CH616672A5 - Process for the preparation of novel cyclic imides - Google Patents
Process for the preparation of novel cyclic imides Download PDFInfo
- Publication number
- CH616672A5 CH616672A5 CH636979A CH636979A CH616672A5 CH 616672 A5 CH616672 A5 CH 616672A5 CH 636979 A CH636979 A CH 636979A CH 636979 A CH636979 A CH 636979A CH 616672 A5 CH616672 A5 CH 616672A5
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- compounds
- general formula
- cyclic imides
- propyl
- Prior art date
Links
- -1 cyclic imides Chemical class 0.000 title description 3
- 238000000034 method Methods 0.000 title description 3
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CWDIBTDSBNWWNE-UHFFFAOYSA-N 2-(2,6-dioxooxan-4-yl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CC(=O)OC(=O)C1 CWDIBTDSBNWWNE-UHFFFAOYSA-N 0.000 description 1
- AKTISSCUDMXOBQ-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)pentanedioic acid Chemical group C1=CC=C2C(=O)N(C(CC(O)=O)CC(=O)O)C(=O)C2=C1 AKTISSCUDMXOBQ-UHFFFAOYSA-N 0.000 description 1
- ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101100387923 Caenorhabditis elegans dos-1 gene Proteins 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 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
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
- C07D211/88—Oxygen atoms attached in positions 2 and 6, e.g. glutarimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung neuer cyclischer Imide. Die neuen Verbindungen besitzen wertvolle therapeutische Eigenschaften und können sowohl als Arzneimittel als auch als Zwischenprodukte für die Herstellung von Arzneimitteln dienen. The present invention relates to a process for the preparation of new cyclic imides. The new compounds have valuable therapeutic properties and can serve both as pharmaceuticals and as intermediates for the production of pharmaceuticals.
Die erfindungsgemäss erhältlichen Verbindungen entsprechen der allgemeinen Formel The compounds obtainable according to the invention correspond to the general formula
Q Q
I I.
worin R für den Methyl-, Äthyl- oder n-Propylrest steht. where R represents the methyl, ethyl or n-propyl radical.
Vorzugsweise betrifft die Erfindung die Herstellung der Verbindung der allgemeinen Formel I, in der R für den n-Propylrest steht. Diese Verbindungen sind in der Lage, das Wachstum von Tumoren zu unterdrücken, wie beispielsweise durch folgende Versuchsanordnung gezeigt werden kann: The invention preferably relates to the preparation of the compound of the general formula I in which R represents the n-propyl radical. These compounds are able to suppress the growth of tumors, as can be shown, for example, by the following experimental setup:
Gibt man weiblichen Sprague-Dawley-Ratten im Gewicht von durchschnittlich 160 g an ihrem 50., 53. und 57. Lebenstag jeweils eine Dosis von 2 mg Dimethylbenzan-thracen in einer Lecithin-Emulsion intravenös, so entwik-keln sich vorwiegend im Bereich der Milchleiste Tumoren, deren Anzahl man auszählen und deren Grösse man durch Messung feststellen kann. Behandelt man Tiere, welchen auf die beschriebene Art Mammatumoren induziert wurden, mit einer Verbindung der allgemeinen Formel I, so verringern sich Tumoranzahl und Tumorgrösse im Vergleich zu den unbehandelten Kontrolltieren. If female Sprague-Dawley rats weighing an average of 160 g are given intravenously in each case a dose of 2 mg of dimethylbenzan-thracen in a lecithin emulsion on their 50th, 53rd and 57th day of life, the development mainly in the area of Milk bar tumors, the number of which can be counted and the size of which can be determined by measurement. If animals which were induced in the manner described breast tumors with a compound of the general formula I are treated, the number and size of the tumors decrease in comparison to the untreated control animals.
Tierexperimentelle Untersuchungen, bei denen die Wirksubstanzen beispielsweise in einer Dosierung von 0,25 % im Futter verabreicht wurden, zeigten, dass die Verbindungen der allgemeinen Formel I, insbesondere diejenige, in der R für den n-Propylrest steht, eine beträchtliche Hemmung des Dimethylbenzanthracen-induzierten Tumors der Ratte aufweisen. Ausserdem konnte gezeigt werden, dass die Substanzen sowohl bei oraler als auch bei introperitonealer Applikation an Mäuse oder Ratten eine relativ geringe akute Toxizität besitzen. Studies in animals, in which the active substances were administered, for example, in a dosage of 0.25% in the feed, showed that the compounds of the general formula I, in particular the one in which R represents the n-propyl radical, significantly inhibited the dimethylbenzanthracene induced tumor of the rat. In addition, it could be shown that the substances have a relatively low acute toxicity when administered orally or introperitoneally to mice or rats.
Verbindungen, in denen R für den Rest einer Mannichbase steht, sind in der DOS 1 545 706 vorbeschrieben, so z.B. das l-(MorphoIinomethyl)-4-phthalimido-piperidindion--2,6 (CG 603), über welches auch in Europ. J. Cancer, Vol. 8, 157-158 (1972) berichtet wurde. Für diese Verbindung wird eine Senkung der Tumorzentren von 2,2 auf 1,3, also eine Reduktion der Tumorzentren um 40%, bei einer Dosierung von 1,37 % im Futter angegeben. Im Gegensatz dazu senkt z.B. das erfindungsgemäss erhältliche l-(n)-Pro-pyl-4-phthalimido-piperidindion-2,6 bei einer Dosierung von 0,25%, das sind weniger als 20% der von der vorbeschriebenen Verbindung verwendeten Menge, die Tumorzentren von 4,1 auf 1,3, das ist eine Reduktion um 70%. Compounds in which R represents the rest of a Mannich base are described in DOS 1 545 706, e.g. the l- (MorphoIinomethyl) -4-phthalimido-piperidinedione - 2,6 (CG 603), about which also in Europ. J. Cancer, Vol. 8, 157-158 (1972). For this compound, a reduction in the tumor centers from 2.2 to 1.3, that is to say a reduction in the tumor centers by 40%, is stated at a dosage of 1.37% in the feed. In contrast, e.g. the l- (n) -pro-pyl-4-phthalimido-piperidinedione-2,6 obtainable according to the invention at a dosage of 0.25%, that is less than 20% of the amount used by the compound described above, the tumor centers of 4, 1 to 1.3, that's a 70% reduction.
Die erfindungsgemäss erhältlichen Verbindungen sind weiter in der Lage, vorteilhafte Wirkungen bei Störungen des Endokriniums auszuüben und eignen sich ferner zur Behandlung von Autoimmunerkrankungen. The compounds obtainable according to the invention are further able to exert advantageous effects in the event of endocrine disorders and are also suitable for the treatment of autoimmune diseases.
Die Verbindungen der allgemeinen Formel I werden hergestellt, indem man ein am Stickstoffatom durch R substituiertes Mono- oder Diamid der ß-Phthalimidoglutarsäure cyclisiert. Diese Ringschlussreaktion kann durch Erhitzen und/oder in Anwesenheit eines die Reaktion fördernden Mittels durchgeführt werden. Als solche Mittel dienen z.B. Essigsäureanhydrid, Thionylchlorid, Acetylchlorid und ähnliche, saure wasserabspaltend wirkende Mittel. The compounds of general formula I are prepared by cyclizing a mono- or diamide of β-phthalimidoglutaric acid substituted by R on the nitrogen atom. This ring closure reaction can be carried out by heating and / or in the presence of an agent promoting the reaction. Such means are e.g. Acetic anhydride, thionyl chloride, acetyl chloride and similar acidic water-releasing agents.
Die nach dem vorstehend beschriebenen Verfahren erhaltenen Verbindungen der allgemeinen Formel I können zur Herstellung von Arzneimitteln in entsprechend dosierten Arznei- und gegebenenfalls Retard-Formen für enterale oder parenterale Verabreichung verwendet werden. Gewünsch-tenfalls können sie auch mit anderen Wirkstoffen kombiniert werden. Zur Herstellung geeigneter Arzneiformen werden die Wirkstoffe mit anorganischen oder organischen pharmakologisch indifferenten Hilfsstoffen verarbeitet. The compounds of the general formula I obtained by the process described above can be used for the production of medicaments in appropriately dosed medicament and, if appropriate, sustained release forms for enteral or parenteral administration. If desired, they can also be combined with other active ingredients. To produce suitable pharmaceutical forms, the active ingredients are processed with inorganic or organic pharmacologically indifferent auxiliaries.
Die Dosierung einer Verbindung der allgemeinen Formel I in pharmazeutischen Präparaten mit tumorhemmender Wirkung beträgt 1 bis 200 mg/kg, vorzugsweise 20 bis 60 mg/kg. Die Applikation erfolgt 1 bis 5mal täglich. The dosage of a compound of general formula I in pharmaceutical preparations with an anti-tumor effect is 1 to 200 mg / kg, preferably 20 to 60 mg / kg. The application takes place 1 to 5 times a day.
Das folgende Beispiel dient zur weiteren Erläuterung der Erfindung. Die Temperaturangaben sind unkorrigiert. Bei der Durchführung des Beispiels wurden maximale Ausbeuten nicht angestrebt. The following example serves to further explain the invention. The temperature information is not corrected. Maximum yields were not sought when the example was carried out.
Beispiel example
150 g ß-Phthalimidoglutarsäure-mono-N-(n-propyl)-amid werden mit einer Mischung von 1000 ml Acetanhydrid und 120 ml Thionylchlorid versetzt und 2 Stunden zum Rück-fluss erhitzt. Man entfernt das Lösungsmittel durch Destillation im Vakuum. Der Rückstand wird aus 800 ml abs. Äthanol umkristallisiert. Man erhält so das l-n-Propyl-4--phalimido-piperidindion-2,6 vom Schmelzpunkt 137-139°C in einer Ausbeute von 123 g, das sind 87% der Theorie. A mixture of 1000 ml of acetic anhydride and 120 ml of thionyl chloride is added to 150 g of β-phthalimidoglutaric acid mono-N- (n-propyl) -amide and the mixture is heated under reflux for 2 hours. The solvent is removed by distillation in vacuo. The residue is abs from 800 ml. Recrystallized ethanol. This gives l-n-propyl-4-phalimido-piperidinedione-2,6 with a melting point of 137-139 ° C. in a yield of 123 g, which is 87% of theory.
Das als Ausgangsmaterial eingesetzte ß-Phthalimidoglutar-säure-mono-N-(n-propyl)-amid kann wie folgt erhalten werden: The ß-phthalimidoglutaric acid mono-N- (n-propyl) -amide used as the starting material can be obtained as follows:
350 g ß-Phthalimido-glutarsäureanhydrid werden in 2000 ml absolutem Dioxan aufgeschlämmt und mit 188 ml Triäthylamin versetzt. Anschliessend werden 112 ml n-Pro-pylamin, gelöst in 200 ml Dioxan, so zugetropft, dass die Reaktionstemperatur 35° nicht überschreitet. Man lässt eine Stunde nachreagieren und versetzt mit Aktivkohle. Nach Filtration wird das Lösungsmittel im Vakuum abdestilliert. Der ölige Rückstand wird in 1000 ml Wasser gelöst und mit 350 g of β-phthalimido-glutaric anhydride are slurried in 2000 ml of absolute dioxane, and 188 ml of triethylamine are added. 112 ml of n-propylamine, dissolved in 200 ml of dioxane, are then added dropwise in such a way that the reaction temperature does not exceed 35 °. The mixture is left to react for an hour and activated carbon is added. After filtration, the solvent is distilled off in vacuo. The oily residue is dissolved in 1000 ml of water and with
5 5
10 10th
15 15
20 20th
25 25th
30 30th
35 35
40 40
45 45
50 50
55 55
60 60
65 65
300 ml 18 % iger Salzsäure versetzt. Beim Stehen unter Kühlung kristallisiert das ß-Phthalimido-glutarsäure-mono--N-(n-propyl)amid in Form weisser Kristalle. Schmelzpunkt 189-191°Cnach Umkristallisation aus Wasser. Die Ausbeute beträgt 343 g, das sind 79% der Theorie. 5 In analoger Weise erhält man bei Verwendung des ent- 300 ml of 18% hydrochloric acid are added. When standing under cooling, the ß-phthalimido-glutaric acid mono - N- (n-propyl) amide crystallized in the form of white crystals. Melting point 189-191 ° C after recrystallization from water. The yield is 343 g, which is 79% of theory. 5 In an analogous way, when using the
616672 616672
sprechenden Amids der ß-Phthalimidoglutarsäure die nachstehend aufgeführten Verbindungen: speaking amide of ß-phthalimidoglutaric acid the compounds listed below:
l-Methyl-4-phthalimido-piperidindion-2,6, Schmelzpunkt 119-121° nach Umkristallisation aus Wasser. l-methyl-4-phthalimido-piperidinedione-2,6, melting point 119-121 ° after recrystallization from water.
l-Äthyi-4-phthalimido-piperidindion-2,6, Schmelzpunkt 165-167°C nach Umkristallisation aus Äthanol. l-ethyi-4-phthalimido-piperidinedione-2,6, melting point 165-167 ° C after recrystallization from ethanol.
v v
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2460304A DE2460304C2 (en) | 1974-12-20 | 1974-12-20 | 1-n-Propyl-4-phthalimido-piperidine-2,6-dione, process for its preparation and pharmaceuticals containing it |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH616672A5 true CH616672A5 (en) | 1980-04-15 |
Family
ID=5933927
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1401675A CH616671A5 (en) | 1974-12-20 | 1975-10-29 | Process for the preparation of novel cyclic imides |
| CH636979A CH616672A5 (en) | 1974-12-20 | 1979-07-09 | Process for the preparation of novel cyclic imides |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1401675A CH616671A5 (en) | 1974-12-20 | 1975-10-29 | Process for the preparation of novel cyclic imides |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS5191268A (en) |
| AT (1) | AT344696B (en) |
| BE (1) | BE836698A (en) |
| CA (1) | CA1058182A (en) |
| CH (2) | CH616671A5 (en) |
| DE (1) | DE2460304C2 (en) |
| DK (1) | DK139386C (en) |
| ES (1) | ES443648A1 (en) |
| FR (1) | FR2294704A1 (en) |
| GB (1) | GB1524237A (en) |
| IE (1) | IE42363B1 (en) |
| NL (1) | NL7514145A (en) |
| SE (1) | SE419860B (en) |
| ZA (1) | ZA756624B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL312367A (en) | 2017-01-31 | 2024-06-01 | Arvinas Operations Inc | Servalon ligands and bifunctional compounds containing them |
| AU2020405129A1 (en) | 2019-12-19 | 2022-06-23 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1545707A1 (en) * | 1965-05-08 | 1969-06-12 | Gruenenthal Chemie | Process for the preparation of dicarboximide derivatives |
| DE1545706A1 (en) * | 1965-05-08 | 1969-10-09 | Gruenenthal Chemie | Dicarboximide derivatives and processes for their preparation |
| DE1545672B2 (en) * | 1965-05-08 | 1974-11-07 | Chemie Gruenenthal Gmbh, 5190 Stolberg | Dicarboximide derivatives and processes for their preparation |
| DE1670391A1 (en) * | 1965-05-08 | 1970-11-05 | Gruenenthal Chemie | Dicarboximide derivatives and processes for their preparation |
| AT278739B (en) * | 1966-11-08 | 1970-02-10 | Kwizda Fa F Johann | Process for the preparation of new anhydrides and imides of substituted dicarboxylic acids |
-
1974
- 1974-12-20 DE DE2460304A patent/DE2460304C2/en not_active Expired
-
1975
- 1975-10-20 AT AT799575A patent/AT344696B/en not_active IP Right Cessation
- 1975-10-21 ZA ZA00756624A patent/ZA756624B/en unknown
- 1975-10-29 CH CH1401675A patent/CH616671A5/en not_active IP Right Cessation
- 1975-10-30 SE SE7512191A patent/SE419860B/en unknown
- 1975-12-01 IE IE2612/75A patent/IE42363B1/en unknown
- 1975-12-03 GB GB49626/75A patent/GB1524237A/en not_active Expired
- 1975-12-04 NL NL7514145A patent/NL7514145A/en not_active Application Discontinuation
- 1975-12-08 FR FR7537471A patent/FR2294704A1/en active Granted
- 1975-12-16 BE BE162793A patent/BE836698A/en not_active IP Right Cessation
- 1975-12-17 CA CA241,947A patent/CA1058182A/en not_active Expired
- 1975-12-18 ES ES443648A patent/ES443648A1/en not_active Expired
- 1975-12-19 JP JP50150719A patent/JPS5191268A/ja active Pending
- 1975-12-19 DK DK583475A patent/DK139386C/en active
-
1979
- 1979-07-09 CH CH636979A patent/CH616672A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE7512191L (en) | 1976-06-21 |
| FR2294704B1 (en) | 1979-09-21 |
| DK583475A (en) | 1976-06-21 |
| IE42363B1 (en) | 1980-07-30 |
| FR2294704A1 (en) | 1976-07-16 |
| BE836698A (en) | 1976-06-16 |
