GB2126219A - Basic esters of benzoic acids and 2-thio-phencarboxylic acids - Google Patents
Basic esters of benzoic acids and 2-thio-phencarboxylic acids Download PDFInfo
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- GB2126219A GB2126219A GB08321954A GB8321954A GB2126219A GB 2126219 A GB2126219 A GB 2126219A GB 08321954 A GB08321954 A GB 08321954A GB 8321954 A GB8321954 A GB 8321954A GB 2126219 A GB2126219 A GB 2126219A
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- methyl
- benzoic acid
- useful salt
- ethyl ester
- ester
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
A compound for use as e.g. a local anaesthetic is a basic ester of the formula I <IMAGE> wherein R is a group of the formula <IMAGE> or <IMAGE> wherein each R1 independently is hydrogen or optionally substituted alkyl, and R2 is an optionally substituted alkyl group, an acyl group, halogen, an optionally substituted alkoxy group, an optionally substituted alkylthio group, nitro, amino or an optionally substituted alkylamino group, whereby R and R2 are the same or different, and R3 is a basic group, on a pharmacologically useful salt thereof. Preferably, R1 is hydrogen or methyl, R2 is methyl, fluorine, bromine, iodine, ethoxy, ethylthio, nitro, amino, ethylamine, or butylamine, and R3 is diethylamino, piperidine or morpholino.
Description
SPECIFICATION
Basic esters of benzoic acids and 2-thiophencarboxylic acids, processes for their preparation and a pharmacological composition containing these esters
The present invention is directed to novel basic esters of benzoic acids and of 2-thiophencarboxylic acids, to processes for their preparation and to pharmaceutical or veterinary compositions, containing these novel esters.
There is a continuing need for novel compounds which e.g. may be used as local anaesthesia active agents, and which show a lower toxicity and an improved effectiveness over the compounds known in the art and which are prepared by processes easy to carry out and which are economical.
The present invention provides basic esters of the formula
wherein R is a group of the formulae
wherein
R, is hydrogen or an occassionally substituted alkyl, and
R2 is an occasionally substituted alkyl, an acyl group, halogen, an occasionally substituted alkoxy, an occasionally substituted alkylthio, nitro, amino or an occasionally substituted alkylamino, whereby R1 and R2 are the same or different, and
R3 is a basic group, and their pharmacologically useful salts.
Preferably, R, is hydrogen or methyl, R2 is methyl, fluorine, bromine, iodine, ethoxy, ethylthio, nitro, amino, ethylamino, or butylamino, and R3 is diethylamino, piperidine or morpholino.
A first process according to this invention for preparing the novel basic esters of formula I
wherein
R and R3 are defined above, and their pharmacologically useful salts, comprises reacting benzoic acids or thiophencarboxylic acids or their acid halides of the formulae
wherein
R' is a hydroxyl group or halogen, and
R, and R2 are defined above, with an alcohol of formula II HO-CH2-CH2-R3 (11) wherein
R3 is defined above, and optionally transforming the product into a pharmacologically useful salt.
A second process of this invention for preparing the novel basic esters of formula I
wherein
R and R3 are define above, and their pharmacologically useful salts, comprises reacting salts of benzoic acids or thiophencarboxylic acids of the formulae
wherein
M is a metal salt, and
R, and R2 are defined above, with a halide of formula Ill Hal-CH2-CH2F3 (Ill) wherein
Hal is a halogen atom, and
R3 is defined above, and optionally transforming the product into a pharmacologically useful salt.
The compounds of the general formula I, wherein R2 is amino, may be prepared by reducing the nitro compounds.
According to this invention a basic group is any group having at least one basic nitrogen atom.
Both of the above described processes may also be realized in the presence of at least one solvent. Occasionally also catalysts may be used.
Somebody skilled in the art may easily determine the suitable reaction temperatures and reaction times. Usually one works at standard pressure, but pressures higher or lower (vacuum) may be used.
The administration of the novel compounds of formula I according to this invention may be realized in usual manners, as this is known in the art for the known compounds.
Preferred embodiments are illustrated in the following examples, wherein also some novel starting materials and intermediates are described.
A. Examples for benzoic acid esters
Example 1
To a solution of sodium methylate, prepared of 2.3 g (0.1 mol) sodium in 100 ml absolute ethanol, are added 13.6 g (0.1 mol) 2methylbenzoic acid and then 15 g (0.11 mol) N (2-chloroethyl)-piperidine are added slowly drop by drop. The mixture was stirred and heated for 5 hours. After cooling, the precipitated sodium chloride was filtered with suction and then washed with ethanol. The filtrate was evaporated in the vacuum of a water jet pump, the residue was diluted with water and extracted with ether.
The base extracted with diluted hydrochloric acid.
The acidic solution was made alkaline and was extracted with ether. After the evaporation of the ether the base was reacted with ether hydrochloric acid into the hydrochloride of the 2methylbenzoic acid-2-piperidino ethyl ester. Mp.
164-1 650C.
Example 2
In the same way as described in example 1 the hydrochloride of 2,6-dimethylbenzoic acid-2piperidinoethyl ester having an mp. 21 1-2130C was obtained, when 2,6-dimethyl-benzoic acid is used instead of 2-methyl-benzoic acid.
Example 3
To a solution of 805 mg (0.035 mol) sodium in 40 ml absolute ethanol are added 5.4 g (0.035 mol) 2-fluoro-6-methyl-benzoic acid, and then 6.1 g (0.045 mol) 2-diethyl-amino-ethylchloride are added drop by drop, and this mixture is reacted, us described in example 1, to yield the hydrochloride of 2-flouro-6-methyl-benzoic acid2-diethyl-aminoethyl ester having an mp. of 136.70.
The starting material was obtained as follows:
18.75 g (0.1 mol) of 2-amino-6-methylbenzoic acid-hydrochloride are diazotizied in 55 ml water and 9 ml concentrated hydrochloric acid with sodium nitrite, and at a temperature of --5 OC 50 ml hexafluorophosphoric acid are added. The precipitated salt was filtered with suction and decomposed in xylene at a temperature of 1 250C.
After cooling, the acid is extracted in a sodium carbonate solution, acidified and extracted in ether. After drying and evaporating the ether, the substance contains as a by-product 2-hydroxy-6methyl-benzoic acid. After the esterification to the ethyl ester, the 2-hydroxy-6-methyl-benzoic acidethyl ester is extracted in sodium carbonate solution, the 2-fluoro-6-methyl-benzoic acid-ethyl ester is distilled and saponified with alcoholic potassium hydroxide. Mp. 124.60.
Example 4
By the method described in example 3, the hydrochloride of 2-bromo-6-methyl-benzoic acid2-diethylaminoethyl ester is prepared from 2bromo-6-methyl-benzoic acid. Mp.183.5 184.50.
Example 5
By the method described in example 3, the hydrochloride of 2-iodo-6-methyl-benzoic acid-2diethylamino-ethyl ester is prepared from the sodium salt of 2-iodo-6-methyl-benzoic acid and 2-diethylamino-ethylchloride and etheric hydrochloric acid. Mp. 792.80.
Example 6
By the method described in example 1, the hydrochloride of 2-ethoxy-6-methyl-benzoic acid2-diethyl-amino-ethyl ester is prepared from 2ethoxy-6-methyl-benzoic acid and 2-diethlaminoethylchloride. Mp. 125--1280.
Example 7
Using N-(2-chloroethyl)-piperidine instead of 2-diethylamino-ethylchloride, in the method described in example 6, the hydrochloride of 2ethoxy-6-methyl-benzoic acid-2-piperidino-ethyl ester is obtained. Mp. 154.60.
