FR2570700A2 - Pyrroloindole derivatives, their preparation and their application in therapy - Google Patents

Pyrroloindole derivatives, their preparation and their application in therapy Download PDF

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FR2570700A2
FR2570700A2 FR8414839A FR8414839A FR2570700A2 FR 2570700 A2 FR2570700 A2 FR 2570700A2 FR 8414839 A FR8414839 A FR 8414839A FR 8414839 A FR8414839 A FR 8414839A FR 2570700 A2 FR2570700 A2 FR 2570700A2
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compound
formula
preparation
pyrrolo
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FR2570700B2 (en
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Dennis Bigg
Claude Morel
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Synthelabo SA
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Synthelabo SA
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Priority to KR1019840007549A priority Critical patent/KR910005851B1/en
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Priority to FR8414839A priority patent/FR2570700B2/en
Priority to DE8484402477T priority patent/DE3472259D1/en
Priority to AT84402477T priority patent/ATE35267T1/en
Priority to EP84402477A priority patent/EP0145591B1/en
Priority to MX203667A priority patent/MX158671A/en
Priority to GR81235A priority patent/GR81235B/en
Priority to DK590984A priority patent/DK164670C/en
Priority to FI844888A priority patent/FI76803C/en
Priority to ES538475A priority patent/ES538475A0/en
Priority to NZ210516A priority patent/NZ210516A/en
Priority to IE3181/84A priority patent/IE57877B1/en
Priority to PT79658A priority patent/PT79658B/en
Priority to HU844605A priority patent/HU190659B/en
Priority to AU36496/84A priority patent/AU572237B2/en
Priority to NO844943A priority patent/NO162020C/en
Priority to IL73786A priority patent/IL73786A/en
Priority to US06/770,079 priority patent/US4617313A/en
Publication of FR2570700A2 publication Critical patent/FR2570700A2/en
Application granted granted Critical
Publication of FR2570700B2 publication Critical patent/FR2570700B2/en
Priority to CS914049A priority patent/CS404991A3/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Pyrrolo[3,2,1-hi]indole derivatives, in the form of racemates or optically active isomers, corresponding to the formula II: in which: R represents a straight or branched (C1-4)alkyl radical and A and B each represent a hydrogen atom or together a bond, as well as their addition salts with pharmaceutically acceptable acids. Application in therapy.

Description

La présente addition a pour objet des dérivés de pyrroloindole, leur préparation et leur application en thérapeutique.The subject of the present invention is pyrroloindole derivatives, their preparation and their therapeutic application.

Le composé du brevet principal répond à la formule (I) donnée en annexe.The compound of the main patent corresponds to the formula (I) given in the appendix.

Les composés de ta présente addition répondent à la formule (II) donnée en annexe dans laquelle R représente un radical (C1 4)alkyle droit ou ramifié, et 4 et B représentent chacun un atome d'hydrogène ou ensemble une liaison.The compounds of the present addition have the formula (II) given in the annex in which R represents a straight or branched (C1 4) alkyl radical, and 4 and B each represent a hydrogen atom or together a bond.

Les composés de l'invention existent sous la forme de racémates ou d'isomères optiquement actifs, et sous forme de bases ou de sels d'addition a des acides pharmaceutiquement acceptables.The compounds of the invention exist in the form of optically active racemates or isomers, and in the form of bases or addition salts with pharmaceutically acceptable acids.

Conformément à l'invention les composes (tI) peuvent être préparés selon le schéma réactionnel donné en annexe.According to the invention, the compounds (tI) can be prepared according to the reaction scheme given in the appendix.

1. Composes pour lesquels A et B sont H
Le composé de départ (rit), dans lequel R1 est un radical alkyle inférieur, en particulier éthyle, et dont la préparation est décrite dans le brevet principal 83 19850, peut être alkylé par réaction avec un iodure d'alkyle, en présence de diisopropylamine et de butyllithium, dans un solvant.1. Compounds for which A and B are H
The starting compound (rit), in which R 1 is a lower alkyl radical, in particular ethyl, and whose preparation is described in the main patent 83 19850, can be alkylated by reaction with an alkyl iodide, in the presence of diisopropylamine and butyllithium, in a solvent.

