CH628049A5 - Process for the preparation of ergolene derivatives - Google Patents
Process for the preparation of ergolene derivatives Download PDFInfo
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- CH628049A5 CH628049A5 CH381477A CH381477A CH628049A5 CH 628049 A5 CH628049 A5 CH 628049A5 CH 381477 A CH381477 A CH 381477A CH 381477 A CH381477 A CH 381477A CH 628049 A5 CH628049 A5 CH 628049A5
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- preparation
- compounds
- derivatives
- ergolene derivatives
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 4
- 238000002360 preparation method Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 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
- 239000012074 organic phase Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- -1 sodium borohydride Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
628049 628049
2 2nd
PATENTANSPRUCH Verfahren zur Herstellung von neuen Ergolenderivaten der Formel I, PATENT CLAIM Process for the production of new ergole derivatives of the formula I,
? /R1 ? / R1
CH -NH-C-IT \ CH -NH-C-IT \
2 2nd
I 10 I 10
N-CH. N-CH.
» /Rl »/ Rl
CH_-NH-C-N^ CH_-NH-C-N ^
\ \
2 2nd
N-CH. N-CH.
II II
worin Ri und R? jeweils Wasserstoff oder eine Alkylgruppe mit 1 bis 4 Kohlenstoffatomen bedeuten oder aber zusammen eine Alkylidenkette mit maximal 5 Kohlenstoffatomen bilden, und deren Salze mit Säuren, dadurch gekennzeichnet, dass man eine Verbindung der Formel II, where Ri and R? each represent hydrogen or an alkyl group with 1 to 4 carbon atoms or together form an alkylidene chain with a maximum of 5 carbon atoms, and their salts with acids, characterized in that a compound of the formula II,
CH2-NH-C-N^ CH2-NH-C-N ^
N-CH. N-CH.
A A
II II
H-N H-N
worin Ri und R: obige Bedeutung haben, selektiv in Stellung 2,3 reduziert und die so erhaltenen Verbindungen der Formel I gegebenenfalls in ihre Säureadditionssalze überführt. wherein R 1 and R: have the above meaning, selectively reduced to position 2,3 and the compounds of the formula I obtained in this way optionally converted into their acid addition salts.
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen Ergolenderivaten der Formel I, The invention relates to a process for the preparation of new ergole derivatives of the formula I,
O R. O R.
« / 1 " / 1
CH -NH-C-N' CH -NH-C-N '
\ \
2 2nd
N-CH. N-CH.
H-N H-N
H-N. H-N.
worin Ri und R2 obige Bedeutung haben, selektiv in Stellung 2,3 reduziert und die so erhaltenen Verbindungen der Formel I gegebenenfalls in ihre Säureadditionssalze überführt. wherein R 1 and R 2 have the above meaning, selectively reduced to position 2,3 and the compounds of the formula I thus obtained are optionally converted into their acid addition salts.
Das Verfahren wird vorteilhafterweise ausgeführt, indem 20 man die Reduktion mittels eines komplexen Hydrides, wie beispielsweise Natriumborhydrid, in Gegenwart von Trifluor-essigsäure, durchgeführt. The process is advantageously carried out by carrying out the reduction using a complex hydride, such as sodium borohydride, in the presence of trifluoroacetic acid.
Die Reduktion kann beispielsweise bei Temperaturen von —10° bis +40°C erfolgen. Als Lösungsmittel verwendet man 25 Trifluoressigsäure, Äther, Tetrahydrofuran, Dioxan oder deren Gemische. Vorzugsweise setzt man einen 1,5 bis 10 molaren Überschuss an Natriumborhydrid ein. Zu Verbindungen der Formel I gelangt man aber auch durch Umsetzen von Verbindungen der Formel II mit überschüssigem Zink-30 staub in konzentrierter Salzsäure. The reduction can take place, for example, at temperatures from -10 ° to + 40 ° C. 25 trifluoroacetic acid, ether, tetrahydrofuran, dioxane or mixtures thereof are used as solvents. A 1.5 to 10 molar excess of sodium borohydride is preferably used. However, compounds of the formula I can also be obtained by reacting compounds of the formula II with excess zinc 30 dust in concentrated hydrochloric acid.
Die erfindungsgemäss hergestellten Verbindungen der Formel I sind bei Raumtemperatur kristalline Verbindungen, die mit anorganischen oder organischen Säuren beständige, bei Raumtemperatur kristallisierte Salze bilden. The compounds of the formula I prepared according to the invention are compounds which are crystalline at room temperature and which form stable salts which crystallize at room temperature with inorganic or organic acids.
3s Die neuen Verbindungen der Formel I, insbesondere 1,1 -Dimethyl-3-[6-methyl-2,3ß-dihydro-9-ergolen-8ß-ylmethyl]harnstoff, zeigen interessante pharmakologische Eigenschaften und können deshalb als Heilmittel Verwendung finden. 3s The new compounds of formula I, in particular 1,1 -dimethyl-3- [6-methyl-2,3ß-dihydro-9-ergolen-8ß-ylmethyl] urea, show interesting pharmacological properties and can therefore be used as medicines.
40 Sie zeichnen sich in der pharmakologischen Prüfung durch ausgeprägte antihypertensive Wirkung aus, wie an der wachen hypertonen Grollmannratte sowie am wachen hyper-tonen Goldblatthund mit Dosen von 0,05 bis 0,5 mg pro kg Körpergewicht des Testtieres festgestellt wurde. Ihre Anwen-45 dung bei Hypertonien jeglicher Genese ist dadurch angezeigt. 40 They are characterized in the pharmacological test by their pronounced antihypertensive effect, as was found in the awake hypertonic Grollmann rat and the awake hyper-toned gold leaf dog with doses of 0.05 to 0.5 mg per kg body weight of the test animal. Their use in hypertension of any origin is indicated.
Die zu verwendenden Dosen variieren naturgemäss je nach Art der Applikation und des zu behandelnden Zustandes. Im allgemeinen werden befriedigende Resultate erreicht mit einer täglichen Dosis von 0,01 bis 2,5 mg pro kg Körperge-50 wicht des Testtieres; diese Dosis kann nötigenfalls in 2 bis 3 Anteilen oder auch als Retardform verabreicht werden. Für grössere Säugetiere liegt die Tagesdosis bei etwa I bis 200 mg. Für orale Applikationen enthalten die Teildosen etwa 0,5 bis 100 mg der Verbindung neben festen oder flüssigen Träger-55 substanzen oder Verdünnungsmitteln. The doses to be used naturally vary depending on the type of application and the condition to be treated. In general, satisfactory results are achieved with a daily dose of 0.01 to 2.5 mg per kg of body weight of the test animal; if necessary, this dose can be administered in 2 to 3 portions or as a slow-release form. For larger mammals, the daily dose is around I to 200 mg. For oral applications, the partial doses contain about 0.5 to 100 mg of the compound in addition to solid or liquid carrier substances or diluents.
Die neuen Verbindungen der Formel I können als Arzneimittel allein oder in entsprechenden Arzneiformen für orale, enterale oder parenterale Verabreichung verwendet werden. The new compounds of the formula I can be used as pharmaceuticals alone or in appropriate pharmaceutical forms for oral, enteral or parenteral administration.
In dem nachfolgenden Beispiel, welches die Erfindung so näher erläutert, ihren Umfang aber in keiner Weise einschränken soll, erfolgen alle Temperaturangaben in Celsiusgraden. In the following example, which explains the invention in greater detail but is not intended to restrict its scope in any way, all the temperatures are given in degrees Celsius.
worin Ri und R: jeweils Wasserstoff oder eine Alkylgruppe Beispiel: where Ri and R: each hydrogen or an alkyl group Example:
mit 1 bis 4 Kohlenstoffatomen bedeuten oder aber zusammen r.s 1,1 -Dimethyl-3-[6-methyl-2,3ß-dihydro-9-ergolen-8ß- with 1 to 4 carbon atoms or together r.s 1,1 -dimethyl-3- [6-methyl-2,3ß-dihydro-9-ergolen-8ß-
eine Alkylidenkette mit maximal 5 Kohlenstoffatomen ylmethyl]harnstoff-hyxdrogenfumarat bilden, und deren Salze mit Säuren, dadurch gekennzeichnet, 10,5 g l,l-Dimethyl-3-[6-methyl-9-ergolen-8ß- form an alkylidene chain with a maximum of 5 carbon atoms ylmethyl] urea-hydrogen fumarate, and their salts with acids, characterized, 10.5 g l, l-dimethyl-3- [6-methyl-9-ergolen-8ß-
dass man eine Verbindung der Formel II, ylmethyl]harnstoff (32,4 mM) werden in 115 ml Trifluoressig- that a compound of formula II, ylmethyl] urea (32.4 mM) are in 115 ml of trifluoroacetic acid
säure gelöst. Portionenweise gibt man 1,95 g Natriumborhy-drid (5 l,5mM) zu. Nach beendeter Natriumborhydrid-Zugabe wird 20 Minuten bei Zimmertemperatur gerührt und anschliessend auf Eis/Wasser gegossen. Unter starkem Rühren gibt man festes Kaliumcarbonat zu, bis die Suspension pH 8 erreicht und schüttelt dreimal mit Methylenchlorid aus. Die vereinigten, organischen Phasen werden mit Natriumsulfat getrocknet, filtriert und eingedampft. Es resultieren 4,5 g beiger Schaum, die an 120 g Kieselgel H (Typ 60) mit Methylenchlorid/Methanol (9:1) +0,3% NH? (konz.) chro- acid dissolved. 1.95 g of sodium borohydride (5 l, 5 mM) are added in portions. After the sodium borohydride addition has ended, the mixture is stirred at room temperature for 20 minutes and then poured onto ice / water. Solid potassium carbonate is added with vigorous stirring until the suspension reaches pH 8 and shaken out three times with methylene chloride. The combined organic phases are dried with sodium sulfate, filtered and evaporated. The result is 4.5 g of beige foam, which on 120 g of silica gel H (type 60) with methylene chloride / methanol (9: 1) + 0.3% NH? (conc.) chro-
3 628049 3 628049
matographiert werden. Die resultierenden 1,6 g werden in Aceton gelöst und mit einer Lösung von 0,55 g Fumarsäure in Aceton versetzt, wobei die Titelverbindung ausfällt. be matographed. The resulting 1.6 g are dissolved in acetone and a solution of 0.55 g of fumaric acid in acetone is added, the title compound precipitating.
s Smp: ab 120° (Zers.) s MP: from 120 ° (dec.)
[aß1 = +20,9° (c = 0,44 in Äthanol/Wasser[l:l]). [aß1 = + 20.9 ° (c = 0.44 in ethanol / water [l: l]).
NMR (CDCb): 6,92 (m, 2H); 6,49 (m, 1H); 6,28 (s, 1H); 4,69 (t, 1 H, J = 6); 4,5 (m, breit, 1H); 2,90 (s, 6H); 2,55 (s, 3 H); 1,45 io (q, IH, J = 11). NMR (CDCb): 6.92 (m, 2H); 6.49 (m, 1H); 6.28 (s. 1H); 4.69 (t, 1H, J = 6); 4.5 (m, broad, 1H); 2.90 (s, 6H); 2.55 (s, 3H); 1.45 io (q, IH, J = 11).
» »
Priority Applications (20)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH381477A CH628049A5 (en) | 1977-03-25 | 1977-03-25 | Process for the preparation of ergolene derivatives |
| DE19782810774 DE2810774A1 (en) | 1977-03-25 | 1978-03-13 | ERGOT DERIVATIVES, THEIR USE AND PRODUCTION |
| DK119778A DK147072C (en) | 1977-03-25 | 1978-03-16 | ANALOGY PROCEDURE FOR THE PREPARATION OF ERGOLEND DERIVATIVES |
| FI780835A FI66375C (en) | 1977-03-25 | 1978-03-16 | PROCEDURE FOR FRAMSTATING AVIA THERAPEUTIC ANVAENDBARA 2,3BETA-DIHYDRO-8BETA-ERGOLENYLMETHYL-UREA-DERIVAT OCH DERAS SYRAADDITIONSSALTER |
| SE7803040A SE7803040L (en) | 1977-03-25 | 1978-03-16 | NEW ORGANIC ASSOCIATIONS, THEIR PREPARATION AND USE |
| GB11112/78A GB1596210A (en) | 1977-03-25 | 1978-03-21 | N-(2,3-dihydro-9-ergolen-8-ylmethyl) ureas |
| NL7803031A NL7803031A (en) | 1977-03-25 | 1978-03-21 | ENERGY DERIVATIVES AND METHODS FOR PREPARING AND USING THESE DERIVATIVES. |
| ES468133A ES468133A1 (en) | 1977-03-25 | 1978-03-22 | N-(2,3-dihydro-9-ergolen-8-ylmethyl) ureas |
| ZA00781714A ZA781714B (en) | 1977-03-25 | 1978-03-23 | Improvements in or relating to organic compounds |
| NZ186775A NZ186775A (en) | 1977-03-25 | 1978-03-23 | 3-(6-alkyl-2,3 -dihydroergol-9-en-8 -ylmethyl)-ureas |
| AU34483/78A AU520738B2 (en) | 1977-03-25 | 1978-03-23 | 8-ureidomethyl ergoline derivatives |
| IE580/78A IE46688B1 (en) | 1977-03-25 | 1978-03-23 | N-(2,3 -dihydro-9-ergolen-8 -yl methyl)ureas |
| IT48557/78A IT1104183B (en) | 1977-03-25 | 1978-03-23 | DERIVATIVES OF THE SIGNAL RUN THEIR PREPARATION AND THEIR APPLICATION AS MEDICATIONS (CASE 100-4781) |
| CA299,678A CA1105009A (en) | 1977-03-25 | 1978-03-23 | Ergot derivatives |
| PT67816A PT67816A (en) | 1977-03-25 | 1978-03-23 | PROCESS FOR THE PREPARATION OF NOVEL ORGANIC COMPOUNDS WITH PHARMACEUTICAL EFFECT |
| BE186239A BE865267A (en) | 1977-03-25 | 1978-03-23 | NEW DERIVATIVES OF RYE ERGOT, THEIR PREPARATION AND THEIR APPLICATION AS MEDICINAL PRODUCTS |
| AT0207078A AT366685B (en) | 1977-03-25 | 1978-03-23 | METHOD FOR PRODUCING NEW ERGOT DERIVATIVES |
| IL54342A IL54342A (en) | 1977-03-25 | 1978-03-23 | 2,3 -dihydroergolen-8 -ylmethylurea derivatives, their production and pharmaceutical compositions containing them |
| JP3316578A JPS53119898A (en) | 1977-03-25 | 1978-03-24 | Improvement in organic compound |
| SU782595601A SU1053755A3 (en) | 1977-03-25 | 1978-03-24 | Process for preparing ergoline derivatives or their salts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH381477A CH628049A5 (en) | 1977-03-25 | 1977-03-25 | Process for the preparation of ergolene derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH628049A5 true CH628049A5 (en) | 1982-02-15 |
Family
ID=4264035
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH381477A CH628049A5 (en) | 1977-03-25 | 1977-03-25 | Process for the preparation of ergolene derivatives |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS53119898A (en) |
| AT (1) | AT366685B (en) |
| AU (1) | AU520738B2 (en) |
| BE (1) | BE865267A (en) |
| CA (1) | CA1105009A (en) |
| CH (1) | CH628049A5 (en) |
| DE (1) | DE2810774A1 (en) |
| DK (1) | DK147072C (en) |
| ES (1) | ES468133A1 (en) |
| FI (1) | FI66375C (en) |
| GB (1) | GB1596210A (en) |
| IE (1) | IE46688B1 (en) |
| IL (1) | IL54342A (en) |
| IT (1) | IT1104183B (en) |
| NL (1) | NL7803031A (en) |
| NZ (1) | NZ186775A (en) |
| PT (1) | PT67816A (en) |
| SE (1) | SE7803040L (en) |
| SU (1) | SU1053755A3 (en) |
| ZA (1) | ZA781714B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3205169A1 (en) * | 1981-02-24 | 1982-10-14 | Sandoz-Patent-GmbH, 7850 Lörrach | NEW ERGOL DERIVATIVES, THEIR PRODUCTION AND THEIR PHARMACEUTICAL COMPOSITIONS |
| DE3411981A1 (en) * | 1984-03-28 | 1985-10-10 | Schering AG, Berlin und Bergkamen, 1000 Berlin | METHOD FOR PRODUCING 2.3-DIHYDROERGOLINES |
| GB2173189B (en) * | 1985-02-21 | 1988-04-27 | Maruko Pharmaceutical Co | Ergoline derivatives and salts thereof and pharmaceutical compositions thereof |
| 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 |
-
1977
- 1977-03-25 CH CH381477A patent/CH628049A5/en not_active IP Right Cessation
-
1978
- 1978-03-13 DE DE19782810774 patent/DE2810774A1/en not_active Withdrawn
- 1978-03-16 SE SE7803040A patent/SE7803040L/en unknown
- 1978-03-16 DK DK119778A patent/DK147072C/en not_active IP Right Cessation
- 1978-03-16 FI FI780835A patent/FI66375C/en not_active IP Right Cessation
- 1978-03-21 NL NL7803031A patent/NL7803031A/en not_active Application Discontinuation
- 1978-03-21 GB GB11112/78A patent/GB1596210A/en not_active Expired
- 1978-03-22 ES ES468133A patent/ES468133A1/en not_active Expired
- 1978-03-23 IT IT48557/78A patent/IT1104183B/en active
- 1978-03-23 IL IL54342A patent/IL54342A/en unknown
- 1978-03-23 PT PT67816A patent/PT67816A/en unknown
- 1978-03-23 IE IE580/78A patent/IE46688B1/en unknown
- 1978-03-23 AU AU34483/78A patent/AU520738B2/en not_active Expired
- 1978-03-23 CA CA299,678A patent/CA1105009A/en not_active Expired
- 1978-03-23 ZA ZA00781714A patent/ZA781714B/en unknown
- 1978-03-23 AT AT0207078A patent/AT366685B/en not_active IP Right Cessation
- 1978-03-23 BE BE186239A patent/BE865267A/en not_active IP Right Cessation
- 1978-03-23 NZ NZ186775A patent/NZ186775A/en unknown
- 1978-03-24 JP JP3316578A patent/JPS53119898A/en active Pending
- 1978-03-24 SU SU782595601A patent/SU1053755A3/en active
Also Published As
| Publication number | Publication date |
|---|---|
| IL54342A0 (en) | 1978-06-15 |
| BE865267A (en) | 1978-09-25 |
| IL54342A (en) | 1981-02-27 |
| FI66375C (en) | 1984-10-10 |
| DK147072C (en) | 1984-09-10 |
| DE2810774A1 (en) | 1978-10-05 |
| DK147072B (en) | 1984-04-02 |
| SU1053755A3 (en) | 1983-11-07 |
| AU3448378A (en) | 1979-09-27 |
| SE7803040L (en) | 1978-09-26 |
| CA1105009A (en) | 1981-07-14 |
| FI780835A (en) | 1978-09-26 |
| IE780580L (en) | 1978-09-25 |
| IT7848557A0 (en) | 1978-03-23 |
| ES468133A1 (en) | 1980-06-16 |
| DK119778A (en) | 1978-09-26 |
| IT1104183B (en) | 1985-10-21 |
| ATA207078A (en) | 1981-09-15 |
| IE46688B1 (en) | 1983-08-24 |
| JPS53119898A (en) | 1978-10-19 |
| FI66375B (en) | 1984-06-29 |
| AU520738B2 (en) | 1982-02-25 |
| PT67816A (en) | 1978-04-01 |
| GB1596210A (en) | 1981-08-19 |
| AT366685B (en) | 1982-04-26 |
| NL7803031A (en) | 1978-09-27 |
| NZ186775A (en) | 1980-12-19 |
| ZA781714B (en) | 1979-11-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |