GB2129792A - Sulpiride derived compound - Google Patents

Sulpiride derived compound Download PDF

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Publication number
GB2129792A
GB2129792A GB08326619A GB8326619A GB2129792A GB 2129792 A GB2129792 A GB 2129792A GB 08326619 A GB08326619 A GB 08326619A GB 8326619 A GB8326619 A GB 8326619A GB 2129792 A GB2129792 A GB 2129792A
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GB
United Kingdom
Prior art keywords
sulpiride
indomethazine
new derivative
methyl
methoxi
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
Application number
GB08326619A
Other versions
GB8326619D0 (en
GB2129792B (en
Inventor
Taya Jose Maria Espinos
Esquire Jean Claude Gaubil
Aldoma Jose Maria San
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Espinos & Bofill Lab SA
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Espinos & Bofill Lab SA
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Publication date
Application filed by Espinos & Bofill Lab SA filed Critical Espinos & Bofill Lab SA
Publication of GB8326619D0 publication Critical patent/GB8326619D0/en
Publication of GB2129792A publication Critical patent/GB2129792A/en
Application granted granted Critical
Publication of GB2129792B publication Critical patent/GB2129792B/en
Expired legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
    • C07D209/28—1-(4-Chlorobenzoyl)-2-methyl-indolyl-3-acetic acid, substituted in position 5 by an oxygen or nitrogen atom; Esters thereof

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

A new compound derived from the sulpiride, having the formula <IMAGE> and named 1-(p-chlorobenzoyl-2-methyl-5-methoxy-3-indolyl-acetate of N-(1-ethyl-2-pirrolidinyl)methyl-2-methoxy-5-sulfamoyl benzamide with antiinflammatory properties and a process for the preparation of said compound consisting in reacting the indomethazine or an indomethazine organic or inorganic salt with sulpiride or a sulpiride organic or inorganic salt in water, water with a hydrosoluble organic solvent, an organic solvent or a mixture of organic solvents at a temperature between 20 and 80 DEG C.

Description

SPECIFICATION Sulpiride derived compound This invention refers to a new compound derived from the sulpiride, wich developed formula is as follows:
This compound named 1 -(p-chlorobenzoyl)-2-methyl-5-methoxi-3-indolylacetate of N-(1 -ethyl-2- pirrolidinyl) methyl-2-methoxi-5-sulfamoylbenzamide appears as a yellow crystalline solid melting at 156-157 C and being formed by the link of an indomethazine molecule with a sulpiride molecule, consequently retaining the remarkable therapeutical properties of the indomethazine strengthened by the sulpiride molecularly linked thereto. This combination provides the new product with the maintenance of the indomethazine antiinflammatory property, while helping its bioavailability and reducing its gastroperturbing effects.
The invention further refers to a process for obtaining the compound named 1-(p-chlornbenzoyl)2-methyl- 5-methoxi-3-indolylacetate of N-(1 -ethyl-2-pirrolidinyl) methyl-2-methoxi-5-sulfamoylbenzamide. This process is of easy fulfillment, allows the use of current solvents and results in a high purity product.
According to the process of the invention, indomethazine or its salts are reacted in molecular ratios with sulpiride or its salts. As indomethazine salt can be used a salt of indomethazine with an organic base or a salt of indomethazine with an inorganic base, and as sulpiride salt can be used a salt of sulpiride with an organic acid or a salt of a sulpiride with an inorganic acid.
Reaction media can be chosen between water, water with a hydrosoluble organic solvent and a mixture of organic solvents, keeping said reaction media at a temperature between 20 and 80"C.
Now it follows without making any limitation whatsoever into the scope of the invention, several examples of the preparation of 1-(p-chlorobenzoyl)-2-methyl-5-methoxi-3-indolylacetate of N-(1 -ethyl-2- pirrolidinyl)methyl-2-methoxi-5-sulfamoylbenzamide.
Example 1 40 g indomethazine were suspended by stirring into 250 ml of ethylacetate.
Suspension was heated at 60"C and 34 g. sulpiride were added thereto. Heating and stirring were continued about 15 minutes and it was then quickly cooled at room temperature. It was filtered and washed with ethyl acetate.
The resultant product was recrystallized into 3250 ml isopropanol. About 60 g. yellow crystalline solid (yield 82%) with melting point 156-157 C were obtained.
Example 2 100 g. indomethazine were added to a solution of 30 g. triethylamine into 300 ml. methanol, while stirring at room temperature.
The solution obtained was poured over another solution of 94 g. sulpiride into 280 ml N acetic acid. It was stirried about 15 minutes. The solution obtained was vacuum isopropanol.
About 160 g. yellow crystals with melting point 156-157"C were obtained.
Example 3 50 g. indomethazine were diluted at room temperature into 1400 ml 0.1 N caustic soda.
47 g. sulpiride were separately diluted into 140 ml N acetic acid and the solution diluted with 1000 ml distilled water.
The two solutions were mixed while stirred. The solution obtained was further stirred at room temperature about 15 minutes and then vacuum concentrated. The solid residues obtained were recrystallized with isopropanol. About 78-80 g. yellow crystallized powder with melting point 156-157 C were obtained.
Example 4 A solution of 100 g. (0.28 m.) indomethazine and 30 g. (0.3) triethylamine into 300 ml methanol at a temperature of 40 C was prepared.
Another solution of 100 g. (0.26 m) sulpiride chlorhydrate into 300 ml distilled water at a temperature of 70 C was separately prepared.
Both solutions were filtered and mixed at 700C and the mixture was stirred at this temperature about one hour. The solution was then cooled and left in the refrigerator several hours. The separated solid was filtered and washed with a mixture of methanol/water (1:1).
Finally it was recrystallized into 7.51. isopropanol. 150 g. yellow crystalline solid with melting point 156-157"C (yield 83%) were obtained.
Molecule formula is C34H39CIN408S.
The basic analysis of the substance obtained turned out the following results: Estimated : C = 58.40, H = 5.62, N = 8.01 Cl = 5.07, S = 4.59 Found : C = 58.34, H = 5.65, N = 8.04 Cl = 5.05, S = 4.50 In the spectrum the following absorption bands would be shown: 3,370cm - 1 ........................................ (2.97 nm) 3,320cm - 1 ........................................ (3.01 nm) 1,650 cm 1 -1 1,610cm-1 ........................................ (6.21nm) nm) 1,230 cm - 1 -1 860cm-1 ........................................ (11.6nm) 825cm-1 ........................................ (12.1 nm) 810cm-1 ........................................ (12.3 nm) 800cm-1 ........................................ (12.nm)

Claims (1)

1. A new derivative of sulpiride named 1-(p-chlorobenzoyl)-2-methyl-5-methoxi-3-indolylacetate of N-(1 -ethyl-2-pirrnlidinyl)methyl-2-methoxi-5-sulfamoyl-benzamide with the formula:
a product of molecular addition formed by an indomethazine molecule and a sulpiride molecule.
2. A process for obtaining a new derivative of sulpiride named 1-(p-chlorobenzoyl)-2-methyl-5-methoxi- 3-indolylacetate of N-(1-ethyl-2-pirrolidinyl) methyl-2-methoxi-5-sulfamoylbenzamide, characterized in that indomethazine and sulpiride are reacted in a molecular ratio, as much as such substances and in the form of salts thereof, in media chosen between water, water with a hydrosoluble organic solvent, an organic solvent and a mixture of organic solvents, keeping the media at a temperature between 20 and 80"C and the compound formed in the reaction is purified and isolated.
3. A process according to claim 2, characterized in that the indomethazine is used in the form of a salt of indomethazine with an organic base.
4. A process according to claim 2, characterized in that the indomethazine is used in the form of a salt of indomethazine with an inorganic base.
5. A process according to claim 2,3 or 4 characterised in that sulpiride is used in the form of a salt of sulpiride with an organic acid.
6. A process according to claim 2,3 or 4 characterised in that sulpiride is used in the form of a salt of sulpiride with an inorganic acid.
7. A new derivative of sulpiride as claimed in claim 1 and according to Example 1.
8. A new derivative of sulpiride as claimed in claim 1 and according to Example 2.
9. A new derivative of sulpiride as claimed in claim 1 and according to Example 3.
9. A new derivative of sulpiride as claimed in claim 1 and according to Example 4.
11. A process for obtaining a new derivative of sulpiride as claimed in claim 2 and according to Example 1.
12. A process for obtaining a new derivative of sulpiride as claimed in claim 2 and according to Example 2.
13. A process for obtaining a new derivative of sulpiride as claimed in claim 2 and according to Example 3.
14. A process for obtaining a new derivative of sulpiride as claimed in claim 2 and according to Example 4.
GB08326619A 1982-10-08 1983-10-05 Sulpiride derived compound Expired GB2129792B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES516786A ES516786A0 (en) 1982-10-08 1982-10-08 PROCEDURE FOR OBTAINING A NEW DERIVATIVE OF THE SULPIRIDE.

Publications (3)

Publication Number Publication Date
GB8326619D0 GB8326619D0 (en) 1983-11-09
GB2129792A true GB2129792A (en) 1984-05-23
GB2129792B GB2129792B (en) 1986-02-12

Family

ID=8484830

Family Applications (1)

Application Number Title Priority Date Filing Date
GB08326619A Expired GB2129792B (en) 1982-10-08 1983-10-05 Sulpiride derived compound

Country Status (7)

Country Link
JP (1) JPS5988463A (en)
BE (1) BE897948A (en)
DE (1) DE3336762A1 (en)
ES (1) ES516786A0 (en)
FR (1) FR2534254B1 (en)
GB (1) GB2129792B (en)
PT (1) PT77463B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003099293A1 (en) * 2002-05-23 2003-12-04 Danmarks Farmaceutiske Universitet Pharmacologically active salts

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2093693A (en) * 1981-02-24 1982-09-08 Ciba Geigy Ag Pharmaceutical preparations for topical application which contain salts of alkanecarboxylic acids novel carboxylic acid salts and the production thereof.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2093693A (en) * 1981-02-24 1982-09-08 Ciba Geigy Ag Pharmaceutical preparations for topical application which contain salts of alkanecarboxylic acids novel carboxylic acid salts and the production thereof.

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003099293A1 (en) * 2002-05-23 2003-12-04 Danmarks Farmaceutiske Universitet Pharmacologically active salts

Also Published As

Publication number Publication date
FR2534254B1 (en) 1985-07-12
ES8407042A1 (en) 1984-09-01
ES516786A0 (en) 1984-09-01
DE3336762A1 (en) 1984-04-12
PT77463A (en) 1983-11-01
GB8326619D0 (en) 1983-11-09
GB2129792B (en) 1986-02-12
BE897948A (en) 1984-01-30
PT77463B (en) 1986-02-26
JPS5988463A (en) 1984-05-22
FR2534254A1 (en) 1984-04-13

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