DE2006433A1 - 1-Amino-3-methyl-2- (2´-ethoxy-5´-chlorophenyl) pentanes, process for their production and their use as active pharmaceutical ingredients - Google Patents
1-Amino-3-methyl-2- (2´-ethoxy-5´-chlorophenyl) pentanes, process for their production and their use as active pharmaceutical ingredientsInfo
- Publication number
- DE2006433A1 DE2006433A1 DE19702006433 DE2006433A DE2006433A1 DE 2006433 A1 DE2006433 A1 DE 2006433A1 DE 19702006433 DE19702006433 DE 19702006433 DE 2006433 A DE2006433 A DE 2006433A DE 2006433 A1 DE2006433 A1 DE 2006433A1
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- amino
- general formula
- chloro
- pentanes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 title description 4
- 239000008186 active pharmaceutical agent Substances 0.000 title 1
- -1 alkyl radical Chemical class 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- OYNNTZYDLDUGIK-UHFFFAOYSA-N 2-(5-chloro-2-ethoxyphenyl)-3-methylpentan-1-amine Chemical class CCOC1=CC=C(Cl)C=C1C(CN)C(C)CC OYNNTZYDLDUGIK-UHFFFAOYSA-N 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 239000000812 cholinergic antagonist Substances 0.000 claims description 3
- 239000002934 diuretic Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 claims 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims 1
- 229940030600 antihypertensive agent Drugs 0.000 claims 1
- 239000002220 antihypertensive agent Substances 0.000 claims 1
- 229940124575 antispasmodic agent Drugs 0.000 claims 1
- 229940030606 diuretics Drugs 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000001882 diuretic effect Effects 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000001077 hypotensive effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QCFXUDLFIPHQPV-UHFFFAOYSA-N 2-(5-chloro-2-ethoxyphenyl)-3-methyl-n,n-di(propan-2-yl)pentan-1-amine Chemical compound CCOC1=CC=C(Cl)C=C1C(CN(C(C)C)C(C)C)C(C)CC QCFXUDLFIPHQPV-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000002921 anti-spasmodic effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000002048 spasmolytic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ADHODZSRIRPKGX-UHFFFAOYSA-N 1-[2-(5-chloro-2-ethoxyphenyl)-3-methylpentyl]azepane Chemical compound CCOC1=CC=C(Cl)C=C1C(C(C)CC)CN1CCCCCC1 ADHODZSRIRPKGX-UHFFFAOYSA-N 0.000 description 1
- ZVBWFFQRJPHKFY-UHFFFAOYSA-N 1-[2-(5-chloro-2-ethoxyphenyl)-3-methylpentyl]piperidine Chemical compound CCOC1=CC=C(Cl)C=C1C(C(C)CC)CN1CCCCC1 ZVBWFFQRJPHKFY-UHFFFAOYSA-N 0.000 description 1
- KFCXWGVCTPCYRF-UHFFFAOYSA-N 1-[2-(5-chloro-2-ethoxyphenyl)-3-methylpentyl]pyrrolidine Chemical compound CCOC1=CC=C(Cl)C=C1C(C(C)CC)CN1CCCC1 KFCXWGVCTPCYRF-UHFFFAOYSA-N 0.000 description 1
- ULOIAOPTGWSNHU-UHFFFAOYSA-N 2-butyl radical Chemical group C[CH]CC ULOIAOPTGWSNHU-UHFFFAOYSA-N 0.000 description 1
- UFMKTNYTQKRKIW-UHFFFAOYSA-N 4-[2-(5-chloro-2-ethoxyphenyl)-3-methylpentyl]morpholine Chemical compound CCOC1=CC=C(Cl)C=C1C(C(C)CC)CN1CCOCC1 UFMKTNYTQKRKIW-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- BQOWUDKEXDCGQS-UHFFFAOYSA-N [CH]1CCCC1 Chemical compound [CH]1CCCC1 BQOWUDKEXDCGQS-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Description
Zusatz zu P 16 43 907.9-42Addition to P 16 43 907.9-42
Das Hauptpatent (Patentanmeldung P 16 43 907.9) betrifft neue am Stickstoffatom substituierte Amide und die entsprechenden Amine, sowie ein Verfahren zur Herstellung dieser Verbindungen.The main patent (patent application P 16 43 907.9) relates to new amides substituted on the nitrogen atom and the corresponding amines, as well as a process for the preparation of these compounds.
Insbesondere betrifft das Hauptpatent Verbindungen der allgemeinen Formel
Pyrazinyl- oder Pyrimidylrest ist, R einen gesättigten oder ungesättigten, geradkettigen oder verzweigten aliphatischen Rest mit 1 bis 5 Kohlenstoffatomen bedeutet, der eine funktionelle Gruppe, z. B. Äthoxy-, Dimethylamino- oder Hydroxylgruppen, tragen kann, R´ und R´´ Wasserstoffatome oder aliphatische Reste mit 1 bis 3 C-Atomen sind oder zusammen mit dem Stickstoffatom, an das sie gebunden sind, einen heterocyclischen Ring, wie einen Piperidin-, Morpholin- oder Pyrrolidinring, bilden und X entweder eine Carbonylgruppe - CO - oder eine Methylenbrücke - CH[tief]2 - bedeutet, wobei im letzteren Fall Ar einen cycloaliphatischen Rest, wie einen Cyclohexyl- oder Cyclopentylrest bedeuten kann.Is pyrazinyl or pyrimidyl radical, R is a saturated or unsaturated, straight-chain or branched aliphatic radical having 1 to 5 carbon atoms, which is a functional group, e.g. B. ethoxy, dimethylamino or hydroxyl groups, R 'and R' 'are hydrogen atoms or aliphatic radicals with 1 to 3 carbon atoms or, together with the nitrogen atom to which they are attached, a heterocyclic ring, such as a piperidine -, morpholine or pyrrolidine ring, and X is either a carbonyl group - CO - or a methylene bridge - CH [deep] 2 -, where in the latter case Ar can be a cycloaliphatic radical, such as a cyclohexyl or cyclopentyl radical.
Die vorliegende Erfindung betrifft neue Verbindungen der allgemeinen Formel I, in der Ar ein 2-Äthoxy-5-chlorphenylrest, R ein sek.-Butylrest und X eine Methylenbrücke ist und R´ und R´´ gleich sind und je ein Wasserstoffatom oder einen niederen Alkylrest mit 2 oder 3 C-Atomen bedeuten oder aber zusammen mit dem Stickstoffatom, an das sie gebunden sind, einem heterocyclischen Ring, z. B. einer Pyrrolidino-, Piperidino-, Hexamethylenimino-, Morpholino- oder 4-Methyl-piperazinogruppe, angehören.The present invention relates to new compounds of general formula I in which Ar is a 2-ethoxy-5-chlorophenyl radical, R is a sec-butyl radical and X is a methylene bridge and R 'and R' 'are the same and each have a hydrogen atom or a lower one Mean an alkyl radical having 2 or 3 carbon atoms or, together with the nitrogen atom to which they are bonded, a heterocyclic ring, e.g. B. a pyrrolidino, piperidino, hexamethyleneimino, morpholino or 4-methyl-piperazino group belong.
Gegenstand der Erfindung sind somit 1-Amino-3-methyl-2-(2´-äthoxy-5-chlorphenyl)-pentane der allgemeinen Formel
in der R´ und R´´ gleich sind und je ein Wasserstoffatom oder einen niederen Alkylrest mit 2 oder 3 C-Atomen bedeuten, oder aber zusammen mit dem Stickstoffatom, an das sie gebunden sind, einem heterocyclischen Ring angehören.in which R 'and R' 'are the same and each represent a hydrogen atom or a lower alkyl radical with 2 or 3 carbon atoms, or together with the nitrogen atom to which they are attached, they belong to a heterocyclic ring.
Die Erfindung betrifft weiterhin ein Verfahren zur Herstellung von Pentanen der allgemeinen Formel II, das dadurch gekennzeichnet ist, dass man Lithiumaluminiumhydrid (AlLiH[tief]4) in wasserfreiem Äther oder in Tetrahydrofuran auf Amide der allgemeinen Formel
Dabei kann in jedem Fall wie folgt gearbeitet werden:In any case, you can work as follows:
In ein 300 ml fassendes, mit einem Rührer, einem Tropftrichter und einem Rückflusskühler ausgerüstetes Reaktionsgefäß werden zunächst 150 ml wasserfreier Äther, dann 0,1 Mol AlLiH[tief]4 (3,8 g) gegeben. Die AlLiH[tief]4-Suspension wird unter Rühren nach und nach mit einer Lösung von 0,1 Mol des jeweiligen Amids der allgemeinen Formel III in 50 bis 55 ml wasserfreiem Äther versetzt, wobei die Zugabegeschwindigkeit so gewählt wird, dass der Äther unter Rückfluss siedet. Wenn die Zugabe des Amids der Formel III beendet ist, wird das Reaktionsgemisch zunächst weitere 4 Stunden unter Rückfluss erhitzt und dann nach Abkühlung hydrolysiert, indem man es nacheinander vorsichtig mit 4 ml Wasser, 3 ml 20%-iger Natronlauge und nochmals 14 ml Wasser versetzt. Dann wird der dabei erhaltene körnige Niederschlag abfiltriert, den man auf dem Filter mit Äther wäscht. Das Filtrat wird eingeengt und mit 4 n Salzsäure angesäuert, worauf die wässrige Phase abgetrennt, mit 4 n Natronlauge alkalisch gemacht und mit Äther extrahiert wird. Der ätherische Auszug wird getrocknet und eingedampft. Der dabei erhaltene ölige Rückstand wird durch Destillieren unter vermindertem Druck gereinigt.First 150 ml of anhydrous ether and then 0.1 mol of AlLiH [deep] 4 (3.8 g) are placed in a 300 ml reaction vessel equipped with a stirrer, a dropping funnel and a reflux condenser. The AlLiH [deep] 4 suspension is gradually mixed with a solution of 0.1 mol of the respective amide of the general formula III in 50 to 55 ml of anhydrous ether, the rate of addition being chosen so that the ether refluxes boils. When the addition of the amide of the formula III has ended, the reaction mixture is first refluxed for a further 4 hours and then after cooling hydrolyzed by carefully adding 4 ml of water, 3 ml of 20% sodium hydroxide solution and another 14 ml of water one after the other. Then the granular precipitate obtained is filtered off, which is washed on the filter with ether. The filtrate is concentrated and acidified with 4N hydrochloric acid, whereupon the aqueous phase is separated off, made alkaline with 4N sodium hydroxide solution and extracted with ether. The essential extract is dried and evaporated. The oily residue obtained is purified by distillation under reduced pressure.
Die auf diese Weise erhaltene Base wird in Äthanol oder Essigsäureäthylester gelöst und durch Einleiten von gasförmigem Chlorwasserstoff in das Mono- oder Dihydrochlorid überführt. Das kristalline Mono- oder Dihydrochlorid wird abgetrennt und dann gewaschen, getrocknet und gegebenenfalls umkristallisiert.The base obtained in this way is dissolved in ethanol or ethyl acetate and converted into the mono- or dihydrochloride by passing in gaseous hydrogen chloride. The crystalline mono- or dihydrochloride is separated off and then washed, dried and, if necessary, recrystallized.
Die nachstehend als Beispiele aufgeführten Verbindungen werden auf diese Weise hergestellt:The compounds listed below as examples are prepared in this way:
Beispiel 1 3-Methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentylamin. Kp.: 121-123°C bei 0,2 mm Hg Ausbeute: 50%Example 1 3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentylamine. B.p .: 121-123 ° C at 0.2 mm Hg yield: 50%
Hydrochlorid: Smp.: 150°C Summenformel: C[tief]14 H[tief]23 Cl[tief]2 N O C H N berechnet: 57,53; 7,93; 4,79; gefunden: 57,68; 8,02; 4,94.Hydrochloride: m.p .: 150 ° C Molecular formula: C [low] 14 H [low] 23 Cl [low] 2 N O C H N calculated: 57.53; 7.93; 4.79; found: 57.68; 8.02; 4.94.
Beispiel 2 1-Diäthylamino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 2 1-Diethylamino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 136°C bei 0,1 mm Hg. Ausbeute: 30%Bp: 136 ° C at 0.1 mm Hg. Yield: 30%
Hydrochlorid: Smp.: 101°C Summenformel: C[tief]18 H[tief]31 Cl[tief]2 N O C H N berechnet: 62,06; 8,97; 4,02; gefunden: 62,09; 9,12; 4,21.Hydrochloride: m.p .: 101 ° C Molecular formula: C [low] 18 H [low] 31 Cl [low] 2 N O C H N calculated: 62.06; 8.97; 4.02; found: 62.09; 9.12; 4.21.
Beispiel 3 1-Dipropylamino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 3 1-Dipropylamino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 155°C bei 0,5 mm Hg. Ausbeute: 30%B.p .: 155 ° C at 0.5 mm Hg.Yield: 30%
Hydrochlorid: Smp.: 110°C Summenformel: C[tief]20 H[tief]33 Cl[tief]2 N O C H N berechnet: 63,81; 9,37; 3,72; gefunden: 64,02; 9,54; 3,92.Hydrochloride: m.p .: 110 ° C. Molecular formula: C [low] 20 H [low] 33 Cl [low] 2 N O C H N calculated: 63.81; 9.37; 3.72; found: 64.02; 9.54; 3.92.
Beispiel 4 1-Diisopropylamino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 4 1-Diisopropylamino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 136-138°C bei 0,2 mm Hg Ausbeute: 35%B.p .: 136-138 ° C at 0.2 mm Hg yield: 35%
Hydrochlorid: Smp.: 169°C Summenformel: C[tief]20 H[tief]33 Cl[tief]2 N O C H N berechnet: 63,81; 9,37; 3,72; gefunden: 64,01; 9,27; 3,89.Hydrochloride: m.p .: 169 ° C Molecular formula: C [low] 20 H [low] 33 Cl [low] 2 N O C H N calculated: 63.81; 9.37; 3.72; found: 64.01; 9.27; 3.89.
Beispiel 5 1-Pyrrolidino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 5 1-Pyrrolidino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 138°C bei 0,02 mm Hg Ausbeute: 50%B.p .: 138 ° C at 0.02 mm Hg yield: 50%
Hydrochlorid: Smp.: 136°C Summenformel: C[tief]18 H[tief]29 Cl[tief]2 N O C H N berechnet: 62,42; 8,44; 4,04; gefunden: 62,43; 8,52; 4,22.Hydrochloride: m.p .: 136 ° C Molecular formula: C [low] 18 H [low] 29 Cl [low] 2 N O C H N calculated: 62.42; 8.44; 4.04; found: 62.43; 8.52; 4.22.
Beispiel 6 1-Piperidino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 6 1-Piperidino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 145°C bei 0,02 mm Hg Ausbeute: 65%B.p .: 145 ° C at 0.02 mm Hg yield: 65%
Hydrochlorid: Smp.: 140°C Summenformel: C[tief]19 H[tief]31 Cl[tief]2 N O C H N berechnet: 63,32; 8,67; 3,89; gef.: 63,15; 8,76; 4,03.Hydrochloride: m.p .: 140 ° C Molecular formula: C [low] 19 H [low] 31 Cl [low] 2 N O C H N calculated: 63.32; 8.67; 3.89; Found: 63.15; 8.76; 4.03.
Beispiel 7 1-Hexamethylenimino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 7 1-Hexamethyleneimino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 165°C bei 0,05 mm Hg Ausbeute: 50%B.p .: 165 ° C at 0.05 mm Hg yield: 50%
Hydrochlorid: Smp.: 134-136°C Summenformel: C[tief]20 H[tief]33 Cl[tief]2 N O C H N berechnet: 64,16; 8,88; 3,74; gefunden: 64,15; 8,80; 3,87.Hydrochloride: m.p .: 134-136 ° C Molecular formula: C [low] 20 H [low] 33 Cl [low] 2 N O C H N calculated: 64.16; 8.88; 3.74; found: 64.15; 8.80; 3.87.
Beispiel 8 1-(N´-Methyl-N-piperazino)-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 8 1- (N'-Methyl-N-piperazino) -3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 150°C bei 0,02 mm Hg Ausbeute: 65%B.p .: 150 ° C at 0.02 mm Hg yield: 65%
Dihydrochlorid: Smp.: 150°C (Zersetzung) Summenformel: C[tief]19 H[tief]33 Cl[tief]3 N[tief]2 O C H N berechnet: 55,41; 8,08; 6,80; gefunden: 55,60; 7,85; 6,80.Dihydrochloride: Mp .: 150 ° C (decomposition) Molecular formula: C [low] 19 H [low] 33 Cl [low] 3 N [low] 2 O C H N calculated: 55.41; 8.08; 6.80; found: 55.60; 7.85; 6.80.
Beispiel 9 1-Morpholino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentanExample 9 1-Morpholino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane
Kp.: 155°C bei 0,2 mm Hg Ausbeute: 60%B.p .: 155 ° C at 0.2 mm Hg yield: 60%
Hydrochlorid: Smp.: 145°C Summenformel: C[tief]18 H[tief]29 Cl[tief]2 N O[tief]2 C H N berechnet: 59,66; 8,07; 3,87; gefunden: 59,59; 8,11; 3,99.Hydrochloride: m.p .: 145 ° C Molecular formula: C [low] 18 H [low] 29 Cl [low] 2 N O [low] 2 C H N calculated: 59.66; 8.07; 3.87; found: 59.59; 8.11; 3.99.
Die neuen Amine der Erfindung wurden bezüglich ihrer pharmakologischen Eigenschaften bei Versuchstieren untersucht und zeigten dabei diuretische (harntreibende) sowie hypotensive (blutdrucksenkende) und spasmolytische (krampflösende) Wirkung.The new amines of the invention were examined with regard to their pharmacological properties in test animals and showed diuretic (diuretic) as well as hypotensive (blood pressure lowering) and spasmolytic (antispasmodic) effects.
Diuretische Eigenschaften: Die harntreibende Wirkung wird bei Ratten untersucht. Die Versuchstiere werden in Stoffwechselkäfige gesetzt. Der ausgeschiedene Harn wird 6 Stunden lang alle 2 Stunden gesammelt und gemessen. Weiterhin wird auch die Ausscheidung an Natrium-, Kalium- und Chlorionen bestimmt. Die zu untersuchenden Stoffe werden oral verabreicht. Die normale Harnausscheidung wird aus der einer Gruppe von Vergleichsversuchstieren geschlossen.Diuretic properties: The diuretic effect is being studied in rats. The test animals are placed in metabolic cages. The excreted urine is collected and measured every 2 hours for 6 hours. The excretion of sodium, potassium and chlorine ions is also determined. The substances to be examined are administered orally. The normal urinary excretion is inferred from that of a group of comparative test animals.
Die bei diesen Versuchen erhaltenen, besonders günstigen Ergebnisse sind in der nachstehenden Tabelle aufgeführt:The particularly favorable results obtained in these tests are listed in the table below:
* Die Erhöhung der Harnausscheidung ist im Verlauf der ersten 4 Stunden nach der Verabreichung des Wirkstoffs besonders stark.* The increase in urine excretion is particularly strong in the course of the first 4 hours after administration of the active ingredient.
Hypotensive EigenschaftenHypotensive properties
Die hypotensive Wirkung wird an betäubten Katzen ermittelt. Die zu untersuchenden Stoffe werden intravenös verabreicht. Die Blutdrucksenkungen liegen in der Größenordnung von 30%. Die Zeit, bis der ursprüngliche arterielle Druck wieder erreicht wird, beträgt ungefähr 5 Minuten.The hypotensive effect is determined on anesthetized cats. The substances to be examined are administered intravenously. The blood pressure drops are of the order of 30%. The time until the original arterial pressure is restored is approximately 5 minutes.
Spasmolytische EigenschaftenAntispasmodic properties
Die untersuchten Verbindungen zeigen eine atropinähnliche spasmolytische Wirkung, die am isolierten Zwölffingerdarm von Ratten untersucht wurde.The compounds investigated show an atropine-like spasmolytic effect, which was investigated on the isolated duodenum of rats.
Toxizitättoxicity
Die Toxizität der erfindungsgemäßen Amine bzw. Pentanderivate der allgemeinen Formel II beträgt bei intravenöser Verabreichung etwa 15 bis 30 mg/kg. Die Verbindung mit der stärksten harntreibenden Wirkung, nämlich das Hydrochlorid des 1-Diisopropylamino-3-methyl-2-(5´-chlor-2´-äthoxyphenyl)-pentans, ist von den aufgeführten Stoffen die am wenigstens toxische.The toxicity of the amines or pentane derivatives of the general formula II according to the invention is about 15 to 30 mg / kg when administered intravenously. The compound with the strongest diuretic effect, namely the hydrochloride of 1-diisopropylamino-3-methyl-2- (5'-chloro-2'-ethoxyphenyl) pentane, is the least toxic of the substances listed.
Aufgrund ihrer interessanten Eigenschaften und ihrer geringen Toxizität können die Pentanderivate der Erfindung als Therapeutika in der Humanmedizin insbesondere zur Behandlung von Kreislaufstörungen verwendet werden. Sie werden beim Menschen in einer Dosis von etwa 5 bis 25 mg per os verabreicht.Because of their interesting properties and their low toxicity, the pentane derivatives of the invention can be used as therapeutic agents in human medicine, in particular for the treatment of circulatory disorders. They are administered per os in a dose of about 5 to 25 mg in humans.
Claims (6)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR6909226A FR2035785A6 (en) | 1969-03-28 | 1969-03-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2006433A1 true DE2006433A1 (en) | 1970-10-01 |
Family
ID=9031435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19702006433 Pending DE2006433A1 (en) | 1969-03-28 | 1970-02-12 | 1-Amino-3-methyl-2- (2´-ethoxy-5´-chlorophenyl) pentanes, process for their production and their use as active pharmaceutical ingredients |
Country Status (7)
| Country | Link |
|---|---|
| BE (1) | BE746287R (en) |
| CH (1) | CH506476A (en) |
| DE (1) | DE2006433A1 (en) |
| ES (1) | ES376793A2 (en) |
| FR (1) | FR2035785A6 (en) |
| GB (1) | GB1243955A (en) |
| NL (1) | NL7002398A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005037807A1 (en) * | 2003-10-14 | 2005-04-28 | Wyeth | Arylalkyl- and cycloalkylalkyl-piperazine derivatives and methods of their use |
| WO2005037207A3 (en) * | 2003-10-14 | 2006-09-21 | Wyeth Corp | Arylalkyl-piperazine derivatives for the treatment of conditions ameliorated by monoamine reuptake including vasomotor symptoms (vms) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7419980B2 (en) * | 2003-10-14 | 2008-09-02 | Wyeth | Fused-aryl and heteroaryl derivatives and methods of their use |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1178400A (en) * | 1966-12-13 | 1970-01-21 | Delalande Sa | Nitrogen Substituted Amines and their process of Preparation. |
-
1969
- 1969-03-28 FR FR6909226A patent/FR2035785A6/fr not_active Expired
-
1970
- 1970-02-02 GB GB482170A patent/GB1243955A/en not_active Expired
- 1970-02-12 DE DE19702006433 patent/DE2006433A1/en active Pending
- 1970-02-20 CH CH250570A patent/CH506476A/en unknown
- 1970-02-20 NL NL7002398A patent/NL7002398A/xx unknown
- 1970-02-20 BE BE746287D patent/BE746287R/en active
- 1970-02-21 ES ES376793A patent/ES376793A2/en not_active Expired
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005037807A1 (en) * | 2003-10-14 | 2005-04-28 | Wyeth | Arylalkyl- and cycloalkylalkyl-piperazine derivatives and methods of their use |
| WO2005037207A3 (en) * | 2003-10-14 | 2006-09-21 | Wyeth Corp | Arylalkyl-piperazine derivatives for the treatment of conditions ameliorated by monoamine reuptake including vasomotor symptoms (vms) |
| US7491723B2 (en) | 2003-10-14 | 2009-02-17 | Wyeth | Alkanol and cycloalkanol-amine derivatives and methods of their use |
| US7524846B2 (en) | 2003-10-14 | 2009-04-28 | Wyeth | Arylalkyl- and cycloalkylalkyl-piperazine derivatives and methods of their use |
Also Published As
| Publication number | Publication date |
|---|---|
| BE746287R (en) | 1970-08-20 |
| CH506476A (en) | 1971-04-30 |
| NL7002398A (en) | 1970-09-30 |
| GB1243955A (en) | 1971-08-25 |
| FR2035785A6 (en) | 1970-12-24 |
| ES376793A2 (en) | 1972-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2702119C2 (en) | Substituted anilinoacetamidoxime derivatives and pharmaceuticals containing them | |
| DE2528360A1 (en) | NEW PYRIMIDINS, THE PROCESS FOR THEIR MANUFACTURING AND THE PHARMACEUTICAL PREPARATIONS CONTAINING THEM | |
| DE2043933B2 (en) | N- (BETA-NAPHTHYLAMINOMETHYL) -AMINOCARBONIC ACIDS AND THESE MEDICINAL PRODUCTS | |
| DE3334757A1 (en) | PIPERAZINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICAL PREPARATIONS CONTAINING THESE COMPOUNDS | |
| DE3216843C2 (en) | 3-Thiomethyl-pyridine derivatives, processes for their preparation and pharmaceuticals containing these compounds | |
| DE1807218A1 (en) | Oxotremorine antagonists and processes for their preparation | |
| DE2713933C2 (en) | ||
| DE2802864A1 (en) | 3-ISOBUTOXY-2-PYRROLIDINO-N-PHENYL-N-BENZYLPROPYLAMINE, METHOD FOR PRODUCING THE SAME AND MEDICINAL PRODUCTS CONTAINING IT | |
| DE3218792C2 (en) | Isoprenylamine derivatives and their acid addition salts, and pharmaceutical compositions containing them | |
| DE2006433A1 (en) | 1-Amino-3-methyl-2- (2´-ethoxy-5´-chlorophenyl) pentanes, process for their production and their use as active pharmaceutical ingredients | |
| DE3025238A1 (en) | BASIC CYCLOAL CANON OXIMETERS, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THEM | |
| DE2609746A1 (en) | PIPERAZINE COMPOUNDS AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS | |
| DE1963317A1 (en) | Chemical processes and products | |
| DE2336670A1 (en) | AMINO ETHERS OF O-THYMOTIC ACID ESTERS | |
| DE2513136B2 (en) | N- (I -benzylpiperid-4-yl) -benzamides, process for their preparation and pharmaceutical preparations containing them | |
| AT387964B (en) | METHOD FOR PRODUCING NEW PIPERAZINE DERIVATIVES AND ENANTIOMERS OR DIASTEREOMERS THEREOF | |
| AT259574B (en) | Process for the production of the new 7- (picolylamino-alkyl) -theophyllins and their acid addition salts | |
| AT237603B (en) | Process for the production of new o-toluidides | |
| AT282593B (en) | PROCESS FOR THE PREPARATION OF NEW RACEMIC OR OPTICALLY ACTIVE (1-2'-NITRILOPHENOXY) -2-HYDROXY-3-ISOPROPYLAMINOPROPANE AND ITS SALTS | |
| DE2557446C2 (en) | 1- (2'-Aroyl-eth-1'-yl) -2- (4 "- acetamido-piperazin-1" - yl-methyl) -benzimidazoles, processes for their preparation and pharmaceuticals containing these compounds | |
| DE69426771T2 (en) | DOPAMINE INCORPORATION INHIBITORS FOR TREATING PARKINSON'S SYNDROME | |
| DE1593918C (en) | Basically substituted phthalans and their pharmacologically non-toxic acid addition salts and processes for their production | |
| DE1235310B (en) | Process for the production of nopinic acid derivatives | |
| AT282592B (en) | PROCESS FOR THE PREPARATION OF NEW RACEMIC OR OPTICALLY ACTIVE (1-2'-NITRILOPHENOXY) -2-HYDROXY-3-ISOPROPYLAMINOPROPANE AND ITS SALTS | |
| AT255034B (en) | Process for the preparation of O, S-dialkoxycarbonylthiamines |