DE2924011C2 - Pyrrolidin- (2) -one- (1) -ylacetic acid-2,6, -dimethylanilide, process for the preparation and medicaments containing this compound - Google Patents
Pyrrolidin- (2) -one- (1) -ylacetic acid-2,6, -dimethylanilide, process for the preparation and medicaments containing this compoundInfo
- Publication number
- DE2924011C2 DE2924011C2 DE19792924011 DE2924011A DE2924011C2 DE 2924011 C2 DE2924011 C2 DE 2924011C2 DE 19792924011 DE19792924011 DE 19792924011 DE 2924011 A DE2924011 A DE 2924011A DE 2924011 C2 DE2924011 C2 DE 2924011C2
- Authority
- DE
- Germany
- Prior art keywords
- deep
- pyrrolidin
- ylacetic acid
- dimethylanilide
- cerebral
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Die Erfindung betrifft das Pyrrolidin-(2)-on-(1)-ylessigsäure-2,6-dimethylanilid, ein neues Arzneimittel mit zerebralprotektiver Wirkung.The invention relates to pyrrolidin- (2) -one- (1) -ylacetic acid-2,6-dimethylanilide, a new medicament with a cerebral protective effect.
Die Pharmakoprophylaxe sowie die Therapie von Krankheiten infolge zerebraler Mangeldurchblutung, hirnatrophischer Krisen sowie zerebraler Alterungsvorgänge gewinnen in letzter Zeit immer mehr an Bedeutung, und es hat bis heute nicht an Versuchen gefehlt, vasotrope und stoffwechselregulierende Verbindungen aufzufinden, die die hier angesprochenen Krankheiten im gewünschten Sinne beeinflussen. Doch konnte durch medikamentöse Behandlung mit Nootropica, zentralen Vasotropica u.a. Therapeutica eine entscheidende Verbesserung nicht erreicht werden.Pharmacoprophylaxis and the therapy of diseases caused by insufficient cerebral blood flow, cerebral atrophic crises and cerebral aging processes have recently become more and more important, and there has been no lack of attempts to find vasotropic and metabolism-regulating compounds that influence the diseases discussed here in the desired sense . However, a decisive improvement could not be achieved through drug treatment with nootropics, central vasotropics and other therapeutic agents.
Es wurde nun überraschenderweise gefunden, daß Pyrrolidin-(2)-on-(1)-ylessigsäure-2,6-dimethylanilid vasoaktive und stoffwechselregulierende Eigenschaften in sich vereinigt, die es zur Behandlung zerebraler Durchblutungsstörungen bis hin zur Migräne, hirnatrophischer Krisen sowie zerebraler Alterungsvorgänge und anderen zerebralen Erkrankungen geeignet macht. Dies ist um so überraschender, als das in der Literatur (Brit. Pat. 10 39 113) bekannte Pyrrolidin-(2)-on-(1)-ylessigsäureanilid keine dieser Wirkungen zeigt.It has now surprisingly been found that pyrrolidin- (2) -one- (1) -ylacetic acid-2,6-dimethylanilide combines vasoactive and metabolism-regulating properties, which are used in the treatment of cerebral circulatory disorders up to migraines, cerebral atrophic crises and cerebral aging processes and other cerebral diseases. This is all the more surprising since the pyrrolidin- (2) -one- (1) -ylacetic anilide known in the literature (Brit. Pat. 10 39 113) does not show any of these effects.
Die erfindungsgemäße Verbindung wird erhalten, indem man in an sich bekannter Weise Pyrrolidin-(2)-on-(1)-ylessigsäure und 2,6-Dimethylanilin zusammen mit N,N'-Dicyclohexylcarbodiimid in organischen Lösungsmitteln, wie Chloroform, Dichlormethan, Tetrahydrofuran, Acetonitril oder Essigsäureäthylester bei Temperaturen zwischen 0°C und der Siedetemperatur des jeweiligen Lösungsmittels umsetzt.The compound according to the invention is obtained by adding pyrrolidin- (2) -one- (1) -ylacetic acid and 2,6-dimethylaniline together with N, N'-dicyclohexylcarbodiimide in organic solvents such as chloroform, dichloromethane, tetrahydrofuran in a manner known per se Reacts acetonitrile or ethyl acetate at temperatures between 0 ° C and the boiling point of the respective solvent.
Ferner eignen sich zur Gewinnung der erfindungsgemäßen Verbindung die üblichen Herstellungsverfahren für Amide, wie z.B. das Verfahren über gemischte Anhydride unter Verwendung von Chlorameisensäureester, sowie die Verwendung aktivierter Ester der Pyrrolidin-(2)-on-(1)-ylessigsäure, wie z.B. Nitrophenylester, Cyanmethylester oder Trichlorphenylester, oder auch die Verwendung des Pyrrolidin-(2)-on-(1)-ylessigsäurechlorids.In addition, the usual production processes for amides, such as the process via mixed anhydrides using chloroformic acid esters, and the use of activated esters of pyrrolidin- (2) -one- (1) -ylacetic acid, such as nitrophenyl ester, are suitable for obtaining the compound according to the invention. Cyanomethyl ester or trichlorophenyl ester, or the use of pyrrolidin- (2) -one- (1) -ylacetic acid chloride.
Zur Untersuchung der pharmakodynamischen Eigenschaften der erfindungsgemäßen Verbindung wurden folgende Methoden verwendet:The following methods were used to investigate the pharmacodynamic properties of the compound according to the invention:
1. Verlängerung der zerebralen Überlebenszeit unter NaNO[tief]2-evozierter Hypoxämie.1. Extension of the cerebral survival time under NaNO [deep] 2-evoked hypoxemia.
Ausgehend von den Ergebnissen von Gibson und Blass (J. Neurochemistry 27, 1976) wird bei männlichen Mäusen mit NaNO[tief]2 (225 mg/kg s.c.) eine zerebrale Hypoxie erzeugt. Die zerebrale Hypoxie-Periode wird durch charakteristisches Krampfverhalten gekennzeichnet und endet mit dem Tod der Versuchstiere. Gemessen wird, ob sich die Überlebenszeit unter zerebral-hypoxischen Bedingungen durch Prämedikation signifikant verlängert.Based on the results of Gibson and Blass (J. Neurochemistry 27, 1976), cerebral hypoxia is produced in male mice with NaNO [deep] 2 (225 mg / kg s.c.). The cerebral hypoxia period is characterized by characteristic convulsive behavior and ends with the death of the test animals. It is measured whether the survival time under cerebral-hypoxic conditions is significantly increased by premedication.
2. Verlängerung der zerebralen Überlebenszeit bei Unterdruck-evozierter Hypoxie.2. Extension of the cerebral survival time in negative pressure evoked hypoxia.
Es ist bekannt, daß Tiere unter abnehmendem Sauerstoffdruck ein charakteristisches neuropathologisches Verhalten zeigen. Dieses neuropathologische Verhalten wird bei männlichen Mäusen durch progredienten Druckabfall in der Beobachtungskammer auf 26,66 k Pa ausgelöst und dient als Indikator der zerebralen Hypoxie-Periode. Sie endet mit dem Tod des Versuchstieres. Untersucht wird, ob sich die Überlebenszeit unter zerebral-hypoxischen Bedingungen durch Prämedikation signifikant verlängert.It is known that animals show characteristic neuropathological behavior under decreasing oxygen pressure. This neuropathological behavior is triggered in male mice by a progressive pressure drop in the observation chamber to 26.66 k Pa and serves as an indicator of the cerebral hypoxia period. It ends with the death of the test animal. It is investigated whether the survival time under cerebral-hypoxic conditions is significantly extended by premedication.
