IL92912A - Pararene derivatives with anti-stone activity, showing a typical signal in 3,101 parts per million in the spectrum of RMN-31C and a process for their preparation - Google Patents

Pararene derivatives with anti-stone activity, showing a typical signal in 3,101 parts per million in the spectrum of RMN-31C and a process for their preparation

Info

Publication number: IL92912A
Authority: IL; Israel
Prior art keywords: reaction mixture; heparin; sodium; aqueous solution; sulfate
Prior art date: 1989-01-30

Application number

IL9291289A

Other languages

English (en)

Hebrew (he)

Other versions

IL92912A0 (en

Original Assignee

Alfa Wassermann Spa

Priority date (The priority date 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 date listed.)

1989-01-30

Filing date

1989-12-28

Publication date

1994-06-24

1989-12-28 Application filed by Alfa Wassermann Spa filed Critical Alfa Wassermann Spa

1990-09-17 Publication of IL92912A0 publication Critical patent/IL92912A0/xx

1994-06-24 Publication of IL92912A publication Critical patent/IL92912A/en

Links

238000001228 spectrum Methods 0.000 title claims abstract description 19
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 title claims abstract description 16
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical class OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 title claims description 67
239000002628 heparin derivative Substances 0.000 title claims description 40
238000000034 method Methods 0.000 title claims description 30
230000008569 process Effects 0.000 title claims description 19
238000002360 preparation method Methods 0.000 title claims description 8
230000002272 anti-calculus Effects 0.000 title 1
229920000669 heparin Polymers 0.000 claims abstract description 59
229960002897 heparin Drugs 0.000 claims abstract description 55
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 23
239000007864 aqueous solution Substances 0.000 claims abstract description 21
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 20
238000011282 treatment Methods 0.000 claims abstract description 16
239000003638 chemical reducing agent Substances 0.000 claims abstract description 15
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
239000011593 sulfur Substances 0.000 claims abstract description 10
229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
125000003277 amino group Chemical group 0.000 claims abstract description 9
239000000243 solution Substances 0.000 claims description 34
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
239000011541 reaction mixture Substances 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 19
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 18
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 17
239000011734 sodium Substances 0.000 claims description 16
239000002585 base Substances 0.000 claims description 15
235000019441 ethanol Nutrition 0.000 claims description 14
229910052708 sodium Inorganic materials 0.000 claims description 14
239000003513 alkali Substances 0.000 claims description 13
229940127215 low-molecular weight heparin Drugs 0.000 claims description 13
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 12
239000011591 potassium Substances 0.000 claims description 12
229910052700 potassium Inorganic materials 0.000 claims description 10
230000007935 neutral effect Effects 0.000 claims description 8
239000012279 sodium borohydride Substances 0.000 claims description 8
229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 7
238000009835 boiling Methods 0.000 claims description 7
238000000502 dialysis Methods 0.000 claims description 7
239000003055 low molecular weight heparin Substances 0.000 claims description 7
229910052749 magnesium Inorganic materials 0.000 claims description 7
239000011777 magnesium Substances 0.000 claims description 7
229910052788 barium Inorganic materials 0.000 claims description 6
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 6
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 5
229910052791 calcium Inorganic materials 0.000 claims description 5
239000011575 calcium Substances 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
238000004108 freeze drying Methods 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
238000001556 precipitation Methods 0.000 claims description 4
238000000746 purification Methods 0.000 claims description 3
206010029148 Nephrolithiasis Diseases 0.000 claims description 2
150000001342 alkaline earth metals Chemical class 0.000 claims 6
238000005342 ion exchange Methods 0.000 claims 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 3
238000005325 percolation Methods 0.000 claims 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 2
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims 2
229910001863 barium hydroxide Inorganic materials 0.000 claims 2
239000007795 chemical reaction product Substances 0.000 claims 2
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 2
235000011152 sodium sulphate Nutrition 0.000 claims 2
239000003795 chemical substances by application Substances 0.000 claims 1
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims 1
239000011654 magnesium acetate Substances 0.000 claims 1
235000011285 magnesium acetate Nutrition 0.000 claims 1
229940069446 magnesium acetate Drugs 0.000 claims 1
TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims 1
229910052943 magnesium sulfate Inorganic materials 0.000 claims 1
235000019341 magnesium sulphate Nutrition 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 11
229910052783 alkali metal Inorganic materials 0.000 abstract description 7
230000002785 anti-thrombosis Effects 0.000 abstract description 4
239000003146 anticoagulant agent Substances 0.000 abstract description 4
230000014508 negative regulation of coagulation Effects 0.000 abstract description 4
229940127219 anticoagulant drug Drugs 0.000 abstract description 3
230000001371 heparinic effect Effects 0.000 abstract 3
-1 alkali metal salts Chemical class 0.000 abstract 1
239000000047 product Substances 0.000 description 38
230000005764 inhibitory process Effects 0.000 description 17
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
229940039748 oxalate Drugs 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
102000004169 proteins and genes Human genes 0.000 description 13
108090000623 proteins and genes Proteins 0.000 description 13
239000012528 membrane Substances 0.000 description 12
230000026731 phosphorylation Effects 0.000 description 12
238000006366 phosphorylation reaction Methods 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
230000000740 bleeding effect Effects 0.000 description 11
150000001875 compounds Chemical class 0.000 description 11
230000004907 flux Effects 0.000 description 11
230000007423 decrease Effects 0.000 description 10
230000001858 anti-Xa Effects 0.000 description 9
238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 9
238000012360 testing method Methods 0.000 description 9
239000011347 resin Substances 0.000 description 7
229920005989 resin Polymers 0.000 description 7
235000017281 sodium acetate Nutrition 0.000 description 7
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
238000007385 chemical modification Methods 0.000 description 6
239000002609 medium Substances 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
239000001632 sodium acetate Substances 0.000 description 6
208000007536 Thrombosis Diseases 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000012153 distilled water Substances 0.000 description 5
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
241000700159 Rattus Species 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 4
ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 4
239000000203 mixture Substances 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000002253 acid Substances 0.000 description 3
239000012736 aqueous medium Substances 0.000 description 3
230000008034 disappearance Effects 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
210000003743 erythrocyte Anatomy 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
229960002442 glucosamine Drugs 0.000 description 2
238000005534 hematocrit Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
239000000725 suspension Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
230000009466 transformation Effects 0.000 description 2
BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
208000015924 Lithiasis Diseases 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
ZYYVLFIENYGQOT-IVMDWMLBSA-N O[C@H]1[C@]2([H])OC[C@@]1([H])OC(O)[C@@H]2N Chemical compound O[C@H]1[C@]2([H])OC[C@@]1([H])OC(O)[C@@H]2N ZYYVLFIENYGQOT-IVMDWMLBSA-N 0.000 description 1
206010038478 Renal lithiasis Diseases 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
206010047249 Venous thrombosis Diseases 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
150000005325 alkali earth metal hydroxides Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
230000002429 anti-coagulating effect Effects 0.000 description 1
238000000211 autoradiogram Methods 0.000 description 1
238000000376 autoradiography Methods 0.000 description 1
ITHZDDVSAWDQPZ-UHFFFAOYSA-L barium acetate Chemical compound [Ba+2].CC([O-])=O.CC([O-])=O ITHZDDVSAWDQPZ-UHFFFAOYSA-L 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
239000001639 calcium acetate Substances 0.000 description 1
235000011092 calcium acetate Nutrition 0.000 description 1
229960005147 calcium acetate Drugs 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
150000003841 chloride salts Chemical class 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000012937 correction Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
235000013681 dietary sucrose Nutrition 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
229940097043 glucuronic acid Drugs 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
IAJILQKETJEXLJ-LECHCGJUSA-N iduronic acid Chemical compound O=C[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-LECHCGJUSA-N 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
238000012886 linear function Methods 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
230000000422 nocturnal effect Effects 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
238000000053 physical method Methods 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
INCIMLINXXICKS-UHFFFAOYSA-M pyronin Y Chemical compound [Cl-].C1=CC(=[N+](C)C)C=C2OC3=CC(N(C)C)=CC=C3C=C21 INCIMLINXXICKS-UHFFFAOYSA-M 0.000 description 1
238000011002 quantification Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000000700 radioactive tracer Substances 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
229940087562 sodium acetate trihydrate Drugs 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
229940039790 sodium oxalate Drugs 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000036325 urinary excretion Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof

Landscapes

Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Polymers & Plastics (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Materials Engineering (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Saccharide Compounds (AREA)
Catalysts (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Pyridine Compounds (AREA)
Materials For Medical Uses (AREA)

IL9291289A 1989-01-30 1989-12-28 Pararene derivatives with anti-stone activity, showing a typical signal in 3,101 parts per million in the spectrum of RMN-31C and a process for their preparation IL92912A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IT8903328A IT1234826B (it)	1989-01-30	1989-01-30	Derivati eparinici e procedimento per la loro preparazione

Publications (2)

Publication Number	Publication Date
IL92912A0 IL92912A0 (en)	1990-09-17
IL92912A true IL92912A (en)	1994-06-24

Family

ID=11105069

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9291289A IL92912A (en)	1989-01-30	1989-12-28	Pararene derivatives with anti-stone activity, showing a typical signal in 3,101 parts per million in the spectrum of RMN-31C and a process for their preparation

Country Status (18)

Country	Link
US (1)	US5104860A (de)
EP (1)	EP0380943B1 (de)
JP (1)	JPH0678369B2 (de)
KR (1)	KR0161667B1 (de)
AT (1)	ATE111107T1 (de)
AU (1)	AU610034B2 (de)
CA (1)	CA2007616C (de)
DE (1)	DE69012154T2 (de)
DK (1)	DK0380943T3 (de)
ES (1)	ES2058609T3 (de)
FI (1)	FI96425C (de)
IE (1)	IE66563B1 (de)
IL (1)	IL92912A (de)
IT (1)	IT1234826B (de)
NO (1)	NO301719B1 (de)
NZ (1)	NZ232115A (de)
PT (1)	PT92991B (de)
ZA (1)	ZA90263B (de)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IT1234826B (it) *	1989-01-30	1992-05-29	Alfa Wassermann Spa	Derivati eparinici e procedimento per la loro preparazione
US5250519A (en) *	1991-03-29	1993-10-05	Glycomed Incorporated	Non-anticoagulant heparin derivatives
IT1254216B (it) *	1992-02-25	1995-09-14	Opocrin Spa	Derivati polisaccaridici di eparina, eparan solfato, loro frazioni e frammenti, procedimento per la loro preparazione e composizioni farmaceutiche che li contengono
IT1260137B (it) *	1992-04-17	1996-03-28	Alfa Wassermann Spa	Glicosaminoglicani semisintetici a struttura eparinica od eparanica modificati nella posizione 2 dell'acido alfa-l-iduronico-2-0-solfato
IT1260136B (it) *	1992-04-17	1996-03-28	Alfa Wassermann Spa	Glicosaminoglicani semisintetici contenenti acido alfa-l-galatturonicosostituito con radicali nucleofili in posizione 3
US5668118A (en) *	1992-07-24	1997-09-16	Cavalier Pharmaceuticals	Method of synthesis of 2-O-desulfated Heparin and use thereof for inhibition of elastase and Cathepspin G
US5296471A (en) *	1992-12-22	1994-03-22	Glycomed Incorporated	Method for controlling o-desulfation of heparin and compositions produced thereby
US5696100A (en) *	1992-12-22	1997-12-09	Glycomed Incorporated	Method for controlling O-desulfation of heparin and compositions produced thereby
US5336620A (en) *	1993-01-27	1994-08-09	American Home Products Corporation	Process for the production of an anticoagulant composition
USD349205S (en)	1993-02-01	1994-08-02	Khuhawar Mamoon M	Shower caddy
IT1264102B1 (it) *	1993-03-29	1996-09-10	Alfa Wassermann Spa	Processo per la sintesi di glicosaminoglicani semisintetici contenenti acido alfa-l-galatturonico sostituito con radicali
IT1264101B1 (it) *	1993-03-29	1996-09-10	Alfa Wassermann Spa	Processo per la sintesi di glicosaminoglicani semisintetici a struttura eparinica od eparanica modificati nella posizione 2
US20020055710A1 (en) *	1998-04-30	2002-05-09	Ronald J. Tuch	Medical device for delivering a therapeutic agent and method of preparation
USD368614S (en)	1995-03-31	1996-04-09	Selfix, Inc.	Under vanity organizer
UA63929C2 (uk) *	1996-11-27	2004-02-16	Aventis Pharm Prod Inc	Фармацевтична композиція та продукт, що містить сполуки з анти-ха активністю і антагоніст агрегації тромбоцитів, спосіб і набір для лікування або профілактики захворювань, які супроводжують тромбоутворення
US6203536B1 (en) *	1997-06-17	2001-03-20	Medtronic, Inc.	Medical device for delivering a therapeutic substance and method therefor
US6106454A (en) *	1997-06-17	2000-08-22	Medtronic, Inc.	Medical device for delivering localized radiation
US6013099A (en) *	1998-04-29	2000-01-11	Medtronic, Inc.	Medical device for delivering a water-insoluble therapeutic salt or substance
US7259152B2 (en)	2000-06-07	2007-08-21	Alfa Wasserman, Inc.	Methods and compositions using sulodexide for the treatment of diabetic nephropathy
AU2007200688B2 (en) *	2000-09-12	2010-02-04	Massachusetts Institute Of Technology	Methods and products related to low molecular weight heparin
DE60138115D1 (de) *	2000-09-12	2009-05-07	Massachusetts Inst Technology	Verfahren und produkte, die mit niedermolekularem heparin assoziiert sind
RU2225175C2 (ru) *	2001-09-03	2004-03-10	Городская больница № 1 г. Тольятти	Способ лечения нефролитиаза
US7575886B2 (en)	2002-03-11	2009-08-18	Momenta Pharmaceuticals, Inc.	Analysis of sulfated polysaccharides
EP1582531A1 (de)	2004-03-24	2005-10-05	Aventis Pharma S.A.	Verfahren zur Oxydierung nicht-fraktionierten Heparins und die Detektion der Anwesenheit oder Abwesenheit von Glykoserin in Heparin und in von Heparin abgeleiteten Produkten
ATE552004T1 (de)	2005-11-30	2012-04-15	Istituto G Ronzoni	Oral verabreichbare heparinderivate
US9139876B1 (en)	2007-05-03	2015-09-22	Momenta Pharmacueticals, Inc.	Method of analyzing a preparation of a low molecular weight heparin
US8435795B2 (en) *	2010-01-19	2013-05-07	Momenta Pharmaceuticals, Inc.	Evaluating heparin preparations
EP2617737B1 (de) *	2010-09-14	2017-03-01	University Of Miyazaki	Hochreines heparin und herstellungsverfahren dafür
US9068957B2 (en)	2011-02-21	2015-06-30	Momenta Pharmaceuticals, Inc.	Evaluating heparin preparations
CN108498532B (zh)	2012-05-09	2021-07-23	坎泰克斯制药股份有限公司	骨髓抑制的治疗
US10052346B2 (en)	2015-02-17	2018-08-21	Cantex Pharmaceuticals, Inc.	Treatment of myelodysplastic syndromes with 2-O and,or 3-O desulfated heparinoids
WO2022015794A1 (en)	2020-07-14	2022-01-20	Optimvia, Llc	Methods for synthesizing non-anticoagulant heparan sulfate
CA3144968A1 (en)	2019-07-09	2021-01-14	Optimvia Llc	Methods for synthesizing anticoagulant polysaccharides