| NL7514145A (en) | 1976-06-22 |
| DK139386C (en) | 1979-07-23 |
| ES443648A1 (en) | 1977-05-01 |
| GB1524237A (en) | 1978-09-06 |
| CA1058182A (en) | 1979-07-10 |
| AT344696B (en) | 1978-08-10 |
| ATA799575A (en) | 1977-12-15 |
| DE2460304A1 (en) | 1976-07-01 |
| SE419860B (en) | 1981-08-31 |
| CH616671A5 (en) | 1980-04-15 |
| DE2460304C2 (en) | 1983-08-04 |
| ZA756624B (en) | 1976-09-29 |
| DK139386B (en) | 1979-02-12 |
| IE42363L (en) | 1976-06-20 |
| JPS5191268A (en) | 1976-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1695556C3 (en) | 3-alkyl-1,2,3,4,4a, 9-hexahydropyrazino [1,2-f] morphanthridine derivatives | |
| DE2356900A1 (en) | SUBSTITUTED CHROMONE-3-CARBONITRILE, CARBOXAMIDES AND CARBONIC ACIDS, THEIR SALTS AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS | |
| EP0028765B1 (en) | Alkyl-urea derivatives for the treatment of lipometabolic diseases; process for their preparation, their use in medicaments for the treatment of lipometabolic disorders, medicaments containing them, process for the preparation of the medicaments, and some alkyl-urea derivatives | |
| DE68910211T2 (en) | Estramustine ester. | |
| DE1949813B2 (en) | 3- (4-PyrWyl) -4- (2-hydroxyphenyl) -5-alkyl-pyrazoles | |
| DE2044172C3 (en) | Pyrrole derivatives, a process for their preparation and pharmaceuticals | |
| DE1967080C3 (en) | t- (3,4-Methylenedioxybeiizoyl) -2methyl-5-methoxy-3-indolylacetic acid ester, process for their preparation and medicinal preparations | |
| DE1470089A1 (en) | Process for the preparation of 3-amino-5-substituted-pyrazinoylguanidines | |
| DE2432392C3 (en) | Tris (2-hydroxyethyl) ammonium orthocresoxyacetate, process for its production and pharmaceuticals based on it | |
| DE1963317A1 (en) | Chemical processes and products | |
| CH616672A5 (en) | Process for the preparation of novel cyclic imides | |
| DE2413125C2 (en) | Indolylacetylamino acid derivatives, processes for their production and medicinal preparations containing these compounds | |
| DE1720034A1 (en) | Process for the preparation of 2-methyl-4 (3H) -pteridinones substituted in the 3-position | |
| DE2533843C2 (en) | 2H-Pyran-2,6 (3H) -dione derivatives and their use | |
| DE2513136B2 (en) | N- (I -benzylpiperid-4-yl) -benzamides, process for their preparation and pharmaceutical preparations containing them | |
| DE2213028B2 (en) | DL-3-FORMYLAMINOTHIACYCLOPENTAN-2-ON, PROCESS FOR THE PRODUCTION THEREOF, AND DL-3-FORMYLAMINO-THIACYCLOPENTAN-2-ON AND OTHER PHARMACEUTICAL COMPOSITIONS CONTAINING ACYLDER DERIVATIVES | |
| DE69124025T2 (en) | Organosilane derivatives, pharmaceutical compositions containing them and process for their preparation | |
| DE69809564T2 (en) | 2- 4- [4- (4,5-DICHLOR-2-METHYLIMIDAZOL-1-YL) BUTYL] PIPERAZIN-1-YL -5-FLUORPYRIMIDINE, ITS PRODUCTION AND THERAPEUTIC USE | |
| DE2029510B2 (en) | Dibenzofuran derivatives and their pharmaceutically acceptable acid addition salts, as well as processes for their preparation and pharmaceuticals containing these compounds | |
| DE2338350A1 (en) | BETA (3,4-DIALKANOYLOXYPHENYL) LALANINE ESTER | |
| DE2038922A1 (en) | Organic thiazolopyrimidines | |
| CH618164A5 (en) | Process for the preparation of novel 1-(2',4',6'-trihydroxphenyl)-1,2-propanedione compounds substituted in the 3-position | |
| DE1770762C3 (en) | Substituted 2-amino-hexahydrobenzo [a] quinolizines | |
| DE2354999C3 (en) | Dibenzo (b, f) azepine derivatives, processes for their preparation and pharmaceutical preparations containing these compounds | |
| DE2323555C3 (en) | N-substituted naphthalic acid imides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |