CS223809B2 - Method of making the derivatives /ergolinyl/-h-,n diethylurea - Google Patents
Method of making the derivatives /ergolinyl/-h-,n diethylurea Download PDFInfo
- Publication number
- CS223809B2 CS223809B2 CS804168A CS416880A CS223809B2 CS 223809 B2 CS223809 B2 CS 223809B2 CS 804168 A CS804168 A CS 804168A CS 416880 A CS416880 A CS 416880A CS 223809 B2 CS223809 B2 CS 223809B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- acid
- salts
- optionally
- ergolinyl
- bond
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 5
- TUMNHQRORINJKE-UHFFFAOYSA-N 1,1-diethylurea Chemical compound CCN(CC)C(N)=O TUMNHQRORINJKE-UHFFFAOYSA-N 0.000 title description 2
- 239000002253 acid Substances 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 8
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 6
- 150000001540 azides Chemical class 0.000 claims description 6
- 239000004202 carbamide Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000009835 boiling Methods 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 5
- 150000002513 isocyanates Chemical class 0.000 claims description 5
- 150000004702 methyl esters Chemical class 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 238000010306 acid treatment Methods 0.000 claims description 3
- 235000010288 sodium nitrite Nutrition 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- -1 alkyl radical Chemical class 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000011976 maleic acid Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011975 tartaric acid Substances 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000012043 crude product Substances 0.000 description 4
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- 229940095064 tartrate Drugs 0.000 description 4
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 3
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 3
- 229960003147 reserpine Drugs 0.000 description 3
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
- 239000003054 catalyst Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical class CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000003016 phosphoric acids Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UIQVGMBTAXORQL-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;methanol Chemical compound OC.OC(=O)C(O)C(O)C(O)=O UIQVGMBTAXORQL-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- JMIPCIOBRCCPRK-OXJNMPFZSA-N 3-[(6aR,9S)-7-prop-2-enyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea Chemical compound C(C=C)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C=34)NC(N(CC)CC)=O JMIPCIOBRCCPRK-OXJNMPFZSA-N 0.000 description 1
- HBDMXONIIVCHRG-FBLFFUNLSA-N 3-[(6ar)-7-butyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC(C2=CC(NC(=O)N(CC)CC)CN([C@@H]2C2)CCCC)=C3C2=CNC3=C1 HBDMXONIIVCHRG-FBLFFUNLSA-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
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- AGWBNBYABZUGEQ-OXJNMPFZSA-N C(C#C)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C=34)NC(N(CC)CC)=O Chemical compound C(C#C)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C=34)NC(N(CC)CC)=O AGWBNBYABZUGEQ-OXJNMPFZSA-N 0.000 description 1
- HECGTWNKRQAKKO-CMANCZGFSA-N C(\C=C/C(=O)O)(=O)O.C(C)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C34)NC(N(CC)CC)=O Chemical compound C(\C=C/C(=O)O)(=O)O.C(C)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C34)NC(N(CC)CC)=O HECGTWNKRQAKKO-CMANCZGFSA-N 0.000 description 1
- VEOBSFAYZINFNZ-MGPUTAFESA-N C1(CC1)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C34)NC(N(CC)CC)=O Chemical compound C1(CC1)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C34)NC(N(CC)CC)=O VEOBSFAYZINFNZ-MGPUTAFESA-N 0.000 description 1
- KKYYLQLHALAFPH-HRAATJIYSA-N C1(CCC1)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C=34)NC(N(CC)CC)=O Chemical compound C1(CCC1)N1C[C@H](C=C2C=3C=CC=C4NC=C(C[C@@H]12)C=34)NC(N(CC)CC)=O KKYYLQLHALAFPH-HRAATJIYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- RYECOJGRJDOGPP-UHFFFAOYSA-N Ethylurea Chemical class CCNC(N)=O RYECOJGRJDOGPP-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZAGRKAFMISFKIO-UHFFFAOYSA-N Isolysergic acid Natural products C1=CC(C2=CC(CN(C2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 241001293945 Pyla Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 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
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- VFNGKCDDZUSWLR-UHFFFAOYSA-N disulfuric acid Chemical compound OS(=O)(=O)OS(O)(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 229960003587 lisuride Drugs 0.000 description 1
- CVQFAMQDTWVJSV-BAXNFHPCSA-N lisuride maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 CVQFAMQDTWVJSV-BAXNFHPCSA-N 0.000 description 1
- ZAGRKAFMISFKIO-QMTHXVAHSA-N lysergic acid Chemical compound C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-QMTHXVAHSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- VTBLQYQCWIPWMA-LRHAYUFXSA-N methyl (6ar)-7-(2-cyanoethyl)-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C1=CC(C=2[C@H](N(CCC#N)CC(C=2)C(=O)OC)C2)=C3C2=CNC3=C1 VTBLQYQCWIPWMA-LRHAYUFXSA-N 0.000 description 1
- UJGNROGECCDUFK-XPKAQORNSA-N methyl (6ar)-7-(cyclopropylmethyl)-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C([C@H]12)C(C=34)=CNC4=CC=CC=3C1=CC(C(=O)OC)CN2CC1CC1 UJGNROGECCDUFK-XPKAQORNSA-N 0.000 description 1
- DWWMKLFIWKHJAO-PQJIZZRHSA-N methyl (6ar)-7-cyclobutyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C([C@H]12)C(C=34)=CNC4=CC=CC=3C1=CC(C(=O)OC)CN2C1CCC1 DWWMKLFIWKHJAO-PQJIZZRHSA-N 0.000 description 1
- DMVBUXRMDPVQAI-RGUGMKFQSA-N methyl (6ar)-7-cyclopropyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C([C@H]12)C(C=34)=CNC4=CC=CC=3C1=CC(C(=O)OC)CN2C1CC1 DMVBUXRMDPVQAI-RGUGMKFQSA-N 0.000 description 1
- QJRVRVSOQHQCBW-LRHAYUFXSA-N methyl (6ar)-7-prop-2-ynyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C1=CC(C=2[C@H](N(CC#C)CC(C=2)C(=O)OC)C2)=C3C2=CNC3=C1 QJRVRVSOQHQCBW-LRHAYUFXSA-N 0.000 description 1
- RNHDWLRHUJZABX-IAQYHMDHSA-N methyl (6ar,9r)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical class C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)OC)C2)=C3C2=CNC3=C1 RNHDWLRHUJZABX-IAQYHMDHSA-N 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/10—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hetero atoms directly attached in position 8
- C07D457/12—Nitrogen atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792924102 DE2924102A1 (de) | 1979-06-13 | 1979-06-13 | Neue (ergolin-yl)-n'.n'-diaethylharnstoffderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| DE19803016691 DE3016691A1 (de) | 1980-04-28 | 1980-04-28 | Neue (ergolin-yl)-n' .n'diaethylharnstoffderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel ii. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS223809B2 true CS223809B2 (en) | 1983-11-25 |
Family
ID=25779537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS804168A CS223809B2 (en) | 1979-06-13 | 1980-06-12 | Method of making the derivatives /ergolinyl/-h-,n diethylurea |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4379790A (da) |
| EP (1) | EP0021206B1 (da) |
| AU (1) | AU541679B2 (da) |
| CA (1) | CA1140922A (da) |
| CS (1) | CS223809B2 (da) |
| DD (1) | DD151449A5 (da) |
| DE (1) | DE3063869D1 (da) |
| DK (1) | DK149059C (da) |
| ES (1) | ES492400A0 (da) |
| HU (1) | HU184786B (da) |
| IE (1) | IE49991B1 (da) |
| IL (1) | IL60261A (da) |
| SU (1) | SU965356A3 (da) |
| YU (1) | YU41929B (da) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH654838A5 (fr) * | 1980-07-25 | 1986-03-14 | Sandoz Ag | Ergolinderivate, verfahren zu deren herstellung, diese enthaltende pharmazeutische zusammensetzungen. |
| CH644606A5 (de) * | 1980-09-23 | 1984-08-15 | Sandoz Ag | Verfahren zur isomerisierung von 9,10-dihydrolysergsaeurederivaten. |
| DE3101535A1 (de) * | 1981-01-14 | 1982-08-12 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue (2-halogen-ergolinyl)-n'.n'-diethyl-harnstoffderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| DE3135305C2 (de) * | 1981-09-03 | 1983-07-21 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 8-Ergolinyl-harnstoffen |
| DE3151912A1 (de) * | 1981-12-23 | 1983-06-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue ergolin-aminoderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| CS231214B1 (en) * | 1982-03-12 | 1984-10-15 | Antonin Cerny | Processing method of 1-substituted n+l8alpha-ergoline+p-n,diethyl urea |
| DE3216870A1 (de) * | 1982-05-03 | 1983-11-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Pharmazeutische zubereitungen mit zytostatischer wirkung |
| DE3309493A1 (de) * | 1983-03-14 | 1984-09-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue ergolin-derivate, verfahren zu ihrer herstellung sowie verwendung als arzneimittel |
| DE3445784A1 (de) * | 1984-12-13 | 1986-06-26 | Schering AG, Berlin und Bergkamen, 1000 Berlin | Verfahren zur herstellung von ergolin-derivaten |
| HU195810B (en) * | 1984-12-24 | 1988-07-28 | Sandoz Ag | Process for preparing new 8alpha-acyl-amino-ergoline derivatives and pharmaceutical compositions containing such compounds |
| EP0208417A3 (en) * | 1985-06-12 | 1989-09-06 | SPOFA Spojené Podniky Pro Zdravotnickou Vyrobu | Use of 1-(8-alpha-ergolinyl)-3,3-diethyl urea derivatives in the treatment of endometritis |
| DE3522894A1 (de) * | 1985-06-24 | 1987-01-02 | Schering Ag | Verwendung von tergurid als geriatrikum |
| DE3528576A1 (de) * | 1985-08-06 | 1987-02-19 | Schering Ag | Verfahren zur herstellung von ergolin-thioharnstoffen |
| DE3533675A1 (de) * | 1985-09-19 | 1987-03-26 | Schering Ag | Neue 12- und 13-brom-ergolinderivate |
| DE3533672A1 (de) * | 1985-09-19 | 1987-03-26 | Schering Ag | Neue 12- und 13-substituierte ergolinderivate |
| DK338789A (da) * | 1988-07-15 | 1990-01-16 | Schering Ag | 2-substituerede ergolinylurinstofderivater og fremgangsmaade til fremstilling deraf, deres anvendelse som laegemidler samt mellemprodukter til fremstilling deraf |
| US20070243240A9 (en) * | 2000-08-24 | 2007-10-18 | Fred Windt-Hanke | Transdermal therapeutic system |
| DE10053397A1 (de) * | 2000-10-20 | 2002-05-02 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
| DE10066158B4 (de) | 2000-08-24 | 2007-08-09 | Neurobiotec Gmbh | Verwendung eines transdermalen therapeutischen Systems zur Behandlung des Restless-Legs-Syndroms |
| DE10064453A1 (de) * | 2000-12-16 | 2002-07-04 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
| DE10226459A1 (de) * | 2002-06-13 | 2004-01-08 | Neurobiotec Gmbh | Verwendung von Dopamin-Partialagonisten zur Behandlung des Restless Legs Syndroms |
| GB0307377D0 (en) * | 2003-03-31 | 2003-05-07 | Merad Pharmaceuticals Ltd | Ergoline derivatives |
| EP2083008A1 (en) * | 2007-12-07 | 2009-07-29 | Axxonis Pharma AG | Ergoline derivatives as selective radical scavengers for neurons |
| USD1101961S1 (en) * | 2023-04-28 | 2025-11-11 | Charles River Laboratories International, Inc. | Cartridge |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH430738A (de) * | 1962-09-05 | 1967-02-28 | Spofa Vereinigte Pharma Werke | Verfahren zur Herstellung von N-(D-1,6-Dimethyl-isoergolenyl-8)-N',N'-dialkyl-harnstoffen |
| DE1212097B (de) * | 1962-09-05 | 1966-03-10 | Sdruzeni Podnikuu Pro Zdravotn | Verfahren zur Herstellung von N-[D-1, 6-Dimethylisoergolenyl-(8)]-N', N'-dialkylharnstoffen |
| US3681497A (en) * | 1966-06-07 | 1972-08-01 | Spofa Vereinigte Pharma Werke | Therapeutic methods of employing hydrogen maleate salt of n-(d-6-methyl-8-isoergolenyl)-n{40 ,n{40 -diethyl-carbamide |
| FR1536759A (fr) * | 1966-09-14 | 1968-08-16 | Spofa Vereinigte Pharma Werke | Procédé de préparation de la n-/d-6-méthyl-8-isoergolényl/-n', n'-diéthyl-urée |
| CH573937A5 (da) * | 1971-08-05 | 1976-03-31 | Spofa Vereinigte Pharma Werke | |
| US3920664A (en) * | 1972-07-21 | 1975-11-18 | Lilly Co Eli | D-2-halo-6-alkyl-8-substituted ergolines and related compounds |
| JPS5448880A (en) * | 1977-09-02 | 1979-04-17 | Tetra Pak Int | Method of designing packaging laminate and packaging laminate |
-
1980
- 1980-06-07 EP EP80103177A patent/EP0021206B1/de not_active Expired
- 1980-06-07 DE DE8080103177T patent/DE3063869D1/de not_active Expired
- 1980-06-09 AU AU59135/80A patent/AU541679B2/en not_active Ceased
- 1980-06-09 IL IL60261A patent/IL60261A/xx unknown
- 1980-06-10 YU YU1544/80A patent/YU41929B/xx unknown
- 1980-06-11 DD DD80221757A patent/DD151449A5/de not_active IP Right Cessation
- 1980-06-12 SU SU802930703A patent/SU965356A3/ru active
- 1980-06-12 HU HU801488A patent/HU184786B/hu not_active IP Right Cessation
- 1980-06-12 DK DK252680A patent/DK149059C/da not_active IP Right Cessation
- 1980-06-12 CS CS804168A patent/CS223809B2/cs unknown
- 1980-06-12 CA CA000353888A patent/CA1140922A/en not_active Expired
- 1980-06-12 IE IE1210/80A patent/IE49991B1/en not_active IP Right Cessation
- 1980-06-13 ES ES492400A patent/ES492400A0/es active Granted
-
1982
- 1982-01-06 US US06/337,355 patent/US4379790A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IE801210L (en) | 1980-12-13 |
| IL60261A0 (en) | 1980-09-16 |
| HU184786B (en) | 1984-10-29 |
| DK149059C (da) | 1986-07-14 |
| EP0021206B1 (de) | 1983-06-22 |
| SU965356A3 (ru) | 1982-10-07 |
| IL60261A (en) | 1983-10-31 |
| AU5913580A (en) | 1980-12-18 |
| IE49991B1 (en) | 1986-01-22 |
| AU541679B2 (en) | 1985-01-17 |
| YU41929B (en) | 1988-02-29 |
| YU154480A (en) | 1983-09-30 |
| ES8101073A1 (es) | 1980-12-16 |
| DK149059B (da) | 1986-01-06 |
| US4379790A (en) | 1983-04-12 |
| ES492400A0 (es) | 1980-12-16 |
| DK252680A (da) | 1980-12-14 |
| DD151449A5 (de) | 1981-10-21 |
| EP0021206A1 (de) | 1981-01-07 |
| CA1140922A (en) | 1983-02-08 |
| DE3063869D1 (en) | 1983-07-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS223809B2 (en) | Method of making the derivatives /ergolinyl/-h-,n diethylurea | |
| EP0297651B1 (en) | Anellated indole derivatives | |
| JPS6363544B2 (da) | ||
| JPS582946B2 (ja) | ８− チオメチルエルゴリンルイノ セイホウ | |
| JPS58150593A (ja) | ８―エルゴリニルチオ尿素誘導体及びその製法 | |
| CS227048B2 (en) | Method of preparing (2-halogenergolinyl)-n,n-diethylurea derivatives | |
| FR2466465A1 (fr) | Derives de d-6-n-propylergolines, leur procede de preparation et compositions pharmaceutiques en contenant | |
| US4283401A (en) | Process for the preparation of 11-bromo-vincaminic acid ester derivatives and their use in protecting animals against cerebral hypoxy | |
| US4356305A (en) | Process for the preparation of halovincamone derivatives | |
| CS247089B2 (en) | Production method of the 2-bromine-8-ergolinyl compounds | |
| JPS632265B2 (da) | ||
| CS256364B2 (en) | Method of 12 and 13 bromergoline's new derivatives production | |
| DD144671A5 (de) | Verfahren zur herstellung von 2-azaergolinen und 2-aza-8(oder 9)ergolenen | |
| HU193780B (en) | Process for producing 2-halogeno-6-methyl-ergol-9-ene derivatives and acid additional salts thereof | |
| JP2575446B2 (ja) | トリアザスピロ化合物 | |
| DE3413659A1 (de) | Neue 2-substituierte ergolin-derivate | |
| US4285865A (en) | Process for the preparation of halogenated 15-hydroxy-E-homoeburnane compounds | |
| FI66185B (fi) | Nytt foerfarande foer bromering av foereningar | |
| JPH0240647B2 (ja) | Purorakuchinbunpyokuseizai | |
| JP3160302B2 (ja) | 水素化へテロ環式化合物 | |
| US4558052A (en) | 10-Bromosandwicine, 10-bromoisosandwicine, pharmaceutical compositions thereof, and methods of treating heart rhythm disorders with them | |
| CA1104135A (en) | Vincamine derivatives | |
| JPH0240044B2 (ja) | Paakinsonshokogunchiryozai | |
| HU208010B (en) | Process for producing agroklavine- and elimoklavine derivatives and pharmaceutical compositions contaiing them | |
| IE46221B1 (en) | 10-bromovincamines |