NO128997B - - Google Patents

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NO128997B
NO128997B NO03276/70A NO327670A NO128997B NO 128997 B NO128997 B NO 128997B NO 03276/70 A NO03276/70 A NO 03276/70A NO 327670 A NO327670 A NO 327670A NO 128997 B NO128997 B NO 128997B
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general formula
ethyl
acid
phenylsulfonyl
imino
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NO03276/70A
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Norwegian (no)
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H Dietrich
C Lehmann
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Ciba Geigy Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/44—Nitrogen atoms not forming part of a nitro radical
    • C07D233/46—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

Analogifremgangsmåte for fremstilling av nye, farmakologisk virksomme derivater av P-aminoalkyl-;benzensulfonamider. Analogy method for the production of new, pharmacologically active derivatives of P-aminoalkyl-benzenesulfonamides.

Det ble funnet at p-subst. fenylsulfonyl-2-imino-imidazolidin med den generelle formel I, It was found that p-subst. phenylsulfonyl-2-imino-imidazolidine of the general formula I,

hvor R^ betyr en cykloalkylrest med 5-8 karbonatomer, where R^ means a cycloalkyl residue with 5-8 carbon atoms,

;betyr hydrogen, en etyl- eller en metylgruppe, ;means hydrogen, an ethyl or a methyl group,

R, betyr en eventuelt forgrenet alkylgruppe med 1-6 karbonatomer, R, means an optionally branched alkyl group with 1-6 carbon atoms,

m betyr 2 eller 3 og m means 2 or 3 and

n betyr 1 eller 2, c.; n means 1 or 2, c.;

såvel som addisjonssalter med uorganiske eller organiske syrer, viser hypoglykemisk virkning på varmblodige dyr. as well as addition salts with inorganic or organic acids, show a hypoglycaemic effect on warm-blooded animals.

I forbindelsene med den generelle formel I kan R^ f.eks. In the compounds of the general formula I, R^ can e.g.

bety cyklopentylgruppen ; hvilken eventuelt kan være substituert med alkylrester med 1 - 3 karbonatomer, cykloheksyl-gruppen, hvilkeikan være substituert med etyl eller metyl og den eventuelt med metyl substituerte cykloheptylgruppen, såvel som cyklooktylgruppen. mean the cyclopentyl group; which may optionally be substituted with alkyl residues with 1 - 3 carbon atoms, the cyclohexyl group, which may be substituted with ethyl or methyl and the optionally methyl-substituted cycloheptyl group, as well as the cyclooctyl group.

R^ kan f.eks. bety metyl-, etyl-, propyl-, isopropyl-, butyl-, sek.butyl-, tert.butyl-, isobutyl-, pentyl-, isopentyl-, 2,2-dimetyl-propyl-, 1-metyl-butyl-, 1-etyl-propyl- eller 1,2-dimetyl-propylgruppen, eller en rettkjedet eller forgrenet heksylrest, f.eks. en n-heksyl-, metyl-pentyl-, dimetyl-butyl-eller etyl-butylgruppe. R^ can e.g. means methyl-, ethyl-, propyl-, isopropyl-, butyl-, sec.butyl-, tert.butyl-, isobutyl-, pentyl-, isopentyl-, 2,2-dimethyl-propyl-, 1-methyl-butyl- , the 1-ethyl-propyl or 1,2-dimethyl-propyl group, or a straight-chain or branched hexyl residue, e.g. an n-hexyl, methyl-pentyl, dimethyl-butyl or ethyl-butyl group.

Etter analogifremgangsmåten ifolge oppfinnelsen fremstilles forbindelsene med den generelle formel I ved at man omsetter et amin med den generelle formel II, According to the analogous method according to the invention, the compounds with the general formula I are prepared by reacting an amine with the general formula II,

hvor R^, R2 og m har den under formel I angitte where R 1 , R 2 and m are as indicated under formula I

betydning, importance,

med en karboksylsyre med den generelle formel III, with a carboxylic acid of the general formula III,

hvor R^ og n hair den under den generelle formel I where R^ and n hair it under the general formula I

angitte betydning, stated meaning,

eller med et reaksjonsdyktig derivat av en slik karboksylsyre og overforer, hvis onsket, de erholdte reaksjonsproduktene i saltet av en uorganisk eller organisk syre. or with a reactive derivative of such a carboxylic acid and, if desired, converts the reaction products obtained into the salt of an inorganic or organic acid.

