HU217842B - 7-amino-1h-indol derivatives - Google Patents

Abstract

The present invention relates to the 7-amino-1H-indole derivatives of formula IIIa wherein G is hydrogen, halogen or cyano, Q is halogen, vagymethyl, and t is an integer of 0 or 1. Compounds of the invention intermediate products for the preparation of antitumor sulfonamide and sulfonic acid ester derivatives of formula (Ia). ŕ

Description

The present invention relates to novel 7-amino-1H-indole derivatives and their preparation. The compounds of the invention serve as starting materials for the preparation of sulfonamide and sulfonic acid ester derivatives having antitumor activity.

Chemotherapeutic agents hitherto used for the treatment of cancer include cyclophosphamide as an alkylating agent; methotrexate and fluorouracil as antimetabolites; adriamycin, mitomycin and bleomycin as antibiotics; vincristine and etoposide as active ingredients of plant origin; and cisplatin and a metal complex. However, the antitumor activity of these agents is unsatisfactory and it is highly desirable to develop a novel antitumor agent.

Further, 2-sulfanylamidoquinoxaline derivatives (US-A 4 931 433) and N- (2-anilino-3-pyridinyl) benzenesulfonamide derivatives (EP-A 472 053) have been described as aromatic sulfonamide antitumor agents.

Publication number T / 71551 discloses novel sulfonamide and sulfonic acid ester derivatives of Formula I, which have excellent antitumor activity and differ in their basic structure from prior art antitumor agents. The indole derivatives of the invention serve as starting materials for the preparation of these derivatives.

Indole derivatives bearing a hydroxy, methoxy or hydrogen substituent on the benzene ring are described in J. Chem. Soc. D, 22, 1437-1438. (1971) (Paul G. Gassman et al.) For a new process for converting various 1-hydroxyindole derivatives into 5-hydroxy and 5alkoxyindole derivatives.

Indole derivatives with or without a methoxy group on the benzene ring are described in Heterocycles, 34, 2349-2362. (1992) (Masanobu Tani et al.) On regioselective bromination of the methoxy derivative of an indole-2-carboxylic acid ethyl ester.

The synthesis of indole derivatives bearing an oxygen atom attached to the benzene ring, namely OH, -OTs, or -OTf - (- otrifluoromethanesulfonyl), is described in Tetrahedron Letters, 30 (16) 2099-2100. (1989) (Yasuoki Muramaki et al.) Describe the use of these compounds in the synthesis of eudistmidine A.

Further, amino-substituted indole derivatives on the benzene ring are described in PCT Patent Publication No. WO 9215761, and indole-substituted amino and methoxy derivatives are described in Medd. Nor. Farm. Sels .; 28. (10-11.), 153-158. (1966) and nitro- and amino-substituted indole derivatives are described in J. Indiana Chem. Soc., 41 (5), 357-361. (1964).

None of the above compounds are suitable as starting materials for the active compounds of formula (Ia).

The indole derivatives of formula (IIIa) of the present invention are intended for the preparation of compounds of formula (Ia), or a pharmaceutically acceptable salt thereof, which is a sulfonamide or sulfonic acid ester derivative of formula (I):

A is an optionally substituted monocyclic or bicyclic aromatic ring,

W is a bond or a group of the formula -CH = CH,

X is -N (R>) - or oxygen,

R ¹ is hydrogen or lower alkyl;

G is hydrogen, halogen, or cyano;

Q is a substituent; t is an integer having a value of 0 to 2, and t = 2 having the same or different substituents on Q.

The indole derivatives of the invention have the general formula (IIIa)

G is hydrogen, halogen, or cyano,

Q is halogen or methyl, and t is an integer equal to 0 or 1.

According to one of the various possible processes for the preparation of compounds of formula I, a sulfonic acid of formula II (wherein Aa is a monocyclic or bicyclic aromatic ring optionally substituted or unsubstituted; and W is as defined above) or a reactive derivative thereof With a compound of formula (III) (wherein Ba is an optionally substituted or unsubstituted benzene ring, Ca is an optionally protected or unsubstituted pyrrole ring, and X is as defined above).

The reactive derivative of the sulfonic acid of formula (II) may be any conventional reactive derivative such as sulfonyl halide, sulfonic anhydride and N-sulfonyl imidazole, of which sulfonyl halide is particularly preferred. Although the range of solvents used in the above reaction is not particularly limited, it is preferable to use a solvent in which the starting material is soluble and which is only slightly reactive with the reagents. Examples of such solvents are pyridine, tetrahydrofuran, dioxane, benzene, ethyl ether, dichloromethane, dimethylformamide and mixtures of two or more thereof. If an acid is liberated over the course of the reaction, such as when a halide or sulfonic acid is used, it is preferred to carry out the reaction in the presence of a suitable acid acceptor. In this regard, the use of a basic solvent such as pyridine is particularly preferred. When a neutral solvent is used, a basic material such as an alkali metal carbonate or an organic tertiary amine may be added. Of course, the range of solvents used in the reaction is not limited to those described above. Although the reaction is usually carried out at room temperature2

EN 217 842 Β, can be performed by cooling or heating as needed. The reaction time is usually from 10 minutes to 20 hours, and is arbitrarily selected according to the type of starting materials and reaction temperature.

If the product obtained has a protected amino or hydroxy group, the product may optionally be subjected to conventional deprotection methods, such as treatment with an acid or alkali, or catalytic reduction to a sulfonamide derivative or a sulfonic acid having a free hydroxyl or amino group. can be converted to an ester derivative.

The starting materials of the formula II and their reactive derivatives include both known and novel compounds. Each of these novel compounds may be prepared using one of the methods described for the preparation of known compounds, or a combination of two or more of these methods. For example, Chem. Bér. 90, 841 (1957), J. Med. Chem. 6, 307 (1963), J. Chem. Soc. (C), 1968, 1265, Chem. Lett., 1992, 1483, J. Am. Chem. Soc., 59, 1837 (1937), J. Med. Chem., 23, 1376 (1980), J. Am. Chem. Soc., 70, 375 (1948). ) and J. Am. Chem. Soc.

78, 2171 (1956).

