DE1288586B - N-AEthyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diaethylcarbamoyloxy) -butyl] -carbamic acid ethyl ester and process for its preparation - Google Patents
N-AEthyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diaethylcarbamoyloxy) -butyl] -carbamic acid ethyl ester and process for its preparationInfo
- Publication number
- DE1288586B DE1288586B DEK64626A DEK0064626A DE1288586B DE 1288586 B DE1288586 B DE 1288586B DE K64626 A DEK64626 A DE K64626A DE K0064626 A DEK0064626 A DE K0064626A DE 1288586 B DE1288586 B DE 1288586B
- Authority
- DE
- Germany
- Prior art keywords
- ethyl
- carbamic acid
- benzyl
- butyl
- ethyl ester
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 claims description 4
- -1 N-ethyl-N- (2-benzyl-2-ethyl-3-hydroxy-butyl) -carbamic acid ethyl ester Chemical compound 0.000 claims description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-M carbonochloridate Chemical compound [O-]C(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-M 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 230000002908 adrenolytic effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 229960002456 hexobarbital Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000004651 carbonic acid esters Chemical class 0.000 description 1
- MTMNJFGEKOYMIV-UHFFFAOYSA-N carbonyl dichloride;toluene Chemical compound ClC(Cl)=O.CC1=CC=CC=C1 MTMNJFGEKOYMIV-UHFFFAOYSA-N 0.000 description 1
- 229940112021 centrally acting muscle relaxants carbamic acid ester Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- VNTQFAZMXKKZNN-UHFFFAOYSA-N ethyl N-[2-ethyl-2-(hydroxymethyl)butyl]carbamate Chemical compound C(C)OC(NCC(CO)(CC)CC)=O VNTQFAZMXKKZNN-UHFFFAOYSA-N 0.000 description 1
- GTOKAWYXANYGFG-UHFFFAOYSA-N ethyl n-propylcarbamate Chemical compound CCCNC(=O)OCC GTOKAWYXANYGFG-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical class OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 210000001625 seminal vesicle Anatomy 0.000 description 1
- 230000004622 sleep time Effects 0.000 description 1
- SQMCFUSVGSBKFK-UHFFFAOYSA-M sodium;5-(cyclohexen-1-yl)-1,5-dimethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].O=C1N(C)C(=O)[N-]C(=O)C1(C)C1=CCCCC1 SQMCFUSVGSBKFK-UHFFFAOYSA-M 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Die Carbamate bzw. Kohlensäureester verschiedener 1,3-Propandiole sind «eit einigen Jahren bekannt und von therapeutischer Bedeutung. Strukturell verwandt sind mit ihnen auch N-substituierte N-(3-Oxyalkyl)-carbamidsäureäthylester, wie sie z.B. in der deutschen Patentschrift 1 150 973 undThe carbamates or carbonic acid esters of various 1,3-propanediols have been known for several years and of therapeutic importance. N-substituted ones are also structurally related to them N- (3-oxyalkyl) -carbamic acid ethyl ester, as for example in the German patent 1 150 973 and
CH, in der belgischen Patentschrift 606 096 beschrieben werden.CH, in Belgian patent specification 606 096.
Es wurde nun gefunden, daß die erfindungsgemäße Verbindung N - Äthyl - N - [2 - benzyl - 2 - äthyl-3 - (Ν',Ν' - diäthylcarbamoyloxy) - butyl] - carbamidsäureäthylester der FormelIt has now been found that the compound according to the invention N - ethyl - N - [2 - benzyl - 2 - ethyl-3 - (Ν ', Ν' - diethylcarbamoyloxy) - butyl] - carbamic acid ethyl ester the formula
s,—s, CH-O —CO-N< s, -s, CH-O -CO-N <
ru/ [ CH2 — N — CO — OC2H5 ru / [CH 2 - N - CO - OC 2 H 5
C7HC 7 H
CACA
eine starke pharmakologische Wirkung, insbesondere auf das Nervensystem ausübt und als Arzneimittel Verwendung finden kann.Has a strong pharmacological effect, especially on the nervous system and as a medicinal product Can be used.
Die neue Verbindung wird erhalten, indem man in an sich bekannter Weise N-Äthyl-N-(2-benzyl-2 - äthyl - 3 - hydroxy - butyl) - carbamidsäureäthylester der FormelThe new compound is obtained by adding N-ethyl-N- (2-benzyl-2 - ethyl - 3 - hydroxy - butyl) - carbamic acid ethyl ester of the formula
CH,CH,
CH3
CH-OHCH 3
CH-OH
I >cI. > c
CH2 — N — CO — OC2H5 QH5 CH 2 - N - CO - OC 2 H 5 QH 5
mit Phosgen umsetzt und das gebildete Chlorcarbonat mit Diäthylamin zur Reaktion bringt.Reacts with phosgene and the chlorocarbonate formed with diethylamine to react.
Die beanspruchte Verbindung weist gegenüber konstitutionell vergleichbaren und ähnlich wirkenden Stoffen, z.B. den N-(3-Oxyalkyl)-carbamidsäureestern, wesentliche Vorteile bezüglich Intensität der Sedierung und der adrenolytischen Wirksamkeit auf, wie aus der nachstehenden Tabelle ersichtlich ist.The claimed connection points towards constitutionally comparable and similarly acting Substances, e.g. the N- (3-oxyalkyl) carbamic acid esters, have significant advantages in terms of intensity sedation and adrenolytic efficacy, as shown in the table below.
In der Tabelle bedeutetIn the table means
I = N-Äthyl-N-[2-benzyl-2-äthyl-3-(N',N'-diäthylcarbamoyloxyj-butylj-carbamidsäureäthylester, I = N-ethyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diethylcarbamoyloxyj-butylj-carbamic acid ethyl ester,
II = N-(2,2-Diäthyl-3-hydroxy-propyl)-carbamidsäureäthylester·), II = N- (2,2-diethyl-3-hydroxypropyl) carbamic acid ethyl ester),
III = N-Methyl-N-(2,2-diäthyl-3-hydroxy-III = N-methyl-N- (2,2-diethyl-3-hydroxy-
propyl)-carbamidsäureäthylester*),ethyl propyl carbamate *),
IV = N-(2,2-Diäthyl-3-hydroxy-butyl)-IV = N- (2,2-diethyl-3-hydroxy-butyl) -
carbamidsäureäthylester*).carbamic acid ethyl ester *).
*) Vergleichsverbindung, bekannt aus der deutschen Patentichrift 1 150973. *) Comparative compound, known from German patent specification 1 150973.
Im einzelnen wurden folgende pharmakologische Prüfungen vorgenommen:The following pharmacological tests were carried out in detail:
1. Akute Toxizität (bestimmt an weißen Mäusen nach subkutaner Injektion der Substanz; angegeben ist der 24-Stunden-Wert als DL» in mg/kg).1. Acute toxicity (determined on white mice after subcutaneous injection of the substance; stated is the 24-hour value as DL »in mg / kg).
2. Sedierende Wirkung. Zur Feststellung der sedierenden Wirkung wurde die prozentuale2. Sedative effect. To determine the sedative effect, the percentage
Verlängerung des Hexobarbitalschlafes in der Weise bestimmt, wie sie von Holten und
Larsen in Acta pharmacol. et toxicol., 12 (1956), S. 346 ff., angegeben worden ist (»Hexobarbital«
= nicht schutzfähige internationale Kurzbezeichnung für 5-(Cyclohexen-l-yl)-5-methyl-N-methylbarbitursäure).
In der Tabelle bedeutet: Die Angabe »SW 1% V2«>
daß die Schlafzeit durch die Einwirkung von einer Gewichtsmenge Prüfsubstanz, die 1% der toxischen
Dosis = DLso entspricht, V2 Stunde vor der Hexobarbital-Natrium-Gabe
appliziert, die angegebene prozentuale Verlängerung erfahren hat. Die Angabe »SW 2% Va« die Verlängerung der Narkose bei
Anwendung von 2% der DL50, und die Angabe »SW 5% V2« die Verlängerung der Narkose bei
Anwendung von 5% der DL50 unter sonst gleichen Bedingungen.Prolongation of hexobarbital sleep as determined by Holten and Larsen in Acta pharmacol. et toxicol., 12 (1956), p. 346 ff. ("Hexobarbital" = non-protectable international abbreviation for 5- (cyclohexen-l-yl) -5-methyl-N-methylbarbituric acid).
In the table: The indication "SW 1% V2" means that the sleep time due to the action of an amount of test substance by weight which corresponds to 1% of the toxic dose = DLso is applied V2 hours before the hexobarbital sodium administration, the stated percentage extension has experienced. The indication "SW 2% Va" the extension of the anesthesia when using 2% of the DL50, and the indication "SW 5% V2" the extension of the anesthesia when using 5% of the DL50 under otherwise identical conditions.
3. Adrenolytische Wirksamkeit (gemessen wird die Konzentration in mg/cm3, die in der Lage3. Adrenolytic effectiveness (the concentration is measured in mg / cm 3 , which is capable of
ist, die durch 1,5 y/cm3 Adrenalin hervorgerufene Kontraktion der Meerschweinchensamenblase im Bad 50% zu senken; diese Werte sind in der Tabelle unter der Bezeichnung »ED50 (mg/cm3)« angegeben). Literatur: Rothlin und B rügger, HeIv. physiologica acta, 3, 519 (1945).is to reduce the contraction of the guinea pig seminal vesicle in the bath caused by 1.5 y / cm 3 of adrenaline by 50%; these values are given in the table under the designation »ED50 (mg / cm 3 )«). Literature: Rothlin and Brügger, HeIv. physiologica acta, 3, 519 (1945).
Der N-Äthyl-N-[2-benzyl-2-äthyl-3-(N',N'-diäthylcarbamoyloxy) - butyl] - carbamidsäureäthylester wird auf folgende Weise hergestellt:The N-ethyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diethylcarbamoyloxy) - butyl] - carbamic acid ethyl ester is produced in the following way:
35 g N-Äthyl-N-(2-benzyl-2-äthyl-3-hydroxybutyl)-carbamidsäureäthylester werden in 100 ml getrocknetem Chloroform gelöst und mit 8OmI 20%iger Phosgen-Toluol-Lösung versetzt. Unter Feuchtigkeitsausschluß läßt man 16 Stunden bei Raumtemperatur stehen und entfernt dann unter Vakuum das Lösungsmittel bei maximal 400C. Der Rückstand wird mit 17 g Diäthylamm und 100 ml getrocknetem Chloroform 2 Stunden unter Rückfluß erhitzt. Nach Abdestillieren des Lösungsmittels nimmt man den Rückstand in Äther auf, filtriert ausgeschiedenes Diäthylaminhydrochlorid ab und schüttelt das Filtrat mit 2 η-Natronlauge aus.35 g of N-ethyl-N- (2-benzyl-2-ethyl-3-hydroxybutyl) -carbamic acid ethyl ester are dissolved in 100 ml of dried chloroform and 80 ml of 20% phosgene-toluene solution are added. With exclusion of moisture is allowed to stand for 16 hours at room temperature and then removed under vacuum, the solvent at 40 0 C. The residue is heated for 2 hours under reflux with 17 g Diäthylamm and 100 ml of dried chloroform. After the solvent has been distilled off, the residue is taken up in ether, precipitated diethylamine hydrochloride is filtered off and the filtrate is shaken out with 2η sodium hydroxide solution.
Die abgetrennte und getrocknete Ätherlösung wird abgedampft und der Rückstand im Feinvakuum destilliert; Ausbeute 43% der Theorie; Flüssigkeit, Kp.o,o5 = 1620C; nls =■■ 1,5018.The separated and dried ether solution is evaporated and the residue is distilled in a fine vacuum; Yield 43% of theory; Liquid, boiling point, o5 = 162 0 C; nl s = ■■ 1.5018.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK64626A DE1288586B (en) | 1967-06-24 | 1967-06-24 | N-AEthyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diaethylcarbamoyloxy) -butyl] -carbamic acid ethyl ester and process for its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK64626A DE1288586B (en) | 1967-06-24 | 1967-06-24 | N-AEthyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diaethylcarbamoyloxy) -butyl] -carbamic acid ethyl ester and process for its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1288586B true DE1288586B (en) | 1969-02-06 |
Family
ID=7231713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEK64626A Pending DE1288586B (en) | 1967-06-24 | 1967-06-24 | N-AEthyl-N- [2-benzyl-2-ethyl-3- (N ', N'-diaethylcarbamoyloxy) -butyl] -carbamic acid ethyl ester and process for its preparation |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1288586B (en) |
-
1967
- 1967-06-24 DE DEK64626A patent/DE1288586B/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| None * |
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