DE3110460A1 - Sodium salt of benzarone sulphuric acid ester, its preparation and pharmaceutical compositions prepared from this compound - Google Patents

Sodium salt of benzarone sulphuric acid ester, its preparation and pharmaceutical compositions prepared from this compound

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Publication number
DE3110460A1
DE3110460A1 DE19813110460 DE3110460A DE3110460A1 DE 3110460 A1 DE3110460 A1 DE 3110460A1 DE 19813110460 DE19813110460 DE 19813110460 DE 3110460 A DE3110460 A DE 3110460A DE 3110460 A1 DE3110460 A1 DE 3110460A1
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Germany
Prior art keywords
benzarone
acid ester
sodium salt
compound
preparation
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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.)
Ceased
Application number
DE19813110460
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German (de)
Inventor
Theodor Prof. Dr. 4400 Münster Eckert
Hans 4660 Gelsenkirchen-Buer Lepper
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Individual
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Individual
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Priority to DE19813110460 priority Critical patent/DE3110460A1/en
Publication of DE3110460A1 publication Critical patent/DE3110460A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/80—Radicals substituted by oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Published without abstract.

Description

Natrium-Salz des Benzaron-Schwefelsäureesters, Sodium salt of benzarone sulfuric acid ester,

seine Herstellung und aus dieser Verbindung hergestellte Arzneizubereitungen Benzaron ist ein vorwiegend bei Venenerkrankungen und zur Thromboseprophylaxe eingesetztes Therapeutikum, dessen gastrointestinale Resorption nur sehr begrenzt ist. Es besteht infolgedessen das therapeutische Bedürfnis, annähernd neutrale Derivate dieser Verbindung parenteral zu applizieren. Dazu ist aber eine Wasserlöslichkeit eines solchen Derivates erforderlich, das zudem noch in der Lage sein sollte, durch enzymatische Vorgänge wieder in Benzaron gespalten zu werden. its manufacture and medicinal preparations made from this compound Benzarone is used primarily for venous diseases and for thrombosis prophylaxis Therapeutic agent whose gastrointestinal absorption is very limited. It exists consequently the therapeutic need for nearly neutral derivatives of this compound to be applied parenterally. In addition, however, such a derivative must be soluble in water required, which should also be able to use enzymatic processes to be split back into benzarone.

Die erfindungsgemäß beschriebene Verbindung erfüllt diese Voraussetzungen. Es handelt sich um das Natrium-Salz des Schwefelsäureesters des Benzaron.The compound described according to the invention fulfills these requirements. It is the sodium salt of the sulfuric acid ester of benzarone.

Die Herstellung dieser Verbindung kann auf folgendem Wege geschehen: 43 g Benzaron ( entsprechend 0,16 Mol) und 39 g Amidoschwefelsäure ( entsprechend 0,4 Mol) werden in einer zur Lösung ausreichenden Menge Pyridin 2 - 3 Stunden auf ca. 900 erwärmt und das Pyridin anschließend im Vakuum abdestilliert. Der Rückstand wird sodann mit Wasser versetzt und mit NaOH alkalisiert. Der entstandene Schwefelsäureester des Benzaron geht dabei als Natrium-Salz in Lösung. Reste von Pyridin werden durch Wasserdampfdestillation entfernt und die Lösung anschließend mit verdünnter H2SO4 neutralisiert. Dabei fällt nach einigem Stehen in der Kälte nicht umgesetztes Benzaron aus. Es wird abfiltriert und die wäßrige Lösung mehrmals mit Äther ausgeschüttelt, um auch die letzten Reste von nicht umgesetztem Benzaron zu entfernen.This connection can be established in the following way: 43 g benzarone (corresponding to 0.16 mol) and 39 g amidosulfuric acid (corresponding to 0.4 mol) are dissolved in a sufficient amount of pyridine for 2-3 hours about 900 and the pyridine is then distilled off in vacuo. The residue is then mixed with water and made alkaline with NaOH. The resulting sulfuric acid ester The benzarone goes into solution as a sodium salt. Remnants of pyridine are due Steam distillation removed and the solution then with dilute H2SO4 neutralized. It falls after standing in the cold for a while not converted benzarone from. It is filtered off and the aqueous solution several times with Shaken out ether in order to add the last remains of unreacted benzarone remove.

Zur Gewinnung des Natrium-Salzes des Benzaron-Schwefelsäureesters wird die neutralisierte Lösung mit festem Na2C03 410H20 bis zur Sättigung versetzt und die Lösung einige Tage in der Kälte stehen gelassen. Dabei fällt das Natrium-Salz des Schwefelsäureesters des Benzaron aus. Zur vollständigen Ausfällung bewährt es sich, die Lösung in Bewegung zu halten.For obtaining the sodium salt of the benzarone sulfuric acid ester solid Na2C03 410H20 is added to the neutralized solution until it is saturated and let the solution stand in the cold for a few days. The sodium salt falls in the process of the sulfuric acid ester of benzarone. It has proven its worth for complete precipitation to keep the solution moving.

Die ausgefallenen Kristalle der Verbindung werden abfiltriert und anschließend gut getrocknet. Zur Entfernung von noch anhaftendem Na2 CO3 wird das Produkt in absolutem Äthylalkohol aufgenommen und die Lösung filtriert. Der Äthylalkohol wird eingedampft, wobei das Natrium-Salz auskristallisiert.The precipitated crystals of the compound are filtered off and then dried well. This is used to remove any Na2 CO3 that is still adhering Product taken up in absolute ethyl alcohol and the solution filtered. The ethyl alcohol is evaporated, whereupon the sodium salt crystallizes out.

Beim Eindampfen bis zur Trockne erhält man eine weitere Menge des Salzes. Das Salz ist gut wasserlöslich und reagiert in wässriger Lösung annähernd neutral. Die Verbindung kristallisiert mit einem Molekül Kristallwasser. Sie ist wasserfrei sehr hygroskopisch. Die Substanz schmilzt bei 95 - 1050 in ihrem Kristallwasser. Bei 175 - 1850 tritt eine schmelzende Modifikation auf, die sich bei weiterem Erhitzen zersetzt.Evaporation to dryness gives a further amount of the Salt. The salt is readily soluble in water and approximately reacts in aqueous solution neutral. The compound crystallizes with one molecule of water of crystallization. she is anhydrous very hygroscopic. The substance melts at 95-1050 in its crystal water. A melting modification occurs at 175-1850, which occurs with further heating decomposed.

C ber. 55,43 % H ber. 3,55 % S ber. 8,70 % C gef. 55,34 % H gef. 3,78 % S gef. 8,51 % Formel: Benzaronschwefelsäurcester - Na-SalzC calc. 55.43% H calc. 3.55% S calc. 8.70% C found. 55.34% H found. 3.78% S found. 8.51% formula: Benzaron sulfuric acid ester - Na salt

Claims (1)

Patentansprüche 1. Natrium-Salz des Benzaron-Schwefelsäureesters 2. IIerstellung des Natrium-Salzes des Benzaron-Schwe£elsaureesters durch Umsetzung von Benzaron mit Amidoschwefelsäure und anschließender Neutralisation.Claims 1. Sodium salt of benzarone sulfuric acid ester 2. Production of the sodium salt of the benzarone sulfuric acid ester by reaction of benzarone with amidosulfuric acid and subsequent neutralization. 3. Herstellung einer therapeutisch verwendbaren Lösung nach Anspruch 1 und 2 dadurch gekennzeichnet, daß die Verbindung vorzugsweise in wässrigen Medien gelöst wird.3. Production of a therapeutically usable solution according to claim 1 and 2, characterized in that the compound is preferably in aqueous media is resolved. 4. Verwendung der Lösung nach Anspruch 3 als parenteral applizierbares Arzneimittel, vorzugsweise bei Venenerkrankungen, ämorrhoiden, periphexen und arteriellen Durchblutungsstörungen sowie zur Thromboseprophylaxe.4. Use of the solution according to claim 3 as a parenterally applicable Medicines, preferably for venous diseases, hemorrhoids, periphexen and arterial Circulatory disorders and for thrombosis prophylaxis.
DE19813110460 1981-03-18 1981-03-18 Sodium salt of benzarone sulphuric acid ester, its preparation and pharmaceutical compositions prepared from this compound Ceased DE3110460A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19813110460 DE3110460A1 (en) 1981-03-18 1981-03-18 Sodium salt of benzarone sulphuric acid ester, its preparation and pharmaceutical compositions prepared from this compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19813110460 DE3110460A1 (en) 1981-03-18 1981-03-18 Sodium salt of benzarone sulphuric acid ester, its preparation and pharmaceutical compositions prepared from this compound

Publications (1)

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DE3110460A1 true DE3110460A1 (en) 1982-12-30

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DE19813110460 Ceased DE3110460A1 (en) 1981-03-18 1981-03-18 Sodium salt of benzarone sulphuric acid ester, its preparation and pharmaceutical compositions prepared from this compound

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DE (1) DE3110460A1 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6103708A (en) * 1998-05-12 2000-08-15 American Home Products Corporation Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
US6110963A (en) * 1998-05-12 2000-08-29 American Home Products Corporation Aryl-oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US6214877B1 (en) 1998-05-12 2001-04-10 John A. Butera 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
US6221902B1 (en) 1998-05-12 2001-04-24 American Home Products Corporation Biphenyl sulfonyl aryl carboxylic acids useful in the treatment of insulin resistance and hyperglycemia
US6232322B1 (en) 1998-05-12 2001-05-15 American Home Products Corporation Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US6310081B1 (en) 1999-05-10 2001-10-30 American Home Products Corporation Biphenyl sulfonyl aryl carboxylic acids useful in the treatment of insulin resistance and hyperglycemia
US6451827B2 (en) 1998-05-12 2002-09-17 Wyeth 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
US6699896B1 (en) * 1998-05-12 2004-03-02 Wyeth Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6451827B2 (en) 1998-05-12 2002-09-17 Wyeth 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
US6391897B2 (en) 1998-05-12 2002-05-21 American Home Products Corporation Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US6214877B1 (en) 1998-05-12 2001-04-10 John A. Butera 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
US6221902B1 (en) 1998-05-12 2001-04-24 American Home Products Corporation Biphenyl sulfonyl aryl carboxylic acids useful in the treatment of insulin resistance and hyperglycemia
US6232322B1 (en) 1998-05-12 2001-05-15 American Home Products Corporation Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US6248764B1 (en) 1998-05-12 2001-06-19 American Home Products Corporation Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
US6110963A (en) * 1998-05-12 2000-08-29 American Home Products Corporation Aryl-oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US7141672B2 (en) 1998-05-12 2006-11-28 Wyeth Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia
US6451845B1 (en) 1998-05-12 2002-09-17 Wyeth Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
US6103708A (en) * 1998-05-12 2000-08-15 American Home Products Corporation Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
US6369072B2 (en) 1998-05-12 2002-04-09 American Home Products Corporation Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US6683107B2 (en) 1998-05-12 2004-01-27 Wyeth Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
US6699896B1 (en) * 1998-05-12 2004-03-02 Wyeth Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia
US6310081B1 (en) 1999-05-10 2001-10-30 American Home Products Corporation Biphenyl sulfonyl aryl carboxylic acids useful in the treatment of insulin resistance and hyperglycemia

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OAV Applicant agreed to the publication of the unexamined application as to paragraph 31 lit. 2 z1
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