CH497378A - 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in - Google Patents
1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used inInfo
- Publication number
- CH497378A CH497378A CH1103365A CH1103365A CH497378A CH 497378 A CH497378 A CH 497378A CH 1103365 A CH1103365 A CH 1103365A CH 1103365 A CH1103365 A CH 1103365A CH 497378 A CH497378 A CH 497378A
- Authority
- CH
- Switzerland
- Prior art keywords
- isopropylamino
- hydroxy
- propane
- isopropoxy
- phenoxy
- Prior art date
Links
- YDOOFGNGBOQBCC-UHFFFAOYSA-N 1-(propan-2-ylamino)-3-(2-propan-2-yloxyphenoxy)propan-2-ol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OC(C)C YDOOFGNGBOQBCC-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 claims abstract description 5
- 230000007062 hydrolysis Effects 0.000 claims abstract description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000001294 propane Substances 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 abstract 1
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- -1 oxycarbonyl radicals Chemical class 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- FZKCAHQKNJXICB-UHFFFAOYSA-N 2,1-benzoxazole Chemical compound C1=CC=CC2=CON=C21 FZKCAHQKNJXICB-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000208011 Digitalis Species 0.000 description 1
- 206010015856 Extrasystoles Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
1-Isopropylamino-2-hydroxy-3-(2'-isopropoxy-phenoxy)-propane, pharmaceutically used in heart and circulatory disorders. Cpds. of formula:- is prepared by cleaving off from 2-hydroxyl group of 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy-phenoxy)-propane a residue that may be cleaved off by hydrolysis or hydrogenolysis, such as alpha-arylalkyl residue, e.g. benzyl, or tert. butoxycarbonyl or lower alkanoyl.
Description
Verfahren zur Herstellung des neuen 1-Isopropylamino-2-hydroxy-3-(2-isopropox phenoxy)-propans und seiner Salze
Gegenstand der Erfindung ist ein Verfahren zur Herstellung des l-Isopropylamino-2-hydroxy-3-(2'-iso- propoxy-phenoxy)-propans der Formel
EMI1.1
Die neue Verbindung besitzt wertvolle pharmakologische Eigenschaften. Insbesondere bewirkt sie eine Hemmung adrenergischer ss-Rezeptoren. So hemmt sie z B. an der mit Dial narkotisierten Katze oder am wachen Hund durch Isoproterenol hervorgerufene Blutdrucksenkungen in Dosen von O,l-lmg/kg i. v. oder 2-3 mg/kg p. o. Sie ist in der Lage, Digitalis-iduzierte Extrasystolen zu unterdrücken, wie z. B. aus Experimenten mit einer Dosis von 0,3-1 mg/kg i. v. am narkotisierten Hund hervorgeht.
Die Verbindung kann dementsprechend bei Herz- und Kreislauferkrankungen als Medikament angewendet werden.
Das erfindungsgemässe Verfahren zur Herstellung der neuen Verbindungen ist dadurch gekennzeichnet, dass man in einem l-Isopropylamino-2-hydroxy-3- (2'-isopropoxy-phenoxy)-propan oder einem Salz davon, das an der 2-Hydroxylgruppe einen durch Hydrolyse oder Hydrogenolyse abspaltbaren Rest aufweist, diesen abspaltet. Solche Reste sind z. B. a-Arylalkylreste, wie ein Benzylrest, Oxycarbonylreste, wie der Benzyloxy carbonylrest oder der tert.-Butoxycarbonylrest, oder Acylreste von Carbonsäuren, wie niedere Alkanoylreste, z. B. der Acetylrest.
Die Hydrolyse und Hydrogenolyse werden in üblicher Weise, letztere besonders mit katalytischer Hydrierung vorgenommen.
Die Ausgangsstoffe sind bekannt oder können nach an sich bekannten Methoden gewonnen werden.
Je nach den Verfahrensbedingungen und Ausgangsstoffen erhält man den Endstoff in freier Form oder in der ebenfalls in der Erfindung inbegriffenen Form seiner Salze. Die Salze des Endstoffs können in an sich bekannter Weise, z. B. mit Alkalien oder Ionenaustauschern, in die freie Base übergeführt werden. Von der letzteren lassen sich durch Umsetzung mit organischen oder anorganischen Säuren, insbesondere solchen, die zur Bildung von therapeutisch verwendbaren Salzen geeignet sind, Salze gewinnen.
Als solche Säuren seien beispielsweise genannt: Halogenwasserstoffsäuren, Schwefelsäuren, Phosphorsäuren, Salpetersäure, Perchlorsäure, aliphatische, alicyclische, aromatische oder heterocyclische Carbon- oder Sulfonsäuren, wie Ameisen-, Essig-, Propion-, Bernstein-, Glykol-, Milch-, Äpfel-, Wein-, Zitronen-, Ascorbin-, Malein-, Hydroxymalein- oder Brenztraubensäure; Phenylessig-, Benzoe-, p-Aminobenzoe-, Anthranil-, p-Hydroxybenzoe-, Salicyl- oder p-Aminosalicylsäure, Embonsäure, Methansulfon-, Äthansulfon-, Hydroxyäthansulfon-, Äthylensulfonsäure; Halogenbenzolsulfon-, Toluolsulfon-, Naphthalinsulfonsäure oder Sulfanilsäure; Methionin, Tryptophan, Lysin oder Arginin.
Diese oder andere Salze der neuen Verbindung, wie z. B. die Pikrate, können auch zur Reinigung der erhaltenen freien Base dienen, indem man die freie Base in Salze überführt, diese abtrennt und aus den Salzen wiederum die Base freimacht. Infolge der engen Beziehungen zwischen der neuen Verbindung in freier Form und in Form ihrer Salze sind im vorausgegangenen und nachfolgend unter der freien Base sinn- und zweck mässig gegebenenfalls auch die entsprechenden Salze zu verstehen.
Die Erfindung betrifft auch diejenigen Ausführungsformen des Verfahrens, nach denen man einen Ausgangsstoff in Form eines unter den Reaktionsbedingungen gebildeten rohen Gemisches oder in Form eines Salzes verwendet.
Die neue Verbindung kann als Racemat oder in Form der Antipoden vorliegen. Das Racemat lässt sich in üblicher Weise in die Antipoden zerlegen.
Die neue Verbindung kann z. B. in Form pharmazeutischer Präparate Verwendung finden, welche sie in freier Form oder gegebenenfalls in Form ihrer Salze in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharmazeutischen organischen oder anorganischen, festen oder flüssigen Trägermaterial enthalten.
In dem folgenden Beispiel sind die Temperaturen in Celsiusgraden angegeben.
Beispiel
12,0 g 1-(Isopropylaminof2-acetoxy-3-(2'-isoprop- oxy-phenoxy)-propan werden in 100 ml Äthanol gelöst und nach Zugabe von 30 ml 2n Natronlaugc während 1 Stunde unter Rückfluss gekocht. Hicrauf dampft man im Vakuum ein und kristallisiert den Rückstand aus Petroläther um. Man erhält so das l-(lsopropylamino) 9-hydroxy-3-(2'-isopropoxy-phenoxy)-propan der Formel
EMI2.1
das nach Umkristallisation aus Essigester/Petroläther bei 60-61 und dessen Hydrochlorid bei 129-130 schmilzt.
Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (2-isopropox phenoxy) propane and its salts
The invention relates to a process for the preparation of l-isopropylamino-2-hydroxy-3- (2'-isopropoxy-phenoxy) -propane of the formula
EMI1.1
The new compound has valuable pharmacological properties. In particular, it inhibits adrenergic ß-receptors. It inhibits, for example, decreases in blood pressure caused by isoproterenol in doses of 0.1-1 mg / kg i in cats anesthetized with Dial or in the awake dog. v. or 2-3 mg / kg p. o. It is able to suppress digitalis-induced extrasystoles, such as B. from experiments with a dose of 0.3-1 mg / kg i. v. on the anesthetized dog.
The compound can accordingly be used as a medicament for heart and circulatory diseases.
The process according to the invention for the preparation of the new compounds is characterized in that in an 1-isopropylamino-2-hydroxy-3- (2'-isopropoxyphenoxy) propane or a salt thereof which is attached to the 2-hydroxyl group by hydrolysis or hydrogenolysis has cleavable residue, splits this off. Such residues are e.g. B. a-Arylalkyl radicals, such as a benzyl radical, oxycarbonyl radicals, such as the benzyloxy carbonyl radical or the tert-butoxycarbonyl radical, or acyl radicals of carboxylic acids, such as lower alkanoyl radicals, e.g. B. the acetyl radical.
The hydrolysis and hydrogenolysis are carried out in the usual way, the latter especially with catalytic hydrogenation.
The starting materials are known or can be obtained by methods known per se.
Depending on the process conditions and starting materials, the end product is obtained in free form or in the form of its salts, which is also included in the invention. The salts of the end product can in a conventional manner, for. B. with alkalis or ion exchangers, are converted into the free base. Salts can be obtained from the latter by reaction with organic or inorganic acids, in particular those which are suitable for the formation of therapeutically useful salts.
Examples of such acids are: hydrohalic acids, sulfuric acids, phosphoric acids, nitric acid, perchloric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as formic, acetic, propionic, succinic, glycolic, lactic, apple , Tartaric, citric, ascorbic, maleic, hydroxymaleic or pyruvic acid; Phenylacetic, benzoic, p-aminobenzoic, anthranil, p-hydroxybenzoic, salicylic or p-aminosalicylic acid, emboxylic acid, methanesulphonic, ethanesulphonic, hydroxyethanesulphonic, ethylene sulphonic acid; Halobenzenesulfonic, toluenesulfonic, naphthalenesulfonic acid or sulfanilic acid; Methionine, tryptophan, lysine or arginine.
These or other salts of the new compound, such as. B. the picrates, can also be used to purify the free base obtained by converting the free base into salts, separating them and in turn frees the base from the salts. As a result of the close relationships between the new compound in free form and in the form of its salts, in the preceding and in the following the free base is meaningfully and appropriately also the corresponding salts.
The invention also relates to those embodiments of the process in which a starting material is used in the form of a crude mixture formed under the reaction conditions or in the form of a salt.
The new compound can be present as a racemate or in the form of the antipodes. The racemate can be broken down into the antipodes in the usual way.
The new connection can e.g. B. in the form of pharmaceutical preparations are used which they contain in free form or optionally in the form of their salts in a mixture with a pharmaceutical organic or inorganic, solid or liquid carrier material suitable for enteral or parenteral administration.
In the following example the temperatures are given in degrees Celsius.
example
12.0 g of 1- (isopropylaminof2-acetoxy-3- (2'-isopropoxy-phenoxy) -propane are dissolved in 100 ml of ethanol and, after the addition of 30 ml of 2N sodium hydroxide solution, refluxed for 1 hour Vacuum and the residue recrystallizes from petroleum ether, giving l- (isopropylamino) 9-hydroxy-3- (2'-isopropoxyphenoxy) propane of the formula
EMI2.1
which, after recrystallization from ethyl acetate / petroleum ether, melts at 60-61 and its hydrochloride at 129-130.
Claims (1)
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1583167A CH455835A (en) | 1964-10-14 | 1964-10-14 | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (2'-isopropoxyphenoxy) propane or its salts |
| CH1583467A CH455837A (en) | 1964-10-14 | 1964-10-14 | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (2'-isopropoxyphenoxy) propane or its salts |
| CH1583367A CH455836A (en) | 1964-10-14 | 1964-10-14 | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (2'-isopropoxyphenoxy) propane or its salts |
| CH1232870A CH498083A (en) | 1965-08-05 | 1965-08-05 | 1-isopropyl-amino-2-hydroxy-3-(2'-ispropoxy - phenoxy) propane and salts with pharmacolo |
| CH1103365A CH497378A (en) | 1965-08-05 | 1965-08-05 | 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in |
| CH1232770A CH498803A (en) | 1965-08-05 | 1965-08-05 | 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological |
| JP40059557A JPS4822688B1 (en) | 1964-10-14 | 1965-09-30 | |
| AT225667A AT268249B (en) | 1964-10-14 | 1965-10-13 | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (2'-isopropoxyphenoxy) propane and its salts |
| NL6513264A NL6513264A (en) | 1964-10-14 | 1965-10-13 | |
| ES0318432A ES318432A1 (en) | 1964-10-14 | 1965-10-13 | Procedure for the obtaining of a secondary amina. (Machine-translation by Google Translate, not legally binding) |
| SE13277/65A SE335357B (en) | 1964-10-14 | 1965-10-13 | |
| AT920067A AT266084B (en) | 1964-10-14 | 1965-10-13 | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (o-isopropoxyphenoxy) propane and its salts |
| AT225767A AT266082B (en) | 1965-08-05 | 1965-10-13 | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (o-isopropoxyphenoxy) propane and its salts |
| JP42060898A JPS4825176B1 (en) | 1964-10-14 | 1967-09-23 | |
| DE19691493568 DE1493568A1 (en) | 1964-10-14 | 1969-04-09 | New 1-amino-2-hydroxy-3-alkoxyphenoxy-propane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1103365A CH497378A (en) | 1965-08-05 | 1965-08-05 | 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH497378A true CH497378A (en) | 1970-10-15 |
Family
ID=4369370
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1103365A CH497378A (en) | 1964-10-14 | 1965-08-05 | 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in |
| CH1232870A CH498083A (en) | 1965-08-05 | 1965-08-05 | 1-isopropyl-amino-2-hydroxy-3-(2'-ispropoxy - phenoxy) propane and salts with pharmacolo |
| CH1232770A CH498803A (en) | 1965-08-05 | 1965-08-05 | 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1232870A CH498083A (en) | 1965-08-05 | 1965-08-05 | 1-isopropyl-amino-2-hydroxy-3-(2'-ispropoxy - phenoxy) propane and salts with pharmacolo |
| CH1232770A CH498803A (en) | 1965-08-05 | 1965-08-05 | 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological |
Country Status (2)
| Country | Link |
|---|---|
| AT (1) | AT266082B (en) |
| CH (3) | CH497378A (en) |
-
1965
- 1965-08-05 CH CH1103365A patent/CH497378A/en not_active IP Right Cessation
- 1965-08-05 CH CH1232870A patent/CH498083A/en not_active IP Right Cessation
- 1965-08-05 CH CH1232770A patent/CH498803A/en not_active IP Right Cessation
- 1965-10-13 AT AT225767A patent/AT266082B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| CH498803A (en) | 1970-11-15 |
| AT266082B (en) | 1968-11-11 |
| CH498083A (en) | 1970-10-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |