JPS5813542B2 - 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
- JPS5813542B2 JPS5813542B2 JP50144580A JP14458075A JPS5813542B2 JP S5813542 B2 JPS5813542 B2 JP S5813542B2 JP 50144580 A JP50144580 A JP 50144580A JP 14458075 A JP14458075 A JP 14458075A JP S5813542 B2 JPS5813542 B2 JP S5813542B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- dimethyl
- acid
- formula
- compound
- 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 37
- 239000002253 acid Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
- 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 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 23
- -1 8,8-disubstituted-6-methylergoline Chemical class 0.000 description 19
- 238000000921 elemental analysis Methods 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 102000003946 Prolactin Human genes 0.000 description 16
- 108010057464 Prolactin Proteins 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 229940097325 prolactin Drugs 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000004364 calculation method Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 239000010410 layer Substances 0.000 description 13
- 241000700159 Rattus Species 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000000155 melt Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-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 8
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 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 4
- 230000028327 secretion Effects 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 150000002688 maleic acid derivatives Chemical class 0.000 description 3
- OSKZYLPFYNARRX-NJZAAPMLSA-N methyl (6ar,9s,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)C(=O)OC)=C3C2=CNC3=C1 OSKZYLPFYNARRX-NJZAAPMLSA-N 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000007787 solid 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
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- UJYGDMFEEDNVBF-UHFFFAOYSA-N Ergocorninine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)C(C)C)C(C)C)C2)=C3C2=CNC3=C1 UJYGDMFEEDNVBF-UHFFFAOYSA-N 0.000 description 2
- 208000001287 Galactorrhea Diseases 0.000 description 2
- 206010017600 Galactorrhoea Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 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
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 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
- 210000000481 breast Anatomy 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- XQUUDUKVJKNJNP-OGGGUQDZSA-N ergocornine Chemical compound C([C@H]1N(C)C2)C([C]34)=CN=C4C=CC=C3C1=C[C@H]2C(=O)N[C@@]1(C(C)C)C(=O)N2[C@@H](C(C)C)C(=O)N3CCC[C@H]3[C@]2(O)O1 XQUUDUKVJKNJNP-OGGGUQDZSA-N 0.000 description 2
- YDOTUXAWKBPQJW-UHFFFAOYSA-N ergocryptine Chemical compound C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-UHFFFAOYSA-N 0.000 description 2
- RHGUXDUPXYFCTE-ZWNOBZJWSA-N ergoline Chemical class C1=CC([C@@H]2[C@H](NCCC2)C2)=C3C2=CNC3=C1 RHGUXDUPXYFCTE-ZWNOBZJWSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229950002454 lysergide Drugs 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate 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
- 230000001624 sedative effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- NLBVQNOAMRYJKH-CRAIPNDOSA-N (6aR,9R)-4,7,9-trimethyl-6a,8-dihydro-6H-indolo[4,3-fg]quinoline-9-carboxylic acid Chemical compound C1=CC(C2=C[C@](C)(CN([C@@H]2C2)C)C(O)=O)=C3C2=CN(C)C3=C1 NLBVQNOAMRYJKH-CRAIPNDOSA-N 0.000 description 1
- ORBSYPFBZQJNJE-HCGVIMEBSA-N (6ar,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carboxylic acid Chemical compound C1=CC([C@H]2CC(CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ORBSYPFBZQJNJE-HCGVIMEBSA-N 0.000 description 1
- ZAGRKAFMISFKIO-IINYFYTJSA-N (6ar,9s)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylic acid Chemical compound C1=CC(C2=C[C@@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-IINYFYTJSA-N 0.000 description 1
- DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
- YAXWOADCWUUUNX-UHFFFAOYSA-N 1,2,2,3-tetramethylpiperidine Chemical compound CC1CCCN(C)C1(C)C YAXWOADCWUUUNX-UHFFFAOYSA-N 0.000 description 1
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-Tetramethylpiperidine Substances CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-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
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229910001148 Al-Li alloy Inorganic materials 0.000 description 1
- 206010063928 Amenorrhoea-galactorrhoea syndrome Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- PRIBVLOAPPUJDL-KNQAVFIVSA-N C1=CC(C=2[C@H](N(C)C[C@@](C=2)(C)C(=O)N(CC)CC)C2)=C3C2=CN(C)C3=C1 Chemical compound C1=CC(C=2[C@H](N(C)C[C@@](C=2)(C)C(=O)N(CC)CC)C2)=C3C2=CN(C)C3=C1 PRIBVLOAPPUJDL-KNQAVFIVSA-N 0.000 description 1
- SMIZBBOTUJYEHS-KNQAVFIVSA-N C1=CC(C=2[C@H](N(C)C[C@@](C=2)(CC)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 Chemical compound C1=CC(C=2[C@H](N(C)C[C@@](C=2)(CC)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 SMIZBBOTUJYEHS-KNQAVFIVSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- NESVMZOPWPCFAU-UHFFFAOYSA-N Ergoclavinine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C)C2)=C3C2=CNC3=C1 NESVMZOPWPCFAU-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
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- 239000003795 chemical substances by application Substances 0.000 description 1
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- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
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- 238000001816 cooling Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
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- OWEUDBYTKOYTAD-MKTPKCENSA-N ergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@@H]1C=C2C3=CC=CC4=NC=C([C]34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 OWEUDBYTKOYTAD-MKTPKCENSA-N 0.000 description 1
- HEFIYUQVAZFDEE-UHFFFAOYSA-N ergocristinine Natural products N12C(=O)C(C(C)C)(NC(=O)C3C=C4C=5C=CC=C6NC=C(C=56)CC4N(C)C3)OC2(O)C2CCCN2C(=O)C1CC1=CC=CC=C1 HEFIYUQVAZFDEE-UHFFFAOYSA-N 0.000 description 1
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- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
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- 230000003400 hallucinatory effect Effects 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
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- 150000002431 hydrogen Chemical class 0.000 description 1
- 229940079826 hydrogen sulfite Drugs 0.000 description 1
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- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 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 compound 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
- OSKZYLPFYNARRX-UHFFFAOYSA-N methyl 7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C1=CC(C2CC(CN(C)C2C2)C(=O)OC)=C3C2=CNC3=C1 OSKZYLPFYNARRX-UHFFFAOYSA-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
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- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 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
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
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- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- 150000003013 phosphoric acid derivatives Chemical class 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
- ZMJJCODMIXQWCQ-UHFFFAOYSA-N potassium;di(propan-2-yl)azanide Chemical compound [K+].CC(C)[N-]C(C)C ZMJJCODMIXQWCQ-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 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
- 230000003248 secreting effect Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 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
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing 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
- C07D457/04—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid 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 in position 8
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Anesthesiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (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 |
|---|---|---|---|
| US05/530,320 US3968111A (en) | 1974-12-06 | 1974-12-06 | 8,8-Disubstituted-6-methylergolines and related compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5182299A JPS5182299A (en, 2012) | 1976-07-19 |
| JPS5813542B2 true JPS5813542B2 (ja) | 1983-03-14 |
Family
ID=24113222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50144580A Expired JPS5813542B2 (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 |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US3968111A (en, 2012) |
| JP (1) | JPS5813542B2 (en, 2012) |
| AR (1) | AR211257A1 (en, 2012) |
| AT (1) | AT348142B (en, 2012) |
| AU (1) | AU505194B2 (en, 2012) |
| BE (1) | BE836309A (en, 2012) |
| BG (1) | BG33289A3 (en, 2012) |
| CA (1) | CA1064918A (en, 2012) |
| CH (1) | CH605937A5 (en, 2012) |
| CS (1) | CS199610B2 (en, 2012) |
| DD (1) | DD123750A5 (en, 2012) |
| DE (1) | DE2554629A1 (en, 2012) |
| DK (1) | DK146128C (en, 2012) |
| ES (1) | ES443279A1 (en, 2012) |
| FR (1) | FR2293204A1 (en, 2012) |
| GB (1) | GB1535214A (en, 2012) |
| GR (1) | GR59201B (en, 2012) |
| HU (1) | HU173985B (en, 2012) |
| IE (1) | IE42198B1 (en, 2012) |
| IL (1) | IL48572A (en, 2012) |
| NL (1) | NL7514177A (en, 2012) |
| PH (1) | PH13133A (en, 2012) |
| PL (1) | PL102611B1 (en, 2012) |
| RO (1) | RO64606A (en, 2012) |
| SE (1) | SE421528B (en, 2012) |
| SU (1) | SU627757A3 (en, 2012) |
| YU (1) | YU304575A (en, 2012) |
| ZA (1) | ZA757510B (en, 2012) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3968111A (en) * | 1974-12-06 | 1976-07-06 | Eli Lilly And Company | 8,8-Disubstituted-6-methylergolines and related compounds |
| USRE30219E (en) * | 1974-12-06 | 1980-02-19 | Eli Lilly And Company | Method of preparing 8,8-disubstituted-6-methylergolines and related compounds |
| US4054567A (en) * | 1975-08-11 | 1977-10-18 | Eli Lilly And Company | 6-Methyl-8β-hydroxymethyl-8-γ-substituted-9-ergolene compounds |
| US4098790A (en) * | 1976-09-15 | 1978-07-04 | Eli Lilly And Company | Ergoline chlorination process |
| US4238486A (en) * | 1979-11-23 | 1980-12-09 | Merck & Co., Inc. | Indolobenzoxazines |
| US4382940A (en) * | 1979-12-06 | 1983-05-10 | Farmitalia Carlo Erba S.P.A. | Ercoline derivatives and therapeutic compositions having CNS affecting activity |
| DE3001752A1 (de) * | 1980-01-16 | 1981-07-30 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | Verfahren zur herstellung von 8(alpha)-substituierten 6-methylergolinen |
| CH644606A5 (de) * | 1980-09-23 | 1984-08-15 | Sandoz Ag | Verfahren zur isomerisierung von 9,10-dihydrolysergsaeurederivaten. |
| US4801712A (en) * | 1985-06-24 | 1989-01-31 | Eli Lilly And Company | 2-Alkyl(or phenyl)thio-6-n-alkylergolines are dopamine D-1 antagonists without D-2 agonist activity |
| US20030181488A1 (en) | 2002-03-07 | 2003-09-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH344731A (de) * | 1956-05-18 | 1960-02-29 | Sandoz Ag | Verfahren zur Herstellung von neuen, am Indolstickstoff alkylierten Derivaten der Lysergsäure-Reihe |
| US2861074A (en) * | 1956-10-22 | 1958-11-18 | Lilly Co Eli | Substituted hydroxyergolenes |
| BE755211A (fr) * | 1969-08-29 | 1971-02-01 | Spofa Usines Pharma Reunies | Procede de preparation des nouvelles amides de l'acide d-6-methyl-8-ergolin/i/yle/acetique et de leurs sels, ainsi que les produits obtenus |
| AR206772A1 (es) * | 1972-07-21 | 1976-08-23 | Lilly Co Eli | Procedimiento para preparar una nueva d-2-halo-6-metil-8-ciano(carboxamido)metil ergolina |
| US3968112A (en) * | 1974-08-02 | 1976-07-06 | Eli Lilly And Company | Synthesis of penniclavine and elymoclavine |
| US3968111A (en) * | 1974-12-06 | 1976-07-06 | Eli Lilly And Company | 8,8-Disubstituted-6-methylergolines and related compounds |
-
1974
- 1974-12-06 US US05/530,320 patent/US3968111A/en not_active Expired - Lifetime
-
1975
- 1975-11-20 CS CS757861A patent/CS199610B2/cs unknown
- 1975-11-28 GR GR49485A patent/GR59201B/el unknown
- 1975-11-28 ZA ZA757510A patent/ZA757510B/xx unknown
- 1975-11-29 RO RO7500084073A patent/RO64606A/ro unknown
- 1975-11-30 IL IL48572A patent/IL48572A/xx unknown
- 1975-12-01 GB GB49208/75A patent/GB1535214A/en not_active Expired
- 1975-12-01 CA CA240,828A patent/CA1064918A/en not_active Expired
- 1975-12-02 AU AU87181/75A patent/AU505194B2/en not_active Expired
- 1975-12-02 PH PH17826A patent/PH13133A/en unknown
- 1975-12-03 HU HU75EI656A patent/HU173985B/hu unknown
- 1975-12-03 AR AR261466A patent/AR211257A1/es active
- 1975-12-03 YU YU03045/75A patent/YU304575A/xx unknown
- 1975-12-03 JP JP50144580A patent/JPS5813542B2/ja not_active Expired
- 1975-12-04 CH CH1580075A patent/CH605937A5/xx not_active IP Right Cessation
- 1975-12-04 DK DK547475A patent/DK146128C/da not_active IP Right Cessation
- 1975-12-04 DE DE19752554629 patent/DE2554629A1/de not_active Withdrawn
- 1975-12-04 NL NL7514177A patent/NL7514177A/xx not_active Application Discontinuation
- 1975-12-04 IE IE2644/75A patent/IE42198B1/en unknown
- 1975-12-04 PL PL1975185227A patent/PL102611B1/pl unknown
- 1975-12-04 SU SU752194708A patent/SU627757A3/ru active
- 1975-12-04 FR FR7537118A patent/FR2293204A1/fr active Granted
- 1975-12-05 DD DD189911A patent/DD123750A5/xx unknown
- 1975-12-05 SE SE7513753A patent/SE421528B/xx unknown
- 1975-12-05 BG BG031707A patent/BG33289A3/xx unknown
- 1975-12-05 ES ES443279A patent/ES443279A1/es not_active Expired
- 1975-12-05 BE BE1007063A patent/BE836309A/xx not_active IP Right Cessation
- 1975-12-05 AT AT928075A patent/AT348142B/de not_active IP Right Cessation
-
1976
- 1976-01-19 US US05/650,582 patent/US4075212A/en not_active Expired - Lifetime
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