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5318520B2 (de) *	1972-07-05	1978-06-15
FR2482611B1 (fr) *	1980-05-14	1986-03-07	Pharmindustrie	Nouveaux polysaccharides sulfates, procedes pour leur preparation et leur utilisation comme medicaments
EP0066908B1 (de) *	1981-05-21	1985-08-28	Akzo N.V.	Antithrombotikum auf Basis von Polysacchariden, Verfahren zur dessen Herstellung und medizinale Zusammensetzungen
IT1195497B (it) *	1983-03-08	1988-10-19	Opocrin Spa	Procedimento per la preparazione di frazioni oligosaccaridiche dotate di proprieta' farmacologiche per degradazione chimica di eparina
DE3422518A1 (de) *	1984-06-16	1985-12-19	B. Braun Melsungen Ag, 3508 Melsungen	Heparin-derivate, verfahren zu ihrer herstellung, diese enthaltende arzneimittel und ihre verwendung bei der behandlung von fettstoffwechselstoerungen
FR2614026B1 (fr) *	1987-04-16	1992-04-17	Sanofi Sa	Heparines de bas poids moleculaire, a structure reguliere, leur preparation et leurs applications biologiques
IT1234508B (it) *	1988-06-10	1992-05-19	Alfa Wassermann Spa	Derivati eparinici e procedimento per la loro preparazione
IT1234826B (it) *	1989-01-30	1992-05-29	Alfa Wassermann Spa	Derivati eparinici e procedimento per la loro preparazione

1989
- 1989-01-30 IT IT8903328A patent/IT1234826B/it active
- 1989-12-28 IL IL9291289A patent/IL92912A/en unknown
1990
- 1990-01-09 US US07/462,462 patent/US5104860A/en not_active Expired - Fee Related
- 1990-01-11 KR KR1019900000266A patent/KR0161667B1/ko not_active Expired - Fee Related
- 1990-01-11 CA CA002007616A patent/CA2007616C/en not_active Expired - Fee Related
- 1990-01-12 DK DK90100593.4T patent/DK0380943T3/da active
- 1990-01-12 DE DE69012154T patent/DE69012154T2/de not_active Expired - Fee Related
- 1990-01-12 EP EP90100593A patent/EP0380943B1/de not_active Expired - Lifetime
- 1990-01-12 AT AT90100593T patent/ATE111107T1/de not_active IP Right Cessation
- 1990-01-12 ES ES90100593T patent/ES2058609T3/es not_active Expired - Lifetime
- 1990-01-15 NZ NZ232115A patent/NZ232115A/en unknown
- 1990-01-15 ZA ZA90263A patent/ZA90263B/xx unknown
- 1990-01-29 IE IE31690A patent/IE66563B1/en not_active IP Right Cessation
- 1990-01-29 NO NO900392A patent/NO301719B1/no not_active IP Right Cessation
- 1990-01-29 JP JP2020343A patent/JPH0678369B2/ja not_active Expired - Fee Related
- 1990-01-29 PT PT92991A patent/PT92991B/pt not_active IP Right Cessation
- 1990-01-29 FI FI900446A patent/FI96425C/fi not_active IP Right Cessation
- 1990-01-29 AU AU48858/90A patent/AU610034B2/en not_active Ceased

Also Published As

Publication number	Publication date
FI900446A0 (fi)	1990-01-29
ZA90263B (en)	1990-10-31
NO900392L (no)	1990-07-31
NZ232115A (en)	1991-05-28
IT1234826B (it)	1992-05-29
IE900316L (en)	1990-07-30
DE69012154T2 (de)	1995-02-23
JPH0678369B2 (ja)	1994-10-05
IT8903328A0 (it)	1989-01-30
JPH02240102A (ja)	1990-09-25
AU4885890A (en)	1990-10-25
FI96425B (fi)	1996-03-15
IL92912A0 (en)	1990-09-17
IE66563B1 (en)	1996-01-24
ATE111107T1 (de)	1994-09-15
NO900392D0 (no)	1990-01-29
EP0380943B1 (de)	1994-09-07
CA2007616C (en)	1996-05-14
EP0380943A1 (de)	1990-08-08
PT92991A (pt)	1990-07-31
CA2007616A1 (en)	1990-07-30
DE69012154D1 (de)	1994-10-13
KR0161667B1 (ko)	1998-11-16
KR900011789A (ko)	1990-08-02
PT92991B (pt)	1995-12-29
AU610034B2 (en)	1991-05-09
US5104860A (en)	1992-04-14
DK0380943T3 (da)	1994-12-19
NO301719B1 (no)	1997-12-01
FI96425C (fi)	1996-06-25
ES2058609T3 (es)	1994-11-01

Legal Events

Date	Code	Title	Description
1996-03-31	KB	Patent renewed
2000-06-01	KB	Patent renewed

Publication	Publication Date	Title
EP0380943B1 (de)	1994-09-07	Heparinderivate und Verfahren zu ihrer Herstellung
US5010063A (en)	1991-04-23	Heparin derivatives and process for their preparation
US5013724A (en)	1991-05-07	Process for the sulfation of glycosaminoglycans, the sulfated glycosaminoglycans and their biological applications
US4981955A (en)	1991-01-01	Depolymerization method of heparin
US4933326A (en)	1990-06-12	Oligosaccharides obtained by heparin depolymerization having antiatherosclerotic activity
EP0014184B2 (de)	1989-10-18	Fragmentiertes Heparin mit selektiver anti-koagulierender Wirksamkeit und Verfahren zu dessen Herstellung
US4783447A (en)	1988-11-08	Process for producing natural heparan sulphate and dermatan sulphate in substantially pure form, and their pharmaceutical use
JPH03243601A (ja)	1991-10-30	血液凝固の制御能をもつムコ多糖組成物およびその製造方法
WO1992002232A1 (en)	1992-02-20	Heparin fragment showing complement inhibition activity
EP0245813B1 (de)	1993-11-03	Heparine, frei von E.D.T.A., Fraktionen und Fragmente von Heparin, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen, welche diese enthalten
JP2714718B2 (ja)	1998-02-16	新規硫酸化多糖及びその薬学的に許容される塩、その製造方法並びにそれを有効成分とする医薬
EP0600934A1 (de)	1994-06-15	Dermatansulfatoligosaccharide, Verfahren zu ihrer Herstellung und diese enthaltende phamazeutische Zusammensetzungen.
KR0184260B1 (ko)	1999-05-01	항트롬보 활성을 지닌 황산화 글리코스아미노글리큐로난
JP2005533878A (ja)	2005-11-10	非常に大きい硫酸化度を持つｋ５多糖体のエピマー化誘導体
JPWO1990008784A1 (ja)	1991-01-10	新規硫酸化多糖及びその薬学的に許容される塩、その製造方法並びにそれを有効成分とする医薬
WO1994029352A1 (en)	1994-12-22	Polysaccharides having high antithrombotic and anticoagulant activity
US5470965A (en)	1995-11-28	Complexable heterogenous oligosaccharides and alpha-hydosanes having therapeutical activity, process for their preparation and related pharmaceutical compositions
KR101104107B1 (ko)	2012-01-12	헤파린으로부터 유도된 다당류의 혼합물, 이의 제조방법 및이를 함유하는 약제학적 조성물