The 2-ethoxy-6-methyl-benzoic acid is synthesized in a two-step synthesis from 2 chloro-6methyl-l -benzonitrile. 2-ethoxy-6- methyl-benzonitrile:
To a sodium methylate solution, prepared of 5.3 g sodium in 75 ml absolute ethanol, are added 20 g (0.132 mol) 2-chloro-6-methylbenzonitrile and this mixture is heated in an autoclave having a glass insertion for 40 hours at a temperature of 1300. After cooling, the precipitated sodium salt is filtered with suction, the filtrate is evaporated in the vacuum of the water jet pump, and the residue is'diluted with ether. After washing, drying and evporating the ether, a product having an Mp. of 3637.5 is obtained.
2-ethoxy-6-methyl-benzoic acid:
The nitrile is saponified either in ethanolic
potassium hydroxide under pressure or in
glycerine at a temperature of 21 00C. Mp. 86- 880.
Example 8
When 2-ethyl-thio-6-methyl-benzoic acid is used instead of 2-ethoxy-6-methyl-benzoic acid.
then, by the method of example 7, the hydrochloride of 2-ethylth io-6-m ethyl-benzoic acid-2-diethylamino-ethyl ester is obtained. Mp.
104.30.
Example 8a
When 2.3 g (0.02 mol) fumaric acid in ethanol are added to 6 g (0.02 mol) base of 2-ethylthio-6 methyl-benzoic acid-2-diethylamino-ethyl ester in ether, then the fumarate crystallizes. Mp. 116.40.
Example 9
By the method of example 1, the hydrochloride of 2-methyl-6-nitro-benzoic acid-2-diethyla mino- ethyl ester is prepared from the sodium salt of 2 m ethyl-6-nitro-benzoic acid, 2-diethyla minoethylchloride and etheric hydrochloric acid. Mp.
159160.50.
Example 10
By the method of example 1, the hydrochloride of 2-methyl-6-nitro-benzoic acid-2-piperidinoethyl ester is prepared from 2-methyl-6-nitrobenzoic acid. Mp. 181.60.
Example 11
By the method of example 10, the hydrochloride of 2-methyl-6-nitro-benzoic aicd-2- morpholino-ethyl ester is prepared when 4-(2chloroethyl)-morpholine is used instead of N-(2chloroethyl)-piperidine. Mp. 1 86.90.
Example 12
By the method described in example 1, the di hydrochloride of diethylam ino-6-methyl-benzoic acid-2-diethlyamino-ethyl ester is prepared from 2-ethylamino-6-methyl-benzoic acid, 2- diethylamino-ethylchloride and etheric hydrochloric acid. Mp. 129.20.
Example 13
By the method described in example 1, 2butylamino-6-methyl-benzoic acid and 2-diethylamino-ethylchloride are reacted to form the base (2-butylamino-6-methyl-benzoic acid-2diethylamino-ethyl ester). When an equimolar amount fumaric acid, as described in example 8a, is added to the base, then the fumarate having an mp. of 99.70 is obtained.
The starting materials are prepared as follows:
The mixture of 10.5 g (0.058 mol) 2-ainino-6- methyl-benzoic acid-ethyl ester in 87 ml benzene and 14.5 ml acetic acid and 14.5 g zinc powder are heated to reflux temperature. Then 6.6 g acetaldehyde in 14.5 ml benzene are added slowly drop by drop, and the mixture is heated for 2.5 hours under reflux. After cooling, the mixture is filtered with suction, washed with benzene, and the filtrate is made alkaline. The benzene layer is separated, the alkaline aqueous solution is extracted with benzene, the combined benzene layers are washed and dried, and after the evaporation of the benzene the 2-ethylamino-6methyl-benzoic acid-ethyl ester is distilled. Bp.
136--1390/1 mm.
4.1 g (0.02 mol) of the ethyl ester in 50 ml ethanol are saponified with 3.25 g potassium hydroxide in 21.5 ml water by refluxing for 8 hours. The ethanol is evaporated, to the residue water is added, the neutral compounds, which may be present, are extracted with ether, the aqueous solution is acidified to a pH of 6.5 and extracted with ether. After washing, drying and evaporating the ether, 2-ethylamino-6-methylbenzoic acid is obtained. Mp. 97.60.
When butyraldehyde is used instead of acetaldehyde, then as described above, 2butylamino-6-methyl-benzoic acid-ethyl ester is obtained Bp 1 56-1 580/0.65 mm.
After saponification, 2-butylamino-6-methyl- benzoic acid is obtained. Mp. 87.90.
Example 14
To 25.5 g (0.92 mol) 2-methyl-6-nitro-benzoic acid-2-diethylamino-ethyl ester in 500 ml concentrated hydrochloric acid are added during one hour 100 g zinc (Il)-chloride, and then the mixture is heated for one hour on the boiling water bath. After cooling, the mixture is made alkaline with 35 percent sodium hydroxide and extracted with ether. After washing the etherical solution, drying and evaporating the ether, the base is reacted with etheric hydrogen chloride to form the dihydrochloride of 2-amino-6-methylbenzoic acid-2-diethylamino-ethyl-ester. Mp.
186188 .
Example 15
By the method described in example 14, the dihydrochloride of 2-amino-6-methyl-benzoic acid-N-(2-piperidino)-ethyl ester is prepared, when 2-methyl-6-nitro-benzoic acid-N-(2piperidino)-ethyl ester is used. Mp. 1 99.80.
B. Examples for 2-thiophencarboxylic acid esters
Example B1 In the same way as with the benzoic acid esters the hydrochloride of 3-methylthiophen-2carboxylic acid-2-diethylamino-ethyl ester is prepared from the sodium salt of 3methylthiophen-2-carboxylic acid, 2- diethylamino-ethylchloride and etheric hydrochloric acid. Mp. 145.70.
Example B2 By the method described in example By, the hydrochloride of 5-methylthiophen-2-carboxylic acid-2-diethyl-amino-ethyl ester is prepared, Mp.
1 45.7 0, when 5-methylthiophen-2-carboxylic acid is used.
While there are shown and described present preferred embodiments of the invention, it is to be distinctly understood that the invention is not limited thereto, but may be oterhwise variously embodied and practised within the scope of the following claims.
Claims (35)
1. A basic ester of the formula I
wherein R is a group of the formula
wherein
each R, independently is hydrogen or optionally substituted alkyl, and
R2 is an optionally substituted alkyl group, an acyl group, halogen, an optionally substituted alkoxy group, an optionally substituted alkylthio group, nitro, amino or an optionally substituted alkylamino group, whereby R, and R2 are the same or different, and R3 is a basic group, or a pharmocologically useful salt thereof.
2. A basic ester as claimed in Claim 1, wherein each R, independently is hydrogen or methyl.
3. A basic ester as claimed in Claim 1 or Claim 2 wherein R2 is methyl, fluorine, bromine, iodine, ethoxy, ethylthio, nitro, amino, ethylamino, or butyla mino.
4. A basic ester as claimed in any preceding claim wherein R3 is diethylamino, piperidino or morpholino.
5. A basic ester as claimed in any preceding claim in the form of salts of a hydrochloride, hydrobromide, fumarate, maleate, hydrogenfumarate or hydrogenmaieate salt.
6. 2-methyl-benzoic acid-2-piperidino ethyl ester or a pharmacoligically useful salt thereof.
7. 2,6-dimethylbenzoic acid-2-piperidino-ethyl ester or a pharmacologically useful salt thereof.
8. 2-fluoro-6-methyl-benzoic acid-2-diethyl amino-ethyl ester or a pharmacologically useful salt thereof.
9. 2-bromo-6-methyl-benzoic acid-2diethylamino-ethyl ester or a pharmacologically useful salt thereof.
10. 2-iodo-6-methyl-benzoic acid-2diethylamino-ethyl ester or a pharmacologically useful salt thereof.
11. 2-ethoxy-6-methyl-benzoic acid-2diethyiamino-ethyl ester or a pharmacologically useful salt thereof.
12. 2-ethoxy-6-methyl-benzoic acid-2piperidino-ethyl ester or a pharmacologically useful salt thereof.
13. 2-ethylthio6-methyl-benzoic acid-2diethylamino-ethyl ester or a pharmacologically useful salt thereof.
14. 2-ethylthio-6-methyl-benzoic acid-2diethylamino-ethyl ester fumarate or a pharmacologically useful salt thereof.
15. 2-methyl-6-nitro-benzoic acid-2diethylamino-ethyl ester or a pharmacologically useful salt thereof.
16. 2-methyl-6-nitro-benzoic acid-2piperidino-ethyl ester or a pharmacologically useful salt thereof.
17. 2-methyl-6-nitro-benzoic acid-2 morphoiino-ethyl ester or a pharmacologically useful salt thereof.
1 8. Diethylamino-6-methyl-benzoic acid-2diethylamino-ethyl ester or a pharmacologically useful salt thereof.
1 9. (2-butylamino-6-methyl-benzoic acid-2diethyl-amino-ethyl ester) optionally as the fumarate.
20. 2-amino-6-methyl-benzoic acid-2diethylamino-ethylester or a pharmacologically useful salt thereof.
21. 2-amino-6-methyl-benzoic acid-N-(2piperidino)-ethyl ester or a pharmacologically useful salt thereof.
22. 3-methylthiophen-2-carboxylic acid-2diethylamino-ethyl ester or a pharmacologicaliy useful salt thereof.
23. 5-methylthiophen-2-carboxylic acid-2diethylamino-ethyl ester or a pharmacologically useful salt thereof.
24. A basic ester as claimed in Claim 1 substantially as hereinbefore described in any one of the Examples.
25. A basic ester as claimed in any preceding claim for use in a method of treatment of the human or animal body by surgery or therapy practised on the body.
26. A basic ester as claimed in Claim 25 for use as a local anaesthetic.
27. A process for preparing a basic ester as claimed in Claim 1 or a pharmacologically useful salt thereof, comprising reacting a benzoic acid or a thiophencarboxylic acid or an acid halide thereof of the formula
wherein
R' is a hydroxyl group or halogen, and
R1 and R2 are defined in Claim 1, with an
alcohol of formula II HOCH2CH2R3 (II) wherein
R3 is defined in Claim 1, and optionally
transforming the ester produced into a
pharmacologically useful salt thereof.
28. A process as claimed in Claim 27, wherein
a benzoic acid chloride or thiophene carboxylic
acid chloride is used as starting material.
29. A process for preparing a basic ester as
claimed in Claim 1 or a pharmacologically useful
salt thereof wherein a salt of a benzoic acid or thioghencarboxylic acid of the formulae
wherein
M is a metal salt, and
R1 and R2 are defined in Claim 1, are reacted with a halide of formula Ill Hal-CH2-CH2-F3 (III) wherein
Hal is a halogen atom, and R3 is defined in Claim 1, and optionally the ester produced is transformed into a pharmacologically useful salt thereof.
30. A process as claimed in Claim 29, wherein the halide of formula Ill is a chloride.
31. A process as claimed in Claim 29 or Claim 30 wherein an alkali metal salt of a benzoic acid or of a thiophencarboxylic acid is used as starting material.
32. A process for producing a basic ester of formula I as defined in Claim 1 substantially as hereinbefor-e described in any one of Examples.
33. A basic ester produced by a process as
claimed in any one of Claims 27 to 32.
34. A pharmacological formulation containing
at least one compound of the formula I as defined
in Claim 1 formulated for pharmacological use.
35. A pharmacological formulation as claimed
in Claim 34, which is a local anaesthetic.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH5115/82A CH651014A5 (en) | 1982-08-27 | 1982-08-27 | BASIC ESTERS OF BENZOESIC ACIDS AND OF 2-THIOPHENIC CARBONIC ACIDS, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE ESTERS. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8321954D0 GB8321954D0 (en) | 1983-09-14 |
| GB2126219A true GB2126219A (en) | 1984-03-21 |
| GB2126219B GB2126219B (en) | 1987-05-28 |
Family
ID=4288176
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08321954A Expired GB2126219B (en) | 1982-08-27 | 1983-08-15 | Basic esters of benzoic acids and 2-thio-phencarboxylic acids |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5998044A (en) |
| CA (1) | CA1244020A (en) |
| CH (1) | CH651014A5 (en) |
| DE (1) | DE3328494A1 (en) |
| FR (1) | FR2532304B1 (en) |
| GB (1) | GB2126219B (en) |
| IT (1) | IT1168211B (en) |
| SE (1) | SE8304457L (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB525199A (en) * | 1939-02-15 | 1940-08-23 | Novocol Chemical M F G Co Inc | Improvements in or relating to local anaesthetic bases and process of preparing same |
| US2372116A (en) * | 1942-03-24 | 1945-03-20 | Pierce | Amino alcohol esters |
| US2404691A (en) * | 1944-08-30 | 1946-07-23 | Squibb & Sons Inc | Chemical compounds |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL19578C (en) * | 1925-01-15 | |||
| US2173827A (en) * | 1936-10-26 | 1939-09-26 | Pitman Moore Company | Alkyl thio-substituted benzoic acid alkamine ester salts, intermediate and process of preparing same |
| US2383074A (en) * | 1942-04-16 | 1945-08-21 | American Cyanamid Co | Alkamine derivatives of o-alkoxymethyl benzoic acid |
| US2831016A (en) * | 1954-05-27 | 1958-04-15 | Univ Missouri | beta-substituted aminoalkyl 2,6-dialkylsubstituted benzoates and method of making the same |
| US3047574A (en) * | 1960-03-28 | 1962-07-31 | Searle & Co | 2-cyclohexyl-4-(2-hydroxyethyl)-3-methylmorpholine esters of substituted benzoic acids |
| FR2432516A1 (en) * | 1978-08-01 | 1980-02-29 | Synthelabo | 4-Phenyl-piperazino-ethanol derivs. - having CNS activity, useful for treating anxiety and depression |
-
1982
- 1982-08-27 CH CH5115/82A patent/CH651014A5/en not_active IP Right Cessation
-
1983
- 1983-08-06 DE DE19833328494 patent/DE3328494A1/en not_active Ceased
- 1983-08-15 GB GB08321954A patent/GB2126219B/en not_active Expired
- 1983-08-17 SE SE8304457A patent/SE8304457L/en not_active Application Discontinuation
- 1983-08-26 CA CA000435456A patent/CA1244020A/en not_active Expired
- 1983-08-26 FR FR838313762A patent/FR2532304B1/en not_active Expired
- 1983-08-26 IT IT48885/83A patent/IT1168211B/en active
- 1983-08-27 JP JP58157049A patent/JPS5998044A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB525199A (en) * | 1939-02-15 | 1940-08-23 | Novocol Chemical M F G Co Inc | Improvements in or relating to local anaesthetic bases and process of preparing same |
| US2372116A (en) * | 1942-03-24 | 1945-03-20 | Pierce | Amino alcohol esters |
| US2404691A (en) * | 1944-08-30 | 1946-07-23 | Squibb & Sons Inc | Chemical compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| CH651014A5 (en) | 1985-08-30 |
| IT8348885A0 (en) | 1983-08-26 |
| FR2532304A1 (en) | 1984-03-02 |
| CA1244020A (en) | 1988-11-01 |
| FR2532304B1 (en) | 1989-05-19 |
| SE8304457D0 (en) | 1983-08-17 |
| SE8304457L (en) | 1984-02-28 |
| JPS5998044A (en) | 1984-06-06 |
| GB2126219B (en) | 1987-05-28 |
| IT1168211B (en) | 1987-05-20 |
| DE3328494A1 (en) | 1984-03-01 |
| GB8321954D0 (en) | 1983-09-14 |
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| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19950815 |