16
심시예 1-213 8992 ±2.01 상기 표 6에 나타낸 바와 같이， 본 발명에 따른 벤젠설폰아미드 유도체는 유 의적으로 SW620 세포의 사멸을 유도하는 것을 알 수 있었다, 실시예 1-62, 1-103, 1—108， 1-115, 1-131, 1-133, 1—136， 1-137, 1—138， 1-158, 1-159, 1-164, 1-166, 1-174, 1-176, 1-177, 1-179, 1-214, 1-220, 1—229, 1-230, 1—231, 1—239, 1-240, 1—243, 1—247의 화합물들은 EC50 200 nM이하의 우수한 억제 효과를 나타내는 것을 확인하였다. 따라서, 본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는， 암 세포 사멸 을 유도하는 효과가 우수하므로, 암의 치료제로 유용하게 사용될 수 있다. Clinical Example 1-213 8992 ± 2.01 As shown in Table 6, the benzenesulfonamide derivative according to the present invention was found to significantly induce the death of SW620 cells, Examples 1-62, 1-103, 1-108, 1-115, 1-131, 1-133, 1-136, 1-137, 1-138, 1-158, 1-159, 1-164, 1-166, 1-174, 1- The compounds of 176, 1-177, 1-179, 1-214, 1-220, 1-229, 1-230, 1-231, 1-239, 1-240, 1-243, 1-247 are EC50 200 shows an excellent inhibitory effect of less than nM Confirmed. Therefore, the benzenesulfonamide derivative of Formula 1 according to the present invention is excellent in inducing cancer cell death, and thus may be usefully used as a therapeutic agent for cancer.
<3-4>본 발명에 따른 벤젠설폰아미드 유도체의 정상세포주에 대한 세포독성 평가 <3-4> Cytotoxicity Evaluation of Normal Cell Lines of Benzenesulfonamide Derivatives According to the Present Invention
본 발명에 따른 밴젠설폰아미드 유도체의 정상세포주에 대한 영향을 평가하 기 위하여 상기와 같은 방법으로 세포독성 실험을 수행하였다. 본 발명에 따른 벤 젠설폰아미드 유도체는 실시예 1-214의 화합물을 대표로 하여 실험하였다.  Cytotoxicity experiments were carried out in the same manner as described above to evaluate the effect of the bansensulfonamide derivatives on the normal cell line according to the present invention. Benzenesulfonamide derivatives according to the invention were tested with the compounds of Examples 1-214 as representative.
정상 세포주는 FHC (colon normal epithelial cell)을 American Type Culture Collection (ATCC)에서 구입하여 사용하였다, 이에 대한 결과를 도 1에 나타내었다. 도 1에 나타낸 바와 같이, 본 발명에 따른 벤젠설폰아미드 유도체는 정상 대장세포주에 대한 세포독성이 lOOuM에서도 나 타나지 않았다. 즉， 본 발명에 따른 화합물은 대장암세포주에만 선택적으로 세포독 성을 나타내어 항암작용이 있음을 시사한다 할 수 있다. 즉, 본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는 정상세포에는 독성 이 없고 암 세포에만 선택적으로 작용하므로, 암의 예방 및 치료에 안전하게 사용 될 수 있다.  Normal cell lines were purchased from the American Type Culture Collection (ATCC) using a colon normal epithelial cell (FHC), the results are shown in FIG. As shown in Figure 1, the benzenesulfonamide derivatives according to the present invention did not show cytotoxicity to the normal colon cell line even in 100uM. That is, the compound according to the present invention can be said to have an anticancer action by selectively showing cytotoxicity only to colorectal cancer cell line. That is, the benzenesulfonamide derivative of Formula 1 according to the present invention is not toxic to normal cells and selectively acts only on cancer cells, and thus can be safely used for the prevention and treatment of cancer.
<3-5>본 발명에 따른 벤젠설폰아미드 유도체의 6가지 암세포주에 대한세포 독성 평가 <3-5> Evaluation of Cytotoxicity of Six Cancer Cell Lines of Benzenesulfonamide Derivatives According to the Present Invention
본 발명에 따른 벤젠설폰아미드 유도체의 6가지 암세포주에 대한 영향을 평 가하기 위하여 상기 실시예 3— 3과 동일한 방법으로 세포독성 실험을 수행하였다. 본 발명에 따른 벤젠설폰아미드 유도체는 실시예 1-214의 화합물을 대표로 하여 실 험하였다.  Cytotoxicity experiments were carried out in the same manner as in Examples 3 to 3 in order to evaluate the effects of the benzenesulfonamide derivatives on the six cancer cell lines according to the present invention. Benzenesulfonamide derivatives according to the invention were tested with the compounds of Examples 1-214 as representative.
대장암 세포주는 COL0201, WiDr, HCT— 15， SW620, S 480, DLD-l, HCT-116, HT-29, LS1034, LoVo, NCIᅳ H508, C0L0205, LS174T의 13개의 세포주를 사용하였다。  Colorectal cancer cell lines were 13 cell lines of COL0201, WiDr, HCT-15, SW620, S 480, DLD-1, HCT-116, HT-29, LS1034, LoVo, NCI ᅳ H508, C0L0205, LS174T.
폐암세포주는 NCI-H1975, A549, NCI-H226, NCI— H1793, NCI-H1650, NCI-H596, NCI-H460, NCI-H1299, NCI-H358, HCC— 44， HCC— 2108의 11개의 페포주를 사용하였다, 췌장암세포주는 Paneᅳ 1, MIA-Paca-2, BxPCᅳ 3， AsPCᅳ 1, Pane 10.05 의 5개의 페포주를 사용하였다. Lung cancer cell lines contain 11 alveoli of NCI-H1975, A549, NCI-H226, NCI— H1793, NCI-H1650, NCI-H596, NCI-H460, NCI-H1299, NCI-H358, HCC— 44, HCC— 2108. Used, Pancreatic cancer cell lines were composed of five alveolar cells: Pane ᅳ 1, MIA-Paca-2, BxPC ᅳ 3, AsPC ᅳ 1, and Pane 10.05.
유방암세포주는 MDM— MB-231, HCC1569, HCC70, HCC1937, HCC1395 의 5개의 페포주를 사용하였다.  Breast cancer cell lines were composed of five alveolar strains: MDM—MB-231, HCC1569, HCC70, HCC1937, and HCC1395.
난소암세포주는 NIH:0VCAR-3, SK-OV-3, Caov— 3， SNU119, UWB1.289의 5개의 페포주를 사용하였다.  Ovarian cancer cell lines were used in five alveolar strains, NIH: 0VCAR-3, SK-OV-3, Caov-3, SNU119, and UWB1.289.
뇌종양세포주는 U343, T98G, SNB-19, A-172, U87의 5개의 페포주를 사용하 였다.  Brain tumor cell lines were used for five alveoli, U343, T98G, SNB-19, A-172, U87.
상기 암세포주는 모두 American Type Culture Collection (ATCC)에서 구입하 여 사용하였다. 이에 대한 결과를 도 2에 나타내었다。 도 2에 나타낸 바와 같이 , 본 발명에 따른 벤젠설폰아미드 유도체는 6가지의 고형 암종에 대한 세포독성을 나타내고 있 으므로, 다양한 암종에 대해 항암작용이 있음을 알 수 있었다.  The cancer cell lines were all purchased from the American Type Culture Collection (ATCC). The results are shown in Fig. 2. As shown in Fig. 2, the benzenesulfonamide derivatives according to the present invention exhibited cytotoxicity against six solid carcinomas, indicating that they have anticancer activity against various carcinomas. Could.
<실시예 4> <Example 4>
간질 개선 효과  Epilepsy Improvement
<4-1> RagD GTP 가수분해 및 LRS의 lysosomal translocat ion의 저해활성 mTOR 야생형 또는 L2427P 돌연변이를 보유하는 NIH3T3 세포를 48 시간 홍안 si- 대조군 또는 si— LRS로 형질 감염시키고， 90 분 동안 류신을 결핍시킨 다음, 15 분 동안 류신으로 재자극 하였다, 세포 용해물을 GTP-아가로오스 비드와 함께 배양 하여 GTP 결합 단백질을 pull— do皿 시켰다. 침전물을 각각 항 -RagD 또는 ARF1 항체 로 면역 블로팅 하였다. ARF1은 음성 대조군으로 사용되었다。 리소좀 분획은 리소 좀 농축 키트 (Thermo Fisher Scientific, # 89839)를 사용하여 수득 하였다. S6K 인산화에 대한 실시예 1-214의 효과를 항-포스포 S6K항체 (Cell Signaling Technology, # 9205)로 면역 블로팅하여 분석 하였다, 이에 대한 결과를 도 3A에 나타내었다. <4-1> RagD GTP hydrolysis and inhibitory activity of lysosomal translocat ion of LRS NIH3T3 cells carrying mTOR wild-type or L2427P mutations were transfected with a 48 hour red eye si-control or si— LRS and deficient in leucine for 90 minutes. After stimulation with leucine for 15 minutes, the cell lysates were incubated with GTP-agarose beads to pull-out GTP binding proteins. Precipitates were immunoblotted with anti-RagD or ARF1 antibodies, respectively. ARF1 was used as a negative control. The lysosomal fraction was obtained using a lysosome enrichment kit (Thermo Fisher Scientific, # 89839). The effect of Example 1-214 on S6K phosphorylation was analyzed by immunoblotting with anti-phospho S6K antibody (Cell Signaling Technology, # 9205), the results are shown in Figure 3A.
도 3A에 나타낸 바와 같이 , mTOR L2427P 돌연변이를 보유하는 NIH3T3 세포에 siᅳ LRS로 형질 감염시킨 경우, 류신 처리에 의한 RagD의 GTP 분해가 억제되고 mTORCl의 성분 중 하나인 Rapt or의 리소좀 이동이 막혀 S6K 인산화가 저해됨을 알 수 있다. 또한, mTOR 야생형 또는 L2427P 돌연변이를 보유하는 NIH3T3 세포를 6 시간 동안 20 mi croM의 실시예 1—214 화합물로 처리하고， 90 분 동안 류신을 결핍시킨 후, 15 분 동안 류신으로 재자극 하였다. 세포용 해물을 GTP—아가로오스 비드와 함 께 배양하여 GTP 결합 단백질을 pul l-do皿 시켰다, 침전물을 각각 항 -RagD 또는 ARF1 항체로 면역 블로팅 하였다. ARF1은 음성 대조군으로 사용되었다. 리소좀 분 획은 리소좀 농축 키트 (Thermo Fi sher Sci ent i f i c , # 89839)를 사용하여 수득 하였 다. S6K 인산화에 대한 실시예 1—186 화합물의 효과를 항-포스포 S6K항체 (Cel l Signal ing Technology, # 9205)로 면역 블로팅하여 분석하였다. 이에 대한 결과를 도 3B에 나타내었다. As shown in FIG. 3A, when NIH3T3 cells carrying the mTOR L2427P mutation were transfected with si ᅳ LRS, GTP degradation of RagD by leucine treatment was inhibited and lysosomal migration of Rapt or, one of the components of mTORCl, was blocked. It can be seen that phosphorylation is inhibited. In addition, NIH3T3 cells carrying the mTOR wild type or L2427P mutation were treated with 20 mi croM of Example 1-214 compound for 6 hours, deficient in leucine for 90 minutes, and then restimulated with leucine for 15 minutes. Cell lysates were cultured with GTP-agarose beads to pul l-do the GTP binding protein, and the precipitates were immunoblotted with anti-RagD or ARF1 antibodies, respectively. ARF1 was used as a negative control. Lysosomal fractions were obtained using a lysosomal enrichment kit (Thermo Fischer Sci ent, # 89839). The effect of Example 1-186 compounds on S6K phosphorylation was analyzed by immunoblotting with anti-phospho S6K antibody (Cel l Signaling Technology, # 9205). The results are shown in FIG. 3B.
도 3B에 나타낸 바와 같이 , mTOR L2427P 돌연변이를 보유하는 NIH3T3 세포에 실시예 1-214 화합물로 처리하게 되면， 류신 처리에 의한 RagD의 GTP 분해가 억제 되고 mTORCl의 성분 중 하나인 Rapt or의 리소좀 이동이 막혀 S6K 인산화가 저해됨 을 알 수 있다.  As shown in FIG. 3B, treatment of NIH3T3 cells carrying the mTOR L2427P mutation with the compound of Example 1-214 inhibits GTP degradation of RagD by leucine treatment and inhibits lysosomal migration of Rapt or, one of the components of mTORCl. Blockage of S6K phosphorylation is inhibited.
<4ᅳ 2>간질과 연관된 mTOR돌연변이 (L2427P)를 발현하는 세포에서 mTORCl활 성 저해효과 Inhibitory Effect of mTORCl Activity on Cells Expressing MTOR Mutation (L2427P) Associated with Epilepsy
L2427P 돌연변이를 발현하고 있는 NIH3T3 세포를 실시예 1-214 화합물의 해 당 농도로 6 시간 동안 처리하였다, S6K 인산화에 대한 화합물의 효과를 항—포스 포 S6K 항체 (Cel l Signal ing Technology, # 9205)로 면역 블로팅하여 분석하였다, 이에 대한 결과를 도 4에 나타내었다.  NIH3T3 cells expressing the L2427P mutation were treated for 6 hours at the corresponding concentrations of the compounds of Examples 1-214. The effect of the compound on S6K phosphorylation was determined by anti—phospho S6K antibody (Cel l Signaling Technology, # 9205). The result was analyzed by immunoblotting, and the results are shown in FIG. 4.
도 4에 나타낸 바와 같이 , mTOR L2427P 돌연변이를 보유하는 NIH3T3 세포에 실시예 1-214 화합물을 농도별로 처리하게 되면 S6K의 인산화가 농도가 증가하면서 감소되는 패턴을 볼 수 있다. S6K의 인산화 정도를 정량화하여 그래프를 그리게 되 면 S6K 인산화 저해 효과에 대한 실시예 1—186 화합물의 IC50 값은 54.99nM 정도로 분석이 된다.  As shown in Figure 4, when the concentration of the Example 1-214 compound in the NIH3T3 cells carrying the mTOR L2427P mutant can be seen that the pattern of phosphorylation of S6K decreases with increasing concentration. If the graph quantifies the degree of phosphorylation of S6K, the IC50 value of Example 1—186 compound for S6K phosphorylation inhibitory effect is analyzed to be about 54.99 nM.
<4-3> 간질 동물모델에서 간질성 발작의 저해효과 <4-3> Inhibitory Effects of Interstitial Seizures in Animal Models of Epilepsy
C57BL/6 mice (주.중앙실험동물)를 구입하여, 동물 사육실 환경을 항온 23°C 로 유지하였고, 광주기 및 암주기를 12시간 간격으로 조절하였다. 동물은 시험물질 각 군당 3마리로 3군， 총 9마리를 사용하였고， 각 군은 실시예 1—214 화합물, 라파 마이신 (양성대조군)， vehi cle (대조물질군)이다. 간질 동물모델을 확립하기 위해, 시간을 두고 임신한 마우스 (embryonic day 14)를 isoflurane( oxygen and Isof lurane vaporizer gauge 3, 0,4L/min)으로 마취시켰다. 자궁 경부를 노출시키 고, 2-3 mg의 mTOR 돌연변이 플라스미드와 결합된 2 ug/ml Fast Green (F7252, Sigma, USA)을 가진 유리 모세관을 사용하여 각 배아의 측심실에 주입하였다, 이후 마우스가 태어나면 GFP 선별을 하고， 생후 30일이 되면 간질 발작 상태를 확인하여 간질 동물모델을 선별하였다. 상기 본 발명의 간질 동물모델은 Nature Medicine, 21 (4) ： 395-400 (2015)에 기재된 방법으로 수행되었다. 실시예 1-214 화합물 (TID, 10 mg/kg, IP 주사), 라파마이신 (QD, 10 rag/kg, IP 주사) 또는 대조물질 (4¾ DMAC, 5% PEG, 5% Tween-80)을 L2427P mTOR 돌연변이를 가진 마우스에 2주간 투여한 후， 행동 발작 빈도를 측정하였다. 이에 대한 결과를 도 5에 나타내었디-, C57BL / 6 mice (C.C. central animals) were purchased, and the environment of the animal feeding room was maintained at 23 ° C., and the photoperiod and the cancer cycle were adjusted at 12 hour intervals. Animals were used in groups of 3, 9 in total, for each group of test substances, and each group was Example 1-214 compound, rapamycin (positive control group), and vehi cle (control group). To establish an epileptic animal model, Over time, pregnant mice (embryonic day 14) were anesthetized with isoflurane (oxygen and Isof lurane vaporizer gauge 3, 0,4 L / min). The cervix was exposed and injected into the lateral ventricle of each embryo using glass capillaries with 2 ug / ml Fast Green (F7252, Sigma, USA) combined with 2-3 mg of the mTOR mutant plasmid. At birth, GFP was screened, and at 30 days of age, epileptic seizures were checked to select an epileptic animal model. The epilepsy animal model of the present invention was carried out by the method described in Nature Medicine, 21 (4): 395-400 (2015). Example 1-214 Compound (TID, 10 mg / kg, IP Injection), Rapamycin (QD, 10 rag / kg, IP Injection) or Control (4¾ DMAC, 5% PEG, 5% Tween-80) with L2427P After 2 weeks of administration to mice with mTOR mutations, the frequency of behavioral attacks was measured. Results of this are shown in FIG. 5,
도 5에 나타낸 바와 같이， mTOR L2427P 돌연변이를 갖는 간질 동물모델에서 대조물질의 경우 24시간 동안 평균적으로 18회의 행동발작 빈도를 나타내는 반면， 실시예 1—214 화합물을 투여한 경우 24시간 평균 3.3회 정도의 행동발작 빈도를 보 임으로서 간질성 발작 저해 효과를 관찰할수 있었다.  As shown in FIG. 5, in the epileptic animal model having the mTOR L2427P mutation, the control had an average frequency of 18 behavioral seizures for 24 hours, whereas Example 1—214 compound had an average of about 24 times for 24 hours. Inhibition of epileptic seizures was observed by showing the frequency of behavioral seizures.
<4~4> 혈액-뇌 장벽 (blood— brain barrier, BBB) 투과성 <4 to 4> blood-brain barrier (BBB) permeability
Pi on BBB-PAMPA 분석 키트를 수동적, 세포간 투과성의 in vitro 모델로 사용 로 하였다. 필터에 고정화 된 인공막을 공여체와 수용체 구획 사이에 두었다, 각 약물은 기증자 구획에 도입된 다음 기증자 및 수용체 구획내의 약물 농도를 측정 하였다, 이에 대한 결과를 도 6에 나타내었다。  The Pi on BBB-PAMPA assay kit was used as an in vitro model of passive, intercellular permeability. A membrane immobilized on the filter was placed between the donor and receptor compartments. Each drug was introduced into the donor compartment and the drug concentrations in the donor and receptor compartments were measured, the results of which are shown in FIG.
도 6에 나타낸 바와 같이, 실시예 1-214 화합물은 기존에 뇌질환 치료제로 사용이 되는 hydroxychloroquine, progesterone, cort i coster one, rivastigmine, carbamazepine과 비교해도 우수한 인공막 투과도 결과를 보이고 있고， mTOR 저해제 (rapamycin, temsirol imus , INK128)와의 비교에서도 가장 우수한 투과도를 보이고 있다. 한편， in vivo BBB 투과성 실험은 다음과 같은 방법에 따라 수행하였다. Test compound를 dimethyl acet ami de/Tween 80/20% 2-hydroxypropylᅳ cyclodextrin (10/10/80 v/v%)°H 녹인 후 male ICR mouse (9주령)에 5mg/kg으로 정 맥주사 (iv, 5ml/kgᅳ)한 다음 0， 30, 60 그리고 90 분에 C02 chamber 에서 안락사 시 킨 후 심장채혈을 통해 혈액을 채취하고 절두하여 뇌를 적출하였다 (n=3/each time point) . 획득한 혈액은 BD microtainer tube (with Lithium Heparin additive) 에 가하여 4°C에서 12000 rpm으로 5분간 원심분리 한 다음 plasma를 분리하고 뇌는 무 게를 잰 후 3배 volume 의 물을 넣어 분쇄시켜 homogenate로 만들었다, 혈액 및 뇌 의 homogenate에 3배 volume 의 internal standard를 포함한 acetonitr i le을 가하 여 protein precipitation 한 다음 상등액을 물과 1:1로 희석시킨 후 LC— MS/MS method를 이용하여 정량분석을 수행하였다. As shown in Figure 6, Examples 1-214 compound shows excellent membrane permeability results compared to hydroxychloroquine, progesterone, cort i coster one, rivastigmine, carbamazepine that are conventionally used as a treatment for brain diseases, mTOR inhibitor (rapamycin , temsirol imus, INK1 2 8) also showed the best permeability. On the other hand, in vivo BBB permeability experiment was performed according to the following method. Dissolve the test compound in dimethyl acet ami de / Tween 80/20% 2-hydroxypropyl ᅳ cyclodextrin (10/10/80 v / v%) ° H and set it to 5 mg / kg in male ICR mouse (9 weeks old). Beer (iv, 5ml / kg ᅳ) was euthanized in a C02 chamber at 0, 30, 60 and 90 minutes, and blood was collected by cardiac collection and truncated (n = 3 / each time point). ). The obtained blood was added to a BD microtainer tube (with Lithium Heparin additive) and centrifuged at 12000 rpm for 5 minutes at 4 ° C. The plasma was separated and the brain weighed and pulverized by adding 3 times the volume of water to homogenate. After the protein precipitation by adding acetonitrile containing three times the volume of the internal standard to the homogenate of blood and brain, the supernatant was diluted 1: 1 with water and quantitatively analyzed using LC—MS / MS method. It was.
이에 대한 결과를 표 7에 나타내었다.  The results are shown in Table 7.
[표 7] TABLE 7
In vivo BBB 투과성  In vivo BBB Permeability
Figure imgf000131_0001
상기 표 7에서 나타낸 바와 같이， brain과 plasma에서 존재하는 화합물의 양 을 비교 하여 BBB를 투과한 양을 측정하는 실험으로 실시예 1—214 화합물 brain/plasma 비율을 측정하였을 시， 평균적으로 약 10 내지 20% 정도의 비율로 화 합물이 brain으로 이동한 것을 관찰할 수 있었다. 이상과 같이, 본 발명의 화합물은 간질 -연관 돌연변이를 발현하고 있는 세포 에서 mTORCl의 활성을 효과적으로 억제하고, 간질 동물모델에서 간질성 발작의 발 현 흿수를 현저하게 감소하는 효과가 있을 뿐만 아니라, 혈액—뇌 장벽 투과성도 매 우 높아 간질 치료제로 개발될 가능성이 매우 높다는 것을 알 수 있었다.
Figure imgf000131_0001
As shown in Table 7, an experiment for measuring the amount of BBB permeation by comparing the amounts of compounds present in the brain and plasma, Example 1—214 compound brain / plasma ratio was measured, on average, about 10 to At 20%, the compound moved to the brain. As described above, the compounds of the present invention effectively inhibit the activity of mTORCl in cells expressing epileptic-associated mutations, and the onset of interstitial seizures in an epileptic animal model. In addition to significantly reducing the current count, the blood-brain barrier permeability is also very high, suggesting that it is very likely to be developed as an antiepileptic drug.
【산업싱- 이용가능성】 [Industrial housing-availability]
본 발명에 따른 화학식 1의 벤젠설폰아미드 유도체는 LRS와 RagD 간의 결합 을 저해하여 mTORCl의 활성화를 억제하는 효과가 매우 우수하므로， mT0R를 저해함 으로써 치료효과가 달성될 수 있는 암, 간질, 염증질환， 면역질환, 당뇨， 비만, 호 흡기계 폐쇄성 질환, 섬유증, 품페병, 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질환, 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행성 질환, 심혈관계질환 및 기생충 감염증으로 이루어진 군에서 선택된 어느 한 질환의 예방 또는 치료제 개발에 매우 유용하게 활용될 수 있어 산업상 이용가능성이 매우 우수 하디- . Benzenesulfonamide derivatives of Formula 1 according to the present invention have a very good effect of inhibiting the binding between LRS and RagD to inhibit the activation of mTORCl, cancer, epilepsy, inflammation that can achieve a therapeutic effect by inhibiting m T0R Diseases, immune disorders, diabetes, obesity, respiratory obstructive diseases, fibrosis, pamp disease, lysosomal storage di sease, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, cardiovascular and parasitic infections It can be very useful in the development of a preventive or therapeutic agent for any disease selected from the group consisting of very high industrial applicability.

Claims

【청구의 범위】 【Scope of Claim】
【청구항 II 【Claim II
하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염 ： [화학식 1] A compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof: [Formula 1]
Figure imgf000133_0001
Figure imgf000133_0001
상기 화학식 1에서， In Formula 1,
R1은 치환 또는 비치환 페닐; 할로; 또는 직선형 또는 분지형 알킬이 고, 상기 R1이 치환된 페닐인 경우 그 치환기는 할로겐 원자, 치환되지 않은 직선형 또는 분지형 d- 알킬 및 1개 이상의 할로겐 원자로 치환된 직선형 또는 분지형 d-C6 알킬로 이루어진 군에서 1개 이상 선택될 수 있으몌 R2는 수소; 또는 직선형 또는 분지형 d- j 알킬이고， R 1 is substituted or unsubstituted phenyl; halo; or straight or branched alkyl, and when R 1 is substituted phenyl, the substituent is a halogen atom, unsubstituted straight or branched d-alkyl and straight or branched dC 6 alkyl substituted with one or more halogen atoms. One or more items may be selected from the group consisting of R 2 is hydrogen; or straight or branched d-j alkyl,
R3은 수소; 치환 또는 비치환 d-C6 직선형 또는 분지형 알킬; C5ᅳ C10 시클로 알킬; 치환 또는 비치환 C5— C20 아릴; 디옥소안트라세닐; 또는 고리 내에 1개 이상 의 헤테로 원자를 포함하는 헤테로 고리 또는 헤테로아릴 고리로서， 이들이 치환되 는 경우 그 치환기는 직선형 또는 분지형의 d— C6 알킬; d-C6 알킬옥시 ; d-C6알킬 아미노기로 치환된 d— C6알킬옥시 ; 모폴린으로 치환된 d— C6알킬옥시 ; d-C6알킬옥 시카보닐; 히드록시카보닐 d— C6알킬; 플루오로 원자 1개 이상으로 치환된 d-Cs알 킬; ― C6알킬아미노; 페닐; 직선형 또는 분지형의 d— C6 알킬， 직선형 또는 분지형 의 CrC6 알킬옥시 , 직선형 또는 분지형의 d-C6 알킬옥시카보닐， 할로겐 원자 및 플 루오로 원자 1개 이상으로 치환된 알킬로 이루어진 군에서 선택되는 1개 이상의 치 환기로 치환된 페닐; 페녹시; 직선형 또는 분지형의 d-Cs 알킬， 할로겐 원자 및 직 선형 또는 분지형의 d-Cs 알킬옥시로 이루어진 군에서 선택되는 1개 이상의 치환기 로 치환된 페녹시 ; 아미노설포닐 ; 할로 ; 시아노 ; 아세틸; 니트로 ; 에티닐; 히드록 시; 모폴리노; 나프틸; 테에닐; 피리딜; 테트라히드로퓨라닐; 카르복실; 티오페 닐; d-C10 사이클로알킬; 벤조디옥소릴; 직선형 또는 분지형의 d-C6 알킬옥시로 치 환된 인돌릴; 디히드로벤조옥시닐; 및 퓨릴메틸설파닐로 이루어진 군에서 1개 이상 선택되는 것이고， 상기 아릴， 헤테로 고리 및 헤테로아릴 고리는 각각 2개 이상의 고리가 융합된 복소환 구조일 수 있고, 또한 고리 내에 카보닐기를 포함할 수 있는 것이거나， R 3 is hydrogen; substituted or unsubstituted dC 6 straight or branched alkyl; C 5 ᅳ C 10 cycloalkyl; Substituted or unsubstituted C 5 — C 20 aryl; dioxoanthracenyl; Or a hetero ring or heteroaryl ring containing one or more heteroatoms in the ring, and when they are substituted, the substituent is straight or branched d—C 6 alkyl; dC 6 alkyloxy ; d—C 6 alkyloxy substituted with dC 6 alkyl amino group; d—C 6 alkyloxy substituted with morpholine; dC 6 alkyloxycarbonyl; hydroxycarbonyl d—C 6 alkyl; d-Csalkyl substituted with one or more fluoro atoms; —C 6 alkylamino; phenyl; Straight or branched d—C 6 alkyl, straight or branched CrC 6 alkyloxy, straight or branched dC 6 alkyloxycarbonyl, a group consisting of alkyl substituted with one or more halogen atoms and fluoro atoms phenyl substituted with one or more substituents selected from; phenoxy; One or more substituents selected from the group consisting of linear or branched d-Cs alkyl, halogen atom and linear or branched d-Cs alkyloxy Phenoxy substituted with ; aminosulfonyl; halo ; cyano ; acetyl; nitro ; ethynyl; Hydroxy; morpholino; naphthyl; theenyl; pyridyl; tetrahydrofuranyl; carboxyl; thiophenyl; dC 10 cycloalkyl; benzodioxoryl; indolyl substituted with straight or branched dC 6 alkyloxy; dihydrobenzooxynyl; and furylmethylsulfanyl, and the aryl, heterocycle, and heteroaryl ring may each have a heterocyclic structure in which two or more rings are fused, and may also include a carbonyl group within the ring. Either there is, or
상기 R2와 R3은 서로 결합하여 고리 내에 1개 이상의 헤테로 원자를 포함하 는 C5— C20 헤테로 고리 또는 헤테로아릴 고리를 형성함. R 2 and R 3 combine with each other to form a C 5 — C 20 hetero ring or heteroaryl ring containing one or more heteroatoms in the ring.
【청구항 2] 제 1항에 있어서, 상기 R1은 페닐, 또는 플루오로, 클로로, 브로모 및 트리플 루오로메틸로 이루어진 군에서 선택되는 치환기 1개 이상으로 치환된 페닐， 또는 메틸， 에틸, 프로필, 이소프로필 및 t—부틸로 이루어진 군에서 선택되는 것인 화합 물 [Claim 2] The method of claim 1, wherein R 1 is phenyl, or phenyl substituted with one or more substituents selected from the group consisting of fluoro, chloro, bromo, and trifluoromethyl, or methyl, ethyl, and propyl. A compound selected from the group consisting of isopropyl and t-butyl.
【청구항 3] 거 U항에 있어서, 상기 R2는 수소, 메틸, 에틸, 프로필, 이소프로필 및 t-부 틸로 이루어진 군에서 선택되는 것인 화합물. [Claim 3] The compound according to claim U, wherein R 2 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, and t-butyl.
【청구항 4】 제 1항에 있어서, 상기 R3은 수소; C5— C10 시클로알킬; 및 치환 또는 비치환 페닐， 나프틸， 벤조퓨라닐, 벤조티오페닐, 안트라세닐, 벤조디옥소릴, 인단일 또는 테트랄린일, 피페리디닐， 피리딜， 피리미디닐， 피라졸릴, 퀴놀릴, 벤조디옥시닐， 인돌릴， 옥소인돌릴， 벤조티아졸릴， 옥소티옥산테닐, 벤지미다졸릴, 옥소벤지미다 졸릴， 티오페닐 벤조티오페닐, 테트라히드로벤조티오페닐 및 카르바졸릴로 이루어 진 군에서 선택되는 것인 화합물. [Claim 4] The method of claim 1, wherein R 3 is hydrogen; C 5 — C 10 cycloalkyl; And substituted or unsubstituted phenyl, naphthyl, benzofuranyl, benzothiophenyl, anthracenyl, benzodioxoryl, indanyl or tetralinyl, piperidinyl, pyridyl, pyrimidinyl, pyrazolyl, quinolyl, benzoyl. Select from the group consisting of deoxynyl, indolyl, oxoindolyl, benzothiazolyl, oxothioxanthenyl, benzimidazolyl, oxobenzimidazolyl, thiophenyl benzothiophenyl, tetrahydrobenzothiophenyl and carbazolyl A compound that becomes something.
【청구항 5] [Claim 5]
거 항에 있어서, 상기 R3은 수소, 시클로프로필, 시클로펜틸， 시클로핵실， 시클로헵 틸, 페닐, sec—부틸페닐, t-부틸페닐, 틀릴， 이소프로필페닐, 디메틸페닐, 에틸페 닐， 메특시페닐， 메특시디메틸페닐， 디메특시페닐， 디메틸아미노에록시페닐， 클로 로페닐， 디클로로페닐, 플루오로페닐, 브로모페닐, 디브로모페닐， 클로로플루오로 페닐, 플루오로메틸페닐, 시아노페닐， 아세틸페닐, 페닐페닐, 니트로페닐， 모폴리 노페닐, 에록시니트로페닐, 에티닐페닐， 디메틸니트로페닐， 디클로로니트로페닐, 클로로니트로페닐， 디메틸니트로페닐, 히드록시페닐, (메록시카보닐)페닐, (에록시 카보닐)페닐， 히드록시메틸페닐， (디메틸아미노)페닐， (트리플루오로메틸)페닐.， 비 스 (트리플루오로메틸)페닐， (히드록시카보닐메틸)페닐， 아미노설포닐페닐, 나프틸, 브로모나프틸, 메틸나프틸， 히드록시나프틸， 인단일, 테트랄린일, (에특시카보닐) 피페리딘일， (t-부록시카보닐)피페리딘일， 피리딜, 플루오로피리딜， 클로로피리딜， 메록시피리딜， 피리미딘일， 트리메틸피라졸릴， 퀴놀릴， 메틸퀴놀릴, 디히드로벤조 디옥신일， 메틸— 1H-인돌일， 메록시벤조티아졸릴, 옥소티옥산텐일, 디메틸옥소벤지 미다졸릴， 에록시카보닐벤조티오펜일, 에록시카보닐테트라히드로벤조티오펜일, 에 틸카르바졸릴， 아세틸벤조디옥솔일, 에틸, 프로필, 이소프로필， t—부틸, 디메틸프 로필, 에록시에틸, 디메특시프로필， 메록시카보닐에틸， 벤질， 페닐에틸, 페닐프로 필， 페닐부틸, 를릴메틸， 를릴에틸， (플루오로페닐)메틸, (플루오로페닐)메틸， (클 로로페닐)메틸， (브로모페닐)메틸， (플루오로페닐)에틸, (클로로페닐)에틸， (브로 모페닐)에틸, (메록시페닐)메틸, (디메록시페닐)메틸， (메록시페닐)에틸, (디메록 시페닐)에틸， 메록시카보닐페닐메틸, [ (트리플루오로메틸)페닐]메틸， [ (트리플루오 로메틸)페닐]에틸, 페녹시에틸， (디메틸페녹시)에틸， 페녹시프로필, (플루오로페녹 시)에틸, (메특시페녹시)에틸， 나프틸메틸， 티에닐메틸， 피리딜메틸, (피리딜)에 틸, 테트라히드로퓨란일메틸， ( 1H-인돌일)메틸, ( 1H-인돌일)에틸, (메록시— 1H-인돌 일)에틸， (디히드로벤조디옥신일)메틸, (퓨릴메틸설파닐)에틸， 히드록시바이페닐， (몰폴리노에록시)페닐， 디히드로페닐， 플루오로히드록시페닐， 메특시니트로페닐, 히드록시카보닐페닐， 메틸벤조퓨라닐, 벤조티오페닐， 벤조퓨라닐, (메록시카르보 닐)벤조티오페닐， (메록시카르보닐페닐)메틸, (메록시카르보닐)나프틸, 트리메틸 페닐, 안트라세닐, 벤조디옥실 옥소인돌릴, 티오페닐에틸, 트리메특시페닐, 시클 로핵실메틸, 시클로헵틸메틸, 시클로핵실에틸 및 디메록시페닐로 이루어진 군에서 선택되는 것인 화합물. According to claim 3, R 3 is hydrogen, cyclopropyl, cyclopentyl, cyclohexyl, cyclohepyl. Tyl, phenyl, sec—butylphenyl, t-butylphenyl, tlyl, isopropylphenyl, dimethylphenyl, ethylphenyl, methoxyphenyl, methoxydimethylphenyl, dimethoxyphenyl, dimethylaminoeroxyphenyl, chlorophenyl, Dichlorophenyl, fluorophenyl, bromophenyl, dibromophenyl, chlorofluorophenyl, fluoromethylphenyl, cyanophenyl, acetylphenyl, phenylphenyl, nitrophenyl, morpholinophenyl, eroxynitrophenyl, ethynyl Phenyl, dimethylnitrophenyl, dichloronitrophenyl, chloronitrophenyl, dimethylnitrophenyl, hydroxyphenyl, (meroxycarbonyl)phenyl, (eroxycarbonyl)phenyl, hydroxymethylphenyl, (dimethylamino)phenyl, (tri Fluoromethyl)phenyl., Bis (trifluoromethyl)phenyl, (hydroxycarbonylmethyl)phenyl, aminosulfonylphenyl, naphthyl, bromonaphthyl, methylnaphthyl, hydroxynaphthyl, indanyl, Tetralinyl, (ethoxycarbonyl) piperidinyl, (t-butoxycarbonyl) piperidinyl, pyridyl, fluoropyridyl, chloropyridyl, meroxypyridyl, pyrimidinyl, trimethylpyrazolyl , quinolyl, methylquinolyl, dihydrobenzodioxinyl, methyl-1H-indolyl, meroxybenzothiazolyl, oxothioxanthenyl, dimethyloxobenzi midazolyl, eroxycarbonylbenzothiophenyl, eroxy Carbonyltetrahydrobenzothiophenyl, ethylcarbazolyl, acetylbenzodioxolyl, ethyl, propyl, isopropyl, t-butyl, dimethylpropyl, eroxyethyl, dimethoxypropyl, meroxycarbonylethyl, Benzyl, phenylethyl, phenylpropyl, phenylbutyl, allylmethyl, allylethyl, (fluorophenyl)methyl, (fluorophenyl)methyl, (chlorophenyl)methyl, (bromophenyl)methyl, (fluorophenyl) ) Ethyl, (chlorophenyl) ethyl, (bromophenyl) ethyl, (meroxyphenyl) methyl, (dimeroxyphenyl) methyl, (meroxyphenyl) ethyl, (dimeroxyphenyl) ethyl, meroxycarbonylphenyl Methyl, [(trifluoromethyl)phenyl]methyl, [(trifluoromethyl)phenyl]ethyl, phenoxyethyl, (dimethylphenoxy)ethyl, phenoxypropyl, (fluorophenoxy)ethyl, (methoxy) Phenoxy)ethyl, naphthylmethyl, thienylmethyl, pyridylmethyl, (pyridyl)ethyl, tetrahydrofuranylmethyl, (1H-indolyl)methyl, (1H-indolyl)ethyl, (meroxy— 1H-indol yl)ethyl, (dihydrobenzodioxinyl)methyl, (furylmethylsulfanyl)ethyl, hydroxybiphenyl, (morpholinoeroxy)phenyl, dihydrophenyl, fluorohydroxyphenyl, meteuk Cinitrophenyl, hydroxycarbonylphenyl, methylbenzofuranyl, benzothiophenyl, benzofuranyl, (meroxycarbonyl)benzothiophenyl, (meroxycarbonylphenyl)methyl, (meroxycarbonyl)naph A compound selected from the group consisting of methyl, trimethyl phenyl, anthracenyl, benzodioxyl oxoindolyl, thiophenylethyl, trimetoxyphenyl, cyclohexylmethyl, cycloheptylmethyl, cyclohexylethyl and dimeroxyphenyl.
【청구항 6】 제 1항에 있어서， 상기 R2와 R3이 서로 결합하여 치환 또는 비치환 모폴린， 피페리딘， 피페라진, 인돌린, 퀴녹살린온 또는 디아제핀 고리를 형성하고， 이들이 치환되는 경우 그 치환기는 직선형 또는 분지형의 (：厂 c6 알킬, 치환 또는 비치환 c5 ~c20 아릴 및 치환 또는 비치환 c5-c20 헤테로아릴로 이루어진 군에서 1개 이상 선 택되는 것인 화합물. 【Claim 6】 The method of claim 1, wherein R 2 and R 3 are combined with each other to form a substituted or unsubstituted morpholine, It forms a piperidine, piperazine, indoline, quinoxalinone or diazepine ring, and when they are substituted, the substituent is straight or branched (: 厂 c 6 alkyl, substituted or unsubstituted c 5 ~ c 20 aryl and one or more compounds selected from the group consisting of substituted or unsubstituted c 5 -c 20 heteroaryl.
【청구항 7】 제 6항에 있어서, 상기 R2와 R3이 서로 결합하여 모폴린， 피페리딘, 피페라 진, 에틸피페라진， 페닐피페라진， (니트로페닐)피페라진, (메톡시페닐)피페라진, 피리딘일피페라진， (클로로퀴놀릴)피페라진， (모폴린카르보닐)피페라진, [ [ (모폴린 카르보닐)니트로페닐]피페라진， 퀴녹살린온, 디히드로퀴녹살린온, 인돌린, 디아제 핀, (페닐설포닐)디아제핀 또는 [ (이소프로필디메틸옥소피라졸릴)페닐]설포닐디아 제핀 고리를 형성하는 것안화합물. [Claim 7] The method of claim 6, wherein R 2 and R 3 are combined with each other to form morpholine, piperidine, piperazine, ethylpiperazine, phenylpiperazine, (nitrophenyl)piperazine, (methoxyphenyl) ) Piperazine, pyridinyl piperazine, (chloroquinolyl) piperazine, (morpholine carbonyl) piperazine, [ [(morpholine carbonyl) nitrophenyl] piperazine, quinoxalinone, dihydroquinoxalinone, Indoline, diazepine, (phenylsulfonyl)diazepine or [(isopropyldimethyloxopyrazolyl)phenyl]sulfonyldiazepine compounds that form a ring.
【청구항 8】 【Claim 8】
제 1항에 있어서, 싱-기 화합물은 The method of claim 1, wherein the singe-group compound is
N—시클로핵실— 4— (4—이소프로필— 2， 3—디메틸ᅳ5—옥소-피라졸—1—일)벤젠설폰아미 에틸 4— [ [4— (4—이소프로필— 2， 3—디메틸 -5—옥소—피라졸— 1-일)페닐 ]설포닐아미 노]벤조에이트 N—cyclohexyl— 4— (4—isopropyl— 2， 3—dimethylᅳ5—oxo-pyrazol—1—yl)benzenesulfonami ethyl 4— [ [4— (4—isopropyl— 2， 3— dimethyl -5—oxo—pyrazole— 1-yl)phenyl ]sulfonylamino]benzoate
4-(4-이소프로필— 2， 3-디메틸— 5—옥소—피라졸— 1ᅳ일 )-Nᅳ페닐—벤젠설폰아미드 N-시클로핵실— 4- ( 4—이소프로필 -2， 3—디메틸ᅳ5—옥소ᅳ피라졸 1-일) -N-메틸 -벤젠 설폰아미드 4-(4-isopropyl— 2, 3-dimethyl— 5—oxo—pyrazol— 1-yl )-N-phenyl—benzenesulfonamide N-cyclohexyl— 4- ( 4—isopropyl -2, 3—dimethyl ᅳ5—Oxopyrazole 1-yl) -N-methyl -benzene sulfonamide
N-(4-터트-부틸페닐) -4-(4-이소프로필 -2 , 3ᅳ디메틸 -5ᅳ옥소—피라졸 -1ᅳ일 )벤젠 설폰아미드 N-(4-tert-butylphenyl)-4-(4-isopropyl-2, 3-dimethyl-5-oxo—pyrazol-1-yl)benzene sulfonamide
4— ( 4ᅳ이소프로필—2 , 3-디메틸— 5—옥소-피라졸— 1-일 ) -N- ( 4—메록시페닐)벤젠설폰 아미드 4— ( 4—isopropyl—2, 3-dimethyl— 5—oxo-pyrazole— 1-yl) -N- (4—meroxyphenyl)benzenesulfone amide
4— (4ᅳ이소프로필 -2 , 3-디메틸— 5-옥소-피라졸 -1—일 )— N-(4-모폴리노페닐)벤젠설 폰아미드 4— (4-isopropyl-2, 3-dimethyl— 5-oxo-pyrazol-1—yl)— N-(4-morpholinophenyl)benzenesulfonamide
N- [ (3， 4-디메록시페닐)메틸] -4-(4-이소프로필 -2 , 3-디메틸—5-옥소-피라졸 -1- 일)벤젠설폰아미드 N- [(3, 4-dimeroxyphenyl)methyl] -4-(4-isopropyl-2, 3-dimethyl—5-oxo-pyrazol-1-yl)benzenesulfonamide
N- [2ᅳ (3， 4—디메록시페닐)에틸] 4ᅳ(4—이소프로필 -2， 3-디메틸— 5—옥소—피라졸— 1—일)벤젠설폰아미드 N- [2ᅳ (3, 4—dimeroxyphenyl)ethyl] 4ᅳ(4—isopropyl -2, 3-dimethyl— 5—oxo—pyrazole— 1—1)Benzenesulfonamide
4一 (4-이소프로필 -2 , 3-디메틸 -5-옥소—피라졸 -1-일 )-N— [ (2—메록시페닐)메틸]벤 젠설폰아미드 4一 (4-isopropyl-2, 3-dimethyl-5-oxo—pyrazol-1-yl)-N— [ (2—meroxyphenyl)methyl]benzenesulfonamide
4-(4-이소프로필— 2， 3—디메틸 -5-옥소-피라졸— 1—일 )— N— (p—를릴)벤젠설폰아미드 N-(4-클로로페닐 )—4— (4-이소프로필— 2，3-디메틸ᅳ 5ᅳ옥소—피라졸 -1—일)벤젠설폰 아미드 4-(4-isopropyl— 2, 3—dimethyl -5-oxo-pyrazole— 1—yl )— N— (p—yllyl)benzenesulfonamide N-(4-chlorophenyl)—4— (4- Isopropyl—2,3-dimethylᅳ 5—oxo—pyrazole -1—yl)benzenesulfone amide
4一 (4-이소프로필ᅳ 2，3-디메틸—5—옥소—피라졸 -1-일) -N- [2-(2-메특시페닐)에틸] 벤젠설폰아미드 4一 (4-isopropylᅳ 2,3-dimethyl—5—oxo—pyrazol -1-yl) -N- [2-(2-methoxyphenyl)ethyl] benzenesulfonamide
4- ( 4-이소프로필 -2 , 3—디메틸 -5-옥소-피라졸— 1-일 ) -N- [ 2- ( 2ᅳ메록시페녹시)에 틸]벤젠설폰아미드 4- ( 4-isopropyl -2 , 3—dimethyl -5-oxo-pyrazole— 1-yl ) -N- [ 2- ( 2-meroxyphenoxy)ethyl]benzenesulfonamide
4-(4—이소프로필— 2ᅳ3—디메틸ᅳ 5-옥소—피라졸— 1-일) -N-(3-메록시페닐)벤젠설폰 아미드 4-(4—isopropyl— 2ᅳ3—dimethylᅳ 5-oxo—pyrazole— 1-yl) -N-(3-meroxyphenyl)benzenesulfone amide
4一 (4—이소프로필 -2 , 3-디메틸— 5-옥소ᅳ피라졸— 1-일 )-N— (2ᅳ메특시페닐)벤젠설^ 아미드 4一 (4—isopropyl -2, 3-dimethyl— 5-oxo-pyrazole— 1-yl )-N— (2-methoxyphenyl)benzenesulf^ amide
4-(4—이소프로필— 2，3—디메틸 -5—옥소—피라졸 -1—일) -N-(3-페닐프로필)벤젠설폰 아미드 4-(4—isopropyl— 2,3—dimethyl -5—oxo—pyrazole -1—yl) -N-(3-phenylpropyl)benzenesulfone amide
4— (4-이소프로필 -2 , 3—디메틸— 5—옥소—피라졸 -1—일 )— N-(3—니트로페닐)벤젠설폰 아미드 4— (4-isopropyl -2 , 3—dimethyl— 5—oxo—pyrazol -1—yl )— N-(3—nitrophenyl)benzenesulfone amide
4-(4-이소프로필 -2 , 3—디메틸—5-옥소ᅳ피라졸 -1ᅳ일) -N— (4—니트로페닐)벤젠설폰 아미드 4-(4-isopropyl-2, 3—dimethyl—5-oxo-pyrazol-1-yl)-N— (4—nitrophenyl)benzenesulfone amide
4-(4—이소프로필 -2，3—디메틸 -5-옥소—피라졸 -1-일) -N-(2—페닐에틸)벤젠설폰아 미드 4-(4—isopropyl-2,3—dimethyl-5-oxo—pyrazol-1-yl)-N-(2—phenylethyl)benzenesulfonamide
4-(4-이소프로필 -2 , 3ᅳ디메틸— 5-옥소-피라졸 -1-일 )-N-(4-페닐부틸)벤젠설폰아 미드 4-(4-isopropyl-2, 3-dimethyl—5-oxo-pyrazol-1-yl)-N-(4-phenylbutyl)benzenesulfonamide
4— ( 4-이소프로필 -2 , 3-디메틸 -5—옥소—피라졸— 1-일)— N- ( 5-퀴놀릴)벤젠설폰아미 드 4— (4-isopropyl-2, 3-dimethyl-5—oxo—pyrazole— 1-yl)— N- (5-quinolyl)benzenesulfonamide
