NO129742B - - Google Patents
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- Publication number
- NO129742B NO129742B NO03272/70A NO327270A NO129742B NO 129742 B NO129742 B NO 129742B NO 03272/70 A NO03272/70 A NO 03272/70A NO 327270 A NO327270 A NO 327270A NO 129742 B NO129742 B NO 129742B
- Authority
- NO
- Norway
- Prior art keywords
- ethyl
- phenylsulfonyl
- imino
- imidazolidine
- amino
- Prior art date
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- -1 ethyl- Chemical group 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- KMGGBHZGPFPRGZ-UHFFFAOYSA-N 2-[4-(3-cyclohexyl-2-iminoimidazolidin-1-yl)sulfonylphenyl]ethanamine;dihydrochloride Chemical compound Cl.Cl.C1=CC(CCN)=CC=C1S(=O)(=O)N1C(=N)N(C2CCCCC2)CC1 KMGGBHZGPFPRGZ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- DISXFZWKRTZTRI-UHFFFAOYSA-N 4,5-dihydro-1h-imidazol-2-amine Chemical class NC1=NCCN1 DISXFZWKRTZTRI-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- FLNXBHJVHXGRFS-UHFFFAOYSA-N N-(2-phenylethyl)acetamide sulfurochloridic acid Chemical compound S(=O)(=O)(O)Cl.C(C)(=O)NCCC1=CC=CC=C1 FLNXBHJVHXGRFS-UHFFFAOYSA-N 0.000 description 2
- MODKMHXGCGKTLE-UHFFFAOYSA-N N-acetylphenylethylamine Chemical compound CC(=O)NCCC1=CC=CC=C1 MODKMHXGCGKTLE-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- IEQUJSXSDUKTLF-UHFFFAOYSA-N n-[2-[4-(3-cyclohexyl-2-iminoimidazolidin-1-yl)sulfonylphenyl]ethyl]acetamide Chemical compound C1=CC(CCNC(=O)C)=CC=C1S(=O)(=O)N1C(=N)N(C2CCCCC2)CC1 IEQUJSXSDUKTLF-UHFFFAOYSA-N 0.000 description 2
- 125000003884 phenylalkyl group Chemical group 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HKTCTLBSJWAWDO-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-1-propylurea Chemical compound CCCN(C(N)=O)S(=O)(=O)C1=CC=C(Cl)C=C1 HKTCTLBSJWAWDO-UHFFFAOYSA-N 0.000 description 1
- LIGJMUDWIGAHRT-UHFFFAOYSA-N 1-(benzenesulfonyl)-4,5-dihydroimidazol-2-amine Chemical class NC1=NCCN1S(=O)(=O)C1=CC=CC=C1 LIGJMUDWIGAHRT-UHFFFAOYSA-N 0.000 description 1
- ZIRLDYOJRFPDFO-UHFFFAOYSA-N 1-butyl-1-(4-methylphenyl)sulfonylurea Chemical compound CCCCN(C(N)=O)S(=O)(=O)C1=CC=C(C)C=C1 ZIRLDYOJRFPDFO-UHFFFAOYSA-N 0.000 description 1
- GCWFLQIRNPJFIC-UHFFFAOYSA-N 1-cyclohexyl-4,5-dihydroimidazol-2-amine;hydrochloride Chemical compound Cl.N=C1NCCN1C1CCCCC1 GCWFLQIRNPJFIC-UHFFFAOYSA-N 0.000 description 1
- GHFPZAMTWHMZEW-UHFFFAOYSA-N 2-[4-(2-imino-3-methylimidazolidin-1-yl)sulfonylphenyl]ethanamine Chemical compound NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)C)=N GHFPZAMTWHMZEW-UHFFFAOYSA-N 0.000 description 1
- CEOHWRLZPYDCNW-UHFFFAOYSA-N 2-[4-(2-imino-3-methylimidazolidin-1-yl)sulfonylphenyl]ethanamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)C)=N CEOHWRLZPYDCNW-UHFFFAOYSA-N 0.000 description 1
- IFZHITIIUYASRA-UHFFFAOYSA-N 2-[4-(3-butyl-2-iminoimidazolidin-1-yl)sulfonylphenyl]ethanamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)CCCC)=N IFZHITIIUYASRA-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NHKCCEIRJLPNHV-UHFFFAOYSA-N C(CC(=O)C)(=O)NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)C1CCCCC1)=N Chemical compound C(CC(=O)C)(=O)NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)C1CCCCC1)=N NHKCCEIRJLPNHV-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- IIHATVARYNQEHQ-UHFFFAOYSA-N N-[2-[4-(2-imino-3-methylimidazolidin-1-yl)sulfonylphenyl]ethyl]-3-oxobutanamide Chemical compound C(CC(=O)C)(=O)NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)C)=N IIHATVARYNQEHQ-UHFFFAOYSA-N 0.000 description 1
- SAGCKQJVMKMXEV-UHFFFAOYSA-N N-[2-[4-(3-cyclohex-3-en-1-yl-2-iminoimidazolidin-1-yl)sulfonylphenyl]ethyl]-3-oxobutanamide Chemical compound C(CC(=O)C)(=O)NCCC1=CC=C(C=C1)S(=O)(=O)N1C(N(CC1)C1CC=CCC1)=N SAGCKQJVMKMXEV-UHFFFAOYSA-N 0.000 description 1
- OOAHCJDVPGESFA-UHFFFAOYSA-N N-[2-[4-[benzenesulfonyl(carbamoyl)amino]cyclohexyl]ethyl]-5-chloro-2-methoxybenzamide Chemical compound COC1=C(C(=O)NCCC2CCC(CC2)N(C(=O)N)S(=O)(=O)C2=CC=CC=C2)C=C(C=C1)Cl OOAHCJDVPGESFA-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Analogifremgangsmåte for fremstilling av nye,
farmakologisk aktive derivater av P-aminoalkyl-benzensulfonamid.
Det ble funnet at p-subst. fenylsulfonyl-2-imino-imidazolidiner med den generelle formel I, hvor 1^ betyr en eventuelt forgrenet alkylrest med 1-6 karbonatomer, en allylgruppe, en cykloalkyl- hhv. cykloalkenylrest med hver 5-8 karbonatomer, en fenylalkylrest med hoyst 9 karbonatomer,
R2 hydrogen, en etyl- eller en metylgruppe, hydrogen eller metylgruppen og
m 2 eller 3,
såvel som deres addisjonssalter med uorganiske eller organiske syrer viser hypoglykemisk virkning på varmblodige dyr.
I forbindelsene med den generelle formel I kan R^ f.eks. ha folgende betydning:
som alkylgruppe 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-, etyl-butylgruppe;
som cykloalkylgruppe cyklopentylgruppen, som eventuelt kan være substituert med alkylrester med 1-3 karbonatomer, cyklo-heksylgruppen, som kan være substituert med etyl eller metyl,
og den eventuelt med metyl substituerte cykloheptylgruppen, såvel som cyklooktylgruppen5
som cykloalkenylgruppe 2-cyklopenten-l-yl-, 2-cykloheksen-l-yl-, 3-cykloheksen-l-yl-, 2-metyl-2-cykloheksen-l-yl-, 3-cyklohepten-1-yl-gruppen, eller en cyklooktenylgruppe;
som fenylalkylgruppe benzyl-, fenyletyl- eller oc-metylfenyl-etylgruppen.
