GB2028794A - A 3-benzoylpropionamide and pharmaceutical compositions containing it - Google Patents
A 3-benzoylpropionamide and pharmaceutical compositions containing it Download PDFInfo
- Publication number
- GB2028794A GB2028794A GB7834860A GB7834860A GB2028794A GB 2028794 A GB2028794 A GB 2028794A GB 7834860 A GB7834860 A GB 7834860A GB 7834860 A GB7834860 A GB 7834860A GB 2028794 A GB2028794 A GB 2028794A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- benzoylpropionamide
- solution
- composition
- pharmaceutical compositions
- 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.)
- Withdrawn
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Classifications
-
- 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
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides the 3- benzoylpropionamide of the formula: <IMAGE> (a sedative and tranquiliser) and pharmaceutical compositions comprising it.
Description
SPECIFICATION
A 3-benzoylpropionamide and pharmaceutical compositions containing it
The present invention relates to the 3-benzoylpropionamide of the formula:
and to pharmaceutical compositions containing it.
We have found that the above compound is pharmaceutically valuable as a sedative. It has in part the characteristics of the benzodiazepines and in part those of butyrophenones without the side-effects of these two classes of drugs. Thus the compound of the invention is of value in the clinical treatment of insomnia with induction of physiological sleep. It has also been found to be of value in the clinical treatment of excitation without any danger of causing depression.
Tests show that the above compound has a remarkable activity in countering the tremors caused in mice and rats by the administration of ketotremorine. The compound of the invention has a sedative effect at doses well below hypnotical ones. An evaluation has been performed on mice, in comparison with chlorpromazine. The compound of the invention, whether injected endoperitoneally or administered per os, reduces the spontaneous motility of mice remarkably, even at such a low dose as 10 mg/kg.
The remarkable difference between the minimum dose capable of reducing the spontaneous motility in the mouse and the dose capable of depressing the r.r. (righting reflux) suggests that there might be some similarity of action between the compound of the invention and neuroleptics. In fact, the compound of the invention shows itself to be capable of increasing the sleeping time of pentobarbital-induced sleep in a way similar two neuroleptics in general and to chlorpromazine in particular. The reduction of the spontaneous motility in mice and rats could be due either to an activity on the CNS (central nervous system) or to a direct activity on the muscles.Thus, we have determined the minimum effective dose of the compound of the invention capable of making the mice unable, for at least two minutes, to cling to a wire netting suspended at a distance of 60 cm from the bench. This dose is greater than 100 mg/kg for the compound of the invention whereas for chlorpromazine it is 2.5 mg/kg. This leads to belief that the reduction of the spontaneous motility in mice obtained by administering less than 100 mg/kg of the tested substance is not to be attributed to a significant reduction of the muscular force of the animals.
According to a further feature of the invention, therefore, there is provided a pharmaceutical composition comprising the compound of the invention in association with a suitable pharmaceutical carrier or diluent.
The pharmaceutical composition can be made by mixing the compound of the invention with the carrier or diluent. The optimum nature of the pharmaceutical composition and the pharmaceutical carrier or diluent will obviously depend upon the desired mode of administration.
As a unit dose, one which is commensurate with the level of activity for the inventive substance and with the wanted effect is selected. A generally useful unit dosage is 0.5 g, but larger or smaller unit doses can be used, which can be divided or multiplied before administration by the patient. Advantageously the pharmaceutical composition will be made up in a dosage unit form, preferably in 0.5 to 2 g units, e.g. tablets or sterile injectable solutions.
The present invention also includes within its scope the compound of the invention for use in a method of treating insomnia with induction of physiological sleep as well as for use in a method of treating excitement (as a tranquilizer). A preferred such use is in a method of treating insomnia accompanied by serious disorder of the nervous system which comprises administering to the patient a therapeutically effective amount (e.g.
0.5 - 2 g/per day) of the compound of the invention at suitable intervals.
The compound of the invention can be prepared from ss-benzoylpropionic acid and 3-amino-butyrolactone using the mixed anhydride method. Both ss-benzoylpropionic acid and 3-amino-butyrolactone can be readily prepared by methods known in literature. Therefore, according to a further feature of the invention, there is provided a process for manufacturing the compound ofthe invention, comprising reacting ss- benzoylpropionic acid in solution in an anhydrous, inert organic solvent, e.g. benzene, with triethylamine and ethyl chloroformate, separating from the solution, the triethylamine chlorhydrate, formed, e.g. by filtration, and adding 3-amino-butyrolactone to the solution.Conveniently, the product is worked up by reducing the volume of the reaction mixture, collecting the precipitate on a filter and crystallizing it, e.g. from ethanol. The invention is illustrated but in no way limited by the following Examples.