4-(4-이소프로필ᅳ 2 , 3-디메틸— 5-옥소—피라졸— 1-일)— N— (3-퀴놀릴)벤젠설폰아미 4-(4-isopropylᅳ 2, 3-dimethyl— 5-oxo—pyrazole— 1-yl)— N— (3-quinolyl)benzenesulfonami
N— (4-플루오로페닐 )—4— (4—이소프로필 -2 , 3-디메틸 -5—옥소—피라졸— 1—일 )벤젠설 폰아미드 N— (4-fluorophenyl )—4— (4—isopropyl -2, 3-dimethyl -5—oxo—pyrazol— 1—yl )benzenesulfonamide
터트—부틸 4— [ [4— (4—이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1—일)페닐]설포닐 아미노]피페리딘 -1-카르복실레이트 N-[2— (4ᅳ클로로페닐 )에틸] -4ᅳ (4-이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1-일) 벤젠설폰아미드 tert—butyl 4— [ [4— (4—isopropyl -2 , 3—dimethyl -5-oxo—pyrazol— 1—yl)phenyl]sulfonyl amino]piperidine -1-carboxylate N-[2— (4-chlorophenyl)ethyl]-4-(4-isopropyl-2, 3—dimethyl-5-oxo—pyrazole— 1-yl) benzenesulfonamide
4一 (4—이소프로필 -2 , 3ᅳ디메틸—5-옥소-피라졸—1ᅳ일)—N— (2—티에닐메틸)벤젠설폰 아미드 4一 (4—isopropyl-2, 3-dimethyl—5-oxo-pyrazol—1-yl)—N— (2—thienylmethyl)benzenesulfone amide
4- ( 4—이소프로필— 2 , 3—디메틸 -5—옥소—피라졸 -1-일)— N— (3-피리딜메틸)벤젠설폰 아미드 4- ( 4—isopropyl— 2 , 3—dimethyl -5—oxo—pyrazol -1-yl)— N— (3-pyridylmethyl)benzenesulfone amide
4一 (4-이소프로필— 2 , 3-디메틸 -5—옥소-피라졸—1-일)— N- [2-(2-피리딜)에틸]벤젠 설폰아미드 4一 (4-isopropyl— 2, 3-dimethyl -5—oxo-pyrazol—1-yl)— N- [2-(2-pyridyl)ethyl]benzene sulfonamide
4— (4-이소프로필 -2 , 3—디메틸— 5—옥소—피라졸 -1—일 )-N— (2-나프틸메틸 )벤젠설폰 아미드 4— (4-isopropyl -2 , 3—dimethyl— 5—oxo—pyrazol -1—yl )-N— (2-naphthylmethyl )benzenesulfonamide
N- [2-(3—플루오로페닐)에틸]— 4-(4-이소프로필— 2 , 3-디메틸 -5-옥소-피라졸— 1- 일)벤젠설폰아미드 N- [2-(3—fluorophenyl)ethyl]— 4-(4-isopropyl— 2, 3-dimethyl -5-oxo-pyrazole— 1- yl)benzenesulfonamide
N一 (5-플루오로 -2-피리딜)— 4-(4—이소프로필— 2 , 3—디메틸 -5ᅳ옥소—피라졸 -1-일 ) 벤젠설폰아미드 N一 (5-fluoro -2-pyridyl)— 4-(4—isopropyl— 2 , 3—dimethyl -5ᅳoxo—pyrazol -1-yl ) benzenesulfonamide
4— ( 4-이소프로필— 2 , 3-디메틸 -5—옥소-피라졸— 1-일) -N— [ (4-메록시페닐)메틸]벤 젠설폰아미드 4— (4-isopropyl— 2, 3-dimethyl -5—oxo-pyrazole— 1-yl) -N— [ (4-meroxyphenyl)methyl]benzenesulfonamide
4— (4-이소프로필— 2， 3—디메틸 -5—옥소—피라졸 -1-일 )— N-(6-퀴놀릴 )벤젠설폰아미 4— (4-isopropyl— 2， 3—dimethyl -5—oxo—pyrazol -1-yl )— N-(6-quinolyl )benzenesulfonami
N— (2 , 3-디히드로— 1， 4-벤조디옥신 -6-일) -4-(4ᅳ이소프로필 -2 , 3-디메틸 -5—옥소— 피라졸— 1—일 )벤젠설폰아미드 N— (2, 3-dihydro— 1，4-benzodioxin -6-yl) -4-(4ᅳisopropyl -2, 3-dimethyl -5—oxo— pyrazol— 1—yl)benzenesulfone amides
N- [ 4— (디메틸아미노)페닐] -4- (4—이소프로필 -2 , 3-디메틸—5ᅳ옥소—피라졸— 1-일 ) 벤젠설폰아미드 N- [ 4— (dimethylamino) phenyl] -4- (4—isopropyl -2, 3-dimethyl—5-oxo—pyrazol— 1-yl) benzenesulfonamide
메틸 3— [ [4— (4—이소프로필— 2 , 3-디메틸—5ᅳ옥소-피라졸— 1—일)페닐]설포닐아미 노]벤조에이트 Methyl 3— [ [4— (4—isopropyl— 2, 3-dimethyl—5-oxo-pyrazol— 1—yl)phenyl]sulfonylamino]benzoate
에틸 3- [ [4-(4—이소프로필ᅳ 2， 3-디메틸— 5-옥소—피라졸— 1ᅳ일)페닐 ]설포닐아미 노]벤조에이트 Ethyl 3- [ [4-(4—isopropylᅳ 2，3-dimethyl— 5-oxo—pyrazol— 1ᅳyl)phenyl ]sulfonylamino]benzoate
4ᅳ (4-이소프로필 -2 , 3-디메틸— 5—옥소-피라졸— 1—일)— N- [3— (트리플루오로메틸 ) 페닐]벤젠설폰아미드 4ᅳ (4-isopropyl-2, 3-dimethyl— 5—oxo-pyrazole— 1—yl)— N- [3— (trifluoromethyl) phenyl] benzenesulfonamide
N-[2— (4—플루오로페닐)에틸] -4-(4—이소프로필 -2， 3-디메틸 -5-옥소—피라졸ᅳ 1- 일)벤젠설폰아미드 N-[2— (4—fluorophenyl)ethyl]-4-(4—isopropyl-2，3-dimethyl -5-oxo—pyrazolᅳ 1- yl)benzenesulfonamide
4一 (4-이소프로필— 2， 3-디메틸— 5—옥소-피라졸 -1—일)— N— (4-이소프로필페닐)벤젠 설폰아미드 N-(3-플루오로페닐)— 4-(4-이소프로필— 2 , 3-디메틸 -5-옥소-피라졸 -1—일 )벤젠설 폰아미드 4一 (4-isopropyl— 2，3-dimethyl— 5—oxo-pyrazol -1—yl)— N— (4-isopropylphenyl)benzene sulfonamide N-(3-fluorophenyl)—4-(4-isopropyl—2,3-dimethyl-5-oxo-pyrazol-1—yl)benzenesulfonamide
N-(3—플루오로페닐) -4-(4-이소프로필 -2， 3—디메틸 -5—옥소-피라졸 -1-일 )-N-메 틸―벤젠설폰아미드 N-(3—fluorophenyl)-4-(4-isopropyl-2，3—dimethyl-5—oxo-pyrazol-1-yl)-N-methyl-benzenesulfonamide
4- (4-이소프로필— 2 , 3ᅳ디메틸— 5-옥소—피라졸 -1-일 )— N— ( 1-나프틸)벤젠설폰아미 드 4- (4-isopropyl— 2, 3-dimethyl— 5-oxo—pyrazol-1-yl)— N— (1-naphthyl)benzenesulfonamide
4-(4—이소프로필— 2 , 3-디메틸 -5—옥소—피라졸— 1-일 )-N— [ (3—메록시페닐)메틸]벤 젠설폰아미드 4-(4—isopropyl— 2, 3-dimethyl -5—oxo—pyrazole— 1-yl )-N— [ (3—meroxyphenyl)methyl]benzenesulfonamide
N-[ (3ᅳ플루오로페닐)메틸 ]ᅳ4— (4-이소프로필— 2 , 3—디메틸 -5-옥소-피라졸 -1—일 ) 벤젠설폰아미드 N-[ (3ᅳfluorophenyl)methyl ]ᅳ4— (4-isopropyl— 2, 3—dimethyl -5-oxo-pyrazol -1—yl) benzenesulfonamide
4-(4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸— 1ᅳ일 )— N— (테트라히드로퓨란— 2-일 메틸)벤젠설폰아미드 4-(4-isopropyl— 2, 3-dimethyl -5—oxo—pyrazole— 1-yl)— N— (tetrahydrofuran— 2-yl methyl)benzenesulfonamide
N— [ 2- ( 2—퓨릴메틸설파닐)에틸]—4- ( 4ᅳ이소프로필 -2 , 3-디메틸—5—옥소-피라졸- 1-일)벤젠설폰아미드 N— [ 2- ( 2—furylmethylsulfanyl)ethyl]—4- ( 4ᅳisopropyl -2 , 3-dimethyl—5—oxo-pyrazol- 1-yl)benzenesulfonamide
4ᅳ(4-이소프로필 -2 , 3-디메틸 -5-옥소-피라졸 1-일) -N— [2-(p-를릴)에틸]벤젠설 폰아미드 4ᅳ(4-isopropyl-2, 3-dimethyl-5-oxo-pyrazol 1-yl) -N— [2-(p-yllyl)ethyl]benzenesulfonamide
4-(4—이소프로필— 2， 3-디메틸 -5-옥소—피라졸 -1-일) -N-(4-메록시페닐) -N—메틸- 벤젠설폰아미드 4-(4—isopropyl— 2, 3-dimethyl -5-oxo—pyrazol -1-yl) -N-(4-meroxyphenyl) -N—methyl- benzenesulfonamide
4-(4-이소프로필— 2ᅳ 3—디메틸 5ᅳ옥소-피라졸 -1—일)— N— [2-(4-메록시페닐)에틸] 벤젠설폰아미드 4-(4-isopropyl— 2-3—dimethyl 5-oxo-pyrazol -1—yl)— N— [2-(4-meroxyphenyl)ethyl] benzenesulfonamide
N- [ (2-클로로페닐 )메틸]— 4— (4—이소프로필— 2 , 3—디메틸 -5-옥소ᅳ피라졸ᅳ 1—일 )벤 젠설폰아미드 N- [ (2-chlorophenyl )methyl]— 4— (4—isopropyl— 2, 3—dimethyl -5-oxopyrazolᅳ 1—yl)benzenesulfonamide
N-(2—플루오로페닐) -4— (4-이소프로필ᅳ 2， 3-디메틸 -5—옥소-피라졸— 1—일 )벤젠설 폰아미드 N-(2—fluorophenyl) -4— (4-isopropylᅳ 2，3-dimethyl -5—oxo-pyrazole— 1—yl)benzenesulfonamide
N— [ (2-플루오로페닐)메틸] -4- (4-이소프로필— 2 , 3ᅳ디메틸— 5-옥소—피라졸— 1—일 ) 벤젠설폰아미드 N— [ (2-fluorophenyl)methyl] -4- (4-isopropyl— 2, 3-dimethyl— 5-oxo—pyrazol— 1—yl ) benzenesulfonamide
4-(4-이소프로필 -2 , 3—디메틸 -5-옥소—피라졸 -1-일 )-N-(p-를릴메틸 )벤젠설폰아 미드 4-(4-isopropyl-2, 3—dimethyl-5-oxo—pyrazol-1-yl)-N-(p-yllylmethyl)benzenesulfonamide
4-(4-이소프로필 -2， 3ᅳ디메틸— 5-옥소—피라졸 -1-일 )— N— (m—를릴메틸 )벤젠설폰아 미드 4-(4-isopropyl-2，3ᅳdimethyl—5-oxo—pyrazol-1-yl)—N—(m—yllylmethyl)benzenesulfonamide
N- ( 2 , 5-디메틸페닐) -4- ( 4-이소프로필 -2， 3—디메틸—5—옥소-피라졸- 1—일)벤젠설 폰아미드 4_(4—이소프로필— 2，3_디메틸 _5_옥소—피라졸— i—일)— N_(m_를릴)벤젠설폰아미드 N- (2, 5-dimethylphenyl) -4- (4-isopropyl-2，3—dimethyl—5—oxo-pyrazol-1—yl)benzenesulfonamide 4 _ (4 —isopropyl— 2 , 3 _dimethyl _ 5 _oxo—pyrazole— i—yl)— N _ (m _rlyl)benzenesulfonamide
4一 (4-이소프로필 -2， 3—디메틸— 5-옥소—피라졸 -1ᅳ일 )-N— ( 0-를릴)밴젠설폰아미드 N一 (4—시아노페닐)ᅳ 4— (4—이소프로필 -2 , 3—디메틸ᅳ5-옥소—피라졸—1-일)벤젠설폰 아미드 4一 (4-isopropyl -2， 3—dimethyl— 5-oxo—pyrazol -1ᅳyl )-N— (0-yllyl)benzenesulfonamide N一 (4—cyanophenyl)ᅳ 4— (4— Isopropyl-2, 3—dimethylᅳ5-oxo—pyrazol—1-yl)benzenesulfonamide
4- (4一이소프로필— 2 , 3—디메틸 -5—옥소-피라졸 -1—일 )-N- [2— (트리플루오로메틸 ) 페닐]벤젠설폰아미드 4- (4一isopropyl— 2 , 3—dimethyl -5—oxo-pyrazol -1—yl )-N- [2— (trifluoromethyl )phenyl]benzenesulfonamide
N-(2 , 4-디메틸페닐)— 4-(4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1ᅳ일 )벤젠설 폰아미드 N-(2, 4-dimethylphenyl)—4-(4-isopropyl-2，3-dimethyl-5-oxo-pyrazol-1-yl)benzenesulfonamide
•1- ( 4-이소프로필 -2， 3-디메틸 -5—옥소—피라졸— 1 -일 )— N— ( 6-메복시—3-피리딜)벤 젠설폰아미드 • 1- ( 4-isopropyl -2， 3-dimethyl -5—oxo—pyrazole— 1 -yl )— N— ( 6-methoxy—3-pyridyl)benzenesulfonamide
4一 (4—이소프로필 -2 , 3-디메틸 -5-옥소ᅳ피라졸 -1-일)— N— (p-를릴 )벤젠설폰아미드 N— (2， 2—디메틸프로필) -4— (4—이소프로필— 2 , 3一디메틸— 5ᅳ옥소-피라졸— 1ᅳ일 )벤젠 설폰아미드 4一 (4—isopropyl -2, 3-dimethyl -5-oxopyrazol -1-yl)— N— (p-yllyl )benzenesulfonamide N— (2， 2—dimethylpropyl) -4— ( 4—Isopropyl— 2 , 3-dimethyl— 5-oxo-pyrazole— 1-yl )benzene sulfonamide
4— (4—이소프로필 -2， 3-디메틸 -5ᅳ옥소-피라졸 -1ᅳ일)— N— (2-피리딜메틸)벤젠설폰 아미드 4— (4—isopropyl-2，3-dimethyl-5-oxo-pyrazol-1-yl)— N— (2-pyridylmethyl)benzenesulfone amide
4-(4—이소프로필ᅳ 2， 3—디메틸— 5-옥소-피라졸 -1—일 )— N-(2—피리딜 )벤젠설폰아미 Nᅳ (3—브로모페닐)— 4-(4-이소프로필 -2， 3-디메틸— 5—옥소-피라졸 -1ᅳ일 )벤젠설폰 아미드 4-(4—isopropyl ᅳ 2， 3—dimethyl— 5-oxo-pyrazol -1—yl )— N-(2—pyridyl )benzenesulfonami N ᅳ (3—bromophenyl)— 4-( 4-isopropyl -2，3-dimethyl— 5—oxo-pyrazol -1-yl )benzenesulfone amide
Ν·— (2-브로모페닐) -4-(4—이소프로필 -2 , 3—디메틸— 5—옥소-피라졸— 1-일)벤젠설폰 아미드 Ν·— (2-bromophenyl) -4-(4—isopropyl-2, 3—dimethyl— 5—oxo-pyrazole— 1-yl)benzenesulfone amide
N-(2 , 4-디브로모페닐) -4-(4ᅳ이소프로필 -2， 3-디메틸 -5-옥소-피라졸 -1-일 )벤젠 설폰아미드 N-(2, 4-dibromophenyl) -4-(4-isopropyl-2，3-dimethyl-5-oxo-pyrazol-1-yl)benzene sulfonamide
N-(2， 5-디브로모페닐) -4ᅳ (4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸— 1-일 )벤젠 설폰아미드 N-(2, 5-dibromophenyl) -4ᅳ (4-isopropyl— 2, 3-dimethyl -5—oxo—pyrazole— 1-yl)benzene sulfonamide
N— (3-에틸페닐) -4-(4-이소프로필 -2 , 3—디메틸ᅳ 5-옥소—피라졸 -1—일)벤젠설폰아 미드 N— (3-ethylphenyl) -4-(4-isopropyl -2, 3—dimethylᅳ 5-oxo—pyrazole -1—yl)benzenesulfonamide
N-( 1 , 1-디메틸프로필 )-4ᅳ(4-이소프로필 -2， 3-디메틸— 5—옥소-피라졸— 1-일 )벤젠 설폰아미드 N-(1,1-dimethylpropyl)-4ᅳ(4-isopropyl-2，3-dimethyl—5—oxo-pyrazole—1-yl)benzene sulfonamide
N一 ( 3 , 5-디메특시페닐 ) -4- ( 4-이소프로필 _2 , 3-디메틸—5—옥소-피라졸 - 1—일)벤젠 설폰아미드 N一 ( 3 , 5-dimethoxyphenyl ) -4- ( 4-isopropyl _2 , 3-dimethyl—5—oxo-pyrazole - 1—yl)benzene sulfonamide
N-시클로펜틸 -4— (4-이소프로필— 2 , 3-디메틸 -5-옥소—피라졸 -1—일)벤젠설폰아미 4—이소프로필 -2— [4- [4一 (4-메록시페닐)피페라진 -1一일 ]설포닐페닐]—1， 5-디메틸 一피라졸— 3—온 N-Cyclopentyl-4—(4-isopropyl—2,3-dimethyl-5-oxo—pyrazol-1—yl)benzenesulfonami 4—isopropyl -2— [4- [4 1 (4-meroxyphenyl) piperazine -1 yl ] sulfonylphenyl]—1, 5-dimethyl 1 pyrazole— 3—one
