RU2045524C1 - Indole derivatives or their pharmaceutically acceptable salts or solvates - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: product: compounds showing 5HT₁-like receptor antagonistic activity. Derivatives of indoles of the general formula (I)

where R₁ and R₂ hydrogen or C_1-4-alkyl; R₃ hydrogen or C_1-3-alkyl, or their pharmaceutically acceptable salts or solvates. EFFECT: improved method of synthesis. 11 cl

Description

I где R₁ водород или C_1-4-алкил;
R₂ водород или С_1-4-алкил;
R₃ водород или С_1-3-алкил,
или их фармацевтически приемлемый солям, или сольватам, обладающий 5НТ₁-подобной рецепторной антагонистической активностью.The invention relates to new derivatives of indole of the General formula

I where R _{1 is} hydrogen or C _1-4 alkyl;
R _{2 is} hydrogen or C _1-4 alkyl;
R ₃ hydrogen or C _1-3 -alkyl,
or their pharmaceutically acceptable salts or solvates having 5HT ₁ -like receptor antagonistic activity.

Selective 5HT ₁ -like receptor antagonistic activity and selective vasoconstrictor activity of compounds I were demonstrated in vitro. In addition, these compounds selectively narrow the carotid arterial bed in anesthetized dogs, with virtually no effect on blood pressure.

 After non-parenteral, including intraduodenal, administration of compounds I, they exhibit an increased bioavailability index.

Determination of the EC ₅₀ value and the equipotential concentration ratio of the EC ₅₀ value (the molar concentration of the compound is necessary to achieve 50% of its maximum effect) and the equipotential concentration ratio with 5-hydroxytryptamine (5HT) were determined for compounds of this invention with a 5HT ₁ -like receptor associated with isolated saphenous vein of a dog according to a well-known method.

 Compounds I did not significantly affect the blood pressure or pulse of anesthetized beagles at doses of 0.3 mg / kg iv.

 The compound of example 1 at a dose of 10 mg / kg of weight intravenously does not have a side effect in rats.

 For comparison, the compound of the known example was taken (see GB Patent No. 2,124,210, Example 26). The bioactivity of this compound upon intraduodenal administration (I.D.) of an anesthetized dog was measured and compared with the compounds of this invention. The results are shown in table. 2.

 Test data clearly show that the bioactivity index is higher for the compounds of this invention relative to the known compounds.

 The intermediate compound 1.

 N-methyl-3- (1,2,3,6-tetrahydro-1-methyl-4-pyridinyl) -1H-indole-5-ethanesulfonamidoxalate.

A solution of N-methyl-1H-indole-5-ethanesulfonamide (1.0 g) in methanol (50 ml) containing potassium hydroxide (5.6 g) and N-methyl-4-piperidone (1.0 ml) are heated at refluxing for 24 h, cool and the resulting solid product is filtered off (1.0 g). A solid sample (0.2 g) was dissolved in a hot methanol solution of oxalic acid (0.06 g), the solution was cooled and the resulting salt precipitated by adding ethyl acetate (20 ml) and dry ether (50 ml). This salt is filtered off and dried in vacuo to give the title compound as a solid (0.12 g), mp. 87-90 ^about C (with shrinkage).

Elemental analysis for C ₁₇ H ₂₃ N ₃ O ₂ S ˙ ˙ C ₂ H ₂ O ₄ ˙ 0.6H ₂ O:
Found, C, 52.2; H 5.6; N 9.5
Calculated, C 52.5; H 6.0; N, 9.7.

 Intermediate 2.

 5-bromo-3- (1-methyl-4-piperidinyl) -1H-indole.

A mixture of 5-bromoindole (39.2 g), N-methyl-4-piperidone (25.0 g) and potassium hydroxide tablets (12.0 g) in methanol (9250 ml) was stirred and heated under reflux for 17 h, and then cooled to 5 ^about With stirring. The resulting mixture was filtered. The residue was washed successively with methanol, water, methanol again and ether and dried in vacuo to give the intermediate tetrahydropyridine (43.3 g) as a powder (m.p. 256-261 ^C) which was used without further characterization in the next step. A solution of ethanol hydrogen chloride was prepared by adding acetyl chloride (20 ml) to ice-cooled stirred ethanol (1.31). Intermediate tetrahydropyridine (43.2 g) was dissolved in a portion (0.95 L) of this solution. The hydrochloride salt of the intermediate precipitates. In order to redissolve this salt, the suspension is heated in a steam bath and a 2N portion is added. hydrochloric acid (10 ml), water (15 ml) and concentrated (11n) hydrochloric acid (10 ml). The resulting solution was added to a pre-hydrogenated suspension of 5% platinum oxide on carbon (7.0 g) in an ethanolic HCl solution (0.35 L of the above solution) and the resulting mixture was hydrogenated at room temperature and atmospheric pressure until the absorption of hydrogen ceased. The resulting mixture was filtered and the solvent was evaporated. The residue was resuspended in ethyl acetate (600 ml). Sodium carbonate (2N, 350 ml) was added with stirring, and the resulting mixture was filtered. The residue was washed with water and ethyl acetate and dried in vacuo to give the title compound (33.4 g) as a powder, mp. 160-165 ^about S.

 Intermediate 3.

 5-bromo-3- (1,2,3,6-tetrahydro-1- (phenylmethyl) -4-pyridinyl) -1H-indole.

Freshly distilled 1-benzyl-4-piperidone (11.7 g) was added to a stirred solution of 5-bromoindole (11.0 g) and 2M potassium hydroxide in methanol (81 ml). The resulting mixture was stirred at reflux for 8 hours and then allowed to cool ^to 25 ° C for 8 hours The solid was collected by filtration, washed with a mixture of methanol and water (2: 1, 2 x 15 mL). And dried under vacuum at 50 ° ^C. for 18 hours to give the title compound as a crystalline solid (18.6 g). Mp 173-175 ^about C (with decomposition).

Intermediate 4
5-bromo-3- [1- (phenylmethyl) -4-piperidinyl] -1H-indole
A solution of intermediate 3 (4.00 g) in ethanolic hydrogen chloride (330 ml), obtained by adding acetyl chloride (1.65 ml) to ethanol (250 ml) with stirring, is hydrogenated over 5% platinum on charcoal (3.0 g ) at room temperature and atmospheric pressure until hydrogenation is complete. The catalyst is removed by filtration. The solid was washed with ethanol (15 ml) and the combined filtrates were evaporated to an oily residue. The residue was partitioned between 2M aqueous sodium carbonate (75 ml) and ethyl acetate (175 ml), the phases were separated and the aqueous layer was again extracted with ethyl acetate (100 ml). The combined organic layers were then washed with water (50 ml), extracted with saturated brine (50 ml), dried over anhydrous magnesium sulfate and the solvent was evaporated to give the title compound as an oil (3.3 g). TLC on SiO ₂ CH ₂ Cl ₂ : EtOH: 0.88 NH ₃ (100: 8: 1) Rg 0.44.

 PRI me R 1. N-methyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfornamide.

Intermediate 1 (free base) (0.36 g, 0.001 mol) in absolute alcohol (70 ml) and anhydrous dimethylformamide (5 ml) is hydrogenated in the presence of 5% palladium on activated carbon (0.36 g) at room temperature and atmospheric pressure. After 20 hours, the absorption of hydrogen (25 cm ³ , theoretically 24 cm ³ ) ceases. The catalyst is filtered off and the solvent is removed in vacuo to give an opaque resin, which cures as a soft white solid (0.3 g). After purification by flash chromatography (SorbSil C60 silica gel, CH ₂ C _l2 (EtOH) 0.88 ammonia 50: 80: 1), a colorless oil (0.21 g) is obtained, which is triturated with ether to give the title compound (0.17 g), melting point 156-158 ^° C TLC SiO _2. (CH ₂ Cl _2: EtOH: 0,88 ammonia 50: 8: 1)
Rf 0.4; detection by UV, 1RA.

 Determination of water: found 0.12% w / w. 0.02 mol. Equiv.

Elemental analysis for C ₁₇ H ₂₅ N ₃ O ₂ S ˙ ˙ O ˙ O2H ₂ O
Calculated C 60.8; H 7.5; N 12.5
Found, C, 60.5; H 7.3; N 12.1
PRI me R 2. N-methyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide (i) (E (N-methyl-2-] 3- (1-methyl -4-piperidinyl) -1H-indol-5-yl] ethenesulfonamide.