Puis on fait réagir le composé alkylé obtenu (IV) avec de lléthylènediamine en présence de triméthylaluminium pour obtenir les composés (II) dans lesquels A eut B sont H. The resulting alkyl compound (IV) is then reacted with ethylenediamine in the presence of trimethylaluminum to give the compounds (II) in which A and B are H.

2. Composés pour lesquels A et B représentent une liaison
On fait réagir le composé alkylé (IV) avec de l'oxyde de manganèse dans un solvant, tel que le chlorure de méthylène, à la température ambiante, puis on fait réagir le composé obtenu (V) avec de l'éthylènediamine en présence de trimé- thylaluminium.2. Compounds for which A and B represent a bond
The alkylated compound (IV) is reacted with manganese oxide in a solvent, such as methylene chloride, at room temperature, and the compound obtained (V) is reacted with ethylenediamine in the presence of trimethylaluminum.

Les exemples suivants illustrent l'invention.The following examples illustrate the invention.

Les spectres et les analyses I R et RMN con f i rmen t la structure des composé s. Spectra, NMR and NMR analyzes give the structure of the compounds.

Exemple 1 méthyl-2 (dihydro-4,5 lH-imidazolyl-2)-2 tétra hydro-1,2,4,5 pyrrolo 3,2,1 hi indole et son fumarate.EXAMPLE 1 2-methyl-4,5-dihydro-1H-imidazol-2-yl-2-tetrahydro-1,2,4,5-pyrrolo 3,2,1 hi indole and its fumarate.

1.1. Méthyl-2 tétrahydro-1,2,4,5 pyrrolo[3,2,1-hi]indole- carboxylate-2 d'éthyle.1.1. Ethyl 2-methyl-1,2,4,5-tetrahydro-pyrrolo [3,2,1-hi] indole-2-carboxylate.

Dans un ballon de Seller de 250 ml, muni d' u n agitation magnétique, d'un thermomètre, d'une arrivée d'argon, d'une ampoule à introduction et placé dans un bain froid, on introduit, sous argon 5,6 ml (0,04 mole) de diisopropylamine et 35 ml de tétrahydrofuranne (THF). On refroidit le mélange réactionnel à -70-750C puis on introduit, en 20 mn, 25 ml (0,04 mole) de butyllithium en solution 1,6 molaire dans de 1 'hexane. In a 250 ml Seller balloon, equipped with a magnetic stirrer, a thermometer, an argon inlet, an introduction bulb and placed in a cold bath, is introduced under argon 5.6. ml (0.04 mole) diisopropylamine and 35 ml tetrahydrofuran (THF). The reaction mixture is cooled to -70-750 ° C. and then 25 ml (0.04 mol) of butyllithium in 1.6 molar solution in hexane are introduced over 20 minutes.

On maintient la température à -70-750C pendant 1 heure et ajoute en 15 minutes une solution de 7 g (0,0322 mole) de tétrahydro-1,2,4,5 pyrrolo 3,2,1-hi indolecarboxylate-2 d'éthyle dans 25 ml de THF.The temperature is maintained at -70-7 ° C. for 1 hour and a solution of 7 g (0.0322 moles) of 1,2,4,5-tetrahydro-pyrrolo 3,2,1-indolecarboxylate-2-d is added over 15 minutes. ethyl in 25 ml of THF.

On maintient encore la température à -70-750C pendant 1 heure et on ajoute alors en 20 mn une solution de 12,4 ml (0,2 mole) d'iodure de méthyle dans 20 ml de THF.The temperature is maintained at -70-7 ° C. for 1 hour and a solution of 12.4 ml (0.2 mol) of methyl iodide in 20 ml of THF is then added over 20 minutes.

On maintient le mélange réactionnel à -70-750C pendant 1 h puis le laisse à la température ambiante pendant 3 h et demie.The reaction mixture is maintained at -70 ° to 750 ° C. for 1 hour and then left at room temperature for 3.5 hours.

On le verse dans de l'eau glacée. On l'extrait à l'éther diéthylique en présence d'une solution saturée de chlorure de sodium. On lave à l'eau et sèche sur Na2SO4. On sépare la phase organique. On évapore à siccité au bain-marie sous vide. On obtient une huile que l'on purifie par passage sur une colonne de silice avec comme éluant du chlorure de méthylène.It is poured into ice water. It is extracted with diethyl ether in the presence of a saturated solution of sodium chloride. Wash with water and dry over Na2SO4. The organic phase is separated. Evaporate to dryness in a vacuum bath. An oil is obtained which is purified by passage through a silica column eluting with methylene chloride.

1.2. Méthyl-2 (dihydro-4,5 lH-imidazolyl-2)-2 tétrahy dro-1,2,4,5 pyrrolo[3,2,1-hilindole et son fumarate.1.2. 2-Methyl- (4,5-dihydro-1H-imidazol-2-yl) -2-tetrahydro-1,2,4,5-pyrrolo [3,2,1-hilindole and its fumarate.

Dans un ballon de Keller de 50 ml muni d'une agitation magnétique, d'un réfrigérant à reflux, d'un thermomètre, d'une arrivée d'argon, d'une ampoule à introduction et d'un appareil de Dean-Stark, on introduit sous argon, successivement, 10 ml de toluène, 5,4 ml (0,013 mole) de triméthylaluminium à 25,2 dans de l'hexane et, tout en refroidissant à OoC, 0,9 mi (soit 0,013 mole) d'éthylènediamine en solution dans 3 ml de toluène.In a 50 ml Keller flask equipped with magnetic stirring, reflux condenser, thermometer, argon inlet, introduction funnel and Dean-Stark apparatus 10 ml of toluene, 5.4 ml (0.013 mol) of trimethylaluminum at 25.2 in hexane are introduced successively under argon and, while cooling to 0 ° C., 0.9 ml (ie 0.013 mol) of ethylenediamine dissolved in 3 ml of toluene.

On agite le mélange pendant 10 minutes, puis on le chauffe à 500C et, à cette température, on ajoute 1,9 9-(0,0082 mole) du produit précédemment obtenu en solution dans 10 ml de toluène. Ensuite on chauffe au reflux pendant 6 heures, puis on laisse refroidir. Après avoir refroidi le mélange entre -10 et -150C, on l'hydrolyse avec 5,4 ml d'eau, tout en agitant, puis on l'extrait avec de l'acétate d'éthyle. On réunit les fractions organiques, on les lave avec une solution de chlorure de sodium, on les sèche, on les filtre et on les évapore. I1 reste un solide de couleur jaune dont on prépare directement le fumarate.The mixture is stirred for 10 minutes and then heated to 500 ° C. and at this temperature 1.9% (0.0082 mol) of the previously obtained product dissolved in 10 ml of toluene is added. Then heated at reflux for 6 hours, then allowed to cool. After cooling the mixture to between -10 and -150C, it was hydrolyzed with 5.4 ml of water, with stirring, and then extracted with ethyl acetate. The organic fractions are combined, washed with sodium chloride solution, dried, filtered and evaporated. It remains a yellow solid whose fumarate is directly prepared.

Pour cela on le reprend avec 25 ml d'é'thanol, on filtre la solution et on lui ajoute une solution filtrée de 0,7 9 (0,006 mole) d'acide fumarique dans 50 ml d'éthanol. On agite la solution obtenue, on la concentre à sec, on reprend le résidu avec de l'acétone, on le filtre, on le sèche sous vide et on le recristallise dans de l'éthanol. On recueille le fumarate qui fond à 192-1940C. For this, it is taken up with 25 ml of ethanol, the solution is filtered and a filtered solution of 0.79 (0.006 mol) of fumaric acid in 50 ml of ethanol is added thereto. The resulting solution is stirred, concentrated to dryness, the residue is taken up with acetone, filtered, dried in vacuo and recrystallized from ethanol. The fumarate melts at 192-1940C.

Exemple 2 Méthyl-2 (dihydro-4,5 lH-imidazolyl-2)-2 dihydro-1,2 pyrrolo[3,2,1-hi]indole et son fumarate.Example 2 2- (2-Dihydro-1H-imidazol-2-yl) -2-dihydro-1,2-pyrrolo [3,2,1-hi] indole and its fumarate.

2.1. Méthyl-2 dihydro-1,2 pyrrolo 3,2,1-hilindole- carboxylate-2 d'éthyle.2.1. 2-Methyl-1,2-dihydro-pyrrolo 3,2,1-hilindole-2-carboxylate ethyl.

Dans un ballon tricol de 100 ml muni d'une agitation magnétique, on introduit 1,3 g (0,0056 mole) de méthyl-2 tétrahydro-1,2,4,5 pyrrolor3,2,1-hiindolecarboxylate-2 d'éthyle et 40 ml de CH2C12. In a 100 ml three-necked flask equipped with a magnetic stirrer, 1.3 g (0.0056 mole) of 2-methyl-1,2,4,5-tetrahydro-2-pyrrolor-2-ylindolecarboxylate are introduced. ethyl and 40 ml of CH2Cl2.

On ajoute à la solution 13 9 (0,15 mole) d'oxyde de manganèse. On agite le mélange réactionnel à la température ambiante pendant 4 h. On essore la solution sur silice et la lave avec CH2C12. On évapore à siccité sous vide. On obtient une huile que lton purifie par chromatographie sur silice avec comme éluant CH2Cl2. 13% (0.15 mole) of manganese oxide is added to the solution. The reaction mixture is stirred at room temperature for 4 hours. The solution is filtered through silica and washed with CH 2 Cl 2. Evaporate to dryness under vacuum. An oil is obtained which is purified by chromatography on silica eluting with CH 2 Cl 2.

2.2. Méthyl-2 (dihydro-4,5 lH-imidazolyl-2)-2 dihydro-1,2 pyrrolo[3,2,1-hi]indole et son fumarate.2.2. 2-Methyl-4,5-dihydro-1H-imidazol-2-yl) 1,2-dihydro-pyrrolo [3,2,1-hi] indole and its fumarate.

Dans un ballon de Keller de 25 ml muni d'une agitation magnétique, d'un réfrigérant -a reflux, d'un thermomètre, d'une arrivée d'argon, d'une ampoule à introduction et d'un appareil de Dean-Stark, on introduit sous argon, successivement, 5 ml de toluène, 1,8 ml (0,0043 mole) de triméthylaluminium à 25,2 % dans de l'hexane et, tout en refroidissant à OOC, 0,3 ml (soit (0,0043 mole) d'éthylènediamine en solution dans 3 ml de toluène.In a 25 ml Keller flask equipped with magnetic stirring, reflux condenser, thermometer, argon inlet, introduction funnel and Stark 5 ml of toluene, 1.8 ml (0.0043 mol) of 25.2% trimethylaluminum in hexane, are successively introduced under argon and, while cooling to OOC, 0.3 ml (either (0.0043 mole) of ethylenediamine dissolved in 3 ml of toluene.

On agite le mélange pendant 10 minutes, puis on le chauffe à 50 C et, à cette température, on ajoute 0,6 g (0,0026 mole) du produit précédemment obtenu en solution dans 5 ml de toluène. Ensuite on chauffe au reflux pendant 6 heures, puis on laisse refroidir. Après avoir refroidi le mélange entre -10 et -150C, on 11 hydrolyse avec 1,8 mi d'eau, tout en agitant, puis on l'extrait avec de l'acétate d'éthyle. On réunit les fractions organiques, on les lave avec une solution de chlorure de sodium, on les sèche, on les filtre et on les évapore. I1 reste un solide de couleur blanche dont on prépare directement le fumarate.The mixture is stirred for 10 minutes, then heated to 50 ° C. and at this temperature, 0.6 g (0.0026 mol) of the previously obtained product dissolved in 5 ml of toluene are added. Then heated at reflux for 6 hours, then allowed to cool. After cooling the mixture to between -10 and -150C, it was hydrolyzed with 1.8 ml of water while stirring and then extracted with ethyl acetate. The organic fractions are combined, washed with sodium chloride solution, dried, filtered and evaporated. It remains a white solid whose fumarate is prepared directly.

Pour cela on le reprend avec 10 ml dréthanol, on filtre la solution et on lui ajoute une solution filtrée de 0,2 g (0,002 mole) d'acide fumarique dans 20 ml d'éthanol. On agite la solution obtenue, on la concentre å sec, on reprend le résidu avec de l'acétone, on le filtre, on le sèche sous vide et on le recristallise dans de l'alcool isopropylique.For this, it is taken up with 10 ml of ethanol, the solution is filtered and it is added a filtered solution of 0.2 g (0.002 mol) of fumaric acid in 20 ml of ethanol. The resulting solution is stirred, concentrated to dryness, the residue is taken up with acetone, filtered, dried in vacuo and recrystallized from isopropyl alcohol.