4一 (4-이소프로필 -2， 3-디메틸 -5-옥소-피라졸— 1—일 )-Ν-(4ᅳ sec—부틸페닐 )벤젠설 폰이-미드 4一 (4-isopropyl-2，3-dimethyl-5-oxo-pyrazole—1—yl)-Ν-(4ᅳ sec—butylphenyl)benzenesulfonimide
에틸 4- [ [4— (4-이소프로필ᅳ 2， 3—디메틸— 5-옥소—피라졸 -1-일)페닐 ]설포닐아미 노]피페리딘 -1ᅳ카르복실레이트 Ethyl 4- [ [4— (4-isopropylᅳ 2，3—dimethyl— 5-oxo—pyrazol -1-yl)phenyl ]sulfonylamino]piperidine -1ᅳcarboxylate
N一인단—5—일— 4- (4—이소프로필 -2 , 3-디메틸 -5-옥소-피라졸—1ᅳ일)벤젠설폰아미 N一indane—5—yl— 4- (4—isopropyl -2, 3-dimethyl -5-oxo-pyrazole—1 yl)benzenesulfonami
N-인단 -2—일— 4— (4—이소프로필— 2 , 3—디메틸—5-옥소—피라졸 -1—일)벤젠설폰아미 N-Indan -2—yl— 4— (4—isopropyl— 2 , 3—dimethyl—5-oxo—pyrazol -1—yl)benzenesulfonami
N一시클로헵틸— 4- ( 4ᅳ이소프로필— 2， 3-디메틸 -5-옥소-피라졸 -1-일 )벤젠설폰아미 드 N一cycloheptyl— 4- (4ᅳisopropyl— 2, 3-dimethyl -5-oxo-pyrazol -1-yl )benzenesulfonamide
4-(4—이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1—일 )— N- [3— (트리플루오로메틸 ) 페닐]벤젠설폰아미드 4-(4—isopropyl-2, 3—dimethyl-5-oxo—pyrazole— 1—yl)— N- [3— (trifluoromethyl) phenyl]benzenesulfonamide
N-(4—아세틸페닐) -4— (4—이소프로필 -2 , 3—디메틸 -5-옥소-피라졸— 1-일)벤젠설폰 아미드 N-(4—acetylphenyl) -4— (4—isopropyl -2, 3—dimethyl -5-oxo-pyrazole— 1-yl)benzenesulfonamide
메틸 4- [ [4-(4—이소프로필 -2 , 3-디메틸—5-옥소—피라졸—1-일)페닐]설포닐아미 노]벤조에이트 Methyl 4- [ [4-(4—isopropyl-2, 3-dimethyl—5-oxo—pyrazol—1-yl)phenyl]sulfonylamino]benzoate
4-(4-이소프로필 -2 , 3-디메틸 -5-옥소—피라졸— 1-일 )-N—피리미딘 -2—일―벤젠설폰 아미드 4-(4-isopropyl-2, 3-dimethyl-5-oxo—pyrazole— 1-yl )-N—pyrimidin -2—yl—benzenesulfonamide
N- [ (2， 4—디메록시페닐)메틸] -4— (4—이소프로필 -2， 3—디메틸 -5—옥소—피라졸ᅳ 1ᅳ 일)벤젠설폰아미드 N- [ (2, 4—dimeroxyphenyl)methyl] -4— (4—isopropyl -2, 3—dimethyl -5—oxo—pyrazole 1 yl)benzenesulfonamide
N-(2-클로로ᅳ4-피리딜 ) -4— (4-이소프로필— 2， 3—디메틸— 5-옥소-피라졸— 1-일 )밴 젠설폰아미드 N-(2-chloro-4-pyridyl) -4— (4-isopropyl— 2, 3—dimethyl— 5-oxo-pyrazole— 1-yl) vanzenesulfonamide
2- [4-(4—에틸피페라진— 1-일)설포닐페닐]—4-이소프로필— 1 , 5-디메틸―피라졸一 3一 2- [4-(4—ethylpiperazine— 1-yl)sulfonylphenyl]—4-isopropyl— 1 , 5-dimethyl—pyrazole 1 3 1
N— [3 , 5—비스 (트리플루오로메틸)페닐]—4— (4-이소프로필— 2，3—디메틸—5-옥소一피 라졸 -1-일)벤젠설폰아미드 N— [3, 5—bis (trifluoromethyl)phenyl]—4— (4-isopropyl— 2,3—dimethyl—5-oxopyrazol-1-yl)benzenesulfonamide
4— (4-이소프로필 -2， 3—디메틸ᅳ 5-옥소—피라졸— 1—일)ᅳ N— (4-피리딜메틸)벤젠설폰 아미드 4— (4-isopropyl -2， 3—dimethylᅳ 5-oxo—pyrazol— 1—yl)ᅳ N— (4-pyridylmethyl)benzenesulfone amide
N-(9—에틸카르바졸— 3-일) -4ᅳ (4-이소프로필ᅳ 2 , 3-디메틸 -5-옥소-피라졸— 1-일 ) 벤젠설폰아미드 N-(9—ethylcarbazole— 3-yl) -4ᅳ (4-isopropylᅳ 2, 3-dimethyl -5-oxo-pyrazole— 1-yl) Benzenesulfonamide
N— (4—브로모—1-나프틸 )-4— (4—이소프로필— 2， 3-디메틸 -5—옥소ᅳ피라졸ᅳ 1—일 )벤 젠설폰아미드 N— (4—bromo—1-naphthyl)-4— (4—isopropyl—2, 3-dimethyl -5—oxo-pyrazol-1—yl)benzenesulfonamide
4-(4-이소프로필 -2 , 3—디메틸—5-옥소-피라졸-1-일)-1 (2-페닐페닐)벤젠설폰아 4-(4-isopropyl-2, 3—dimethyl—5-oxo-pyrazol-1-yl)-1 (2-phenylphenyl)benzenesulfonate
U]드 U]de
4-(4-이소프로필 -2 , 3-디메틸ᅳ5-옥소-피라졸-1—일) —(2—메틸-1-나프틸)벤젠 설폰아미드 4-(4-isopropyl-2, 3-dimethylᅳ5-oxo-pyrazol-1—yl) —(2—methyl-1-naphthyl)benzene sulfonamide
N—[2-(4—브로모페닐)에틸] -4— (4ᅳ이소프로필— 2 , 3—디메틸— 5—옥소-피라졸 -1ᅳ일 ) 벤젠설폰아미드 N—[2-(4—bromophenyl)ethyl]-4— (4-isopropyl— 2, 3—dimethyl— 5—oxo-pyrazol-1-yl) benzenesulfonamide
4-(4—이소프로필 -2 , 3-디메틸ᅳ5—옥소-피라졸-l-일)—N- [2—(5—메톡시ᅳlH-인돌- 3ᅳ일)에틸]벤젠설폰아미드 4-(4—isopropyl-2, 3-dimethylᅳ5—oxo-pyrazol-l-yl)—N- [2—(5—methoxyᅳlH-indole-3ᅳyl)ethyl]benzenesulfonamide
4-(4—이소프로필 -2 , 3-디메틸ᅳ 5—옥소ᅳ피라졸 -1-일 )-N-(2—메틸— 1H-인돌— 5—일 ) .벤젠설폰아미드 4-(4—isopropyl-2, 3-dimethyl- 5—oxo-pyrazol-1-yl)-N-(2—methyl— 1H-indole— 5—yl).benzenesulfonamide
N-( 1H-인돌— 5ᅳ일메틸) -4— (4—이소프로필 -2， 3—디메틸—5-옥소-피라졸ᅳ 1ᅳ일)벤젠 설폰아미드 N-(1H-indole—5-ylmethyl)-4—(4—isopropyl-2，3—dimethyl-5-oxo-pyrazol-1-yl)benzene sulfonamide
4-(4ᅳ이소프로필—2 , 3-디메틸—5-옥소-피라졸—1-일) -N-(6-메록시ᅳ 1 , 3—벤조티아 졸 -2—일)벤젠설폰아미드 4-(4-isopropyl—2, 3-dimethyl—5-oxo-pyrazol—1-yl) -N-(6-meroxy—1, 3—benzothiazol-2—yl)benzenesulfonamide
N- [ 2- ( 1H-인돌 -3ᅳ일)에틸]—4— ( 4-이소프로필— 2 , 3—디메틸—5—옥소—피라졸— 1-일 ) 벤젠설폰아미드 N- [ 2- ( 1H-indole -3-yl) ethyl]—4— ( 4-isopropyl— 2 , 3—dimethyl—5—oxo—pyrazole— 1-yl) benzenesulfonamide
4-(4—이소프로필 -2 , 3-디메틸 -5—옥소—피라졸— 1-일) -N-(2—메틸— 8—퀴놀릴)벤젠 설폰아미드 4-(4—isopropyl-2, 3-dimethyl-5—oxo—pyrazole— 1-yl) -N-(2—methyl— 8—quinolyl)benzene sulfonamide
N一 (4-에록시—2—니트로-페닐)— 4-(4—이소프로필 -2 , 3—디메틸— 5—옥소-피라졸ᅳ 1— 일)벤젠설폰아미드 N一 (4-eroxy—2—nitro-phenyl)— 4-(4—isopropyl-2, 3—dimethyl— 5—oxo-pyrazolᅳ 1— yl)benzenesulfonamide
N-(3， 4—디클로로페닐 )-4-(4—이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1-일 )벤젠 설폰아미드 N-(3, 4—dichlorophenyl)-4-(4—isopropyl-2, 3—dimethyl-5-oxo—pyrazole—1-yl)benzene sulfonamide
N- [2-(2-클로로페닐)에틸]—4— (4—이소프로필— 2 , 3-디메틸—5-옥소 -피리 -졸— 1ᅳ일) 벤젠설폰아미드 N- [2-(2-chlorophenyl)ethyl]—4— (4—isopropyl— 2, 3-dimethyl—5-oxo -pyri -sol— 1-yl) benzenesulfonamide
N- [ (4—클로로페닐)메틸] -4— (4-이소프로필 -2 , 3—디메틸 -5-옥소—피라졸— 1—일 )벤 젠설폰아미드 N- [ (4—chlorophenyl)methyl] -4— (4-isopropyl-2, 3—dimethyl -5-oxo—pyrazol— 1—yl)benzenesulfonamide
N-(3 , 5—디클로로페닐 )-4— (4—이소프로필— 2 , 3-디메틸 -5-옥소—피라졸—1—일)벤젠 설폰아미드 N-(3, 5—dichlorophenyl)-4— (4—isopropyl— 2, 3-dimethyl -5-oxo—pyrazol—1—yl)benzene sulfonamide
N-( 1， 2—디메록시프로필 )-4— (4—이소프로필 -2 , 3—디메틸 -5-옥소—피라졸 -1-일 )벤 젠설폰아미드 N-(1, 2—dimeroxypropyl)-4— (4—isopropyl-2, 3—dimethyl-5-oxo—pyrazol-1-yl)ben Gensulfonamide
N-(5-클로로ᅳ2-플루오로―페닐 )-4— (4—이소프로필 -2 , 3-디메틸— 5-옥소—피라졸- 1—일)벤젠설폰아미드 N-(5-chloro-2-fluoro-phenyl)-4— (4—isopropyl-2, 3-dimethyl— 5-oxo—pyrazol- 1—yl)benzenesulfonamide
N一 (4-에티닐페닐) -4- (4—이소프로필 -2， 3-디메틸— 5-옥소-피라졸 -1—일 )밴젠설폰 아미드 N 一 (4-ethynylphenyl) -4- (4—isopropyl-2，3-dimethyl— 5-oxo-pyrazol -1—yl) benzenesulfone amide
N- [ (4-플루오로페닐 )메틸] -4-(4-이소프로필— 2 , 3-디메틸 -5—옥소—피라졸ᅳ 1—일 ) 벤젠설폰아미드 N- [ (4-fluorophenyl )methyl] -4-(4-isopropyl— 2, 3-dimethyl -5—oxo—pyrazolᅳ 1—yl) benzenesulfonamide
Ν-(2 , 4ᅳ디메틸— 6—니트로—페닐) -4-(4-이소프로필 -2， 3—디메틸 -5ᅳ옥소ᅳ피라졸— 1-일)벤젠설폰아미드 Ν-(2, 4-dimethyl— 6—nitro—phenyl) -4-(4-isopropyl-2，3—dimethyl-5—oxo-pyrazole— 1-yl)benzenesulfonamide
N一 (2， 5ᅳ디클로로 -4-니트로-페닐 )— 4-(4-이소프로필— 2， 3-디메틸— 5—옥소—피라졸 一 1-일)벤젠설폰아미드 N 1 (2, 5-dichloro-4-nitro-phenyl)— 4-(4-isopropyl— 2, 3-dimethyl— 5—oxo—pyrazole 1 1-yl)benzenesulfonamide
Nᅳ (4—클로로—3-니트로-페닐 )-4-(4-이소프로필 -2 , 3—디메틸— 5-옥소—피라졸一 1一 일)벤젠설폰아미드 Nᅳ (4—chloro—3-nitro-phenyl)-4-(4-isopropyl-2, 3—dimethyl—5-oxo—pyrazole 1 1 yl)benzenesulfonamide
Ν-(2 , 3-디메틸 -6—니트로-페닐 )-4-(4—이소프로필 -2， 3—디메틸— 5—옥소-피라졸一 1一일)벤젠설폰아미드 Ν-(2, 3-dimethyl -6—nitro-phenyl)-4-(4—isopropyl-2，3—dimethyl— 5—oxo-pyrazole 1 1 yl)benzenesulfonamide
4ᅳ(4-이소프로필— 2 , 3—디메틸 -5—옥소-피라졸—1—일) -N—( l—나프틸메틸)벤젠설폰 아미드 4ᅳ(4-isopropyl—2, 3—dimethyl -5—oxo-pyrazol—1—yl) -N—( l—naphthylmethyl)benzenesulfone amide
Ν—[ (3ᅳ브로모페닐)메틸]—4-(4—이소프로필 -2 , 3ᅳ디메틸 -5-옥소-피라졸 -1-일)벤 젠설픈아미드 Ν—[ (3-bromophenyl)methyl]—4-(4—isopropyl-2, 3-dimethyl-5-oxo-pyrazol-1-yl)benzenesulfenamide
Ν— [2-(3-브로모페닐 )에틸] -4-(4-이소프로필 -2，3—디메틸— 5-옥소—피라졸ᅳ 1-일 ) 벤젠설폰아미드 Ν— [2-(3-bromophenyl)ethyl]-4-(4-isopropyl-2，3—dimethyl—5-oxo—pyrazolᅳ 1-yl) benzenesulfonamide
Ν- [ (2-브로모페닐)메틸]— 4- (4-이소프로필— 2， 3-디메틸— 5—옥소—피라졸 -1-일 )벤 젠설폰아미드 Ν- [ (2-bromophenyl)methyl]— 4- (4-isopropyl— 2，3-dimethyl— 5—oxo—pyrazol -1-yl )benzenesulfonamide
Ν- [2-(3—클로로페닐)에틸]—4— (4—이소프로필 -2 , 3—디메틸— 5-옥소—피라졸ᅳ 1-일 ) 벤젠설폰아미드 Ν- [2-(3—chlorophenyl)ethyl]—4— (4—isopropyl-2, 3—dimethyl— 5-oxo—pyrazolᅳ 1-yl) benzenesulfonamide
4一 (4—이소프로필 -2， 3-디메틸 -5-옥소-피라졸— 1-일 )-Ν- [ [3- (트리플루오로메틸 ) 페닐]메틸]벤젠설폰아미드 4一 (4—isopropyl-2，3-dimethyl-5-oxo-pyrazole—1-yl)-Ν- [[3-(trifluoromethyl)phenyl]methyl]benzenesulfonamide
4- -이소프로필 -2 , 3—디메틸 -5—옥소—피라졸 -1—일 )-Ν— [ [2— (트리플루오로메틸 ) 페닐]메틸]벤젠설폰아미드 4- -isopropyl - 2 , 3—dimethyl -5—oxo—pyrazol -1—yl )-Ν— [ [2— (trifluoromethyl ) phenyl]methyl]benzenesulfonamide
4— (4-이소프로필 -2 , 3—디메틸 -5ᅳ옥소-피라졸— 1—일 )-Ν- [ [4— (트리플루오로메틸 ) 페닐]메틸]벤젠설폰아미드 4— (4-isopropyl -2, 3—dimethyl -5ᅳoxo-pyrazole— 1—yl )-Ν- [ [4— (trifluoromethyl) phenyl]methyl]benzenesulfonamide
4- (4-이소프로필 -2 , 3ᅳ디메틸 -5—옥소-피라졸 -1—일 )-Ν-(ο-를릴메틸)벤젠설폰아 미드 4- (4-isopropyl -2, 3-dimethyl -5—oxo-pyrazol -1—yl)-Ν-(ο-allylmethyl)benzenesulfonate mid
N一 (3—클로로페닐 )一4— (4-이소프로필— 2， 3—디메틸— 5-옥소—피라졸— 1—일 )밴젠설폰 아미드 N 1 (3—chlorophenyl) 4— (4-isopropyl— 2, 3—dimethyl— 5-oxo—pyrazole— 1—yl) benzenesulfone amide
N-(2—클로로페닐)ᅳ 4-(4—이소프로필— 2， 3—디메틸 -5-옥소—피라졸ᅳ 1-일 )벤젠설폰 όΐτι]亡 N-(2—chlorophenyl)ᅳ 4-(4—isopropyl— 2， 3—dimethyl -5-oxo—pyrazolᅳ 1-yl)benzenesulfone όΐτι]亡
Ν-[ (3-클로로페닐 )메틸]— 4— (4-이소프로필— 2 , 3—디메틸 -5-옥소—피라졸 -1ᅳ일 )벤 젠설폰아미드 Ν-[ (3-chlorophenyl )methyl]— 4— (4-isopropyl— 2 , 3—dimethyl -5-oxo—pyrazol -1-yl )benzenesulfonamide
4- ( 4—브로모 -2 , 3ᅳ디메틸 -5—옥소-피라졸— 1—일) -Ν— ( 2—페녹시에틸)벤젠설폰아미 4- ( 4—bromo -2 , 3ᅳdimethyl -5—oxo-pyrazole— 1—yl) -Ν— ( 2—phenoxyethyl)benzenesulfonami
Ν- [2— (2-플루오로페닐)에틸] -4— (4—이소프로필 -2 , 3-디메틸— 5ᅳ옥소—피라졸—1- 일)벤젠설폰아미드 Ν- [2— (2-fluorophenyl)ethyl] -4— (4—isopropyl -2, 3-dimethyl— 5ᅳoxo—pyrazol—1- yl)benzenesulfonamide
Ν— [ (4-브로모페닐 )메틸] -4-(4-이소프로필— 2， 3—디메틸 -5—옥소—피라졸— 1ᅳ일 )벤 젠설폰아미드 Ν— [ (4-bromophenyl )methyl] -4-(4-isopropyl— 2, 3—dimethyl -5—oxo—pyrazole— 1-yl )benzenesulfonamide
Ν— [ 2- ( 2—브로모페닐)에틸]—4- ( 4—이소프로필— 2， 3—디메틸—5—옥소—피라졸 - 1-일 ) 벤젠설폰아미드 Ν— [ 2- ( 2—bromophenyl)ethyl]—4- ( 4—isopropyl— 2， 3—dimethyl—5—oxo—pyrazole - 1-yl ) benzenesulfonamide
4-(4—이소프로필 -2，3-디메틸 -5-옥소—피라졸 -1—일)— Ν- [2-(ο-를릴)에틸]벤젠설 폰아미드 4-(4—isopropyl-2,3-dimethyl-5-oxo—pyrazol-1—yl)— Ν- [2-(ο-yllyl)ethyl]benzenesulfonamide
4- ( 4—이소프로필— 2 , 3-디메틸—5-옥소-피라졸 - 1-일) [ 2— ( 3-메록시페닐)에틸] 벤젠설폰아미드 4- ( 4—isopropyl— 2 , 3-dimethyl—5-oxo-pyrazole - 1-yl) [ 2— ( 3-meroxyphenyl)ethyl] benzenesulfonamide
4一 (4—이소프로필 -2 , 3—디메틸 -5ᅳ옥소-피라졸 -1—일 )-Ν— [2— [2- (트리플루오로메 틸)페닐]에틸]벤젠설폰아미드 4一 (4—isopropyl-2, 3—dimethyl-5-oxo-pyrazol-1—yl)-Ν— [2— [2- (trifluoromethyl)phenyl]ethyl]benzenesulfonamide
4一(4-이소프로필— 2， 3—디메틸— 5-옥소-피라졸 -1ᅳ일 )— Ν- [2— [3— (트리플루오로메 틸)페닐]에틸]벤젠설폰아미드 4一(4-isopropyl— 2, 3—dimethyl— 5-oxo-pyrazol -1-yl)— Ν- [2— [3— (trifluoromethyl)phenyl]ethyl]benzenesulfonamide
4— (4-이소프로필— 2， 3-디메틸 -5-옥소—피라졸— 1-일)— Ν- [2— [4- (트리플루오로메 틸)페닐]에틸]벤젠설폰아미드 4— (4-isopropyl— 2, 3-dimethyl -5-oxo—pyrazole— 1-yl)— Ν- [2— [4- (trifluoromethyl)phenyl]ethyl]benzenesulfonamide
4— (4-이소프로필— 2， 3—디메틸 -5—옥소-피라졸 -1—일) -Ν-[4- (트리플루오로메틸 ) 페닐]벤젠설폰아미드 4— (4-isopropyl— 2, 3—dimethyl -5—oxo-pyrazol -1—yl) -Ν-[4- (trifluoromethyl) phenyl]benzenesulfonamide
Ν-(2 , 3-디히드로— 1 , 4—벤조디옥신— 6-일메틸 )-4— (4ᅳ이소프로필 -2 , 3ᅳ디메틸一 5- 옥소-피라졸 -1-일)벤젠설폰아미드 Ν-(2, 3-dihydro— 1, 4—benzodioxin— 6-ylmethyl )-4— (4-isopropyl-2, 3-dimethyl一 5-oxo-pyrazol-1-yl)benzene Sulfonamide
4一 (4ᅳ클로로— 2， 3-디메틸—5ᅳ옥소-피라졸 -1-일)— Ν-(2-페녹시에틸)벤젠설폰아미 4一 (4—클로로 -2， 3—디메틸— 5-옥소—피라졸 -1-일 )— Ν— [ (2—플루오로페닐)메틸]벤젠 설폰아미드 4一 (4-chloro— 2， 3-dimethyl—5-oxo-pyrazol -1-yl)— Ν-(2-phenoxyethyl)benzenesulfonami 4一 (4—chloro -2， 3—dimethyl— 5-oxo—pyrazol -1-yl )— Ν— [ (2—fluorophenyl)methyl]benzene Sulfonamide
4-(4—클로로— 2 , 3—디메틸 -5—옥소-피라졸 -1-일 )— N— [ (3-플루오로페닐)메틸]벤젠 설폰아미드 4-(4—chloro— 2 , 3—dimethyl -5—oxo-pyrazol -1-yl )— N— [ (3-fluorophenyl)methyl]benzene sulfonamide
4-(4—클로로 -2 , 3ᅳ디메틸— 5—옥소-피라졸ᅳ1 일) -Nᅳ [ (4-플루오로페닐)메틸]벤젠 설폰아미드 4-(4—Chloro -2, 3ᅳdimethyl— 5—oxo-pyrazoleᅳ1 yl) -Nᅳ [(4-fluorophenyl)methyl]benzene sulfonamide
4ᅳ(4-클로로 -2 , 3-디메틸— 5-옥소-피라졸 -1-일)— N-(3， 4ᅳ디클로로페닐)벤젠설폰 아미드 4ᅳ(4-chloro-2, 3-dimethyl—5-oxo-pyrazol-1-yl)—N-(3, 4ᅳdichlorophenyl)benzenesulfone amide
4-(4-클로로— 2 , 3-디메틸— 5ᅳ옥소-피라졸 -1-일 )— N-(5-클로로— 2—플루오로―페닐 ) 벤젠설폰아미드 4-(4-chloro— 2, 3-dimethyl— 5-oxo-pyrazol -1-yl )— N-(5-chloro— 2—fluoro-phenyl ) benzenesulfonamide
4— (4-클로로—2 , 3-디메틸 -5-옥소-피라졸 -1—일 )— N- [4- (디메틸아미노)페닐]벤젠 설폰아미드 4— (4-chloro—2, 3-dimethyl -5-oxo-pyrazol -1—yl )— N- [4- (dimethylamino)phenyl]benzene sulfonamide
4-(4—클로로— 2， 3—디메틸一 5-옥소-피라졸— 1-일) -N-(2-피리딜메틸 )벤젠설폰아미 드 4-(4—chloro— 2， 3—dimethyl一 5-oxo-pyrazole— 1-yl) -N-(2-pyridylmethyl )benzenesulfonamide
메틸 3- [ [4— (4-클로로 -2， 3ᅳ디메틸 -5—옥소-피라졸 -1—일 )페닐]설포닐아미노]벤 조에이트 Methyl 3- [ [4— (4-chloro -2， 3ᅳdimethyl -5—oxo-pyrazol -1—yl )phenyl]sulfonylamino]benzoate
4- ( 4—클로로 -2 , 3—디메틸 -5-옥소—피라졸— 1-일) -N— ( 1H-인돌 -5—일메틸)벤젠설폰 아미드 4- ( 4—chloro -2 , 3—dimethyl -5-oxo—pyrazole— 1-yl) -N— ( 1H-indole -5—ylmethyl)benzenesulfone amide
4— ( 4-클로로—2， 3-디메틸 -5ᅳ옥소-피라졸— 1ᅳ일 ) -N- ( 1一나프틸메틸)벤젠설폰아미 드 4— (4-chloro—2，3-dimethyl -5-oxo-pyrazol—1-yl) -N- (1一naphthylmethyl)benzenesulfonamide
4— (4-클로로 -2 , 3—디메틸—5-옥소—피라졸—1-일)— N— [ (3 , 4—디메록시페닐)메틸]벤 젠설폰아미드 4— (4-chloro -2 , 3—dimethyl—5-oxo—pyrazol—1-yl)— N— [ (3 , 4—dimeroxyphenyl)methyl]benzenesulfonamide
4一 (4-클로로—2 , 3-디메틸ᅳ 5-옥소—피라졸 -1—일 HH5-퀴놀릴)벤젠설폰아미드 4— (4-클로로 -2 , 3-디메틸— 5-옥소—피라졸— 1-일 )— N- [ (2 , 4-디메록시페닐)메틸]벤 젠설폰아미드 4一 (4-chloro—2, 3-dimethylᅳ 5-oxo—pyrazole -1—yl HH5-quinolyl)benzenesulfonamide 4— (4-chloro -2, 3-dimethyl— 5-oxo—pyrazole — 1-yl )— N- [ (2, 4-dimeroxyphenyl)methyl]benzenesulfonamide
4-(4—브로모 -2， 3-디메틸 -5ᅳ옥소-피라졸— 1-일) -N- [ (3 , 4—디메록시페닐)메틸]벤 젠설폰아미드 4-(4—bromo-2，3-dimethyl-5ᅳoxo-pyrazole—1-yl) -N- [(3, 4—dimeroxyphenyl)methyl]benzenesulfonamide
4ᅳ (4-브로모 -2 , 3-디메틸 -5—옥소-피라졸—1-일)— N— (5-퀴놀릴)벤젠설폰아미드 4- (4-브로모 -2， 3—디메틸 -5-옥소—피라졸— 1—일 )— N— [4- (디메틸아미노)페닐]벤젠 설폰아미드 4ᅳ ( 4 -bromo-2, 3-dimethyl-5—oxo-pyrazol—1-yl)— N— (5-quinolyl)benzenesulfonamide 4- (4-bromo-2，3—dimethyl -5-oxo—pyrazole— 1—yl )— N— [4- (dimethylamino)phenyl]benzene sulfonamide
메틸 3- [ [4— (4—브로모—2 , 3-디메틸— 5—옥소—피라졸— 1-일)페닐]설포닐아미노]벤 조에이트 Methyl 3- [ [4— (4—bromo—2, 3-dimethyl— 5—oxo—pyrazol— 1-yl)phenyl]sulfonylamino]benzoate
4-(4—브로모— 2 , 3—디메틸 -5ᅳ옥소—피라졸 -1—일) -N- [ (3-플루오로페닐)메틸]벤젠 설폰아미드 4-(4—bromo— 2 , 3—dimethyl -5-oxo—pyrazol -1—yl) -N- [ (3-fluorophenyl)methyl]benzene Sulfonamide
4一 (4-브로모ᅳ 2 , 3—디메틸 -5-옥소—피라졸— 1—일 )-N— [ (2-플루오로페닐)메틸]벤젠 설폰아미드 4一 (4-bromoᅳ 2 , 3—dimethyl -5-oxo—pyrazol— 1—yl )-N— [ (2-fluorophenyl)methyl]benzene sulfonamide
4- (4—브로모 -2，3ᅳ디메틸ᅳ 5-옥소ᅳ피라졸 -1-일 )-N— (2—피리딜메틸 )벤젠설폰아미 드 4- (4—bromo-2,3-dimethyl-5-oxo-pyrazol-1-yl)-N— (2—pyridylmethyl)benzenesulfonamide
4— (4—브로모ᅳ2 , 3-디메틸 -5-옥소-피라졸— 1-일 )— N— (2， 3_디히드로— 1， 4—벤조디옥 신 -6—일)벤젠설폰아미드 4— (4—bromoᅳ2, 3-dimethyl -5-oxo-pyrazole— 1-yl)— N— (2, 3_dihydro— 1, 4—benzodioxin -6—yl)benzenesulfone amides
N— [3， 5—비스 (트리플루오로메틸)페닐] -4-(4—브로모 -2， 3ᅳ디메틸— 5—옥소-피라졸 -1-일)벤젠설폰아미드 N— [3, 5—bis (trifluoromethyl)phenyl] -4-(4—bromo -2, 3—dimethyl— 5—oxo-pyrazol -1-yl)benzenesulfonamide
4-(4-브로모ᅳ 2 , 3-디메틸 -5ᅳ옥소—피라졸 -1-일)— N— (3 , 4-디클로로페닐)벤젠설폰 아미드 4-(4-bromo ᅳ 2 , 3-dimethyl -5 oxo—pyrazol -1-yl)— N— (3 , 4-dichlorophenyl)benzenesulfone amide
4-(4-브로모ᅳ 2， 3—디메틸 -5-옥소ᅳ피라졸 -1—일 )— N-(5-클로로—2-플루오로-페닐 ) 벤젠설폰아미드 4-(4-bromo-2，3—dimethyl-5-oxo-pyrazol-1—yl)—N-(5-chloro—2-fluoro-phenyl)benzenesulfonamide
N— [3， 5-비스 (트리플루오로메틸)페닐]— 4— (4-클로로 -2 , 3ᅳ디메틸— 5—옥소-피라졸 N— [3, 5-bis (trifluoromethyl) phenyl]— 4— (4-chloro -2, 3-dimethyl— 5—oxo-pyrazole
—1—일)벤젠설폰아미드 —1—1)Benzenesulfonamide
4-(4-클로로 -2， 3—디메틸— 5ᅳ옥소-피라졸— 1-일 )— N— (2， 3-디히드로 -1， 4-벤조디옥 신 -6-일)벤젠설폰아미드 4-(4-chloro-2，3—dimethyl— 5-oxo-pyrazol— 1-yl )— N— (2， 3-dihydro-1， 4-benzodioxin-6-yl)benzenesulfonamide
4ᅳ (4—브로모 -2 , 3—디메틸 -5—옥소-피라졸— 1-일 —N—시클로펜틸—벤젠설폰아미드 4-(4—브로모 -2， 3—디메틸— 5ᅳ옥소—피라졸 -1—일 )-N-시클로헵틸—벤젠설폰아미드 4- ( 4-브로모ᅳ 2 , 3-디메틸 -5ᅳ옥소-피라졸- 1-일 ) -N—페닐—벤젠설폰아미드 4ᅳ (4—bromo -2, 3—dimethyl -5—oxo-pyrazole— 1-yl —N—cyclopentyl—benzenesulfonamide 4-(4—bromo -2, 3—dimethyl— 5—oxo —Pyrazole -1—yl)-N-cycloheptyl—benzenesulfonamide 4- (4-bromoᅳ 2, 3-dimethyl -5ᅳoxo-pyrazol-1-yl) -N—phenyl—benzenesulfonamide
4- (2 , 3—디메틸 -5—옥소— 4ᅳ페닐-피라졸 -1-일) -N-(2—페녹시에틸)벤젠설폰아미드 4- [4-(4—클로로페닐) -2 , 3—디메틸— 5-옥소-피라졸— 1-일] -N— (2—페녹시에틸 )벤젠 설폰아미드 4- (2, 3—dimethyl -5—oxo— 4-phenyl-pyrazol -1-yl) -N-(2—phenoxyethyl)benzenesulfonamide 4- [4-(4—chlorophenyl) -2 , 3—dimethyl— 5-oxo-pyrazole— 1-yl] -N— (2—phenoxyethyl)benzene sulfonamide
2- [3- [ [4— (4-이소프로필ᅳ 2 , 3ᅳ디메틸 -5—옥소ᅳ피라졸— 1—일)페닐 ]설포닐아미노] 페닐]아세트산 2- [3- [ [4— (4-isopropylᅳ 2 , 3ᅳdimethyl -5—oxopyrazole— 1—yl)phenyl ]sulfonylamino] phenyl]acetic acid
N-(2—히드록시페닐)— 4— (4-이소프로필 -2， 3-디메틸— 5-옥소-피라졸ᅳ 1—일 )벤젠설 폰아미드 N-(2—hydroxyphenyl)— 4— (4-isopropyl-2，3-dimethyl— 5-oxo-pyrazolᅳ 1—yl )benzenesulfonamide
N一 (4-히드록시페닐) -4-(4-이소프로필 -2， 3-디메틸 -5—옥소-피라졸— 1-일 )벤젠설 폰아미드 N一 (4-hydroxyphenyl) -4-(4-isopropyl-2，3-dimethyl-5—oxo-pyrazole—1-yl)benzenesulfonamide
4ᅳ [ 2 , 3—디메틸 -5—옥소 -4— [ 4ᅳ (트리플투오로메틸)페닐]피라졸 - 1-일 ] -N- ( 2—페녹 시에틸)벤젠설폰아미드 4ᅳ [ 2 , 3—dimethyl -5—oxo -4— [ 4ᅳ (trifltuoromethyl)phenyl]pyrazole - 1-yl ] -N- ( 2—phenoxyethyl)benzenesulfonamide
N一 [3- (히드록시메틸)페닐]ᅳ -4— (4-이소프로필 -2 , 3—디메틸 -5—옥소-피라졸 -1—일 ) 벤젠설폰아미드 N 一 [3- (hydroxymethyl) phenyl] ᅳ -4— (4-isopropyl -2, 3—dimethyl -5—oxo-pyrazol -1—yl) Benzenesulfonamide
N-(6—히드록시 -1—나프틸 )-4— (4-이소프로필 -2， 3—디메틸— 5-옥소—피라졸 -1—일) 벤젠설폰아미드 N-(6—hydroxy -1—naphthyl)-4— (4-isopropyl-2，3—dimethyl— 5-oxo—pyrazol -1—yl) benzenesulfonamide
4— (4-이소프로필— 2 , 3-디메틸 -5-옥소-피라졸 -1ᅳ일) -N-(2-페녹시프로필)벤젠설 폰아미드 4— (4-isopropyl— 2,3-dimethyl-5-oxo-pyrazol-1-yl)-N-(2-phenoxypropyl)benzenesulfonamide
N- [2-(2-플루오로페녹시 )에틸]—4— (4—이소프로필 -2 , 3—디메틸 -5—옥소 피라졸ᅳ 1—일)벤젠설폰아미드 N- [2-(2-fluorophenoxy)ethyl]—4— (4—isopropyl-2, 3—dimethyl -5—oxo pyrazolᅳ 1—yl)benzenesulfonamide
N— [4- [2— (디메틸아미노)에특시]페닐]—4— (4-이소프로필— 2，3-디메틸ᅳ 5—옥소一피 라졸— 1-일)벤젠설폰아미드 N— [4- [2— (dimethylamino)ethyl]phenyl]—4— (4-isopropyl—2,3-dimethylᅳ 5—oxopyrazole—1-yl)benzenesulfonamide
메틸 3— [ [4— (4-이소프로필 -2 , 3—디메틸ᅳ5-옥소—피라졸—1ᅳ일)페닐]설포닐아미 노]프로파노에이트 Methyl 3— [ [4— (4-isopropyl-2, 3—dimethylᅳ5-oxo—pyrazol—1ᅳyl)phenyl]sulfonylamino]propanoate
N— (4—히드록시—3-메틸―페닐) -4— (4—이소프로필— 2， 3-디메틸ᅳ 5ᅳ옥소ᅳ피라졸 -1— 일)벤젠설폰아미드 N— (4—hydroxy—3-methyl—phenyl) -4— (4—isopropyl— 2, 3-dimethyl 5 oxo pyrazole -1— yl)benzenesulfonamide
N-(6-아세틸ᅳ 1， 3—벤조디옥소 1-5—일) -4— (4—이소프로필ᅳ 2， 3ᅳ디메틸— 5-옥소—피 라졸 -1—일)벤젠설폰아미드 N-(6-acetylᅳ 1，3—benzodioxo 1-5—yl) -4— (4—isopropylᅳ 2，3—dimethyl— 5-oxo—pyrazol -1—yl)benzenesulfonamide
4ᅳ ( 4-이소프로필ᅳ 2 , 3—디메틸 -5-옥소—피라졸 -1ᅳ일) -N— ( 1 , 3， 5ᅳ트리메틸피라졸- 4-—일)벤젠설폰아미드 4ᅳ (4-isopropylᅳ 2, 3—dimethyl -5-oxo—pyrazol-1ᅳyl) -N— (1, 3， 5ᅳtrimethylpyrazol- 4-—yl)benzenesulfonamide
2-(4-인돌린—1-일설포닐페닐 )—4—이소프로필 -1 , 5—디메틸ᅳ피라졸— 3一온 2-(4-indoline—1-ylsulfonylphenyl)—4—isopropyl-1, 5—dimethyl-pyrazole—3-ion
4-(4—이소프로필— 2 , 3-디메틸ᅳ5—옥소ᅳ피라졸—1—일시테트랄린-1-일—벤젠설폰 아미드 4-(4—Isopropyl—2, 3-dimethylᅳ5—oxopyrazole—1—ylsitetralin-1-yl—benzenesulfone amide
Ν ,Ν-디에틸— 4— (4-이소프로필— 2， 3-디메틸 -5—옥소-피라졸— 1-일 )벤젠설폰아미드 Ν,Ν-diethyl— 4— (4-isopropyl— 2，3-dimethyl -5—oxo-pyrazole— 1-yl )benzenesulfonamide
4-(4—이소프로필 -2， 3—디메틸 -5—옥소ᅳ피라졸 -1-일)벤젠설폰아미드 4-(4—isopropyl-2，3—dimethyl-5—oxo-pyrazol-1-yl)benzenesulfonamide
4— (4-이소프로필 -2 , 3-디메틸— 5—옥소-피라졸— 1—일) -Ν—메틸 -Νᅳ페닐—벤젠설폰아 미드 4— (4-isopropyl -2, 3-dimethyl— 5—oxo-pyrazole— 1—yl) -Ν—methyl -Νᅳphenyl—benzenesulfonamide
Ν—벤질ᅳ 4-(4ᅳ이소프로필— 2 , 3—디메틸 -5ᅳ옥소-피라졸— 1-일)벤젠설폰아미드 메틸 2- [ [4— (4-이소프로필ᅳ 2 , 3—디메틸ᅳ 5—옥소-피라졸 -1—일)페닐]설포닐아미 노]ᅳ 2-페닐—아세테이트 Ν—benzylᅳ 4-(4-isopropyl— 2, 3—dimethyl -5—oxo-pyrazole— 1-yl)benzenesulfonamide methyl 2- [ [4— (4-isopropylᅳ 2, 3—dimethyl ᅳ 5—oxo-pyrazole -1—yl)phenyl]sulfonylamino]ᅳ 2-phenyl—acetate
Ν-(2—에록시에틸) -4- (4-이소프로필— 2， 3-디메틸— 5ᅳ옥소-피라졸— 1-일 )벤젠설폰 아미드 Ν-(2—eroxyethyl) -4- (4-isopropyl— 2，3-dimethyl— 5ᅳoxo-pyrazole— 1-yl )benzenesulfone amide
Ν-(2 , 6ᅳ디메틸페닐)— 4- (4-이소프로필— 2， 3-디메틸 -5-옥소ᅳ피라졸— 1-일)벤젠설 폰아미드 Ν-(2, 6-dimethylphenyl)— 4- (4-isopropyl— 2, 3-dimethyl-5-oxo-pyrazole— 1-yl)benzenesulfonamide
4-(4-이소프로필 -2 , 3—디메틸 -5—옥소—피라졸 -1-일 )-Ν— (9-옥소티옥산텐 -2—일 ) 벤젠설폰아미드 4-(4-isopropyl-2, 3—dimethyl-5—oxo—pyrazol-1-yl)-Ν— (9-oxothioxanthene-2—yl) Benzenesulfonamide
4-(4—이소프로필 -2， 3ᅳ디메틸ᅳ 5-옥소—피라졸 -1-일) -N-(4-메록시 -3 , 5—디메틸— 페닐)벤젠설폰아미드 4-(4—isopropyl-2，3ᅳdimethylᅳ 5-oxo—pyrazol-1-yl) -N-(4-meroxy-3, 5—dimethyl—phenyl)benzenesulfonamide
N-( 1 , 3—디메틸— 2-옥소—벤지미다졸 -5-일 )-4- (4-이소프로필 -2 , 3—디메틸 -5—옥소 -피라졸— 1—일 )밴젠설폰아미드 N-( 1, 3—dimethyl— 2-oxo—benzimidazol -5-yl )-4- (4-isopropyl -2, 3—dimethyl -5—oxo -pyrazole— 1—yl) benzenesulfonamide
에틸 5ᅳ [ [4- (4—이소프로필— 2 , 3-디메틸— 5-옥소-피라졸 -1—일 )페닐 ]설포닐아미 노]벤조티오펜 -2-카르복실레이트 Ethyl 5ᅳ [ [4- (4—isopropyl— 2, 3-dimethyl— 5-oxo-pyrazol -1—yl )phenyl ]sulfonylamino]benzothiophene -2-carboxylate
4— [4-(4—이소프로필— 2 , 3-디메틸 -5-옥소-피라졸 -1-일)페닐]설포닐—1 , 3-디히드 로퀴녹살린— 2-온 4— [4-(4—isopropyl—2,3-dimethyl-5-oxo-pyrazol-1-yl)phenyl]sulfonyl—1,3-dihyde roquinoxalin—2-one
N-터트—부틸— 4-(4—이소프로필 -2， 3ᅳ디메틸 -5—옥소—피라졸 -1-일)벤젠설폰아미 드 N-tert—butyl—4-(4—isopropyl-2，3-dimethyl-5—oxo—pyrazol-1-yl)benzenesulfonamide
N-(3—플루오로 -2—메틸―페닐) -4— (4—이소프로필ᅳ 2 ' 3—디메틸— 5—옥소—피라졸 -1ᅳ 일)벤젠설폰아미드 N-(3—fluoro -2—methyl—phenyl) -4— (4—isopropylᅳ 2 ' 3—dimethyl— 5—oxo—pyrazole -1—yl)benzenesulfonamide
4- [ [4— (4-이소프로필ᅳ 2 , 3-디메틸—5-옥소—피라졸 -1—일)페닐 ]설포닐아미노]밴 젠설폰아미드 4- [ [4— (4-isopropylᅳ 2, 3-dimethyl—5-oxo—pyrazol -1—yl)phenyl ]sulfonylamino]vanzenesulfonamide
4-이소프로필— 1 , 5—디메틸—2ᅳ [4- [4— (3—페닐퀴녹살린—2—일)피페라진 -1—일]설포 닐페닐]피라졸—3-온 4-isopropyl— 1 , 5—dimethyl—2ᅳ [4- [4— (3—phenylquinoxaline—2—yl)piperazine -1—yl]sulfonylphenyl]pyrazol—3-one
4一이소프로필 -2- [4-[ [4-[4-(4-이소프로필 -2， 3-디메틸— 5-옥소-피라졸 -1-일)페 닐]설포닐 -1， 4-디아제판 -1-일]설포닐]페닐] -1， 5—디메틸-피라졸— 3-온 4一isopropyl-2- [4-[ [4-[4-(4-isopropyl-2，3-dimethyl— 5-oxo-pyrazol-1-yl)phenyl]sulfonyl-1，4- Diazepan -1-yl] sulfonyl] phenyl] -1, 5—dimethyl-pyrazole— 3-one
4—이소프로필 -1 , 5—디메틸— 2- [4- [4- [4— (모폴린 -4—카르보닐) -2-니트로—페닐 ]피 페라진 -1—일 ]설포닐페닐 ]피라졸 -3-온 4—isopropyl-1, 5—dimethyl— 2- [4- [4- [4— (morpholine-4—carbonyl) -2-nitro—phenyl ]piferazine -1—yl ]sulfonylphenyl ] Pyrazole-3-one
4-이소프로필 -1， 5—디메틸ᅳ 2- [4- [4— (2—피리딜)피페라진— 1—일 ]설포닐페닐]피라 조一 오 4-isopropyl -1, 5—dimethylᅳ 2- [4- [4— (2—pyridyl)piperazine— 1—yl ]sulfonylphenyl]pyrazine 1
N一 (2， 2-디메틸프로필)— 4-(4-이소프로필— 2 ' 3-디메틸 -5—옥소—피라졸 -1-일 )벤젠 설폰아미드 N一 (2， 2-dimethylpropyl)— 4-(4-isopropyl— 2 ' 3-dimethyl -5—oxo—pyrazol -1-yl )benzene sulfonamide
4—이소프로필— 2— [4— [4-(4—메특시페닐)피페라진 -1—일]설포닐페닐]—1 , 5-디메틸 一피라졸 -3-온 4—isopropyl— 2— [4— [4-(4—methoxyphenyl)piperazine -1—yl]sulfonylphenyl]—1 , 5-dimethyl 一pyrazol -3-one
N-[2-(3 , 4-디메록시페닐)에틸]— 2-[ [4— (4—이소프로필 -2 , 3-디메틸 -5-옥소—피라 졸 -1—일)페닐 ]설포닐아미노]벤자미드 N-[2-(3, 4-dimeroxyphenyl)ethyl]— 2-[ [4— (4—isopropyl-2, 3-dimethyl-5-oxo—pyrazol-1—yl)phenyl]sulfonyl Amino]benzamide
에틸 2- [ [4-(4-이소프로필 -2， 3-디메틸 -5—옥소-피라졸— 1-일 )페닐]설포닐아미 노] -4， 5， 6， 7—테트라히드로벤조티오펜 -3-카르복실레이트 Ethyl 2- [ [4-(4-isopropyl-2，3-dimethyl-5—oxo-pyrazole—1-yl)phenyl]sulfonylamino]-4，5，6，7—tetrahydrobenzothi Ophene-3-carboxylate
2一 [4— [4ᅳ(7—클로로—4—퀴놀릴)피페라진 -1-일]설포닐페닐] -4—이소프로필 -1 , 5- 디메틸-피라졸 -3ᅳ온 2一 [4— [4ᅳ(7—chloro—4—quinolyl)piperazine -1-yl]sulfonylphenyl] -4—isopropyl -1, 5- Dimethyl-pyrazole-3-one
4一이소프로필 -1 , 5-디메틸—2ᅳ[4-( 1-피페리딜설포닐)페닐]피라졸 -3-온 4Isopropyl -1, 5-dimethyl—2ᅳ[4-(1-piperidylsulfonyl)phenyl]pyrazol-3-one
Nᅳ이소프로필—4ᅳ (4—이소프로필— 2 , 3—디메틸—5-옥소-피라졸 -1—일)벤젠설폰아미 드 Nᅳisopropyl—4ᅳ (4—isopropyl—2, 3—dimethyl—5-oxo-pyrazol -1—yl)benzenesulfonamide
Nᅳ시클로프로필 -4-(4—이소프로필— 2， 3-디메틸— 5-옥소-피라졸 -1-일)벤젠설폰아 미드 NᅳCyclopropyl -4-(4—isopropyl— 2，3-dimethyl— 5-oxo-pyrazol -1-yl)benzenesulfonamide
4-이소프로필 -1， 5-디메틸— 2— (4—모폴리노설포닐페닐)피라졸 -3—온 4-isopropyl -1, 5-dimethyl— 2— (4—morpholinosulfonylphenyl)pyrazole -3—one
4-(4-이소.프로필— 2，3—디메틸— 5—옥소—피라졸 -1-일) -N-(2-페녹시에틸)벤젠설폰 아미드 4-(4-iso.propyl— 2,3—dimethyl— 5—oxo—pyrazol -1-yl) -N-(2-phenoxyethyl)benzenesulfone amide
N一 [ 2- ( 3， 5—디메틸페녹시)에틸]—4- ( 4—이소프로필 -2， 3-디메틸 -5-옥소—피라졸一 1-일)밴젠설폰아미드 N一 [ 2- ( 3， 5—dimethylphenoxy)ethyl]—4- ( 4—isopropyl -2，3-dimethyl -5-oxo—pyrazol 一 1-yl)benzenesulfonamide
4一 (4-이소프로필 -2， 3ᅳ디메틸ᅳ 5—옥소—피라졸 -1ᅳ일) -N-프로필-벤젠설폰아미드 4一 (4-isopropyl-2，3-dimethyl-5—oxo—pyrazol-1-yl) -N-propyl-benzenesulfonamide
^(4-히드록시- [ 1 , 1 ' -바이페닐]—3ᅳ일)ᅳ4-(4-이소프로필—2 , 3-디메틸—5—옥소— 2， 5—디히드로— 1H—피라졸— 1—일 )벤젠설폰아미드 ^(4-hydroxy- [ 1 , 1 '-biphenyl]—3-yl)-4-(4-isopropyl—2, 3-dimethyl—5—oxo— 2, 5—dihydro— 1H—pyrazole — 1—day )Benzenesulfonamide
N-(2ᅳ히드록시페닐 )-4— (4-이소프로필— 2 , 3-디메틸 -5-옥소— 2 , 5—디히드로—1H-피 라졸 -1—일)밴젠설폰아미드 N-(2-hydroxyphenyl)-4— (4-isopropyl—2,3-dimethyl-5-oxo—2,5—dihydro—1H-pyrazol-1—yl)benzenesulfonamide
N-(5—히드록시나프탈렌— 2—일) -4— (4—이소프로필— 2 , 3—디메틸 -5-옥소— 2 , 5-디히 드로 -1H—피라졸ᅳ 1-일)벤젠설폰아미드 N-(5—hydroxynaphthalene— 2—yl) -4— (4—isopropyl— 2, 3—dimethyl -5-oxo— 2, 5-dihydro -1H—pyrazolᅳ 1-yl)benzenesulfone amides
4-(4—브로모 -2 , 3-디메틸ᅳ 5-옥소ᅳ 2 , 5-디히드로— 1Hᅳ피라졸— 1-일)— Ν-(2 , 4-디메 틸페닐)벤젠설폰아미드 4-(4—bromo-2, 3-dimethylᅳ 5-oxoᅳ 2, 5-dihydro— 1Hᅳpyrazole— 1-yl)— Ν-(2, 4-dimethylphenyl)benzenesulfonamide
4一 (4ᅳ이소프로필 -2，3-디메틸 -5—옥소 -2 , 5-디히드로— 1H-피라졸— 1—일 )-Nᅳ (4— (2— 몰포리노에록시 )페닐 )밴젠설폰아미드 4 一 (4-isopropyl-2，3-dimethyl-5—oxo-2, 5-dihydro— 1H-pyrazol— 1—yl )-N ᅳ (4— (2— morpholinoeroxy ) phenyl ) Benzenesulfonamide
N一 (2 , 4—디히드록시페닐) -4— (4-이소프로필 -2 , 3—디메틸— 5—옥소— 2 , 5—디히드로ᅳ 1H-피라졸 -1—일)밴젠설폰아미드 N 一 (2, 4—dihydroxyphenyl) -4— (4-isopropyl -2, 3—dimethyl— 5—oxo— 2, 5—dihydro 1H-pyrazol -1—yl) benzenesulfonamide
4-(4—브로모— 2 , 3—디메틸 -5—옥소 -2， 5—디히드로 -1H-피라졸 -1—일 )— N-(4— (트리플 루오로메틸)페닐)벤젠설폰아미드 4-(4—bromo— 2 , 3—dimethyl -5—oxo -2， 5—dihydro -1H-pyrazol -1—yl )— N-(4— (trifluoromethyl)phenyl)benzenesulfone amides
N-(3—플루오로 -4—히드록시페닐)— 4-(4—이소프로필— 2， 3-디메틸— 5-옥소— 2， 5-디 히드로 -1H—피라졸 -1—일)벤젠설폰아미드 N-(3—fluoro-4—hydroxyphenyl)— 4-(4—isopropyl— 2, 3-dimethyl— 5-oxo— 2, 5-dihydro -1H—pyrazol -1—yl)benzene Sulfonamide
4-(4-이소프로필 -2 , 3ᅳ디메틸— 5—옥소 -2， 5—디히드로 -1H—피라졸 -1—일 )-N-(2-메 록시— 4—니트로페닐)벤젠설폰아미드 4-(4-isopropyl-2, 3-dimethyl—5—oxo-2，5—dihydro-1H—pyrazol-1—yl)-N-(2-meroxy—4—nitrophenyl)benzenesulfone amides
3-(4-(4—이소프로필 -2 , 3-디메틸 -5ᅳ옥소—2 , 5—디히드로 -1H-피라졸— 1—일 )페닐설 폰아미도)벤조산 4- (4-이소프로필— 2， 3—디메틸 -5-옥소 -2 , 5-디히드로 -1H-피라졸— 1-일 )— N— (2一메 특시ᅳ 5-니트로페닐)밴젠설폰아미드 3-(4-(4—isopropyl-2, 3-dimethyl-5-oxo—2, 5—dihydro-1H-pyrazole— 1—yl)phenylsulfonamido)benzoic acid 4- (4-isopropyl— 2, 3—dimethyl -5-oxo -2, 5-dihydro -1H-pyrazole— 1-yl )— N— (2-methyl-5-nitrophenyl)benzenesulfone amides
4-(4-이소프로필 -2， 3—디메틸— 5—옥소 -2 , 5—디히드로 -1H-피라졸 -1—일) -N— (2一메 틸벤조퓨란 -5—일)벤젠설폰아미드 4-(4-isopropyl -2，3—dimethyl— 5—oxo -2, 5—dihydro -1H-pyrazol -1—yl) -N— (2一methylbenzofuran -5—yl)benzene Sulfonamide
N-(벤조 [b]티오펜—5—일) -4— (4-이소프로필 -2，3—디메틸 -5—옥소— 2 , 5-디히드로— 1H-피라졸ᅳ 1—일 )벤젠설폰아미드 N-(benzo [b]thiophen—5—yl) -4— (4-isopropyl -2,3—dimethyl -5—oxo— 2, 5-dihydro— 1H-pyrazolᅳ 1—yl)benzene Sulfonamide
N- (벤조퓨란 -5—일 )-4-(4-이소프로필— 2 , 3—디메틸 -5—옥소— 2 , 5—디히드로 -1H一피 라졸 - 1-일)벤젠설폰아미드 N- (benzofuran -5—yl)-4-(4-isopropyl— 2, 3—dimethyl -5—oxo— 2, 5—dihydro -1H1pyrazole - 1-yl)benzenesulfonamide
N- (벤조퓨란 -5-일메틸 )-4— (4-이소프로필— 2， 3-디메틸 -5—옥소 -2 , 5ᅳ디히드로ᅳ 1H-피라졸 -1—일)벤젠설폰아미드 N- (benzofuran -5-ylmethyl )-4— (4-isopropyl— 2, 3-dimethyl -5—oxo -2, 5ᅳdihydroᅳ 1H-pyrazol -1—yl)benzenesulfonamide
메틸 5— (4-(4-이소프로필 -2 , 3-디메틸— 5-옥소— 2， 5—디히드로 -1H-피라졸ᅳ 1-일 ) 페닐설폰아미도)벤조 [b]티오펜—2-카르복실레이트 Methyl 5— (4-(4-isopropyl-2, 3-dimethyl— 5-oxo— 2， 5—dihydro -1H-pyrazolᅳ 1-yl ) phenylsulfonamido) benzo [b] thiophene— 2-carboxylate
메틸 4-( (4-(4ᅳ이소프로필— 2 , 3—디메틸 -5-옥소— 2， 5-디히드로— 1H-피리-졸—1—일 ) 페닐설폰아미도)메틸 )벤조에이트 Methyl 4-( (4-(4ᅳisopropyl— 2, 3—dimethyl -5-oxo— 2， 5-dihydro— 1H-pyri-zol—1—yl ) phenylsulfonamido)methyl ) benzoate
메틸 6ᅳ(4-(4—이소프로필— 2， 3-디메틸— 5—옥소— 2， 5ᅳ디히드로 -1H—ᅵ피라졸— 1ᅳ일 ) 페닐설폰아미도 )—2—나프토에이트 Methyl 6ᅳ(4-(4—isopropyl— 2， 3-dimethyl— 5—oxo— 2， 5—dihydro -1H— pyrazole— 1—yl ) phenylsulfonamido )—2—naphthoate
4— (4—이소프로필— 2 , 3-디메틸— 5—옥소 -2 , 5—디히드로 -1H—피라졸 -1-일 )-Nᅳ메시틸 벤젠설폰아미드 4— (4—isopropyl— 2 , 3-dimethyl— 5—oxo -2 , 5—dihydro -1H—pyrazol -1-yl ) -Nᅳmesityl benzenesulfonamide
N-(9 , 1으디옥소ᅳ 9 , 10-디히드로안트라센 -2—일 )—4— (4—이소프로필 - 2， 3—디메틸— 5一옥소 -2， 5ᅳ디히드로— 1H-피라졸 -1—일)벤젠설폰아미드 N-(9, 1-dioxo-9, 10-dihydroanthracene -2—yl)—4— (4—isopropyl-2, 3—dimethyl— 5-oxo-2, 5-dihydro— 1H-pyrazole -1—1)benzenesulfonamide
4ᅳ (4-이소프로필 -2 , 3-디메틸— 5-옥소 -2， 5-디히드로 -1H—피라졸— 1—일)— N- (이소 퀴놀린—5-일)벤젠설폰아미드 4ᅳ (4-isopropyl -2, 3-dimethyl— 5-oxo -2， 5-dihydro -1H—pyrazol— 1—yl)— N- (isoquinoline—5-yl)benzenesulfonamide
N- (벤조 [d] [ 1 , 3]디옥실—5—일) -4— (4-이소프로필— 2 , 3—디메틸 -5-옥소 -2 , 5-디히 드로 -1H—피라졸—1-일)벤젠설폰아미드 N- (benzo [d] [ 1 , 3] dioxyl—5—yl) -4— (4-isopropyl— 2 , 3—dimethyl -5-oxo -2, 5-dihydro -1H—pyrazole— 1-day) Benzenesulfonamide
N- (벤조 [d] [ 1 , 3]디옥실— 5-일메틸)— 4-(4-이소프로필— 2 , 3—디메틸 -5—옥소 -2， 5ᅳ 디히드로 -1H-피라졸 -1—일 )벤젠설폰아미드 N- (benzo [d] [1, 3] dioxyl— 5-ylmethyl)— 4-(4-isopropyl— 2, 3—dimethyl -5—oxo -2， 5ᅳ dihydro -1H-pyrazole -1—1)benzenesulfonamide
4- -이소프로필 -2， 3-디메틸— 5—옥소 -2 , 5-디히드로 -1H-피라졸 -1ᅳ일 )— N— (2—옥 소인돌린 -5—일)벤젠설폰아미드 4- -isopropyl -2, 3-dimethyl— 5—oxo -2, 5-dihydro -1H-pyrazol -1-yl)— N— (2—oxoindolin -5—yl)benzenesulfonamide
4一 (4—브로모—2， 3-디메틸— 5-옥소 -2 , 5—디히드로— 1H-피라졸— 1—일 )-N— (4— (트리플 루오로메틸)페닐)벤젠설폰아미드 4一 (4—bromo—2， 3-dimethyl— 5-oxo -2 , 5—dihydro— 1H-pyrazol— 1—yl ) -N— (4— (trifluoromethyl)phenyl)benzenesulfone amides
4- -이소프로필— 2 , 3-디메틸 -5-옥소 -2 , 5—디히드로— 1H-피라졸— 1-일 )— N— (2- (티 오펜— 2—일)에틸)벤젠설폰아미드 4-(4-이소프로필— 2 , 3-디메틸— 5-옥소 -2 5-디히드로— 1H一피라졸 -1—일) -Ν- (3， 4 5—트리메특시페닐 )벤젠설폰아미드 4- -isopropyl— 2 , 3-dimethyl -5-oxo -2 , 5—dihydro— 1H-pyrazole— 1-yl )— N— (2- (thiophen— 2—yl)ethyl)benzenesulfone amides 4-(4-isopropyl— 2, 3-dimethyl— 5-oxo -2 5-dihydro— 1H pyrazol -1—yl) -Ν- (3, 4 5—trimethoxyphenyl) benzenesulfonamide
Ν一 (시클로핵실메틸)— 4-(4—이소프로필— 2 , 3—디메틸 -5-옥소 -2 , 5—디히드로 -1Hᅳ피 라졸 -1—일)벤젠설폰아미드 Ν一 (cyclohexylmethyl)— 4-(4—isopropyl— 2 , 3—dimethyl -5-oxo -2 , 5—dihydro -1Hᅳpyrazol -1—yl)benzenesulfonamide
Ν- (시클로헵틸메틸) -4— (4-이소프로필 -2 3-디메틸— 5—옥소 -2 , 5-디히드로— 1H-피 라졸ᅳ 1—일)벤젠설폰아미드 Ν- (cycloheptylmethyl) -4— (4-isopropyl -2 3-dimethyl— 5—oxo -2, 5-dihydro— 1H-pyrazolᅳ 1—yl)benzenesulfonamide
Ν一 (2-시클로핵실에틸 )-4— (4-이소프로필— 2 3—디메틸 -5-옥소— 2 5-디히드로 -1Η- 피라졸—1-일)벤젠설폰아미드 Ν一 (2-cyclohexylethyl )-4— (4-isopropyl— 2 3—dimethyl -5-oxo— 2 5-dihydro -1Η- pyrazol—1-yl)benzenesulfonamide
Ν一 (3 4—디메록시페닐 )-4— (4-이소프로필 -2 , 3-디메틸 -5—옥소 -2 , 5—디히드로 -1Η- 피라졸—1—일)벤젠설폰아미드로 이루어진 군에서 선택되는 것을 특징으로 하는 화합 물 Ν一 (3 4—dimeroxyphenyl)-4—(4-isopropyl-2, 3-dimethyl-5—oxo-2, 5—dihydro-1Η-pyrazol-1—yl)benzenesulfonamide Compounds characterized by being selected from the group
【청구항 9】 【Claim 9】
하기 반웅식에 의해 제조되는 제 1항의 화합물 또는 이의 약학적으로 The compound of claim 1 or its pharmaceutical form prepared by the following reaction method
ί한 염의 제조방법 : ί Manufacturing method of salt:
[반웅식 1] [Banwoongsik 1]
Figure imgf000151_0001
Figure imgf000151_0001
상기 반웅식 1에서 In reaction 1 above,
l , R2 , R3는 상기 청구항 게 1항에서 정의한 바와 같다, l, R2, and R3 are as defined in claim 1 above,
【청구항 10] [Claim 10]
제 1항 내지 제 7항 중 어느 한 항의 화합물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 암, 간질, 염증질환， 면역질환, 당뇨, 비만， 호흡기계 폐쇄성 질환, 섬유증, 품페병, 리소좀 축적질환 ( lysosomal storage di sease) , 알츠 하이머 질환, 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행성 질환, 심혈관계질환 및 기생충 감염증으로 이루어진 군에서 선택된 어느 한 질환의 예방 또는 치료용 약학적 조성물, Cancer, epilepsy, inflammatory disease, immune disease, diabetes, obesity, respiratory obstructive disease, fibrosis, Poompe disease, A pharmaceutical composition for the prevention or treatment of any one disease selected from the group consisting of lysosomal storage diseases, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, cardiovascular diseases and parasitic infections,
【청구항 11】 제 9항에 있어서， 상기 암은 라파마이신 (rapamycin) 저항성을 나타내는 암인 것을 특징으로 하는 조성물. 【Claim 11】 The composition according to claim 9, wherein the cancer is a cancer that exhibits rapamycin resistance.
【청구항 12] [Claim 12]
제 1항 내지 제 7항 중 어느 한 항의 화합물 또는 이의 약학적으로 허용가능한 염을 필요로 하는 개체에 유효량으로 투여하여 암, 간질， 염증질환, 면역질환, 당 뇨, 비만， 호흡기계 폐쇄성 질환, 섬유증, 품페병, 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질환， 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행 성 질환, 심혈관계질환 및 기생충 감염증으로 이루어진 군에서 선택된 어느 한 질 환을 치료하는 방법ᅳ The compound of any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof is administered in an effective amount to an individual in need to treat cancer, epilepsy, inflammatory disease, immune disease, diabetes, obesity, respiratory obstructive disease, Method for treating any one disease selected from the group consisting of fibrosis, Poompe disease, lysosomal storage disease, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, cardiovascular diseases and parasitic infections.
【청구항 13] [Claim 13]
제 1항 내지 제 7항 중 어느 한 항의 화합물 또는 이의 약학적으로 허용가능한 염의 암， 간질， 염증질환， 면역질환, 당뇨, 비만， 호흡기계 폐쇄성 질환, 섬유증, 품페병， 리소좀 축적질환 ( lysosomal storage di sease) , 알츠하이머 질환, 파킨슨 질환 및 헌팅턴 질환과 같은 신경퇴행성 질환, 심혈관계질환 및 기생층 감염증으로 이루어진 군에서 선택된 어느 한 질환의 치료제 제조를 위한 용도. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, can be used to treat cancer, epilepsy, inflammatory disease, immune disease, diabetes, obesity, respiratory obstructive disease, fibrosis, phlegm disease, and lysosomal storage disease. di sease), for the manufacture of a treatment for any disease selected from the group consisting of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, cardiovascular diseases and parasitic infections.
【청구항 14】 【Claim 14】
제 12항에 있어서， 상기 암은 라파마이신 (rapamycin) 저항성을 나타내는 암인 것을 특징으로 하는 방법 . The method of claim 12, wherein the cancer is a cancer that exhibits rapamycin resistance.
【청구항 153 【Claim 153
제 13항에 있어서, 상기 암은 라파마이신 (rapamycin) 저항성을 나타내는 암인 것을 특징으로 하는 치료제 제조를 위한 용도. The use for manufacturing a therapeutic agent according to claim 13, wherein the cancer is a cancer that exhibits rapamycin resistance.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021007474A1 (en) * 2019-07-11 2021-01-14 Cura Therapeutics, Llc Phenyl compounds and pharmaceutical compositions thereof, and their therapeutic applications
US11701334B2 (en) 2018-01-10 2023-07-18 Cura Therapeutics, Llc Pharmaceutical compositions comprising phenylsulfonamides, and their therapeutic applications

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3786163A4 (en) 2018-04-26 2021-12-29 Medicinal Bioconvergence Research Center Novel compound as mtor inhibitor and use thereof
KR102426016B1 (en) 2020-01-07 2022-08-01 한국과학기술연구원 Novel 1-phenyl-1H-pyrazole derivatives and use thereof
WO2023002011A1 (en) * 2021-07-23 2023-01-26 Institut National De La Sante Et De La Recherche Medicale (Inserm) Gram-negative bacteria efflux pump inhibitors

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011100840A1 (en) * 2010-02-17 2011-08-25 UNIVERSITé LAVAL Substituted 2-imidazolidones and analogs
WO2013023274A1 (en) * 2011-08-16 2013-02-21 Universite Laval Substituted 2-imidazolidinones and 2-imidazolones and their use in the treatment of cancer

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6734190B2 (en) 2002-07-29 2004-05-11 Wyeth Dihydrodipyrazolopyridinylbenzamide and -sulfonamide inhibitors of B7-1
KR101210273B1 (en) * 2008-12-18 2012-12-10 한국전자통신연구원 Method for composing On-Chip network topology

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011100840A1 (en) * 2010-02-17 2011-08-25 UNIVERSITé LAVAL Substituted 2-imidazolidones and analogs
WO2013023274A1 (en) * 2011-08-16 2013-02-21 Universite Laval Substituted 2-imidazolidinones and 2-imidazolones and their use in the treatment of cancer

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
CONGIU, C. ET AL.: "Synthesis and Carbonic Anhydrase I, II, IX and XII Inhibition Studies of 4-N,N-disubstituted Sulfanilamides Incorporating 4,4,4-trifllloro-3-oxo-but-1-enyl, Phenacylthiourea and Imidazol-2(3H)-one/thionemoieties", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 24, 2014, pages 1776 - 1779, XP028835162 *
DATABASE Chemical Abstract 18 August 2004 (2004-08-18), retrieved from STN Database accession no. 728027-54-1 *
DATABASE Chemical Abstract 18 June 2004 (2004-06-18), retrieved from STN Database accession no. 695207-50-2 *
DATABASE CHEMICAL ABSTRACT 21 August 2007 (2007-08-21), Database accession no. 945155-67-9 *
DATABASE CHEMICAL ABSTRACT 24 April 2006 (2006-04-24), Database accession no. 881590-48-3 *
DATABASE CHEMICAL ABSTRACT 5 March 2007 (2007-03-05), Database accession no. 924828-06-8 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11701334B2 (en) 2018-01-10 2023-07-18 Cura Therapeutics, Llc Pharmaceutical compositions comprising phenylsulfonamides, and their therapeutic applications
WO2021007474A1 (en) * 2019-07-11 2021-01-14 Cura Therapeutics, Llc Phenyl compounds and pharmaceutical compositions thereof, and their therapeutic applications

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