CA2798383A1 - Process for the preparation of bimosiamose - Google Patents
Process for the preparation of bimosiamose Download PDFInfo
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- CA2798383A1 CA2798383A1 CA2798383A CA2798383A CA2798383A1 CA 2798383 A1 CA2798383 A1 CA 2798383A1 CA 2798383 A CA2798383 A CA 2798383A CA 2798383 A CA2798383 A CA 2798383A CA 2798383 A1 CA2798383 A1 CA 2798383A1
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- bis
- hexane
- phenyl
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- carboethoxymethylphenyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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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
- 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
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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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
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- 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]
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
A process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-a-D-mannopyranosyloxy)-phenyl] hexane (I) which comprises the steps of converting the compound (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) into the (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, which is reacted with adipoyl chloride to 1,4-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxybenzoyl]-butane (B) which is catalytically reduced to 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxy- phenyl] -hexane (C), which is reacted with boron tribromide in a solvent to 1,6-Bis-[3-(3- carboethoxy-methylphenyl)-4-hydroxyphenyl]-hexane (D), which is reacted with a mannopyranosyl derivative to obtain 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-(tetra-0- pivaloyl-a-D-mannopyranosyloxy)-phenyl]-hexane (E), which is reacted to form 1,6-Bis- [3-(3-carboxymethyl-phenyl)-4-(2-a-D-mannopyranosyloxy)-phenyl] hexane, which is re- crystallized, leads to the product (I) with high purity.
Claims (15)
1. A process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl] hexane, compound of formula (I) which comprises the steps of converting the compound (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) into the (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, which is reacted with adipoyl chloride to obtain 1,4-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxybenzoyl]-butane (B) which then is catalytically reduced to form 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxyphenyl]-hexane (C), which is reacted with boron tribromide in a solvent to obtain 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-hydroxyphenyl]-hexane (D), which is reacted with a protected mannopyranosyl derivative to obtain the 1,6-Bis-[3-(3-carbo-ethoxy-methylphenyl)-4-(tetra-O-protected-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane-derivative, which then is reacted under basic reaction conditions to form 1,6-Bis-[3-(3-carboxymethyl-phenyl)-4-(2-.alpha..alpha.-D-mannopyranosyloxy)-phenyl]-hexane, which optionally is recrystallized from one, two or several organic solvents and/or water to obtain the product Bimosiamose of formula (I).
2. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-a-D-manno-pyranosyloxy)-phenyl] hexane (I) according to claim 1, comprising the following process steps:
a) (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted under acidic conditions to form (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester which then is reacted with adipoyl chloride in a solvent to obtain 1,4-Bis-[3-(3-carboethoxymethylphenyl)-methoxybenzoyl] -butane (B), without the isolation of the intermediate (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, b) 1,4-Bis- [3 -(3 -carboethoxymethylphenyl)-4-methoxybenzoyl] -butane (B) is reduced by using hydrogen and a metal catalyst to form 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxyphenyl]-hexane (C), c) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) is reacted with boron tribromide in a solvent to obtain 1,6-Bis-[3-(3-carboethoxymethyl-phenyl)-4-hydroxyphenyl]-hexane (D), d) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) is reacted with a mannopyranosyl-derivative, in particular a tetra-O-pivaloyl-D-manno-pyranosyl-halide or a tetra-O-acetyl-D-mannopyranosyl-halide, to obtain 1,6-Bis-
a) (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted under acidic conditions to form (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester which then is reacted with adipoyl chloride in a solvent to obtain 1,4-Bis-[3-(3-carboethoxymethylphenyl)-methoxybenzoyl] -butane (B), without the isolation of the intermediate (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, b) 1,4-Bis- [3 -(3 -carboethoxymethylphenyl)-4-methoxybenzoyl] -butane (B) is reduced by using hydrogen and a metal catalyst to form 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxyphenyl]-hexane (C), c) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) is reacted with boron tribromide in a solvent to obtain 1,6-Bis-[3-(3-carboethoxymethyl-phenyl)-4-hydroxyphenyl]-hexane (D), d) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) is reacted with a mannopyranosyl-derivative, in particular a tetra-O-pivaloyl-D-manno-pyranosyl-halide or a tetra-O-acetyl-D-mannopyranosyl-halide, to obtain 1,6-Bis-
[3-(3-carboethoxy-methylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane (E), or the corresponding 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-
4-(tetra-O-acetyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane, e) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane (E) or the corresponding 1,6-Bis-[3-(3-carboethoxy-methyl-phenyl)-4-(tetra-O-acetyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane is reacted under basic reaction conditions to form 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl] hexane (I), f) optionally the 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane is recrystallized from one or several organic solvents and/or water or mixtures thereof to obtain the product of formula (I), Bimosiamose.
3. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to claim 1 or 2, comprising the following process steps:
a) (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted under acid conditions to form (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester which then is reacted with adipoyl chloride and a Lewis acid in a solvent to obtain 1,4-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxybenzoyl] -butane (B) in a purity of more than 95% and a yield of at least 70%, without isolation of the intermediate (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, b) 1,4-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxybenzoyl]-butane (B) is reduced using hydrogen and a metal catalyst to form 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxyphenyl]-hexane (C), c) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) is reacted with boron tribromide in a solvent at a temperature range between -20°C
to +20°C
to obtain 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D), d) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) is reacted with a tetra-O-pivaloyl-D-mannopyranosyl-halide in the presence of a catalytic amount of a Lewis acid and at a temperature range between -10°C to +15°C to obtain 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-manno-pyranosyloxy)-phenyl]-hexane (E), e) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane (E) is reacted with sodium methylate and subsequently with aqueous sodium hydroxide to form 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl] hexane (I), f) 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane is recrystallized from an organic solvent or from a mixture of an organic solvent and water to obtain the product of formula (I), Bimosiamose, in a purity of more than 98%.
4. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 3, comprising the following process steps:
a) (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is prepared from 2-Methoxyphenyl-boronic acid and a molar excess of 10% or more of 3-Bromophenylacetic acid at a temperature range between +60°C to +99°C, and then the (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted under acid conditions to form (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester which then is reacted with adipoyl chloride and aluminum chloride in a solvent to obtain 1,4-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxybenzoyl]-butane (B), without isolation of the intermediate (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, b) 1,4-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxybenzoyl]-butane (B) is reduced using hydrogen, a Pd-catalyst and a mixture of ethanol, ethylacetate and trifluoroacetic acid to form 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C), c) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) is reacted with boron tribromide in dichloromethane at a temperature range from -
3. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to claim 1 or 2, comprising the following process steps:
a) (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted under acid conditions to form (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester which then is reacted with adipoyl chloride and a Lewis acid in a solvent to obtain 1,4-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxybenzoyl] -butane (B) in a purity of more than 95% and a yield of at least 70%, without isolation of the intermediate (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, b) 1,4-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxybenzoyl]-butane (B) is reduced using hydrogen and a metal catalyst to form 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxyphenyl]-hexane (C), c) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) is reacted with boron tribromide in a solvent at a temperature range between -20°C
to +20°C
to obtain 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D), d) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) is reacted with a tetra-O-pivaloyl-D-mannopyranosyl-halide in the presence of a catalytic amount of a Lewis acid and at a temperature range between -10°C to +15°C to obtain 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-manno-pyranosyloxy)-phenyl]-hexane (E), e) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane (E) is reacted with sodium methylate and subsequently with aqueous sodium hydroxide to form 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl] hexane (I), f) 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane is recrystallized from an organic solvent or from a mixture of an organic solvent and water to obtain the product of formula (I), Bimosiamose, in a purity of more than 98%.
4. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 3, comprising the following process steps:
a) (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is prepared from 2-Methoxyphenyl-boronic acid and a molar excess of 10% or more of 3-Bromophenylacetic acid at a temperature range between +60°C to +99°C, and then the (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted under acid conditions to form (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester which then is reacted with adipoyl chloride and aluminum chloride in a solvent to obtain 1,4-Bis-[3-(3-carboethoxy-methylphenyl)-4-methoxybenzoyl]-butane (B), without isolation of the intermediate (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester, b) 1,4-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxybenzoyl]-butane (B) is reduced using hydrogen, a Pd-catalyst and a mixture of ethanol, ethylacetate and trifluoroacetic acid to form 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C), c) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) is reacted with boron tribromide in dichloromethane at a temperature range from -
5°C to +5°C to obtain 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D), followed by hydrolysis of the reaction mixture with an excess of ethanol, and subsequent treatment of the hydrolyzed mixture in boiling ethanol in order to re-convert dimers and condensation products into the reaction product 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D), d) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) is reacted with tetra-O-pivaloyl-D-mannopyranosyl fluoride in the presence of a catalytic amount of boron trifluoride diethyletherate at a temperature range from -5°C to +10°C to obtain 1,6-Bis-[3-(3-carboethoxy-methylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane (E), e) 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-(tetra-O-pivaloyl-.alpha.-D-mannopyranosyl-oxy)-phenyl]-hexane (E) is reacted with sodium methylate in a mixture of tetrahydrofuran and methanol at a temperature range between +15°C to +25°C and subsequently with aqueous sodium hydroxide at a temperature range between 0°C
to +10°C to form 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyl-oxy)-phenyl] hexane (I), f) 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane (I) is recrystallized from tetrahydrofuran or from a mixture of tetrahydrofuran and water to obtain the product of formula (I), Bimosiamose, in a purity of more than 98.5 % and in the crystal form of its polymorph FORM 2.
5. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 4, in which as step a) the compound (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted to (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester by first reacting compound (A) with thionyl chloride and then reacting with ethanol.
to +10°C to form 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyl-oxy)-phenyl] hexane (I), f) 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane (I) is recrystallized from tetrahydrofuran or from a mixture of tetrahydrofuran and water to obtain the product of formula (I), Bimosiamose, in a purity of more than 98.5 % and in the crystal form of its polymorph FORM 2.
5. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 4, in which as step a) the compound (2'-Methoxy-biphenyl-3-yl)-acetic acid (A) is converted to (2'-Methoxy-biphenyl-3-yl)-acetic acid ethyl ester by first reacting compound (A) with thionyl chloride and then reacting with ethanol.
6. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 5, in which as a step f) the compound 1,6-bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane (I) is recrystallized from an ethanol/water mixture in order to obtain Bimosiamose in the crystal form of its polymorph FORM 2.
7. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 5, in which as step f) the compound 1,6-bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]-hexane (I) is recrystallized from an isopropanol/water mixture to obtain Bimosiamose with a purity of at least 99.0% and in the crystal form of its polymorph FORM 2.
8. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-manno-pyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 7, in which as step b) the intermediate 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-methoxyphenyl]-hexane (C) and in step c) the intermediate 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) are not isolated as solid products.
9. Process for the preparation of 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl] hexane (I) according to one of the claims 1 to 8, in which as step d) the intermediate 1,6-Bis-[3-(3-carboethoxymethylphenyl)-4-hydroxyphenyl]-hexane (D) is reacted with a mixture of the .alpha./.beta.-stereoisomers of tetra-O-pivaloyl-D-mannopyranosyl halide.
10. 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl]
hexane (I) prepared by a process according to one of the claims 1 to 9 and having a purity of at least 99 %, in particular 99.5 %.
hexane (I) prepared by a process according to one of the claims 1 to 9 and having a purity of at least 99 %, in particular 99.5 %.
11. Pharmaceutical composition comprising 1,6-Bis-[3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-phenyl] hexane (I) prepared by a process according to one of the claims 1 to 9 and having a purity of at least 99 %, in particular 99.5 %, and at least one further pharmaceutically acceptable carrier.
12. Bimosiamose and/or a salt of Bimosiamose and/or a stereoisomeric or polymorphic form thereof for the treatment, prophylaxis or diagnosis of hypersensitivity pneumonitis and pulmonary sarcoidosis.
13. Pharmaceutical composition comprising Bimosiamose and/or a salt of Bimosiamose and/or a stereoisomeric or polymorphic form thereof and at least one further pharmaceutically inactive ingredient for the treatment, prophylaxis or diagnosis of hypersensitivity pneumonitis and/or pulmonary sarcoidosis.
14. Pharmaceutical composition comprising Bimosiamose and/or a salt of Bimosiamose and/or a stereoisomeric or polymorphic form thereof and at least one further pharmaceutically active ingredient for the treatment, prophylaxis or diagnosis of hypersensitivity pneumonitis and pulmonary sarcoidosis.
15. Bimosiamose and/or a salt of Bimosiamose and/or a stereoisomeric or polymorphic form thereof for the treatment, prophylaxis or diagnosis of particular inflammations, pulmonary emphysema and eye diseases, where particular inflammations means:
eye inflammation, anaphylaxis, periodontal disease, otitis, ulcer, ulcerative colitis, mucitis, pneumonia, abdominal inflammation, and cystitis; and where eye diseases means:
corneal injury, corneal ulcer, infectious diseases in the ophthalmologic field, dry eye sensation, eye diseases, retinal macular degeneration, pterygium, uveitis and lacrimal gland disease.
eye inflammation, anaphylaxis, periodontal disease, otitis, ulcer, ulcerative colitis, mucitis, pneumonia, abdominal inflammation, and cystitis; and where eye diseases means:
corneal injury, corneal ulcer, infectious diseases in the ophthalmologic field, dry eye sensation, eye diseases, retinal macular degeneration, pterygium, uveitis and lacrimal gland disease.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10162276.9 | 2010-05-07 | ||
| EP10162276 | 2010-05-07 | ||
| PCT/EP2011/057130 WO2011138365A1 (en) | 2010-05-07 | 2011-05-04 | Process for the preparation of bimosiamose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2798383A1 true CA2798383A1 (en) | 2011-11-10 |
Family
ID=44276097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2798383A Abandoned CA2798383A1 (en) | 2010-05-07 | 2011-05-04 | Process for the preparation of bimosiamose |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP2566580A1 (en) |
| JP (1) | JP2013525467A (en) |
| KR (1) | KR20130056238A (en) |
| CN (1) | CN103002951A (en) |
| AU (1) | AU2011249843A1 (en) |
| CA (1) | CA2798383A1 (en) |
| RU (1) | RU2012152633A (en) |
| WO (1) | WO2011138365A1 (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5444050A (en) * | 1994-04-29 | 1995-08-22 | Texas Biotechnology Corporation | Binding of E-selectin or P-selectin to sialyl Lewisx or sialyl-Lewisa |
| UA52607C2 (en) | 1995-06-29 | 2003-01-15 | Тексіс Байотекнолоджі Корпорейшн | Biphenyls derivatives, a pharmaceutical composition on basis thereof and a process for inhibition (variants) |
| US5712387A (en) * | 1996-05-20 | 1998-01-27 | Texas Biotechnology Corporation | High yield stereospecific mannosylation |
| US5919768A (en) | 1996-06-26 | 1999-07-06 | Texas Biotechnology Corporation | Di- and trivalent small molecule selectin inhibitors |
| EP1903049A1 (en) * | 2006-09-08 | 2008-03-26 | Revotar Biopharmaceuticals AG | Crystalline forms of 1,6-Bis [3-(3-carboxymethylphenyl)-4-(2-alpha -D-mannopyranosyloxy)-phenyl] hexane |
| EP1897533A1 (en) * | 2006-09-08 | 2008-03-12 | Revotar Biopharmaceuticals AG | Use of 1,6-Bis [3-(3-carboxymethylphenyl)-4-(2-alpha -D-mannopyranosyl-oxy)-phenyl] hexane for the preparation of cosmetic compositions |
| EP1958637A1 (en) * | 2007-02-14 | 2008-08-20 | Revotar Biopharmaceuticals AG | Pharmaceutical composition for the treatment of IL-8 mediated diseases |
-
2011
- 2011-05-04 CA CA2798383A patent/CA2798383A1/en not_active Abandoned
- 2011-05-04 JP JP2013508490A patent/JP2013525467A/en not_active Withdrawn
- 2011-05-04 EP EP11720069A patent/EP2566580A1/en not_active Withdrawn
- 2011-05-04 WO PCT/EP2011/057130 patent/WO2011138365A1/en not_active Ceased
- 2011-05-04 AU AU2011249843A patent/AU2011249843A1/en not_active Abandoned
- 2011-05-04 RU RU2012152633/04A patent/RU2012152633A/en not_active Application Discontinuation
- 2011-05-04 CN CN2011800230987A patent/CN103002951A/en active Pending
- 2011-05-04 KR KR1020127029201A patent/KR20130056238A/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013525467A (en) | 2013-06-20 |
| KR20130056238A (en) | 2013-05-29 |
| CN103002951A (en) | 2013-03-27 |
| WO2011138365A1 (en) | 2011-11-10 |
| AU2011249843A1 (en) | 2012-11-29 |
| RU2012152633A (en) | 2014-06-20 |
| EP2566580A1 (en) | 2013-03-13 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20150505 |