DK160250B - Analogifremgangsmaade til fremstilling af 4-substituerede piperidinoalkanon-derivater eller farmaceutisk acceptable salte deraf - Google Patents
Analogifremgangsmaade til fremstilling af 4-substituerede piperidinoalkanon-derivater eller farmaceutisk acceptable salte deraf Download PDFInfo
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- DK160250B DK160250B DK133080A DK133080A DK160250B DK 160250 B DK160250 B DK 160250B DK 133080 A DK133080 A DK 133080A DK 133080 A DK133080 A DK 133080A DK 160250 B DK160250 B DK 160250B
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- 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
- C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
- C07D211/82—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
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- 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
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
DK 160250 B
Den foreliggende opfindelse angår en analogifremgangs-måde til fremstilling af hidtil ukendte 4-substituerede pipe-ridinoalkanon-derivater eller farmaceutisk acceptable salte deraf, der er anvendelige som antihistaminer, antiallergiske 5 midler og bronchodilatorer.
Beslægtede piperidinderivater med antihistamin-egenskaber findes beskrevet i US patentskrifterne nr. 3.806.526, 3.829.433, 3.862.173, 3.878.217, 3.931.197, 3.941.795, 3.946.022 og 3.965.257, jfr. det følgende.
10 Fremgangsmåden ifølge opfindelsen til fremstilling af 4-substituerede piperidinoalkanon-derivater af formlen
C—R
15 JLr2 (I)
cT
N 0 ru (CH2)n-H_Q_i_R3 ch3 20 hvor R1 betegner hydroxy, R2 betegner hydrogen, n er et helt tal fra 3 til 5, og R3 er -COOH eller -COO-alkyl, hvor alkylgruppen indeholder 1-6 carbonatomer og er ligekædet eller forgrenet, 25 eller farmaceutisk acceptable salte af disse forbindelser, er ejendommelig ved, at man alkylerer en substitueret piperi-din af formlen
30 SS
L-R2 (VI)
H
35 med en ω-halogenalkyl-substitueret phenylketon af formlen
0 CHS
hai-(cH2)ni-0-f*6 (VID
CH3
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2 i hvilke formler Hal er halogen, R6 er -COO-alkyl, hvor alkylgruppen indeholder 1-6 carbonatomer og er ligekædet eller forgrenet, og R1, R2 og n er som angivet ovenfor, i et passende opløsningsmiddel i nærværelse af en base og 5 eventuelt i nærværelse af en katalytisk mængde kaliumiodid i et tidsrum på mellem 4 og 120 timer ved en temperatur mellem 70°C og tilbagesvalingstemperatur, efterfulgt af en base-hydrolyse, når R3 skal være -COOH, hvorefter man, når der ønskes et farmaceutisk acceptabelt salt, omsætter den 10 opnåede forbindelse (I) med en farmaceutisk acceptabel syre eller base.
Af formlen I fremgår det, at de her omhandlede forbindelser er 4-(hydroxydiphenylmethyl)-piperidin-derivater som gengivet ved formlen III: 15 . C—OH (III) 20 V *j} _ (CHa)n-C-—c-R3 CH3 i hvilken n og R3 er som angivet for formlen I.
Eksempler på ligekædede eller forgrenede alkylgrupper 25 med 1-6 carbonatomer som nævnt ovenfor er methyl, ethyl, n-propyl, isopropyl, n-butyl, sek.butyl, tert.butyl, n-pentyl, neopentyl og n-hexyl.
Særligt foretrukne er de forbindelser af formlen I, hvori n er 3, og af disse forbindelser er sådanne, hvori R3 30 er -COOH, de mest foretrukne.
De farmaceutisk acceptable syreadditionssalte af de fremstillede forbindelser er salte med enhver egnet uorganisk eller organisk syre. Ikke-toxiske salte af de fremstillede forbindelser med uorganiske og organiske baser omfatter 35 f.eks. saltene af alkalimetaller, såsom natrium, kalium og lithium, jordalkalimetaller, f.eks. calcium og magnesium,
DK 160250 B
3 de lette metaller af gruppe IIIA, f.eks. aluminium, samt organiske aminer, såsom primære, sekundære og tertiære aminer, f.eks. cyclohexylamin, ethylamin, pyridin, methylamino-ethanol og piperazin. Saltene fremstilles på sædvanlig måde, 5 f.eks. ved behandling af en forbindelse af formlen I med en passende syre eller base.
Forbindelserne af formlen I er som nævnt anvendelig som antihistaminer, antiallergiske midler og bronchodilatorer og kan indgives alene eller sammen med passende farmaceutiske 10 bærere i fast eller flydende form, f.eks. som tabletter, kapsler, pulvere, opløsninger, suspensioner eller emulsioner.
Forbindelser, der er strukturelt nært beslægtede med de her omhandlede forbindelser I, og som også udviser antihistamin-virkning, er f.eks. kendt fra US patentskrifter-15 ne nr. 3.806.526, nr. 3.862.173 og nr. 3.946.022.
Ved dyreforsøg med forbindelserne ot- (p-tert. butyl-phenyl)-4-(α-hydroxy-a-phenylbenzyl)-1-piperidinbutanol og 4 - [ 4 - [ 4 - (hydroxydiphenylmethyl) -1-piperidinyl ] -1-hydroxybu-tyl]-a,a-dimethylbenzeneddikesyre har det ved afprøvning af 20 antihistamin-virkningen vist sig, at carboxylsyre-forbindel-sen (den sidstnævnte af de to forbindelser) associeres og dissocieres hurtigere end den førstnævnte, kendte forbindelse.
Den indgivne mængde af de her omhandlede forbindelser 25 kan variere over et bredt område til tilvejebringelse i en enhedsdosis af en effektiv mængde på mellem ca. 0,01 og ca.
20 mg pr. kg legemsvægt om dagen til opnåelse af den ønskede virkning. Således kan f.eks. de ønskede virkninger opnås ved indgivning af en enhedsdosisform såsom en tablet indehol-30 dende 1-50 mg af den aktive forbindelse, taget 1-4 gange daglig.
Som eksempel på forbindelsernes anvendelighed kan nævnes, at ethyl-4-[4- (hydroxydiphenylmethyl)-1-piperidinyl3- 1-oxo-butyl ] -a, a-dimethylbenzenacetat-hydrochlorid i en 35 koncentration på 1 x 10"7 giver en kendelig formindskelse af histamin-fremkaldt sammentrækning af isolerede ileal-
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4 muskler fra marsvin.
Forbindelserne af formlen I fremstilles ved alkylering af et substitueret piperidin-derivat af formlen ^0^· (VI) tf
H
10 med en ω-halogenalkyl-substitueret penylketon af formlen 0 CHs \ II Γ\ (VI1) hal-(CH2)n-C-^jHC-R; CH3 15 i hvilke formler R1, R2 og n er som angivet for formlen I,
Hal er halogen, såsom chlor, brom eller iod, og R6 er -COO-alkyl, hvor alkylgruppen indeholder 1-6 carbonatomer og er ligekædet eller forgrenet, hvilken alkylering efterfølges af en base-hydrolyse, når R3 i formlen I skal være -COOH.
20 Alkyleringen udføres i et passende opløsningsmiddel, fortrinsvis i nærværelse af en base og eventuelt i nærværelse af en katalytisk mængde kaliumiodid over et tidsrum på mellem ca. 4 og ca. 120 timer og ved temperaturer mellem ca. 70°C og tilbagesvalingstemperaturen for opløsningsmidlet. Eksem- 25 pier på egnede opløsningsmidler til alkyleringsreaktionen er alkoholer, f.eks. methanol, ethanol, isopropylalkohol og n-butanol, ketoner, f.eks. methylisobutylketon, carbonhydri-der, f.eks. benzen, toluen og xylen, og halogenerede carbon-hydrider, f.eks. chlorbenzen eller methylenchlorid, samt 30 dimethylformamid. Egnede baser til alkyleringsreaktionen omfatter uorganiske baser, f.eks. natriumbicarbonat, kalium-carbonat og kaliumbicarbonat, og organiske baser såsom tri-alkylaminer, f.eks. triethylamin, og pyridin, men der kan også anvendes et overskud af en forbindelse af formlen VI.
35 En base-hydrolyse af de forbindelser, hvori R3 er -COO-alkyl, til dannelse af de tilsvarende forbindelser, hvori R3 er
DK 160250 B
5 -COOH, opnås ved behandling med en uorganisk base som f.eks. natrium- eller kaliumhydroxid i en vandig lavere alkohol såsom vandig methanol, ethanol, isopropylalkohol eller n-butanol ved tilbagesvalingstemperatur i et tidsrum mellem 5 ca. 1/2 og ca. 12 timer. Forbindelserne af formlen VI kan fås i handelen.
Forbindelserne af formlen VII fremstilles ved omsætning af en passende ligekædet eller forgrenet, lavere alkyl-C^-Cg-ester af α,α-dimethylphenyleddikesyre, der er en kendt 10 forbindelse eller kan fremstilles efter kendte metoder, med en o-halogenalkanoylfC^g)halogen-forbindelse, hvori halogenet er chlor, brom eller iod, under de generelle betingelser for en Friedel Crafts-acylering. Denne reaktion udføres i et opløsningsmiddel såsom carbondisulfid, tetrachlorethan 15 eller nitrobenzen, hvoraf carbondisulfid er at foretrække. Reaktionstiden varierer fra ca. 1/2 til ca. 8, fortrinsvis fra ca. 3 til ca. 5 timer, og reaktionstemperaturen varierer fra ca. 0 til ca. 25“C. De anvendte ω-halogenalkanoyl-(C^_g)halogenforbindelser fås i handelen eller kan let frem-20 stilles efter kendte metoder.
De følgende eksempler skal tjene til nærmere illustration af fremgangsmåden ifølge opfindelsen.
Eksempel 1 25 Ethvl-4-Γ 4-Γ 4-(hvdroxvdiphenvlmethvl)-1-pjperidinvl1-l-oxo-butvl1-g.g-dimethvlbenzenacetat-hvdrochlorid (A) Til 700 ml carbondisulfid indeholdende 36,5 g (0,254 mol) 4-chlorbutyrylchlorid sættes 74,5 g (0,56 mol) aluminiumchlorid under omrøring i et isbad (ca. -10°C), og 30 omrøringen fortsættes i ca. 15 minutter ved ca. 25°c, hvorefter blandingen afkøles til 5°C og tilsættes 48,4 g (0,294 mol) ethyl-α,α-dimethylphenylacetat i 100 ml carbondisulfid. Reaktionsblandingen omrøres på isbad i 3½ time og omrøres derefter i 15½ time ved 25°C, hvorpå den hældes ud i HCl/is-35 vand og ekstraheres med chloroform. Ekstrakten vaskes med fortyndet natriumcarbonat-opløsning, vand og mættet natri-
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6 umchlorid-opløsning, tørres over magnesiumsulfat og inddampes, hvilket giver ethyl-4- (4-chlor-l-oxobutyl) -a,a-dimethyl-phenylacetat som et fast stof.
(B) En blanding af 4,5 g (0,0163 mol) 4-(a,a-diphe-5 nyl)-piperidinmethanol, 6,1 g (0,0205 mol) ethyl-4-(4-chlor- l-oxo-butyl)-a,a-dimethylphenylacetat, 5 g (0,05 mol) kalium-bicarbonat og 0,05 g kaliumiodid i 50 ml toluen omrøres og holdes under tilbagesvaling i 72 timer, hvorefter den filtreres. Til filtratet sættes ether og derefter etherisk hydro- 10 genchlorid, og det herved fremkomne bundfald samles og omkrystalliseres flere gange fra methanol/butanon og butanon, hvilket giver ethyl-4- [ 4- [4- (hydroxydiphenylmethyl) -1-piperi-dinyl ] -1-oxo-butyl ] -a, a-dimethylbenzenacetat-hydrochlorid med smp.
15 205,5-208°C.
Eksempel 2 4-Γ4-Γ4- (Hydroxydiphenylmethyl -l-piperidinvll -l-oxobutvll-a. Qj-dimethvlbenzeneddikesyre 20 En blanding af 1 g ethyl-4-[4-[4-(hydroxydiphenylme thyl) -1-piperidinyl] -1-oxobutyl] -α,α-dimethylbenzenacetat-hydrochlorid, 25 ml methanol og 5 ml 25%'s natriumhydroxidopløsning omrøres og holdes under tilbagesvaling i 2 timer, hvorefter den inddampes til et fast stof, der neutraliseres 25 med fortyndet saltsyre og ekstraheres med varm toluen. Efter filtrering af toluen-ekstrakten og inddampniiig til en remanens, der omkrystalliseres fra chloroform/toluen, fås 4-[4-[4 - (hydroxydiphenylmethyl) -1-piperidinyl ] -1-oxobutyl] -a, a-dimethylbenzeneddikesyre.
30
Claims (2)
1. Analogifremgangsmåde til fremstilling af 4-substituerede piperidinalkanon-derivater af formlen OO 6* ir o ch3 10 (CH2)n-?— TU hvor R1 betegner hydroxy, 3 R2 betegner hydrogen, n er et helt tal fra 3 til 5, og R3 er -COOH eller -COO-alkyl, hvor alkylgruppen inde-15 holder 1-6 carbonatomer og er ligekædet eller forgrenet, eller farmaceutisk acceptable salte af disse forbindelser, kendetegnet ved, at man alkylerer en substitueret piperidin af formlen 2« 00 r·' ni cV
25 H med en ω-halogenalkyl-substitueret phenylketon af formlen
0 CH3 Hal-(CH2)n-C—^—C-R6 (VII) CH3 30. hvilke formler Hal er halogen, R6 er -COO-alkyl, hvor alkylgruppen indeholder 1-6 carbonatomer og er ligekædet eller forgrenet, og R1, R2 og n er som angivet ovenfor, i et passende opløsningsmiddel i nærværelse af en base og eventuelt i nærværelse af en katalytisk mængde kaliumiodid 35 i et tidsrum på mellem 4 og 120 timer ved en temperatur mellem 70°C og tilbagesvalingstemperatur, efterfulgt af en DK 160250B base-hydrolyse, når R3 skal være -COOH, hvorefter man, når der ønskes et farmaceutisk acceptabelt salt, omsætter den opnåede forbindelse (I) med en farmaceutisk acceptabel syre eller base.
2. Fremgangsmåde ifølge krav 1, kendetegnet ved, at der anvendes en sådan udgangsforbindelse, at den opnåede forbindelse bliver ethyl-4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxo-butyl]-a,α-dimethylbenzenacetat.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/028,872 US4254130A (en) | 1979-04-10 | 1979-04-10 | Piperidine derivatives |
US2887279 | 1979-04-10 |
Publications (3)
Publication Number | Publication Date |
---|---|
DK133080A DK133080A (da) | 1980-10-11 |
DK160250B true DK160250B (da) | 1991-02-18 |
DK160250C DK160250C (da) | 1991-07-22 |
Family
ID=21845986
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK133080A DK160250C (da) | 1979-04-10 | 1980-03-27 | Analogifremgangsmaade til fremstilling af 4-substituerede piperidinoalkanon-derivater eller farmaceutisk acceptable salte deraf |
Country Status (18)
Country | Link |
---|---|
US (1) | US4254130A (da) |
JP (1) | JPS55139360A (da) |
AT (1) | AT376207B (da) |
AU (1) | AU536463B2 (da) |
BE (1) | BE882704A (da) |
CA (1) | CA1123439A (da) |
CH (1) | CH648019A5 (da) |
DE (1) | DE3005948A1 (da) |
DK (1) | DK160250C (da) |
ES (1) | ES489933A0 (da) |
FR (1) | FR2453853A1 (da) |
IL (1) | IL59157A (da) |
IT (1) | IT1144079B (da) |
NL (1) | NL190664C (da) |
NO (1) | NO154964C (da) |
NZ (1) | NZ192615A (da) |
SE (1) | SE448727B (da) |
ZA (1) | ZA80331B (da) |
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US20080161324A1 (en) * | 2006-09-14 | 2008-07-03 | Johansen Lisa M | Compositions and methods for treatment of viral diseases |
ITMI20070987A1 (it) * | 2007-05-16 | 2008-11-17 | Dipharma Francis Srl | Procedimento per la preparazione di composti chetonici |
US20100092479A1 (en) * | 2008-08-18 | 2010-04-15 | Combinatorx (Singapore) Pte. Ltd. | Compositions and methods for treatment of viral diseases |
EP2289867A3 (en) | 2009-08-19 | 2012-04-25 | Jubilant Organosys Limited | A process for producing 4-(4-halo-1-oxybutyl)-alpha,alpha-dimethylbenzene acetic acid or alkyl esters thereof |
US20110130711A1 (en) * | 2009-11-19 | 2011-06-02 | Follica, Inc. | Hair growth treatment |
EP2371817A1 (en) | 2010-04-01 | 2011-10-05 | Arevipharma GmbH | Process for the preparation of 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-(diphenylmethoxy)-1-piperidinyl]-1-butanone and acid addition salts thereof |
EP2578570A1 (en) | 2011-10-07 | 2013-04-10 | Almirall, S.A. | Novel process for preparing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(r)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one via novel intermediates of synthesis. |
EP2641900A1 (en) | 2012-03-20 | 2013-09-25 | Almirall, S.A. | Novel polymorphic Crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one, heminapadisylate as agonist of the ß2 adrenergic receptor. |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1242169A (en) * | 1969-04-09 | 1971-08-11 | Ucb Sa | Piperidine derivatives |
BE794598A (fr) * | 1972-01-28 | 1973-05-16 | Richardson Merrell Inc | Nouveaux derives olefiniques de piperidines substituees en 4 et leur procede de preparation |
BE794596A (fr) * | 1972-01-28 | 1973-05-16 | Richardson Merrell Inc | Piperidinoalcanone-oximes substituees et leur procede de preparation |
US3806526A (en) * | 1972-01-28 | 1974-04-23 | Richardson Merrell Inc | 1-aroylalkyl-4-diphenylmethyl piperidines |
US3878217A (en) * | 1972-01-28 | 1975-04-15 | Richardson Merrell Inc | Alpha-aryl-4-substituted piperidinoalkanol derivatives |
ZA728544B (en) * | 1972-01-28 | 1974-02-27 | Richardson Merrell Inc | Alpha-aryl-4-substituted piperidinoalkanol derivatives |
US3965257A (en) * | 1972-01-28 | 1976-06-22 | Richardson-Merrell Inc. | Compositions and methods for the treatment of the symptoms of histamine induced allergic reactions |
US3931197A (en) * | 1974-02-08 | 1976-01-06 | Richardson-Merrell Inc. | Substituted piperidine derivatives |
US3941795A (en) * | 1974-02-08 | 1976-03-02 | Richardson-Merrell Inc. | α-ARYL-4-SUBSTITUTED PIPERIDINOALKANOL DERIVATIVES |
US3946022A (en) * | 1974-03-04 | 1976-03-23 | Richardson-Merrell Inc. | Piperidine derivatives |
US3922276A (en) * | 1974-12-11 | 1975-11-25 | Robins Co Inc A H | 1-Substituted-4-benzylidenepiperidines |
US3956296A (en) * | 1974-12-11 | 1976-05-11 | A. H. Robins Company, Incorporated | 1-Substituted-4-benzylpiperidines |
-
1979
- 1979-04-10 US US06/028,872 patent/US4254130A/en not_active Expired - Lifetime
-
1980
- 1980-01-15 NZ NZ192615A patent/NZ192615A/xx unknown
- 1980-01-18 IL IL59157A patent/IL59157A/xx unknown
- 1980-01-18 CA CA344,022A patent/CA1123439A/en not_active Expired
- 1980-01-21 ZA ZA00800331A patent/ZA80331B/xx unknown
- 1980-01-29 AU AU55018/80A patent/AU536463B2/en not_active Expired
- 1980-02-07 NL NL8000762A patent/NL190664C/xx not_active IP Right Cessation
- 1980-02-15 IT IT47919/80A patent/IT1144079B/it active
- 1980-02-16 DE DE19803005948 patent/DE3005948A1/de active Granted
- 1980-02-26 CH CH1528/80A patent/CH648019A5/de not_active IP Right Cessation
- 1980-03-06 AT AT0126080A patent/AT376207B/de not_active IP Right Cessation
- 1980-03-26 ES ES489933A patent/ES489933A0/es active Granted
- 1980-03-27 DK DK133080A patent/DK160250C/da not_active IP Right Cessation
- 1980-04-02 JP JP4207180A patent/JPS55139360A/ja active Pending
- 1980-04-08 SE SE8002635A patent/SE448727B/sv not_active IP Right Cessation
- 1980-04-09 NO NO801015A patent/NO154964C/no unknown
- 1980-04-09 FR FR8007993A patent/FR2453853A1/fr active Granted
- 1980-04-09 BE BE0/200162A patent/BE882704A/fr not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
NL190664C (nl) | 1994-06-16 |
NZ192615A (en) | 1982-02-23 |
IL59157A0 (en) | 1980-05-30 |
NO801015L (no) | 1980-10-13 |
NL190664B (nl) | 1994-01-17 |
FR2453853A1 (fr) | 1980-11-07 |
JPS55139360A (en) | 1980-10-31 |
NO154964C (no) | 1987-01-21 |
ATA126080A (de) | 1984-03-15 |
FR2453853B1 (da) | 1982-07-09 |
SE448727B (sv) | 1987-03-16 |
CA1123439A (en) | 1982-05-11 |
DE3005948A1 (de) | 1980-10-30 |
ZA80331B (en) | 1981-01-28 |
IT1144079B (it) | 1986-10-29 |
BE882704A (fr) | 1980-07-31 |
AT376207B (de) | 1984-10-25 |
AU536463B2 (en) | 1984-05-10 |
IL59157A (en) | 1984-02-29 |
DK160250C (da) | 1991-07-22 |
NO154964B (no) | 1986-10-13 |
AU5501880A (en) | 1980-10-16 |
CH648019A5 (de) | 1985-02-28 |
ES8103734A1 (es) | 1981-03-16 |
DK133080A (da) | 1980-10-11 |
DE3005948C2 (da) | 1989-10-05 |
IT8047919A0 (it) | 1980-02-15 |
ES489933A0 (es) | 1981-03-16 |
SE8002635L (sv) | 1980-10-11 |
NL8000762A (nl) | 1980-10-14 |
US4254130A (en) | 1981-03-03 |
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Legal Events
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PUP | Patent expired |