DE2158801C3 - - Google Patents
Info
- Publication number
- DE2158801C3 DE2158801C3 DE19712158801 DE2158801A DE2158801C3 DE 2158801 C3 DE2158801 C3 DE 2158801C3 DE 19712158801 DE19712158801 DE 19712158801 DE 2158801 A DE2158801 A DE 2158801A DE 2158801 C3 DE2158801 C3 DE 2158801C3
- Authority
- DE
- Germany
- Prior art keywords
- respiratory
- compounds according
- formula
- compounds
- substituted
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 18
- -1 dipropylaminomethyl Chemical group 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- HRTNGSCQAGSUOB-UHFFFAOYSA-N 1-(3-phenylprop-2-enyl)benzimidazole Chemical group C1=NC2=CC=CC=C2N1CC=CC1=CC=CC=C1 HRTNGSCQAGSUOB-UHFFFAOYSA-N 0.000 claims description 2
- 150000001556 benzimidazoles Chemical class 0.000 claims description 2
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
- 230000000241 respiratory Effects 0.000 description 8
- BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Chemical compound [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 6
- 230000002048 spasmolytic Effects 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 230000000202 analgesic Effects 0.000 description 4
- 230000004936 stimulating Effects 0.000 description 4
- ZDHWSRRZUPRQBD-UHFFFAOYSA-N 2-[but-2-enoyl(ethyl)amino]-N,N-dimethylbutanamide;2-[but-2-enoyl(propyl)amino]-N,N-dimethylbutanamide Chemical compound CN(C)C(=O)C(CC)N(CC)C(=O)C=CC.CN(C)C(=O)C(CC)N(CCC)C(=O)C=CC ZDHWSRRZUPRQBD-UHFFFAOYSA-N 0.000 description 3
- IWTYTFSSTWXZFU-QPJJXVBHSA-N [(E)-3-chloroprop-1-enyl]benzene Chemical compound ClC\C=C\C1=CC=CC=C1 IWTYTFSSTWXZFU-QPJJXVBHSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000003555 analeptic Effects 0.000 description 3
- 230000001077 hypotensive Effects 0.000 description 3
- 229940042542 prethcamide Drugs 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N Papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drugs Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 229960001789 papaverine Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000304 vasodilatating Effects 0.000 description 2
- 230000000261 vasodilator Effects 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- WBDCCRNAPCOHAV-UHFFFAOYSA-N 4-(1H-benzimidazol-2-ylmethyl)morpholine Chemical compound N=1C2=CC=CC=C2NC=1CN1CCOCC1 WBDCCRNAPCOHAV-UHFFFAOYSA-N 0.000 description 1
- WDIHJSXYQDMJHN-UHFFFAOYSA-L Barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 210000004351 Coronary Vessels Anatomy 0.000 description 1
- 210000001198 Duodenum Anatomy 0.000 description 1
- 206010058061 Gastrointestinal oedema Diseases 0.000 description 1
- 206010017999 Gastrointestinal pain Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229960005195 Morphine hydrochloride Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive Effects 0.000 description 1
- 230000001396 anti-anti-diuretic Effects 0.000 description 1
- 230000003276 anti-hypertensive Effects 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- 229910001626 barium chloride Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000001882 diuretic Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- XCKKIKBIPZJUET-VYKNHSEDSA-N morphine hydrochloride Chemical compound Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XCKKIKBIPZJUET-VYKNHSEDSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organs Anatomy 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000035812 respiration Effects 0.000 description 1
- 230000036391 respiratory frequency Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Description
(ID(ID
in der R die in Anspruch 1 angegebene Bedeutung hat, mit Cinnamylchlorid der Formel IIIin which R has the meaning given in claim 1, with cinnamyl chloride of the formula III
Cl-CH,-CH=CH-<Cl-CH, -CH = CH- <
(HD(HD
3535
umsetzt.implements.
3. Arzneimittel mit hypotensiver, gefäßerweiternder, atmungsstimulierender, analgetischer und spasmolytischer Wirkung, enthaltend eine Verbindung nach Anspruch 1.3. Medicines with hypotensive, vasodilator, breath-stimulating, analgesic and Spasmolytic action containing a compound according to Claim 1.
4545
Die Erfindung betrifft in 2-Stellung substituierte 1-Cinnamylbenzimidazolderivate, ein Verfahren zu ihrer Herstellung und Arzneimittel.The invention relates to 1-cinnamylbenzimidazole derivatives substituted in the 2-position, to a method their manufacture and medicinal products.
Gegenstand der Erfindung sind in 2-Stellung substituierte I-Cinnamylbenzimidazolderivate der allgemeinen Formel IThe invention relates to I-cinnamylbenzimidazole derivatives of the general type which are substituted in the 2-position Formula I.
N-CH7-CH =N-CH 7 -CH =
(I)(I)
in der R die Morpholinomethyl-, Dipropylaminomethyl- oder Pyrrolidinomethylgruppe bedeutet und ihre Hydrochloride.in which R denotes the morpholinomethyl, dipropylaminomethyl or pyrrolidinomethyl group and their Hydrochloride.
Die erfindungsgemäßen Verbindungen lassen sich nach einem Verfahren herstellen, das dadurch gekennzeichnet ist, daß man in an sich bekannter Weise ein in 2-Stellung substituiertes Benzimidazolderivat der allgemeinen Formel IlThe compounds according to the invention can be prepared by a process which is characterized is that one in a conventional manner a substituted in the 2-position benzimidazole derivative of the general Formula Il
in der R die vorstehend angegebene Bedeutung besitzt, mit Cinnamylchlorid der Formel INin which R has the meaning given above, with cinnamyl chloride of the formula IN
CI-CH2-CH=CHCI-CH 2 -CH = CH
(IH)(IH)
umsetzt.implements.
Die Umsetzung erfolgt zweckmäßig in Dimethylformamid als Lösungsmittel in Gegenwart von Natriumhydrid. The reaction is expediently carried out in dimethylformamide as the solvent in the presence of sodium hydride.
Die erfindungsgemäßen Verbindungen haben wertvolle pharmakologische Eigenschaften. Die Erfindung betrifft somit ferner Arzneimittel mit hypotensiver, gefäßerweiternder, atmungsstimulierender, analgetischer und spasmolytischer Wirkung, die eine Verbindungderallgemeinen Formel I enthalten.The compounds according to the invention have valuable pharmacological properties. The invention thus also relates to drugs with hypotensive, vasodilating, respiratory stimulating, analgesic and spasmolytic action, which is a connectiongeneral Formula I included.
Die erfindungsgemäßen Verbindungen wurden an Versuchstieren auf ihre pharmakologischen Wirkungen untersucht und zeigten dabei blutdrucksenkende, gefäßerweiternde, atmungsanaleptische, analgetische, entzündungshemmende, spasmolytische und diuretische Eigenschaften. Nachstehend sind einige Versuchsergebnisse zusammengestellt.The compounds according to the invention were tested for their pharmacological effects on test animals examined and showed antihypertensive, vasodilator, respiratory analeptic, analgesic, anti-inflammatory, spasmolytic and diuretic properties. Below are some experimental results compiled.
1. Hypotensive Wirkung1. Hypotensive effect
Bei intravenöser oder intraduodenaler Verabreichung rufen die erfindungsgemäßen Verbindungen bei der anesthesierten Ratte eine Senkung des arteriellen Blutdrucks hervor. So wurde z. B. bei intravenöser Verabreichung der weiter unten als Verbindung Nr. 3 bezeichneten Substanz in einer Dosis von 2 mg/kg eine Senkung des arteriellen Blutdrucks um 35% während einer Zeitdauer von über 45 Minuten erzielt.When administered intravenously or intraduodenally, the compounds of the invention call upon the anesthetized rat showed a decrease in arterial blood pressure. So was z. B. with intravenous Administration of the substance referred to below as Compound No. 3 at a dose of 2 mg / kg a Achieved a 35% reduction in arterial blood pressure over a period of 45 minutes.
2. Gefäßerweiternde Eigenschaften2. Vasodilatory properties
Die erfindungsgemäßen Verbindungen erhöhen denThe compounds of the invention increase the
Durchsatz bzw. die Flüssigkeitsdurchflußmenge der Herzkranzgefäße beim isolierten Meerschweinchen-Throughput or the fluid flow rate of the coronary vessels in the isolated guinea pig
herz, wenn sie der durch dieses Organ fließendenheart when you are flowing through this organ
Flüssigkeit (Perfusionsflüssigkeit) zugesetzt wird.Liquid (perfusion liquid) is added.
So bewirkt z. B. die weiter unten als Verbindung Nr. 2 bezeichnete Substanz in einer Konzentration von 2,5 mg/ml Perfusionsflüssigkeit eine Erhöhung der Durchflußmenge um 70%.So z. B. the substance referred to below as compound no. 2 in a concentration of 2.5 mg / ml perfusion fluid increases the flow rate by 70%.
3. Atmungsstimulierende Wirkung3. Respiratory stimulating effect
Die erfindungsgemäßen Verbindungen weisen eine atmungsstimulierende Wirkung auf. Sie werden nachstehend mit dem bekannten analeptischen Atmungsmittel Prethcamide (The Merck Index (1968), S. 294, rechte Spalte) verglichen.The compounds according to the invention have a respiration-stimulating effect. They are below with the well-known analeptic respiratory agent Prethcamide (The Merck Index (1968), p. 294, right Column) compared.
Die geprüften Verbindungen wurden in Dosen von 5 oder 10 mg/kg intravenös an anästherisierte Meerschweinchen verabreicht, deren Atmung durch die intravenöse Injektion von 10 mg/kg Morphinhydrochlorid herabgesetzt worden war. Die Ergebnisse sind in der nachstehenden Tabelle I zusammengestellt.The compounds tested were administered intravenously to anesthetized guinea pigs at doses of 5 or 10 mg / kg administered their respiration by intravenous injection of 10 mg / kg of morphine hydrochloride had been lowered. The results are shown in Table I below.
Vergleich der atmungsstimulierenden WirkungComparison of the respiratory stimulating effect
Untersuchte VerbindungInvestigated connection
ErfindungsgemäßeAccording to the invention
Verbindungs-Nr.Connection no.
(gemäß Bezeichnung(according to the designation
weiter unten)further down)
PrethcamidePrethcamide
1100
1100
11001100
1100
1100
11001100
N-CH2-CH=CHN-CH 2 -CH = CH
1010
1010
1010
70 60 5070 60 50
6565
100
100
100100
100
100
Die Ergebnisse der Vergleichsversuche zeigen, daß die erfindungsgemäßen Verbindungen dem bekannten analeptischen Atmungsmittel Prethcamide sowohl hinsichtlich der Erhöhung der Atmungsfrequenz als auch der Erhöhung der Atmungsamplitude überlegen sind.The results of the comparative experiments show that the compounds according to the invention correspond to the known analeptic respiratory agent Prethcamide both in terms of increasing the respiratory rate as well are superior to increasing the respiratory amplitude.
4. Analgetische Eigenschaften4. Analgesic properties
Die erfindungsgemäßen Verbindungen vermindern bei oraler Verabreichung an die Maus die Zahl der auf eine intraperitoneale Injektion von Essigsäure folgenden Schmerziuckungen bzw. -krümmungen. So wurde z. B. bei oraler Verabreichung der Verbindung Nr. 2 in einer Dosis von 100 mg/kg eine Verringerung der Zahl der Schmerzzuckungen um 45% erzielt.When administered orally to the mouse, the compounds according to the invention reduce the number of an intraperitoneal injection of acetic acid following painful convulsions. So became z. B. when the compound No. 2 is orally administered at a dose of 100 mg / kg, a decrease in the number the pain jerks achieved by 45%.
5. Spasmolytische Wirkung5. Spasmolytic effect
Die erfindungsgemäßen Verbindungen wirken als Zusatz zum Nährmedium den am isolierten Rattenzwölffingerdarm durch Bariumchlorid hervorgerufenen Kontraktionen entgegen. Diese Wirkung wird unter Verwendung von Papaverin als Vergleichssubstanz bestimmt.The compounds according to the invention act as an additive to the nutrient medium on the isolated rat duodenum counteracts contractions caused by barium chloride. This effect is under Use of papaverine as reference substance determined.
So zeigt z. B. die Verbindung Nr. 3 eine zur Wirkung des Papaverins äquivalente spasmolytische Wirkung.So shows z. B. Compound No. 3 has a spasmolytic effect equivalent to that of papaverine.
Die erfindungsgemäßen Verbindungen sind für die Behandlung von Hochdruckzuständen, Kreislauf- bzw. Durchblutungsstörungen, schmerzhaften Entzündungen, Eingeweidespasmen und Ödemen indiziert. Sie werden oral in Form von Tabletten, Dragees oder Kapseln mit einem Wirkstoffgehalt von 50 bis 350 mg (1- bis 3mal täglich), rektal in Form von Suppositorien mit einem Wirkstoff gehalt vor. 50 bis 350 mg (1- bis 2mal täglich) und parenteral in Form von Ampullen mit einem Wirkstoffgehalt von 5 bis 250 mg (1 bis 3 Injektionen täglich) verabreicht.The compounds according to the invention are suitable for the treatment of high pressure conditions, circulatory or Circulatory disorders, painful inflammation, intestinal spasms and edema indicated. she are taken orally in the form of tablets, coated tablets or capsules with an active ingredient content of 50 to 350 mg (1 to 3 times a day), rectally in the form of suppositories with an active ingredient content. 50 to 350 mg (1- to 2 times a day) and parenterally in the form of ampoules with an active ingredient content of 5 to 250 mg (1 to 3 Injections daily).
Das nachfolgende Beispiel erläutert die Erfindung.The following example explains the invention.
1 -Cinnamyl-2-morpholinomethylbenzimidazolhydrochlorid 1 -Cinnamyl-2-morpholinomethylbenzimidazole hydrochloride
(Verbindung Nr. 1)(Connection no. 1)
Eine Lösung von 0,275 Mol 2-Morpholinomethylbenzimidazol in'400 ml Dimethylformamid wird innerhalb 15 Minuten bei Raumtemperatur mit 13,2 g Natriumhydrid versetzt, wobei man darauf achtet, daß die Temperatur des Reaktionsgemisches 40°C nicht übersteigt. Nach beendeter Zugabe hält man das Reaktionsgemisch 10 Minuten bei einer Temperatur von 50°C, läßt es sich dann auf 30°C abkühlen und gibt im Laufe von 10 Minuten 42 g Cinnamylchlorid zu. Dann hält man das Reaktionsgemisch 20 Minuten bei einer Temperatur von 8O0C und läßt es sich anschließend wieder auf Raumtemperatur abkühlen, worauf man es mit Wasser verdünnt und das dabei gebildete öl mit Chloroform extrahiert. Der Extrakt wird getrocknet und eingedampft. Das Rohprodukt wird in Methanol gelöst und mit Chlorwasserstoffsäure versetzt. Das erhaltene Produkt wird durch Umkristallisieren aus einem Aceton/Äther-Gemisch (60/40) gereinigt.A solution of 0.275 mol of 2-morpholinomethylbenzimidazole in 400 ml of dimethylformamide is admixed with 13.2 g of sodium hydride at room temperature over the course of 15 minutes, taking care that the temperature of the reaction mixture does not exceed 40.degree. When the addition is complete, the reaction mixture is kept at a temperature of 50 ° C. for 10 minutes, then allowed to cool to 30 ° C. and 42 g of cinnamyl chloride are added over the course of 10 minutes. Then the reaction mixture is kept 20 minutes at a temperature of 8O 0 C and allowed it to cool back to room temperature, after which it is diluted with water and extracted with chloroform, the thus formed oil. The extract is dried and evaporated. The crude product is dissolved in methanol and hydrochloric acid is added. The product obtained is purified by recrystallization from an acetone / ether mixture (60/40).
Schmelzpunkt: 183° C
Ausbeute: 51%
Summenformel: C21H24CI N3OMelting point: 183 ° C
Yield: 51%
Molecular formula: C21H24CI N3O
4545
Elementaranalyse·.
Berechnet: C 68,19,
gefunden: C 67,99,Elemental Analysis ·.
Calculated: C 68.19,
found: C 67.99,
H 6,54, N 11,36;
H 6,53, N 11,42%.H 6.54, N 11.36;
H 6.53, N 11.42%.
Die in der nachstehenden Tabelle II aufgeführten Verbindungen werden analog der im vorstehenden Beispiel beschriebenen Arbeitsweise hergestellt.The compounds listed in Table II below are analogous to those above Example of the procedure described.
Verbindungconnection
Formshape
—CH2N(n-CjH7)2 -CH 2 N (n-CjH 7 ) 2
HCL
HCLHCL
HCL
SummcnformelSummation formula
MolekulargewichtMolecular weight
Smp.
Γ C)M.p.
Γ C)
C23H30ClN3
C21H24ClN3 C 23 H 30 ClN 3
C 21 H 24 ClN 3
383,95
353,88383.95
353.88
126126
216216
BerechnetElemental analysis
Calculated
Nr.connection
No.
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7042636A FR2115067B1 (en) | 1970-11-27 | 1970-11-27 | |
| FR7042636 | 1970-11-27 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2158801A1 DE2158801A1 (en) | 1972-06-22 |
| DE2158801B2 DE2158801B2 (en) | 1977-01-27 |
| DE2158801C3 true DE2158801C3 (en) | 1977-09-15 |
Family
ID=9064819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712158801 Granted DE2158801B2 (en) | 1970-11-27 | 1971-11-26 | 1-CINNAMYLBENZIMIDAZOLE DERIVATIVES SUBSTITUTED IN 2-POSITION, METHOD FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US3758459A (en) |
| AU (1) | AU457142B2 (en) |
| BE (1) | BE775040A (en) |
| CA (1) | CA955253A (en) |
| CH (1) | CH523889A (en) |
| CS (1) | CS174851B2 (en) |
| DE (1) | DE2158801B2 (en) |
| ES (1) | ES397205A1 (en) |
| FR (1) | FR2115067B1 (en) |
| GB (1) | GB1311419A (en) |
| IL (1) | IL38149A (en) |
| LU (1) | LU64306A1 (en) |
| NL (1) | NL7116314A (en) |
| SE (1) | SE378245B (en) |
| SU (1) | SU432718A3 (en) |
| ZA (1) | ZA717617B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2244500B1 (en) * | 1973-07-03 | 1977-07-01 | Delalande Sa | |
| DE2861987D1 (en) * | 1977-08-01 | 1982-09-30 | Ciba Geigy Ag | Benzimidazole-2 derivatives, their preparation and their use for the preparation of medicaments |
| JPH07137179A (en) * | 1993-07-19 | 1995-05-30 | Xerox Corp | Production of assembly of movably-connected two members |
-
1970
- 1970-11-27 FR FR7042636A patent/FR2115067B1/fr not_active Expired
-
1971
- 1971-11-04 CH CH1614071A patent/CH523889A/en not_active IP Right Cessation
- 1971-11-08 BE BE775040A patent/BE775040A/en unknown
- 1971-11-12 ZA ZA717617A patent/ZA717617B/en unknown
- 1971-11-15 IL IL38149A patent/IL38149A/en unknown
- 1971-11-16 GB GB5302071A patent/GB1311419A/en not_active Expired
- 1971-11-18 AU AU35877/71A patent/AU457142B2/en not_active Expired
- 1971-11-19 CS CS8113A patent/CS174851B2/cs unknown
- 1971-11-20 ES ES397205A patent/ES397205A1/en not_active Expired
- 1971-11-22 LU LU64306D patent/LU64306A1/xx unknown
- 1971-11-26 NL NL7116314A patent/NL7116314A/xx unknown
- 1971-11-26 DE DE19712158801 patent/DE2158801B2/en active Granted
- 1971-11-26 SU SU1718586A patent/SU432718A3/en active
- 1971-11-26 SE SE7115183A patent/SE378245B/xx unknown
- 1971-11-26 US US00202596A patent/US3758459A/en not_active Expired - Lifetime
- 1971-11-26 CA CA128,736*7A patent/CA955253A/en not_active Expired
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