FR2583048A1 - Pyrrolo[3,2,1-hi]indole derivatives, their preparation and their application in therapeutics - Google Patents
Pyrrolo[3,2,1-hi]indole derivatives, their preparation and their application in therapeutics Download PDFInfo
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- FR2583048A1 FR2583048A1 FR8508709A FR8508709A FR2583048A1 FR 2583048 A1 FR2583048 A1 FR 2583048A1 FR 8508709 A FR8508709 A FR 8508709A FR 8508709 A FR8508709 A FR 8508709A FR 2583048 A1 FR2583048 A1 FR 2583048A1
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- JLTRNSWADPSQBA-UHFFFAOYSA-N 4-azatricyclo[5.3.1.04,11]undeca-1(11),2,5,7,9-pentaene Chemical class C1=CC2=CC=CC3=C2N1C=C3 JLTRNSWADPSQBA-UHFFFAOYSA-N 0.000 title claims abstract 3
- 239000003814 drug Substances 0.000 title claims abstract 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- -1 alkenyl radical Chemical class 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Chemical group 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Chemical group 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000003760 magnetic stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- WLFGGJFWKXTOGJ-UHFFFAOYSA-N 2,3-dihydroindol-1-amine Chemical compound C1=CC=C2N(N)CCC2=C1 WLFGGJFWKXTOGJ-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000003982 neuronal uptake Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000001769 paralizing effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229910000498 pewter Inorganic materials 0.000 description 1
- 239000010957 pewter Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 150000005592 pyrroloindoles Chemical class 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001177 vas deferen Anatomy 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
La présente invention a pour objet des dérivés de pyrrolo-indole, leur préparation et leur application en thérapeutique.The present invention relates to pyrrolo-indole derivatives, their preparation and their therapeutic application.
Les composés de l'invention répondent à la formule (I) donnée en annexe dans laquelle
R représente un radical (C3 5)alcényle, et
R1 et R2 représentent chacun, indépendamment l'un de l'autre, un atome d'hydrogène, un atome d'halogène ou un radical (C1 4)alkyle. The compounds of the invention correspond to the formula (I) given in the annex in which
R represents a radical (C3 5) alkenyl, and
R1 and R2 are each independently of one another a hydrogen atom, a halogen atom or a (C1 4) alkyl radical.
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 à 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 composés (I) peuvent être préparés selon le schéma réactionnel donné en annexe.According to the invention, the compounds (I) can be prepared according to the reaction scheme given in the appendix.
L'ester de départ (II) dans lequel R' est un alkyle, en particulier éthyle, peut être obtenu à partir de N-amino
indoline, elle-même étant préparée selon la méthode décrite par A.N. Kost et coll. (C.A., 54, 19641).The starting ester (II) in which R 'is alkyl, in particular ethyl, can be obtained from N-amino
indoline, itself being prepared according to the method described by AN Kost et al. (CA, 54, 19641).
Selon l'invention, on hydrogène l'ester de départ (II) à l'aide d'acide chlorhydrique en présence d'étain à la température ambiante.According to the invention, the starting ester (II) is hydrogenated with hydrochloric acid in the presence of tin at room temperature.
Puis on alcényle le composé (III) par réaction avec un halogénure d'alcényle RX, en présence de diisopropylamine et de butyllithium, dans un solvant, et on fait réagir le composé alcénylé obtenu (IV) avec de l'éthylènediamine en présence de triméthylaluminium.The compound (III) is then alkenylated by reaction with an alkenyl halide RX, in the presence of diisopropylamine and butyllithium, in a solvent, and the alkenyl compound obtained (IV) is reacted with ethylenediamine in the presence of trimethylaluminium. .
L'exemple suivant illustre l'invention ; les analyses et les spectres IR et RMN confirment la structure des composés. The following example illustrates the invention; analyzes and IR and NMR spectra confirm the structure of the compounds.
Exemple. Allyl-2 chloro-8 (dihydro-4,5 lH-imidazolyl-2)-2 tétrahydro-1,2,4,5 pyrrolo[3,2,1-hi]indole et son fumarate.Example. Allyl-2-chloro-8 (4,5-dihydro-1H-imidazol-2-yl) -2,2,4,5-tetrahydro-pyrrolo [3,2,1-hi] indole and its fumarate.
1. Chloro-8 tétrahydro-1,2,4,5 pyrrolo[3,2,1-hi]indole- carboxylate-2 d'éthyle.1. Ethyl 8-chloro-1,2,4,5-tetrahydro-pyrrolo [3,2,1-hi] indole-2-carboxylate.
Dans un ballon tricol de 1 1, muni d'un système d'agitation magnétique et d'un réfrigérant, on introduit 25 g (0,1 mole) de chloro-8 dihydro-4,5 pyrrolo [3,2,1-hi]indolecarboxylate-2 d'éthyle et 500 ml d'éthanol saturé en acide chlorhydrique.In a 3-necked flask equipped with a magnetic stirring system and a condenser, 25 g (0.1 mol) of 8-chloro-4,5-dihydro-pyrrolo [3,2,1- hi] indolecarboxylate-2 ethyl and 500 ml of ethanol saturated with hydrochloric acid.
On ajoute 200 ml d'éthanol et on sature en acide chlorhydrique à -5O0C. Puis on ajoute à la suspension 35,6 g (0,3 at.g) d'étain en grenaille.200 ml of ethanol are added and saturated with hydrochloric acid at -50 ° C. 35.6 g (0.3 at.g) of pewter tin are then added to the suspension.
On agite le mélange réactionnel à 2O0C pendant 21 h, on évapore le solvant sous vide et dissout le résidu dans 600 ml d'éthanol. On sature en ammoniac jusqu'à pH9. On filtre la suspension, la rince à l'éthanol. On évapore le solvant sous vide. On dissout le résidu dans de l'eau, on extrait la phase aqueuse à l'éther. On lave la phase éthérée avec une solution de chlorure de sodium, puis on la sèche sur sulfate de sodium. On purifie, le résidu par chromatographie sur colonne de silice en éluant avec du chlorure de méthylène 2.Allyl-2 chloro-8 tétrahydro-1,2,4,5 pyrrolo[3,2,1-hi] indolecarboxylate-2 d'éthyle
Dans un ballon de Keller de 150 ml muni d'un système d'agitation magnétique et sous argon, on introduit 2,4 g (0,024 mole) de diisopropylamine et 20 ml de tétrahydrofuranne. On refroidit la solution à -78 C et on ajoute du n-butyllithium en solution 16 M dans de l'hexane (15 ml, 0,024 mole). On agite la solution à -780C pendant 1 h 30 puis on ajoute 5 g (0,020 mole) de l'ester précédemment obtenu dans 22 ml de tétrahydrofuranne, on agite à -780C pendant 45 mn puis on ajoute 3,6 g (0,030 mole) de bromure d'allyle dans 10 ml de tétrahydrofuranne. On agite le mélange réactionnel pendant 1 h à -780C et pendant 1 h à 200 C, on hydrolyse avec 20 ml d'eau.On extrait la phase aqueuse avec 400 ml d'éther ; on lave la phase éthérée à l'eau, puis avec une solution saturée de chlorure de sodium et on la sèche sur sulfate de magnésium.The reaction mixture is stirred at 20 ° C. for 21 h, the solvent is evaporated under vacuum and the residue is dissolved in 600 ml of ethanol. It is saturated with ammonia to pH9. The suspension is filtered and rinsed with ethanol. The solvent is evaporated under vacuum. The residue is dissolved in water and the aqueous phase is extracted with ether. The ethereal phase is washed with sodium chloride solution and then dried over sodium sulfate. The residue is purified by chromatography on a column of silica eluting with methylene chloride 2.Allyl-2-chloro-8-tetrahydro-1,2,4,5-pyrrolo [3,2,1-hi] indolecarboxylate-2 ethyl
In a 150 ml Keller flask equipped with a magnetic stirring system and under argon, 2.4 g (0.024 mol) of diisopropylamine and 20 ml of tetrahydrofuran are introduced. The solution was cooled to -78 ° C and n-butyllithium in 16 M solution in hexane (15 ml, 0.024 mol) was added. The solution is stirred at -7 ° C. for 1 h 30, then 5 g (0.020 mol) of the ester obtained above are added in 22 ml of tetrahydrofuran, the mixture is stirred at -7 ° C. for 45 min and then 3.6 g (0.030 mol) are added. ) of allyl bromide in 10 ml of tetrahydrofuran. The reaction mixture is stirred for 1 h at -7 ° C. and for 1 h at 200 ° C., hydrolyzed with 20 ml of water. The aqueous phase is extracted with 400 ml of ether; the ether phase is washed with water and then with a saturated solution of sodium chloride and dried over magnesium sulfate.
On évapore les solvants sous vide, et on utilise l'ester obtenu tel quel dans la réaction suivante.The solvents are evaporated under vacuum, and the ester obtained as such is used in the next reaction.
3. Allyl-2 chloro-8 (dihydro-4,5 1H imidazolyl-2)-2 tétra hydro-1,2,4,5 pyrrolo [3,2,1-hi]indole et son fumarate.3. Allyl-2-chloro-8 (4,5-dihydro-1H-imidazol-2-yl) -2-tetrahydro-1,2,4,5-pyrrolo [3,2,1-hi] indole and its fumarate.
Dans un ballon de Keller de 150 ml muni d'un système d'agitation magnétique, d'un réfrigérant et sous argon, on introduit 12,17 ml (0,04 mole) de triméthylaluminium à 25,2 S dans l'hexane et 30 ml de toluène. On refroidit la solution à -100C et on ajoute 2,4 g (0,04 mole) dtéthylènediamine dans 10 ml de toluène. A 500C, on ajoute 0,02 mole de l'ester obtenu précédemment dans 20 ml de toluène. On agite le mélange réactionnel à 110 C pendant 6 h. On hydrolyse à -100C avec 20 ml d'eau et on ajoute 100 ml d'acétate d'éthyle. On agite le mélange 30 mn à 200C, puis on sèche la phase organique sur sulfate de magnésium.In a 150 ml Keller flask equipped with a magnetic stirring system, a condenser and under argon, 12.17 ml (0.04 mole) of 25.2 S trimethylaluminum in hexane are introduced. 30 ml of toluene. The solution is cooled to -100 ° C. and 2.4 g (0.04 mol) of ethylene diamine in 10 ml of toluene are added. At 500 ° C., 0.02 mole of the ester obtained previously in 20 ml of toluene is added. The reaction mixture is stirred at 110 ° C. for 6 hours. It is hydrolyzed at -100 ° C. with 20 ml of water and 100 ml of ethyl acetate are added. The mixture is stirred for 30 minutes at 200 ° C. and the organic phase is then dried over magnesium sulphate.
On évapore les solvants sous vide et prépare directement le fumarate.The solvents are evaporated under vacuum and the fumarate is prepared directly.
Dans un ballon monocol de 250 ml muni d'un système d'agitation magnétique, on introduit l'imidazoline brute obtenue et 80 ml d'éthanol puis on ajoute 1,74 g (0,015 mole) d'acide fumarique. On agite la solution pendant 10 mn à 20 C. On évapore l'éthanol sous vide et on reprend le résidu dans l'acétone. Le fumarate obtenu fond à 224-50C.In a 250 ml monocolumn flask equipped with a magnetic stirring system, the crude imidazoline obtained and 80 ml of ethanol are introduced and then 1.74 g (0.015 mol) of fumaric acid are added. The solution is stirred for 10 min at 20 ° C. The ethanol is evaporated under vacuum and the residue is taken up in acetone. The fumarate obtained melts at 224-50C.
Les cpmposés de l'invention préparés à titre d'exemples sont représentés dans le tableau suivant. The compositions of the invention prepared by way of example are shown in the following table.
Tableau
<tb> Composé <SEP> R <SEP> R1 <SEP> R2 <SEP> Sel <SEP> F(0 C) <SEP>
<tb> <SEP> 1 <SEP> allyle <SEP> H <SEP> H <SEP> fumarate <SEP> 186-8 C <SEP>
<tb> <SEP> 2 <SEP> allyle <SEP> 8C1 <SEP> H <SEP> fumarate <SEP> 224-5 C <SEP>
<tb> <SEP> 3 <SEP> allyle <SEP> 8F <SEP> H <SEP> fumarate <SEP> 170-2 C <SEP>
<tb> <SEP> 4 <SEP> allyle <SEP> 6Cl <SEP> H <SEP> fumarate <SEP> 154-6 C <SEP>
<tb>
Les composés de l'invention ont été soumis à des essais
pharmacologiques qui ont montré leur intérêt en tant que 2-antagonistes. <tb> Compound <SEP> R <SEP> R1 <SEP> R2 <SEP> Salt <SEP> F (0 C) <SEP>
<tb><SEP> 1 <SEP> allyl <SEP> H <SEP> H <SEP> fumarate <SEP> 186-8 C <SEP>
<tb><SEP> 2 <SEP> allyl <SEP> 8C1 <SEP> H <SEP> fumarate <SEP> 224-5 C <SEP>
<tb><SEP> 3 <SEP> allyl <SEP> 8F <SEP> H <SEP> fumarate <SEP> 170-2C <SEP>
<tb><SEP> 4 <SEP> allyl <SEP> 6Cl <SEP> H <SEP> fumarate <SEP> 154-6C <SEP>
<Tb>
The compounds of the invention have been subjected to tests
pharmacological studies that have shown their interest as 2-antagonists.
A cet effet les composés ont été étudiés dans le test de
potentialité et de sélectivité des antagonistes à l'égard
des récepteurs 2 in vitro.For this purpose the compounds were studied in the test of
potentiality and selectivity of antagonists with regard to
receptors 2 in vitro.
La détermination de la valeur pA2 à l'égard des effets
inhibiteurs de la clonidine, i2-agoniste bien connu, a eu
lieu sur le vas deferens du rat stimulé à une fréquence de
0,1 Hz en présence de 300nM de prazosine et de 1 M de cocai
ne, selon la méthode décrite par G.M. Drew (European Journal of Pharmacology, 42, (1977) 123-130).The determination of the pA2 value for effects
clonidine inhibitors, a well-known i2-agonist, has been
place on the rat vas deferens stimulated at a frequency of
0.1 Hz in the presence of 300nM prazosin and 1M 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 deso < 2-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, de l'obésité et du diabète.The compounds of the invention are strong deso-2 antagonists that can be used for the treatment of depression (either alone or in combination with a product).
which inhibits the mechanisms of neuronal uptake), the treatment of hypotension, the treatment of postoperative paralytic ileum, the treatment of asthma, obesity and diabetes.
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 liquid-es, sirops ou suspen
sions buvables, et peuvent contenir les excipients appropriés.The pharmaceutical compositions can be in a form
suitable for oral, rectal or parenteral administration, for example in the form of capsules, tablets, granules, capsules or liquid solutions, syrups or suspens
may be drinkable, and may contain the appropriate excipients.
La posologie quotidienne peut aller de 0,1 à 30 mg/kg p.o.
Annexe
Annex
Schéma réactionnel
R' = alkyle,de préférence éthyle x = halogène R '= alkyl, preferably ethyl x = halogen
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8508709A FR2583048B1 (en) | 1985-06-10 | 1985-06-10 | INDOLE PYRROLO (3,2,1-HI) DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8508709A FR2583048B1 (en) | 1985-06-10 | 1985-06-10 | INDOLE PYRROLO (3,2,1-HI) DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2583048A1 true FR2583048A1 (en) | 1986-12-12 |
| FR2583048B1 FR2583048B1 (en) | 1987-10-23 |
Family
ID=9320036
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8508709A Expired FR2583048B1 (en) | 1985-06-10 | 1985-06-10 | INDOLE PYRROLO (3,2,1-HI) DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Country Status (1)
| Country | Link |
|---|---|
| FR (1) | FR2583048B1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0139584A2 (en) * | 1983-10-17 | 1985-05-02 | Synthelabo | Imidazoline derivatives, their preparation and therapeutical use |
-
1985
- 1985-06-10 FR FR8508709A patent/FR2583048B1/en not_active Expired
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0139584A2 (en) * | 1983-10-17 | 1985-05-02 | Synthelabo | Imidazoline derivatives, their preparation and therapeutical use |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2583048B1 (en) | 1987-10-23 |
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| Date | Code | Title | Description |
|---|---|---|---|
| ST | Notification of lapse |