DE1768370C - Diethyl alpha- (2-dibenzofuranyl) malonate - Google Patents
Diethyl alpha- (2-dibenzofuranyl) malonateInfo
- Publication number
- DE1768370C DE1768370C DE1768370C DE 1768370 C DE1768370 C DE 1768370C DE 1768370 C DE1768370 C DE 1768370C
- Authority
- DE
- Germany
- Prior art keywords
- dibenzofuranyl
- diethyl
- malonate
- diethyl alpha
- alpha
- 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
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title claims description 10
- 239000000969 carrier Substances 0.000 claims 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 3
- 206010018691 Granuloma Diseases 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- -1 2-dibenzofuranyl Chemical group 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010039073 Rheumatoid arthritis Diseases 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N Sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory Effects 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 201000004624 dermatitis Diseases 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
- 239000000203 mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XOGVXXZJULSKDB-UHFFFAOYSA-N C1(=CC=CC=2OC3=C(C21)C=CC=C3)CC(=O)OCC Chemical compound C1(=CC=CC=2OC3=C(C21)C=CC=C3)CC(=O)OCC XOGVXXZJULSKDB-UHFFFAOYSA-N 0.000 description 1
- 229940113118 Carrageenan Drugs 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 208000005679 Eczema Diseases 0.000 description 1
- 235000009161 Espostoa lanata Nutrition 0.000 description 1
- 240000001624 Espostoa lanata Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 210000003491 Skin Anatomy 0.000 description 1
- 208000006641 Skin Disease Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 201000005794 allergic hypersensitivity disease Diseases 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agents Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 230000001684 chronic Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 231100000406 dermatitis Toxicity 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 231100001003 eczema Toxicity 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 201000005569 gout Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutic aid Substances 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
Description
Die Erfindung betrifft das Diüthyl-a-(2-dibenzo« funwyO-malonat der FormelThe invention relates to diethyl-a- (2-dibenzo " funwyO-malonat the formula
COOC2HjCOOC 2 HY
CHCH
COOC2H5 COOC 2 H 5
Es wurde gefunden, daß die Verbindung und diese enthaltendes Anliphlogisticum ein sehr interessantes entzündungshemmendes Mittel ist. Die antiphlogistische Wirkung wurde durch den aus Proceedings Society Experimental Biology Medicine, 111 (1962), S. 544, bekannten, durch Carrageenan induzierten Ödem-Test bestimmt. Hierzu wurden weibliche Ratten vom Wistar-Stamm verwendet, die zwischen 120 und 15Og wogen, Die Verbindung wurde auf oralem Weg in einer Suspension einer 10%igen Akaziengummilösung in verschiedenen Dosierungen verabreicht. It has been found that the compound and anliphlogisticum containing it is a very interesting is anti-inflammatory agent. The anti-inflammatory effect was determined by the Proceedings Society Experimental Biology Medicine, 111: 544 (1962), induced by carrageenan Edema test determined. For this purpose, female rats from the Wistar strain were used, which were between 120 and weighed 150 g. The compound was administered orally in a suspension of a 10% acacia gum solution administered in various dosages.
Ferner wurde die entzündungshemmende Wirksamkeil durch den Granulom-Kügelchen-Test (R. Meier, W. Schuler, P. Desaules, Experientia, 6 [1950],Furthermore, the anti-inflammatory active wedge was determined by the granuloma bead test (R. Meier, W. Schuler, P. Desaules, Experientia, 6 [1950],
5. 1469) geprüft. Es wurden hierfür Wistar-Ratten verwendet, bei denen unter der Haut zwei Baumwollkügelchen eingesetzt wurden. Der Versuch wurde für jede verwendete Dosis an Gruppen von jeweils sieben Tieren durchgeführt. Die zu prüfende Verbindung wurde oral und in einer Suspension einer 0,5% igen wäßrigen Methylcelluloselösung, und zwar 6 Tage lang einmal täglich verabreicht. Am Ende des5. 1469) checked. Wistar rats were used for this used, in which two cotton balls were placed under the skin. The attempt was made performed on groups of seven animals for each dose used. The connection to be tested was taken orally and in a suspension of a 0.5% aqueous methyl cellulose solution, namely Administered once a day for 6 days. At the end of
6. Tages wurde, nachdem die Ratten getötet worden waren, die Volumenabnahme der Granuloma bestimmt. On the 6th day after the rats were sacrificed, the decrease in volume of the granulomas was determined.
In den obigen Versuchen wurde als Vergleichssubstanz Acetylsalicylsäure verwendet. Die hierbei erzielten Ergebnisse sowie die LD50-Werte sind nachstehend angegeben.In the above experiments, acetylsalicylic acid was used as a comparison substance. The results achieved here and the LD 50 values are given below.
Rallen,
per os
mg/kgDose at
Rails,
per os
mg / kg
Udem,
prozentuale
Abnahme
des ÖdemsCarrageenin
Udem,
percentage
acceptance
of the edema
kügelchen,
prozentuale
Gewichts
abnahme des
Granulomscotton
globules,
percentage
Weight
decrease of the
Granuloma
benzofuranyl)-
malonatDiethyl-a- (2-di-
benzofuranyl) -
malonat
100
20050
100
200
27,8
48,616.7
27.8
48.6
24,9
38,618.8
24.9
38.6
säureAcetylsalicylic
acid
50
10020th
50
100
21,4
38,611.4
21.4
38.6
19,0
30,815.2
19.0
30.8
LD,n-WerteLD, n values
i. p.
mg/kgMii
ip
mg / kg
per os
mg/kguse
per os
mg / kg
i. p.
mg/kg Ri
ip
mg / kg
oralkill
orally
a-(2-dibenzo-
furanyl)-
malonatDiethyl
a- (2-dibenzo-
furanyl) -
malonat
14301330 to
1430
säureAcetylsalicylic
acid
Aus den gefundenen Werten geht hervor, daß das Diathyl-u-(2-dibenzofuranyl)-molonat der Vergleiohssubstanz bedeutend Überlegen istThe values found show that the diethyl u- (2-dibenzofuranyl) molonate is the comparative substance is significantly superior
Das DlU(hyl-«-C2-dlbcnzofiirunyl)-malonal findet als s aktiver Bestandteil in einem therapeutischen Mittel Verwendung. Ausgezeichnete Ergebnisse wurden bei der Behandlung einiger Hautkrankheiten, beispielsweise von Ekzemen und allengischer Dermatitis, durch die Anwendung von Salben erzielt, die 0,1 bis ίο 1 % des Diäthyl-a-(2-dibenzofuranyl)-malonats in Mischung mit üblichen pharmazeutischen Trägerstoffen enthielten.The DlU (hyl - «- C2-dlbcnzofiirunyl) -malonal takes place as s active ingredient in a therapeutic agent Use. Excellent results have been obtained in treating some skin diseases, for example of eczema and allergy dermatitis, achieved by the application of ointments that range from 0.1 to ίο 1% of the diethyl a- (2-dibenzofuranyl) -malonate in mixture with conventional pharmaceutical excipients.
Ferner ist das Diäthyl-a-(2-dibenzofuranyl)-malonat auch sehr wirksam bei der Heilung von beispielsweise rheumatischem Fieber, chronischer rheumatischer Arthritis, rheumaartiger Arthritis und Gicht, wobei die Ergebnisse bei den üblichen Verabreichungsformen, wie oraler, intramuskulärer sowie rektaler Gabe zufriedenstellend waren.Furthermore, the diethyl α- (2-dibenzofuranyl) malonate is also very effective in curing, for example rheumatoid fever, chronic rheumatoid arthritis, rheumatoid arthritis and gout, the results with the usual forms of administration, such as oral, intramuscular and rectal Gabe were satisfactory.
Das Diäthyl-a-(2-dibenzofuranyl)-malonat wird dadurch hergestellt, daß man Äthyl-2-dibenzofuranylacetat in an sich bekannter Weise mit 1 bis 1,5 Mol Natriumäthylat, gelöst in einem mehr als äquimolaren Überschuß an Diäthylcarbonat, erhitzt.The diethyl a- (2-dibenzofuranyl) malonate is thereby produced that ethyl 2-dibenzofuranylacetate in a known manner with 1 to 1.5 mol Sodium ethylate dissolved in a more than equimolar excess of diethyl carbonate is heated.
8,6 g Natrium werden in 240 ecm wasserfreiem Äthanol gelöst, und dann wird das Lösungsmittel auf einem Ölbad abdestilliert. Der Rückstand von Natriumäthylat wird nun in 250 ecm Diäthylcarbonat gelöst und dann langsam im Verlauf von 2,5 Stunden mit einer Lösung von 69 g Äthyl-2-dibenzofuranylacetat in 250 ecm Diäthylcarbonat versetzt. Hierauf wird die Badtemperatur auf 1500C erhöht, bis das Lösungsmittel vollständig entfernt ist. Das Gemisch wird dann in Eiswasser gegossen, mit Salzsäure angesäuert und 3- bis 4mal mit Diäthyläther extrahiert. Die vereinigten Ätherextrakte werden über Natriumsulfat getrocknet und anschließend zur Trockne abgedampft. Der Rückstand wird aus Isopropyläther umkristallisiert, wobei 6,7 g Diäthyl-a-(2-dibenzofuranyl)-malonat vom F. 84,5 bis 85° C erhalten werden.8.6 g of sodium are dissolved in 240 ecm of anhydrous ethanol and then the solvent is distilled off on an oil bath. The residue of sodium ethylate is now dissolved in 250 ecm of diethyl carbonate and then slowly added in the course of 2.5 hours with a solution of 69 g of ethyl 2-dibenzofuranyl acetate in 250 ecm of diethyl carbonate. The bath temperature is then increased to 150 ° C. until the solvent has been completely removed. The mixture is then poured into ice water, acidified with hydrochloric acid and extracted 3 to 4 times with diethyl ether. The combined ether extracts are dried over sodium sulfate and then evaporated to dryness. The residue is recrystallized from isopropyl ether, 6.7 g of diethyl a- (2-dibenzofuranyl) malonate having a melting point of 84.5 ° to 85 ° C. are obtained.
Claims (3)
Family
ID=
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