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US4440926A Expired / Lapsed US ⏱️ 0.0 years remaining

Heparin esters and processes for their preparation

Assignee: Pharmindustrie
•
Filing: 1981-04-29
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Granted: 1984-04-03
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Expires: 2001-04-29
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Abstract

Abstract Esters of heparin, which are derived from heparin by replacement of the carboxyl groups of heparin by groups of the formula: <IMAGE> (I) in which R is a hydrogen atom or a methyl group and A is a hydrogen atom or a methyl, phenyl, <IMAGE> X representing a chlorine atom or a nitro, alkyl containing 1 to 4 carbon atoms or methoxy group and Y representing a hydrogen or chlorine atom, the replacement being a partial or total replacement when A is other than a hydrogen atom or a methyl or phenyl group and the replacement being a partial replacement corresponding to a 10% to 90% esterification percentage of the carboxyl groups when A is a hydrogen atom or a methyl or phenyl group, and the alkali metal, alkaline earth metal, magnesium, quaternary ammonium and amine salts of the said esters. These compounds are intermediate products for preparing medicaments.

Inventors

  • 👤 Jean S. Mardiguian

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 12:21
CPC Classifications
C; C08; C08B; C08B37/00; A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; C08B37/006; C08B37/0063; C08B37/0075

Claims Analysis

Total Claims: 16
Claim 1
Independent Claim 177 words
Esters of heparin, which are derived from heparin by replacement of the carboxyl groups of heparin by groups of the formula: ##STR13## in which R is hydrogen or methyl and A is hydrogen, methyl, phenyl, ##STR14## X representing chlorine, nitro, alkyl containing 1 to 4 carbon atoms or methoxy and Y representing hydrogen or chlorine, the replacement being a partial or total replacement when A is other than hydrogen, methyl or phenyl, and, when A is hydrogen, methyl or phenyl, the replacement being a partial replacement corresponding to a 10% to 90% esterification percentage of the carboxyl groups and the esters being selective esters wherein are esterified, partially or wholly, either only the carboxyl groups of the D-glucuronic acid linkages, only the carboxyl groups of the D-glucuronic acid and unsulfated L-iduronic acid linkages, only the carboxyl groups of the unsulfated L-iduronic acid and sulfated L-iduronic acid linkages, or only the carboxyl groups of the sulfated L-iduronic acid linkages, and the alkali metal, alkaline earth metal, magnesium, quaternary ammonium and triethylamine, pyridine and imidazole salts of said esters.
Claim 2
Dependent Claim 177 words
Esters of heparin, which are derived from heparin by replacement of the carboxyl groups of heparin by groups of the formula: ##STR13## in which R is hydrogen or methyl and A is hydrogen, methyl, phenyl, ##STR14## X representing chlorine, nitro, alkyl containing 1 to 4 carbon atoms or methoxy and Y representing hydrogen or chlorine, the replacement being a partial or total replacement when A is other than hydrogen, methyl or phenyl, and, when A is hydrogen, methyl or phenyl, the replacement being a partial replacement corresponding to a 10% to 90% esterification percentage of the carboxyl groups and the esters being selective esters wherein are esterified, partially or wholly, either only the carboxyl groups of the D-glucuronic acid linkages, only the carboxyl groups of the D-glucuronic acid and unsulfated L-iduronic acid linkages, only the carboxyl groups of the unsulfated L-iduronic acid and sulfated L-iduronic acid linkages, or only the carboxyl groups of the sulfated L-iduronic acid linkages, and the alkali metal, alkaline earth metal, magnesium, quaternary ammonium and triethylamine, pyridine and imidazole salts of said esters.
Claim 3
Dependent Claim 20 words
Heparin esters according to claim 1 wherein, in the groups of formula (I), R is hydrogen and A is ##STR15##
Claim 4
Dependent Claim 20 words
Heparin esters according to claim 1 which are non-selective esters in which A is other than hydrogen, methyl or phenyl.
Claim 5
Dependent Claim 26 words
Heparin esters according to claim 1 which are selective esters in which are esterified, partially or wholly, only the carboxyl groups of the D-glucuronic acid linkages.
Claim 6
Dependent Claim 31 words
Heparin esters according to claim 1 which are selective esters in which are esterified, partially or wholly, only the carboxyl groups of the D-glucuronic acid linkages and unsulfated L-iduronic acid linkages.
Claim 7
Dependent Claim 31 words
Heparin esters according to claim 1 which are selective esters in which are esterified, partially or wholly, only the carboxyl groups of the unsulfated L-iduronic acid and sulfated L-iduronic acid linkages.
Claim 8
Dependent Claim 27 words
Heparin esters according to claim 1 which are selective esters in which are esterified, partially or wholly, only the carboxyl groups of the sulfated L-iduronic acid linkages.
Claim 9
Dependent Claim 24 words
Alkali metal salts of esters according to claim 1, 2, 3, 4, 5, 6 or 7 in which the alkali metal cation is sodium.
Claim 10
Dependent Claim 26 words
Alkaline earth metal salts of esters according to claim 1, 2, 3, 4, 5, 6 or 7 in which the alkaline earth metal cation is calcium.
Claim 11
Dependent Claim 15 words
Magnesium salts of esters according to claim 1, 2, 3, 4, 5, 6 or 7.
Claim 12
Dependent Claim 26 words
Quaternary ammonium salts of esters according to claim 1, 2, 3, 4, 5, 6 or 7 in which the quaternary ammonium cation is the benzethonium cation.
Claim 13
Dependent Claim 57 words
A process for preparing the compounds according to claim 6 wherein an alcohol of the formula: ##STR16## wherein R and A have the same definition as in formula (I), is reacted with heparin in an aqueous medium having a pH of from 2 to 3 in the presence of a water-soluble condensation agent of the carbodiimide type.
Claim 14
Dependent Claim 58 words
A process for preparing the compounds according to claim 7 wherein an alcohol of the formula: ##STR17## in which R and a have the same definition as in formula (I), is reacted with heparin in an aqueous medium having a pH of from 3.5 to 4.5 in the presence of a water-soluble condensation agent of the carbodiimide type.
Claim 15
Dependent Claim 96 words
A process for preparing the compounds according to claim 4, in which: (a) a quaternary ammonium salt is reacted with heparin in an aqueous medium, the pH of which is between 3 and 4; and (b) the so obtained acid quaternary ammonium salt of heparin in which are salified, in addition to the sulfate groups, only the carboxyl groups of the D-glucuronic acid linkages is reacted with a halogen derivative of the formula: ##STR18## in which Hal is a chlorine, bromine or iodine atom and R and A have the same definition as in formula (I).
Claim 16
Dependent Claim 135 words
A process for preparing the compounds according to claim 5, in which: (a) a quaternary ammonium salt is reacted with heparin in an aqueous medium, the pH of which is from 2 to 2.5; (b) the carboxyl groups of the D-glucuronic acid and unsulfated L-iduronic acid linkages of the product so obtained are selectively neutralized by addition of a determined amount of quaternary ammonium hydroxide in a dimethylformamide medium; and (c) the so obtained acid quaternary ammonium salt of heparin in which are salified, in addition to the sulfate groups, only the carboxyl groups of the D-glucuronic acid and unsulfated L-iduronic acid linkages is reacted with a halogen derivative of the formula: ##STR19## in which Hal is a chlorine, bromine or iodine atom and R and A have the same definition as in formula (I).

References Cited (Backward Citations)

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USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1987-04-03 1987-10-03 1988-04-03 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1991-04-03 1991-10-03 1992-04-03 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1995-04-03 1995-10-03 1996-04-03 $7700.00 Window Closed / Lapsed

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