AU613386B2 - Preparation of a new diosmine derivative - Google Patents
Preparation of a new diosmine derivativeInfo
- Publication number
- AU613386B2 AU613386B2 AU20128/88A AU2012888A AU613386B2 AU 613386 B2 AU613386 B2 AU 613386B2 AU 20128/88 A AU20128/88 A AU 20128/88A AU 2012888 A AU2012888 A AU 2012888A AU 613386 B2 AU613386 B2 AU 613386B2
- Authority
- AU
- Australia
- Prior art keywords
- diosmine
- preparation
- derivative
- new
- aluminium
- 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.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
6 13 38 8,.
COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952-62 COMPLETE SPECIFICATION
(ORIGINAL)
FOR OFFICE USE: Appliz-ation Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority: R la'ed Art: Class Int. Class Name of 'Applicant: Address of Applicant: Actual Inventor: Address for Service: TO BE COMPLETED BY APPLICANT FABRICA ESPAROLA DE PRODUCTOS QUIMICOS Y FARMACEUTICOS, S.A.
Lejona-Lamiaco (Vizcaya/Spain) Apartado 555 Bilbao Aurelio Orjales VENERO and Ramon Mosquera PESTANA care of R.K. MADDERN ASSOCIATES, 345 King William Street, Adelaide, South Australia, 5000 Complete Specification for the invention entitled: "PREPARATION OF A NEW DIOSMINE DERIVATIVE" The following statement is a full description of this invention, including the best method of performing it known toxwac us.
la PREPARATION OF A NEW DIOSMINE DERIVATIVE Diosmine is a polyhydroxylated flavone with eight hydroxyl groups, two of them are phenolic and the other six being in the sugar rest, and is able to undergo different reactions being esterification one of them.
Diosmine can give esters when it is treated with a reactive derivative of organic and inorganic acids in a suitable solvent. In particular Diosmine forms esters from sulfuric acid when it reacts with a sulfating agent, varying the esterification index with the conditions of the reactions, especially with the molar ratio of diosmine/sulfating agent. In certain conditions it is 'possible to esterify all the hydroxyl groups of the molecule and to afford the octasulfate of diosmine.
The sulfur trioxide-pyridine complex or the sulfur trioxide-trialkylamine complexes are used as sulfating i agents. The first of these is obtained from chlorosulfonic acid or from the sulfur trioxide and the pyridine, and it can be prepared and purified previous to its use or formed i in situ in the reaction vessel. The sulfur trioxide-pyridine i 20. complex sulfates substances such as hydrazine, diethylamine, phenol and naphthalene, and it has been used in preparation of carbohydrate, sterol and phenol sulfate esters. The sulfur trioxide-trialkylamine complexes, especially those formed with trimethylamine and triethylamine, are also useful to carry out the reaction. They are mild agents, sulfating alcohols or phenols.
In the present invention, the preparation of a new diosmine derivative is described. The diosmine derivative is an aluminium a-ddiosmine octasulfate which has a great pharmacological interest.
The product administered orally in doses of 200 mg/kg to rats with gastric lesions induced by pure ethanol (following 'the technique of A. Robert et al., Gastroenterology, 77, 433-443 (1979)) significantly protected the gastric mucosa.
2 In another experiment carried out in accordance with Shay et al's method (Gastroenterology, 5, 43-61 (1945)) the aluminium ae.
4 diosmine octasulfate significantly protected the glandular and aglandular region of the stomach at doses of 100 and 200 mg/kg., when it was administered orally immediately after the pilorus ligation.
Besides the gastric mucosa protective activity and acid-consuming capacity of the aluminium and diosmine octasulfate, it lacks of undesirable side effects.
o2 10. The preparation of the aluminium aft4\ diosmine octasulfate is carried out by the reaction of the diosmine with the sulfur trioxide-pyridine complex or with the sulfur trioxide-trialkylamine complexes, using the sulfating agents in an excess.
15. The solvent employed in the sulfation of Diosmine is chosen among pyridine, dimethylformamide and dimethylacetamide and the temperature at which the reaction oo° takes places can oscilate between 402 and 1100 C without o°~to a substantial variation in the result of the process, but at low temperatures the completion of the reaction a 00 takes more time.
The aluminium salt of the diosmine octasulfate can be made from the corresponding sodium salt or from the o corresponding ammonium salt by adding aluminium 25.hydroxychloride in an aqueous solution.
The followi.ng examples of the preparation of the So,\t. o- 'C-v-EL aluminium a~44ddiosmine octasulfate illustrate the invention but are not exhaustive.