Omsetningen av et amin med den generelle formel II med en karboksylsyre med den generelle formel III kan f.eks. finne sted på den måten at man med tilsvarende syre overforer forst aminet i ammonium-saltet med den generelle formel III, og derefter overforer dette ved torr oppvarming i amidet med den generelle formel I. Ifdlge en foretrukket utforelsesform av fremgangsmåten ifblge oppfinnelsen omsetter man et amin med den generelle formel II med en karboksylsyre med den generelle formel III i nærvær av et vannavspaltende middel i et inert opplbsningsmiddel. Et særlig egnet vannavspaltende middel er f.eks. N,N'-dicykloheksyl-karbodiimid. Videre kan som vannavspaltende middel karbonyl-dipyrazol anvendes. Som inert opplbsningsmiddel kommer i betraktning f.eks. hydrokarboner, som benzen, toluen eller xylen, eter, som dietyleter, dioksan eller tetrahydrofuran, klorerte hydrokarboner, som metylenklorid, kloroform, trikloretylen og lavere ketoner, som aceton eller metyletylketon. The reaction of an amine of the general formula II with a carboxylic acid of the general formula III can e.g. take place in such a way that one first transfers the amine in the ammonium salt with the general formula III with a corresponding acid, and then transfers this by dry heating into the amide with the general formula I. According to a preferred embodiment of the method according to the invention, an amine is reacted of the general formula II with a carboxylic acid of the general formula III in the presence of a water splitting agent in an inert solvent. A particularly suitable water splitting agent is e.g. N,N'-dicyclohexyl carbodiimide. Furthermore, carbonyl-dipyrazole can be used as a water-splitting agent. As an inert solvent comes into consideration e.g. hydrocarbons, such as benzene, toluene or xylene, ethers, such as diethyl ether, dioxane or tetrahydrofuran, chlorinated hydrocarbons, such as methylene chloride, chloroform, trichloroethylene and lower ketones, such as acetone or methyl ethyl ketone.

Som reaksjonsdyktige derivater av en karboksylsyre med den generelle formel III, kommer fblgende f.eks. i betraktning: halogenider, særlig klorider, lavere alkylestere, særlig metyl- eller etylester, fenylester, amider, lavere mono- hhv. dialkylamider, særlig N-metyl- og N,N-dimetylamidet, difenylamidet, videre N-acylamider, som f.eks. acetylamidet og benzoylamidet. As reactive derivatives of a carboxylic acid with the general formula III, the following e.g. in consideration: halides, especially chlorides, lower alkyl esters, especially methyl or ethyl esters, phenyl esters, amides, lower mono- or dialkylamides, especially the N-methyl- and N,N-dimethylamide, the diphenylamide, further N-acylamides, such as e.g. the acetylamide and the benzoylamide.

Omsetningen av de foran nevnte reaksjonsdyktige derivatene av kar-boksylsyrer skjer fortrinnsvis ved romtemperatur eller ved oppvarming i et av de foran nevnte inerte organiske opplbsnings-midler. Reaksjonen kan i alminnelighet gjennomfbres uten til-setning av kondensasjonsmidler, og, hvis onsket, kan slike midler, f.eks. alkalimetallalkoholater og alkalimetallhydroksyder, imidler-tid tilsettes. The conversion of the above-mentioned reactive derivatives of carboxylic acids takes place preferably at room temperature or by heating in one of the above-mentioned inert organic solvents. The reaction can generally be carried out without the addition of condensing agents, and, if desired, such agents, e.g. alkali metal alcoholates and alkali metal hydroxides, however, are added.

Et halogenid av en karboksylsyre med den generelle formel III omsettes ifblge oppfinnelsen fortrinnsvis i nærvær av et syre- According to the invention, a halide of a carboxylic acid with the general formula III is reacted preferably in the presence of an acid

bindende middel. Som slike kan uorganiske baser eller salter, binding agent. As such, inorganic bases or salts,

som f.eks. en alkalihydroksyd, -acetat, -hydrogenkarbonat, -karbonat og -fosfat, som natriumhydroksyd, -acetat, -hydrogenkarbonat, -karbonat og -fosfat, eller de tilsvarende kaliumforbind-elser anvendes. Videre kan også kalsiumoksyd, -karbonat, såvel som -fosfat og magnesiumkarbonat anvendes. I stedet for uorganiske baser eller salter egner seg også organiske baser, som f.eks. pyridin, trimetyl- eller trietylamin, diisopropylamin, eller kol-lidin. Disse^kan, tilsatt i overskudd, også tjene som opplbsningsmiddel. like for example. an alkali hydroxide, acetate, hydrogen carbonate, carbonate and phosphate, such as sodium hydroxide, acetate, hydrogen carbonate, carbonate and phosphate, or the corresponding potassium compounds are used. Furthermore, calcium oxide, -carbonate, as well as -phosphate and magnesium carbonate can also be used. Instead of inorganic bases or salts, organic bases are also suitable, such as e.g. pyridine, trimethyl- or triethylamine, diisopropylamine, or collidine. These, added in excess, can also serve as a solvent.

I stedet for aminer med den generelle formel II, kan man ved omsetningen ifblge oppfinnelsen med et karboksylsyreklorid også an-vende N-alkalimetallderivater av disse forbindelser, som Æ.eks. natrium-, kalium- eller litiumderivater. Instead of amines with the general formula II, in the reaction according to the invention with a carboxylic acid chloride, N-alkali metal derivatives of these compounds can also be used, such as sodium, potassium or lithium derivatives.

UtgangsforbindeIser med den generelle formel II er på sin side nye forbindelser og kan f.eks. fremstilles ved at man omsetter et reaksjonsdyktig derivat av en sulfonsyre med den generelle formel IV, Starting compounds with the general formula II are in turn new compounds and can e.g. is produced by reacting a reactive derivative of a sulphonic acid with the general formula IV,

hvor R betyr en enkel alkyl- hhv. arylrest, f.eks. en metyl-, hhv. en fenylgruppe, where R means a simple alkyl or aryl residue, e.g. a methyl-, respectively a phenyl group,

m har den under formel I angitte betydning, m has the meaning given under formula I,

med 2-amino-2-imidazolin-derivater med den generelle formel V, with 2-amino-2-imidazoline derivatives of the general formula V,

hvor R^ og R2 har den under formel I angitte betydning. og derefter hydrolytisk avspalter acylbeskyttelsesgruppen (R-CO-). De intermediært erholdte av formel II avledede N-acylforbindelsene er likeledes hittil ikke beskrevet i litteraturen. Som reaksjonsdyktige derivater av en sulfonsyre med den generelle formel IV kommer halogenider, særlig klorider og anhydrider med den generelle formel IVa, hvor R har den under formel IV angitte betydning, i betraktning. Anhydrider med den generelle formel IVa kan på enkel måte erholdes ved omsetning av tilsvarende substituerte sulfonsyrehalogenider med salter av tilsvarende substituerte sulfonsyrer. Karboksylsyrene med den generelle formel III kan fremstilles på enkel måte ved omsetning av alkoholater med den generelle formel VI, where R 1 and R 2 have the meaning given under formula I. and then hydrolytically cleaves off the acyl protecting group (R-CO-). The intermediately obtained N-acyl compounds derived from formula II have likewise not been described in the literature so far. As reactive derivatives of a sulfonic acid with the general formula IV, halides, especially chlorides and anhydrides with the general formula IVa, where R has the meaning given under formula IV, come into consideration. Anhydrides of the general formula IVa can be obtained in a simple way by reacting correspondingly substituted sulfonic acid halides with salts of correspondingly substituted sulfonic acids. The carboxylic acids with the general formula III can be prepared in a simple way by reacting alcoholates with the general formula VI,

hvor R^ har den under den generelle formel I angitte betydning, og hvor where R^ has the meaning given under the general formula I, and where

m betyr et enverdig metall, m means a monovalent metal,

med halogenalkansyrer med den generelle formel VII, with haloalkanoic acids of the general formula VII,

eller dennes lavere alkylestere, samt eventuell efterfdlgende hydrolyse. De erholdte syrene blir, hvis onsket, på i og for seg kjent måte overfort i reaksjonsdyktige, funksjonelle derivater. or its lower alkyl esters, as well as any subsequent hydrolysis. The acids obtained are, if desired, transferred in a manner known per se into reactive, functional derivatives.

