GB2096138A - 7-(2-diethylaminoethyl)theophylline acetylsalicylate and a process for the preparation thereof - Google Patents
7-(2-diethylaminoethyl)theophylline acetylsalicylate and a process for the preparation thereof Download PDFInfo
- Publication number
- GB2096138A GB2096138A GB8207789A GB8207789A GB2096138A GB 2096138 A GB2096138 A GB 2096138A GB 8207789 A GB8207789 A GB 8207789A GB 8207789 A GB8207789 A GB 8207789A GB 2096138 A GB2096138 A GB 2096138A
- Authority
- GB
- United Kingdom
- Prior art keywords
- process according
- theophylline
- solvent
- diethylaminoethyl
- acetylsalicylate
- 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.)
- Granted
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
7-(2-diethylaminoethyl)theophylline acetylsalicylate is a new compound having pharmaceutical applications. The compound can be prepared by reacting 7-(2-diethylaminoethyl)-theophylline with acetylsalicylic acid.
Description
SPECIFICATION 7-(2-diethylaminoethyl)-theophyl line acetylsalicylate and a process for the preparation thereof
This invention relates to a new compound 7 (2-diethylaminoethyl)-theophylline acetylsalicylate, and to a process for the preparation thereof.
Since the introduction of theophylline into therapeutical treatment, with the recognition of its action on the blood and respiratory stystems, it has held a leading place amongst similarly indicated drugs. At the same time, in view of the need to have theophylline derivatives having a greater pharmacological activity and devoid, as far as possible, of the side effects and physico-chemical drawbacks of the alkaloid per se, there has been offered a number of more or less manageable and active theophylline salts which have been accepted to a greater or lesser extent, the culmination of this acceptance being the preparation, in 1946, of 7-(2-diethylaminoethyl)-theophylline (Etamiphylline) which, being a chemical base, with facility for forming salts, offers optimum pharmacological characteristics.During thirty years of use this theophylline derivative has shown its qualities by being converted into a number of salts with different therapeutic activities (iodomethylate, hydrochloride, camphosulphonate and dehydrocho late). The therapeutic actions referred to above may be summed up as: an increase in the cardio-respiratory action with general vasodilation and bronchodilation, spasmolytic action and promotion of diuresis.
Acetylsalicylic acid, in spite of its being introduced almost a century ago, is still widely used in modern pharmacology, occupying a leading role not only within its pharmacological group, but also in the overall range of drugs integrating the present day therapeutical arsenal.
This reputation has been promoted and maintained by its pharmaco-therapeutic activity in a number of different areas which appear alone or in combination in very many clinical pictures. Its activity is developed against such frequent symptoms as pain (analgesic/antialgic action), inflammation (antiphlogistic antiinflammatory and antirheumatic action) and fever (antipyretic), against which acetylsalicylic acid has always acted effectively.
The general effect of the salicylic acid derivatives is a depression of the central nervous system, the point of action being located in the subcortical space.
The antialgic action is probably due to its acting on the stria terminalis, on which it may have a depressive action. Its activity is manifested especially on pain derived from an inflammatory process in organs of a tegumentary, rather than visceral structure, such as headaches, neuralgias and particularly arthralgias.
The antiinflammatory action, not fully described in view of its variety according to the originiating causes, may be generalised with a
PGs synthesis inhibiting activity, suppressing their participation in the inflammation, vasodilation, increase of permeability, etc. It may also block certain reactions in which quinines and SRS-A participate.
The antipyretic action is due to its activity on the central nervous system, particularly on the hypothalamus where the body temperature thermoregulating centre is located, either directly or by prior reiease of prostaglandins.
As a result of the hypothalmic action, the well known effects of acetylsalicyclic acid, such as sweating and vasodilation, are stimulated.
More recently a new activity, that of platelet antiaggregant, has been discovered. Sufficient experience has been obtained of this activity to add it to the other actions.
