DE2509471A1 - Verfahren zur herstellung neuer heterocyclischer verbindungen - Google Patents
Verfahren zur herstellung neuer heterocyclischer verbindungenInfo
- Publication number
- DE2509471A1 DE2509471A1 DE19752509471 DE2509471A DE2509471A1 DE 2509471 A1 DE2509471 A1 DE 2509471A1 DE 19752509471 DE19752509471 DE 19752509471 DE 2509471 A DE2509471 A DE 2509471A DE 2509471 A1 DE2509471 A1 DE 2509471A1
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- methyl
- compounds
- addition salts
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 18
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 62
- -1 2-pyridylthiomethyl Chemical group 0.000 claims description 27
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 18
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 229910052783 alkali metal Chemical group 0.000 claims description 3
- 150000001340 alkali metals Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
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- 239000000203 mixture Substances 0.000 description 7
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- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 5
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- 230000003291 dopaminomimetic effect Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
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- 230000004936 stimulating effect Effects 0.000 description 4
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 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 3
- 239000004480 active ingredient Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229960001948 caffeine Drugs 0.000 description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
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- 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
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- 201000006474 Brain Ischemia Diseases 0.000 description 2
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- 208000009132 Catalepsy Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
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- 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 2
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- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
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- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
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- 206010047853 Waxy flexibility Diseases 0.000 description 2
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- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
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- 235000019359 magnesium stearate Nutrition 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture 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
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- 229960000278 theophylline Drugs 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- DFBTUSRLMAAUHX-UHFFFAOYSA-N 4-[(3,4-dimethoxyphenyl)methyl]imidazolidin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CC1NC(=O)NC1 DFBTUSRLMAAUHX-UHFFFAOYSA-N 0.000 description 1
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- ULBZRLXAMNKBPM-UHFFFAOYSA-N 4-amino-1h-pyrazolo[3,4-b]pyridine-5-carboxylic acid Chemical class NC1=C(C(O)=O)C=NC2=C1C=NN2 ULBZRLXAMNKBPM-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
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- 125000001544 thienyl group Chemical group 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
- 239000003029 tricyclic antidepressant agent 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
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (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 |
|---|---|---|---|
| CH356374A CH593972A5 (enrdf_load_stackoverflow) | 1974-03-14 | 1974-03-14 | |
| CH1013874 | 1974-07-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2509471A1 true DE2509471A1 (de) | 1975-09-18 |
Family
ID=25693324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752509471 Ceased DE2509471A1 (de) | 1974-03-14 | 1975-03-05 | Verfahren zur herstellung neuer heterocyclischer verbindungen |
Country Status (18)
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4147789A (en) * | 1974-03-14 | 1979-04-03 | Sandoz Ltd. | 6-Methyl-8-thiomethyl-ergolene derivatives |
| EP0003667A1 (en) * | 1978-02-08 | 1979-08-22 | Eli Lilly And Company | Ergoline compounds, their preparation and pharmaceutical compositions containing them |
| US4798834A (en) * | 1987-08-31 | 1989-01-17 | Eli Lilly And Company | Optionally substituted (3β-9,10-didehydro-2,3-dihydro ergoline as serotonergic function enhancement |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5293797A (en) * | 1976-01-30 | 1977-08-06 | Sandoz Ag | Improvement in organic compound |
| GB1555751A (en) * | 1977-02-02 | 1979-11-14 | Farmaceutici Italia | Ergoline deritatives |
| US4382940A (en) * | 1979-12-06 | 1983-05-10 | Farmitalia Carlo Erba S.P.A. | Ercoline derivatives and therapeutic compositions having CNS affecting activity |
| GB2120242A (en) * | 1982-04-30 | 1983-11-30 | Erba Farmitalia | Ergoline derivatives |
| CH649998A5 (de) * | 1982-08-09 | 1985-06-28 | Sandoz Ag | Ergolinderivate, ein verfahren zu ihrer herstellung und heilmittel, enthaltend diese ergolinderivate als wirkstoff. |
| IT1215261B (it) * | 1985-04-05 | 1990-01-31 | Poli Ind Chimica Spa | Composizioni farmaceutiche adattivita' antigalattopoietica. |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1901750A1 (de) * | 1968-01-18 | 1969-09-04 | Sandoz Ag | Neue heterocyclische Verbindungen und Verfahren zu deren Herstellung |
-
1975
- 1975-02-12 IE IE542/75A patent/IE41533B1/en unknown
- 1975-03-05 SE SE7502469A patent/SE420094B/xx unknown
- 1975-03-05 DE DE19752509471 patent/DE2509471A1/de not_active Ceased
- 1975-03-05 DK DK89375AA patent/DK141701B/da not_active IP Right Cessation
- 1975-03-06 FI FI750644A patent/FI60865C/fi not_active IP Right Cessation
- 1975-03-06 NO NO75750748A patent/NO750748L/no unknown
- 1975-03-10 NL NL7502807A patent/NL7502807A/xx not_active Application Discontinuation
- 1975-03-10 GB GB9807/75A patent/GB1497681A/en not_active Expired
- 1975-03-11 FR FR7507472A patent/FR2263774B1/fr not_active Expired
- 1975-03-12 PH PH16903A patent/PH12966A/en unknown
- 1975-03-12 ES ES435538A patent/ES435538A1/es not_active Expired
- 1975-03-12 IL IL46809A patent/IL46809A/xx unknown
- 1975-03-12 DD DD184721A patent/DD118428A5/xx unknown
- 1975-03-13 CA CA221,971A patent/CA1071192A/en not_active Expired
- 1975-03-13 JP JP50029600A patent/JPS589111B2/ja not_active Expired
- 1975-03-13 AU AU79057/75A patent/AU500890B2/en not_active Ceased
-
1981
- 1981-03-12 HK HK84/81A patent/HK8481A/xx unknown
- 1981-12-30 MY MY331/81A patent/MY8100331A/xx unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1901750A1 (de) * | 1968-01-18 | 1969-09-04 | Sandoz Ag | Neue heterocyclische Verbindungen und Verfahren zu deren Herstellung |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4147789A (en) * | 1974-03-14 | 1979-04-03 | Sandoz Ltd. | 6-Methyl-8-thiomethyl-ergolene derivatives |
| EP0003667A1 (en) * | 1978-02-08 | 1979-08-22 | Eli Lilly And Company | Ergoline compounds, their preparation and pharmaceutical compositions containing them |
| US4798834A (en) * | 1987-08-31 | 1989-01-17 | Eli Lilly And Company | Optionally substituted (3β-9,10-didehydro-2,3-dihydro ergoline as serotonergic function enhancement |
Also Published As
| Publication number | Publication date |
|---|---|
| PH12966A (en) | 1979-10-19 |
| MY8100331A (en) | 1981-12-31 |
| FR2263774A1 (enrdf_load_stackoverflow) | 1975-10-10 |
| DK89375A (enrdf_load_stackoverflow) | 1975-09-15 |
| SE420094B (sv) | 1981-09-14 |
| ES435538A1 (es) | 1977-03-16 |
| JPS589111B2 (ja) | 1983-02-18 |
| JPS50123698A (enrdf_load_stackoverflow) | 1975-09-29 |
| HK8481A (en) | 1981-03-20 |
| FI750644A7 (enrdf_load_stackoverflow) | 1975-09-15 |
| DK141701C (enrdf_load_stackoverflow) | 1980-10-20 |
| GB1497681A (en) | 1978-01-12 |
| IL46809A (en) | 1978-04-30 |
| FI60865C (fi) | 1982-04-13 |
| IE41533L (en) | 1975-09-14 |
| FR2263774B1 (enrdf_load_stackoverflow) | 1978-08-04 |
| NL7502807A (nl) | 1975-09-16 |
| DD118428A5 (enrdf_load_stackoverflow) | 1976-03-05 |
| NO750748L (enrdf_load_stackoverflow) | 1975-09-16 |
| CA1071192A (en) | 1980-02-05 |
| IE41533B1 (en) | 1980-01-30 |
| DK141701B (da) | 1980-05-27 |
| AU500890B2 (en) | 1979-06-07 |
| AU7905775A (en) | 1976-09-16 |
| IL46809A0 (en) | 1975-07-28 |
| SE7502469L (enrdf_load_stackoverflow) | 1975-09-15 |
| FI60865B (fi) | 1981-12-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8110 | Request for examination paragraph 44 | ||
| 8131 | Rejection |