NO780226L - NEW PROSTAGLANDIN ANALOG AND PROCEDURES FOR THEIR PREPARATION - Google Patents

NEW PROSTAGLANDIN ANALOG AND PROCEDURES FOR THEIR PREPARATION

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Publication number
NO780226L
NO780226L NO780226A NO780226A NO780226L NO 780226 L NO780226 L NO 780226L NO 780226 A NO780226 A NO 780226A NO 780226 A NO780226 A NO 780226A NO 780226 L NO780226 L NO 780226L
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compound
formula
atoms
residue
branched
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NO780226A
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Norwegian (no)
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Wilhelm Bartmann
Gerhard Beck
Ulrich Lerch
Herman Teufel
Bernward Schoelkens
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Hoechst Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Furan Compounds (AREA)

Description

Nye prostaglandin-analoge og fremgangsmåteNew prostaglandin analogues and method

til deres fremstilling.to their production.

Oppfinnelsens gjenstand er prostaglandin-analoge med den generelle formel I: The object of the invention is prostaglandin analogue of the general formula I:

hvori in which

R1 ., og R 2 hver betyr hydrogen eller en hydroksylgruppe, idetR 1 ., and R 2 each means hydrogen or a hydroxyl group, as

1 2 1 2

R og R er forskjellige,R and R are different,

R 3 betyr en mettet eller umettet, rettlinjet eller forgrenet alifatisk hydrokarbonrest med 1-8 C-atomer, en rettlinjet eller forgrenet okso-alkylrest med 2-8 C-atomer, samt dets oksimer, oksimetre, etylenglykol- og etylenthioglykolacetaler, en rettlinjet eller forgrenet hydroksyalkylrest med 2-8 C-atomer, idet OH-gruppen er endeplassert, eller en rettlinjet eller forgrenet karboksyalkylrest med 2-8 C-atomer. R 3 means a saturated or unsaturated, linear or branched aliphatic hydrocarbon residue with 1-8 C atoms, a linear or branched oxo-alkyl residue with 2-8 C atoms, as well as its oximes, oximeters, ethylene glycol and ethylene thioglycol acetals, a straight or branched hydroxyalkyl residue with 2-8 C atoms, the OH group being terminally positioned, or a straight or branched carboxyalkyl residue with 2-8 C atoms.

R 4 betyr et hydrogenatome eller en rettlinjet eller forgrenet alkylgruppe med inntil 10 karbonatomer, R 4 means a hydrogen atom or a straight or branched alkyl group with up to 10 carbon atoms,

X betyr en mettet, forgrenet alkylengruppe med 2-5 C-atomer, eller en aryl- eller benzylrest, som på sin side kan være substi- X means a saturated, branched alkylene group with 2-5 C atoms, or an aryl or benzyl residue, which in turn can be substituted

tuert med en eller flere lavere alkyl- eller alkoksygrupper,tuated with one or more lower alkyl or alkoxy groups,

en eller flere halogenatomer eller trifluormetylgrupper, eller betyr en a-eller (3-furfurylrest, one or more halogen atoms or trifluoromethyl groups, or means an α-or (3-furfuryl residue,

samt de fysiologisk holdbare salter av forbindelsen med formel I med organiske og uorganiske baser og deres estere med alifatiske, cykloalifatiske eller aralifatiske alkoholer med 1-8 C-atomer i esterdelen. as well as the physiologically stable salts of the compound of formula I with organic and inorganic bases and their esters with aliphatic, cycloaliphatic or araliphatic alcohols with 1-8 C atoms in the ester part.

Oppfinnelsens gjenstand er videre en fremgangsmåte til fremstilling av forbindelsene med formel I, idet fremgangsmåten erkarakterisert vedat en forbindelse med formel II The object of the invention is further a method for preparing the compounds of formula I, the method being characterized by a compound of formula II

3 12 hvori R og X har den under formel I nevnte betydning og R og R betyr sammen oksygen, ved omsetning med egnet acyleringsmiddel overføren i en forbindelse med formel I og den dannede forbin delse reduseres eventuelt til en forbindelse med formel I, hvori 1 2 3 12 in which R and X have the meaning mentioned under formula I and R and R together mean oxygen, by reaction with a suitable acylating agent the transfer in a compound of formula I and the compound formed part is optionally reduced to a compound of formula I, in which 1 2

en av restene R og R betyr hydrogen og den annen en hydroksylgruppe, og hvis ønsket overføres en forbindelse med formel I etter vanlig fremgangsmåte i et fysiologisk . tålbart salt eller i en ester. one of the residues R and R represents hydrogen and the other a hydroxyl group, and if desired, a compound of formula I is transferred according to the usual procedure in a physiological . tolerable salt or in an ester.

3 Av de for substituentene R nevnte rester er lavere alkylrester, spesielt metyl-, etyl-, propyl- og isobutylgruppen foretrukket når R 3 betyr en mettet, rettlinjet eller forgrenet rest, videre lavere alkylrester, spesielt allyresten, når R<3>betyr en umettet, rettlinjet rest. Av de nevnte okso-alkylrester egner det seg spesielt de rettlinjede eller forgrenede C2~C^-oksoalkylrester med endeplasserte oksogrupper, samt deres oksimer, oksimeter, et/lenglykol og etylenthioglykolacetal, fortrinnsvis 3-okaopropyl- og 2-dimetyl-3-oksopropylresten av hydroksyalkyl-restene, spesielt de rettlinjede eller forgrenede C2~C^-hydroksy-alkylrester, fortrinnsvis 3-hydroksypropyl- og 2-dimetyl-3-hydroksypropylresten av karboksyalkylresten, spesielt de rettlinjede eller forgrenede C2_C^-karboksyalkylrester, fortrinnsvis 3 Of the residues mentioned for the substituents R, lower alkyl residues, especially the methyl, ethyl, propyl and isobutyl group are preferred when R 3 means a saturated, straight-line or branched residue, further lower alkyl residues, especially the allyl residue, when R<3> means a unsaturated, rectilinear residue. Of the mentioned oxo-alkyl radicals, the straight-line or branched C2~C4-oxoalkyl radicals with terminal oxo groups, as well as their oximes, oximeters, ethylene glycol and ethylenethioglycol acetal, are particularly suitable, preferably the 3-okaopropyl and 2-dimethyl-3-oxopropyl radicals of the hydroxyalkyl residues, especially the straight-line or branched C2-C^-hydroxyalkyl residues, preferably the 3-hydroxypropyl and 2-dimethyl-3-hydroxypropyl residue of the carboxyalkyl residue, especially the straight-line or branched C2-C^-carboxyalkyl residues, preferably

2-karboksyetyl- og 2-dimetyl-2-karboksyetylresten. 2-carboxyethyl and 2-dimethyl-2-carboxyethyl residues.

Av de for X nevnte grupper er følgende foretrukket: Of the groups mentioned for X, the following are preferred:

etylidengruppen the ethylidene group

isopropylen- og isobutylengruppen, the isopropylene and isobutylene group,

fenylen- og benzylengruppen, som på sin side kan være substituert med en eller flere metyl-, etyl-, metoksy- og/eller etoksygrupper med en eller flere fluor- og/eller kloratomer samt med en eller flere trifluormetylgrupper. Spesielt kommer det for X i betraktning isobutylen-, etyliden-, 3-klorfenylen- samt 2-metoksybenzylen-gruppen. the phenylene and benzylene group, which in turn may be substituted with one or more methyl, ethyl, methoxy and/or ethoxy groups with one or more fluorine and/or chlorine atoms and with one or more trifluoromethyl groups. In particular, the isobutylene, ethylidene, 3-chlorophenylene and 2-methoxybenzylene groups come into consideration for X.

R 4 er fortrinnsvis rettlinjet eller forgrenete alkyl-grupper med inntil 4 karbonatomer. R 4 is preferably straight or branched alkyl groups with up to 4 carbon atoms.

For fremgangsmåten ifølge oppfinnelsen kommer det som acyleringsmiddel i betraktning de frie karboksylsyrer samt deres reaksjonsdyktige derivater. Ved anvendelse av karboksylsyrer gjen-nomfører man reaksjonen fortrinnsvis i denne syre som oppløsnings-middel ved temperaturer mellom 0° og 70°C. I noen tilfeller er det fordelaktig å avpuffe reaksjonsoppløsning for unngåelse av bireaksjoner (Jfr. J.E. Pike, F.H. Lincoln, W.P. Schneider, J.Org.Chem. 34, 3553 (1969)). For the method according to the invention, free carboxylic acids and their reactive derivatives come into consideration as acylating agents. When using carboxylic acids, the reaction is preferably carried out in this acid as solvent at temperatures between 0° and 70°C. In some cases it is advantageous to debuff the reaction solution to avoid side reactions (Cf. J.E. Pike, F.H. Lincoln, W.P. Schneider, J.Org.Chem. 34, 3553 (1969)).

Til acylering kan det videre anvendes de tilsvarende karboksylsyrehalogenider eller karboksylsyreanhydrider. Reaksjonen gjennomføres da fortrinnsvis i aprotiske oppløsnings-midler i nærvær av en base ved temperaturer mellom 0 og 80°C. For acylation, the corresponding carboxylic acid halides or carboxylic acid anhydrides can also be used. The reaction is then preferably carried out in aprotic solvents in the presence of a base at temperatures between 0 and 80°C.

Til f remstilling.rav forbindelsen ifølge oppfinnelsen kommer det videre i betraktning omsetning av alkoholer med de tilsvarende ketener. Denne reaksjon gjennomføres likeledes i aprotiske opp-løsningsmidler ved værelsetemperatur. For the preparation of the compound according to the invention, reaction of alcohols with the corresponding ketenes is also taken into account. This reaction is also carried out in aprotic solvents at room temperature.

For fremstilling av slike forbindelser med formel I, hvor en av restene R og R 2 betyr en hydroksylgruppe og den andre hydrogen, reduseres de etter ovennevnte fremgangsmåte fremstilte 15-0-acyl-A-prostaglandiner. Som reduksjonsmiddel kommer det her-til i betraktning fremfor alt komplekse hydrider som formår å redusere en ketogruppe uten å angripe ester- eller karboksyl-gruppene. Spesielt har det vist seg egnet her anvendelsen av natriumborhydrid i metanol/vann som oppløsningsmiddel. For the production of such compounds of formula I, where one of the residues R and R 2 represents a hydroxyl group and the other hydrogen, the 15-0-acyl-A-prostaglandins produced according to the above-mentioned method are reduced. As a reducing agent, here above all complex hydrides which manage to reduce a keto group without attacking the ester or carboxyl groups come into consideration. In particular, the use of sodium borohydride in methanol/water as a solvent has proven suitable here.

Utgangsforbindelsene med formel II kan fremstilles ifølge DOS 2 435 331. The starting compounds of formula II can be prepared according to DOS 2 435 331.

De omtalte forbindelser fremstilt ifølge oppfinnelsen utmerker seg ved spasmogene, bronchodilatoriske, blodtrykksenkende mavesaftsekresjonshemmende, leuteolytiske og abortive egenskaper spesielt ved blodtrykksenkende virkning som hver er overlegen de ikkeacylerte utgangsforbindelser. De for blodtrykksenkende virkning uønskede bivirkninger på den glatte muskulatur iakttas ikke i disse tilfeller. The mentioned compounds produced according to the invention are distinguished by spasmogenic, bronchodilatory, blood pressure-lowering gastric juice secretion-inhibiting, luteolytic and abortive properties, especially by blood pressure-lowering action, each of which is superior to the non-acylated starting compounds. Undesirable side effects on smooth muscle due to the blood pressure-lowering effect are not observed in these cases.

På grunn av de farmakologiske virkninger kan forbindelsene ifølge oppfinnelsen anvendes som legemidler. Due to the pharmacological effects, the compounds according to the invention can be used as pharmaceuticals.

De kan komme til anvendelse i form av deres vandige oppløsninger eller suspensjoner eller også oppløst eller suspen-dert i farmakologisk ufarlige organiske oppløsningsmidler som en- eller flerverdige alkoholer, f.eks. etanol, etylenglykol eller glycerol, oljer som f.eks. solsikkeolje eller lebertran, o etere som f.eks. eietylenglykoldimetyleter eller også polyetere som f.eks. polyetylenglykol eller også i nærvær av andre farmakologisk ufarlige polymerbærere som f.eks. polyvinylpyrrolidon. They can be used in the form of their aqueous solutions or suspensions or also dissolved or suspended in pharmacologically harmless organic solvents such as monohydric or polyhydric alcohols, e.g. ethanol, ethylene glycol or glycerol, oils such as sunflower oil or cod liver oil, or ethers such as ethylene glycol dimethyl ether or also polyethers such as e.g. polyethylene glycol or also in the presence of other pharmacologically harmless polymer carriers such as e.g. polyvinylpyrrolidone.

Som tilberedninger kan det komme på tale de vanlige galeniske infusjons- eller injeksjonsoppløsninger og tabletter, samt lokalt anvendbare tilberedninger som kremer, emulsjoner, suppositorier, spesielt også aerosoler. Preparations include the usual galenic infusion or injection solutions and tablets, as well as locally applicable preparations such as creams, emulsions, suppositories, especially aerosols.

En ytterligere anvendelse av de nye forbindelser ligger i kombinasjonen med andre virksomme stoffer. Blant andre egnede stoffer hører fremfor alt: Diuretika, som f.eks. urosemid, antidiabetika, som f.eks. glycodiazin, tolbutamid, glibenclamid, phenformin, bu-formin, metformin, kretsløpsmidler i videste forstand, f.eks. coronardilatatorer, som chromonar eller prenylamin, blodtrykksenkende stoffer som reserpin, a-metyl-dopa eller clonidiner eller anitarrytmika, lipidsenkere, geriatrika og andre stoff-vekselvirksomme preparater, psykofarmaka, som f.eks. klor-diazepoksyd, diazepam eller meprobamat, samt vitaminer eller prostaglandiner eller prostaglandin-lignende forbindelser som også prostaglandinantagonister og prostaglanding-biosyntesehemmere som f.eks. ikke-steroidale antiphlogistika. A further application of the new compounds lies in the combination with other active substances. Other suitable substances include above all: Diuretics, such as e.g. urosemide, antidiabetics, such as e.g. glycodiazine, tolbutamide, glibenclamide, phenformin, bu-formin, metformin, circulatory agents in the broadest sense, e.g. coronary dilators, such as chromonar or prenylamine, blood pressure-lowering substances such as reserpine, α-methyl-dopa or clonidines or antiarrhythmics, lipid-lowering agents, geriatrics and other drug-interacting preparations, psychopharmaceuticals, such as e.g. chlordiazepoxide, diazepam or meprobamate, as well as vitamins or prostaglandins or prostaglandin-like compounds such as prostaglandin antagonists and prostaglanding biosynthesis inhibitors such as e.g. non-steroidal antiphlogistics.

Eksempel 1 Example 1

9- keto- 15 3~ formyloksy- 16, 16- dimetyl- 18- oksa- prosta- 5, 10, 13-triensyre. 9- keto- 15 3~ formyloxy- 16, 16- dimethyl- 18- oxa-prosta- 5, 10, 13-trienoic acid.

200 mg 16,16-dimetyl-18-oksa-prostaglanding A2opptas i 7,5 ml maursyre som på forhånd er blitt avpufret noe ved til-setning av 50 mg soda. Man lar det stå en dag ved værelsetemperatur under fuktighetsutelukkelse. Deretter opptar man med kloroform,ekstraherer den organiske fase to ganger med vann, tørker og inndamper. Residuet renses ved kromatografi på kiselgel med cyklohexan/eddikester/iseddik 90/10/1. 200 mg of 16,16-dimethyl-18-oxa-prostaglandin A2 is taken up in 7.5 ml of formic acid which has previously been somewhat buffered by the addition of 50 mg of soda ash. It is allowed to stand for a day at room temperature under exclusion of moisture. The mixture is then taken up with chloroform, the organic phase is extracted twice with water, dried and evaporated. The residue is purified by chromatography on silica gel with cyclohexane/acetic ester/glacial acetic acid 90/10/1.

Man får 110 mg av det ønskede produkt.You get 110 mg of the desired product.

DC (Cyklohexan/eddikester/iseddik 60/40/1)DC (Cyclohexane/acetic ester/glacial acetic acid 60/40/1)

Rf ro 0,70.Rf ro 0.70.

NMR ( 60 mHz , CDC13) ( cT -verdi)NMR (60 mHz, CDCl3) (cT value)

8,1 singulett 1H (-0-C0-H), 7,45 oppspaltet dublett 1H (CH-CH-C=0), 6,15 oppspaltet dublett 1H (=CH-C=0); 5,15 - 5,85 8.1 singlet 1H (-0-C0-H), 7.45 cleaved doublet 1H (CH-CH-C=0), 6.15 cleaved doublet 1H (=CH-C=0); 5.15 - 5.85

■ i ■ i

multiplett 4H (olefiniske protoner), 3,9-4,4 multiplett 1H (CH-OOCH), 3,25 kvartett 2H, J= 7 Hz (CH2OCH2CH3), 3,1 singulett 2H (CI^OEt), 0,9-2,6 protoner, herunder singuletter ved 0,9 og 1,0 ppm ((CH3)2C), triplett ved 1,15, J = 7Hz (CH2CH_3) . multiplet 4H (olefinic protons), 3.9-4.4 multiplet 1H (CH-OOCH), 3.25 quartet 2H, J= 7 Hz (CH2OCH2CH3), 3.1 singlet 2H (CI^OEt), 0.9 -2.6 protons, including singlets at 0.9 and 1.0 ppm ((CH3)2C), triplet at 1.15, J = 7Hz (CH2CH_3) .

Eksempel 2 Example 2

9- keto- 15a- acetoksy- 16, 16- dimetyl- 18- oksa- prosta- 5, 10, 13-triensyre. " 9- keto- 15a- acetoxy- 16, 16- dimethyl- 18- oxa-prosta- 5, 10, 13-trienoic acid. "

100 mg 16,16-dimetyl-18-oksa-PGA2(fremstilt ifølge DOS 2 435 331 eller belgisk patent nr. 831.649) has en liten kolbe med nitrogen. Deretter tildrypper man iløpet av en halv time 3 ml eddiksyreanhydrid og setter til den klare oppløsning 20 mg kaliumkarbonat. Det omrøres 10 timer ved værelsetemperatur. Reaksjonens avslutning fastslås ved hjelp av tynnsjiktkromato-gram (kiselgel-elueringsmiddel: cyklohexan, eddikester, iseddik = 60 : 40: 1). Etter avsluttet reaksjon, opptas reaksjonsblan-dingen i 40 ml CHC13og elueres 3 ganger med 10 ml H20. CHC13~fasen tørkes med MgSO^og inndampes. Residuet kromatograferes på kiselgel. (Elueringsmiddel som ovenfor). 100 mg of 16,16-dimethyl-18-oxa-PGA2 (manufactured according to DOS 2,435,331 or Belgian patent no. 831,649) has a small flask with nitrogen. Then, over the course of half an hour, 3 ml of acetic anhydride are added drop by drop and 20 mg of potassium carbonate is added to the clear solution. It is stirred for 10 hours at room temperature. The completion of the reaction is determined by means of a thin-layer chromatogram (silica gel eluent: cyclohexane, acetic ester, glacial acetic acid = 60:40:1). After completion of the reaction, the reaction mixture is taken up in 40 ml CHCl 3 and eluted 3 times with 10 ml H 2 O. The CHC13~ phase is dried with MgSO^ and evaporated. The residue is chromatographed on silica gel. (Eluent as above).

Fraksjonene 9-16 inneholder 68 mg omtrent farveløs ol je. Fractions 9-16 contain 68 mg of approximately colorless oil.

Rf = 0,6 5 Rf = 0.6 5

Kjernemagnetisk resonans (i CDCl^) cT-verdier:Nuclear magnetic resonance (in CDCl^) cT values:

0,9; 1,0 singuletter, tilsammen 6 H J = 3 Hz (>C(CH3)2); 0.9; 1.0 singlets, total 6 H J = 3 Hz (>C(CH3)2);

1,15 triplett 3 H J = 7 Hz (CH2CH3); 1,5-2,6 multiplett 10 H (CH2,CH); 2,0 singulett 3 H (C0 CH3); 3,05 singulett 2H(CH2-0CH2-CH3); 3,25 kvartett 2 H J = 7 Hz (-CH2-0-CH2-CH3); 3,8-4,3-multiplett 1H (HC-0); 5,15-5,85 Multiplett 4H (olefiniske protoner); 6,15 oppspaltet dublett 1H (CH=CH-C=0)7,45 oppspaltet dublett 1H (CH=CH-C=0), 7,5 bred singulett 1H (-C00H). 1.15 triplet 3 H J = 7 Hz (CH2CH3); 1.5-2.6 multiplet 10 H (CH2,CH); 2.0 singlet 3 H (C0 CH3); 3.05 singlet 2H(CH2-OHCH2-CH3); 3.25 quartet 2 H J = 7 Hz (-CH2-0-CH2-CH3); 3,8-4,3-multiplet 1H (HC-0); 5.15-5.85 Multiplet 4H (olefinic protons); 6.15 cleaved doublet 1H (CH=CH-C=0)7.45 cleaved doublet 1H (CH=CH-C=0), 7.5 broad singlet 1H (-C00H).

i i in i

Claims (5)

1. Forbindelse med formel I: 1. Compound of Formula I: hvoriin which 1 2 R og R hver betyr hydrogen eller en hydroksylgruppe, idet 1 2 R og R er forskjellige, R 3 betyr en mettet eller umettet, rettlinjet eller forgrenet alifatisk hydrokarbonrest med 1-8 C-atomer, en rettlinjet eller forgrenet okso-alkylrest med 2-8 C-atomer, samt det oksimer, oksimetere, etylenglykol-og etylenthioglykolacetaler, en rettlinjet eller forgrenet hydroksyalkylrest med 2-8 C-atomer, idet OH-gruppen er endeplassert eller en rettlinjet eller forgrenet karboksyalkylrest med 2-8 C-atomer, R 4 betyr et hydrogenatom eller en rettlinjet eller forgrenet ..'..'■.'. alkylgruppe med inntil 10 karbonatomer, X betyr en mettet, forgrenet alkylengruppe med 2-5 C-atomer eller en aryl- eller benzylrest på sin side kan være substituert med en eller flere lavere alkyl- eller alkoksygrupper med en eller flere halogenatomer eller trifluormetylgrupper, eller betyr en a-eller 6-furfurylrest,t££? samt de fysiologisk [ho-ldjbare salter av forbindelsen med formel I med organiske og uorganiske baser og deres estere med alifatiske, cykloalifatiske eller aralifatiske alkholer med 1-8 C-atomer i esterdelen.1 2 R and R each means hydrogen or a hydroxyl group, 1 2 R and R are different, R 3 means a saturated or unsaturated, linear or branched aliphatic hydrocarbon residue with 1-8 C atoms, a linear or branched oxo-alkyl residue with 2-8 C atoms, as well as the oximes, oximeters, ethylene glycol and ethylene thioglycol acetals, a linear or branched hydroxyalkyl residue with 2-8 C atoms, as The OH group is terminal or a linear or branched carboxyalkyl residue with 2-8 C atoms, R 4 means a hydrogen atom or a straight or branched ..'..'■.'. alkyl group with up to 10 carbon atoms, X means a saturated, branched alkylene group with 2-5 C atoms or an aryl or benzyl residue in turn may be substituted by one or more lower alkyl or alkoxy groups with one or more halogen atoms or trifluoromethyl groups, or means an α- or 6-furfuryl residue,t££? as well as the physiologically acceptable salts of the compound of formula I with organic and inorganic bases and their esters with aliphatic, cycloaliphatic or araliphatic alcohols with 1-8 C atoms in the ester part. 2. Fremgangsmåte til fremstilling av forbindelse med formel I, ifølge krav 1, karakterisert ved at en forbindelse med formel II: 2. Process for producing a compound of formula I, according to claim 1, characterized in that a compound of formula II: hvori R 3 og X har den i formel I angitte betydning, og 1 2 R og R betyr sammen oksygen, ved omsetning med et egnet acyleringsmiddel overføres i en forbindelse med formel I, og den dannede forbindelse reduseres eventuelt til en forbindelse med 1 2 formel I, hvori en av restene R og R betyr hydrogen, og den andre en hydroksylgruppe, og hvis ønsket overfø res en forbindelse med formel I etter vanlige fremgangsmåter til et fysiologisk tålbart salt eller en ester.in which R 3 and X have the meaning given in formula I, and 1 2 R and R together mean oxygen, by reaction with a suitable acylating agent is transferred into a compound of formula I, and the compound formed is optionally reduced to a compound with 1 2 formula I, in which one of the radicals R and R represents hydrogen, and the other a hydroxyl group, and if desired, a compound of formula I is transferred by usual methods to a physiologically tolerable salt or an ester. 3. Fremgangsmåte til fremstilling av legemidler, karakterisert ved at en forbindelse med den i krav 1 angitte formel I, en ester eller et fysiologisk tålbart salt av syren I, eventuelt med vanlige farmasøytiske bærere og/ eller stabilisatorer .bringes i en terapeutisk egnet anvendelses-f orm.3. Process for the production of medicinal products, characterized in that a compound with the formula I specified in claim 1, an ester or a physiologically tolerable salt of the acid I, possibly with usual pharmaceutical carriers and/or stabilizers, is brought into a therapeutically suitable application for worm. 4. Legemiddel, karakterisert ved et innhold av en forbindelse av den i krav 1 nevnte formel I, en ester eller et fysiologisk tålbart salt av syren I, eller be-stående av en slik forbindelse.4. Medicinal product, characterized by a content of a compound of the formula I mentioned in claim 1, an ester or a physiologically tolerable salt of the acid I, or consisting of such a compound. 5. Anvendelse av forbindelse av en i krav 1 nevnte formel I, en ester eller et fysiologisk tålbart salt av denne forbindelse etter behandling av høyt blodtrykk.5. Use of a compound of formula I mentioned in claim 1, an ester or a physiologically tolerable salt of this compound after treatment of high blood pressure.
NO780226A 1977-01-21 1978-01-20 NEW PROSTAGLANDIN ANALOG AND PROCEDURES FOR THEIR PREPARATION NO780226L (en)

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