FI78074B - Foerfarande foer framstaellning av farmakologiskt vaerdefulla substituerade 2-fenyl-2-pyridyloxi- och -tio-etylaminer. - Google Patents
Foerfarande foer framstaellning av farmakologiskt vaerdefulla substituerade 2-fenyl-2-pyridyloxi- och -tio-etylaminer. Download PDFInfo
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- FI78074B FI78074B FI823246A FI823246A FI78074B FI 78074 B FI78074 B FI 78074B FI 823246 A FI823246 A FI 823246A FI 823246 A FI823246 A FI 823246A FI 78074 B FI78074 B FI 78074B
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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Description
λ 78074
Menetelmä valmistaa farmakologisesti arvokkaita substituoituja 2-fenyyli-2-pyridyylioksi- ja -tio-etyyliamiineja. -Förfarande för framställning av farmakologiskt värdefulla substituerade 2-fenyl-2-pyridyloxi- och -tio-etylaminer.
Keksinnön kohteena on menetelmä valmistaa farmakologisesti arvokkaita substituoituja 2-fenyyli-2-pyridyylioksi- ja -tio-etyyliamiine ja, joiden kaava I on / *3 0 N, X ^/«4
„ CH - CHo - N
R1 —f- I 1 x
Rs jossa
Rl ja R2/ jotka voivat olla samanlaisia tai erilaisia, ovat vety, halogeeniatomi, metyyli, metoksi, amino tai nitro, R3 on vety, halogeeni tai metyyli ja R4 ja R5, jotka voivat olla samanlaisia tai erilaisia ovat vety tai 1-2 hiiliatominen alkyyliryhmä tai ne muodostavat yhdessä typpiatomin kanssa pyrrolidino- tai morfolinorenkaan ja X on O tai S, ja niiden fysiologisesti sopivia happoadditio-suoloja.
Keksinnön mukaan uudet kaavan I mukaiset yhdisteet voidaan valmistaa saattamalla yleiskaavan II mukainen fenyylietyyli-amiini >V «-». v " '“CJr 2 78074 jossa Ri, R2, R4 ja R5 tarkoittavat samaa kuin edellä ja Y on halogeniatomi tai hydroksiryhmä, tai tämän yhdisteen happoaddi-tiosuola reagoimaan yleiskaavan III mukaisen pyridiinijohdoksen kanssa /-vz <' N (III)
R3^W
jossa R3 tarkoittaa samaa kuin edellä ja Z on hydroksi- tai merkapto-ryhmä.
Yleiskaavan II mukaisilla lähtöaineilla, joissa Y on hydroksi-ryhmä, tapahtuu kondensaatio yleiskaavan III mukaisen yhdisteen kanssa happamessa väliaineessa korotetuissa lämpötiloissa. Tässä reaktiossa tulevat kysymykseen vahvat epäorgaaniset tai orgaaniset hapot, esim. väkevät mineraalihapot kuten kloori-vetyhappo, bromivetyhappo, rikkihappo, polyfosforihappo, edelleen etikkahappoanhydridi, forforipentoksidi tai trifluori-etikkahappo.
Yleiskaavan II mukaiset fenyylietyyliamiinit, joissa Y on halo-geeniatomi, saatetaan reagoimaan yleiskaavan III mukaisen pyridiinijohdoksen kanssa parhaiten käyttämällä emäksistä ainetta ja parhaiten faasinsiirto-olosuhteissa (so. lisäämällä yhtä tai useampaa pitkäketjuista tertiääristä amiinia, kuten bentsyyli- tributyyli-ammonium-halogenidia tai tetrabutyyli-ammonium-halogenidia tai lisäämällä bentsyyli-trifenyyli-fosfoniumkloridia).
Emäksisinä aineina tulevat kysymykseen epäorgaaniset emäkset kuten alkali- tai maa-alkalihydroksidit tai -karbonaatit, orgaaniset emäkset kuten pyridiini, piperidiini, tertiääriset amiinit tai myös alkalalkoholaatit.
Yleiskaavan I mukaiset yhdisteet, joissa R4 ja/tai R5 on vety, voidaan sinänsä tunnetulla tavalla alkyloida, esim. saattamalla reagoimaan dialkyylisulfaatin tai alkyylihalogenidin kanssa.
3 78074 Lähtöaineet ovat yleisiä kemikaaleja, joita voidaan hankkia kaupasta tai jotka voidaan valmistaa yleisesti tunnetuilla menetelmillä.
Yleiskaavan I mukaiset lopputuotteet voidaan haluttaessa muuttaa tavanomaisilla menetelmillä fysiologisesti vaarattomiksi happo-additiosuoloikseen. Tähän tarkoitukseen sopivat hapoiksi sekä epäorgaaniset hapot kuten halogeenivetyhapot, rikkihappo, fos-forihappo ja aminosulfonihappo, että myös orgaaniset hapot kuten muurahaishappo, etikkahappo, propionihappo, maitohappo, glukoo-lihappo, glukoonihappo, maleiinihappo, meripihkahappo, viini-happo, bentsyylihappo, salisyylihappo, sitruunahappo, askorbii-nihappo, p-tolueenisulfonihappo tai oksietaanisulfonihappo.
Japanilaisesta julkaisusta 53 141 271 tunnetaan yhdiste, jonka kaava on
Het-Ri-Z-R2-NH-Y
jossa Y on happoryhmä. Tunnetussa yhdisteessä on ryhmät Het (esim. pyridyyli) suoraan sidottu hiiliatomiin, ei siis O tai S-atomin kautta, kuten kaavan I mukaisssa yhdisteissä. Tunnetut yhdisteet eroavat kaavan I mukaisista uusista yhdisteistä N-asyyliryhmän suhteen. Lisäksi näitä tunnettuja yhdisteitä kuvataan mahanesteen eritystä hidastavina yhdisteinä, kun taas kaavan I mukaiset yhdisteet ovat osoittautuneet käyttökelpoisiksi antidepressiivisinä yhdisteinä.
Yleiskaavan I mukaiset uudet yhdisteet ja niiden happoadditiosuo-lat ovat arvokkaita farmaseuttisia aineita; ne tehoavat hyvin 4 78074 antidepressiiveille spesifisissä biokemiallisissa ja farmakologisissa koejärjestelyissä. Siten niillä on kyky estää hiirillä tertabentsaiinilla indusoitua ptoosistaj EDsg-arvo on suuruusluokkaa 1 mg/kg. Tätä testiä käytetään antidepressiivisten ominaisuuksien standarditestinä (International Journal of Neuropharmacology 8, 73 (1969)).
Keksinnön mukaisilla yhdisteillä on osoittautunut olevan erittäin suotuisa vaikutus myös testissä, jossa tutkitaan reserpiini antagonismia, so. reserpiinillä aiheutetun hypotermiavaikutuksen kumoamista antidepressiivisesti tehokkailla aineilla. Lisäksi on todettu, että ne estävät serotoniinin ja adrenaliinin palautumista neuroneihin.
Uudet yhdisteet ovat erityisen arvokkaita johtuen rakenteesta, joka poikkeaa tähän mennessä tunnetuista antidepressiiveistä; niiden vaikutus on yhtä hyvä tai parempi kuin tunnettujen kaupallisten tuotteiden ja samalla niillä on alhaisempi toksisuus.
Erityisesti maininnan arvoisia ovat sellaiset yleiskaavan I mukaiset yhdisteet, joissa on bromiatomi p-asemassa, X on happiatomi, R2 on vety, R3 ja R4 tarkoittavat metyyliryhmiä. Erityisen huomattavia ovat seuraavat yhdisteet: 2-(p-bromifenyyli)-2-(pyridyyli)-(3)-oksi)-N,N-dimetyyli-etyyli-amiini.
Farmakologiset kokeet
On tunnettua, että erilaiset depressiomuodot aiheuttavat bio-geenisten amiinien, erityisesti noradrenaliinin ja serotoniinin, vähenemisen tietyillä alueilla aivoissa. Biogeenisia amiineja voidaan näin ollen lisätä estämällä imeytymisen neurooneihin.
Farmakologinen koe on suoritettu homogenisoiduilla eristetyillä rotan aivoilla. Näin saatu synoptosoni-suspensio inkuboitiin 5 78074 deutterisoidulla noradrenaliinilla tai serotonilla ja erilaisilla koeliuoksen pitoisuuksilla vedessä 10 minuuttia lämpötilassa 37°C. Inkuboinnin päätyttyä väliaine erotettiin suodattamalla ja synaptosoni-suspension radioaktiviteetti mitattiin.
Lisäksi suoritettiin kontrollikoe ilman koeyhdisteitä radioaktiivisen amiinin adsorptiomäärän määrittämiseksi. Arvolla IC50 tarkoitetaan sitä koeyhdisteen määrää mooleissa, joka on riittävä 50 %:n adsorptio (Uptake) estämiseksi. Keksinnön mukaan valmistetuilla uusilla yhdisteillä arvot ovat suuruusluokkaa 10~6 _ io~7 moolia. Koetulokset on esitetty seuraavassa taulukossa.
Seroto- Noradre-
Tetra- niini naliini- benatsiini esto esto
Yhdiste hiiri, ED50 IC50 (mol) IC50 (mol) 2-(3,4-dikloorifenyyli)- 2-(3-pyridyylioksi)-N,N- dimetyylietyyliamiini 1,76 0,345*10-6 0,086*10“^ 2-(p-bromifenyyli)-2-(4-pyridyylioksi)-N,N- dimetyylietyyliamiini 2,0 0,42 ·10“6 0,75 ·10-6 2-(p-bromifenyyli)-2-(3-pyridyylioksi)-N,N- dimetyylietyyliamiini 1,1 0,4 ·10“6 0,54 ·10“6 2-(2-kloori-4-bromife-nyyli)-2-(3-pyridyyli-oksi)-N,N-dimetyyli-etyylamiini 3,6 6 78074 (ed. sivulta jatkoa)
Seroto- Noradre-
Tetra- niini naliini- benatsiini esto esto
Yhdiste hiiri, ED50 IC50 (®ol) IC50 (mol) 2-fenyyli-2-(3-pyridyy-lioksi)-N,N-dimetyyli- etyyliamiini 4,7 2,7 ·10“® 4,3 ·10"6 2-fenyyli-2-(2-pyridyy-lioksi)-N,N-dimetyyli- etyyliamiini 1,6 7,8 »10-^ 1,2 *10”® 2-(4-bromi-6-kloorife-nyyli)-2-(2-pyridyyli-oksi)-N,N-dimetyyli- etyyliamiini 8,4 - 0,26 ·10-® [2-(4-bromifenyyli)-2-(pyridyyli-(2)-tio)-N,N-dimetyyli etyyli- amiini ]____________________2X9_________-_________
Seuraavat esimerkit selventävät keksintöä lähemmin:
Esimerkki 1 2-p-bromifenyyli-2-(3-pyridyylioksi)-N,N-dimetyyli-etyyliamiini- dihydrokloridi 29,9 g 2-kloori-2-p-bromifenyyli-N,N-dimetyyli-etyyliamiini-hydrokloridia (0,1 moolia) ja 14,3 g 3-hydroksipyridiiniä (0,15 moolia) kuumennetaan 16 tuntia refluksoiden seoksessa, joka sisältää 150 ml 25 %:sta natriumhydroksidia ja 150 ml tolu- 7 78074 eenia sekä 0,5 g bentsyylitrifenyylifosfoniumkloridia. Liuotin tislataan pois orgaanisesta faasista, jolloin jäljelle jää jäännös, joka liuotetaan alkoholiin. Otsikkoyhdisteen dihydrokloridi saadaan suolahapolla. Puhdistamista varten otsikkoyhdiste käsitellään sykloheksaanissa aktiivihiilellä ja piimaalla. Dihydro-kloridin saanto on 20 g (44 % teoreettisesta). Sulamispiste 128 - 129°C (etanoli).
Edellä kuvatulla menetelmällä saatiin seuraavat yleiskaavan I mukaiset yhdisteet:
Pyridyy-
Esim. R2 R3 R4 R5 X iin Sp.°C
no.___________________________________________liitos_______ 2 H H H CH3 CH3 O 2 162 - 162 3 H H H CH3 CH3 O 3 151 - 152 4 4-Br H 2-C1 CH3 CH3 O 3 135 - 136 5 4-Br H 5-C1 CH3 CH3 O 2 234 - 235 6 4-Br H 6-C1 CH3 CH3 O 2 193 - 194 7 4-Br H H CH3 CH3 O 2 162 - 163 8 4-Br H H CH3 CH3 S 2 190 - 191 9 4-Br H H Morfoliini O 3 95-97 10 4-Br H H Pyrrolidiini 0 3 152 - 153 11 4-Br H H CH3 CH3 O 4 112 (haj) 12 4-C1 H H CH3 CH3 O 3 126 (haj) 13 3-C1 4-C1 H CH3 CH3 O 3 175 - 176 14 4-OCH3 H H CH3 CH3 O 3 103 - 105 15 3-OCH3 H H H H O 2 222 - 223 16 4-CH3 H H CH3 CH3 O 3 180 - 181
Claims (2)
- 8 78074 Patenttivaatimus Menetelmä valmistaa farmakologisesti arvokkaita substituoituja 2-fenyyli-2-pyridyylioksi- ja -tio-etyyliamiineja, joiden kaava I on /3 0 ... R2 X ^ R4 — CH - CH2 - N ">-ζχ jossa Rl ja R21 jotka voivat olla samanlaisia tai erilaisia, ovat vety, halogeeniatomi, metyyli, metoksi, amino tai nitro, R3 on vety, halogeeni tai metyyli ja R4 ja R5, jotka voivat olla samanlaisia tai erilaisia ovat vety tai 1-2 hiiliatominen alkyyliryhmä tai ne muodostavat yhdessä typpiatomin kanssa pyrrolidino- tai morfolinorenkaan ja X on O tai S, ja niiden fysiologisesti sopivia happoadditio-suoloja, tunnettu siitä, että yleiskaavan II mukainen fenyylietyyliamiini RaW T R f* >1- CH - CH2 - N (II) l—h \n r5 jossa Rl, R2, R4 ja R5 tarkoittavat samaa kuin edellä ja Y on halogeeniatomi tai hydroksiryhmä, tai tämän yhdisteen happo-additiosuola saatetaan reagoimaan yleiskaavan III mukaisen pyridiinijohdoksen kanssa 9 78074 β 'βι dii) R3 jossa R3 on vety, halogeeniatomi tai metyyliryhmä ja Z on hydroksi- tai merkaptoryhmä, ja näin saatu lopputuote mahdollisesti muunnetaan fysiologisesti sopivaksi happoadditio-suolaksi. Förfarande för framställning av farmakologiskt värdefulla substituerade 2-fenyl-2-pyridyloxi- och -tio-etylaminer med formeln I /3 0
- 2 Xv-v. X ^ r4 "‘-O- H"CH2 ’ "xr5 där Rl och R2* vilka kan vara likadana eller oiikä, är väte, en halogenatom, metyl, metoxi, amino eller nitro, R3 Mr väte, halogen eller metyl och R4 och R5, vilka kan vara likadana eller olika, är väte eller en alkylgrupp med 1-2 kolatomer eller de bildar tillsammans med kväveatomen en pyrrolidino- eller morfolinoring och X är 0 eller S, och deras fysiologiskt lämpliga syraadditions-salter, kännetecknat därav, att en fenyletylamin med den allmänna formeln II
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3138550 | 1981-09-28 | ||
| DE19813138550 DE3138550A1 (de) | 1981-09-28 | 1981-09-28 | Substituierte 2-phenyl-2-(pyridyloxy)-ethylamine und isostere verbindungen, verfahren zu ihrer herstellung und verwendung |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI823246A0 FI823246A0 (fi) | 1982-09-22 |
| FI823246L FI823246L (fi) | 1983-03-29 |
| FI78074B true FI78074B (fi) | 1989-02-28 |
| FI78074C FI78074C (fi) | 1989-06-12 |
Family
ID=6142812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI823246A FI78074C (fi) | 1981-09-28 | 1982-09-22 | Foerfarande foer framstaellning av farmakologiskt vaerdefulla substituerade 2-fenyl-2-pyridyloxi- och -tio-etylaminer. |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4666910A (fi) |
| EP (1) | EP0075752B1 (fi) |
| JP (1) | JPS5869865A (fi) |
| KR (1) | KR880002705B1 (fi) |
| AR (1) | AR231534A1 (fi) |
| AT (1) | ATE18551T1 (fi) |
| AU (1) | AU550614B2 (fi) |
| CA (1) | CA1171086A (fi) |
| DE (2) | DE3138550A1 (fi) |
| DK (1) | DK156718C (fi) |
| ES (1) | ES8308543A1 (fi) |
| FI (1) | FI78074C (fi) |
| GB (1) | GB2106902B (fi) |
| GR (1) | GR77657B (fi) |
| IE (1) | IE53959B1 (fi) |
| IL (1) | IL66870A (fi) |
| NO (1) | NO159999C (fi) |
| NZ (1) | NZ202015A (fi) |
| PH (1) | PH23219A (fi) |
| PT (1) | PT75611B (fi) |
| ZA (1) | ZA827055B (fi) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8320699D0 (en) * | 1983-08-01 | 1983-09-01 | Wellcome Found | Ethylenediamines |
| GB0004153D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004152D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102639D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102640D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| US6800652B2 (en) | 2002-08-16 | 2004-10-05 | Pfizer Inc. | Diaryl compounds |
| GB0219154D0 (en) * | 2002-08-16 | 2002-09-25 | Pfizer Ltd | Diaryl compounds |
| SE0203304D0 (sv) * | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Coumpounds |
| CA2541809A1 (en) * | 2003-10-09 | 2005-04-21 | Millennium Pharmaceuticals, Inc. | Thioether-substituted benzamides as inhibitors of factor xa |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2734845A (en) * | 1956-02-14 | Aqueous suspension of procaine penicil- | ||
| US2734846A (en) * | 1956-02-14 | Aqueous suspension of procaine penicil- | ||
| FR1511398A (fr) * | 1966-02-16 | 1968-01-26 | Takeda Chemical Industries Ltd | Procédé de préparation de nouveaux dérivés de picoline |
| BE790592A (fi) * | 1971-10-28 | 1973-04-26 | Oreal | |
| US4011324A (en) * | 1976-01-20 | 1977-03-08 | Pfizer Inc. | Esters and amides of pyrimido[4,5-b]quinolin-4(3H)-one-2-carboxylic acids as antiulcer agents |
| JPS53141271A (en) * | 1977-05-13 | 1978-12-08 | Yamanouchi Pharmaceut Co Ltd | Heterocyclic compounds and process for their preparation |
-
1981
- 1981-09-28 DE DE19813138550 patent/DE3138550A1/de not_active Withdrawn
-
1982
- 1982-09-06 DE DE8282108196T patent/DE3269839D1/de not_active Expired
- 1982-09-06 AT AT82108196T patent/ATE18551T1/de not_active IP Right Cessation
- 1982-09-06 EP EP82108196A patent/EP0075752B1/de not_active Expired
- 1982-09-22 FI FI823246A patent/FI78074C/fi not_active IP Right Cessation
- 1982-09-24 AR AR290759A patent/AR231534A1/es active
- 1982-09-24 IL IL66870A patent/IL66870A/xx unknown
- 1982-09-27 IE IE2330/82A patent/IE53959B1/en not_active IP Right Cessation
- 1982-09-27 PT PT75611A patent/PT75611B/pt not_active IP Right Cessation
- 1982-09-27 CA CA000412268A patent/CA1171086A/en not_active Expired
- 1982-09-27 JP JP57168221A patent/JPS5869865A/ja active Granted
- 1982-09-27 ZA ZA827055A patent/ZA827055B/xx unknown
- 1982-09-27 NZ NZ202015A patent/NZ202015A/en unknown
- 1982-09-27 DK DK428582A patent/DK156718C/da not_active IP Right Cessation
- 1982-09-27 ES ES515972A patent/ES8308543A1/es not_active Expired
- 1982-09-27 AU AU88738/82A patent/AU550614B2/en not_active Ceased
- 1982-09-27 NO NO823253A patent/NO159999C/no unknown
- 1982-09-27 KR KR8204342A patent/KR880002705B1/ko active
- 1982-09-27 GB GB08227449A patent/GB2106902B/en not_active Expired
- 1982-09-28 GR GR69383A patent/GR77657B/el unknown
-
1984
- 1984-08-28 US US06/645,007 patent/US4666910A/en not_active Expired - Fee Related
-
1985
- 1985-03-07 PH PH31952A patent/PH23219A/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: BOEHRINGER INGELHEIM KG |