CH556323A - N-napthyl-n-alpha-hydroxyphenethyl- - amines - Google Patents
N-napthyl-n-alpha-hydroxyphenethyl- - aminesInfo
- Publication number
- CH556323A CH556323A CH477673A CH477673A CH556323A CH 556323 A CH556323 A CH 556323A CH 477673 A CH477673 A CH 477673A CH 477673 A CH477673 A CH 477673A CH 556323 A CH556323 A CH 556323A
- Authority
- CH
- Switzerland
- Prior art keywords
- hydrogen atom
- formula
- radical
- lower alkyl
- acid addition
- Prior art date
Links
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- -1 alkylene radical Chemical group 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims 1
- 239000003908 antipruritic agent Substances 0.000 abstract description 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 2
- 125000002252 acyl group Chemical group 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 239000000043 antiallergic agent Substances 0.000 abstract 1
- 230000000572 bronchospasmolytic effect Effects 0.000 abstract 1
- 150000002576 ketones Chemical class 0.000 abstract 1
- 229910052987 metal hydride Inorganic materials 0.000 abstract 1
- 150000004681 metal hydrides Chemical class 0.000 abstract 1
- 229940124549 vasodilator Drugs 0.000 abstract 1
- 239000003071 vasodilator agent Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000004480 active ingredient Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- CWKVFRNCODQPDB-UHFFFAOYSA-N 1-(2-aminoethylamino)propan-2-ol Chemical group CC(O)CNCCN CWKVFRNCODQPDB-UHFFFAOYSA-N 0.000 description 1
- VTSPJLHFXSMCCC-UHFFFAOYSA-N 1-(3,4-dihydroxyphenyl)-2-(2-ethylimidazol-1-yl)ethanone;hydrochloride Chemical compound Cl.CCC1=NC=CN1CC(=O)C1=CC=C(O)C(O)=C1 VTSPJLHFXSMCCC-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- VEYCCHNUJNXSRR-UHFFFAOYSA-N 4-naphthalen-1-ylbutan-2-one Chemical compound C1=CC=C2C(CCC(=O)C)=CC=CC2=C1 VEYCCHNUJNXSRR-UHFFFAOYSA-N 0.000 description 1
- VZVBXISLBQEWKU-UHFFFAOYSA-N 5-(2-amino-1-hydroxyethyl)benzene-1,3-diol Chemical compound NCC(O)C1=CC(O)=CC(O)=C1 VZVBXISLBQEWKU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LPDOGIKTLWZIOL-UHFFFAOYSA-N OC1=CC=C(C=C1)C(CNC(CC1=CC=C(C2=CC=CC=C12)O)C)O Chemical compound OC1=CC=C(C=C1)C(CNC(CC1=CC=C(C2=CC=CC=C12)O)C)O LPDOGIKTLWZIOL-UHFFFAOYSA-N 0.000 description 1
- PLULGMYUFGQQLZ-UHFFFAOYSA-N OC=1C=C(C=C(C=1)O)C(CNC(C)CCC1=CC=CC2=CC=CC=C12)O Chemical compound OC=1C=C(C=C(C=1)O)C(CNC(C)CCC1=CC=CC2=CC=CC=C12)O PLULGMYUFGQQLZ-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- GJQBHOAJJGIPRH-UHFFFAOYSA-N benzoyl cyanide Chemical class N#CC(=O)C1=CC=CC=C1 GJQBHOAJJGIPRH-UHFFFAOYSA-N 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 230000001813 broncholytic effect Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- VQXINLNPICQTLR-UHFFFAOYSA-N carbonyl diazide Chemical class [N-]=[N+]=NC(=O)N=[N+]=[N-] VQXINLNPICQTLR-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QHGUCRYDKWKLMG-UHFFFAOYSA-N octopamine Chemical compound NCC(O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-BKFZFHPZSA-N platinum-200 Chemical compound [200Pt] BASFCYQUMIYNBI-BKFZFHPZSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- NVIFVTYDZMXWGX-UHFFFAOYSA-N sodium metaborate Chemical compound [Na+].[O-]B=O NVIFVTYDZMXWGX-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
N-naphtyl-N-alpha-hydroxyphenethyl-amines. Novel cpds. of formula (where A = 2-6C alkylene; R1 = H, lower alkyl or OR6 where R6 = H or lower acyl; R2 = H, lower alkyl or alkoxy; R3 = H, Me or Et; R4 = H, lower alkyl or alkoxy; R5 = H, OR6 or alkylsulphonamido) are vasodilators, anti-pruritic agents, antiallergic agents, bronchospasmolytics and uterospasmolytics. They may be prepd. e.g. by redn. of the corresp. ketone cpd. with complex metal hydride or by the Meerwein-Ponndorf redn.
