DE3000901A1 - Anxiolytic and neuroleptic ergoline derivs. - prepd. from 8-beta-bromo-acetyl-ergoline and a piperazine - Google Patents
Anxiolytic and neuroleptic ergoline derivs. - prepd. from 8-beta-bromo-acetyl-ergoline and a piperazineInfo
- Publication number
- DE3000901A1 DE3000901A1 DE19803000901 DE3000901A DE3000901A1 DE 3000901 A1 DE3000901 A1 DE 3000901A1 DE 19803000901 DE19803000901 DE 19803000901 DE 3000901 A DE3000901 A DE 3000901A DE 3000901 A1 DE3000901 A1 DE 3000901A1
- Authority
- DE
- Germany
- Prior art keywords
- ergoline
- acetylergoline
- group
- piperazine
- beta
- 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.)
- Withdrawn
Links
- 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 title abstract description 3
- 239000002249 anxiolytic agent Substances 0.000 title abstract description 3
- 230000000949 anxiolytic effect Effects 0.000 title abstract description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title abstract 4
- 239000003176 neuroleptic agent Substances 0.000 title 1
- 230000000701 neuroleptic effect Effects 0.000 title 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- PIINXYKJQGMIOZ-UHFFFAOYSA-N 1,2-dipyridin-2-ylethane-1,2-dione Chemical group C=1C=CC=NC=1C(=O)C(=O)C1=CC=CC=N1 PIINXYKJQGMIOZ-UHFFFAOYSA-N 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 239000003586 protic polar solvent Substances 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 abstract description 2
- 125000004076 pyridyl group Chemical group 0.000 abstract description 2
- 229940005530 anxiolytics Drugs 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229940025084 amphetamine Drugs 0.000 description 3
- 230000002631 hypothermal effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- IXRNQIKIVWWFBH-UHFFFAOYSA-N n-(1-phenylethenyl)acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC=C1 IXRNQIKIVWWFBH-UHFFFAOYSA-N 0.000 description 1
- UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 1
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61P25/20—Hypnotics; Sedatives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Anesthesiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (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)
Abstract
Description
Ergolinderivate, deren Herstellung und Verwendung.Ergoline derivatives, their production and use.
Die Erfindung bezieht sich auf Sj3-Acetylergolin-Derivate und ein Verfahren zu deren Herstellung.The invention relates to Sj3-acetylergoline derivatives and a Process for their manufacture.
Die Erfindung schafft 8ß-Acetylergolin-Derivate der aligemeinen Formel I worin R ein Wasserstoffatom oder eine Methylgruppe, R1 ein Wasserstoffatom oder eine Methoxygruppe und R2 eine Pyridyl-, Pyrazinyl- oder Pyridazinylgruppe, eine unsubstituierte oder substituierte Phenylgruppe, in welcher die Substituenten Chlor-, Brom- oder Fluoratome, Alkoxygruppen mit 1- 4 Kohlenstoffatomen und Methyl- und die Trifluormethylgruppe sein können, bedeuten,sowie deren pharmazeutisch verwendbaren Additionssalze (Säureadditionssalze).The invention provides 8β-acetylergoline derivatives of the general formula I. wherein R is a hydrogen atom or a methyl group, R1 is a hydrogen atom or a methoxy group and R2 is a pyridyl, pyrazinyl or pyridazinyl group, an unsubstituted or substituted phenyl group in which the substituents are chlorine, bromine or fluorine atoms, alkoxy groups with 1-4 carbon atoms and Methyl and the trifluoromethyl group can be, as well as their pharmaceutically acceptable addition salts (acid addition salts).
Substituent R2 als Alkoxy-substituierte Phenylgruppe kann also eine Phenylgruppe sein, die mit den Resten Methoxy, Athoxy, n-Propoxy, i-Propoxy, n-Butoxy und i-Butoxy substituiert sein.Substituent R2 as an alkoxy-substituted phenyl group can therefore be a Be a phenyl group with the radicals methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy and i-butoxy may be substituted.
Die Erfindung schafft auch ein Verfahren zur Herstellung von 8ß-Acetylergolin-Derivaten der allgemeinen Formel I, wobei das Verfahren das Umsetzen eines 8ß-Bromacetyl-6-methylergolin (beschrieben in der belgischen PS 861480) mit einer nukleophilen Verbindung der allgemeinen Formel II umfaßt, worin R2 wie oben definiert ist. Die Reaktion kann sowohl in Anwesenheit einer Base wie Trimethylamin oder Kaliumcarbonat als auch in Abwesenheit einer Base erfolgen. Die Umsetzung erfolgt in einem Lösungsmittel, wie z. B. Methanol, Athanol, Aceton, Dimethylformamid oder Chloroform bei einer Temperatur von etwa 25 0C - 60 0C für eine Dauer von 1 - 4 Stunden.The invention also provides a process for the preparation of 8ß-acetylergoline derivatives of the general formula I, the process comprising reacting an 8ß-bromoacetyl-6-methylergoline (described in Belgian PS 861480) with a nucleophilic compound of the general formula II wherein R2 is as defined above. The reaction can take place either in the presence of a base such as trimethylamine or potassium carbonate or in the absence of a base. The reaction takes place in a solvent, such as. B. methanol, ethanol, acetone, dimethylformamide or chloroform at a temperature of about 25 0C - 60 0C for a period of 1 - 4 hours.
Die Produkte können mit bekannten Verfahren isoliert und gereinigt werden, z. B. mithilfe der Chromatographie und/oder Kristallisation als freie Basen oder als Salze der pharmazeutisch verwendbaren Säuren.The products can be isolated and purified using known methods be e.g. B. using chromatography and / or crystallization as free bases or as salts of the pharmaceutically acceptable acids.
Die erfindungsgemäßen Verbindungen und deren pharmazeutisch verwendbare Additionssalze finden Verwendung als anxiolytische und neurolytische Mittel.The compounds according to the invention and their pharmaceutically usable ones Addition salts find use as anxiolytic and neurolytic agents.
Die Wirkungsprofile der zentralen sedativen pharmakologischen Aktivität erhält man von Irwin's Beobachtungen des Verhaltens von Mäusen (Irwin S., Psychopharmacologia, Berl., 13, 222, 1968), wobei auch Angaben der orientativen akuten Toxizität nach 7 Tagen der Beobachtung erhalten werden, sowie durch Antagonismus hinsichtlich zentral Amphetamin-induzierter Hypothermia. Die Ergebnisse einiger erfindungsgemäßer Verbindungen werden in Tabelle 1 angegeben.The action profiles of the central sedative pharmacological activity is obtained from Irwin's observations of the behavior of mice (Irwin S., Psychopharmacologia, Berl., 13, 222, 1968), with information on orientative acute toxicity as well 7 days of observation can be obtained, as well as by antagonism regarding central Amphetamine-induced hypothermia. The results of some compounds of the invention are given in Table 1.
Zur Feststellung des Antagonismus hinsichtlich der zentralen Amphetamin-induzierten Hypothermia (Janssen P.A.J. , Niemegeers C.J.E., Schellekens K.H.L. und Lenaerts F., Arzneimittelforsch. 17, (7) 841, 1967) wurden die Verbindungen männlichen Mäusen oral verabreicht und zwar in einer Dosis zwischen 1 -10 mg/kg, 30 Minuten vor der intraperitonealen Injektion von 10 mg/kg d-Amphetaminsulfat. Der Antagonismus hinsichtlich Hypothermia wurde 60 Minuten nach der Amphitamingabe ausgewertet.To determine the antagonism in terms of the central amphetamine-induced Hypothermia (Janssen P.A.J., Niemegeers C.J.E., Schellekens K.H.L. and Lenaerts F., drug research. 17, (7) 841, 1967) the compounds became male mice administered orally at a dose between 1 -10 mg / kg, 30 minutes before intraperitoneal injection of 10 mg / kg d-amphetamine sulfate. The antagonism regarding Hypothermia was scored 60 minutes after the amphitamine administration.
Die erfindungsgemäßen Verbindungen erwiesen sich auch bis zu einer oralen Dosis von 25 mg/kg als inaktiv bei der Induktion von Muskelrelaxation (Irwin's Versuch bei Mäusen) und motorischer 1 nkoord in at ion "Rotarod''-Versuch bei Ratten).The compounds of the invention were also found to be up to one oral dose of 25 mg / kg as inactive in inducing muscle relaxation (Irwin's Experiment in mice) and motor coordination in at ion "Rotarod" experiment in rats).
Die Referenzzahlen der Verbindungen werden in den nachfolgenden Beispielen erklärt.The reference numbers of the compounds are given in the examples below explained.
Tabelle 1
Beispiel 1 6-Methyl-8ß-(4'-phenylpiperazin)-acetylergolin (355/1083) Eine Lösung von 2,5 g 88-Bromacetyl-6-methylergolin und 2,34 g N-Phenylpiperazin in 30 ml Äthanol ließ man 4 Stunden bei Raumtemperatur stehen. Die Lösung wurde dann im Vakuum verdampft und der Rückstand mit Chlorofrom aufgenommen und mit Wasser gewaschen. Nach Verdampfen des Lösungsmittels im Vakuum wurde der Rückstand chromatographisch an einer Silikagel-Säule mithilfe einer Mischung von Chloroform : Methanol (99 : 1 Volumenverhältnis) als Eluent untersucht. Die Fraktionen, die das gleiche Produkt enthielten, wurden kombiniert und mit 2 Mole Methansulfonsäure behandelt. Das erhaltene Salz wurde aus Äthanol umkristallisiert und ergab 3 g 6-Methyl-8ß-(4'-phenylpiperazin)-acetylergolin-bis-methansulfonat, Kp. 219 - 221 OC Beispiel 2 6-Methyl-8ß-t4'-(p.chlorphenyl)-piperazi7-acetylergolin (355/1084) Man verfuhr wie in Beispiel 1, jedoch wurde N-(p.Chlorphenyl) piperazin verwendet. Man erhielt das Bis-Methansulfonat der Titelverbindung in 60 %iger Ausbeute; Schmelzpunkt: 242 -2440 C.Example 1 6-methyl-8ß- (4'-phenylpiperazine) acetylergoline (355/1083) A solution of 2.5 g of 88-bromoacetyl-6-methylergoline and 2.34 g of N-phenylpiperazine in 30 ml of ethanol the mixture was left to stand for 4 hours at room temperature. The solution was then evaporated in vacuo and the residue taken up with chlorofrom and washed with water washed. After evaporating the solvent in vacuo, the residue was chromatographed on a silica gel column using a mixture of chloroform: methanol (99: 1 volume ratio) as an eluent. The fractions that have the same product were combined and treated with 2 moles of methanesulfonic acid. The received Salt was recrystallized from ethanol and gave 3 g of 6-methyl-8ß- (4'-phenylpiperazine) -acetylergoline-bis-methanesulfonate, Bp. 219-221 OC Example 2 6-Methyl-8β-t4 '- (p.chlorphenyl) -piperazi7-acetylergoline (355/1084) The procedure was as in Example 1, except that N- (p-chlorophenyl) piperazine was used used. The bis-methanesulfonate of the title compound was obtained in 60% yield; Melting point: 242-2440 C.
Beispiel 3 6-Methyl-8f3-£4'-(p.methoxyphenyl)-piperazin7-acetylergolin (355/1087) Es wurde wie in Beispiel 1 verfahren, jedoch wurde N-(p.Methoxyphenyl)-piperazin verwendet; man erhielt das Bis-Methansulfonat der Titelverbindung in 65 %iger Ausbeute; Schmelzpunkt: 216 - 2180 C.Example 3 6-Methyl-8f3- £ 4 '- (p.methoxyphenyl) -piperazine-7-acetylergoline (355/1087) The procedure was as in Example 1, except that N- (p.Methoxyphenyl) -piperazine used; the bis-methanesulfonate of the title compound was obtained in 65% yield; Melting point: 216-2180 C.
Beispiel 4 1g6-Dimethyl-8ß-/4'(p.chlorphenyl)-piperazin7-acetylergolin Man arbeitete wie in Beispiel 2, jedoch wurde 8ß-Bromacetyl-1,6-dimethylergolin verwendet. Man erhielt das Bis-Methansulfonat der Titelverbindung in 60 %iger Ausbeute; Schmelzpunkt: 256 - 2580 C.Example 4 1g6-Dimethyl-8β- / 4 '(p.chlorphenyl) -piperazine-7-acetylergoline The procedure was as in Example 2, except that 8β-bromoacetyl-1,6-dimethylergoline was used used. The bis-methanesulfonate of the title compound was obtained in 60% yield; Melting point: 256-2580 C.
Beispiel 5 6-Methyl-10-methoxy-8ß-(4'-phenylpiperazin)-acetylergolin Man verfuhr wie in Beispiel 1, verwendete jedoch 8ß-Bromacetyl-6-methyl-10-methoxyergolin und erhielt das Bis-Methansulfonat der Titelverbindung in 70 %iger Ausbeute.Example 5 6-methyl-10-methoxy-8β- (4'-phenylpiperazine) acetylergoline The procedure was as in Example 1, except that 8β-bromoacetyl-6-methyl-10-methoxyergoline was used and obtained the bis-methanesulfonate of the title compound in 70% yield.
Beispiel 6 1,6-Dimethyl-10-methoxy-8ß-(4'-phenylpiperazin)-acetylergolin Es wurde wie in Beispiel 1 verfahren, jedoch wurde 8ß-Bromacetyl-1,6-dimethyl-10-methoxyergolin verwendet. Man erhielt das Bis-Methansulfonat der Titelverbindung in 67 %iger Ausbeute.Example 6 1,6-Dimethyl-10-methoxy-8β- (4'-phenylpiperazine) acetylergoline The procedure was as in Example 1, except that 8β-bromoacetyl-1,6-dimethyl-10-methoxyergoline was used used. The bis-methanesulfonate of the title compound was obtained in 67% yield.
Beispiel 7 6-Methyl -8ß-[4'-(2'-pyridyl)-piperazin]-actylergolin Man arb-eitete wie in Beispiel 1, verwendete jedoch N-(2-Pyridyl)-ei perazin und erhielt das Bis-Methansulfonat der Titelverbindung in 60 %iger Ausbeute,Example 7 6-Methyl-8ß- [4 '- (2'-pyridyl) -piperazine] -actylergoline Man Worked as in Example 1, but used N- (2-pyridyl) -ei perazine and obtained the bis-methanesulfonate of the title compound in 60% yield,
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7906023 | 1979-02-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3000901A1 true DE3000901A1 (en) | 1980-08-28 |
Family
ID=10503318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803000901 Withdrawn DE3000901A1 (en) | 1979-02-20 | 1980-01-11 | Anxiolytic and neuroleptic ergoline derivs. - prepd. from 8-beta-bromo-acetyl-ergoline and a piperazine |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS55113779A (en) |
| BE (1) | BE879822A (en) |
| DE (1) | DE3000901A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0197241A1 (en) * | 1985-01-16 | 1986-10-15 | FARMITALIA CARLO ERBA S.r.l. | Piperazin-1-yl-ergoline derivatives, process for preparing them and pharmaceutical compositions containing them |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3138844A1 (en) | 2018-05-07 | 2019-11-14 | Neuroceuticals Inc. | Medical tube position confirmation system |
| ES3041572T3 (en) | 2018-09-20 | 2025-11-13 | Otsuka Clinical Solutions Inc | Medical tube position confirmation system |
| CA3156565A1 (en) | 2019-10-31 | 2021-05-06 | Shinya Miike | Medical tube position confirmation system |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3583991A (en) * | 1968-01-18 | 1971-06-08 | Sandoz Ltd | 6-methyl-8-piperazinyl-methylergalene (ergoline) derivatives |
| DE2754028A1 (en) * | 1976-12-06 | 1978-06-08 | Farmaceutici Italia | ERGOLIN DERIVATIVES, METHOD FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS |
-
1979
- 1979-11-05 BE BE0/197964A patent/BE879822A/en not_active IP Right Cessation
-
1980
- 1980-01-11 DE DE19803000901 patent/DE3000901A1/en not_active Withdrawn
- 1980-02-20 JP JP1928980A patent/JPS55113779A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3583991A (en) * | 1968-01-18 | 1971-06-08 | Sandoz Ltd | 6-methyl-8-piperazinyl-methylergalene (ergoline) derivatives |
| DE2754028A1 (en) * | 1976-12-06 | 1978-06-08 | Farmaceutici Italia | ERGOLIN DERIVATIVES, METHOD FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0197241A1 (en) * | 1985-01-16 | 1986-10-15 | FARMITALIA CARLO ERBA S.r.l. | Piperazin-1-yl-ergoline derivatives, process for preparing them and pharmaceutical compositions containing them |
| US4728649A (en) * | 1985-01-16 | 1988-03-01 | Farmitalia Carlo Erba | 3-oxo-piperazin-1-yl-ergolines exhibiting antidopaminergic activity |
Also Published As
| Publication number | Publication date |
|---|---|
| BE879822A (en) | 1980-03-03 |
| JPS55113779A (en) | 1980-09-02 |
| JPS6245870B2 (en) | 1987-09-29 |
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