Efter fremgangsmåten ifolge oppfinnelsen fremstilles forbindelser med den generelle formel I ved at man omsetter en forbindelse med den generelle formel II,
hvor R^, R2, m og R^ har den under formel I angitte betydning, med diketen og, hvis onsket, overforer det erholdte reaksjons-produktet i saltet til en uorganisk eller organisk syre. Omsetningen skjer f.eks. ved temperaturer mellom -20°C til +30°C, fortrinnsvis ved -10° til 0°, i et inert organisk opplosningsmiddel. Som opplosningsmiddel kommer f.eks. i betraktning: hydrokarboner, som benzen, toluen eller xylen, eter, som dietyleter, dioksan eller tetrahydrofuran, klorerte hydrokarboner, som metylenklorid og lavere ketoner, som aceton eller metyletylketon. Utgangsforbindelsene med den generelle formel II er på sin side nye forbindelser og kan f.eks. fremstilles på den måten, at man omsetter et reaksjonsdyktig derivat av en sulfonsyre med den generelle formel III,
hvor R betyr en enkel alkyl- hhv. arylrest, f.eks. en metyl-, hhv. en fenylgruppe, og
R 3 og m har den i formel I angitte betydning,
med 2-amino-2-imidazolin-derivater med den generelle formel IV,
hvor R^ og R2 har den under formel I angitte betydning, og derefter hydrolytisk avspalter acylbeskyttelsesgrupperi (R-CO-). Den intermediært erholdte av formel II avledede N-acylforbindelsen er hittil heller ikke beskrevet i litteraturen. Som reaksjonsdyktige derivater av en sulfonsyre med den generelle formel III kommer i betraktning halogenider, spesielt klorider og anhydrider med den generelle formel Illa,
hvor R^ og m har den under formel I angitte betydning.
Anhydrider med den generelle formel Illa kan på enkel måte erholdes ved omsetning av tilsvarende substituerte sulfonsyre-halogenider med salter av tilsvarende substituerte sulfon-syrer.
Efter en annen fremgangsmåte kommer man frem til utgangsstoffer med den generelle formel II, idet man omsetter substituerte p-(aminoalkyl)-benzensulfonamider (fremstilt analogt E. Miller, J.Amer.Chem.Soc. 62, 2101 (1940)) med den generelle formel V,
hvor R, har den under formel I angitte betydning,
med substituerte N-(2-bromalkyl)-cyanamider i alkaliskt medium.
De nye aktivstoffene med den generelle formel I eller de farmasoytisk aksepterbare saltene av disse kan anvendes perorait, rektalt eller parenteralt. For saltdannelse kan anvendes fysiologiskt aksepterbare uorganiske eller organiske syrer, f.eks. saltsyre bromhydrogensyre, svovelsyre, fosfor-syre, metansulfonsyre, eddiksyre, melkesyre, ravsyre, vinsyre og maleihsyre, såvel som blodsukkersenkende sulfonylurinstoffer, som f.eks. p-toluensulfonyl-butyl-urinstoff, p-klorbenzensulfonyl-propyi-urinstoff og p-[2-(2-metoksy-5-klor-benzamido)-etyl]-fenylsulfonyl-cykloheksyl-urinstoff. De dagelige doser ligger mellom 0,1 og 100 mg/kg for varmblodige dyr. Egnede dose-enhetsformer som dragéer eller tabletter inneholder fortrinnsvis 10 - 200 mg av et aktivstoff ifolge oppfinnelsen, hvorved aktivstoffinnholdet utgjor 20-80 vekts-%.
De efterfolgende eksempler redegjor nærmere for fremstillingen av de nye forbindelser med den generelle formel I. Temperaturene er angitt i Celsiusgrader.
EKSEMPEL 1
35,8 g l-[p-(2-aminoetyl)-fenylsulfonyl]-2-imino-3-metyl-imidazolidin-dihydroklorid opplbses i 200 ml vann, tilsettes 500 ml 2-n natronlut, den frie basen ekstraheres med metylenklorid og ekstraktet torkes med natriumsulfat. I den således erholdte til -10° avkjolte losningen av l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-metyl-imidazolidin inndryppes under omroring en opplosning av 8,5 g diketen i 15 ml metylenklorid. Reaksjonsblandingen efterrores 1 time ved -10° til 0°, og derefter inndampes til torrhet i rotasjonsfordamperen under vakuum og ved en vannbadtemperatur på ca. '40°. Résidumet omkrystalliseres i eddikester. Det rene l-[p-(2-acetoacetamido-etyl ) -f enylsulf onyl] -2-imino-3-metyl-imidazolidin smelter ved 120 - 121°.
Ved omsetning med 8,5 g diketen erholdes analogt:
a) fra 38,1 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-allyl-imidazolidin-dihydroklorid med smp. 232 - 233° 1-[p-(2^acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-allyl-imidazolidin med smp. 91 - 91,5°. b) fra 39,7 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-butyl-imidazolidin-dihydroklorid med smp. 259 - 260° l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-butyl-imidazolidin med smp. 138 - 139°. c) fra 42,5 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(3-metylpent-2-yl)-imidazolidin-dihydroklorid (stivnet glassaktig) l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-(3-metylpent-2-yl)-imidazolidin som olje. d) fra 40,9 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cyklopentyl-imidazolidin-dihydroklorid med spaltningspunkt 270° l-[p- (2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-cyklo-pentyl-imidazolidin med smp. 118 - 119°. e) fra 42,1 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(cykloheks-3-enyl)-imidazolidin-dihydroklorid med smp. 245 - 247° l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-(cykloheks-3-enyl)-imidazolidin med smp. 102 - 103°. f) fra 42,3 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid med smp. 247 - 250° l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin med smp. 107 - 108°. g) fra 43,7 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(4-metyl-cykloheksyl)-imidazolidin-dihydroklorid med spaltningspunkt 260° l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-(4-metyl-cykloheksyl)-imidazolidin med smp. 119 - 120°. h) fra 43,7 g l-[2-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheptyl-imidazolidin-dihydroklorid med spaltningspunkt 2 80° l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-cyklo-heptyl-imidazolidin med smp. 102°. i) fra 44,5 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-(2-fenyl-etyl)-imidazolidin-dihydroklorid 1-[p-(2-acetoacetamido-etyl) f enylsulf onyl] -2-imino- 3- (2-fenyl-etyl)-imidazolidin med smp. 113 - 117°. j) fra 43,1 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-benzyl-imidazolidin-dihydroklorid l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl-2-imino-3-benzyl-imidazolidin med smp. 136,5 - 138°. k) fra 43,7 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-4-metyl-imidazolidin-dihydroklorid l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-4-metyl-imidazolidin med smp. 130 - 133°. 1) fra 42,5 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-butyl-4-etyl-imidazolidin-dihydroklorid l-[p-(2-acetoacetamido-etyl)-fenylsulfonyl]-2-imino-3-butyl-4-etyl-imidazolidin med smp. 93 - 94°. m) fra 43,7 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cyklopentyl-4-etyl-imidazolidin-dihydroklorid l-[p-(2-aceto-ac etami do-etyl)-feny1sulfonyl]-2-imino-3-cyklopenty1-4-ety 1 - imidazolidin med smp. 80 - 82°.
■ n) fra 41,1 g l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-butyl-4-metyl-imidazolidin-dihydroklorid l[p-(2-acetoacetamido-etyl )-fenylsulfonyl]-2-imino-3-butyl-4-metyl-imidazolidin med smp. 104,5 - 105,5°. o) fra 45,4 g l-[p-(2-(N-metyl-amino)-propyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid l-[p-(2-(N-metyl-acetoacetamido)-propyl)-fenylsulfonyl]-2-imino-3-cyklo-heksyl-imidazolidin med smp. 104 - 107°. p) fra 43,7 g l-[p-(2-amino-propyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydroklorid l-[p-(2-aceto-acetamido-propyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin med smp. 91 - 92°.
De som utgangsmaterialer anvendte dihydrokloridene av de
i 3-stilling, forskjellig substituerte l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-imidazolidininer, kan erholdes f.eks.
på enkel måte ved omsetning av p-acylamido-etyl-benzen-sulfoklorid med tilsvarende substituerte 2-amino-imidazoliner med formel IV, og en efterfolgende med vandig saltsyre gjennomfort hydrolytisk avspaltning av alkylresten i p-acylamido-etylgruppen. I det folgende beskrives fremgangsmåten for l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydrokloridet: a) I en opplosning av 17 g natriumhydroksyd i 170 ml vann til-fores 40,8 g l-cykloheksyl-2-amino-imidazolin-hydroklorid.
Den erholdte klare losningen blandes med en opplosning av 52,4 g p-(2-acetamido-etyl)-benzen-sulfoklorid i 200 ml aceton, hvorved en oppvarming inntrer. Blandingen oppvarmes 1/2 time til 90°, og derefter inndampes til torrhet i vakuum. Det således erholdte, rå l-[p-(2-acetamido-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin smelter efter omkrystallisering i eddikester ved 181 - 183°.
Det anvendte sulfoklorid kan fremstilles på folgende måte:
I 35,0 g klorsulfonsyre innfores porsjonsvis under omroring 16,3 g N-fenetylacetamid. Den erholdte blandingen omrores 3 timer ved 60° og helles til is, hvorved p-(2-acetamido-etyl) -benzensulfoklorid utskilles i krystallinsk form. Det avsuges, vaskes med vann og torkes i vakuum. Råproduktet blir videre bearbeidet. (3) En opplosning av 39,2 g av det ifolge ovennevnte forskrift fremstilte l-[p-(2-acetamido-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin i 370 ml 2-n saltsyre kokes 6 timer under tilbakelop og inndampes derefter til torrhet i vakuum. Det rå, oljeaktige l-[p-(2-amino-etyl)-fenylsulfonyl]-2-imino-3-cykloheksyl-imidazolidin-dihydrokloridet opptaes i varm etanol. Ved avkjoling utkrystalliserer det fra den etanoliske opplosningen og smelter ved 247 - 250°.
Claims (1)
- Analogifremgangsmåte for fremstilling av nye, farmakologisk aktive derivater av p-aminoalkyl-benzensulfonamid med den generelle formel I,hvor R^ betyr en eventuelt forgrenet alkylrest med 1-6 karbonatomer, en allylrest, en cykloalkyl-hhv. cykloalkenylreat med hver 5-8 karbonatomer, en fenylalkylrest med hoyst 9 karbonatomer, 1*2 hydrogen, en etyl- eller en metylgruppe, R2 hydrogen eller en metylgruppe og m 2 eller 3, såvel som deres addisjonssalter med uorganiske eller organiske syrer, karakterisert ved at man omsetter en forbindelse med den generelle formel II, hvor R^, R2, m og R^ har den under formel I angitte betydning, med diketen, og, hvis onsket, overforer de erholdte reaksjons-produkter i saltet til en uorganisk eller organisk syre.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1339669A CH518943A (de) | 1969-09-04 | 1969-09-04 | Verfahren zur Herstellung von neuen Derivaten des p-Aminoalkyl-benzolsulfonamids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO129742B true NO129742B (no) | 1974-05-20 |
Family
ID=4392065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO03272/70A NO129742B (no) | 1969-09-04 | 1970-08-27 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US3708493A (no) |
| AT (1) | AT294822B (no) |
| BE (1) | BE755681A (no) |
| CA (1) | CA920136A (no) |
| CH (1) | CH518943A (no) |
| DE (1) | DE2043756C3 (no) |
| DK (1) | DK123356B (no) |
| ES (1) | ES383340A1 (no) |
| FI (1) | FI52462C (no) |
| FR (1) | FR2070667B1 (no) |
| GB (1) | GB1305836A (no) |
| IE (1) | IE34501B1 (no) |
| IL (1) | IL35221A (no) |
| NL (1) | NL164555C (no) |
| NO (1) | NO129742B (no) |
| PL (1) | PL73405B1 (no) |
| SE (1) | SE367409B (no) |
| SU (1) | SU376941A3 (no) |
| YU (1) | YU34037B (no) |
| ZA (1) | ZA706035B (no) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4094235A (en) * | 1974-07-31 | 1978-06-13 | Universite Laval | Apparatus for the production of textured products |
| CN101311167B (zh) * | 2007-05-25 | 2011-04-06 | 天津药物研究院 | 1-苯基咪唑烷-2,4-二酮类衍生物及其用途 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3538085A (en) * | 1966-03-24 | 1970-11-03 | Geigy Chem Corp | 1-phenylsulfonyl-2-imino-imidazolidines and hexahydropyrimidines |
| CH505829A (de) * | 1968-03-14 | 1971-04-15 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Derivaten des p-Aminoalkylbenzolsulfonamids |
-
0
- BE BE755681D patent/BE755681A/xx unknown
-
1969
- 1969-09-04 CH CH1339669A patent/CH518943A/de not_active IP Right Cessation
-
1970
- 1970-08-27 NL NL7012723.A patent/NL164555C/xx not_active IP Right Cessation
- 1970-08-27 SE SE11644/70A patent/SE367409B/xx unknown
- 1970-08-27 FI FI702360A patent/FI52462C/fi active
- 1970-08-27 NO NO03272/70A patent/NO129742B/no unknown
- 1970-08-27 DK DK440470AA patent/DK123356B/da not_active IP Right Cessation
- 1970-09-01 US US00068797A patent/US3708493A/en not_active Expired - Lifetime
- 1970-09-03 AT AT801970A patent/AT294822B/de not_active IP Right Cessation
- 1970-09-03 ZA ZA706035A patent/ZA706035B/xx unknown
- 1970-09-03 YU YU2201/70A patent/YU34037B/xx unknown
- 1970-09-03 SU SU1474221A patent/SU376941A3/ru active
- 1970-09-03 FR FR707032043A patent/FR2070667B1/fr not_active Expired
- 1970-09-03 PL PL14296570A patent/PL73405B1/pl unknown
- 1970-09-03 ES ES383340A patent/ES383340A1/es not_active Expired
- 1970-09-03 IE IE1144/70A patent/IE34501B1/xx unknown
- 1970-09-03 GB GB4210370A patent/GB1305836A/en not_active Expired
- 1970-09-03 DE DE2043756A patent/DE2043756C3/de not_active Expired
- 1970-09-03 CA CA092250A patent/CA920136A/en not_active Expired
- 1970-09-03 IL IL35221A patent/IL35221A/en unknown
-
1972
- 1972-09-18 US US00290032A patent/US3794737A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| YU220170A (en) | 1978-05-15 |
| PL73405B1 (no) | 1974-08-31 |
| FR2070667A1 (no) | 1971-09-17 |
| FR2070667B1 (no) | 1974-02-22 |
| US3708493A (en) | 1973-01-02 |
| US3794737A (en) | 1974-02-26 |
| YU34037B (en) | 1978-10-31 |
| NL164555B (nl) | 1980-08-15 |
| AT294822B (de) | 1971-12-10 |
| IE34501B1 (en) | 1975-05-28 |
| DE2043756C3 (de) | 1979-10-25 |
| DE2043756A1 (de) | 1971-04-01 |
| SE367409B (no) | 1974-05-27 |
| ES383340A1 (es) | 1973-01-01 |
| SU376941A3 (no) | 1973-04-05 |
| IL35221A (en) | 1973-04-30 |
| FI52462C (fi) | 1977-09-12 |
| GB1305836A (no) | 1973-02-07 |
| IE34501L (en) | 1971-03-04 |
| DE2043756B2 (de) | 1979-03-01 |
| CH518943A (de) | 1972-02-15 |
| CA920136A (en) | 1973-01-30 |
| FI52462B (no) | 1977-05-31 |
| IL35221A0 (en) | 1970-11-30 |
| BE755681A (fr) | 1971-03-03 |
| NL7012723A (no) | 1971-03-08 |
| DK123356B (da) | 1972-06-12 |
| NL164555C (nl) | 1981-01-15 |
| ZA706035B (en) | 1971-04-28 |
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