Description
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen Verbindungen der Formel 1
EMI1.1
in der
B einen Alkylenrest mit 1 bis 4 Kohlenstoffatomen,
R1 ein Wasserstoffatom, einen niederen Alkyl- oder Alkoxyrest oder die Gruppe -OR6,
R2 ein Wasserstoffatom oder einen niederen Alkyl- oder Alkoxyrest,
R3 ein Wasserstoffatom, einen Methyl- oder Äthylrest,
R4 ein Wasserstoffatom, einen niederen Alkyl- oder Alkoxyrest, R5 ein Wasserstoffatom, die Gruppe -OR6 oder einen Alkylsulfonamidorest,
R6 ein Wasserstoffatom oder einen niederen Acylrest und R9 ein Wasserstoffatom oder eine Methylgruppe bedeutet.
Die Kohlenstoffketten der genannten Reste können gegebenenfalls unverzweigt oder verzweigt sein. Die Verbindungen der Formel 1 können als Racemate oder in optisch aktiven Formen vorliegen, und zwar als freie Basen oder als Säureadditionssalze.
Gemäss der Erfindung werden die neuen Verbindungen dadurch hergestellt, dass man unter den Bedingungen der reduktiven Aminierung eine Oxoverbindung der Formel 2
EMI1.2
mit einemAmin der Formel 3
EMI1.3
umsetzt.
Als Reduktionsmittel werden Wasserstoff und Hydrierungskatalysatoren, z. B. Raney-Nickel, Platin, Palladium, oder komplexe Hydride, z. B. Natriumboranat, verwendet.
Die Ausgangsstoffe kann man nach üblichen Methoden erhalten. Die Amine der Formel 3 sind beispielsweise über entsprechende Isonitrosoketone, Cyanhydrine, Benzoylcyanide und Azidoketone zugänglich. Es ist jedoch nicht erforderlich, zunächst die freien Amine herzustellen und zu isolieren; vielmehr können die genannten Verbindungen als solche der reduktiven Aminierung unterworfen werden.
Gewünschtenfalls werden die zunächst erfindungsgemäss erhaltenen Substanzen in die optisch aktiven Formen aufgespalten und/oder in gewünschte Säureadditionssalze bzw.
freie Basen übergeführt. Zu diesen Trennungen bzw. Umsetzungen bedient man sich ebenfalls der üblichen Methoden.
Die erfindungsgemäss erhältlichen Verbindungen sind wertvolle Wirkstoffe für Arzneimittel. Sie haben peripher gefässerweiternde, juckreizstillende und anti allergische Wirkung und bewirken Bronchospasmolyse und Uterusspasmolyse. Die genannten Wirkungen sind stark ausgeprägt und halten lange an; zugleich sind die unerwünschten Nebenwirkungen deutlich geringer als bei den bekannten Verbindungen derselben Wirkungsrichtung.
Als bevorzugte Wirkstoffe sind diejenigen erfindungsgemäss erhältlichen Verbindungen zu nennen, in denen B eine Mono- oder Dimethylengruppe bedeutet und worin das dem Stickstoffatom benachbarte Kohlenstoffatom durch eine Methylgruppe substituiert ist (R9 = CH3), und in denen R, Wasserstoff oder OR6, R2 Wasserstoff, R4 Wasserstoff, Methyl oder Methoxy und R5 Wasserstoff, OR6 oder CH3-SO2-NH- bedeutet.
Für die Anwendung als Arzneimittel werden die erfindungsgemäss erhältlichen Wirkstoffe mit den in der galenischen Pharmazie gebräuchlichen Hilfsstoffen zu den üblichen Arzneimittelformen verarbeitet, z. B. zu Tabletten, Dragees, Kapseln, Pudern, Salben, Tinkturen, Tropfen, Injektionslösungen, Aerosolen.
Die Einzeldosis für die orale Anwendung (Tabletten, Dragees, Kapseln) beträgt etwa 2 bis 80 mg, vorzugsweise 5 bis 20 mg. Für die parenterale Anwendung als Broncholytikum werden Lösungen mit etwa 50y bis 5 mg Wirkstoff pro Einzeldosis hergestellt. Für die Gefässerweiterung ist eine höhere parenterale Einzeldosis erforderlich (etwa 0,5 bis 20 mg Wirkstoff). Die Anwendung in Form von Aerosolen erfolgt zweckmässig mit Dosiervorrichtungen, die pro Hub etwa 0,05 bis 2 mg Wirkstoff als Einzeldosis abgeben.
Das erfindungsgemässe Verfahren zur Herstellung der neuen Wirkstoffe ist in den folgenden Beispielen näher er läutert:
Beispiel 1 1 -(3,5 -Dihydroxyphenyl) -2-[4-( 1 -naphthyl) -2-butylamino] - äthanol (Sm 263)
Ein Gemisch von 8,5 g 1 -(3,5 -Dihydroxyphenyl) -2-amino- äthanol, 10 g 4-(1-Naphthyl)-2-butanon, 6 g Eisessig, 200 ml Methanol und 4 g Platinoxyd wird unter Normalbedingungen hydriert. Nach beendeter Aufnahme wird der Katalysator abfiitriert und die Lösung eingedampft. Der Rückstand wird in 100 ml Wasser gelöst, mit konzentrierter Salzsäure angesäuert und zweimal ausgeäthert. Die Wasserphase wird anschliessend mit wässerigem Ammoniak alkalisch gestellt, zweimal mit 100 ml Essigester extrahiert, mit Natriumsulfat getrocknet und eingedampft.
Der Rückstand wird mit Acetonitril versetzt und man erhält 1-(3,5-Dihydroxyphenyl 2-[4-( 1 -naphthyl) -2-butylamino] -äthanol (Fp 166-169 C).
Beispiel 2 1 -(4-Hydroxyphenyl) -2-[1 -(4-hydroxy-1 -naphthyl) -2 propylamino]-äthanol (Sm 542)
7,65 g 1-(p-Hydroxyphenyl)-2-aminoäthanol, 10 g 2 (4-Hydroxy-1-naphthyl)-aceton, 6 g Eisessig, 4 g Platinoxyd und 200 ml Methanol werden bei Normalbedingungen hydriert. Nach beendeter Aufnahme wird der Katalysator abgetrennt, die Lösung eingedampft und der Rückstand mit Wasser und wässerigem Ammoniak versetzt. Nach zweimaligem Extrahieren mit Essigester wird mit Natriumsulfat getrocknet und eingedampft. Das erhaltene 1-(4-Hydroxyphenyl) 2-[l-(4-hydroxy-l -naphthyl) -2-propylamino]-äthanol wird mit wässeriger Salzsäure in das Hydrochlorid überführt, welches bei 199-202 C schmilzt.
Analog werden hergestellt: Nr. Verbindung Salz mit Schmelzpunkt in C a 1 -(4-Hydroxyphenyl) -2 -[1 -(4 -methoxy-1 -naphthyl) -2 -propyl- (Base) 190-192 amino]-äthanol (Sm 541) b 1-(4-Hydroxyphenyl)-2-[2-(4-methyl-1-naphthyl)-äthylamino]- HCI 162 äthanol (Sm 537) c 1 -(3 -Hydroxyphenyl) -2 -[2-(4 -methoxy-1 -naphthyl) -äthylamino] - HCI 142-144 äthanol (Sm 505) d 1 -(4-Hydroxyphenyl) -2 [2 -(4-hydroxy-1 -naphthyl) -äthylamino] - HCI 97 äthanol (Sm 245) kristallisiert mit 1 HzO e 1 -(3,4 -Dihydroxyphenyl) -2 -[2 -(4-methoxy-1 -naphthyl) -äthyl- HCI 195-196 amino]-äthanol (Sm 278) f 1 -(3 4-Dihydroxyphenyl) -2 -[2 -(4-hydroxy-1 -naphthyl) -äthyl- HBr 167-169 amino]-äthanol (Sm 279) g <RTI
ID=2.9> 1-(3,4-Dihydroxyphenyl)-2-[2-(4,8-dimethoxy-1-naphthyl)- HCI 198-199 amino]-äthanol (Sm 290) h 1 -(4 -Hydroxyphenyl) -2-[2-(1 -naphthyl) -äthylamino] - (Base) 143-146 äthanol (Sm 506) i 1 -(3,5 -Dihydroxyphenyl) -2-[2 -(4-hydroxy-1 -naphthyl) - HBr 222 äthylamino]-äthanol (Sm 261)
The invention relates to a process for the preparation of new compounds of formula 1
EMI1.1
in the
B is an alkylene radical with 1 to 4 carbon atoms,
R1 is a hydrogen atom, a lower alkyl or alkoxy radical or the group -OR6,
R2 is a hydrogen atom or a lower alkyl or alkoxy radical,
R3 is a hydrogen atom, a methyl or ethyl radical,
R4 is a hydrogen atom, a lower alkyl or alkoxy radical, R5 is a hydrogen atom, the group -OR6 or an alkylsulfonamido radical,
R6 represents a hydrogen atom or a lower acyl radical and R9 represents a hydrogen atom or a methyl group.
The carbon chains of the radicals mentioned can optionally be unbranched or branched. The compounds of formula 1 can exist as racemates or in optically active forms, specifically as free bases or as acid addition salts.
According to the invention, the new compounds are prepared by an oxo compound of the formula 2 under the conditions of the reductive amination
EMI1.2
with an amine of Formula 3
EMI1.3
implements.
Hydrogen and hydrogenation catalysts, e.g. B. Raney nickel, platinum, palladium, or complex hydrides, e.g. B. sodium boranate used.
The starting materials can be obtained by customary methods. The amines of formula 3 are accessible, for example, via corresponding isonitrosoketones, cyanohydrins, benzoyl cyanides and azido ketones. However, it is not necessary to first prepare and isolate the free amines; Rather, the compounds mentioned can be subjected to reductive amination as such.
If desired, the substances initially obtained according to the invention are split into the optically active forms and / or into desired acid addition salts or
transferred to free bases. The usual methods are also used for these separations or conversions.
The compounds obtainable according to the invention are valuable active ingredients for pharmaceuticals. They have peripheral vasodilator, antipruritic and anti-allergic effects and cause bronchospasmolysis and uterine spasmolysis. The effects mentioned are very pronounced and last a long time; at the same time, the undesirable side effects are significantly lower than with the known compounds of the same direction of action.
Preferred active ingredients are those compounds obtainable according to the invention in which B is a mono- or dimethylene group and in which the carbon atom adjacent to the nitrogen atom is substituted by a methyl group (R9 = CH3), and in which R, hydrogen or OR6, R2 is hydrogen, R4 denotes hydrogen, methyl or methoxy and R5 denotes hydrogen, OR6 or CH3-SO2-NH-.
For use as medicaments, the active ingredients obtainable according to the invention are processed into the usual medicament forms with the auxiliaries customary in galenic pharmacy, eg. B. tablets, coated tablets, capsules, powders, ointments, tinctures, drops, injection solutions, aerosols.
The single dose for oral use (tablets, coated tablets, capsules) is about 2 to 80 mg, preferably 5 to 20 mg. For parenteral use as a broncholytic, solutions containing about 50 to 5 mg of active ingredient per single dose are prepared. A higher parenteral single dose is required for vasodilation (about 0.5 to 20 mg of active ingredient). The application in the form of aerosols is expediently carried out with metering devices which deliver about 0.05 to 2 mg of active ingredient as a single dose per stroke.
The process according to the invention for preparing the new active ingredients is explained in more detail in the following examples:
Example 1 1 - (3,5-Dihydroxyphenyl) -2- [4- (1 -naphthyl) -2-butylamino] - ethanol (Sm 263)
A mixture of 8.5 g of 1 - (3,5-dihydroxyphenyl) -2-amino-ethanol, 10 g of 4- (1-naphthyl) -2-butanone, 6 g of glacial acetic acid, 200 ml of methanol and 4 g of platinum oxide is under Hydrogenated normal conditions. After the uptake is complete, the catalyst is filtered off and the solution is evaporated. The residue is dissolved in 100 ml of water, acidified with concentrated hydrochloric acid and extracted twice with ether. The water phase is then made alkaline with aqueous ammonia, extracted twice with 100 ml of ethyl acetate, dried with sodium sulfate and evaporated.
Acetonitrile is added to the residue and 1- (3,5-dihydroxyphenyl 2- [4- (1-naphthyl) -2-butylamino] ethanol (melting point 166-169 ° C.) is obtained.
Example 2 1 - (4-Hydroxyphenyl) -2- [1 - (4-hydroxy-1-naphthyl) -2 propylamino] ethanol (Sm 542)
7.65 g of 1- (p-hydroxyphenyl) -2-aminoethanol, 10 g of 2 (4-hydroxy-1-naphthyl) acetone, 6 g of glacial acetic acid, 4 g of platinum oxide and 200 ml of methanol are hydrogenated under normal conditions. After the uptake is complete, the catalyst is separated off, the solution is evaporated and the residue is mixed with water and aqueous ammonia. After extracting twice with ethyl acetate, it is dried with sodium sulfate and evaporated. The 1- (4-hydroxyphenyl) 2- [l- (4-hydroxy-l-naphthyl) -2-propylamino] -ethanol obtained is converted into the hydrochloride, which melts at 199-202 ° C., with aqueous hydrochloric acid.
The following are prepared analogously: No. Compound Salt with melting point in C a 1 - (4-hydroxyphenyl) -2 - [1 - (4-methoxy-1-naphthyl) -2-propyl- (base) 190-192 amino] ethanol (Sm 541) b 1- (4-hydroxyphenyl) -2- [2- (4-methyl-1-naphthyl) ethylamino] - HCl 162 ethanol (Sm 537) c 1 - (3-hydroxyphenyl) -2 - [ 2- (4-methoxy-1-naphthyl) -äthylamino] - HCI 142-144 ethanol (Sm 505) d 1 - (4-hydroxyphenyl) -2 [2 - (4-hydroxy-1-naphthyl) -äthylamino] - HCl 97 ethanol (Sm 245) crystallizes with 1 HzO e 1 - (3,4-dihydroxyphenyl) -2 - [2 - (4-methoxy-1-naphthyl) ethyl HCl 195-196 amino] ethanol (Sm 278 ) f 1 - (3 4-Dihydroxyphenyl) -2 - [2 - (4-hydroxy-1-naphthyl) -ethyl-HBr 167-169 amino] -ethanol (Sm 279) g <RTI
ID = 2.9> 1- (3,4-dihydroxyphenyl) -2- [2- (4,8-dimethoxy-1-naphthyl) - HCl 198-199 amino] ethanol (Sm 290) h 1 - (4 -hydroxyphenyl ) -2- [2- (1 -naphthyl) -äthylamino] - (base) 143-146 ethanol (Sm 506) i 1 - (3,5-dihydroxyphenyl) -2- [2 - (4-hydroxy-1 - naphthyl) - HBr 222 ethylamino] ethanol (Sm 261)
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1962497A DE1962497C3 (en) | 1969-12-12 | 1969-12-12 | Naphthylalkyl-a-hydroxyphenethyl-amines, their preparation and pharmaceuticals containing them |
| CH1818970A CH556322A (en) | 1969-12-12 | 1970-12-09 | PROCESS FOR MANUFACTURING NEW NAPHTHYLALKYLAMINES. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH556323A true CH556323A (en) | 1974-11-29 |
Family
ID=25720616
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH477673A CH556323A (en) | 1969-12-12 | 1970-12-09 | N-napthyl-n-alpha-hydroxyphenethyl- - amines |
| CH477773A CH564509A5 (en) | 1969-12-12 | 1970-12-09 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH477773A CH564509A5 (en) | 1969-12-12 | 1970-12-09 |
Country Status (1)
| Country | Link |
|---|---|
| CH (2) | CH556323A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE883400L (en) * | 1987-11-13 | 1989-05-13 | Fuisz Technologies Ltd | Phenethanolamine derivatives |
| US20100168245A1 (en) | 2006-08-10 | 2010-07-01 | Wainer Irving W | Preparation of (r,r)-fenoterol and (r,r)-or (r,s)-fenoterol analogues and their use in treating congestive heart failure |
| BR112012022552A8 (en) | 2010-03-10 | 2017-12-05 | Stanford Res Inst Int | use of fenoterol and fenoterol analogs in the treatment of gliobastomas and astrocytomas and pharmaceutical composition comprising said compounds |
-
1970
- 1970-12-09 CH CH477673A patent/CH556323A/en not_active IP Right Cessation
- 1970-12-09 CH CH477773A patent/CH564509A5/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH564509A5 (en) | 1975-07-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |