JPS6242897B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides substitutions represented by the following general formula ()
This invention relates to dl-4,5,6,7-tetrahydro-2H-benzo[c]pyrroles and pharmaceutically acceptable acid addition salts thereof. (In the formula, R ¹ is hydrogen or R ² ; Am is N
(R ² ) ₂ and R ² is independently methyl, ethyl or propyl. ) A compound of formula () is a compound of formula () dl-5-amino-4,5,6,7-
A tetrahydro-2H-benzo[c]pyrrole compound can be reacted with an aldehyde and then reduced with a metal hydride or reacted with an alkyl halide and then an acyl halide and then reduced with a metal hydride to form the formula ( ) in which R ¹ is hydrogen and Am is N(R ² ) ₂ , the latter is further reacted with an alkyl halide and a base,
In formula (), R ¹ is R ² and Am is N(R ² ) ₂
It is produced by obtaining a compound that is. Compounds of formula () are useful as dopamine agonists, including for use in the treatment of Parkinson's syndrome, and as prolactin inhibitors. Furthermore, the compound represented by the following general formula (A) and its acid addition salt when Am is amino are useful as new intermediates. (wherein R ¹ is hydrogen or R ³ —CO; Am
is amino or NH—CO—R ³ ; R ³ is methyl, ethyl or propyl. However, Am
is amino, R ¹ is not R ³ —CO. ) Pharmaceutically acceptable acid addition salts of compounds represented by formulas () and (A) include hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc. salts derived from non-toxic inorganic acids and non-toxic organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids and alkanedioic acids, fuaromatic acids, aliphatic and aromatic sulfonic acids. Contains salts derived from. Accordingly, the above pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, methaline acid salts, pyrophosphates, hydrochlorides, hydrobromides, hydroiodides,
Hydrofluoride, Acetate, Propionate, Decanoate, Caprate, Acrylate, Formate, Isobutyrate, Caproate, Heptanoate,
Propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, butine.
1,4-dioutschate, hexyne-1,6-dioutschate, benzoate, chlorbenzoate,
Methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorbenzenesulfonate, toluenesulfonate, chloro Benzene sulfonate, xylene sulfonate, phenyl acetate, phenyl propionate, phenyl butyrate,
Citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, etc. This includes: The acid addition salt of the intermediate represented by formula (A) is
Since the main purpose is the isolation and purification of the intermediate in question, it is not limited to salts formed with the above-mentioned non-toxic anions. Examples of compounds falling within the range represented by formula () include dl-5-dimethylamino-4,5,6,7,-
Tetrahydro-2H-benzo[c]pyrrole methanesulfonate; dl-2-methyl-5-diethylamino-4,
5,6,7-tetrahydro-2H-benzo [c]
Pyrrole maleate; dl-2-ethyl-5-dipropylamino-4,
5,6,7-tetrahydro-2H-benzo [c]
Pyrrole hydrochloride; N,N,2-trimethyl-dl-5-amino-4,
5,6,7-tetrahydro-2H-benzo [c]
Pyrrole; N-methyl-N-ethyl-dl-5-amino-
4,5,6,7-tetrahydro-2H-benzo[c]pyrrole; N-methyl-N-propyl-dl-2-methyl-
5-amino-4,5,6,7-tetrahydro-
2H-benzo[c]pyrrole; Here, the compound represented by the formula () is 4,
It is named as 5,6,7-tetrahydro-2Hbenzo[c]pyrrole, but there are also 4,5,
It can also be named as 6,7-tetrahydroisoindole. The presence of a substituent at the 5-position of this benzo[c]pyrrole or isoindole ring creates an indiscreet center in these molecules. Therefore, the compound of formula () will include two optical isomers as a dl pair or racemate. The dl pair represented by formula () can be separated into its respective optical antipodes by methods well known to those skilled in the art. General formula (A) (wherein R ¹ is hydrogen or R ³ —CO; Am
is amino or NH—CO—R ³ ; R ³ is methyl, ethyl or propyl. However, Am
is amino, R ¹ is not R ³ —CO. ) The novel intermediate represented by and its acid addition salt when Am is amino are produced by the method (A) or (B) below. (A) Formula () (In the formula, R ³ is as above.) The compound represented by is reacted with sodium glycine, and then a ring-closing reaction is performed in the presence of acetic anhydride to form a compound in which Am is NH—CO—R ³ and R ¹ is R ³ -
Obtaining a compound of formula (A) which is CO and further reacting it with a base, Am is amino,
A compound of formula (A) is obtained in which R ¹ is hydrogen. (B) Formula (XI) (In the formula, R ³ is as above.) A compound represented by the formula (A) in which Am is NH—CO—R ³ and R ¹ is hydrogen is obtained by reacting the compound represented by the above with copper powder in the presence of quinoline. and further basic hydrolysis to obtain the compound where Am is amino,
A compound of formula (A) is obtained in which R ¹ is hydrogen. Compounds of the formula () having an amino (denoted by Am) in the 5-position of the tetrahydro-2H-benzo[c]pyrrole ring can be prepared starting from 4-acetamidocyclohexanone () by at least two different compounds. can be manufactured via the route. The first is
This is shown in the reaction diagram below. When following the reaction diagram, first 4-acetamidocyclohexanone (Fraser, Swingle:
Can. J. Chem., 482065 (1970)) is reacted with dimethyl acetal of dimethylformamide to give 2-dimethylaminomethylene-4-acetamidocyclohexanone (). Reaction of this compound with sodium glycine followed by ring closure in the presence of acetic anhydride yields dl-2-acetyl-5-acetamido-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole (, ^R3
is methyl) is obtained. When this compound is treated with a base, dl-amino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole ()
is obtained. In order to selectively alkylate the latter amino group at the C-5 position, a reductive alkylation reaction (formaldehyde,
(reacted with an aldehyde such as acetaldehyde or propionaldehyde) is used.
This dialkyl compound, for example dl-5-dipropylamino-4,5,6,7-tetrahydro-
The pyrrole ring nitrogen of 2H-benzo[c]pyrrole () was converted into alkyl halide R ² X under basic conditions.
By alkylating with (methyl iodide, ethyl bromide, etc.), dl-2-(C ₁ -
C ₃ alkyl)-5-disubstituted amino-4,5,
6,7-tetrahydro-2H-benzo[c]pyrrole () can be obtained. In addition to the reductive alkylation described above, other methods can be used for the alkylation of the C-5 amino group to effect the conversion from V to. For example, direct alkylation with an alkyl halide, especially iododaisy, and reaction of the resulting secondary amine with a suitable acyl halide (acetyl chloride, crotyl chloride, etc.) and further metal hydride reducing agents (aluminum hydride, diborane, etc.), a 5-dialkylamino compound is obtained. This latter method is particularly suitable for producing products in which the C-5 amino group is unequally substituted. A second method that can be used to prepare compounds of formula () is shown in the reaction scheme below. When following the reaction route diagram, 4-acylamidocyclohexanone is used as a starting material, as in the case of the reaction route diagram. In this raw material,
In the presence of an acid catalyst such as P-toluenesulfonic acid,
The enol ether, 4-acetamido-1-ethoxycyclohexene (), is obtained by the action of ethyl orthoformate. This derivative has 1,
2,4,5-tetrazinedicarboxylic acid dimethyl ester (Sauer, etal: Chem.Ber., 981435
(1965)) to give the pyridazine diester (). Reduction of this diester with zinc-acetic acid or other suitable metal-acid reducing system results in ring reduction, resulting in dl-1,3-dicarbomethoxy-5-acetamide-4,5,6,
7-tetrahydro-2H-benzo[c]pyrrole
(x) is obtained. Selective hydrolysis of this diester with base yields the corresponding dicarboxylic acid (XI), which is decarboxylated with copper powder in the presence of quinoline to give dl-5-acetamido-4,5,6,
7-tetrahydro-2H benzo[c]pyrrole (XII) is obtained. Hydrolysis of this acyl group under basic conditions yields the free amine, dl-5-amino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole (this product follows the reaction route (identical to compound () in the figure). In the raw material 4-acylamidocyclohexanone, in addition to acetyl, acyl protecting groups such as propionyl, butyryl, isobutyryl, benzoyl, dinitrobenzoyl, and phenylacetyl can be used. The invention is further illustrated by the following references and examples. Reference example A Production of dl-5-amino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole 4-acetamidocyclohexanone 15.5g
(Fraser, Swingle: Can.J.Chem., 482065
(prepared according to (1970)), dimethylformamide/dimethylacetal 80g, triethylamine
Prepare a reaction solution consisting of 1.5 ml and 500 ml of benzene, and stir until the volume of this mixture becomes about half of the initial volume.
Benzene was distilled off over 1.5 hours. Next, 250 ml of benzene was added, heated just below the boiling point for about 2 hours, and concentrated to about half the initial volume (250 ml).
Repeat this operation one more time to make 1/3 of the initial volume.
(167ml). The mixture was cooled and filtered. The resulting cake was produced in the above reaction.
It was dl-4-acetamido-2-dimethylaminomethylenecyclohexanone. Yield: 6.45g.
The residue obtained by drying the liquid was dissolved in chloroform,
Chromatography using 200 g of Florisil and elution with chloroform-methanol with increasing methanol content (0-5%) resulted in an additional dl.
5.55 g of -4-acetamido-2dimethylaminomethylenecyclohexanone was obtained. Total amount: 12g. When crystallized from benzene, the melting point was 132-133°C. Elemental analysis Calculated value: C, 62.83; H, 8.63; N, 13.32 Experimental value: C, 63.07; H, 8.38; N, 13.12 Glycine potassium was obtained by reacting 9 g of glycine and 6.7 g of potassium hydroxide in 400 ml of aqueous ethanol. was generated. To this, dl-4-acetamido-2-dimethylaminomethylenecyclohexanone
22.6 g was added and heated to reflux temperature in a nitrogen stream for 1.75 hours. The reaction mixture was cooled, diluted with ether,
passed. Add 400 g of acetic anhydride to the 28.7 g of cake you took.
ml and heated to reflux temperature in a nitrogen stream for 1 hour. The reaction mixture was cooled and volatile components were distilled off under reduced pressure. The residue was suspended in chloroform and filtered.
The liquid was chromatographed on 350 g of Florisil. While increasing the amount of methanol (0-2%),
DL produced by elution with chloroform-methanol
-2-acetyl-5-acetamide-4,5,
The fractions containing 6,7-tetrahydro-2H-benzo[c]pyrrole (ascertained by TLC) were combined and the solvent was distilled off. The residue was crystallized from ether to give dl-2- with a melting point of 151-153°C. Acetyl-
17.7 g of 5-acetamido-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole was obtained. Elemental analysis Calculated value: C, 65.43; H, 7.32; N, 12.72 Experimental value: C, 65.72; H, 7.34; N, 12.45 dl-2-acetyl-5-acetamide-4,
A hydrolysis mixture consisting of 5.1 g of 5,6.7-tetrahydro-2H-benzo[c]pyrrole, 50 g of sodium hydroxide, 50 ml of water and 200 ml of ethanol was heated to reflux temperature in a nitrogen stream for about 16 hours and then cooled. This cooled mixture was diluted with water to obtain an alkaline aqueous solution, which was extracted several times with methylene chloride. The extracts were combined, washed with saturated brine, and dried. When the solvent was distilled off, the generated dl-5-amino-4,5,
A residue containing 6,7-tetrahydro-2H-benzo[c]pyrrole was obtained. This was dissolved in chloroform, filtered through 105 g of alumina (activity), and the liquid was concentrated to form a yellow solid.
-5-amino-4,5,6,7-tetrahydro-
2.52 g of 2-H-benzo[c]pyrrole was obtained. Reference example B Production of dl-5-acetamido-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole 4-acetamidocyclohexanone (Fraser, Swingle: Can.J.Chem., 482065
(1970)) was added to 6.7 g of absolute ethanol.
25 ml of ethyl orthoformate containing several crystals of P-toluenesulfonic acid monohydrate was added, and the mixture was stirred at room temperature for about 16 hours. The volatiles are distilled off under reduced pressure, the residue consisting of diethyl ketal is dissolved in 200 ml of toluene, and the toluene is evaporated in a nitrogen stream until the diethyl ketal has been converted to 1-ethoxycyclohexene.
After cooling, the solution was cooled, washed with aqueous sodium bicarbonate and dried, the toluene was distilled off, and the residue was recrystallized from ether-hexane to give a solution with a melting point of 100-102.
6.2 g of 4-acetamido-1-ethoxycyclohexene was obtained. A solution of 3 g of 4-acetamido-1-ethoxycyclohexene dissolved in 40 ml of dioxane was added to 1,
3.2 g of 2,4,5-tetrazine dicarboxylic acid ester (prepared by Sauer, et al: Chem. Ber., 981435 (1965)) was slowly added to a solution in 100 ml of dioxane. The mixture was stirred at room temperature for about 3 days, and TLC showed the presence of one major spot with several smaller spots. The reaction mixture was evaporated under reduced pressure and the residue was dissolved in chloroform and chromatographed on Florisil 200g.
Elution was performed with chloroform-methanol with increasing amounts of methanol (2-5%), fractions showing a single main spot by TLC were combined, and the solvent was removed under reduced pressure. The residue was triturated with ether to give 3.21 g of crystals, melting point 137-139°C. This was recrystallized from ether-methanol to give dl-6-acetamido-1,4-dicarbomethoxy-5,6,
A pure product of 7,8-tetrahydrobenzo[d]pyridazine was obtained. Melting point 143-144℃. Elemental analysis Calculated value: C, 54.72; H, 5.58; N, 13.67 Experimental value: C, 54.75; H, 5.64; N, 13.49 dl-6-acetamido-1,4-dicarbomethoxy-5,6,7, Dissolve 2.59 g of 8-tetrahydrobenzo[d]pyridazine in 100 ml of glacial acetic acid,
5 g of zinc was added and stirred at room temperature for 1 day. After 6 hours, 5 g of zinc powder was added. The reaction mixture was filtered to remove unreacted zinc powder, and the liquid was poured onto ice cubes.
The mixture was made basic with 14N ammonium hydroxide and extracted several times with a chloroform-isopropanol mixture. The organic layers were combined, washed with saturated brine, and dried.
When the solvent was distilled off, the dl-5-acetamido-1,3-dicarbomethoxy-4,
5,6,7-tetrahydro-2H-benzo [c]
1.83 g of pyrrole was obtained. Recrystallization from methanol gave a crystalline material with a melting point of 231-232°C. Elemental analysis Calculated value: C, 57.14; H, 6.16; N, 9.52 Experimental value: C, 57.05; H, 5.99; N, 9.26 dl-5-acetamido-1,3-dicarbomethoxy-4,5,6, 7-tetrahydro-2H-benzo[c]pyrrole 1.8g, tetrahydrofuran
A mixture of 80 ml and 20 ml of 2N aqueous sodium hydroxide solution was heated to reflux temperature in a nitrogen stream for about 3 hours.
After cooling, volatile components were distilled off under reduced pressure, and the residue was dissolved in 25 ml of water and acidified by adding 1N hydrochloric acid. The dicarboxylic acid produced, namely dl-5-acetamide-
Since 1,3-dicarboxy-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole precipitates because it is insoluble in an acidic solution, it was collected. Benzene - recrystallized from methanol, melting point 233 -
A crystalline dicarboxylic acid at 235°C (decomposed) was obtained. Elemental analysis Calculated value: C, 54.13; H, 5.30; N, 10.52 Experimental value: C, 53.90; H, 5.37; N, 10.45 dl-5-acetamido-1,3-dicarboxy-4,5,6,7 -Tetrahydro-2H-benzo[c]pyrrole 850mg, copper powder 50mg and quinoline 25
ml mixture was heated to 200° C. under a stream of nitrogen. Gas evolution was observed as the temperature approached 150°C. After heating at 200-210°C for 15 minutes, the reaction mixture was poured onto ice. This aqueous mixture was extracted with chloroform and the extract was separated.
It was washed successively with 0.1N hydrochloric acid, 10% aqueous sodium hydroxide solution, and water. The solvent was removed under reduced pressure to give 0.26 g of a dark oil. Chromatography was performed using 15 g of Florisil and chloroform containing 0-1% methanol as an eluent to obtain 40 mg of dl-5-acetamido-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole. This product was identified as a deacetylated product of dl-5-acetamido-2-acetyl-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole obtained in Reference Example A. Example 1 Method for producing dl-5-diethylamino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole dl-5-amino-4,5,6, obtained in Reference Example A
7-tetrahydro-2H-benzo[c]pyrrole
2.52g was dissolved in 100ml of methanol. to this,
1.2 g of sodium cyanoborohydride was added, followed by 6 ml of acetaldehyde. The mixture was stirred at ambient temperature under nitrogen for about 16 hours, then diluted with aqueous sodium bicarbonate. This was extracted with chloroform, and the extract was washed with saturated brine. The chloroform solution was dried and concentrated, and the residue was redissolved in chloroform and chromatographed on 35 g of Florisil, eluting with chloroform-methanol with increasing amounts of methanol (2-4%). The solid obtained by merging the fractions shown by TLC to contain substances different from the starting material.
1.84g was rechromatographed on Florisil.
dl-5-diethylamino-4,5, by TLC
A fraction containing 6,7-tetrahydro-2H-benzo[c]pyrrole was collected and the solvent was distilled off under reduced pressure to obtain 0.66 g of a residue. This was dissolved in ether and treated with excess maleic acid-ether solution. The obtained dl-5-diethylamino-4,
5,6,7-tetrahydro-2H-benzo [c]
Pyrrole maleate was recrystallized from methanol-ether to obtain 385 mg of pure product with a melting point of 81-83°C. Elemental analysis Calculated value: C, 62.32, H, 7.84; N, 9.08 Experimental value: C, 62.37; H, 7.57; N, 8.94 Example 2 dl-5-dipropylamino-4,5,6,7-
Method for producing tetrahydro-2H-benzo[c]pyrrole The same procedure as in Example 1 was carried out using propionaldehyde instead of acetaldehyde, and dl-5
-dipropylamino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole maleate was obtained. Recrystallization from isopropanol-ether gave a melting point of 134-136°C. Elemental analysis Calculated value: C, 64.26; H, 8.39; N, 8.33 Experimental value: C, 64.32; H, 8.68; N, 8.17 Example 3 dl-2-methyl-5-dipropylamino-4,
Process for producing 5,6,7-tetrahydro-2H-benzo[c]pyrrole dl-5-dipropylamino-4,5,6,7-
Tetrahydro-2H-benzo[c]pyrrole 680mg
(2mmol) in dimethylacetamide (DMA) 75ml
Dissolved in t-butoxypotassium 1.1g
(10 mmol) was added and stirred for 20 minutes in a nitrogen stream. Then 0.13 ml (2.1 mmol) of methyl iodide
5 ml of DMA solution was added dropwise, and the mixture was stirred at room temperature for 5 hours.
Further, 0.13 ml of methyl iodide was added and stirring was continued for 3.5 hours. This mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water and saturated brine, dried, and the solvent was distilled off. The residue was dissolved in ether and chromatographed on 35 g of Florisil.
Eluted with ether. By TLC, dl-2-methyl-5-dipropylamino-4,5,6,7-
A fraction containing tetrahydro-2H-benzo[c]pyrrole was collected and the solvent was distilled off under reduced pressure. NMR of the residue obtained here shows that this product is dl-2-methyl-5-dipropylamino-4,5,6,7-
It was shown to be tetrahydro-2H-benzo[c]pyrrole. The usefulness of compounds of formula () in the treatment of Parkinson's syndrome is demonstrated by their effect on turning behavior in tests using 6-hydroxydopamine-lesioned rats. . In this test, Ungestedt et al. (Ungestedt, Arbuthnott: Brain
Res., 24485 (1970) in nigro-neostriatal-lesioned rats.
rats) are used. Upon injection of a compound with dopamine agonist activity, the rat rotates in a circle opposite the injury site. After a certain incubation period (depending on the compound), the number of revolutions is counted for 15 minutes. The test compound was dissolved in water and injected intraperitoneally at a dose of 1 mg/Kg. dl-5-dipropylamino-4,
5,6,7-tetrahydro-2H-benzo [c]
Pyrrole maleate was found to be effective for one-third of the rats performing rotational movements in the above test.
An average of 34 rotations occurred per rat. Compounds of formula () are also useful as prolactin inhibitors. Therefore, it can be used to treat abnormal milk secretion and galactorrhea after delivery. The usefulness of these compounds in the treatment of diseases requiring a reduction in the amount of prolactin in mammals is evident from the fact that they are shown to have a prolactin inhibitory effect in the tests described below. Male adult rats of the Spragg-Dawley strain weighing approximately 200 g were housed in a light-controlled, air-conditioned room (irradiation time from 6 a.m. to 8 p.m.) with ad libitum access to laboratory animal feed (labchow) and water. Eighteen hours before administration of the test isoindole compound, each rat received an intraperitoneal injection of 2.0 mg of reserpine. The purpose of this reserpine was to uniformly increase the amount of prolactin secreted. The test compound is
It was dissolved in water and administered intraperitoneally at various doses from 5 mg/Kg to 50 mcg/Kg. Each compound was administered to 10 rats per group at each dose, and an equal volume of vehicle was administered to a control group consisting of 10 untreated rats.
One hour after administration, all rats were decapitated and prolactin was quantified using 150 μl of serum. Subtracting the prolactin concentration of the control rats from the prolactin concentration of the treated rats and dividing the difference by the prolactin concentration of the control rats yields the formula ()
The inhibition rate of prolactin secretion by the compound is obtained. This inhibition rate (%) is shown in Table 1. In the same table, the first column is the compound name, and the second to fourth columns are the prolactin inhibition rate (%) at each dose.

[Table] To use a compound of formula () to suppress prolactin secretion, treat Parkinson's syndrome, or for other pharmacological purposes, an effective amount of the compound or a pharmaceutically acceptable salt thereof should be administered to patients with Parkinson's disease or It is administered to patients who require prolactin suppression to alleviate Parkinson's symptoms or reduce elevated prolactin levels. Oral administration is preferred, but when parenteral administration is used, it is preferable to use a suitable dosage form and administer subcutaneously. Other parenteral administration methods, such as intraperitoneal, intramuscular or intravenous administration, are equally effective. Pharmaceutically acceptable water-soluble salts are used, particularly for intravenous or intramuscular administration. For oral administration, a compound of formula (), in free base or salt form, may be combined with standard excipients.
Fill into snap-fit gelatin capsules or compress into tablets. The oral dose is approximately
0.01 to 10 mg/Kg, and parenteral doses are likewise approximately 0.0025 to 2.5 mg/Kg. When administered intraperitoneally to mice, dl-5-dipropylamino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole maleate was administered at a dose of 10-30mg/
There were no fatal cases at doses of 100-300 mg/Kg, and doses of 100-300 mg/Kg were fatal. In addition, with administration of 30mg/Kg,
Some toxic side effects were observed.

Claims (1)

[Claims] 1. General formula (wherein R ¹ is hydrogen or R ² ; Am is N
(R ² ) ₂ ; R ² is independently methyl, ethyl or propyl. ) Tetrahydro-2H-benzo [c]
Pyrrole compounds and pharmaceutically acceptable acid addition salts thereof. 2. The compound of claim 1, wherein each R ₂ is the same group. 3 d1-5-diethylamino-4,5,6,7
-Tetrahydro-2H-benzo[c]pyrrole. 4 d1-5-di-n-propylamino-4,
5,6,7-tetrahydro-2H-benzo[c]
The compound of claim 1 which is pyrrole. 5. The compound of claim 1 which is d1-2-methyl-5-di-n-propylamino-4,5,6,7-tetrahydro-2H-benzo[c]pyrrole. 6 General formula (wherein R ¹ is hydrogen; Am is N(R ² ) ₂ ; R ² is ethyl) or a pharmaceutically acceptable thereof A prolactin secretion inhibitor containing an acid addition salt as an active ingredient. 7 General formula (In the formula, R ¹ is hydrogen; Am is N(R ² ) ₂ ; R ² is propyl.) Tetrahydro-2H-benzo[c]
A therapeutic agent for Parkinson's syndrome containing a pyrrole compound or a pharmaceutically acceptable acid addition salt thereof as an active ingredient.