Example 1
1 mole of ss-benzoylpropionic acid prepared by methods known in literature is dissolved in 5 times its weight of an hydros benzene and reacted with 1 mole of triethylamine and 1 mole of ethyl chloroformate at a temperature between 0 and 5"C. After 30 minutes the triethylamine chlorhydrate is filtered off under anhydrous conditions. To the filtered solution is added 1 mole of 3-amino-butyrolactone (prepared by methods known in literature), at a temperature between 0 and 5"C. CO2 is liberated. After about 2 hours the volume of reaction mixture is reduced to half. The precipitate is collected on a filter and crystallized from ethanol. The resultant 3-(3'-benzoylpropionamido)butyrolactone of the above formula is characterized by
NMR, IR and UV analysis.
Example 2
The 3-(3'-benzoylpropionamido)butyrolactone prepared as described in Example 1, is used for making 0.5 g tablets, adding starch, lactose, etc. as carriers.
The daily dose of the compound of the invention varies from 0.5 to 2.0 g for the treatment of insomnia accompanied by serious disorder of the nervous system. The acute endoperitoneal toxicity of the compound of the invention has been found to be low, i.e. the LD50 is > 3000 mg/kg.
Claims (7)
1. The 3-benzoylpropionamide of the formula:
2. A process for manufacturing the compound claimed in claim 1, comprising reacting p- benzoylpropionic acid in solution in an an hydrous, inert organic so Ivent with triethylamine and ethyl chloroformate, separating from the solution the triethylamine chlorhydrate formed and then adding 3-amino-butyrolactone to the solution.
3. The compound claimed in claim 1 when produced by a process claimed in claim 2.
4. A pharmaceutical composition comprising the compound claimed in claim 1 or 3 in association with a suitable pharmaceutical carrier or diluent.
5. A composition according to claim 4 in dosage unit form containing 0.5 to 2.0 g of the compound claimed in claim 1 or 3 per dosage unit.
6. The compound claimed in claim 1 or 3 or composition claimed in claim 4 or 5 for use in treating insomnia with induction of physiological sleep.
7. The compound claimed in claim 1 or 3 or composition claimed in claim 4 or 5 for use as a tranquilizer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7834860A GB2028794A (en) | 1978-08-29 | 1978-08-29 | A 3-benzoylpropionamide and pharmaceutical compositions containing it |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7834860A GB2028794A (en) | 1978-08-29 | 1978-08-29 | A 3-benzoylpropionamide and pharmaceutical compositions containing it |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2028794A true GB2028794A (en) | 1980-03-12 |
Family
ID=10499318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7834860A Withdrawn GB2028794A (en) | 1978-08-29 | 1978-08-29 | A 3-benzoylpropionamide and pharmaceutical compositions containing it |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2028794A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0045161A1 (en) * | 1980-07-24 | 1982-02-03 | Imperial Chemical Industries Plc | Amides of 4-oxo-5-amidohexanoic acid derivatives |
| EP0053017A1 (en) * | 1980-11-24 | 1982-06-02 | Imperial Chemical Industries Plc | Amide derivatives |
| EP0151964A2 (en) * | 1984-02-02 | 1985-08-21 | Laboratorio Farmaceutico C.T. s.r.l. | New derivatives of alpha-amino-gamma-butyrolactone, method for the preparation thereof and pharmaceutical compositions containing them |
-
1978
- 1978-08-29 GB GB7834860A patent/GB2028794A/en not_active Withdrawn
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0045161A1 (en) * | 1980-07-24 | 1982-02-03 | Imperial Chemical Industries Plc | Amides of 4-oxo-5-amidohexanoic acid derivatives |
| EP0053017A1 (en) * | 1980-11-24 | 1982-06-02 | Imperial Chemical Industries Plc | Amide derivatives |
| EP0151964A2 (en) * | 1984-02-02 | 1985-08-21 | Laboratorio Farmaceutico C.T. s.r.l. | New derivatives of alpha-amino-gamma-butyrolactone, method for the preparation thereof and pharmaceutical compositions containing them |
| EP0151964A3 (en) * | 1984-02-02 | 1986-03-05 | Laboratorio Farmaceutico C.T. s.r.l. | New derivatives of alpha-amino-gamma-butyrolactone, method for the preparation thereof and pharmaceutical compositions containing them |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |