CA1062253A - Process for preparing 6-methyl-8-(substituted) methylergolines - Google Patents
Process for preparing 6-methyl-8-(substituted) methylergolinesInfo
- Publication number
- CA1062253A CA1062253A CA240,916A CA240916A CA1062253A CA 1062253 A CA1062253 A CA 1062253A CA 240916 A CA240916 A CA 240916A CA 1062253 A CA1062253 A CA 1062253A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- methyl
- compounds
- compound
- prolactin
- 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
- -1 6-methyl-8-(substituted) methylergolines Chemical class 0.000 title abstract description 3
- 238000004519 manufacturing process Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 231100000252 nontoxic Toxicity 0.000 claims description 7
- 230000003000 nontoxic effect Effects 0.000 claims description 7
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 230000002140 halogenating effect Effects 0.000 claims description 4
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 claims description 2
- 229960002327 chloral hydrate Drugs 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- 102000003946 Prolactin Human genes 0.000 abstract description 18
- 108010057464 Prolactin Proteins 0.000 abstract description 18
- 229940097325 prolactin Drugs 0.000 abstract description 18
- 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 compound 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 abstract description 7
- 238000006073 displacement reaction Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 229960003133 ergot alkaloid Drugs 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- ODTCIYCTILPXFR-NTVGDFDMSA-N [(6ar,10ar)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-yl]methanamine Chemical compound C1=CC([C@@H]2[C@H](NCC(C2)CN)C2)=C3C2=CNC3=C1 ODTCIYCTILPXFR-NTVGDFDMSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- RHGUXDUPXYFCTE-ZWNOBZJWSA-N ergoline Chemical class C1=CC([C@@H]2[C@H](NCCC2)C2)=C3C2=CNC3=C1 RHGUXDUPXYFCTE-ZWNOBZJWSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000011282 treatment Methods 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
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 206010063928 Amenorrhoea-galactorrhoea syndrome Diseases 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- ASSUGCSGSXLJKH-SKNXHYNKSA-N N-[[(6aR,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]methyl]formamide Chemical class C(=O)NCC1CN[C@@H]2CC3=CNC4=CC=CC([C@H]2C1)=C34 ASSUGCSGSXLJKH-SKNXHYNKSA-N 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 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
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000000079 gynecomastia Diseases 0.000 description 2
- 230000006651 lactation Effects 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
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 201000004240 prostatic hypertrophy Diseases 0.000 description 2
- 238000001953 recrystallisation Methods 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 description 2
- QVRCMEVTUIOJFP-OJDRRSAWSA-N (6aR,10aR)-9-isocyano-9-methyl-6,6a,7,8,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline Chemical compound [N+](#[C-])C1(CN[C@@H]2CC3=CNC4=CC=CC([C@H]2C1)=C34)C QVRCMEVTUIOJFP-OJDRRSAWSA-N 0.000 description 1
- FGBDDLRAORVDCA-SKNXHYNKSA-N (6ar,10ar)-9-(isocyanomethyl)-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[N+]#[C-])C2)=C3C2=CNC3=C1 FGBDDLRAORVDCA-SKNXHYNKSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 208000004054 Chiari-Frommel Syndrome Diseases 0.000 description 1
- 208000001287 Galactorrhea Diseases 0.000 description 1
- 206010017600 Galactorrhoea Diseases 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
- 206010054107 Nodule Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000023599 acquired hyperprolactinemia Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000008195 breast development Effects 0.000 description 1
- 208000011803 breast fibrocystic disease Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 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
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 208000031424 hyperprolactinemia Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002527 isonitriles Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 201000002140 prolactin producing pituitary tumor Diseases 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 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
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 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 (1)
| Publication Number | Publication Date |
|---|---|
| CA1062253A true CA1062253A (en) | 1979-09-11 |
Family
ID=24113213
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA240,915A Expired CA1062252A (en) | 1974-12-06 | 1975-12-02 | 6-methyl-8-(substituted) methylergolines |
| CA240,916A Expired CA1062253A (en) | 1974-12-06 | 1975-12-02 | Process for preparing 6-methyl-8-(substituted) methylergolines |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA240,915A Expired CA1062252A (en) | 1974-12-06 | 1975-12-02 | 6-methyl-8-(substituted) methylergolines |
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
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1976
- 1976-07-12 SU SU762379565A patent/SU724085A3/ru active
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1977
- 1977-04-11 ES ES457709A patent/ES457709A1/es not_active Expired
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1984
- 1984-04-24 JP JP59083605A patent/JPS6017795B2/ja not_active Expired
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