On recueille le fumarate qui fond a 184-186 C. The fumarate is collected which melts at 184-186 C.

Les composés de l'invention préparés à titre d'exemples sont représentés dans le tableau suivant. The compounds of the invention prepared by way of example are shown in the following table.

Tableau

Figure img00060001
Board
Figure img00060001

Figure img00060002
Figure img00060002

<tb> Composé <SEP> R <SEP> A <SEP> B <SEP> sel <SEP> F( C)
<tb> <SEP> 1 <SEP> CH3 <SEP> H <SEP> H <SEP> narate <SEP> 192-194
<tb> <SEP> 2 <SEP> C2H5 <SEP> H <SEP> H <SEP> fumarate <SEP> 162-164
<tb> <SEP> 3 <SEP> nC3H7 <SEP> H <SEP> H <SEP> fumarate <SEP> 202-204
<tb> <SEP> 4 <SEP> nC4H9 <SEP> H <SEP> H <SEP> fumarate <SEP> 171-173
<tb> <SEP> 5 <SEP> CH3 <SEP> liaison <SEP> fumarate <SEP> 184-186
<tb>
Les composés de l'invention ont été soumis à des essais pharmacologiques qui ont montré leur intérêt en tant que a2-antagonistes . <tb> Compound <SEP> R <SEP> A <SEP> B <SEP> salt <SEP> F (C)
<tb><SEP> 1 <SEP> CH3 <SEP> H <SEP> H <SEP> narate <SEP> 192-194
<tb><SEP> 2 <SEP> C2H5 <SEP> H <SEP> H <SEP> fumarate <SEP> 162-164
<tb><SEP> 3 <SEP> nC3H7 <SEP> H <SEP> H <SEP> fumarate <SEP> 202-204
<tb><SEP> 4 <SEP> nC4H9 <SEP> H <SEP> H <SEP> fumarate <SEP> 171-173
<tb><SEP> 5 <SEP> CH3 <SEP> binding <SEP> fumarate <SEP> 184-186
<Tb>
The compounds of the invention have been subjected to pharmacological tests which have shown their interest as α2-antagonists.

A cet effet les composés ont été étudiés dans le test de potentialité et de sélectivité des antagonistes à l'égard des récepteurs a 2 in vitro.For this purpose, the compounds were studied in the test for the potentiality and selectivity of antagonists with respect to in vitro receptors.

La détermination de la valeur pA2 à l'égard des effets inhibiteurs de la clonidine, 02 agoniste bien connu, a eu lieu sur le vas deferens du rat stimulé a une fréquence de 0,1 Hz en présence de 30 nM de prazosine et de 1 uM de cocaine, selon la méthode décrite par G.M. Drew (European
Journal of Pharmacology, 42, (1977) 123-130.The determination of the pA2 value for the inhibitory effects of clonidine, a well-known agonist, occurred on the vas deferens of the rat stimulated at a frequency of 0.1 Hz in the presence of 30 nM prazosin and 1 uM cocaine, according to the method described by GM Drew (European
Journal of Pharmacology, 42, (1977) 123-130.

Les pA2 des composés de l'invention vont de 7 à 9.The pA2 of the compounds of the invention range from 7 to 9.

Les composés de l'invention sont des a2-antagonistes puissants qui peuvent être utilisés pour le traitement de la dépression (soit seuls, soit en association avec un produit qui inhibe les mécanismes de captation neuronale), le traitement de l'hypotension, le traitement de l'ileum paralytique post-opératoire, le traitement de l'asthme et de l'obésité.The compounds of the invention are potent α2-antagonists that can be used for the treatment of depression (either alone or in combination with a product that inhibits neuronal uptake mechanisms), treatment of hypotension, treatment of the postoperative paralytic ileum, the treatment of asthma and obesity.

Les compositions pharmaceutiques peuvent être sous une forme appropriée pour l'administration par voie orale, rectale ou parentérale ; par exemple sous la forme de capsules, comprimés, granulés, gélules ou solutés liquides, sirops ou suspensions buvables, et contenir les excipients appropriés.The pharmaceutical compositions may be in a form suitable for oral, rectal or parenteral administration; for example in the form of liquid capsules, tablets, granules, capsules or solutes, syrups or oral suspensions, and containing the appropriate excipients.

La posologie quotidienne peut aller de 0,1 à 10 mg/kg p.o.
Annexe

Figure img00080001
The daily dosage can range from 0.1 to 10 mg / kg po
Annex
Figure img00080001

Schema réactionnel

Figure img00080002
Reaction scheme
Figure img00080002

Figure img00080003
Figure img00080003

<tb> (III) <SEP> (il)
<tb> <SEP> I
<tb> <SEP> R
<tb> <SEP> C02R1
<tb> <SEP> H2N-(CH2)2-NH2 <SEP> (II)
<tb> <SEP> W <SEP> (CH3)3A1
<tb> <SEP> (A <SEP> et <SEP> B <SEP> = <SEP> líaison)
<tb> <tb> (III) <SEP> (he)
<tb><SEP> I
<tb><SEP> R
<tb><SEP> C02R1
<tb><SEP> H2N- (CH2) 2 -NH2 <SEP> (II)
<tb><SEP> W <SEP> (CH3) 3A1
<tb><SEP> (A <SEP> and <SEP> B <SEP> = <SEP> the season)
<Tb>

Claims (5)

A et B représentent chacun un atome d'hydrogène ou ensemble une liaison, ainsi que leurs sels d'addition aux acides pharmaceutiquement acceptables.A and B each represent a hydrogen atom or together a bond, as well as their addition salts with pharmaceutically acceptable acids. dans laquelle R .représente un radical 'C1 4)alkyle droit ou ramifié, et wherein R represents a straight or branched (C1 4) alkyl radical, and
Figure img00090001
Figure img00090001
 racémates ou d'isomères optiquement actifs, répondant à la formule II  racemates or optically active isomers of formula II Dérivés de pyrrolo[3,2,1-hi]indole, sous la forme de Derivatives of pyrrolo [3,2,1-hi] indole, in the form of Revendications claims 2. Composés selon la revendication 1, dans lesquels R est le radical méthyle, éthyle, n-propyle ou n-butyle et A et B représentent chacun un atome d'hydrogène.2. Compounds according to claim 1, wherein R is methyl, ethyl, n-propyl or n-butyl and A and B each represent a hydrogen atom. 3. Procédé de préparation des composés selon la revendication 1, procédé caractérisé en ce que - soit on alkyle un composé de formule III 3. Process for the preparation of the compounds according to claim 1, characterized in that either a compound of formula III is alkylated.
Figure img00090002
Figure img00090002
 avec un iodure de (C1 4)alkyle puis on fait réagir l'ester alkylé obtenu t  with a (C1 4) alkyl iodide and then the alkyl ester obtained is reacted t
Figure img00090003
Figure img00090003
 avec de lXéthylènediamine en présence de triméthylaluminium, - soit on oxyde le composé de formule (IV)  with ethylenediamine in the presence of trimethylaluminium, or the compound of formula (IV) is oxidized
Figure img00100001
Figure img00100001
 avec de l'oxyde de manganèse puis on fait réagir l'ester obtenu (V) with manganese oxide and then reacting the ester obtained (V)
Figure img00100002
Figure img00100002
 avec de l'éthylènediamine en présence de triméthylaluminium. with ethylenediamine in the presence of trimethylaluminum. 4. Médicament caractérisé en ce qu'il consiste en un composé selon la revendication 1 ou la revendication 2.4. Medicinal product characterized in that it consists of a compound according to claim 1 or claim 2. 5. Composition pharmaceutique caractérisée en ce qu'elle contient un composé selon la revendication 1 ou la revendication 2 en association avec un excipient approprié. 5. Pharmaceutical composition characterized in that it contains a compound according to claim 1 or claim 2 in combination with a suitable excipient.
FR8414839A 1983-12-12 1984-09-27 PYRROLO-INDOLE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION Expired FR2570700B2 (en)

Priority Applications (19)

Application Number Priority Date Filing Date Title
KR1019840007549A KR910005851B1 (en) 1983-12-12 1984-07-30 Process for producing pyryolo (3,2,1-hi) indole derivative
FR8414839A FR2570700B2 (en) 1984-09-27 1984-09-27 PYRROLO-INDOLE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
DE8484402477T DE3472259D1 (en) 1983-12-12 1984-12-03 Pyrrolo(3,2,1-hi)indole derivatives, their preparation and their therapeutical use
AT84402477T ATE35267T1 (en) 1983-12-12 1984-12-03 PYRROLO(3,2,1-HI)INDOLDERIVATE, THEIR PRODUCTION AND THERAPEUTIC APPLICATION.
EP84402477A EP0145591B1 (en) 1983-12-12 1984-12-03 Pyrrolo(3,2,1-hi)indole derivatives, their preparation and their therapeutical use
MX203667A MX158671A (en) 1983-12-12 1984-12-10 PROCEDURE FOR PREPARING DERIVATIVES OF PYROLE (3,2,1-HI) INDOL
NZ210516A NZ210516A (en) 1983-12-12 1984-12-11 Pyrrolo(3,2,1-hi)indoles and pharmaceutical compositions
DK590984A DK164670C (en) 1983-12-12 1984-12-11 PYRROLOOE3,2,1-HIAAINDOL DERIVATIVES, PROCEDURES FOR PREPARING THEREOF, AND MEDICINES CONTAINING SUCH COMPOUNDS
FI844888A FI76803C (en) 1983-12-12 1984-12-11 Process for the preparation of 2- (4,5-dihydro-1H-imidazol-2-yl-1,2,4,5-tetrahydropyrrolo / 3,2,1-hi
ES538475A ES538475A0 (en) 1983-12-12 1984-12-11 A PROCEDURE FOR PREPARING DERIVATIVES OF PYROLE (3,2,1-HI) INDOL
GR81235A GR81235B (en) 1983-12-12 1984-12-11 Method for the preparation of pyrrolo (3,2,1-hi) indole derivatives
IE3181/84A IE57877B1 (en) 1983-12-12 1984-12-11 Pyrrolo(3,2,1-hi)indole derivatives,their preparation and pharmaceutical compositions containing them
PT79658A PT79658B (en) 1983-12-12 1984-12-11 PROCESS FOR THE PREPARATION OF PYRROLO <3,2,1-HI> INDOLE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
HU844605A HU190659B (en) 1983-12-12 1984-12-11 Process for preparing pyrrolo/3,2,1-hi/indole derivatives and pharmaceutical compositions containing such compounds
AU36496/84A AU572237B2 (en) 1983-12-12 1984-12-11 Imidazoline substituted pyrrolo (3,2,1-hi) indole derivatives
NO844943A NO162020C (en) 1983-12-12 1984-12-11 ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY ACTIVE PYRROLO-INDOL DERIVATIVES.
IL73786A IL73786A (en) 1983-12-12 1984-12-12 2-(4,5-dihydro-1h-imidazol-2-yl)-1,2,4,5-tetrahydropyrrolo(3,2,1-hi)indoles,their preparation and pharmaceutical compositions containing them
US06/770,079 US4617313A (en) 1983-12-12 1985-08-28 Alpha2 -antagonistic 2-(4,5-dihydro-1H-imidazol-2-yl)-pyrrolo[3,2,1-hi]indoles
CS914049A CS404991A3 (en) 1983-12-12 1991-12-23 Pyrroloindole derivatives, process of their preparation and pharmaceutical compositions comprising said derivatives

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FR8414839A FR2570700B2 (en) 1984-09-27 1984-09-27 PYRROLO-INDOLE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION

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FR2570700B2 FR2570700B2 (en) 1986-11-21

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Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 96, no. 15, 12 avril 1982, pages 60,61, réf. no. 115832x, Columbus, Ohio, US; H. DABIRE et al.: "Pre- and postsynaptic alpha-adrenoceptor blockade by (imidazolinyl-2)-2-benzodioxane 1-4(170 150): antagonistic action on the central effects of clonidine" & ARCH. INT. PHARMACODYN.. THER. 1981, 254(2), 252-70 *

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