For fremstilling av derivater av karboksylsyrene med den generelle formel III, hvor n er lik 2, har man den mulighet å anlagre tilsvarende alkanoler til akrylsyrederivater. For the preparation of derivatives of the carboxylic acids with the general formula III, where n is equal to 2, one has the option of adding corresponding alkanols to acrylic acid derivatives.

Efter en annen fremgangsmåte, kommer man frem til utgangsstoffer med den generelle formel II, ved at man substituerer p-(2-aminoalkyl)-benzensulfonamidet (fremstilt analogt E. Miller, J.Amer. Chem.Soc. 62, 21ol (194o)) med den generelle formel VIII, According to another method, starting substances with the general formula II are obtained by substituting the p-(2-aminoalkyl)-benzenesulfonamide (prepared analogously to E. Miller, J.Amer. Chem.Soc. 62, 21ol (194o) ) with the general formula VIII,

hvor m har den under formel I angitte betydning, where m has the meaning given under formula I,

med substituerte N-(2-bromalkyl)-cyanamider i alkalisk medium. with substituted N-(2-bromoalkyl)-cyanamides in alkaline medium.

De nye aktivstoffene eller de farmasbytisk aksepterbare saltene av disse kan administreres peroralt eller parenteralt. For salt-dannelse kan anvendes fysiologisk aksepterbare uorganiske eller organiske syrer, f.eks. saltsyre, bromhydrogensyre, svovelsyre, fosforsyre, metansulfonsyre, eddiksyre, melkesyre, ravsyre, vin-syre og maleinsyre, såvel som blodsukkersenkende sulfonylurin-stoffer, som f.eks. p-toluensulfonyl-butyl-urinstoff, p-klor-benzensulfonyl-propyl-urinstoff og p-[^2-(2-metoksy-5-klor-benza-mido)-etyl]-fenylsulfonyl-cykloheksyl-urinstoff. De daglige doser ligger mellom lo og loo mg/kg for varmblodige dyr. The new active substances or the pharmaceutically acceptable salts thereof can be administered orally or parenterally. Physiologically acceptable inorganic or organic acids can be used for salt formation, e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulphonic acid, acetic acid, lactic acid, succinic acid, tartaric acid and maleic acid, as well as blood sugar-lowering sulphonylureas, such as e.g. p-toluenesulfonyl-butyl-urea, p-chloro-benzenesulfonyl-propyl-urea and p-[^2-(2-methoxy-5-chloro-benza-mido)-ethyl]-phenylsulfonyl-cyclohexyl-urea. The daily doses are between lo and loo mg/kg for warm-blooded animals.

De efterfdlgende eksempler redegjbr nærmere for fremstillingen The following examples explain the preparation in more detail

av de nye forbindelser med den generelle formel I og av hittil ikke beskrevne mellomprodukter, men representerer på ingen måte de eneste utfbrelsesformene for fremstillingen. Temperaturene er angitt i Celsiusgrader. of the new compounds with the general formula I and of hitherto undescribed intermediates, but in no way represent the only embodiments of the preparation. The temperatures are indicated in degrees Celsius.

EKSEMPEL 1 EXAMPLE 1

En opplosning av 40,9 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cyklopentyl-imidazolidin-dihydroklorid med smp. 2 70°c i 100 ml vann tilsettes 150 ml 2-n natronlut og den frisatte basen ekstraheres med metylenklorid. Ekstraktet som er torket med natriumsulfat tilsettes ved 0° 20,6 g N,N'-dicyklo-heksyl-karbodiimid. Deretter tildrypper man ved 0° en opplosning av 9,0 g metoksyeddiksyre i 30 ml metylenklorid i lopet av 5 minutter. Etter to timers omroring ved 0° filtreres det utfelte N,N'-dicykloheksylurinstoffet fra og det klare fil-tratet inndampes. Det således erholdte rå l-[p-(2-metoksy-acetamido-etyl)-fenylsulfonyl]-2-imino-3-cyklopentylimidazolidin omkrystalliseres i eddikester-aceton. Det inneholder 1 mol krystallvann og smelter ved 151 - 151,5°. A solution of 40.9 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclopentyl-imidazolidine dihydrochloride with m.p. 2 70°c in 100 ml of water, 150 ml of 2-n caustic soda is added and the liberated base is extracted with methylene chloride. The extract which has been dried with sodium sulphate is added at 0° to 20.6 g of N,N'-dicyclohexylcarbodiimide. A solution of 9.0 g of methoxyacetic acid in 30 ml of methylene chloride is then added dropwise at 0° over the course of 5 minutes. After two hours of stirring at 0°, the precipitated N,N'-dicyclohexylurea is filtered off and the clear filtrate is evaporated. The thus obtained crude 1-[p-(2-methoxy-acetamido-ethyl)-phenylsulfonyl]-2-imino-3-cyclopentylimidazolidine is recrystallized in acetate-acetone. It contains 1 mole of crystal water and melts at 151 - 151.5°.

På analog måte erholdes med hver gang 20,6 g N,N'-dicykloheksyl-karbodiimid og 9,0 g metoksyeddiksyre: a) fra 42,4 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid med smp. 24 7 - 250° l-[p- (2-metoksyacetamido-etyl)-fenylsulfonyl]-2-imino-3-cyklo-heksyl-imidazolidin med smp. 150 - 151° (monohydrat; i eddikester)5 b) fra 43,8 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(4-metylcykloheksyl)-imidazolidin-dihydroklorid med smp. 260° l-[p- (2-metoksyacetamido-etyl)-fenylsulfonyl]-2-imino-3-(4-metylcykloheksyD-imidazolidin, smp. 159 - 160° (hemihydrat; In an analogous manner, 20.6 g of N,N'-dicyclohexylcarbodiimide and 9.0 g of methoxyacetic acid are obtained each time: a) from 42.4 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2 -imino-3-cyclohexyl-imidazolidine dihydrochloride with m.p. 24 7 - 250° 1-[p-(2-methoxyacetamido-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine with m.p. 150 - 151° (monohydrate; in acetic ester) 5 b) from 43.8 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-(4-methylcyclohexyl)-imidazolidine dihydrochloride with m.p. 260° 1-[p-(2-methoxyacetamido-ethyl)-phenylsulfonyl]-2-imino-3-(4-methylcyclohexyD-imidazolidine, m.p. 159 - 160° (hemihydrate;

i eddikester). in vinegar).

EKSEMPEL 2 EXAMPLE 2

En opplosning av 42,3 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid med smp. 24 7 - 250°C i 200 ml vann tilsettes 300 ml 2-n natronlut og ekstraheres med metylenklorid. Ekstraktet, som er torket med natriumsulfat, tilsettes 50,5 g trietylamin. Deretter tildrypper man ved romtemperatur en opplosning av 13,5 g etoksyacetylklorid i 100 ml metylenklorid i lbpet av 20 minutter og rorer den erholdte blandingen en time ved romtemperatur. Deretter vaskes reaksjonslosningen forst med 100 ml 2-n natronlut og deretter to ganger med 100 ml vann. De forente vandige fasene ekstraheres nå to ganger med metylenklorid og de erholdte metylen-kloridekstraktene forenes med den vaskede reaksjonslosningen. Ved inndampning av den med natriumsulfat torkede metylenklorid-losningen erholder man det rå l-[p-(2-etoksy-acetamido-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin, hvilket A solution of 42.3 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine dihydrochloride with m.p. 24 7 - 250°C in 200 ml of water, 300 ml of 2-n caustic soda is added and extracted with methylene chloride. To the extract, which has been dried with sodium sulphate, 50.5 g of triethylamine is added. A solution of 13.5 g of ethoxyacetyl chloride in 100 ml of methylene chloride is then added dropwise at room temperature over a period of 20 minutes and the resulting mixture is stirred for one hour at room temperature. The reaction solution is then washed first with 100 ml of 2-N caustic soda and then twice with 100 ml of water. The combined aqueous phases are now extracted twice with methylene chloride and the methylene chloride extracts obtained are combined with the washed reaction solution. By evaporating the sodium sulfate-dried methylene chloride solution, the crude 1-[p-(2-ethoxy-acetamido-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine is obtained, which

smelter ved omkrystallisasjon i eddikester —petroleter med 111 - 113°. melts on recrystallization in acetic ester — petroleum ether at 111 - 113°.

På analog måte erholdes med 50,5 g trietylamin: In an analogous way, 50.5 g of triethylamine is obtained:

a) fra 43,7 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cyklopentyl-imidazolidin-dihydroklorid med smp. 270° og 13,5 a) from 43.7 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclopentyl-imidazolidine dihydrochloride with m.p. 270° and 13.5

g etoksyacetylklorid l-[p- (2-etoksyacetamido-etyl)-fenylsul-fonyl]-2-imino-3-cyklopentyl-imidazolidin med smp. 105 - 106,5° (i eddikester); g ethoxyacetyl chloride 1-[p-(2-ethoxyacetamido-ethyl)-phenylsulfonyl]-2-imino-3-cyclopentyl-imidazolidine with m.p. 105 - 106.5° (in vinegar);

EKSEMPEL 3 EXAMPLE 3

Analogt eksempel 1 erholdes ved anvendelse av hver gang 20,6 g N ,N.j.-dicykloheksyl-karbodiimid: fra 42,3 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid og 11,8 g propoksy-eddiksyre l-[p- (2- (propoksy-acetamido)-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin, smp. lOO - 102°. Analogous example 1 is obtained by using each time 20.6 g of N,N.j.-dicyclohexyl-carbodiimide: from 42.3 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl- imidazolidine dihydrochloride and 11.8 g of propoxy-acetic acid 1-[p-(2-(propoxy-acetamido)-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine, m.p. 100 - 102°.

fra 42,3 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid og 11,8 g isopropoksy-eddiksyre l-[p-(2-(isopropoksy-acetamido)-etyl)-fenylsulfonyl]-2- imino-3-cykloheksyl-imidazolidin, smp. 105 - 107°. from 42.3 g of l-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine dihydrochloride and 11.8 g of isopropoxyacetic acid l-[p-(2-(isopropoxy -acetamido)-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine, m.p. 105 - 107°.

fra 43,7 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(2-metyl-cykloheksyl)-imidazolidin-dihydroklorid og 10,4 g 3- metoksy-propionsyre l-[p- (3-metoksy-propionamido)-etyl)-fenylsulfonyl]-2-imino-3- (2-metyl-cykloheksyl-imidazolidin, smp. 130 - 132°. from 43.7 g of l-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-(2-methyl-cyclohexyl)-imidazolidine dihydrochloride and 10.4 g of 3-methoxy-propionic acid l- [p-(3-methoxy-propionamido)-ethyl)-phenylsulfonyl]-2-imino-3-(2-methyl-cyclohexyl-imidazolidine, m.p. 130 - 132°.

fra 42,3 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cyklo- from 42.3 g of 1-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclo-

heksyl-imidazolidin-dihydroklorid og 11,8 g 3-acetoksypropion-syre 1- [p-(2-(3-etoksy-propionamido)-etyl)-fenylsulfonyl] -2-imino-3-cykloheksyl-imidazolidin, smp. 13o - 132°. hexyl-imidazolidine dihydrochloride and 11.8 g of 3-acetoxypropionic acid 1-[p-(2-(3-ethoxy-propionamido)-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine, m.p. 13o - 132°.

fra 43,7 g 1-jjp-(2-amino-etyl) -f enylsulf onyl] -2-imino-3-(2-metyl-cykloheksyl)-imidazolidin-dihydroklorid og 13,2 g 3-isopropoksy-propionsyre l-[p-(2-(3-isopropoksypropionamido)-etyl)-fenylsulfonyl]-2-imino-3-(2-metylcykloheksyl)-imidazolidin, smp. 128 - 13o°. from 43.7 g of 1-[(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-(2-methyl-cyclohexyl)-imidazolidine dihydrochloride and 13.2 g of 3-isopropoxy-propionic acid l -[p-(2-(3-isopropoxypropionamido)-ethyl)-phenylsulfonyl]-2-imino-3-(2-methylcyclohexyl)-imidazolidine, m.p. 128 - 13o°.

fra 43,7 g 1-[p- (2-amino-propyl) -f enylsulf onyl] -2-imino-3-cykloheksyl-imidazolidin-dihydroklorid og 9,o g metoksyeddiksyre l-[p-(2-(metoksy-acetamido)-propyl-fenylsulfonyl] -2-imino-3-cykloheksyl-imidazolidin, smp. 12o - 121°. from 43.7 g of 1-[p-(2-amino-propyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine dihydrochloride and 9.0 g of methoxyacetic acid 1-[p-(2-(methoxy- acetamido)-propyl-phenylsulfonyl]-2-imino-3-cyclohexyl-imidazolidine, mp 12o - 121°.

fra 43,7 g l-[p-(2-amino-etyl)-fenylsulfonyl] -2-imino-3-cykloheksyl-4-metyl-imidazolidin-dihydroklorid og lo,4 g etoksy-eddiksyrejjL- p-(2-etoksy-acetamido)-etyl)-fenylsul-fonyl] -2-imino-3-cykloheksyl-4-metyl-imidazolidin, smp. 115-117°. from 43.7 g of l-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-4-methyl-imidazolidine dihydrochloride and 10.4 g of ethoxy-acetic acidjjL-p-(2- ethoxy-acetamido)-ethyl)-phenylsulfonyl]-2-imino-3-cyclohexyl-4-methyl-imidazolidine, m.p. 115-117°.

fra 42,1 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(3-cykloheksen-l-yl)-imidazolidin-dihydroklorid og 9,o g metoksyeddiksyre l-[p-(2-metoksy-acetamido)-etyl)-fenylsulfonyl]-2-imino-3-(3-cykloheksen-l-yl)-imidazolidin. from 42.1 g of l-[p-(2-amino-ethyl)-phenylsulfonyl]-2-imino-3-(3-cyclohexen-1-yl)-imidazolidine dihydrochloride and 9.0 g of methoxyacetic acid l-[p- (2-Methoxy-acetamido)-ethyl)-phenylsulfonyl]-2-imino-3-(3-cyclohexen-1-yl)-imidazolidine.

Claims (1)

Analogifremgangsmåte for fremstilling av nye, farmakologisk aktive derivater av p-aminoalkyl-benzensulfonamidet med den generelle formel I,Analogous process for the preparation of new, pharmacologically active derivatives of the p-aminoalkylbenzenesulfonamide of the general formula I, hvor betyr en cykloalkylrest med 5-8 karbonatomer ,R2 betyr hydrogen, en etyl- eller en metylgruppe, R^ betyr en eventuelt forgrenet alkylgruppe med 1-6 karbonatomer, m betyr 2 eller 3 og n betyr 1 eller 2, såvel som deres addisjonssalter med uorganiske eller organiske syrer, karakterisert ved at man omsetter en forbindelse med den generelle formel II, hvor R^, R. og m har den under formel I angitte betydning, med en karboksylsyre med den generelle formel III, hvor R^ og n har den under den generelle formel I angitte betydning, eller med et reaksjonsdyktig derivat av en slik karboksylsyre og overforer det erholdte reaksjonsproduktet, hvis onsket, i saltet til en uorganisk eller organisk syre.where means a cycloalkyl residue with 5-8 carbon atoms, R2 means hydrogen, an ethyl or a methyl group, R^ means an optionally branched alkyl group with 1-6 carbon atoms, m means 2 or 3 and n means 1 or 2, as well as their addition salts with inorganic or organic acids, characterized by reacting a compound with the general formula II, where R^, R. and m have the meaning indicated under formula I, with a carboxylic acid of the general formula III, where R^ and n have the meaning given under the general formula I, or with a reactive derivative of such a carboxylic acid and transfers the reaction product obtained, if desired, in the salt of an inorganic or organic acid.
NO03276/70A 1969-09-04 1970-08-27 NO128997B (en)

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SE367824B (en) 1974-06-10
FR2070671B1 (en) 1973-12-21
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DE2043773B2 (en) 1979-06-28
FI52573C (en) 1977-10-10
CH518945A (en) 1972-02-15
SU398039A3 (en) 1973-09-17
CH519501A (en) 1972-02-29
DK131674C (en) 1976-01-19
BG17962A3 (en) 1974-03-05
GB1306602A (en) 1973-02-14
FR2070671A1 (en) 1971-09-17
CS166015B2 (en) 1976-01-29
DE2043773C3 (en) 1980-02-21
ES383344A1 (en) 1973-01-01
AT294824B (en) 1971-12-10
FI52573B (en) 1977-06-30
NL165155B (en) 1980-10-15
IL35224A0 (en) 1970-11-30
BE755685A (en) 1971-03-03
DE2043773A1 (en) 1971-03-18
PL73403B1 (en) 1974-08-30
IE34504L (en) 1971-03-04
CA920601A (en) 1973-02-06
IL35224A (en) 1973-11-28
ZA706044B (en) 1971-04-28
DK131674B (en) 1975-08-18
NL7012732A (en) 1971-03-08
NL165155C (en) 1981-03-16

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