A mixture of intermediate 2 (1.00 g) N-methylethanesulfonamide (530 mg), tri-ortho-tolylphosphine (300 mg), palladium acetate (50 ml) and triethylamine (730 ml) in dry acetonitrile (added to bring the entire volume to 10 ml) was stirred and heated in a sealed tube at ¹²⁰ ° C for 1.25 hours and then at ⁸⁰ ° C for 16 h. the reaction was repeated in the same volume of 10 times. In each case the sealed vial was heated at 100-110 ^C for 3.5 hours. The sealed ampoule was cooled, the contents were combined and the solvent was evaporated. The residue was chromatographed on silica gel (450 g) using a mixture of dichloromethane, ethanol and ammonia (at the beginning of 80: 80: 1, gradually increasing the polarity to 65: 8: 1). The fractions containing the product are combined and evaporated to obtain a semi-solid. It is quickly triturated in a mixture of cyclohexane and ethyl acetate (1: 1, 100 ml) to obtain a solid product, which is filtered and dried to obtain the title compound (6.85 g) in the form of a powder, so pl. 190-192 ^about S.

 (ii) N-methyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide.

A solution of the product from step (i) (5.78 g) in a mixture of ethanol hydrogen chloride obtained by adding acetyl chloride (1.71 g, 21.8 mmol) to 1MS ethanol (400 ml) with stirring, and dimethylformamide (300 ml) , added to the above to dissolve the starting material, is hydrogenated at room temperature and atmospheric pressure using 10% palladium-carbon (5.00 g, 50% w / w with water) as a catalyst until the absorption of hydrogen ceases. The resulting mixture was filtered and the resulting filtrate was evaporated to obtain a solid product. This solid was partitioned between 2N sodium carbonate (60 ml) and ethyl acetate (200 ml), and the resulting mixture was heated until the solid was dissolved. The phases are separated, the aqueous phase is extracted with ethyl acetate (200 ml) and the combined organic phases are washed with saturated brine (100 ml), dried over anhydrous sodium sulfate and evaporated to give a gum. This resin was crystallized from ethyl acetate (60 ml) to give the title compound (4.30 g) as crystals with mp. 170-171 ^about S.

Elemental analysis for C ₁₇ H ₂₅ N ₃ O ₂ S:
Calculated C 60.9; H 7.5; N 12.5
Found, C, 60.9; H 7.6; N, 12.4
PRI me R 3. N-methyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide.

A solution of 4-hydrazino-N-methyl-benzeneethanesulfonamide (0.5 g) and 1-methyl-4-piperidine acetaldehyde (0.35 g) in a mixture of water (10 ml) and 2N. hydrochloric acid (1.0 ml, 2.00 mmol) was stirred for 2 days at room temperature. The next portion of the aldehyde (0.35 g) was added and stirring was continued for another 30 minutes. The resulting solution was then basified with 8% sodium bicarbonate to pH 8 and extracted with chloroform (3 x 50 ml). The combined organic extracts were dried (Na ₂ SO ₄ ) and evaporated in vacuo to give the crude hydrazone as an oil (1.0 g). A solution of hydrazone (1.0 g) in chloroform (20 ml) containing a polyphosphate ester (10 g) was heated under reflux for 8 minutes. This solution was poured onto ice (200 g), stirred for 2 hours, treated with 2M sodium carbonate (20 ml) and extracted with chloroform (3 x 50 ml).

The combined organic extracts were dried (Na ₂ SO ₄ ), evaporated in vacuo and the residue was purified by flash chromatography (silica 9385, 100 g), eluting with CH ₂ Cl ₂ : EtOH: NH ₃ (75: 8: 1) to obtaining impure material in the form of a yellow oil. Repeated chromatography with flash evaporation (9385 silicon dioxide, 100 g) and elution with CH ₂ Cl ₂ : EtOH: NH ₃ (100: 8: 1) gave the product as an oil (0.05 g). This was crystallized from ethyl acetate to give the title compound as a solid, mp. 156-157 ° ^C. The melting

TLC SiO ₂ , CH ₂ Cl ₂ : EtOH: NH ₃ (50: 8: 1)
R _f 0.6
PRI me R 4. N, N-dimethyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide.

Sodium hydride (60% w / w with paraffin) was carefully added to a stirred solution of the product of Example 1 in dry dimethylformamide (20 ml). The resulting mixture was stirred at room temperature in a nitrogen atmosphere for 0.25 hours, then a solution of methyl iodide (440 mg) in dry dimethylformamide (1 ml) was added to the stream. The resulting mixture was stirred at room temperature for 2.5 hours. The reaction mixture was quenched with water (3 ml), evaporated in vacuo, and the residue was chromatographed on silica (150 g), eluted with dichloromethane, ethanol and ammonia (80: 10: 1) to receiving resin. This resin was quickly triturated in diethyl ether and the title compound was crystallized in powder form (238 mg), mp. 170-172 ^about S.

TLC SiO ₂ (CH ₂ Cl ₂ : EtOH: NH ₃ 50: 8: 1)
R _f 0.57.

 PRI me R 5.

(i) (E) -N, N-dimethyl-2- [3- (1-methyl-4-piperidinyl) -1H-indol-5-yl] etensulfonamide
A mixture of 5-bromo-3- (1-methyl-4-piperidinyl) -1H-indole (2.0 g), N, N-dimethylethanesulfonamide (1.184 g), tri-ortho-tolylphosphine (0.6 g), acetate palladium (0.1 g), triethylamine (1.0 ml) and anhydrous acetonitrile (12 ml) was heated in two 10-mm sealed ampoules under stirring at 107 ^C (oil bath temperature) for 2.25 h. The reaction mixture was combine, the solvent is removed on a rotary evaporator and the foam residue is purified by chromatography, eluting with a mixture of dichloromethane, ethanol, 0.88 ammonia (100: 80: 1). As a result of rotary evaporation of the appropriate fractions, the product is obtained in the form of a foam (1.92 g) TLC SiO ₂ (isopropanol ethanol water 0.88 ammonia, 20: 20: 8: 1).

R _f (primary) + 0.55 (smaller) + 0.4 (traces).

 (ii) N, N-dimethyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide.

A solution of the product from step (i) (5 g) in 200 ml of ethanol is added to a suspension of 5% palladium on activated carbon (1.5 g) in ethanol (100 ml). The resulting mixture was hydrogenated at 65 psi at room temperature for 17 hours. The mixture was filtered and the resulting filtrate was evaporated, leaving a solid product (1.0 g), which was washed with isopropanol (3 x 20 ml) to obtain a solid product (0.8 g) t. melting point 215-225 ° ^C.

After crystallization from hot ethanol (60 ml), the title compound is obtained in the form of microneedles (0.29 g), so pl. 228-232 ^about S.

TLC SiO ₂ (isopropanol ether water 0.88 ammonia, 20: 20: 8: 1)
R _f 0.5.

PRI me R 6. 3- (1-methyl-4-piperidinyl) 1H-indole-5-ethanesulfonamide
(i) (E) -2- [3- (1-methyl-4-piperidinyl) -1H-indol-5-yl] ethenesulfonamide.

A mixture of intermediate 2 (2.0 g), vinyl sulfonamide (0.88 g) palladium acetate (100 mg), tri (ortho-tolyl) phosphine (0.60 g), triethylamine (1.0 g) and acetonitrile (14 ml) was divided into two equal portions and placed into two sealed ampoules (10 ml) and heated at ¹⁰⁰ ° C for 4 hours. to each vial was added an additional amount vinilsulfonamida (0.22 g) and the resulting mixture was heated at ¹⁰⁰ ° C for an additional 16 hrs. The resulting mixture was evaporated to dryness in vacuo and the residue was purified by chromatography (silica 9385, 400g) eluting with CH ₂ Cl: EtOH: NH ₃ (100: 8: 1) to yield the s Chapter compound as a solid (0.8 g) m.p. 208-209 ^about S.

 (ii) 3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide.

A mixture of the product from step (i) (0.8 g) in ethanol hydrogen chloride (80 ml) is hydrogenated over pre-reduced palladium on charcoal (50% paste with water, 0.8 g) until the consumption of hydrogen ceases. The catalyst was filtered off, washed with hot ethanol (50 ml) and the filtrate was evaporated in vacuo to give a crude material (0.15 g). Then the crystalline residue is heated to 70 ^about With 2 N. hydrochloric acid (200 ml), filtered and the resulting filtrate was evaporated to dryness in vacuo (azeotropic distillation with toluene). The residue was combined with the crude product obtained previously and purified by flash chromatography (silica 9385, 100 g), eluting with CH ₂ Cl ₂ : EtOH: NH ₃ (50: 8: 1) to give the title compound as a solid (0.3 g) mp more than 95 ^° C (foaming).

TLC SiO ₂ (CH ₂ Cl ₂ : EtOH: NH ₃ , 25: 8: 1)
Rf 0.5.

 Example 7. N-methyl-3- (4-piperidinyl) -1H-indole-5-ethanesulfonamide hydrochloride.

 (i) (E) -N-methyl-2 [3- (1- (phenylmethyl) -4-piperidinyl] -1H-indol-5-yl] etensulfonamide.

In each of the three sealed ampoules, a mixture of intermediate 4 (1.10 g), N-methyl-ethenesulfonamide (422 mg), triethylamine (843 μl), tri-ortho-tolylphosphine (242 mg) and palladium acetate (39 mg) dry acetonitrile (volume adjusted to 10 ml) was stirred and heated at ¹⁰⁰ ° C for 4 hours. After cooling ^to 25 ° the contents of ampoules were combined, and the solvent was evaporated in vacuo at 40 ^C to give an oily residue.

 This residue was purified by silica gel column chromatography (Merok 7229, 300 g), eluting with a mixture of dichloromethane, ethanol, 0.88 ammonia (300: 8: 1 to 200: 8: 1 to 100: 8: 1). The appropriate fractions were combined and the solvent was evaporated in vacuo to give the title compound as a foam (2.14 g).

TLC SiO ₂ (CH ₂ Cl ₂ : EtOH: 0.88 NH ₃ , 200: 8: 1)
R _f 0.41
(ii) N-methyl-3- (4-piperidinyl) -1H-indole-5-ethanesulfonamide, hydrochloride.

A solution of the product from step (i) (2.14 g) in ethanol hydrogen chloride (350 ml, obtained by adding acetyl chloride (860 g) to ethanol (350 ml) with stirring, is hydrogenated over 10% palladium on charcoal previously reduced (6, 4 g) at ²⁵ ° C and 1 atm for 18 h. The reaction mixture was purged with nitrogen and the solution was added ammonium formate (8.2 g) in methanol (100 ml). The resulting mixture was stirred and brought to reflux under a nitrogen atmosphere for 10 min, cooled ^to 25 ° C, and then the catalyst was removed by filtration. Pos evaporation of the filtrate in vacuo gives a solid residue (8.5 g), which is again dissolved in water (75 ml) and saturated with solid sodium chloride.The precipitate formed is filtered off, washed with ice water (1.5 ml) and ether (10 ml) and dried in vacuo at ⁴⁵ ° C for 18 hours to give the title compound as a crystalline solid (640 mg), m.p. 253-255 ° ^C.

TLC SiO ₂ (CH ₂ Cl ₂ : EtOH: 0.88 NH ₃ 25: 8: 1)
R _f 0.14.

 PRI me R 8. N-ethyl-3- (4-piperidinyl) -1H-indole-5-ethanesulfonamide.

 (i) (E) -N-ethyl-2- [3- (1- (phenylmethyl) -4-piperidinyl] -1H-indol-5-yl] etensulfonamide.

Acetate plates (50 ml), tri-ortho-tolylphosphine (300 ml), triethylamine (650 mg), N-ethyl ethylene sulfonamide (275 mg) and intermediate 4 (710 mg) were placed in each of two 10 ml sealed ampoules. Each mixture was adjusted to 110 L with dry acetonitrile. The vials heated at 100 ^C for 16 hours, then left at room temperature for 4 days. The contents of the sealed ampoules are combined, and the solvent and triethylamine are removed in vacuo. The residue was chromatographed on silica (205 mg, merck 9385), eluting with dichloromethane, ethanol and ammonia (100: 8: 1) to give a foamy substance (759 mg). This foam is crystallized from a hot mixture of ethyl acetate and cyclohexane to give the title compound (582 mg) as microcrystals, mp. 178-180 ^about S.

 (ii) N-ethyl-3- (4-piperidinyl) -1H-indole-5-ethanesulfonamide.

A solution of the product from step (i) (370 mg) in ethanol hydrogen chloride, obtained by adding acetyl chloride (105 g, 1.34 mmol) to 1MS ethanol (50 ml) with stirring, is hydrogenated over pre-reduced 10% palladium oxide on coal (50% w / w with H ₂ O; 1.13 g), at room temperature and atmospheric pressure, until the flow of hydrogen ceases. The resulting mixture was filtered and the resulting filtrate was evaporated to a foam (280 mg), which was dissolved in methanol (4 ml). Sodium carbonate (2N. 1 ml) was added and the solvent was evaporated. The residue was partitioned between water (10 ml) and ethyl acetate (50 ml). The aqueous phase was extracted with ethyl acetate (50 ml) and the combined organic fractions were dried (Na ₂ SO ₄ ) and evaporated to give a gum (235 mg), which crystallized from a mixture of ethyl acetate and ether (10 ml, mainly ethyl acetate) to obtain the title compound connection (104 mg) in the form of a powder, so pl. 95-100 ^about C.

TLC SiO ₂ (CH ₂ Cl ₂ : EtOH: NH ₃ , 25: 5: 1)
R _f 0.3.

 PRI me R 9. N-methyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide, hydrochloride.

A solution of the product of example 1 (50 mg) in hot ethanol (0.5 ml) was added to ethanol chloride in hydrogen obtained by adding acetyl chloride (33 mg, 0.420 mmol) to ethanol (1 ml) at room temperature under stirring at room temperature temperature. The solid product crystallizes out of the initially clear solution. The resulting suspension was stirred and cooled ^to 5 ° C for 15 minutes, then filtered with suction. The residue was washed with a little ethanol, then dried at 60 ° ^C in vacuo for 1 h to afford the title compound (44mg) as microcrystals, m.p. 237-239 ^about S.

TLC SiO ₂ (CH ₂ Cl ₂ : EtOH: NH ₃ , 50: 8: 1)
R _f 0.45.

Claims (12)

Indole derivatives of the general formula

where R ₁ and R ₂ hydrogen or C ₁ C ₄ -alkyl;
R ₃ hydrogen or C ₁ C ₃ -alkyl,
or their pharmaceutically acceptable salts or solvates. 2. Derivatives of indole according to claim 1, where R ₁ hydrogen or C ₁ C ₃ -alkyl. 3. Indole derivatives according to claim 1 or 2, where R _{2 is} hydrogen or C ₁ - C ₃ -alkyl. 4. Derivatives of indole according to claims 1 to 3, where R ₂ C ₁ C ₃ -alkyl. 5. Indole derivatives according to claims 1 to 4, where R ₃ means C ₁ C ₃ -alkyl.  6. The indole derivatives according to claim 1, which is N-methyl-3- (1-methyl-4- -piperidinyl) -1H-indole-5-ethanesulfonamide or its pharmaceutically acceptable salts or solvates.  7. The indole derivative according to claim 1, which is N, N-dimethyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide or its pharmaceutically acceptable salts or solvates.  8. The indole derivative according to claim 1, which is N-ethyl-3- (4-piperidinyl) -1H-indole-5-ethanesulfonamide or its pharmaceutically acceptable salts or solvates.  9. The indole derivative according to claim 1, which is N-methyl-3- (4-piperidinyl) -1H-indole-5-ethanesulfonamide or its pharmaceutically acceptable salts or solvates.  10. The indole derivative according to claim 1, which is 3- (1-methyl-4-piperidinyl) 1H-indole-5-ethanesulfonamide or a pharmaceutically acceptable salt or solvate thereof. 11. The derivative of indole according to claim 1, showing the activity of agonists of 5-HT ₁ -like recipes. Priority by signs:
06/14/88 all the values of the radicals R ₁ R ₃ .  06/17/88 N-methyl-3- (1-methyl-4-piperidinyl) -1H-indole-5-ethanesulfonamide.

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