JPS5946235B2 - シンキエルゴリンユウドウタイノ セイホウ - Google Patents
シンキエルゴリンユウドウタイノ セイホウInfo
- Publication number
- JPS5946235B2 JPS5946235B2 JP50144581A JP14458175A JPS5946235B2 JP S5946235 B2 JPS5946235 B2 JP S5946235B2 JP 50144581 A JP50144581 A JP 50144581A JP 14458175 A JP14458175 A JP 14458175A JP S5946235 B2 JPS5946235 B2 JP S5946235B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- ergoline
- acid
- compounds
- structural formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 27
- AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical class O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims 2
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 241000700159 Rattus Species 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 229960003133 ergot alkaloid Drugs 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- ZYACKOKSHZQYDS-NTVGDFDMSA-N (6ar,10ar)-9-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline Chemical compound C1=CC([C@@H]2[C@H](NCC(C2)C)C2)=C3C2=CNC3=C1 ZYACKOKSHZQYDS-NTVGDFDMSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 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 2
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 2
- 206010063928 Amenorrhoea-galactorrhoea syndrome Diseases 0.000 description 2
- 208000001287 Galactorrhea Diseases 0.000 description 2
- 206010017600 Galactorrhoea Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 230000006651 lactation Effects 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- -1 p-toluenesulfonyloxy Chemical group 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 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 2
- 229960003147 reserpine Drugs 0.000 description 2
- 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 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- NRNPZUVPUBSFMI-SKNXHYNKSA-N (6ar,10ar)-9-(bromomethyl)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2CC(CBr)CN([C@@H]2C2)C)=C3C2=CNC3=C1 NRNPZUVPUBSFMI-SKNXHYNKSA-N 0.000 description 1
- RWEOYCPQPSGJQB-NTVGDFDMSA-N (6ar,10ar)-9-(nitromethyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline Chemical class C1=CC([C@@H]2[C@H](NCC(C2)C[N+](=O)[O-])C2)=C3C2=CNC3=C1 RWEOYCPQPSGJQB-NTVGDFDMSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-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
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000004054 Chiari-Frommel Syndrome Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101100448208 Human herpesvirus 6B (strain Z29) U69 gene Proteins 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 1
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical group S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 206010051482 Prostatomegaly Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- LPMRLAHSKOBNRK-SKNXHYNKSA-N [(6ar,10ar)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-yl]methyl methanesulfonate Chemical compound C1=CC([C@@H]2[C@H](NCC(C2)COS(=O)(=O)C)C2)=C3C2=CNC3=C1 LPMRLAHSKOBNRK-SKNXHYNKSA-N 0.000 description 1
- 208000023599 acquired hyperprolactinemia Diseases 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 208000031424 hyperprolactinemia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-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
- 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
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection 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
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical group [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
- 238000005303 weighing Methods 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
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Endocrinology (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 (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/530,318 US3985752A (en) | 1974-12-06 | 1974-12-06 | 6-Methyl-8-(substituted) methylergolines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5182300A JPS5182300A (en, 2012) | 1976-07-19 |
| JPS5946235B2 true JPS5946235B2 (ja) | 1984-11-10 |
Family
ID=24113213
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50144581A Expired JPS5946235B2 (ja) | 1974-12-06 | 1975-12-03 | シンキエルゴリンユウドウタイノ セイホウ |
| JP59083605A Expired JPS6017795B2 (ja) | 1974-12-06 | 1984-04-24 | 新規エルゴリン誘導体の製造法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59083605A Expired JPS6017795B2 (ja) | 1974-12-06 | 1984-04-24 | 新規エルゴリン誘導体の製造法 |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US3985752A (en, 2012) |
| JP (2) | JPS5946235B2 (en, 2012) |
| AR (2) | AR208104A1 (en, 2012) |
| AT (2) | AT348141B (en, 2012) |
| AU (1) | AU498226B2 (en, 2012) |
| BE (1) | BE836308A (en, 2012) |
| BG (3) | BG33435A3 (en, 2012) |
| CA (2) | CA1062252A (en, 2012) |
| CH (2) | CH617197A5 (en, 2012) |
| CS (2) | CS200483B2 (en, 2012) |
| DD (2) | DD123748A5 (en, 2012) |
| DE (1) | DE2554000A1 (en, 2012) |
| DK (2) | DK547675A (en, 2012) |
| ES (3) | ES443276A1 (en, 2012) |
| FR (1) | FR2293203A1 (en, 2012) |
| GB (1) | GB1526835A (en, 2012) |
| GR (2) | GR60026B (en, 2012) |
| HU (3) | HU173724B (en, 2012) |
| IE (1) | IE42372B1 (en, 2012) |
| IL (1) | IL48573A (en, 2012) |
| MX (1) | MX3113E (en, 2012) |
| NL (1) | NL7514058A (en, 2012) |
| PH (1) | PH12630A (en, 2012) |
| PL (3) | PL102195B1 (en, 2012) |
| RO (2) | RO65456A (en, 2012) |
| SE (2) | SE421422B (en, 2012) |
| SU (3) | SU685155A3 (en, 2012) |
| YU (2) | YU304875A (en, 2012) |
| ZA (1) | ZA757624B (en, 2012) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4166182A (en) * | 1978-02-08 | 1979-08-28 | Eli Lilly And Company | 6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds |
| AU526764B2 (en) * | 1978-09-08 | 1983-01-27 | Farmitalia Carlo Erba S.P.A. | Ergoline derivatives |
| HU180467B (en) * | 1979-07-12 | 1983-03-28 | Gyogyszerkutato Intezet | Process for producing new ergol-8-ene- and ergoline-sceleted compounds |
| US4683313A (en) * | 1985-06-24 | 1987-07-28 | Eli Lilly And Company | 2-alkyl(or phenyl)thio-6-N alkyl ergolines and 4-dialkylaminotetrahydrobenz[c,d]indoles |
| JPH02174820A (ja) * | 1988-12-27 | 1990-07-06 | Sekisui Chem Co Ltd | トイレット |
| WO2000054776A1 (en) * | 1999-03-17 | 2000-09-21 | Eugen Eigenmann | Use of prolactin inhibitors for the treatment of fertility problems in animal species |
| DE10053397A1 (de) | 2000-10-20 | 2002-05-02 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
| US20070243240A9 (en) * | 2000-08-24 | 2007-10-18 | Fred Windt-Hanke | Transdermal therapeutic system |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1695752C3 (de) * | 1966-07-29 | 1974-06-06 | Societa Farmaceutici Italia, Mailand (Italien) | 1 ,ö-Dimethyl-ebeta-N-carbobenzoxyaminomethyl-2,3-dihydro-1 Oalpha-ergolin und ein Verfahren zu seiner Herstellung |
| BE712054A (en, 2012) * | 1967-03-16 | 1968-07-15 |
-
1974
- 1974-12-06 US US05/530,318 patent/US3985752A/en not_active Expired - Lifetime
-
1975
- 1975-01-01 AR AR261512A patent/AR208104A1/es active
- 1975-01-01 AR AR261511A patent/AR207664A1/es active
- 1975-11-20 CS CS757859A patent/CS200483B2/cs unknown
- 1975-11-20 CS CS757860A patent/CS199609B2/cs unknown
- 1975-11-27 GB GB48901/75A patent/GB1526835A/en not_active Expired
- 1975-11-28 GR GR49484A patent/GR60026B/el unknown
- 1975-11-28 GR GR49483A patent/GR60025B/el unknown
- 1975-11-28 MX MX004193U patent/MX3113E/es unknown
- 1975-11-28 PH PH17816A patent/PH12630A/en unknown
- 1975-11-30 IL IL48573A patent/IL48573A/xx unknown
- 1975-12-01 DE DE19752554000 patent/DE2554000A1/de not_active Withdrawn
- 1975-12-02 CA CA240,915A patent/CA1062252A/en not_active Expired
- 1975-12-02 AU AU87182/75A patent/AU498226B2/en not_active Expired
- 1975-12-02 CA CA240,916A patent/CA1062253A/en not_active Expired
- 1975-12-02 NL NL7514058A patent/NL7514058A/xx not_active Application Discontinuation
- 1975-12-03 YU YU03048/75A patent/YU304875A/xx unknown
- 1975-12-03 JP JP50144581A patent/JPS5946235B2/ja not_active Expired
- 1975-12-03 SE SE7513640A patent/SE421422B/xx not_active IP Right Cessation
- 1975-12-03 YU YU03047/75A patent/YU304775A/xx unknown
- 1975-12-03 SE SE7513641A patent/SE421423B/xx not_active IP Right Cessation
- 1975-12-04 RO RO7584088A patent/RO65456A/ro unknown
- 1975-12-04 DK DK547675A patent/DK547675A/da unknown
- 1975-12-04 FR FR7537117A patent/FR2293203A1/fr active Granted
- 1975-12-04 PL PL1975185226A patent/PL102195B1/pl unknown
- 1975-12-04 DK DK547575AA patent/DK142321B/da not_active IP Right Cessation
- 1975-12-04 PL PL1975185225A patent/PL102198B1/pl unknown
- 1975-12-04 HU HU75EI657A patent/HU173724B/hu unknown
- 1975-12-04 PL PL1975208580A patent/PL106884B1/pl unknown
- 1975-12-04 RO RO7584087A patent/RO64281A/ro unknown
- 1975-12-04 ZA ZA757624A patent/ZA757624B/xx unknown
- 1975-12-04 HU HU75EI848A patent/HU175228B/hu unknown
- 1975-12-04 HU HUEI000658 patent/HU173847B/hu unknown
- 1975-12-04 SU SU752194455A patent/SU685155A3/ru active
- 1975-12-04 CH CH1580275A patent/CH617197A5/de not_active IP Right Cessation
- 1975-12-04 CH CH1580175A patent/CH619465A5/de not_active IP Right Cessation
- 1975-12-04 SU SU752194702A patent/SU694075A3/ru active
- 1975-12-05 AT AT927875A patent/AT348141B/de not_active IP Right Cessation
- 1975-12-05 DD DD189914A patent/DD123748A5/xx unknown
- 1975-12-05 IE IE2657/75A patent/IE42372B1/en unknown
- 1975-12-05 BG BG033760A patent/BG33435A3/xx unknown
- 1975-12-05 DD DD189913A patent/DD123749A5/xx unknown
- 1975-12-05 AT AT927975A patent/AT347050B/de not_active IP Right Cessation
- 1975-12-05 BE BE1007062A patent/BE836308A/xx not_active IP Right Cessation
- 1975-12-05 ES ES443276A patent/ES443276A1/es not_active Expired
- 1975-12-05 BG BG031705A patent/BG33287A3/xx unknown
- 1975-12-05 BG BG031706A patent/BG33288A3/xx unknown
- 1975-12-05 ES ES443275A patent/ES443275A1/es not_active Expired
-
1976
- 1976-07-12 SU SU762379565A patent/SU724085A3/ru active
-
1977
- 1977-04-11 ES ES457709A patent/ES457709A1/es not_active Expired
-
1984
- 1984-04-24 JP JP59083605A patent/JPS6017795B2/ja not_active Expired
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