DE2651574A1 - 3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors - Google Patents

3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors

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Publication number
DE2651574A1
DE2651574A1 DE19762651574 DE2651574A DE2651574A1 DE 2651574 A1 DE2651574 A1 DE 2651574A1 DE 19762651574 DE19762651574 DE 19762651574 DE 2651574 A DE2651574 A DE 2651574A DE 2651574 A1 DE2651574 A1 DE 2651574A1
Authority
DE
Germany
Prior art keywords
phenoxymethyl
piperidino
formula
compound
indole
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.)
Withdrawn
Application number
DE19762651574
Other languages
German (de)
Inventor
Wolfgang Dr Med Bartsch
Karl Prof Dr Med Dietmann
Walter-Gunar Dr Rer Nat Friebe
Wolfgang Dr Rer Nat Kampe
Gisbert Dr Med Sponer
Fritz Dr Phil Wiedemann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Diagnostics GmbH
Original Assignee
Boehringer Mannheim GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Boehringer Mannheim GmbH filed Critical Boehringer Mannheim GmbH
Priority to DE19762651574 priority Critical patent/DE2651574A1/en
Priority to US05/846,057 priority patent/US4146630A/en
Priority to AR269873A priority patent/AR218643A1/en
Priority to IL53323A priority patent/IL53323A/en
Priority to YU02664/77A priority patent/YU266477A/en
Priority to ZA00776647A priority patent/ZA776647B/en
Priority to NL7712220A priority patent/NL7712220A/en
Priority to AU30466/77A priority patent/AU510284B2/en
Priority to IT29456/77A priority patent/IT1087490B/en
Priority to FI773346A priority patent/FI62077C/en
Priority to CS777291A priority patent/CS228106B2/en
Priority to DD7700201951A priority patent/DD133801A5/en
Priority to GB46415/77A priority patent/GB1541547A/en
Priority to PL1977213346A priority patent/PL112683B1/en
Priority to PL1977201997A priority patent/PL110782B1/en
Priority to CH1367177A priority patent/CH636099A5/en
Priority to CA290,495A priority patent/CA1086740A/en
Priority to HU77BO1689A priority patent/HU177410B/en
Priority to SE7712720A priority patent/SE7712720L/en
Priority to BE182523A priority patent/BE860701A/en
Priority to FR7733907A priority patent/FR2370744A1/en
Priority to LU7778498A priority patent/LU78498A1/xx
Priority to DK500677A priority patent/DK500677A/en
Priority to SU772541695A priority patent/SU1041033A3/en
Priority to JP13559177A priority patent/JPS5363385A/en
Priority to AT808277A priority patent/AT361476B/en
Publication of DE2651574A1 publication Critical patent/DE2651574A1/en
Priority to CS785461A priority patent/CS228110B2/en
Priority to ES472746A priority patent/ES472746A1/en
Priority to ES472747A priority patent/ES472747A1/en
Priority to SU782675553A priority patent/SU890975A3/en
Priority to SU782674802A priority patent/SU826955A3/en
Priority to AR27565679A priority patent/AR222324A1/en
Priority to AR275657A priority patent/AR221081A1/en
Priority to AR275655A priority patent/AR221868A1/en
Priority to AT649879A priority patent/AT361479B/en
Priority to CH367682A priority patent/CH639086A5/en
Priority to CH233783A priority patent/CH643554A5/en
Priority to YU01288/83A priority patent/YU128883A/en
Priority to YU01289/83A priority patent/YU128983A/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles

Abstract

Aminopropanol derivs. of formula (I) and their physiologically acceptable salts are new. In (I), R1 and R2 are H, lower alkyl (opt. substd. by OH or alkanoyloxy), or COZ; X is OH, alkoxy or NR6R7; R6 and R7 are H or lower alkyl or hydroxyalkyl; R3 is H or OR8; R8 is H, lower alkanoyl or aroyl opt. substd. by halo lower alkyl or alkoxy, alkoxycarbonyl, OH, alkylthio, CN, NO2 or CF3; R4 and R5 are H, halo, OH, lower alkyl, alkoxy or alkylthio, COOH, benzyloxy, benzyloxycarbonyl or alkoxycarbonyl; X and Y are N or -C(R9)=; R9 is H, lower alkyl opt. substd. by OR8, or COZ. (I) are vasodilators (hypotensives) and inhibitors of beta-adrenergic receptors. In an example, 4- 2-hydroxy-3-(4-phenoxymethylpiperidino)propoxy indole was prepd. from 4-(2,3-epoxypropoxy)indole and 4-phenoxymethyl-piperidine.

