GB2028325A - Benzene and thiophene- carbothioic acid 2-aminoalkyl ester acid salts - Google Patents
Benzene and thiophene- carbothioic acid 2-aminoalkyl ester acid salts Download PDFInfo
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- GB2028325A GB2028325A GB7927694A GB7927694A GB2028325A GB 2028325 A GB2028325 A GB 2028325A GB 7927694 A GB7927694 A GB 7927694A GB 7927694 A GB7927694 A GB 7927694A GB 2028325 A GB2028325 A GB 2028325A
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
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Abstract
The invention comprises benzene and 2 - thiophene carbothioic acid 2- aminoalkyl ester acid salts having the formula: <IMAGE> wherein R is 2-thiophene, benzene or substituted benzene; n is 2 or 3 and X<-> is a chlorine or bromine radical and methods of using the compounds and compositions.
Description
SPECIFICATION
Benzene and thiophene-carbothioic acid 2-arninoalkyl ester acid salts
The present invention is concerned with certain carbothioic acid - 2 - aminoalkylesters possessing mucolytic activity and is particularly concerned with the use of benzene and substituted benzene and 2 thiophene - carbothioic acid - 2 - aminoalkylester acid salts in combating and controlling mucus build-up in an animal exhibiting lung congestion and compositions containing these compounds for use as mucolytic agents.
The prior art disclosed synthesis of benzene carbothioic acid - 2 - aminoethylester hydrochloride,
W.O. Foye et al, J. Pharm. Sci. 51 168-71(1962) but there is no disclosure of mucolytic activity. Substitution on the benzene ring has not been disclosed.
The prior art discloses certain mucolytic agents such as N - acetyl - cysteine having a free sulphhydryl group, which group compounds of the present invention do not have. A.L. Sheffner, Ann. N.Y. Acad.
Sci. 106, 298-310 (1963) established the use of gastric mucin muco-protein as a test media in development of N - acetyl - L - cysteine as a mucolytic agent in the treatment of lung disease.
The compounds of the present invention are benzene, substituted benzene and 2 - thiophenecarbothioic acid - 2 - aminoalkylester acid salts illustrated generally by the following formula:
Formula I wherein;
R represents 2-thiophene, benzene or benzene substituted by one to three radicals which may be halogen atoms, or lower-alkyl, lower-alkoxy, carboxy ortrifluoromethyl groups and may be the same or different and in various positions relative to one another in the ring,
X- is a chlorine or bromine radical and n is 2 or3.
The compounds have mucolytic activity and are useful in dissolving and diluting mucus in warmblooded animals exhibiting orsuffereing from lung congestion.
The compounds described hereinafter and represented by the foregoing Formula I have been shown buy a modification of the method of S.J. Carne et al, J. Phys. 242, 116(1974) as described hereinbelow to have mucolytic activity in animals.
Compounds for which mucolytic activity was found to be of the same order of magnitude as N acetyl - L - cysteine on rat stomach mucus are the preferred compounds which are as follows:
1) Benzenecarbothioic acid, 2-aminoethyl ester monohydrochloride,
2) 4-Chlorobenzenecarbothioic acid, 2 aminoethyl ester monohydrochloride,
3) 3-Methylbenzenecarbothioic acid, 2 aminoethyl ester monohydrochloride,
4) 4-Methoxybenzenecarbothioic acid, 2
aminoethyl ester monohydrochloride,
5) 2-Thiophenecarbothioic acid, 2 - aminoethyl
ester monohydrochloride.
The method used to demonstrate the mucolytic
activity of the compounds of the present invention is
as follows.
Female Sprague-Dawley (Charles River Labs) rats
weighing 120-180 g are fasted for 16 hours on wire,
housed two animals per cage. To mininize cop
rophogia, the lights are left on during the fast. Two
cc of water are given orally to each rat to minimize
internal debris. Thirty minutes lates the rats are sac
rificed by cervical dislocation. The stomachs are
removed, trimmed of excess tissue and the epithelial
portion discarded. The glandular portion is cut suffi
ciently along the greater and lesser curvature to
cause eversion of the stomach before placing it in
the drug solution. Stomachs with a fecal odour or
containing visible fecal matter are discarded.
Stomachs are placed in 10 cc of an aqueous solution
containing 2.5 mg of the test compound/ml for 40
minutes, the aqueous solution being made up from
water or a 50% aqeuous solution of polyethylene
glycol of MW 300 (PEG 300) depending on the solu
bility of the test compound. After this drug exposure
stomachs are placed in 10 cc of Alcian Blue aqueous
dye solution (Solution 1 prepared as described
below) for 90 minutes and the dye complexes with the stomach mucus. After two successive 10-minute washes in 10 cc of 0.25 M sucrose solution (Solution 2 prepared as described below), the stomachs are
placed in 10 cc of 0.5 M aqueous magnesium
chloride solution (Solution 3 prepared as described
below) for one hour to remove the complexed dye.
The supernatant magnesium chloride solution is
shaken with 10 cc of diethyl ether in a 60 cc separat
ory funnel to remove lipids. The aqueous phase is
drained into a Spectronic 20 tube and the percent transmission is read at 605 m,a in a Spectronic 20
spectrophotometer. The percent transmission is
converted to ,ag/ml of Alcian Blue from a standard
curve. (P. Whiteman, Biochem. J. 131,351-57 (1973)).
Each drug or drug vehicle (control) is tested on three
stomachs. Mean differences between treated and
control values are expressed as percentages.
The aqueous Alcian Blue solution referred to as
Solution 1 herein contains 0.05% w/v Alcian Blue
dye. It is made up by dissolving 54.8 g of sucrose
(0.15 M) and 6.8 g of sodium acetate with stirring in
900 cc of deionized water using a magnetic stirrer.
The pH is adjusted to pH 5.8. 500 mg Alcian Blue 8
GN (supplied by Matheson Coleman & Bell as
#8E13) is then added and the mixture topped up to 1 litre in a volumetric flask with deionized water and
the solution stored in a refrigerator. The solution
should only be used for 1 week after being made up.
The aqueous sucrose solution referred to as Solu
tion 2 herein is made up by dissolving 85.6 g of suc
rose in deionized water in a one litre volumetric flask
and then making up with deionized water to one
litre. The solution should only be used for one week
after making up.
The aqueous magnesium chloride solution refer
red to as Solution 3 herein is made up by dissolving
101.7 g of Mg Cl2.6H2O (A.C.S.) in deionized water in
a one litre volumetric flask and then making up to 1
litre with deionized water.
It is an object of the present invention to provide
certain novel carbothioic acid, 2-aminoalkylester acid salts having mucolytic activity in a warm-blooded animal.
Afurtherobjectisto provide a method of using benzene and substituted benzene and 2-thiophene carbothioic acid - 2 - aminoalkylester acid salts as mucolytic agents to combat mucus build-up in a warm-blooded animal suffering from lung congestion.
A further object is to provide pharmaceutical compositions containing the compounds useful for controlling congestion due to mucus in a warm-blooded animal body.
In the definition ofthe symbols and in Formula I given above, and where they appear elsewhere throughout the claims and specification hereof, the following terms have the following significance.
"Benzene substituted by one to 3 radicals" as used herein shall mean a phenyl radical which is substituted by one to 3 radicals selected from the groups as hereinabove defined underthe definition of R and these substituents can be in various available positions in the phenyl nucleus and when more than one substituent is present, may be the same or different and may be in various position combinations relative to each other. The lower-alkyl and lower-alkoxy substituents each have preferably from one to four carbon atoms which can be arranged as straight or branched chains. Examples of the preferred substituents are methyl, ethyl, propyl, butyl, fluoro, bromo, chloro, iodo, methoxy, ethoxy, butoxy, carboxy and trifluoromethyl radicals.
The benzene and substituted benzene and thiophenecarbothioic acid, 2-aminoalkylester acid salts are prepared by procedures represented by the following equation:
wherein R, n and X- are as defined hereinabove.
Generally, the reactants are mixed and heated over a steam jet until a mass of crystals are formed.
The mass of crystals is then broken up, triturated with ligroine and recrystallized from anhydrous ethanol.
The invention may be put into practice in various ways and certain specific embodiments will be described by way of example to illustrate the invention, Examples 1 to 9 describe the preparation of compounds of the present invention and Examples 10 to 12 describe pharamaceutical compositions in accordance with the invention.
Example 1
Benzenecarbothioic Acid, 2-Aminoethylester
Monohydrochloride.
A mixture of benzoyl chloride, 15 ml (about 0.13 mole) and 2-aminoethanethiol hydrochloride, 4.54 g (0.04 mole) was heated (protected from moisture) over a steam jet for 2 hours. Slight cooling produced a mass of crystals. Aftertrituration with ligroine at a temperature of 60-1 10'C, filtration and drying, the crystals melted at 177-180"C. Several recrystallizations from anhydrous ethanol produced a colourless solid which melted at 178.5-179.5"C. Nuclear Magnetic Resonance (NMR), Mass Spectrophotometer (MS) and Infra Red (IR) analyses all corroborated that the product was the compound given in the title of this example, and had the structure of Formula I. The yield was 5.1 g (59.1%).
Analysis: CalculatedforCgH,2CINOS: C,49.65;
H,5.55;
N,6.43
Found: C,49.58; H,5.59;
N,6.49
Example 2 4ChlorobenzenecarbothioicAcid, 2-Aminoethyl
Ester Monobydrochloride.
A mixture of freshly distilled p-ch lorobenzoyl chloride, 60 ml (0.47 mole) and 2-aminoethanethiol hydrochloride, 18.18 g (0.16 mole) was heated (protected from moisture) over a steam jet for 2 hours. A solid crystalline mass formed as the reaction wentto completion. After careful trituration with warm ligroine at a temperature of 60-110 C crystals were separated by filtration while washing with ligroine.
After two recrystallizations from anhydrous ethanol, the product, 39.0 g (yield 96.5%), melted at 208-209.5"C. NMR, MS and IR analyses all corroborated that the product was the compound given in the title of this example and had the structure of
Formula I.
Analysis: Calculated for C9H11Cl2SNO: C,42.87;
H,4.40;
N,5.55
Found: C,42.79; H,4.43;
N,5.59
Example 3 4-Methylbenzenecarbothioic Acid, 2-Aminoethyl
EsterMonohydrochloride.
A mixture of freshly distilled p-toluoyl chloride, b.p. 122"C (at 32 mm of mercury pressure) 30 ml (about 0.18 moles) and 2-aminoethanethiol hydroch loride, 9.68 g (0.085 moles) was heated (protected from moisture) over a steam jetfor 2.25 hours. A solid crystalline mass formed on completion of the reaction. The mass was crushed and carefullytriturated with warm ligroine at a temperature of 60-1 10"C and crystals were separated by filtration and washed with warm ligroine. After two recrystallizations from an hydros ethanol, the product, 19.07 g (yield 97%), melted at 206.5-208"C. NMR, MS and
IR analyses all corroborated that the product was the compound given in the title of this example and had the structure of Formula I.
Analysis: Calculated for C10H14NOCIS: C,51.83;
H,6.09;
N,6.04
Found: C,51.57; H,6.06;
N,6.11
Example 4 4-Methoxybenzenecarbothioic Acid, 2-Aminoethyl
Ester Monohydrochloride.
A mixture of p-anisoyl chloride, 23 ml (about 0.135 mole) and 2-aminoethanethiol hydrochloride, 7.4 g (0.065 mole) was heated (protected from moisture) over a steam jet for about 2 hours. The resultant crystalline mass was crushed and carefullytriturated with warm ligroine at a temperature of 60-11 0'C and crystals were separated by filtration and washed with warm ligroine. After two recrystallizations from anhydrous ethanol, the product, 14.6 g (yield 90.6%) melted at 191.5-193"C. NMR, MS and IR analysis all corroborated that the product was the compound given in the title of this example and had the structure of Formula I.
Analysis: Calculated for C10H14ClNO2S: C,48.48;
H,5.69;
N,5.65
Found: C,48.42; H,5.73;
N,5.66
Examples 5A to 5F
When in the procedure of Example 1, benzoyl chloride is replaced by equal molar amounts of
3,4,5-trimethoxybenzoyl chloride, 4-fluorobenzoyl chloride, 3-trifluoromethylbenzoyl chloride, 3,4-dichlorobenzoyl chloride, 3,4-dimethylbenzoyi chloride, and
4-carboxybenzoyl chloride there are obtained
3,4,5-trimethoxybenzenecarbothioic acid, 2 - aminoethyl ester hydrochloride (Example 5A), 4-fluorobenzenecarbothioic acid, 2 - aminoethyl ester hydrochloride (Example 5B), 3-trifluoromethylbenzenecarbothioic acid, 2-aminoethyl ester hydrochloride (Example 5C), 3,4-dichlorobenzenecarbothioic acid, 2-aminoethyl ester hydrochloride (Example 5D), 3,4-dimethylbenzenecarbothioic acid, 2-aminoethyl ester hydrochloride (Example 5E) and 4-carboxybenzenecarbothioic acid, 2-aminoethyl ester hydrochloride (Example 5F).
Example 6
When in the procedure of Example 1, 2-aminoethanethiol hydrochloride is replaced by equal molar amounts of 3-aminopropanethiol hydrochloride, there is obtained benzenecarbothioic acid - 3 - aminopropylester hydrochloride.
Examples 7A to 7C
When in the procedure of Example 1, 2-aminoethanethiol hydrochloride is replaced by equal molar amounts of 3-aminopropanethiol hydrochloride and benzoyl chloride is replaced by
p-chlorobenzoyl chloride,
p-toluoyl chloride, or
p-anisoyl chloride there are obtained
4-chlorobenzenecarbothioic acid, 3-aminopropyl ester hydrochloride (Example 7A),
4-methylbenzenecarbothioic acid, 3-aminopropyl ester hydrochloride (Example 7B) and
4-methoxybenzenecarbothioic acid, 3-aminopropyl ester hydrochloride (Example 7C).
Example 8
2-Thiophenecarbothioic Acid, 2-Aminoethyl Ester
Hydrochloride.
A mixture of freshly distilled 2-thiophenecarbonyl chloride, 15.8 g (0.108 mole) and 2-aminoethanethiol hydrochloride, 11.3 g (0.1 mole) was heated (protected from moisture) over a steam jet for 6 hours.
The resulting solid crystalline mass was crushed and triturated with warm ligroine at a temperature of 60-1 10"C and filtered to collect the crystals. After two recrystallizations from anhydrous ethanol, the pro duct, 8.41 g (yield 75.5%) melted at 195-196.50C.
NMR, MS and IR all corroborated that the product was the compound given in the title of this example and had the structure of Formula I.
Analysis: Calculated for C7H10ClNOS2: C,37.58;
H,4.51;
N,6.26
Found: C,37.68; H,4.50;
N,6.30
Example 9
When in the procedure of Example 8, 2-aminoethanethiol hydrochloride is replaced by equal molar amounts of 3-aminopropanethiol hydrochloride, there is obtained thiophenecarbothioic acid, 3-aminopropyl ester hydrochloride.
The pharmaceutical compositions of this invention comprise compounds of Formula I above in an amount sufficient to provide effective action against lung congestion in warm-blooded animal subjects when applied topically as an inhalant.
The compounds of Formula I are administered in an amount sufficient to induce liquefaction of mucus in the respiratory tract of warm-blooded animals in need thereof. Intratracheal adminstration of the compounds of Formula I may be effected by various inhalation or instillation means such as nose drops, sprays, or aerosols. Examples of pharmaceutically acceptable liquid carriers are water and polyethylene glycol-300 (MW 300). Another suitable means of administration is by insufflation of micronized particles or ultra-fine powders utilizing only the energy of the inspiratory action or by use of aerosol propellants.Generally, the amount of the compound in the inhalant composition will vary from about 0.5% to 50 or 75 weight%. Solutions or suspensions having about 0.5 to 20% by weight preferably 5% to 10% or 0.5% to 5% by weight of the mucolytic agent of Formula I are suitable for application by spraying with for example an atomizer, nebulizer, or aerosol.
Dusts containing about 25-75% or more active agent in micronized form are also suitable, about 50% being preferred.
It will be readily apparent to those skilled in the medical arts that the correct dosage of a compound to be employed with any particular mammalian subject is determined by the severity of the condition requiring mucolytictherapy, as well as the age, sex, weight and general physical condition of the subject.
Individual doses ranging from 5-100 mg for inhalation by man are suitable and may be required for the mucolytic effect.
The pharmaceutical compositions may take the form of dilutions of the micronized compounds in dusts or solutions and suspensions in liquids suitably dispersed for inhalation as illustrated by the following Examples lOto 12.
Example 10 Powder forAdministration via an InhalerDevice.
4-Chlorobenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride of Example 2,
micronized 2.5 9
Lactose powder 2.5 g
The powders are blended aseptically and filled into hard gelatin capsules each containing 50 mg of the mixture. This is suitable for dispersion into the inspired breath by means of a breath-operated inhaler device containing means for rupture of the capsule wall priorto dosing.
Example 11
Sterile Solution for Administration via an Inhaler
Device.
1. Active Ingredients (any one or more of
the products of Examples 1 to 9) 100 mg
2. Alcohol 95%, q.s. 1.0 cc
Constituents 1 and 2 are dissolved by warming and the mixture administered by means of a breath-operated inhaler device.
Example 12
Aqueous Solution.
1. Active Ingredient (the compounds of
Examples 1,3 or 5A to 5F) lOg 2. Distilled water 90 g
Total 100 g
Constituent 1 is dissolved in the water and the mixture diluted to dosage form and administered by means of an inhaler device or aerosol.
Claims (22)
1. In a method of combating mucus build-up in an animal body for the purpose of alleviating lung congestion in an animal suffereing therefrom by administering via inhalation an amount of a compound effective for dissolving the mucus causing the congestion, the use of a compound having the formula:
wherein;
R represents a 2-thiophene, a benzene or a substituted benzene radical, the substituted benzene radical being substituted by one to 3 radicals which may be the same or different, and which are halogen, lower-alkyl, lower-alkoxy, carboxy, or trifluoromethyl radicals; X is a chlorine or bromine radical, and nis2or3.
2. a use as claimed in Claim 1 in which the compound is benzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
3. A use as claimed in Claim 1 in which the compound is 4-chlorobenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
4. A use as claimed in Claim 1 in which the compound is 4-methylbenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
5. A use as claimed in Claim 1 in which the compound is 4-methoxybenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
6. A use as claimed in Claim 1 in which the compound is 2-thiophenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
7. A use as claimed in Claim 1 in which the compound is a compound prepared substantially as specifically described in any one of Examples 1 to 9.
8. A pharmaceutical composition adapted for use as a mucolytic agent in an animal body suffering from lung congestion comprising
a) a compound of the formula
wherein;
R represents a 2-thiophene, a benzene or a substituted benzene radical, the substituted benzene radical being substituted by one to 3 radicals, which may be the same or different and which are halogen, lower alkyl, lower alkoxy, carboxy or trifluoromethyl radicals, X is a chlorine or bromine radical, and
n is 2 or3, and
b) a pharmaceutically acceptable carrier therefore.
9. A pharmaceutical composition in inhalable liquid form adapted for use as a mucolytic agent in an animal body suffering from lung congestion comprising
a) 0.5 to 20% by weight of a compound of the formula
wherein;
R represents a 2-thiophene, a benzene or a substituted benzene radical, the substituted benzene radical being substituted by one to 3 radicals, which may be the same or different and which are halogen, lower alkyl, lower alkoxy, carboxy or trifluoromethyl radicals, X is a chlorine or bromine radical, and
n is 2 or3, and
b) a pharmaceutically acceptable carriertherefore.
10. Apharmaceutical composition in insufflatable powder form adapted for use as a mucolytic agent in an animal body suffering from lung congestion comprising
a) 25 to 75% or a micronized compound of the formula
wherein;
R represents a 2-thiophene, a benzene or a substituted benzene radical, the substituted benzene radi cal being substituted by one to 3 radicals, which may be the same or different and which are halogen, lower alkyl, lower alkoxy, carboxy or trifluoromethyl radicals, X is a chlorine or bromine radical, and n is2 or3, and b) a pharmaceutically acceptable powder carrier therefor.
11. A composition as claimed in Claim 8,9 or 10 in which the compound is benzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
12. A composition as claimed in Claim 8,9 or 10 in which the compound is 4-chlorobenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
13. A composition as claimed in Claim 8,9 or 10 in which the compound is 4-methylbenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
14. A composition as claimed in Claim 8, 9 or 10 on which the compound is 4-methoxybenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
15. A composition as claimed in Claim 8, 9 or 10 in which the compound is 2-thiophenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
16. A composition as claimed in Claim 8 substantially as specifically described herein with reference to Example 10,11 or 12.
17. Asubstituted benzene orthiophenecarbothioic acid, 2- aminoalkyl ester acid salt having the formula:
wherein;
R represents a 2-thiophene, or a benzene radical substituted by one to three radicals, which may be the same or different, which are halogen, lower alkyl,
lower alkoxy, ca rboxy or trifluoromethyl radi
cals, X- is a chlorine or bromine radical, and n is 2 or3.
18. 4-chlorobenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
19. 4-methylbenzenecarbothioic acid,
2-aminoethyl ester monohydrochloride.
20. 4-methoxybenzenecarbothioic acid, 2-aminoethyl ester monohydrochloride.
21. 2-thiophenecarbothioic acid, 2-aminoethyl
ester monohydrochloride.
22. A compound as claimed in Claim 17 substan
tially as specifically described herein with reference
to any one of Examples 2 to 9.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US93274778A | 1978-08-10 | 1978-08-10 |
Publications (2)
Publication Number | Publication Date |
---|---|
GB2028325A true GB2028325A (en) | 1980-03-05 |
GB2028325B GB2028325B (en) | 1982-11-17 |
Family
ID=25462846
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB7927694A Expired GB2028325B (en) | 1978-08-10 | 1979-08-08 | Benzene and thiophene-carbothioic acid 2-aminoalkyl ester acid salts |
Country Status (17)
Country | Link |
---|---|
JP (2) | JPS5536486A (en) |
AU (1) | AU520791B2 (en) |
BE (1) | BE878169A (en) |
CA (1) | CA1125297A (en) |
CH (1) | CH642062A5 (en) |
DE (1) | DE2932402A1 (en) |
DK (1) | DK159655C (en) |
EG (1) | EG14416A (en) |
ES (1) | ES483269A1 (en) |
FI (1) | FI69060C (en) |
FR (2) | FR2433016A1 (en) |
GB (1) | GB2028325B (en) |
IE (1) | IE48794B1 (en) |
IL (1) | IL57859A (en) |
IT (1) | IT1118828B (en) |
PH (1) | PH16277A (en) |
ZA (1) | ZA794171B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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IT1170862B (en) * | 1981-03-31 | 1987-06-03 | Sigma Tau Ind Farmaceuti | MERCAPTOACIL-CARNITINE PROCEDURE FOR THEIR PREPARATION AND THERAPEUTIC USE |
JP3635780B2 (en) * | 1996-04-08 | 2005-04-06 | 株式会社デンソー | Honeycomb structure forming apparatus and forming method |
CN110597249B (en) * | 2019-08-23 | 2022-08-05 | 深圳市优必选科技股份有限公司 | Robot and recharging positioning method and device thereof |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2342142A (en) * | 1937-09-09 | 1944-02-22 | Squibb & Sons Inc | Esters of sulphur-containing benzoic acids and process of preparing them |
US3328442A (en) * | 1963-12-18 | 1967-06-27 | Massachusetts College Of Pharm | Anti-radiation compounds and their preparation |
DE2335079C3 (en) * | 1973-02-21 | 1979-02-15 | Laboratories Made S.A., Madrid | Aminoalkyl derivatives of 3,5-dimethylbenzoic acid and their salts and processes for their preparation |
US4210666A (en) * | 1978-08-10 | 1980-07-01 | A. H. Robins Company, Inc. | Mucolytic thiophenecarboxamido alkyl mercaptans |
IL57881A (en) * | 1978-08-10 | 1982-12-31 | Robins Co Inc A H | Pharmaceutical compositions containing benzamidoalkyl merccaptans |
-
1979
- 1979-07-20 IL IL57859A patent/IL57859A/en unknown
- 1979-08-03 CH CH716879A patent/CH642062A5/en not_active IP Right Cessation
- 1979-08-03 PH PH22851A patent/PH16277A/en unknown
- 1979-08-08 GB GB7927694A patent/GB2028325B/en not_active Expired
- 1979-08-08 IE IE1520/79A patent/IE48794B1/en unknown
- 1979-08-08 EG EG487/79A patent/EG14416A/en active
- 1979-08-09 DK DK333879A patent/DK159655C/en not_active IP Right Cessation
- 1979-08-09 FR FR7920412A patent/FR2433016A1/en active Granted
- 1979-08-09 AU AU49756/79A patent/AU520791B2/en not_active Ceased
- 1979-08-09 BE BE0/196671A patent/BE878169A/en not_active IP Right Cessation
- 1979-08-09 FI FI792474A patent/FI69060C/en not_active IP Right Cessation
- 1979-08-09 IT IT68643/79A patent/IT1118828B/en active
- 1979-08-09 ES ES483269A patent/ES483269A1/en not_active Expired
- 1979-08-09 DE DE19792932402 patent/DE2932402A1/en active Granted
- 1979-08-09 CA CA333,424A patent/CA1125297A/en not_active Expired
- 1979-08-10 JP JP10212879A patent/JPS5536486A/en active Granted
- 1979-08-10 ZA ZA00794171A patent/ZA794171B/en unknown
-
1980
- 1980-02-14 FR FR8003290A patent/FR2453150A1/en active Granted
-
1987
- 1987-10-27 JP JP62271595A patent/JPS63119423A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
GB2028325B (en) | 1982-11-17 |
ES483269A1 (en) | 1980-04-16 |
FR2433016A1 (en) | 1980-03-07 |
DE2932402A1 (en) | 1980-02-21 |
FI69060B (en) | 1985-08-30 |
JPH0262530B2 (en) | 1990-12-26 |
IE48794B1 (en) | 1985-05-15 |
ZA794171B (en) | 1980-08-27 |
IT7968643A0 (en) | 1979-08-09 |
DK159655B (en) | 1990-11-12 |
CH642062A5 (en) | 1984-03-30 |
IL57859A0 (en) | 1979-11-30 |
DK159655C (en) | 1991-04-08 |
JPS6341899B2 (en) | 1988-08-19 |
EG14416A (en) | 1984-06-30 |
JPS5536486A (en) | 1980-03-14 |
FR2453150B1 (en) | 1983-05-20 |
DK333879A (en) | 1980-02-11 |
DE2932402C2 (en) | 1988-12-22 |
BE878169A (en) | 1979-12-03 |
IE791520L (en) | 1980-02-10 |
CA1125297A (en) | 1982-06-08 |
IT1118828B (en) | 1986-03-03 |
AU520791B2 (en) | 1982-02-25 |
FI792474A (en) | 1980-02-11 |
FR2433016B1 (en) | 1983-05-13 |
FI69060C (en) | 1985-12-10 |
AU4975679A (en) | 1980-02-14 |
PH16277A (en) | 1983-08-26 |
FR2453150A1 (en) | 1980-10-31 |
IL57859A (en) | 1983-02-23 |
JPS63119423A (en) | 1988-05-24 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19920808 |