NO800660L - PROCEDURE FOR PREPARING PIPERIDE INGREDIENTS - Google Patents
PROCEDURE FOR PREPARING PIPERIDE INGREDIENTSInfo
- Publication number
- NO800660L NO800660L NO800660A NO800660A NO800660L NO 800660 L NO800660 L NO 800660L NO 800660 A NO800660 A NO 800660A NO 800660 A NO800660 A NO 800660A NO 800660 L NO800660 L NO 800660L
- Authority
- NO
- Norway
- Prior art keywords
- piperidine
- formula
- benzyloxy
- preparing
- procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 239000004615 ingredient Substances 0.000 title 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- ILJHWVWEYBJDDM-UHFFFAOYSA-N 4-phenylmethoxypiperidine Chemical compound C=1C=CC=CC=1COC1CCNCC1 ILJHWVWEYBJDDM-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 4
- 229940073608 benzyl chloride Drugs 0.000 claims description 4
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- GKGCPWOZAGTHMX-UHFFFAOYSA-N (4-hydroxypiperidin-1-yl)-(4-nitrophenyl)methanone Chemical compound C1CC(O)CCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 GKGCPWOZAGTHMX-UHFFFAOYSA-N 0.000 description 2
- -1 1-p-Nitrobenzoyl-4-benzyloxy-piperidine Chemical compound 0.000 description 2
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002921 anti-spasmodic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 2
- 229910001626 barium chloride Inorganic materials 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960001789 papaverine Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- LAOQIHVQAMCKLS-UHFFFAOYSA-N 4-phenylmethoxypiperidine hydrobromide Chemical compound Br.C(C1=CC=CC=C1)OC1CCNCC1 LAOQIHVQAMCKLS-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 206010046823 Uterine spasm Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001595 contractor effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003170 musculotropic effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
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
- C07D211/36—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av 4-benzyloksy-piperidin med formel I The present invention relates to a method for the production of 4-benzyloxy-piperidine with formula I
og farmasøytisk tålbare syreaddisjonssalter derav, og det særegne ved fremgangsmåten i henhold til oppfinnelsen er : a) 4-hydroksy-piperidin kondenseres med p-nitrobenzoyl-klorid i nærvær av et syrebindehde middel, til å gi et and pharmaceutically acceptable acid addition salts thereof, and the distinctive feature of the method according to the invention is: a) 4-hydroxy-piperidine is condensed with p-nitrobenzoyl chloride in the presence of an acid-binding agent, to give a
beskyttet piperidin, med formel IIprotected piperidine, of formula II
b) forbindelsen med formel II benzyleres med benzyl-klorid i nærvær av et kondenserende middel og et syrebindende b) the compound of formula II is benzylated with benzyl chloride in the presence of a condensing agent and an acid scavenger
middel, til å gi forbindelsen III med formelagent, to give the compound III of formula
c) aminogruppen i piperidinet frigis, og c) the amino group in the piperidine is released, and
d) om ønsket omdannes den resulterende base til et salt. d) if desired, the resulting base is converted to a salt.
Det følgende eksempel illustrerer fremstillingen av forbindelsen med formel I. The following example illustrates the preparation of the compound of formula I.
EKSEMPELEXAMPLE
a) l-p-Nitrobenzoyl-4-hydroksy-piperidina) 1-p-Nitrobenzoyl-4-hydroxy-piperidine
Til en Erlenmeyer-kolbe på 1 liter utstyrt mfed magnetisk To an Erlenmeyer flask of 1 liter equipped mfed magnetic
rørverk og anbragt i et vannbad, inneholdende en løsning av 30,34 g (0,3 mol) 4-hydroksy-piperidin og 58,04 g vannfritt kalium-karbonat (0,42 mol) i 260 ml vann tilsettes 260 kloroform. 48,43 g (0,261 mol) p-nitrobenzoyl-klorid tilsettes porsjonsvis til den omrørte reaksjonsblanding. pipework and placed in a water bath, containing a solution of 30.34 g (0.3 mol) 4-hydroxy-piperidine and 58.04 g anhydrous potassium carbonate (0.42 mol) in 260 ml of water, 260 chloroform is added. 48.43 g (0.261 mol) of p-nitrobenzoyl chloride are added in portions to the stirred reaction mixture.
Den heterogene blanding omrøres i 30 minutter ved tomtempera-tur og fortynnes så ved tilsetning av 260 ml eter. Etter omrøring i ytterligere 15 minutter avsuges bunnfallet på filter under et svakt undertrykk, hvoretter det vaskes med 5 x 50 ml vann, inntil det er fullstendig fravær av Cl ,ioner. The heterogeneous mixture is stirred for 30 minutes at room temperature and then diluted by adding 260 ml of ether. After stirring for a further 15 minutes, the precipitate is sucked off the filter under a slight negative pressure, after which it is washed with 5 x 50 ml of water, until there is a complete absence of Cl , ions.
Det blekgule produkt tørkes i vakuum i 2 til 10 timer ved oppvarming ved 40-50°C til å gi 52,39 g produkt (utbytte 80%). Smeltepunkt = 205-206°C.(Kofler-blokk). The pale yellow product is dried in vacuo for 2 to 10 hours by heating at 40-50°C to give 52.39 g of product (80% yield). Melting point = 205-206°C. (Kofler block).
b) 1-p-Nitrobenzoyl-4-benzyloksy-piperidinb) 1-p-Nitrobenzoyl-4-benzyloxy-piperidine
Under ett avtrekk tilsettes til en kraftig omrørt suspensjon Under one hood, add to a vigorously stirred suspension
av 33,21 g (0,133 mol) l-p-nitrobenzoyl-4-hydroksy-piperidin i 176 ml benzyl-klorid en o<p>pløsning av 53,2 g natrium-hydroksyd (50 vektprosent løsning. 0,665 mol) og 2,25 g TBAS (tetrabutylammonium-hydrogen-sulfat) tilsettes så porsjonsvis dertil, pga. den eksoterme karakter av reaksjonen. of 33.21 g (0.133 mol) of 1-p-nitrobenzoyl-4-hydroxy-piperidine in 176 ml of benzyl chloride a solution of 53.2 g of sodium hydroxide (50% by weight solution. 0.665 mol) and 2.25 g TBAS (tetrabutylammonium-hydrogen-sulphate) is then added in portions thereto, because the exothermic nature of the reaction.
Den godt omrørte blanding oppvarmes til 50°C i 4 timer, fortynnes så med 345 ml vann for å oppløse utfelt NaCl, og til slutt med 210 ml kloroform. The well-stirred mixture is heated to 50°C for 4 hours, then diluted with 345 ml of water to dissolve precipitated NaCl, and finally with 210 ml of chloroform.
Blandingen dékanteres. Den vandige fase ekstraheres med 100 ml CHC13og den totale organiske fase vaskes ved 3 x 100 ml vann og tørkes over natten .over MgS04. Etter filtrering fjernes kloroform under vakuum i en rotasjonsfordamper, og den resterende produktløsning i benzylklorid helles utover 1760 The mixture is decanted. The aqueous phase is extracted with 100 ml CHCl 3 and the total organic phase is washed with 3 x 100 ml water and dried overnight over MgSO 4 . After filtration, chloroform is removed under vacuum in a rotary evaporator, and the remaining product solution in benzyl chloride is poured over 1760
ml cykloheksan, under kraftig omrøring.ml of cyclohexane, with vigorous stirring.
Det resulterende meget blekgule bunnfall omrøres i omtrentThe resulting very pale yellow precipitate is stirred for approx
3 timer i blandingen, hvoretter det filtreres, vaskes med cykloheksan og tørkes vinder vakuum ved 40°C til å gi 39 ,24 g produkt (utbytte: 86,5%). Smeltepunkt = 119°C (Kofler-blokk). 3 hours in the mixture, after which it is filtered, washed with cyclohexane and dried under vacuum at 40°C to give 39.24 g of product (yield: 86.5%). Melting point = 119°C (Kofler block).
c) 4-benzyloksy-piperidin- hydrobromidc) 4-benzyloxy-piperidine hydrobromide
Til en omrørt suspensjon av 22,12 g (0,065 mol) 1-p-nitrobenzoyl-4-benzyloksy-piperidin i 390 ml 96% etanol tilsettes ION vandig kalium-hydroksyd (97,5ml/0,975 mol). Reaksjons-blandingen omrører over natten ved romtemperatur og den neste dag ved 50°C i 4 timer, under en nitrogenatmosfære. To a stirred suspension of 22.12 g (0.065 mol) of 1-p-nitrobenzoyl-4-benzyloxy-piperidine in 390 ml of 96% ethanol is added ION aqueous potassium hydroxide (97.5 ml/0.975 mol). The reaction mixture is stirred overnight at room temperature and the next day at 50°C for 4 hours, under a nitrogen atmosphere.
Etanol fjernes under vakuum i en rotasjonsfordamper (bad: 35-40°C). Resten oppløses på nytt i 160 ml vann og 60 g rent NaCl tilsettes for utsalting av produktet som ekstraheres Ethanol is removed under vacuum in a rotary evaporator (bath: 35-40°C). The residue is redissolved in 160 ml of water and 60 g of pure NaCl is added to salt out the product that is extracted
med 160 ml eter.with 160 ml of ether.
Blandingen av NaCl og natriumsaltet av p-nitrobenzosyren frafiltreres, filtratet dekanteres av og eterfasen tørkes over natten over MgS04etter ekstraksjon av den vandig fase med 3 x 160 ml eter. The mixture of NaCl and the sodium salt of the p-nitrobenzoic acid is filtered off, the filtrate is decanted off and the ether phase is dried overnight over MgSO 4 after extraction of the aqueous phase with 3 x 160 ml of ether.
Oppløsningsmidlet tørkes under vakuum, uten oppvarming. Det dannes lange blekgule nåler fra utgangsoljen og de gir 12,28 g produkt (98,8%) . The solvent is dried under vacuum, without heating. Long pale yellow needles are formed from the starting oil and they yield 12.28 g of product (98.8%).
Basen er sterkt hygroskopisk.The base is highly hygroscopic.
Den olje oppløses i 660 ml tørr de-peroksydert eter og 55 ml av en oppløsning (omtrent 1,3M) gassformet brom-hydrogensyre i tørr de-peroksydert eter tilsettes så dertil porsjonsvis The oil is dissolved in 660 ml of dry de-peroxidized ether and 55 ml of a solution (approximately 1.3 M) of gaseous hydrobromic acid in dry de-peroxidized ether is then added portionwise
(en sterkere konsentrert oppløsning, f.eks. med en konsentrasjon på omtrent 4M, kan fordelaktig anvendes) under avkjøling i et isbad. (a more highly concentrated solution, e.g. with a concentration of about 4M, can advantageously be used) while cooling in an ice bath.
Det resulterende hydrobromid-bunnfall filtreres hurtig, vaskes med eter og tørkes under vakuum, uten oppvarming. The resulting hydrobromide precipitate is quickly filtered, washed with ether and dried under vacuum, without heating.
Det tørre salt er ikke hygroskopisk.The dry salt is not hygroscopic.
Denne fremgangmsåte gir 16,75 g salt (95%).This progress yield 16.75 g of salt (95%).
Det noe beige produkt avfarges ved omkrystallisering fra omtrent 270 ml benzen (med filtrering om nødvendig i varm tilstand). Smeltepunkt = 134°C (Kofler-blokk). The somewhat beige product is decolorized by recrystallization from about 270 ml of benzene (with filtration if necessary while hot). Melting point = 134°C (Kofler block).
4-benzyloksy-piperidin og dets farmasøytisk -tålbare syrer har nyttige farmakologiske egenskaper. 4-Benzyloxy-piperidine and its pharmaceutically acceptable acids have useful pharmacological properties.
Spesielt har de en anti-spasmodisk virkning på den glatte muskulatur og er terepeutisk nyttige for behandling av arterielle (arteritis, angina pectoris), digestive, viscerale (hepatiske og nefretiske kolikker), vesikalske og uterine spasmer. In particular, they have an anti-spasmodic effect on the smooth muscles and are therapeutically useful for the treatment of arterial (arteritis, angina pectoris), digestive, visceral (hepatic and nephrotic colic), vesical and uterine spasms.
Resultatene av toksikologiske og farmakologiske undersøkelser som viser de nevnte egenskaper er gitt i det følgende. The results of toxicological and pharmacological investigations which show the aforementioned properties are given below.
a) Akutt giftigheta) Acute toxicity
LDj-q ble bestemt med Swiss NMRI mus med 4-benzyloksy-piperidin LDj-q was determined with Swiss NMRI mice with 4-benzyloxy-piperidine
hydrobromide:hydrobromide:
b) Antispasmodisk virkning b) Antispasmodic action
Testene gjennomføres med isolert duodenum fra rotter som The tests are carried out with isolated duodenum from rats that
holdes i live i oksygenert tyfode-væske ved en temperatur på 37°C (20 ml celle, Vålett type vannbad for isolerte organer). kept alive in oxygenated typhoid fluid at a temperature of 37°C (20 ml cell, Vålett type water bath for isolated organs).
Tonisitet og bevegelser av det isolerte -organ opptegnes under anvendelse av metoden i henhold til Magnus R. (Arch. Ges. Physiol. 1904, 102. 123) ved hjelp av en spenningsmåler for-bundet til en elektronisk rekorder av typen "Electromed". Tonicity and movements of the isolated organ are recorded using the method according to Magnus R. (Arch. Ges. Physiol. 1904, 102. 123) by means of a voltage meter connected to an electronic recorder of the "Electromed" type.
Antagonismen som utøves av testmaterialet undersøkes i forhold til de muskolotropiske kontrakterende virkninger av barium-kloridet. The antagonism exerted by the test material is examined in relation to the musculotropic contracting effects of the barium chloride.
Papaverin anvendes som sammenliknings-antagonistisk material. Papaverine is used as comparison-antagonistic material.
Den molare konsentrasjon av test-material som nedsetter virkningene av barium-klorid med en faktor på 50% bestemmes. The molar concentration of test material which reduces the effects of barium chloride by a factor of 50% is determined.
De oppnådde resultater er angitt i den følgende tabell. The results obtained are indicated in the following table.
Det fremgår av de oppnådde resultater at aktiviteten av 4-benzyloksy-piperidin stort sett tilsvarer aktiviteten av papaverin. It appears from the results obtained that the activity of 4-benzyloxy-piperidine largely corresponds to the activity of papaverine.
4-benzyloksy-piperidin og foretrukket dets farmasøytisk tålbare salter, tilføres mennesker oralt (typisk som kapsler inneholdende 10 mg aktiv bestanddel, 3-5 ganger daglig) eller parenteralt, typisk ved intramuskulær tilførsel (som en vandig op<p>løsning inneholdende 5 g aktiv bestanddel, 3-2 ganger daglig. 4-benzyloxy-piperidine and preferably its pharmaceutically acceptable salts, are administered to humans orally (typically as capsules containing 10 mg of active ingredient, 3-5 times daily) or parenterally, typically by intramuscular administration (as an aqueous solution containing 5 g active ingredient, 3-2 times daily.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7906070A FR2450816A1 (en) | 1979-03-09 | 1979-03-09 | NOVEL PIPERIDINE DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO800660L true NO800660L (en) | 1980-09-10 |
Family
ID=9222953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO800660A NO800660L (en) | 1979-03-09 | 1980-03-07 | PROCEDURE FOR PREPARING PIPERIDE INGREDIENTS |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0015817A1 (en) |
| JP (1) | JPS55122761A (en) |
| AU (1) | AU5594080A (en) |
| BE (1) | BE882122A (en) |
| ES (1) | ES489042A1 (en) |
| FR (1) | FR2450816A1 (en) |
| GB (1) | GB2044260A (en) |
| IT (1) | IT8067364A0 (en) |
| NO (1) | NO800660L (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE13425T1 (en) | 1981-10-15 | 1985-06-15 | Synthelabo | PIPERIDINE DERIVATIVES, PROCESSES FOR THEIR PRODUCTION AND THEIR USE AS MEDICINAL PRODUCTS. |
| US4529730A (en) * | 1981-10-21 | 1985-07-16 | Synthelabo | Piperidine derivatives, their preparation and pharmaceutical compositions containing them |
| GB8321157D0 (en) * | 1983-08-05 | 1983-09-07 | Fordonal Sa | Piperidine derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3260723A (en) * | 1963-08-27 | 1966-07-12 | Parke Davis & Co | 4-phenoxy piperidines; alpha4-phenoxy piperideines |
-
1979
- 1979-03-09 FR FR7906070A patent/FR2450816A1/en active Granted
-
1980
- 1980-02-21 GB GB8005923A patent/GB2044260A/en not_active Withdrawn
- 1980-02-25 EP EP80400258A patent/EP0015817A1/en not_active Withdrawn
- 1980-02-27 AU AU55940/80A patent/AU5594080A/en not_active Abandoned
- 1980-02-28 ES ES489042A patent/ES489042A1/en not_active Expired
- 1980-03-07 BE BE0/199707A patent/BE882122A/en unknown
- 1980-03-07 JP JP2906880A patent/JPS55122761A/en active Pending
- 1980-03-07 IT IT8067364A patent/IT8067364A0/en unknown
- 1980-03-07 NO NO800660A patent/NO800660L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR2450816A1 (en) | 1980-10-03 |
| IT8067364A0 (en) | 1980-03-07 |
| GB2044260A (en) | 1980-10-15 |
| BE882122A (en) | 1980-09-08 |
| FR2450816B1 (en) | 1981-05-22 |
| EP0015817A1 (en) | 1980-09-17 |
| ES489042A1 (en) | 1980-09-16 |
| AU5594080A (en) | 1980-09-11 |
| JPS55122761A (en) | 1980-09-20 |
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