The interference by acetylsalicylic on the platelet function, based on the inhibition of platelet release and subsequent aggregation caused by adrenaline, adenosine phosphate and small amounts of collagen and thrombin has been confirmed. Thus acetylsalicylic acid makes the formation of the thrombus, induced by the platelets, difficult, thereby hindering the clinical derivations that this has.
It has, unexpectedly been found that it is possible to produce the acetylsalicylate salt of 7-(2-diethylaminoehtyl)-theophylline and that the properties of the compound are the combined properties of the two constituent parts.
The combination of the anti-aggregant and, therefore, anti-thrombotic activity of acetylsalicylic acid with the vasodilating activity of 7 (2-diethylaminoethyl)-theophylline offers excellent therapeutical advantages in the treatment of thromboembolic disease.
The compound of the invention offers the advantage of an excellent solubility, which allows suitable concentrations for quickly obtaining high blood levels by parenteral and oral administration.
The formula of the compound is CgH80 413H21N5O2, the molecular weight is 459.50 and the pH of a 5% solution is 6.02.
The process for preparing the compound according to the invention comprises reacting 7-(2-diethylaminoethyl)-theophylline in a solvent medium with acetylsalicylic acid.
The solvent medium may for example, be a ketone, such as acetone or methylethyl ketone, an alcohol, such as ethanol, isopropanol, n-propanol or tert-butanol or a chlorinated solvent such as chloroform or methylene chloride.
The following Example illustrates the invention.
EXAMPLE 1 80.1 9 (1 mole) of acetylsalicylic acid were dissolved in 360 ml of acetone. There was added to this solution a previously prepared solution of 279.3 g (1 mole) of 7-(2 diethylaminoethyl)--:heophylline base in 300 ml of acetone.
The solution thus obtained was stirred for 8 hours at room temperature. Thereafter the resulting white precipitate was filtered off and washed once with 500 ml of acetone.
The new substance thus obtained, after drying for 4 hours at 1 50 C, had a m.p. 109 to 111 C. The yield was 390 g (85%).
CLAli\nS 1. 7-(2-diethylaminoethyl)-theophylline acetylsalicylate.
2. A process for the preparation of 7-(2diethylaminoethyl)-theophylline acetylsalicylate, wherein 7-(2-diethylaminoethyl)-theophylline is reacted in a solvent medium with acetylsalicylic acid.
3. A process according to claim 2, wherein the solvent medium is a ketone.
4. A process according to claim 3, wherein the solvent is acetone or methylethyl ketone.
5. A process according to claim 2, wherein the solvent rriedium is an alcohol.
6. A process according to claim 5, wherein the solvent is ethanol, iso-propanol, npropanol or tert-butanol.
7. A process according to claim 2, wherein the solvent medium is a chlorinated solvent.
8. A process according to claim 7, wherein the solvent is chloroform or methylene chloride.
9. A process according to claim 2, substantially as described in the Example.
1 0. 7-(2-diethylaminoethyl)-theophylline acetylsalicylate whenever produced by a process according to any of claims 2 to 9.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (9)
1. 7-(2-diethylaminoethyl)-theophylline acetylsalicylate.
2. A process for the preparation of 7-(2diethylaminoethyl)-theophylline acetylsalicylate, wherein 7-(2-diethylaminoethyl)-theophylline is reacted in a solvent medium with acetylsalicylic acid.
3. A process according to claim 2, wherein the solvent medium is a ketone.
4. A process according to claim 3, wherein the solvent is acetone or methylethyl ketone.
5. A process according to claim 2, wherein the solvent rriedium is an alcohol.
6. A process according to claim 5, wherein the solvent is ethanol, iso-propanol, npropanol or tert-butanol.
7. A process according to claim 2, wherein the solvent medium is a chlorinated solvent.
8. A process according to claim 7, wherein the solvent is chloroform or methylene chloride.
9. A process according to claim 2, substantially as described in the Example.
1 0. 7-(2-diethylaminoethyl)-theophylline acetylsalicylate whenever produced by a process according to any of claims 2 to 9.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES501162A ES8202009A1 (en) | 1981-04-07 | 1981-04-07 | 7-(2-diethylaminoethyl)theophylline acetylsalicylate and a process for the preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2096138A true GB2096138A (en) | 1982-10-13 |
| GB2096138B GB2096138B (en) | 1984-08-01 |
Family
ID=8482205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8207789A Expired GB2096138B (en) | 1981-04-07 | 1982-03-17 | 7-(2-diethylaminoethyl)-theophylline acetylsalicylate and a process for the preparation thereof |
Country Status (6)
| Country | Link |
|---|---|
| CH (1) | CH647780A5 (en) |
| DE (1) | DE3212909A1 (en) |
| ES (1) | ES8202009A1 (en) |
| GB (1) | GB2096138B (en) |
| IT (1) | IT1153967B (en) |
| PT (1) | PT74716B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0169466A2 (en) * | 1984-07-21 | 1986-01-29 | Hoechst Aktiengesellschaft | Mixture of xanthin derivatives and O-acetyl-salicylic acid, or their pharmacologically acceptable salts, and its use |
| FR2631030A1 (en) * | 1988-05-05 | 1989-11-10 | Coma Julia Concepcion | PROCESS FOR OBTAINING 7- (2-DIETHYLAMINO-ETHYL) -THOPHYLLIN ACETYL-SALICYLATE AND ITS APPLICATION TO THE PREPARATION OF ANTI-AGGLUTINANT AND ANTI-THROMBOTIC AGENTS |
-
1981
- 1981-04-07 ES ES501162A patent/ES8202009A1/en not_active Expired
-
1982
- 1982-03-17 GB GB8207789A patent/GB2096138B/en not_active Expired
- 1982-03-22 CH CH1743/82A patent/CH647780A5/en not_active IP Right Cessation
- 1982-03-30 IT IT20487/82A patent/IT1153967B/en active
- 1982-04-06 DE DE19823212909 patent/DE3212909A1/en active Granted
- 1982-04-06 PT PT74716A patent/PT74716B/en unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0169466A2 (en) * | 1984-07-21 | 1986-01-29 | Hoechst Aktiengesellschaft | Mixture of xanthin derivatives and O-acetyl-salicylic acid, or their pharmacologically acceptable salts, and its use |
| EP0169466A3 (en) * | 1984-07-21 | 1986-05-21 | Hoechst Aktiengesellschaft | Mixture of xanthin derivatives and o-acetyl-salicylic acid, or their pharmacologically acceptable salts, and its use |
| US4880791A (en) * | 1984-07-21 | 1989-11-14 | Hoechst Aktiengesellschaft | Combination product composed of xanthine derivatives and O-acetylsalicylic acid or its pharmacologically tolerated salts, and its use |
| FR2631030A1 (en) * | 1988-05-05 | 1989-11-10 | Coma Julia Concepcion | PROCESS FOR OBTAINING 7- (2-DIETHYLAMINO-ETHYL) -THOPHYLLIN ACETYL-SALICYLATE AND ITS APPLICATION TO THE PREPARATION OF ANTI-AGGLUTINANT AND ANTI-THROMBOTIC AGENTS |
| US4908111A (en) * | 1988-05-05 | 1990-03-13 | Laboratories Boi, S.A. | Process for the preparation of 7-(2-diethylaminoethyl)-theophylline acetyl salicylate and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| ES501162A0 (en) | 1982-02-01 |
| IT8220487A0 (en) | 1982-03-30 |
| PT74716A (en) | 1982-05-01 |
| DE3212909C2 (en) | 1990-07-26 |
| GB2096138B (en) | 1984-08-01 |
| DE3212909A1 (en) | 1982-11-18 |
| IT1153967B (en) | 1987-01-21 |
| PT74716B (en) | 1983-11-14 |
| CH647780A5 (en) | 1985-02-15 |
| ES8202009A1 (en) | 1982-02-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19930317 |