The starting compounds of formula (III) include both new and known compounds. The starting compounds of formula (III) wherein HX- is an amino group (H ₂ N-) can be prepared by reduction of the corresponding nitro compound according to a conventional procedure for reducing the nitro group. The reduction is preferably carried out catalytically using palladium-on-carbon or using zinc powder and hydrogen chloride. The catalytic reduction is generally carried out in an organic solvent such as methanol, tetrahydrofuran or dimethylformamide at atmospheric or elevated pressure.

The starting compounds of formula (III) wherein H-X- is hydroxy (HO-) can be prepared by diazotizing the corresponding amino compound of formula (IIa) and hydrolyzing the resulting diazo compound.

The novel compounds of formula (IIIa) may be prepared by one of the methods described for the preparation of known compounds or by combining two or more of these processes. A new starting compound can be prepared, for example, according to Can. J. Chem., 42, 1235 (1964), Chem. Abst.

59, 8855 (1963) or Tetrahedron Lett., 30, 2129 (1989). as shown in Schemes.

In the formulas of Scheme 1, each Q, which is the same or different, is a substituent; G is halogen and t is an integer from 0 to 2.

In Scheme 2, Q and t are as defined above.

In Scheme 3, Q, G and t are as defined above, DPPA is diphenylphosphoryl azide.

In Scheme 4, Q, G and t are as defined above; DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

Example 1

7-Bromo-1H-indole [Compound (1)]

To a solution of 2-bromo-nitrobenzene (5.05 g, 25 mmol) in tetrahydrofuran (-40 ° C) was added 100 ml of a 1.0 mol / l (100 mmol) solution of vinyl magnesium bromide in tetrahydrofuran under nitrogen. The resulting mixture was stirred for 40 minutes and then poured into 500 mL of saturated aqueous ammonium chloride solution. The resulting mixture was extracted with ethyl ether. The organic layer was dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column to give 2.89 g of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.56 (1H, dd, J = 2.9, 1.8 Hz), 6.94 (1H, t, J = 7.8 Hz), 7.30 (1H, d, J = 7.8Hz), 7.40 (1H, t, J = 2.9Hz), 7.56 (1H, d, J = 7.8Hz), 11.16 -11.46 (1H, broad m).

Example 2

7-Amino-1H-indole (Compound 2)

To a solution of the compound prepared in Example 1 (2.70 g, 13.8 mmol) in tetrahydrofuran (50 mL) at -70 ° C was added dropwise 16.5 mL of 2.5 M (41.3 mmol) under nitrogen atmosphere. ) a solution of n-butyllithium in hexane. The resulting mixture was stirred at -70 ° C for 15 minutes and then at -20 to -10 ° C for 30 minutes. The resulting mixture was again cooled to -70 ° C and 3.9 ml (18 mmol) of diphenylphosphoryl azide was added dropwise. The resulting mixture was stirred at -70 ° C for 1 hour and then at -40 ° C for 1 hour. To the resulting mixture was added 22.3 ml at -40 ° C,

3.4 M (75.8 mmol) sodium bis (2-methoxyethoxy) aluminum hydride in toluene. The resulting mixture was stirred at -30 to -20 ° C for 30 minutes, then at room temperature for 30 minutes, and then pH 7.0 phosphate buffer was added. The resulting mixture was filtered to remove insoluble materials, and the filtrate was extracted with ethyl ether. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and then with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated. The residue was chromatographed on a silica gel column to give 1.29 g of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 5.01 (2H, bs), 6.25-6.33 (2H, m), 6.70 (1H, dd, J = 7.9 , 7.3 Hz), 6.78 (1H, dd, J = 7.9, 0.7 Hz), 7.23 (1H, t, J = 2.7 Hz), 10.48-10.72 (1H, broad m).

In the same manner as in Examples 1 and 2, the following starting materials were prepared from 2-bromonitrobenzene derivatives:

7-amino-4-methoxy-1H-indole,

7-amino-4-bromo-1H-indole.

Example 3

7-Bromo-3-chloro-4-methyl-1H-indole (Compound 3)

To a solution of 7-bromo-4-methyl-1H-indole (2.8 g, 27.6 mmol) in 2-bromo-5-methyl-nitrobenzene prepared in a similar manner to Example 1 was 4.0 g. 0 mmol N-chlorosuccinimide was added. The received

After stirring at room temperature overnight, 50 ml of 1 N aqueous sodium hydroxide solution were added. The resulting mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column to obtain 6.7 g of the title compound.

1 H-NMR (CDCl ₃ ) δ ppm: 2.74 (3H, s), 6.75-7.26 (3H, m), 8.23 (1H, broad s).

Example 4

7-Amino-3-chloro-4-methyl-1H-indole (Compound 4)

From 6.37 g (26.1 mmol) of the compound prepared in Example 3, 2.6 g of the title compound is obtained in a manner similar to that described in Example 2.

1 H-NMR (CDCl ₃ ) δ ppm: 2.70 (3H, s), 6.39-7.14 (3H, m), 8.15 (1H, broad s).

Example 5

3-Cyano-7-nitro-1H-indole [Compound 5]

3-Formyl-7-nitro-1H-indole (10.15 g, 53.4 mmol) was dissolved in dimethylformamide (150 mL) and added to the solution.

3.93 g, 56.0 mmol of hydroxylamine hydrochloride and

Pyridine (4.5 mL, 55.6 mmol) was added. The resulting mixture was stirred at 70-80 ° C for 2 hours, then 6.3 g (56.8 mmol) of selenium dioxide and about 5 g of magnesium sulfate were added. The resulting mixture was heated at 70-80 ° C for 2.5 hours and then filtered to remove insolubles. The filtrate was evaporated, water was added to the residue to precipitate crystals, and the crystals were filtered off, washed with water and then with ethyl ether, and dissolved in a mixture of tetrahydrofuran and acetone. The resulting mixture was filtered to remove insolubles, the filtrate was evaporated and ethyl acetate was added. The precipitated crystals were collected by filtration to give 8.61 g of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 7.48 (1H, t, J = 8.1 Hz), 8.17 (1H, d, J = 8.1 Hz), 8.27 (1H, d, J = 8.1 Hz), 8.47 (1H, s), 12.70-13.00 (1H, broad).

Example 6

7-Amino-3-cyano-1H-indole (Compound 6)

The compound of Example 5 (2.80 g, 15.0 mmol) was suspended in methanol (100 mL) and hydrogenated in the presence of palladium on carbon at normal temperature and atmospheric pressure. After filtration of the catalyst, the filtrate was evaporated to dryness to give 2.31 g of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 5.32, 5.34 (2H, s + s), 6.47 (1H, d, J = 7.5 Hz), 6.81 ( 1H, d, J = 7.9 Hz),

6.94 (1H, dd, J = 7.9, 7.5 Hz), 8.13 (1H, s), 11.55-11.90 (1H, broad).

Example 7

7-Amino-3,4-dichloro-1H-indole (Compound 7)

7-Bromo-4-chloro-1H-indole prepared from 2-bromo-5-chloro-nitrobenzene in a manner similar to Example 1 is chlorinated in a similar manner to that in Reference Example 3. The bromine atom of the resulting product is converted to the title compound by exchange of an amino group as described in Reference Example 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 5.26 (2H, s),

6.29 (1H, d, J = 8.1 Hz), 6.74 (1H, d, J = 8.1 Hz), 7.45-7.51 (1H, m), 11.08-11 , 27 (1 H, m).

In a manner similar to that described above, 7-amino-4-tert-butyldimethylsilyloxy-3-chloro-1H-indole was prepared.

Example 8

7-Amino-3-chloro-1H-indole (Compound 8)

7-Nitro-1H-indole (1.076 g, 6.64 mmol) was dissolved in acetonitrile (30 mL) and N-chlorosuccinimide (920 mg, 6.89 mmol) was added. The resulting mixture was stirred at room temperature for 36 hours. To the resulting mixture was added a saturated aqueous sodium bicarbonate solution to form a precipitate. The precipitate was filtered off and washed with water to give 1.2 g of 3-chloro-7-nitro-1H-indole as a powder. 863 mg (4.39 mmol) of this powder are suspended in 10 ml of ethanol and 4.95 g (21.9 mmol) of stannous chloride dihydrate and 100 μ 100 of concentrated hydrochloric acid are added. The resulting mixture was refluxed for 30 minutes and then a saturated aqueous solution of sodium bicarbonate was added. The resulting mixture was filtered to remove insolubles, and ethyl acetate was added to the filtrate and extracted. The organic layer was dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column to give 490 mg of the title compound.

The title compound can also be prepared by hydrogenation of 3-chloro-7-nitro-1H-indole on a platinum catalyst with carbon at standard temperature and atmospheric pressure.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 5.14 (2H, s), 6.36 (1H, dd, J = 7.5, 1.0 Hz), 6.68 (1H, dd, J = 7.9, 0.73 Hz), 6.81 (1H, dd, J = 7.9, 7.5 Hz), 7.39 (1H, d, J = 2.7 Hz), 10.85 (1H, broad s).

Example 9

To a mixture of 5-bromo-7-nitro-1H-indole (9) in 1 ml of ethanol and 40 ml of 6N hydrochloric acid was added 5.05 g, 17.7 mmol of 1-acetyl-5-bromo-7-nitro- indoline is added. The resulting mixture was refluxed for 3 hours, then neutralized with sodium carbonate and extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column to give 4.13 g of 5-bromo-7-nitroindoline. To this mixture was added 301 mg (1.24 mmol) of toluene (10 mL) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (580 mg, 2.55 mmol) was added. The resulting mixture was refluxed with stirring for 3.5 hours and then filtered to remove insolubles. The filtrate was evaporated and the residue was chromatographed on a silica gel column to give 252 mg of the title compound.

HU 217,842 Β

Example 10

5-Bromo-3-formyl-7-nitro-1H-indole (Compound 10)

To dimethylformamide (1.0 g, 14 mmol) was added 210 mg of nitrogen under nitrogen atmosphere at 0 ° C.

1.4 mmol phosphorus oxychloride. The resulting mixture was stirred for 30 minutes and then 240 mg (1.0 mmol) of Reference Example 12 was added at 0 ° C. The resulting mixture was stirred at 0 ° C for 20 minutes and then at 100 ° C for 30 minutes, cooled in ice and then poured into ice water. The resulting mixture was stirred for 30 minutes while maintaining its pH between 7 and 8 by addition of 1 N aqueous sodium hydroxide solution. The resulting precipitate was filtered off and purified by silica gel column chromatography. 239 mg of the title compound are obtained.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 8.31 (1H, d, J = 1.8 Hz), 8.55 (1H, s), 8.65 (1H, d, J = 1) , 8 Hz), 10.05 (1H, s), 12.89 (1H, broad s).

Example 11

7-Amino-5-bromo-m-3-cyano-1H-indole (Compound 11)

From the compound prepared in Example 10, 5-bromo-3-cyano-7-nitro-1H-indole (214 mg, 0.8 mmol) prepared in a similar manner to Example 5 was dissolved in 10 mL of methanol and 10 mL of tetrahydrofuran. hydrogen in the presence of an oxide catalyst at a pressure of 3.0 kg / cm ² . The catalyst was filtered off and the filtrate was evaporated to dryness to give 189 mg of the title compound.

1 H-NMR (DMSO-d 6) δ (ppm): 5.68-5.71 (2H, m), 6.60 (1H, d, J = 2.0 Hz), 6.91 (1H, d, J = 2.0 Hz), 8.16 (1H, s).

Reference Example 1

N- (1H-indol-7-yl) -4-nitrobenzenesulfonamide (Compound 12)

1.50 g (11.3 mmol) of the compound prepared in Example 2 are dissolved in 40 ml of pyridine. To the resulting solution was added 4-nitrobenzenesulfonyl chloride (2.57 g, 11.6 mmol) at room temperature with stirring. The resulting mixture was stirred at room temperature overnight and then the solvent was distilled off under reduced pressure. Ethyl acetate and 0.2 N hydrochloric acid were added to the residue. The organic phase is removed, washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by silica gel column chromatography to give 3.50 g of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.42 (1H, dd, J = 2.8, 2.0 Hz), 6.66 (1H, d, J = 7.6 Hz), 6.83 (1H, dd, J = 8.0, 7.6 Hz), 7.31 (1H, dd, J = 3.2, 2.8 Hz), 7.36 (1H, d, J = 8.0 Hz), 7.94-8.02 (2H, m), 8.30-8.38 (2H, m), 10.23 (1H, s), 10.74-10.87 (1H , m).

Reference Example 2

N- (3-Chloro-1H-indol-7-yl) -4-nitrobenzenesulfonamide (Compound 13)

Dissolve 8.98 g (28.3 mmol) of the compound prepared in Reference Example 1 in a mixture of dichloromethane (280 mL) and dimethylformamide (7 mL) and add N-chlorosuccinimide (4.16 g, 31.2 mmol) under nitrogen atmosphere. next to. The resulting mixture was stirred at room temperature for 1.5 hours and water (50 mL) was added. The resulting mixture was evaporated to about 80 mL, then ethyl acetate and 0.2 N hydrochloric acid were added. The organic phase is recovered, washed with saturated aqueous sodium bicarbonate solution and then with saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo. The resulting material was purified by silica gel column chromatography to give 7.98 g of the title compound. M.p. 199.5-200.5 ° C (crystallized from chloroform).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.72 (1H, d, J = 7.6 Hz), 6.96 (1H, dd, J = 8.0, 7.6 Hz), 7.31 (1H, d, J = 8.0 Hz), 7.47-7.53 (1H, m), 7.92-8.02 (2H, m), 8.30-8.41 ( 2H, m), 10.33 (1H, s), 11.07-11.22 (1H, m).

Reference Example 3

4-Bromomethyl-N- (1H-indol-7-yl) -benzenesulfonamide (Compound 14)

4-Bromomethylbenzenesulfonyl chloride is reacted with the compound prepared in Example 2 at room temperature in the presence of an equimolar amount of pyridine in tetrahydrofuran to give the title compound as described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 4.70 (2H, s), 6.40 (1H, dd, J = 3.1, 1.1 Hz), 6.71 (1H, ddd) , J = 7.4, 3.2, 0.92 Hz), 6.81 (1H, ddd, j = 8.1, 7.4, 0.92 Hz), 7.29-7.32 (2H , m), 7.57 (2H, d, J = 8.2 Hz), 7.73 (2H, d, J = 8.4 Hz), 9.96 (1H, broad s), 10.75 ( IH, broad s).

Reference Example 4

3-Chloro-N- (3-chloro-1H-indol-7-yl) -benzenesulfonamide (Compound 15)

2.18 g (7.11 mmol) of 3-chloro-N- (1H-indol-7-yl) -benzenesulfonamide prepared in Reference Example 1 were chlorinated in a similar manner to Reference Example 2 to give 1.86 g of the title compound. win.

180-181 ° C (crystallized from dichloromethane / diisopropyl ether).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.73 (1H, d, J = 7.6 Hz), 6.97 (1H, dd, J = 8.0, 7.6 Hz), 7.30 (1H, d, J = 8.0 Hz), 7.45-7.51 (1H, m), 7.51-7.76 (4H, m), 10.09 (1H, s) , 11.02 - 11.18 (1H, m).

Reference Example 5

4- [N- (1H-indol-7-yl) sulfamoyl] -benzoic acid (Compound 16)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.40 (1H, dd, J = 2.9, 1.9 Hz), 6.67 (1H, d, J = 7.5 Hz), 6.82 (1H, dd, J = 7.9, 7.5 Hz), 7.31 (1H, dd, J = 2.9, 2.7 Hz), 7.33 (1H, d, J = 7.9Hz), 7.81-7.88 (2H, m), 7.99-8.07 (2H, m), 10.07 (1H, s), 10.73-10.83 (1H , m), 13.30-13.58 (1H, broad).

HU 217,842 Β

Reference Example 6

3-Chloro-N- (3-chloro-4-methoxy-1H-indol-7-yl) -benzenesulfonamide (Compound 17): mg of the title compound was prepared in a similar manner as in Reference Example 2, 100 mg. from 3-chloro-N- (4-methoxy-1H-indol-7-yl) -benzenesulfonamide prepared in a similar manner to Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 3.79 (3H, s), 6.37 (1H, d, J = 8.4 Hz), 6.45 (1H, d, J = 8 , 4Hz), 7.24-7.31 (1H, m), 7.48-7.77 (4H, m), 9.76 (1H, s), 11.06-11.17 (1H, m).

Reference Example 7

3-Chloro-N- (3-chloro-4-hydroxy-1H-indol-7-yl) -benzenesulfonamide (Compound 18)

N- (4-tert-Butyldimethylsilyloxy-3-chloro-1H-indol-7-yl) -3-chlorobenzenesulfonamide (220 mg, 0.47 mmol) prepared in a similar manner to Reference Example 1 was added. 2 ml of a 1:10 mixture of aqueous hydrogen fluoride and acetonitrile. The resulting mixture was stirred at room temperature overnight and then water was added. The resulting mixture was extracted with ethyl acetate, and the organic phase was dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column to give 141 mg of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.15 (1H, dd, J = 8.2, 1.5 Hz), 6.26 (1H, d, J = 8.2 Hz), 7.12 (1H, s), 7.47-7.64 (4H, m), 9.54 (1H, s), 10.85 (1H, s).

Reference Example 8

6-Chloro-N- (3-chloro-1H-indol-7-yl) -3-pyridinesulfonamide (Compound 19) 6-Chloro-3-pyridinesulfonyl chloride was reacted with the product of Example 2 as described in Reference Example 1. in a similar manner to afford 6-chloro-N- (1H-indol-7-yl) -3-pyridinesulfonamide, this product is chlorinated in the same manner as in Reference Example 2 to swallow the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.73 (1H, d, J = 7.7 Hz), 6.97 (1H, dd, J = 7.9, 7.7 Hz), 7.30 (1H, d, J = 7.9 Hz), 7.46 (1H, d, J = 2.6 Hz), 7.67 (1H, d, J = 8.4 Hz), 8, 03 (1H, dd, J = 8.4, 2.6 Hz), 8.62 (1H, d, J = 2.6 Hz), 10.18-10.34 (1H, broad), 11.06 -11.17 (1H, m).

Reference Example 9

6-Chloro-N- (3-cyano-1H-indol-7-yl) -3-pyridinesulfonamide (Compound 20)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.77 (1H, d, J = 7.9 Hz), 7.12 (1H, t, J = 7.9 Hz), 7.50 ( 1H, d, J = 7.9 Hz), 7.72 (1H, d, J = 8.4 Hz), 8.06 (1H, dd, J = 8.4,

2.6Hz), 8.23 (1H, d, J = 2.6Hz), 8.65 (1H, d, J = 2.6Hz), 10.34-10.48 (1H, broad) , 11.98-12.12 (1H, m).

Reference Example 10

N- (3-Chloro-1H-indol-7-yl) -4-sulfamoyl-benzenesulfonamide (Compound 21)

767 mg, 3.0 mmol of the compound prepared in Example 5 are treated with 264 mg, 2.0 mmol of the compound prepared in Example 2 in a similar manner as in Reference Example 1 and the resulting reaction mixture is prepared in a manner similar to that described in Reference Example 1. treated. 445 mg of N- (1H-indol-7-yl) -4-sulfamoyl-benzenesulfonamide are obtained. The product was chlorinated as described in Reference Example 2 to give 349 mg of the title compound.

Melting point: The product begins to partially black at about 220 ° C and decomposes gradually (crystallized from a mixture of ethanol and n-hexane) at about 240 ° C.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.75 (1H, d, J = 7.6 Hz), 6.96 (1H, dd, J = 8.0, 7.6 Hz), 7.29 (1H, d, J = 7.6 Hz), 7.50 (1H, dd, J = 2.8 Hz), 7.58 (2H, s), 7.90-7.98 (4H) , m), 10.23 (1H, s), 11.07 - 11.17 (1H, m).

Reference Example 11

N- (3-Chloro-1H-indol-7-yl) -4- (methylthio) benzenesulfonamide (Compound 22)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.48 (3H, s), 6.82 (1H, dd, J = 7.9, 1.5 Hz), 6.96 (1H, dd) , J = 8, l,

7.5 Hz), 7.25 (1H, dd, J = 7.9, 0.92 Hz), 7.33 (2H, d, J = 8.8 Hz), 7.49 (1H, d, J = 2.7 Hz), 7.62 (2H, d, J = 8.6 Hz), 9.96 (1H, broad s), 1.02 (1H, broad s).

Reference Example 12

4-Acetamido-N- (3-chloro-4-methyl-1H-indol-7-yl) -benzenesulfonamide (Compound 23)

The title compound was prepared in a manner similar to that described in Reference Example 1.

Melting point: The product decomposes gradually at about 225 ° C (recrystallized from ethanol / n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.03 (3H, s), 2.56 (3H, s), 6.54-6.60 (2H, m), 7.33 (1H , d, J = 2.6 Hz), 7.60 (2H, d, J = 9.0 Hz), 7.64 (2H, d, J = 9.0 Hz), 9.63 (1H, broad s), 10.24 (1H, broad s), 10.92 (1H, broad s).

Reference Example 13

4-Cyano-N- (3-cyano-1H-indol-7-yl) -benzenesulfonamide (Compound 24)

The title compound was prepared in a manner similar to that described in Reference Example 1.

250.5-252 ° C (crystallized from ethyl acetate / n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.67 (1H, d, J = 7.7 Hz), 7.05 (1H, t, J = 7.9 Hz), 7.44 ( 1H, d, J = 7.7Hz), 7.78-7.87 (2H, m), 7.97-8.05 (2H, m), 8.16-8.23 (1H, m) , 10.28-10.43 (1 H, broad), 1. 1.92-12.09 (1H, m).

Reference Example 14

N- (4-Bromo-1H-indol-7-yl) -4-nitrobenzenesulfonamide (Compound 25)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d6 δ (ppm): 6.35-6.41 (1H, m), 6.56 (1H, d, J = 8.4 Hz), 7.06 (1H, dd, J = 8.4, 0.8 Hz),

HU 217,842 Β

7.41-7.48 (1H, m), 7.92-8.02 (2H, m), 8.30-8.41 (2H, m), 10.34 (1H, s), 11, 18-11.32 (1H, m).

Reference Example 75

N- (3-Chloro-1H-indol-7-yl) -4- [2- (methylsulfonyl) ethyl] -benzenesulfonamide (Compound 26)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

Melting point: The product begins to discolor at about 181 DEG C., decomposes at 201-203 DEG C. (crystallized from a mixture of ethanol and n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.92 (3H, s), 3.01-3.07 (2H, m), 3.40-3.46 (2H, m), 6.81 (1H, d, J = 7.9 Hz), 6.94 (1H, dd, J = 7.9, 7.7 Hz), 7.24 (1H, d, J = 7.7 Hz) ), 7.45 (2H, d, J = 8.2 Hz), 7.49 (1H, d, J = 2.7 Hz), 7.68 (2H, d, J = 8.2 Hz), 9.99 (1H, broad s), 11.03 (1H, broad s).

Reference Example 16

4-Acetamide-3-chloro-N- (3-chloro-1H-indol-7-yl) -benzenesulfonamide (Compound 27)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.14 (3H, s), 6.77 (1H, d, J = 7.7 Hz), 6.98 (1H, dd, J = 7.9, 7.7 Hz),

7.29 (1H, d, J = 7.9 Hz), 7.50 (1H, d, J = 2.7 Hz), 7.64 (1H, dd, J = 8.6, 2.2 Hz), 7.75 (1H, d, J = 2.2 Hz), 8.04 (1H, d, J = 8.6 Hz), 9.69 (1H, broad s), 10.04 (1H, broad s) ), 11.11 (1H, bs).

Reference Example 17

N- (3-Cyano-1H-indol-7-yl) -8-quinoline sulfonamide (Compound 28)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.68 (1H, d, J = 7.3 Hz), 6.89 (1H, dd, J = 7.9, 7.7 Hz), 7.25 (1H, d, J = 8.1 Hz), 7.69-7.74 (2H, m), 8.21 (1H, d, J = 2.9 Hz),

8.30 (1H, dd, J = 8.2.1.3 Hz), 8.35 (1H, dd, J = 7.4, 1.4 Hz), 8.54 (1H, dd, J = 8, 3, 1.7 Hz), 9.15 (1H, dd, J = 4.3,

1.7 Hz), 10.04 (1H, broad s), 12.14 (1H, broad s).

Reference Example 18

5-Chloro-N- (3-cyano-1H-indol-7-yl) -2-thiophenesulfonamide (Compound 29)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.88 (1H, ddd, J = 7.2, 2.2, 0.73 Hz), 7.16 (1H, dd, J = 7, 9, 7.7 Hz), 7.20 (1H, d, J = 4.0 Hz), 7.36 (1H, d, J = 4.2 Hz),

7.51 (1H, d, J = 8.1 Hz), 8.23 (1H, d, J = 3.1 Hz), 10.42 (1H, broad s), 12.01 (1H, broad s) ).

Reference Example 19

4-Acetyl-N- (3-cyano-1H-indol-7-yl) -benzenesulfonamide (Compound 30)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.60 (3H, s),

6.74 (1H, d, J = 7.7 Hz), 7.05 (1H, dd, J = 7.9, 7.7 Hz),

7.42 (1H, d, J = 7.9 Hz), 7.81-7.88 (2H, m), 8.03-8.10 (2H, m), 8.21 (1H, s) , 10.18-10.50 (1H, broad), 11.92-12.07 (1H, m).

Reference Example 20

N- (3-Chloro-1H-indol-7-yl) -4- (N-methoxy-sulfamoyl) -benzenesulfonamide (Compound 31)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 3.65 (3H, s),

6.73 (1H, d, J = 7.6 Hz), 6.96 (1H, dd, J = 8.0, 7.6 Hz),

7.30 (1H, d, J = 8.0 Hz), 7.50 (1H, d, J = 2.4 Hz), 7.98 (4H, s), 10.29 (1H, broad s) , 10.76 (1H, broad s), 11.12 (1H, broad s).

Reference Example 21

N- (3-Cyano-1H-indol-7-yl) - (β-styrenesulfonamide) (Compound 32)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d 6) δ (ppm): 7.14-7.20 (2H, m), 7.32 (2H, s), 7.35-7.47 (4H, m), δ , 60-7.68 (2H, m), 8.23 (1H, s), 9.70-10.03 (1H, broad), 11.85-12.12 (1H, broad).

Reference Example 22

3-Chloro-N- (3-cyano-1H-indol-7-yl) -2-methyl-benzenesulfonamide (Compound 33)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.61 (3H, s),

6.69 (1H, d, J = 7.7 Hz), 7.04 (1H, t, J = 7.9 Hz), 7.36 (1H, dd, J = 8.1, 7.9 Hz) ), 7.42 (1H, d, J = 7.9 Hz),

7.73 (1H, dd, J = 8.1.1.1 Hz), 7.77 (1H, dd, J = 8.0, 0.82 Hz), 8.25 (1H, d, J = 3, 1 Hz), 10.37 (1H, s), 11.99 (1H, broad s).

Reference Example 23

N- (3-Cyano-1H-indol-7-yl) -2-furansulfonamide (Compound 34)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d 6) δ (ppm): 6.62 (1H, ddd, J = 3.7, 1.8, 0.37 Hz), 6.78 (1H, d, J = 7, 5 Hz), 7.04 (1H, d, J = 3.5 Hz), 7.12 (1H, t, J = 7.9 Hz), 7.49 (1H, d, J = 8.1 Hz) ), 7.99-8.00 (1H, m), 8.23 (1H, d, J = 3.1 Hz), 10.49 (1H, broad s), 12.04 (1H, broad s).

Reference Example 24

N- (3-Methyl-1H-indol-7-yl) -4- (methylsulfonyl) -benzenesulfonamide (Compound 35)

3-Formyl-7-nitro-1H-indole (300 mg, 1.58 mmol) in 25 mL

To a suspension of 2-propanol is added 580 mg, 15.3 mmol of sodium borohydride and 150 mg of 10% palladium-on-carbon. The resulting mixture was refluxed for 6 hours and water was added. The resulting mixture was filtered to remove the catalyst, the filtrate was extracted with ethyl acetate, the organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and dried in vacuo.

The solvent is removed by evaporation. The residue was dissolved in pyridine (5 mL) and treated with 4- (methylsulfonyl) benzenesulfonyl chloride (170 mg, 0.67 mmol) in a similar manner to that described in Reference Example 1. The reaction mixture was treated in the same manner as in Reference Example 1 to obtain 149 mg of the title compound.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.18 (3H, s),

3.24 (3H, s), 6.69 (1H, d, J = 7.7 Hz), 6.81 (1H, t, J = 7.7 Hz), 7.06 (1H, broad s) , 7.25 (1H, d, J = 7.8 Hz),

7.95 (2H, d, J = 8.8 Hz), 8.04 (2H, d, J = 8.2 Hz), 10.14 (1H, broad s), 10.40 (1H, broad s) ).

Reference Example 25

3-Cyano-N- (3-cyano-1H-indol-7-yl) -benzenesulfonamide (Compound 36)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.71 (1H, d, J = 7.2 Hz), 7.09 (1H, dd, J = 8.0, 7.6 Hz), 7.49 (1H, d, J = 8.0 Hz), 7.74 (1H, dd, J = 8.0, 7.6 Hz), 7.94 (1H, d, J = 8.0 Hz) ), 8.11-8.14 (2H, m), 8.23 (1H, d, J = 2.8Hz),

10.30 (1H, broad s), 12.05 (1H, broad s).

Reference Example 26

N- (3-Chloro-1H-indol-7-yl) -4- (N-methyl-methanesulfonamido-benzenesulfonamide (Compound 37)) The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

199-201 ° C (dec.) (Crystallized from ethanol / n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.98 (3H, s),

3.24 (3H, s), 6.83 (1H, dd, J = 7.7, 0.37 Hz), 6.96 (1H, dd, J = 7.9, 7.7 Hz), 7 , 26 (1H, dd, J = 7.9, 0.55 Hz),

7.48 (1H, d, J = 2.7 Hz), 7.50-7.54 (2H, m), 7.72-7.76 (2H, m), 10.04 (1H, broad s) ), 11.02 (1H, broad s).

Reference Example 27

N- (3-Chloro-1H-indol-7-yl) -4 - [(methanesulfonamido) methyl] -benzenesulfonamide (Compound 38)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

Melting point: The product begins to discolor at about 180 ° C, decomposes at 189-191 ° C (recrystallized from a mixture of ethanol and n-hexane).

Ή NMR (DMSO-d _b) δ (ppm): 2.81 (3H, s);

4.19 (2H, d, J = 6.0 Hz), 6.79 (1H, d, J = 7.7 Hz), 6.94 (1H, dd, J = 7.9, 7.7 Hz) ), 7.24 (1H, d, J = 7.9 Hz), 7.47 (2H, d, J = 8.8 Hz), 7.47-7.49 (1H, m), 7.64 (1H, t, J = 6.4Hz), 7.72 (2H, d, J = 8.4Hz), 10.00 (1H, s), 11.03 (1H, broad s).

Reference Example 28

N- (3-Chloro-1H-indol-7-yl) -4- (1-pyrrolidinylsulfonylbenzenesulfonamide (Compound 39))

In a similar manner to that described in Reference Example 1, the title compound was prepared from 4- (1-pyrrolidinylsulfonyl) benzenesulfonyl chloride and the compound prepared in Example 8.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 1.55-1.59 (4H, m), 3.07-3.11 (4H, m), 6.71 (1H, d, J = 7.6 Hz),

6.95 (1H, ddd, J = 8.2, 7.4, 1.2 Hz), 7.30 (1H, d, J = 8.0 Hz), 7.46 (1H, d, J = 2.4 Hz), 7.89 (2H, d, J = 8.8 Hz), 7.92 (2H, d, J = 8.4 Hz), 10.18 (1H, broad s), 11, 03 (1H, bs).

Reference Example 29

N- (3-Cyano-1H-indol-7-yl) -1-methyl-4-imidazole sulfonamide (Compound 40)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 3.61 (3H, s), 7.00 (1H, dd, J = 7.7, 0.92 Hz), 7.07 (1H, dd) , J = 7.9,

7.7 Hz), 7.35 (1H, d, J = 7.9 Hz), 7.75-7.76 (2H, m),

8.19 (1H, d, J = 3.1 Hz), 10.03 (1H, broad s), 11.92 (1H, broad s).

Reference Example 30

N- (3-Cyano-1H-indol-7-yl) -5-methyl-3-pyridinesulfonamide (Compound 41)

The title compound was prepared in a manner similar to that described in Reference Example 1.

Melting point: The product begins to decompose gradually at about 288 ° C (crystallized from a mixture of ethanol and n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.33 (3H, s),

6.75 (1H, d, J = 7.7 Hz), 7.09 (1H, dd, J = 7.9, 7.7 Hz),

7.48 (1H, d, J = 7.9 Hz), 7.87-7.91 (1H, m), 8.22 (1H, d, J = 3.1 Hz), 8.58-8 , 67 (2H, m), 10.28 (1H, bs), 11.95-12.08 (1H, m).

Reference Example 31

N- (3-Chloro-1H-indol-7-yl) -4- (N-methylsulfamoylbenzenesulfonamide [Compound 42]

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.39 (3H, d, J = 5.2 Hz), 6.71 (1H, dd, J = 7.8, 2.0 Hz), 6.96 (1H, dd, J = 8.0, 7.6 Hz), 7.30 (1H, d, J = 8.0 Hz), 7.48 (1H, d, J = 2.8 Hz) ), 7.68 (1H, q, J = 4.9 Hz), 7.87-7.93 (4H, m), 10.20 (1H, broad s), 11.08 (1H, broad s) .

Reference Example 32

N- (3-Chloro-1H-indol-7-yl) -4- [2- (methanesulfonamidophetyl] -benzenesulfonamide (Compound 43). The title compound was prepared in a similar manner as described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.73-2.81 (5H, m), 3.13-3.19 (2H, m), 6.82 (1H, d, 1 = 1, Ί Hz),

6.95 (1H, dd, J = 8.1.1.7 Hz), 7.09 (1H, t, J = 5.9 Hz),

7.24 (1H, d, J = 8.1 Hz), 7.39 (2H, d, J = 8.2 Hz),

7.48 (1H, d, J = 2.7 Hz), 7.68 (2H, d, J = 8.4 Hz), 9.97 (1H, broad s), 11.02 (1H, broad s) ).

Reference Example 33

5-Bromo-N- (3-cyano-1H-indol-7-yl) -2-pyridinesulfonamide (Compound 44)

The title compound was prepared in a manner similar to that described in Reference Example 1. The products are melting8

245.5-246.5 ° C (dec.) (Crystallized from ethyl acetate / n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.82 (1H, d, J = 7.7 Hz), 7.07 (1H, dd, J = 7.9, 7.7 Hz), 7.44 (1H, d, J = 7.9 Hz), 7.80 (1H, d, J = 8.2 Hz), 8.23 (1H, d, J = 2.2 Hz), 8, 29 (1H, dd, J = 8.2, 2.2 Hz), 8.92 (1H, d, J = 2.2 Hz), 10.42-10.67 (1H, broad), 11.93 -2.08 (1H, m).

Reference Example 34

N- (3-Cyano-1H-indol-7-yl) -2-naphthalenesulfonamide (Compound 45)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 6.74 (1H, dd, J = 7.6, 2.8 Hz), 7.00 (1H, dd, J = 7.9, 7, 7Hz), 7.39 (1H, dd, J = 8.0, 0.46Hz), 7.61-7.72 (2H, m), 7.80 (1H, dd, J = 8.6 , 1.8 Hz), 8.01 (1H, d, J = 8.1 Hz), 8.08 (1H, s), 8.10 (1H, s), 8.21 (1H, dd, J) = 2.9 Hz), 8.34 (1H, d, J = 1.6 Hz), 10.23 (1H, broad s), 12.01 (1H, broad s).

Reference Example 35

4-Amino-N- (5-bromo-3-cyano-1H-indol-7-yl) -benzenesulfonamide (Compound 46) from 4-Nitrobenzenesulfonyl chloride and Example 11 in Reference Example 1 N- (5-bromo-3-cyano-1H-indol-7-yl) -4-nitrobenzenesulfonamide prepared in a similar manner as described above is hydrogenated in the presence of a platinum oxide catalyst at normal temperature and atmospheric pressure to give the title compound.

1 H-NMR (DMSO-d 6) δ (ppm): 6.07 (2H, bs),

6.52 (2H, d, J = 8.4 Hz), 6.97-6.99 (1H, m), 7.36 (2H, dd, J = 8.7, 1.6 Hz), 7 , 51 (1H, broad s), 8.25 (1H, s), 9.93 (1H, d, J = 5.5 Hz), 11.97 (1H, broad s).

Reference Example 36

N- (3-Chloro-1H-indol-7-yl) -4- (N-ethylsulfamoyl) -benzenesulfonamide (Compound 47)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2. M.p. 213-215 ° C (crystallized from ethanol / n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 0.90 (3H, t, J = 7.2Hz), 2.76 (2H, dq, Jd = 5.8Hz, Jq = 7.2 Hz);

6.70 (1H, d, J = 7.4 Hz), 6.95 (1H, dd, J = 8.0, 7.6 Hz), 7.29 (1H, d, J = 8.0 Hz), 7.47 (1H, d, J = 2.8 Hz), 7.78 (1H, t, J = 5.6 Hz), 7.90 (4H, s), 10.18 (1H, broad s) , 11.06 (1H, broad s).

Reference Example 37

N- (3-Chloro-1H-indol-7-yl) -4- (N, N-dimethylsulfamoyl) -benzenesulfonamide (Compound 48)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.57 (6H, s),

6.71 (1H, dd, J = 7.4, 0.6 Hz), 6.97 (1H, dd, J = 8.0,

7.6 Hz), 7.31 (1H, d, J = 8.0 Hz), 7.47 (1H, d, J = 2.8 Hz), 7.86 (2H, d, J = 8, 4 Hz), 7.91 (2H, d, J = 8.4 Hz),

10.19 (1H, broad s), 11.04 (1H, broad s).

Reference Example 38

N- (3-Chloro-1H-indol-7-yl) -4- (1-pyrrolidinylcarbonite) -benzenesulfonamide (Compound 49)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 1.79 (2H, dt, Jd = 12.8 Hz, Jt = 6.4 Hz), 1.85 (2H, dt, Jd = 13.6 Hz, Jt = 6.8 Hz), 3.22 (2H, t, J = 6.4 Hz), 3.44 (2H, t, J = 6.8 Hz), 6.78 (1H, d, J = 7.2 Hz), 6.96 (1H, dd, J = 8.0, 7.2 Hz), 7.28 (1H, d, J = 8.0 Hz), 7.47 (1H, d, J = 2.4 Hz, 7.60 (2H, d, J = 8.0 Hz), 7.74 (2H, d, J = 8.4 Hz), 10.06 (1H, broad s) ), 11.01 (1H, broad s).

Reference Example 39

N- (3,4-Dichloro-1H-indol-7-yl) -4- (sulfamoylmethyl) -benzenesulfonamide (Compound 50)

The title compound was prepared in a manner similar to that described in Reference Example 1. Melting point: The product begins to decompose gradually at about 297 ° C (crystallized from ethanol / n-hexane).

1 H-NMR (DMSO-d ₆ ) δ (ppm): 4.34 (2H, s),

6.72 (1H, d, J = 8.1 Hz), 6.93 (2H, s), 6.94 (1H, d, J = 8.1 Hz), 7.51 (2H, d, J = 8.1 Hz), 7.57 (1H, dd, J = 2.7, 0.55 Hz), 7.75 (2H, d, J = 8.2 Hz), 10.10 (1H, broad s), 11.44 (1H, broad s).

Reference Example 40

N- (3-Cyano-1H-indol-7-yl) -4- [2- (methylsulfonyl) ethyl] -benzenesulfonamide (Compound 51)

The title compound was prepared in a manner similar to that described in Reference Example 1.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.94 (3H, s), 3.03-3.08 (2H, m), 3.42-3.47 (2H, m), δ , 77 (1H, dd, J = 7.7, 0.37 Hz), 7.05 (1H, t, J = 7.9 Hz), 7.41 (1H, d, J = 8.1 Hz) , 7.46 (2H, d, J = 8.2 Hz), 7.66 (2H, d, J = 8.2 Hz), 8.20 (1H, s), 10.09 (1H, broad s) ), 1.92 (1H, bs).

Reference Example 41

N- (3-Chloro-1H-indol-7-yl) -4- (N-methylacetamido) benzenesulfonamide (Compound 52)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 1.84 (3H, bs), 3.16 (3H, s), 6.81 (1H, d, J = 7.7 Hz), δ , 96 (1H, dd, J = 8.0, 7.6 Hz), 7.27 (1H, d, J = 7.9 Hz), 7.45-7.49 (2H, m), 7, 47 (1H, d, J = 2.7 Hz), 7.70-7.75 (2H, m), 10.02 (1H, broad s), 11.01 (1H, broad s).

Reference Example 42

N- (3-Chloro-1H-indol-7-yl) -4- [2- (N-methyl-methanesulfonamido) -ethyl] -benzenesulfonamide (Compound 53)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2.

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.69 (3H, s),

2.76 (3H, s), 2.86 (2H, t, J = 7.5 Hz), 3.26 (2H, t, J = 7.5 Hz), 6.78 (1H, dd, J) = 7.4, 0.55 Hz), 6.94 (1H, t, J = 7.7 Hz), 7.24 (1H, dd, J = 7.7, 0.37 Hz), 7.39 (2H, d,

HU 217,842 Β

J = 8.2 Hz), 7.48 (1H, d, J = 2.6 Hz), 7.66 (2H, d, J = 8.2 Hz), 9.94 (1H, broad s), 11.02 (1H, broad s).

Reference Example 43

N- (3-Chloro-1H-indol-7-yl) -4 - [(N-methylmethanesulfone-5-amido) methyl] -benzenesulfonamide (Compound 54)

The title compound was prepared in a manner similar to that described in Reference Examples 1 and 2. 200.5-202 ° C (crystallized from ethanol). 10

1 H-NMR (DMSO-d ₆ ) δ (ppm): 2.63 (3H, s),

2.94 (3H, s), 4.27 (2H, s), 6.80 (1H, d, J = 7.3 Hz),

6.95 (1H, dd, J = 8.1.1 7.5 Hz), 7.25 (1H, d, J = 7.9 Hz),

7.45 (2H, d, J = 8.2 Hz), 7.47 (1H, d, J = 2.7 Hz)

7.74 (2H, d, J = 8.2 Hz), 10.00 (1H, s), 11.00 (1H, broad s).

Claims (1)

Patent Claim Point The 7-amino-1H-indole derivatives of the general formula (IIIa): wherein G is hydrogen, halogen or cyano, Q is halogen or methyl, and t is an integer equal to 0 or 1.