1 A mixture of 10 g. of diosmine and 25 g. of the sulfur trioxide-pyridine complex in 100 ml. of pyridine is heated at a temperature of 60Q C for 5 hours with The upper layer of pyridine is separated by i V(ri^ CI- 3 decantation and the lower one is neutralized with concentrated aqueous sodium hydroxide. Ethyl alcohol is added dropwise until a precipitate begins to form. This deposit is filtered off and more ethyl alcohol is added to the liquid part. The new solid formed is separated by filtration and is washed several times with ethyl alcohol.
It is dried at room temperature in vus (16.7 It is p dissolved in 200 ml. of distilled water and 130 ml. of a i 15% solution of aluminium hydroxychloride is added. The 10.resulting yellow solid is filtered, washed several times OB« with water and is dried in vacuum at room temperature c 0 o (26 M.P. higher than 250QC.
S IR (3490, 1640 cm C28H64Al 6 0 7 9
S
8 calculated: Al 18,34 S 10,90 o 15. found 18,71 10,81 0 00 l* EXAMPLE 2 00 g. of diosmine and 24 g. of the sulfur complex is heated in 40 ml. of a dimethylformamide for 2 hours at a temperature of The mixture is cooled at room temperature and then poured into 400 ml. of acetone with stirring. The upper layer is separated by decantation and the lower layer is washed twice acetone. It is the dissolved in water and 150 ml. of a 15% solution of aluminium hydroxychloride is added. The solid which forms is filtered, washed in water and dried.
17 g. of the product described in Example 1. are obtained.
L, I~ ~I _ii~ U-YI_-~L -I
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES8702270A ES2004465A6 (en) | 1986-05-09 | 1987-07-31 | Preparation of a new diosmine derivate. |
| EP87500053A EP0302155B1 (en) | 1986-05-09 | 1987-07-31 | Preparation of a new diosmine derivate |
| ES8702270 | 1987-07-31 | ||
| EP87500053 | 1987-07-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2012888A AU2012888A (en) | 1989-02-02 |
| AU613386B2 true AU613386B2 (en) | 1991-08-01 |
Family
ID=26112482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU20128/88A Ceased AU613386B2 (en) | 1987-07-31 | 1988-07-29 | Preparation of a new diosmine derivative |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS6463590A (en) |
| AR (1) | AR247216A1 (en) |
| AT (1) | AT397504B (en) |
| AU (1) | AU613386B2 (en) |
| CA (1) | CA1318317C (en) |
| FI (1) | FI88924C (en) |
| GR (1) | GR880100499A (en) |
| NO (1) | NO171165C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3730858B2 (en) * | 2000-12-01 | 2006-01-05 | 株式会社エヌ・ティ・ティ・ドコモ | Mail system, server, and mail transmission / reception device |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR6967M (en) * | 1968-01-22 | 1969-05-19 | ||
| EP0075626A1 (en) * | 1981-09-29 | 1983-04-06 | American Cyanamid Company | Novel rutin nona- and deca(H-)sulfate salts, methods of preparing novel salts, and use of novel salts of complement inhibitors |
-
1988
- 1988-07-19 AT AT0185388A patent/AT397504B/en not_active IP Right Cessation
- 1988-07-26 FI FI883508A patent/FI88924C/en not_active IP Right Cessation
- 1988-07-28 JP JP63189532A patent/JPS6463590A/en active Granted
- 1988-07-28 GR GR880100499A patent/GR880100499A/en unknown
- 1988-07-28 CA CA000573330A patent/CA1318317C/en not_active Expired - Fee Related
- 1988-07-29 AU AU20128/88A patent/AU613386B2/en not_active Ceased
- 1988-07-29 AR AR88311551A patent/AR247216A1/en active
- 1988-07-29 NO NO883363A patent/NO171165C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR247216A1 (en) | 1994-11-30 |
| FI88924C (en) | 1993-07-26 |
| AU2012888A (en) | 1989-02-02 |
| FI883508A0 (en) | 1988-07-26 |
| JPS6463590A (en) | 1989-03-09 |
| NO171165B (en) | 1992-10-26 |
| ATA185388A (en) | 1993-09-15 |
| FI883508A (en) | 1989-02-01 |
| AT397504B (en) | 1994-04-25 |
| FI88924B (en) | 1993-04-15 |
| NO171165C (en) | 1993-02-03 |
| NO883363L (en) | 1989-02-01 |
| CA1318317C (en) | 1993-05-25 |
| NO883363D0 (en) | 1988-07-29 |
| JPH0555518B2 (en) | 1993-08-17 |
| GR880100499A (en) | 1989-04-12 |
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