3. Schutz vor Elektroschock-induzierter Amnesie.3. Protection against electric shock-induced amnesia.
Ausgehend von den Ergebnissen von Taber und Banuazizi (Psychopharmakologia 9, 1966) läßt man männliche Mäuse erlernen, zur Vermeidung eines Elektroschocks ein bestimmtes Käfigkompartiment nicht zu begehen. Das Erlernte wird über Kopfelektroden mit Elektroschock extingiert (Elektroschock-Amnesie).On the basis of the results of Taber and Banuazizi (Psychopharmakologia 9, 1966), male mice can learn not to enter a certain cage compartment in order to avoid an electric shock. What has been learned is extinguished with an electric shock using head electrodes (electric shock amnesia).
Es wird untersucht, ob sich die Verweilzeit im elektroschockfreien Kompartiment des Käfigs als Maß für das Erinnerungsvermögen der Versuchstiere durch Prämedikation signifikant verlängert.It is investigated whether the dwell time in the electroshock-free compartment of the cage as a measure of the memory of the test animals is significantly increased by premedication.
Als Referenzsubstanzen dienten in allen Versuchen: Papaverin, Cinnarizin, Meclofenoxat, Piracetam, Vincamin, Propanolol, Pyritinol, Complamin und Pyrrolidin-(2)-on-(1)-ylessigsäureanilid.The following were used as reference substances in all tests: papaverine, cinnarizine, meclofenoxate, piracetam, vincamine, propanolol, pyritinol, complamin and pyrrolidin- (2) -one- (1) -ylacetic anilide.
In der nachfolgenden Tabelle werden die in den aufgeführten Versuchsmodellen erarbeiteten pharmakologischen Wirkqualitäten der erfindungsgemäßen Verbindung mit den handelsüblichen Referenzsubstanzen verglichen.In the table below, the pharmacologically active qualities of the compound according to the invention, which were developed in the test models listed, are compared with the commercially available reference substances.
TabelleTabel
Wie aus der Tabelle ersichtlich, zeigt die erfindungsgemäße Verbindung ein völlig neuartiges, zerebral-protektives Wirkprofil.As can be seen from the table, the compound according to the invention shows a completely new, cerebral-protective profile of action.
Die erfindungsgemäße Verbindung zeigt eine ausgezeichnete Wirkqualität sowie eine gute Verträglichkeit bei einer sehr geringen Toxizität:The compound according to the invention shows an excellent quality of action and good tolerability with a very low toxicity:
DL[tief]50: 1766 mg/kg - Maus p. o.DL [low] 50: 1766 mg / kg - mouse p. O.
DL[tief]50: 421 mg/kg - Maus i. v.DL [low] 50: 421 mg / kg - mouse i. v.
Die ausgezeichnete Wirkqualität und die gute Verträglichkeit, verbunden mit einer thrombozytenaggregationshemmenden Eigenschaft, wie sie für diesen Indikationsbereich erwünscht ist, machen die Substanz zur Behandlung von Krankheiten des zerebroischämischen wie zerebro-atrophischen Formenkreises incl. des organischen Psychosyndroms und der Migräne hervorragend geeignet. Darüber hinaus zeigt die Verbindung eine gute tranquilisierende Eigenschaft.The excellent quality of action and the good tolerability, combined with a platelet aggregation-inhibiting property, as it is desired for this range of indications, make the substance excellently suitable for the treatment of diseases of the cerebro-ischemic and cerebro-atrophic types, including organic psychosyndromes and migraines. In addition, the compound shows good tranquilizing properties.
Der neue Wirkstoff kann in bekannter Weise unter Verwendung pharmazeutisch geeigneter Lösungsmittel oder Trägerstoffe in die üblichen Darreichungsformen, wie Tabletten, Kapseln, Dragees, Pillen, Emulsionen, Suspensionen und Lösungen übergeführt werden.The new active ingredient can be converted into the usual dosage forms, such as tablets, capsules, coated tablets, pills, emulsions, suspensions and solutions, in a known manner using pharmaceutically suitable solvents or carriers.
Als Hilfsstoffe seien beispielsweise aufgeführt:Examples of auxiliaries are:
Nichttoxische, organische Lösungsmittel, wie pflanzliche Öle (z.B. Erdnußöl, Sojaöl), Alkohole (z.B. Polyäthylenglykol, Glycerin), feste Trägerstoffe, wie z.B. Gesteinsmehle (Kaoline, Talkum, Silikate), Zucker (z.B. Milchzucker, Traubenzucker), Emulgiermittel (z.B. Fettsäureester, Fettalkoholäther), Dispergiermittel (z.B. Methylcellulose, Stärke) und Gleitmittel (z.B. Talkum, Stearinsäure, Kakaobutter).Non-toxic, organic solvents such as vegetable oils (e.g. peanut oil, soybean oil), alcohols (e.g. polyethylene glycol, glycerine), solid carriers such as rock flour (kaolins, talc, silicates), sugar (e.g. lactose, grape sugar), emulsifiers (e.g. fatty acid esters, Fatty alcohol ethers), dispersants (e.g. methyl cellulose, starch) and lubricants (e.g. talc, stearic acid, cocoa butter).
Die Herstellung der erfindungsgemäßen Verbindung wird im folgenden Beispiel erläutert.The preparation of the compound according to the invention is illustrated in the following example.
Beispielexample
Pyrrolidin-(2)-on-(1)-ylessigsäure-2,6-dimethylanilidPyrrolidin- (2) -one- (1) -ylacetic acid-2,6-dimethylanilide
14,3 g (0,1 Mol) Pyrrolidin-(2)-on-(1)-ylessigsäure C[tief]6H[tief]9NO[tief]3 [143,1] und 12,1 g (0,1 Mol) 2,6-Dimethylanilin C[tief]8N[tief]11N [121,2] werden in 100 ml Chloroform abs. mit 20,6 g (0,1 Mol) N,N'-Dicyclohexylcarbodiimid C[tief]13H[tief]22N[tief]2 [206,3] 3 Stunden unter Rückfluß erhitzt. Nach dem Abkühlen wird vom ausgefallenen N,N-Dicyclohexyl-harnstoff abgesaugt, das Filtrat eingeengt und der Rückstand umkristallisiert.14.3 g (0.1 mol) of pyrrolidin- (2) -one- (1) -ylacetic acid C [deep] 6H [deep] 9NO [deep] 3 [143.1] and 12.1 g (0.1 Mol) 2,6-dimethylaniline C [deep] 8N [deep] 11N [121.2] in 100 ml of chloroform abs. heated under reflux for 3 hours with 20.6 g (0.1 mol) of N, N'-dicyclohexylcarbodiimide C [deep] 13H [deep] 22N [deep] 2 [206.3]. After cooling, the precipitated N, N-dicyclohexylurea is filtered off with suction, the filtrate is concentrated and the residue is recrystallized.
Ausbeute: 18,7 g (76 % d. Theorie)Yield: 18.7 g (76% of theory)
C[tief]14H[tief]18N[tief]2O[tief]2 [246,3]C [deep] 14H [deep] 18N [deep] 2O [deep] 2 [246.3]
Schmelzpunkt: 153°C (Wasser)Melting point: 153 ° C (water)
Elementaranalyse: C[tief]14H[tief]18N[tief]2O[tief]2 [246,3]Elemental analysis: C [deep] 14H [deep] 18N [deep] 2O [deep] 2 [246.3]
Ber.: C = 68,27 % H = 7,37 % N = 11,37 % O = 12,99 %Calc .: C = 68.27% H = 7.37% N = 11.37% O = 12.99%
gef.: C = 68,12 % H = 7,37 % N = 11,39 % O = 12,94 %found: C = 68.12% H = 7.37% N = 11.39% O = 12.94%
C = 68,09 % H = 7,42 % N = 11,34 % O = 13,09 %C = 68.09% H = 7.42% N = 11.34% O = 13.09%
IR-Spektrum:IR spectrum:
Gerät: Perkin-Elmer Modell 257Device: Perkin-Elmer Model 257
(KBr): kleines Ny[tief]NH: 3260 cm[hoch]-1,(KBr): small Ny [deep] NH: 3260 cm [high] -1,
kleines Ny[tief]CO (Ring, Amid): 1650 - 1700 cm[hoch]-1 (überlagerte Banden).small Ny [deep] CO (ring, amide): 1650 - 1700 cm [high] -1 (overlaid bands).
[hoch]1H-NMR-Spektrum:[high] 1H-NMR spectrum:
Gerät: Hitachi Perkin-Elmer, 60 MHz, Modell R-24Device: Hitachi Perkin-Elmer, 60 MHz, model R-24
Lösungsmittel: CDCL[tief]3 (TMS intern kleines Delta = 0)Solvent: CDCL [deep] 3 (TMS internal small delta = 0)
NH 7,85 (s), CH[tief]arom 7,0 (s), CH[tief]2 4,1 (s), CH[tief]2 3,6 (t), CH[tief]2-CH[tief]2 2,2 (m), CH[tief]2 2,1 (s).NH 7.85 (s), CH [deep] arom 7.0 (s), CH [deep] 2 4.1 (s), CH [deep] 2 3.6 (t), CH [deep] 2- CH [deep] 2 2.2 (m), CH [deep] 2 2.1 (s).
MS-Spektrum:MS spectrum:
Gerät: Varian Mat 311 A: Elektronenenergie 70ev, 200 A, Ionenquellentemperatur 200°C, Festprobenverdampfung bzw. Gaseinlaß für die Referenzsubstanz PFK, Scankontrolle sowie Datenerfassung und -verarbeitung über ein Finnigan-Incos-System; M[hoch]+: m/e 246 (60 %).Device: Varian Mat 311 A: electron energy 70ev, 200 A, ion source temperature 200 ° C, solid sample evaporation or gas inlet for the reference substance PFK, scan control as well as data acquisition and processing via a Finnigan Incos system; M [high] +: m / e 246 (60%).
Dünnschichtchromatographie:Thin layer chromatography:
DC-Fertigplatten Kieselgel 60 F[tief]254 (Merck).Pre-fabricated silica gel plates TLC 60 F [deep] 254 (Merck).
Sprühreagenz: Bromkresolgrün (0,05 %, Merck).Spray reagent: bromocresol green (0.05%, Merck).
R[tief]f = 0,83R [deep] f = 0.83
Laufmittel:Eluent:
Chloroform / Methanol / Ammoniak (25 %)Chloroform / methanol / ammonia (25%)
70 26 4 (V/V/V)70 26 4 (V / V / V)
R[tief]f = 0,36R [deep] f = 0.36
Laufmittel:Eluent:
Chloroform / MethanolChloroform / methanol
190 10 (V/V)190 10 (V / V)
Claims (3)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792924011 DE2924011C2 (en) | 1979-06-13 | 1979-06-13 | Pyrrolidin- (2) -one- (1) -ylacetic acid-2,6, -dimethylanilide, process for the preparation and medicaments containing this compound |
| IT21464/80A IT1141287B (en) | 1979-06-13 | 1980-04-17 | PYROLIDIN ACIDS AMIDS- (2) -ON- (1) -ILALKYL-CARBOXYLS, PROCEDURE FOR THEIR PREPARATION AND MEDICINAL PRODUCTS CONTAINING THEM |
| US06/155,952 US4341790A (en) | 1979-06-13 | 1980-06-03 | Pyrrolidinylalkylcarboxylic acid amide derivatives, their preparation and pharmaceutical compositions containing them |
| FR8012840A FR2458544A1 (en) | 1979-06-13 | 1980-06-10 | NOVEL PYRROLIDIN- (2) -ON- (1) -YLALCOYL-CARBOXYLIC ACID AMIDES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICAMENTS |
| GB8019199A GB2053909B (en) | 1979-06-13 | 1980-06-12 | Pyrrolidinylalkycarboxylic acid amide derivatives their preparation and pharmaceutical compositions containing them |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792924011 DE2924011C2 (en) | 1979-06-13 | 1979-06-13 | Pyrrolidin- (2) -one- (1) -ylacetic acid-2,6, -dimethylanilide, process for the preparation and medicaments containing this compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2924011A1 DE2924011A1 (en) | 1980-12-18 |
| DE2924011C2 true DE2924011C2 (en) | 1982-04-08 |
Family
ID=6073182
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792924011 Expired DE2924011C2 (en) | 1979-06-13 | 1979-06-13 | Pyrrolidin- (2) -one- (1) -ylacetic acid-2,6, -dimethylanilide, process for the preparation and medicaments containing this compound |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2924011C2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3701494A1 (en) * | 1986-01-21 | 1987-07-23 | Nippon Shinyaku Co Ltd | PYROGLUTAMIDE DERIVATIVES |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2515179A1 (en) * | 1981-07-24 | 1983-04-29 | Hoffmann La Roche | PYRROLIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION, INTERMEDIATES FOR THEIR SYNTHESIS AND THEIR THERAPEUTIC APPLICATION |
| DE3336024A1 (en) * | 1983-10-04 | 1985-04-18 | Boehringer Ingelheim KG, 6507 Ingelheim | 4-AMINO-L-BENZYL-PYRROLIDINONE AND ITS ACID ADDITION SALTS, METHOD FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS |
| US6423739B1 (en) | 2000-02-23 | 2002-07-23 | Daiichi Pharmaceutical Co., Ltd. | Method for aiding cerebral recovery following neurodegeneration |
| US6348489B1 (en) * | 2000-04-11 | 2002-02-19 | Daiichi Pharmaceutical Co., Ltd. | Method of treating traumatic brain injury and other neuronal disorders |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1039113A (en) | 1964-08-06 | 1966-08-17 | Ucb Sa | New n-substituted lactams |
| DE2808067A1 (en) | 1977-03-03 | 1978-09-07 | Parke Davis & Co | N- (SUBSTITUTED AMINOALKYL) -2-OXO-1- PYRROLIDINE ACETAMIDE AND METHOD FOR THE PREPARATION |
-
1979
- 1979-06-13 DE DE19792924011 patent/DE2924011C2/en not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1039113A (en) | 1964-08-06 | 1966-08-17 | Ucb Sa | New n-substituted lactams |
| DE2808067A1 (en) | 1977-03-03 | 1978-09-07 | Parke Davis & Co | N- (SUBSTITUTED AMINOALKYL) -2-OXO-1- PYRROLIDINE ACETAMIDE AND METHOD FOR THE PREPARATION |
Non-Patent Citations (3)
| Title |
|---|
| Ehrhart-Ruschig: Arzneimittel, Bd. 2, 1972, S. 260 |
| Gibson und Blass (J. Neurochemistry 27, 1976) |
| Taber und Banuazizi (Psychopharmakologia 9, 1966) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3701494A1 (en) * | 1986-01-21 | 1987-07-23 | Nippon Shinyaku Co Ltd | PYROGLUTAMIDE DERIVATIVES |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2924011A1 (en) | 1980-12-18 |
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Owner name: DAIICHI PHARMACEUTICAL CO., LTD., TOKIO/TOKYO, JP |
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Free format text: WUESTHOFF, F., DR.-ING. FRHR. VON PECHMANN, E., DIPL.-CHEM. DR.RER.NAT. BEHRENS, D., DR.-ING. GOETZ, R., DIPL.-ING. DIPL.-WIRTSCH.-ING. HELLFELD VON, A., DIPL.-PHYS. DR.RER.NAT. BRANDES, J., DIPL.-CHEM. DR.RER.NAT., PAT.-ANWAELTE WUERTENBERGER, G., RECHTSANW., 8000 MUENCHEN |