Description

Ein neues Aminopropanol-Derivat und Verfahren zu dessen HerstellungA new aminopropanol derivative and process for its preparation

Die vorliegende Erfindung betrifft 4 4-[2-Hydroxy-3-[4-(phenoxymethyl)-piperiding -propoxy9-indol der Formel 1 dessen pharmakologisch vertraegliche Salze, Verfahren zu dessen Herstellung sowie pharmazeutische Zubereitungen mit einem Gehalt an der Verbindung der Formel 1.The present invention relates to 4 4- [2-hydroxy-3- [4- (phenoxymethyl) piperidine propoxy9-indole of the formula 1 its pharmacologically acceptable salts, processes for its production and pharmaceutical preparations containing the compound of formula 1.

Da die Verbindung der Formel I ein asymmetrisches Kohlenstoffatom besitzt, sind ferner Gegenstand der Erfindung die optisch aktiven Formen und racemischen Gemische der Verbindung.Since the compound of formula I has an asymmetric carbon atom possesses, the invention also relates to the optically active forms and racemic forms Mixtures of the compound.

Die Verbindung der Formel I und ihre pharmakologisch vertraeglichen Salze besitzen bei geringer Toxizitaet ausgepraegte blutdrucksenkende Eigenschaften; auperdem wird eine Hemmung adrenergischer ß-Rezeptoren beobachtet.The compound of formula I and its pharmacologically acceptable Salts have pronounced antihypertensive properties with low toxicity; In addition, an inhibition of adrenergic ß-receptors is observed.

Die Herstellung der neuen Verbindung ist dadurch gekennzeichnet, dap man in an sich bekannter Weise entweder a) eine Verbindung der allgemeinen Formel II in der Y einen reaktiven Rest darstellt und X die Gruppe bedeutet, wobei Z eine Hydroxylgruppe oder auch zusammen mit Y ein Sauerstoffatom sein kann, mit der Verbindung der Formel III umsetzt oder b)eine Verbindung der Formel IV mit einer Verbindung der allgemeinen Formel V in der X und Y die oben genannte Bedeutung haben, umsetzt und fuer den Fall, daß X die Gruppe bedeutet, anschließend reduziert.The preparation of the new compound is characterized in that, in a manner known per se, either a) a compound of the general formula II in which Y represents a reactive radical and X represents the group denotes, where Z can be a hydroxyl group or, together with Y, an oxygen atom, with the compound of the formula III converts or b) a compound of the formula IV with a compound of the general formula V in which X and Y have the meaning given above, and in the event that X represents the group means then reduced.

Die gemaeß Verfahren a) oder b) erhaltene Verbindung der Formel I kann anschließend gegebenenfalls in ihre pharmakologisch vertraeglichen Salze umgewandelt werden.The compound of formula I obtained according to process a) or b) can then optionally be converted into their pharmacologically acceptable salts will.

Reaktive Reste Y in Verbindungen der Formeln II und V sind insbesondere Saeurereste, z. B. von Halogenwasserstoffsaeuren und Sulfonsaeuren.Reactive radicals Y in compounds of the formulas II and V are in particular Acid residues, e.g. B. of hydrohalic acids and sulfonic acids.

Verbindungen der allgemeinen Formel II sind in Helv. 54, 2418 (1971), das Piperidin-Derivat der allgemeinen Formel III in der deutschen Patentanmeldung P 25 49 999.4 beschrieben.Compounds of the general formula II are in Helv. 54, 2418 (1971), the piperidine derivative of the general formula III in the German patent application P 25 49 999.4 described.

Die erfindungsgemäßen Verfahren werden zweckmaepig in einem unter den Reaktionsbedingungen inerten organischen Loesungsmittel, z. B. Toluol, Dioxan, Aethylenglykoldimethylaether, Aethanol, n-Butanol oder Dimethylformamid, gegebenenfalls in Gegenwart eines saeurebindenden Mittels, durchgefuehrt.The methods according to the invention are expediently in one under organic solvents inert to the reaction conditions, e.g. B. toluene, dioxane, Ethylene glycol dimethyl ether, ethanol, n-butanol or dimethylformamide, if appropriate in the presence of an acid-binding agent.

Die Umsetzung der Verbindung der Formel IV mit den Substanzen der allgemeinen Formel V gemaep Verfahren b) erfolgt zweckmäeßig unter Sauerstoffausschluß in Gegenwart eines Saeureakzeptors. Man kann aber auch Alkalisalze der Jdroxyverbindung der Formel lv einsetzen.The reaction of the compound of formula IV with the substances of General formula V according to process b) is expediently carried out with the exclusion of oxygen in the presence of an acid acceptor. But you can also use alkali metal salts of the hydroxy compound of the formula lv.

Die gegebenenfalls durchzufuehrende Reduktion der Gruppe erfolgt mittels komplexer Metallhydride wie z. B. Natriumborhydrid, oder durch katalytische lSydrierung mit Edelmetallkatalysatoren.Any reduction of the group to be carried out takes place by means of complex metal hydrides such. B. sodium borohydride, or by catalytic hydrogenation with noble metal catalysts.

Zur Ueberfuehrung der Verbindung der Formel I in ihre pharmakologisch unbedenklichen Salze setzt man diese vorzugsweise in einem organischen Loesungsmittel mit einer anorganischen oder organischen Saeure, z. B.To convert the compound of the formula I into its pharmacological harmless salts are preferably used in an organic solvent with an inorganic or organic acid, e.g. B.

Salzsaeure, Bronzasserstoffsaeure, Phosphorsaeure, Schwefelsaeure Essigsaeure, Zitronensaeure, Maleinsaeure oder Benzoesaeure, um.Hydrochloric acid, hydrobronide acid, phosphoric acid, sulfuric acid Acetic acid, citric acid, maleic acid or benzoic acid.

Die erfindungsgemäße Verbindung der Formel I fällt gemaß Verfahren a) oder b) in Form eines racemischen Gemisches an. Die Trennung des Racemats in die optisch aktiven Formen geschieht nach an sich bekannten Methoden über die diastereoisomeren Salze. Als aktive Säuren können vorwiegend Weinsäure, Apfelsäure, Camphersäure und Camphersulfonsäure verwendet werden.The compound of formula I according to the invention falls according to procedure a) or b) in the form of a racemic mixture. The separation of the racemate in the optically active forms take place according to methods known per se via the diastereoisomers Salts. Mainly tartaric acid, malic acid, camphoric acid and Camphorsulfonic acid can be used.

Zur Herstellung von Arzneimitteln wird die Verbindung der Formel I in an sich bekannter Weise mit geeigneten pharmazeutischen Trägersubstanzen, Aroma-, Geschmacks- und Farbstoffen gemischt und beispielsweise als Tabletten oder Dragees ausgeformt oder unter Zugabe entsprechender Hilfsstoffe in Wasser oder Öl, wie z.B. Olivenöl, suspendiert oder gelöst.For the production of medicaments, the compound of the formula I in a manner known per se with suitable pharmaceutical carrier substances, aroma, Flavors and colors mixed and for example as tablets or dragees shaped or with the addition of appropriate auxiliaries in water or oil, e.g. Olive oil, suspended or dissolved.

Die erfindungsgemäße neue Verbindung der Formel I und ihre Salze können in flüssiger oder fester Form enteral oder parenteral appliziert werden. Als Injektionsmedium kommt vorzugsweise Wasser zur Anwendung, welches die bei Injektionslösungen üblichen Zusatze wie Stabilisierungsmittel, Lösungsvermittler oder Puffer enthält. Derartige Zusätze sind z.B.The novel compound of the formula I according to the invention and its salts can be administered enterally or parenterally in liquid or solid form. As an injection medium comes preferably water for use, which is the case with injection solutions the usual additives such as stabilizers, solubilizers or buffers. Such additives are e.g.

Tartrat- und Citratpuffer, Äthanol, Komplexbildner (wie Athylendiamintetraessigsäure und deren nicht-toxische Salze), hochmolekulare Polymere (wie flüssiges Polyäthylenoxyd) zur Viskositätsregulierung. Feste Trägerstoffe sind z.B. Stärke, Lactose, Mannit, Methylcellulose, Talkum, hochdisperse Kieselsäuren, höher-molekulare Fettsäuren (wie Stearinsäure), Gelatine, Agar-Agar, Calciumphosphat, Magnesiumstearat, tierische und pflanzliche Fette und feste hochmolekulare Polymere (wie Polyäthylenglykole); für orale Applikation geeignete Zubereitungen können gewünschtenfalls Geschmacks- und Süßstoffe enthalten.Tartrate and citrate buffers, ethanol, complexing agents (such as ethylenediaminetetraacetic acid and their non-toxic salts), high molecular weight polymers (such as liquid polyethylene oxide) for viscosity regulation. Solid carriers are e.g. starch, lactose, mannitol, Methyl cellulose, talc, highly dispersed silicas, higher molecular fatty acids (such as stearic acid), gelatin, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats and solid high molecular weight polymers (such as polyethylene glycols); Preparations suitable for oral application can, if desired, taste and contain sweeteners.

Die Erfindung wird durch das folgende Beispiel näher erläutert: Beispiel 5-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]-propoxy}-indol Die Loesung von 6.0 g 4-(2.3-Epoxypropoxy)-indol und 6.0 g 4-(Phenoxymethyl)-piperidin in 50 ml n-Butanol wird 4-6 Stunden zum Sieden erhitzt Anschließend dampft man das toesungsmfttel im Vakuum ab. Der Rückstand wird in ca. 500-400 ml 0.5 N Essigsaeure aufgenommen und die Loesung mit Aether ausgeschuettelt. Die Aetherphase wird verworfen und die Wasserphase mit Kaliumcarbonatloesung alkalisch gestellt. Das ausgefallene Oel wird mit Aether/Essigester (1:1) mehrfach extrahiert. Man trocknet die organiscbe Phase, behandelt mit Aktivkohle und dampft die Loesung im Vakuum ein. Der Rueckstand wird in -einer Mischung aus 60 ml Aether und 25 ml Essigester geloest und die Loesung mit 3.ß g Essigsaeure versetzt. Man laeßt ueber Nacht kristallisieren und saugt dann ab. Nach Umkristallisieren aus Isopropanol erhaelt man 8.0 g (- 57 % d.Th.) 4-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]propoxy}-indol als Acetat vom Schmp. 127-129°C.The invention is explained in more detail by the following example: example 5- {2-Hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole The solution of 6.0 g 4- (2.3-epoxypropoxy) indole and 6.0 g 4- (phenoxymethyl) piperidine in 50 ml n-butanol is heated to boiling for 4-6 hours. Then the toesungsmfttel is evaporated Vacuum off. The residue is taken up in approx. 500-400 ml of 0.5 N acetic acid and the solution shaken out with ether. The ether phase is discarded and the water phase made alkaline with potassium carbonate solution. The precipitated oil is with ether / ethyl acetate (1: 1) extracted several times. The organic phase is dried and treated with activated charcoal and evaporates the solution in a vacuum. The residue is in a mixture of 60 ml of ether and 25 ml of ethyl acetate dissolved and the solution with 3 .3 g of acetic acid offset. Leave to crystallize overnight and then suction off. After recrystallization 8.0 g (-57% of theory) 4- {2-hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole are obtained from isopropanol as acetate with a melting point of 127-129 ° C.

Herstellung des Benzoats: 7.3 g 4-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]-propoxy}-indol werden in 25 ml Essigester geloest. Dazu gibt man eine Loesung von 2.3 g Benzoesaeure in 25 ml Essigester. Der ausgefallene Niederschlag wird abgesaugt und aus ca. 50 ml Isopropanol umkristallisiert. 1an erhaelt 4.4 g 5-{2-Hydroxy-4-[4-(phenoxymethyl)-piperidino]-propoxy}-indol als Benzoat vom Schmp. 146-1470C.Preparation of the benzoate: 7.3 g of 4- {2-hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole are dissolved in 25 ml of ethyl acetate. A solution of 2.3 g of benzoic acid is added to this in 25 ml of ethyl acetate. The deposited precipitate is filtered off with suction and from approx ml of isopropanol recrystallized. One receives 4.4 g of 5- {2-hydroxy-4- [4- (phenoxymethyl) piperidino] propoxy} indole as a benzoate of m.p. 146-1470C.

Claims (4)

P a t e n t a n s p r ü c h e 1. 4-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]-propoxy}-indol der Formel I sowie dessen pharmakologisch verträgliche Salze.Patent claims 1. 4- {2-Hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole of the formula I. and its pharmacologically acceptable salts. 2. Verfahren zur Herstellung von 4-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]-propoxy}-indol der Formel I sowie dessen pharmakologisch verträglichen Salzen, dadurch gekennzeichnet, daß man in an sich bekannter Weise entweder a) eine Verbindung der allgemeinen Formel II in der Y einen reaktiven Rest darstellt un.2. Process for the preparation of 4- {2-hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole of the formula I. and its pharmacologically acceptable salts, characterized in that either a) a compound of the general formula II in which Y represents a reactive radical un. X die Gruppe bedeutet, wobei Z eine Hydroxylgruppe oder auch zusammen mit Y ein Sauerstoffatom sein kann, mit der Verbindung der Formel III umsetzt oder b) eine Verbindung der Formel IV mit einer Verbindung der allgemeinen Formel V in der X und Y die oben genannte Bedeutung haben, umsetzt und fuer den Fall, daß X die Gruppe bedeutet, anschließend reduziert, und gegebenenfalls die so erhaltenen Verbindungen der allgemeinen Formel I in ihre pharmakologisch verträglichen Salze überführt.X the group denotes, where Z can be a hydroxyl group or, together with Y, an oxygen atom, with the compound of the formula III converts or b) a compound of the formula IV with a compound of the general formula V in which X and Y have the meaning given above, and in the event that X represents the group means, then reduced, and, if appropriate, the compounds of the general formula I thus obtained are converted into their pharmacologically acceptable salts. 3. Verwendung von 4-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]-propoxy}-indol und dessen pharmakologisch verträglichen Salze zur Herstellung von Arzneimitteln- mit blutdrucksenkender Wirkung.3. Use of 4- {2-hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole and its pharmacologically acceptable salts for the production of pharmaceuticals with antihypertensive effects. 4. Arzneimittel, gekennzeichnet durch einen Gehalt an 4-{2-Hydroxy-3-[4-(phenoxymethyl)-piperidino]-propoxy}-indol und/oder dessen pharmakologisch verträglichen Salzen und üblichen Trägerstoffen.4. Medicinal products, characterized in that they contain 4- {2-hydroxy-3- [4- (phenoxymethyl) piperidino] propoxy} indole and / or its pharmacologically acceptable salts and customary carriers.
DE19762651574 1976-11-12 1976-11-12 3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors Withdrawn DE2651574A1 (en)

Priority Applications (39)

Application Number Priority Date Filing Date Title
DE19762651574 DE2651574A1 (en) 1976-11-12 1976-11-12 3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors
US05/846,057 US4146630A (en) 1976-11-12 1977-10-27 Blood pressure lowering and adrenergic β-receptor inhibiting 3-(4-phenoxymethylpiperidino)-propyl-phenyl ethers
AR269873A AR218643A1 (en) 1976-11-12 1977-11-07 PROCEDURE FOR PREPARING 3- (4-PHENOXY-METHYL-PIPERIDINE) -PROPOXI DERIVATIVES OF INDOL, INDAZOL, BEZIMIDAZOLE AND BENZOTRIAZOL AND ITS SALTS
IL53323A IL53323A (en) 1976-11-12 1977-11-07 1-(4-phenoxymethylpiperidino)-2-hydroxy-3-(indolyl(indazolyl,benzimidazolyl or benzotriazolyl)oxy)propanes,their preparation and pharmaceutical compositions containing them
YU02664/77A YU266477A (en) 1976-11-12 1977-11-07 Process for preparing amino propanols and salts thereof
ZA00776647A ZA776647B (en) 1976-11-12 1977-11-07 New piperidinopropyl derivatives and the preparation thereof
NL7712220A NL7712220A (en) 1976-11-12 1977-11-07 NEW AMINOPROPANOL DERIVATIVES, PROCESS FOR THE PREPARATION OF SUCH DERIVATIVES AND MEDICINAL PRODUCTS WITH THESE DERIVATIVES AS AN ACTIVE COMPOUND.
AU30466/77A AU510284B2 (en) 1976-11-12 1977-11-08 3(-(4-phenoxymethyl piperidino)-propoxy) indole or indazole or benzimidazole or benzotriazole
IT29456/77A IT1087490B (en) 1976-11-12 1977-11-08 AMINOPROPANOLIC DERIVATIVES, PROCESS FOR THEIR PREPARATION AND DRUGS THAT CONTAIN THEM
FI773346A FI62077C (en) 1976-11-12 1977-11-08 PROCEDURE FOR THE FRAMEWORK OF PHARMACEUTICAL PRODUCTS PHENOXYETHYLPIPERIDINOPROPANOLDERIVAT
CS777291A CS228106B2 (en) 1976-11-12 1977-11-08 Production of novel derivatives of 3-/4-phenoxymethylpiperidino/-propanol
DD7700201951A DD133801A5 (en) 1976-11-12 1977-11-08 NEW AMINO-PROPANOL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICAMENTS CONTAINING SUCH COMPOUNDS
GB46415/77A GB1541547A (en) 1976-11-12 1977-11-08 4-phenoxymethylpiperidine derivatives
PL1977213346A PL112683B1 (en) 1976-11-12 1977-11-09 Process for preparing novel derivatives of aminopropanol
PL1977201997A PL110782B1 (en) 1976-11-12 1977-11-09 Method of producing new derivatives of aminopropanol
CH1367177A CH636099A5 (en) 1976-11-12 1977-11-09 METHOD FOR PRODUCING PIPERIDINOPROPANOL DERIVATIVES.
CA290,495A CA1086740A (en) 1976-11-12 1977-11-09 Piperidinopropyl derivatives and the preparation thereof
BE182523A BE860701A (en) 1976-11-12 1977-11-10 NEW DERIVATIVES OF AMINOPROPANOL VASODILATORS AND BETA-ADRENERGIC RECEPTOR INHIBITORS
SE7712720A SE7712720L (en) 1976-11-12 1977-11-10 PIPERIDINOPROPYL DERIVATIVE
HU77BO1689A HU177410B (en) 1976-11-12 1977-11-10 Process for preparing new piperidino-propanol derivatives
FR7733907A FR2370744A1 (en) 1976-11-12 1977-11-10 NEW AMINOPROPANOL DERIVATIVES, PROCESS FOR THEIR PREPARATION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
LU7778498A LU78498A1 (en) 1976-11-12 1977-11-11
DK500677A DK500677A (en) 1976-11-12 1977-11-11 AMINOPROPANOL DERIVATIVES PREPARATIONS AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
SU772541695A SU1041033A3 (en) 1976-11-12 1977-11-11 Process for preparing derivatives of aminopropanol or their salts
JP13559177A JPS5363385A (en) 1976-11-12 1977-11-11 Novel aminopropanole derivative process for preparing same and medicine having vasodilating and betaaacceptor interupiing efect
AT808277A AT361476B (en) 1976-11-12 1977-11-11 METHOD FOR PRODUCING NEW AMINO PROPANOL DERIVATIVES AND THEIR SALTS
CS785461A CS228110B2 (en) 1976-11-12 1978-08-21 Production of novel derivatives of 3-/4-phenoxymethylpi
ES472747A ES472747A1 (en) 1976-11-12 1978-08-22 Blood pressure lowering and adrenergic " -receptor inhibiting 3-(4-phenoxymethylpiperidino)-propyl-phenyl ethers
ES472746A ES472746A1 (en) 1976-11-12 1978-08-22 Blood pressure lowering and adrenergic " -receptor inhibiting 3-(4-phenoxymethylpiperidino)-propyl-phenyl ethers
SU782675553A SU890975A3 (en) 1976-11-12 1978-10-20 Method of preparing derivatives of aminopropanol or their salts
SU782674802A SU826955A3 (en) 1976-11-12 1978-10-20 Method of preparing aminopropanol derivatives
AR27565679A AR222324A1 (en) 1976-11-12 1979-02-28 A PROCEDURE FOR PREPARING 3- (4-PHENOXY-METHYL-PIPERIDINE) -PROPOXI DERIVATIVES OF INDOL, INDAZOL, BENZIMIDAZOLE AND BENZOTRIAZOL AND ITS SALTS
AR275657A AR221081A1 (en) 1976-11-12 1979-02-28 PROCEDURE FOR PREPARING DERIVATIVES OF PHENOXIMETIL-PIPERIDINO-PROPOXI-INDOL
AR275655A AR221868A1 (en) 1976-11-12 1979-02-28 A PROCEDURE FOR PREPARING 3- (4-PHENOXY-METHYL-PIPERIDINE) -PROPOXI DERIVATIVES OF INDOL, INDAZOL, BENZIMIDAZOLE AND BENZOTRIAZOL AND ITS SALTS
AT649879A AT361479B (en) 1976-11-12 1979-10-04 METHOD FOR PRODUCING NEW AMINOPROPANOL DERIVATIVES AND THEIR SALTS
CH367682A CH639086A5 (en) 1976-11-12 1982-06-14 METHOD FOR PRODUCING PIPERIDINOPROPANOL DERIVATIVES.
CH233783A CH643554A5 (en) 1976-11-12 1983-05-02 METHOD FOR PRODUCING PIPERIDINOPROPANOL DERIVATIVES.
YU01288/83A YU128883A (en) 1976-11-12 1983-06-09 Process for preparing 4-(2-hydroxy-3-(4-phenoxy-methyl-pyperidino)-propoxy)indol and salts and esters thereof
YU01289/83A YU128983A (en) 1976-11-12 1983-06-09 Process for preparing 4-(2-hydroxy-3-(4-phenoxy-methyl-pyperidino)-propoxy)indol and salts and esters thereof

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DE19762651574 DE2651574A1 (en) 1976-11-12 1976-11-12 3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2737630A1 (en) * 1977-08-20 1979-03-01 Boehringer Mannheim Gmbh 3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors
DE2905877A1 (en) 1979-02-16 1980-08-28 Boehringer Mannheim Gmbh NEW AMINOPROPANOL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
EP0025111A1 (en) * 1979-08-10 1981-03-18 Sandoz Ag 3-Aminopropoxyaryl derivatives, their preparation and pharmaceutical compositions containing them
DE3721260A1 (en) * 1987-06-27 1989-01-12 Beiersdorf Ag NEW INDOLYL PROPANOLS, METHOD FOR THEIR PRODUCTION AND THEIR USE, AND PREPARATIONS CONTAINING THE COMPOUNDS
CN110974975A (en) * 2019-12-12 2020-04-10 四川百利药业有限责任公司 Quick-release antibody drug conjugate

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA9610736B (en) 1995-12-22 1997-06-27 Warner Lambert Co 2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists
ZA9610745B (en) * 1995-12-22 1997-06-24 Warner Lambert Co 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610738B (en) 1995-12-22 1997-06-24 Warner Lambert Co Subtype selective nmda receptor ligands and the use thereof
ZA9610741B (en) 1995-12-22 1997-06-24 Warner Lambert Co 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2737630A1 (en) * 1977-08-20 1979-03-01 Boehringer Mannheim Gmbh 3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors
DE2905877A1 (en) 1979-02-16 1980-08-28 Boehringer Mannheim Gmbh NEW AMINOPROPANOL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
EP0025111A1 (en) * 1979-08-10 1981-03-18 Sandoz Ag 3-Aminopropoxyaryl derivatives, their preparation and pharmaceutical compositions containing them
DE3721260A1 (en) * 1987-06-27 1989-01-12 Beiersdorf Ag NEW INDOLYL PROPANOLS, METHOD FOR THEIR PRODUCTION AND THEIR USE, AND PREPARATIONS CONTAINING THE COMPOUNDS
US4935414A (en) * 1987-06-27 1990-06-19 Beiersdorf Ag New indolylpropanols, processes for their preparation and their use, and preparations containing the compounds
CN110974975A (en) * 2019-12-12 2020-04-10 四川百利药业有限责任公司 Quick-release antibody drug conjugate
CN110974975B (en) * 2019-12-12 2023-10-20 成都百利多特生物药业有限责任公司 Quick-release antibody drug conjugate

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ZA776647B (en) 1978-09-27
SU1041033A3 (en) 1983-09-07

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