UA61921C2 - Синтетичні полісахариди, спосіб їх виготовлення та фармацевтичні композиції, які їх містять - Google Patents

Синтетичні полісахариди, спосіб їх виготовлення та фармацевтичні композиції, які їх містять Download PDF

Info

Publication number: UA61921C2
Authority: UA; Ukraine
Prior art keywords: methyl; glucopyranosyl; sulfo; tri; compound
Prior art date: 1996-07-19

Application number

UA99020967A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Пьєр Александр Дріге

Філіпп Дюшоссуа

Жан-Марк Ербер

Моріс Петіту

БУККЕЛЬ Констант ВАН

Петер ГРОТЕНХЕЙС

Корнелія Дреф-Тромп

Йоханнес БАСТЕН

Original Assignee

Санофі - Синтелябо

Акцо Нобель Н.В.

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.)

1996-07-19

Filing date

1997-07-18

Publication date

2003-12-15

1997-07-18 Application filed by Санофі - Синтелябо, Акцо Нобель Н.В. filed Critical Санофі - Синтелябо

2003-12-15 Publication of UA61921C2 publication Critical patent/UA61921C2/uk

Links

150000004676 glycans Chemical class 0.000 title claims abstract description 68
229920001282 polysaccharide Polymers 0.000 title claims abstract description 49
239000005017 polysaccharide Substances 0.000 title claims abstract description 49
238000000034 method Methods 0.000 title claims description 78
239000008194 pharmaceutical composition Substances 0.000 title claims description 11
150000002772 monosaccharides Chemical class 0.000 claims abstract description 41
150000003839 salts Chemical class 0.000 claims abstract description 41
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
-1 sulpho groups Chemical group 0.000 claims abstract description 17
108090000190 Thrombin Proteins 0.000 claims abstract description 12
229960004072 thrombin Drugs 0.000 claims abstract description 12
150000002402 hexoses Chemical class 0.000 claims abstract description 5
150000002972 pentoses Chemical class 0.000 claims abstract description 5
150000008266 deoxy sugars Chemical class 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 361
239000000203 mixture Substances 0.000 claims description 140
239000002253 acid Substances 0.000 claims description 68
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 59
150000002016 disaccharides Chemical class 0.000 claims description 38
159000000000 sodium salts Chemical class 0.000 claims description 30
239000013543 active substance Substances 0.000 claims description 20
239000002243 precursor Substances 0.000 claims description 19
125000006239 protecting group Chemical group 0.000 claims description 19
229910052799 carbon Inorganic materials 0.000 claims description 18
150000001768 cations Chemical class 0.000 claims description 16
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 9
150000007513 acids Chemical class 0.000 claims description 8
229910052700 potassium Inorganic materials 0.000 claims description 8
239000011591 potassium Substances 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
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 7
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
150000001450 anions Chemical class 0.000 claims description 6
229910052708 sodium Inorganic materials 0.000 claims description 6
239000011734 sodium Substances 0.000 claims description 6
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
239000004019 antithrombin Substances 0.000 claims description 5
150000003214 pyranose derivatives Chemical class 0.000 claims description 5
150000001721 carbon Chemical group 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
230000007170 pathology Effects 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
239000002585 base Substances 0.000 claims description 3
230000002378 acidificating effect Effects 0.000 claims description 2
229910052783 alkali metal Inorganic materials 0.000 claims description 2
230000015271 coagulation Effects 0.000 claims description 2
238000005345 coagulation Methods 0.000 claims description 2
125000001033 ether group Chemical group 0.000 claims description 2
229940126601 medicinal product Drugs 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 10
230000004064 dysfunction Effects 0.000 claims 1
231100000252 nontoxic Toxicity 0.000 claims 1
230000003000 nontoxic effect Effects 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 abstract description 3
102000004411 Antithrombin III Human genes 0.000 abstract 1
108090000935 Antithrombin III Proteins 0.000 abstract 1
229960005348 antithrombin iii Drugs 0.000 abstract 1
150000001732 carboxylic acid derivatives Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 585
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 324
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 258
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 181
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 142
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
239000000243 solution Substances 0.000 description 133
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 101
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 87
239000000741 silica gel Substances 0.000 description 81
229910002027 silica gel Inorganic materials 0.000 description 81
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 72
238000004809 thin layer chromatography Methods 0.000 description 71
238000005481 NMR spectroscopy Methods 0.000 description 68
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
238000004458 analytical method Methods 0.000 description 66
238000003786 synthesis reaction Methods 0.000 description 57
230000015572 biosynthetic process Effects 0.000 description 56
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 55
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
150000002500 ions Chemical class 0.000 description 51
239000000377 silicon dioxide Substances 0.000 description 48
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 46
238000003756 stirring Methods 0.000 description 46
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 44
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 42
150000002482 oligosaccharides Chemical class 0.000 description 41
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 40
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
239000012074 organic phase Substances 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 39
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
238000002360 preparation method Methods 0.000 description 36
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 35
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
238000004587 chromatography analysis Methods 0.000 description 34
150000003569 thioglycosides Chemical class 0.000 description 30
239000007864 aqueous solution Substances 0.000 description 28
229910052943 magnesium sulfate Inorganic materials 0.000 description 27
235000019341 magnesium sulphate Nutrition 0.000 description 27
235000017557 sodium bicarbonate Nutrition 0.000 description 26
229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
229920001542 oligosaccharide Polymers 0.000 description 24
239000012299 nitrogen atmosphere Substances 0.000 description 22
235000012239 silicon dioxide Nutrition 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 20
239000000126 substance Substances 0.000 description 20
239000012141 concentrate Substances 0.000 description 18
235000008504 concentrate Nutrition 0.000 description 18
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
229930182475 S-glycoside Natural products 0.000 description 17
239000002808 molecular sieve Substances 0.000 description 17
239000000047 product Substances 0.000 description 17
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 17
239000000937 glycosyl acceptor Substances 0.000 description 16
238000000746 purification Methods 0.000 description 16
150000004044 tetrasaccharides Chemical group 0.000 description 16
229960000583 acetic acid Drugs 0.000 description 15
239000012300 argon atmosphere Substances 0.000 description 13
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000003146 anticoagulant agent Substances 0.000 description 12
229920000669 heparin Polymers 0.000 description 12
229960002897 heparin Drugs 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
239000012312 sodium hydride Substances 0.000 description 12
229910000104 sodium hydride Inorganic materials 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound 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 description 11
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 11
239000012043 crude product Substances 0.000 description 11
PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 11
239000011347 resin Substances 0.000 description 11
229920005989 resin Polymers 0.000 description 11
239000000725 suspension Substances 0.000 description 11
235000020357 syrup Nutrition 0.000 description 11
239000006188 syrup Substances 0.000 description 11
JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
238000000605 extraction Methods 0.000 description 10
239000012047 saturated solution Substances 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 9
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 9
235000019345 sodium thiosulphate Nutrition 0.000 description 9
150000004043 trisaccharides Chemical class 0.000 description 9
DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 8
230000002785 anti-thrombosis Effects 0.000 description 8
238000004364 calculation method Methods 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000002904 solvent Substances 0.000 description 8
PZUPAGRIHCRVKN-UHFFFAOYSA-N 5-[5-[3,4-dihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]-5-[3,4,5-trihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound OCC1OC(O)C(O)C(O)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(COC4C(C(O)C(O)CO4)O)O3)O)C(COC3C(C(O)C(O)CO3)O)O2)O)C(COC2C(C(O)C(O)CO2)O)O1 PZUPAGRIHCRVKN-UHFFFAOYSA-N 0.000 description 7
239000012298 atmosphere Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 6
MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
239000000370 acceptor Substances 0.000 description 6
229940127219 anticoagulant drug Drugs 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
238000004949 mass spectrometry Methods 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000000843 powder Substances 0.000 description 6
238000007127 saponification reaction Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
229940035024 thioglycerol Drugs 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 6
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 5
229910015900 BF3 Inorganic materials 0.000 description 5
108010074860 Factor Xa Proteins 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
229910000024 caesium carbonate Inorganic materials 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
238000000451 chemical ionisation Methods 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
150000002463 imidates Chemical class 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229940040102 levulinic acid Drugs 0.000 description 5
150000004804 polysaccharides Polymers 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
229910052702 rhenium Inorganic materials 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
239000003826 tablet Substances 0.000 description 5
229920000858 Cyclodextrin Polymers 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
150000002009 diols Chemical class 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
239000005457 ice water Substances 0.000 description 4
230000003993 interaction Effects 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
239000003921 oil Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
239000012071 phase Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
230000007017 scission Effects 0.000 description 4
238000007920 subcutaneous administration Methods 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
230000019635 sulfation Effects 0.000 description 4
238000005670 sulfation reaction Methods 0.000 description 4
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
238000011282 treatment Methods 0.000 description 4
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 3
BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
229920002683 Glycosaminoglycan Polymers 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
230000009471 action Effects 0.000 description 3
239000012190 activator Substances 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
229960004676 antithrombotic agent Drugs 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
210000005056 cell body Anatomy 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000003381 deacetylation reaction Methods 0.000 description 3
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
238000007429 general method Methods 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
230000011987 methylation Effects 0.000 description 3
238000007069 methylation reaction Methods 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
239000011736 potassium bicarbonate Substances 0.000 description 3
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 3
229910000343 potassium bisulfate Inorganic materials 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
235000018102 proteins Nutrition 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
230000009424 thromboembolic effect Effects 0.000 description 3
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
SDTORDSXCYSNTD-UHFFFAOYSA-N 1-methoxy-4-[(4-methoxyphenyl)methoxymethyl]benzene Chemical compound C1=CC(OC)=CC=C1COCC1=CC=C(OC)C=C1 SDTORDSXCYSNTD-UHFFFAOYSA-N 0.000 description 2
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
206010003178 Arterial thrombosis Diseases 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
102000004211 Platelet factor 4 Human genes 0.000 description 2
108090000778 Platelet factor 4 Proteins 0.000 description 2
241000700159 Rattus Species 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
208000007536 Thrombosis Diseases 0.000 description 2
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
YFHNDHXQDJQEEE-UHFFFAOYSA-N acetic acid;hydrazine Chemical compound NN.CC(O)=O YFHNDHXQDJQEEE-UHFFFAOYSA-N 0.000 description 2
150000001253 acrylic acids Chemical class 0.000 description 2
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
230000002429 anti-coagulating effect Effects 0.000 description 2
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
230000001580 bacterial effect Effects 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
150000001720 carbohydrates Chemical class 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
230000006196 deacetylation Effects 0.000 description 2
201000010099 disease Diseases 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
238000013171 endarterectomy Methods 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
235000012907 honey Nutrition 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000009434 installation Methods 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
125000005524 levulinyl group Chemical group 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
229930014626 natural product Natural products 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
230000002265 prevention Effects 0.000 description 2
YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
238000007154 radical cyclization reaction Methods 0.000 description 2
239000012429 reaction media Substances 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
230000009466 transformation Effects 0.000 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
229920002554 vinyl polymer Polymers 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
HEVMDQBCAHEHDY-UHFFFAOYSA-N (Dimethoxymethyl)benzene Chemical compound COC(OC)C1=CC=CC=C1 HEVMDQBCAHEHDY-UHFFFAOYSA-N 0.000 description 1
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
RPVFYIHRKXUWDA-UHFFFAOYSA-N 2,2,6,6-tetramethyl-1-(2,2,6,6-tetramethylpiperidin-1-yl)oxypiperidine Chemical compound CC1(C)CCCC(C)(C)N1ON1C(C)(C)CCCC1(C)C RPVFYIHRKXUWDA-UHFFFAOYSA-N 0.000 description 1
HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical compound CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 1
QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
ZNGINKJHQQQORD-UHFFFAOYSA-N 2-trimethylsilylethanol Chemical compound C[Si](C)(C)CCO ZNGINKJHQQQORD-UHFFFAOYSA-N 0.000 description 1
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
RMTFNDVZYPHUEF-XZBKPIIZSA-N 3-O-methyl-D-glucose Chemical compound O=C[C@H](O)[C@@H](OC)[C@H](O)[C@H](O)CO RMTFNDVZYPHUEF-XZBKPIIZSA-N 0.000 description 1
WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
DBTMGCOVALSLOR-UHFFFAOYSA-N 32-alpha-galactosyl-3-alpha-galactosyl-galactose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(OC2C(C(CO)OC(O)C2O)O)OC(CO)C1O DBTMGCOVALSLOR-UHFFFAOYSA-N 0.000 description 1
KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
IGPUFFYCAUBNIY-UHFFFAOYSA-N 4-oxopentanoyl 4-oxopentanoate Chemical compound CC(=O)CCC(=O)OC(=O)CCC(C)=O IGPUFFYCAUBNIY-UHFFFAOYSA-N 0.000 description 1
KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010002388 Angina unstable Diseases 0.000 description 1
101100322085 Arabidopsis thaliana CAC3 gene Proteins 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
206010003658 Atrial Fibrillation Diseases 0.000 description 1
239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
108010039209 Blood Coagulation Factors Proteins 0.000 description 1
102000015081 Blood Coagulation Factors Human genes 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
101100182914 Caenorhabditis elegans mak-1 gene Proteins 0.000 description 1
101100346155 Caenorhabditis elegans oma-2 gene Proteins 0.000 description 1
101100042265 Caenorhabditis elegans sem-2 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
206010008190 Cerebrovascular accident Diseases 0.000 description 1
229910052684 Cerium Inorganic materials 0.000 description 1
241000543381 Cliftonia monophylla Species 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 1
WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
RXVWSYJTUUKTEA-UHFFFAOYSA-N D-maltotriose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 RXVWSYJTUUKTEA-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
241000698776 Duma Species 0.000 description 1
208000000059 Dyspnea Diseases 0.000 description 1
206010013975 Dyspnoeas Diseases 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
241000283074 Equus asinus Species 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
241000060457 Hannia Species 0.000 description 1
229920002971 Heparan sulfate Polymers 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
206010020608 Hypercoagulation Diseases 0.000 description 1
238000006809 Jones oxidation reaction Methods 0.000 description 1
WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
241001446467 Mama Species 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241000343235 Maso Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
101100440233 Mus musculus Cmpk2 gene Proteins 0.000 description 1
101100521345 Mus musculus Prop1 gene Proteins 0.000 description 1
241000378195 Myadestes obscurus Species 0.000 description 1
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
241001057495 Neda Species 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
241001387976 Pera Species 0.000 description 1
208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
108700017836 Prophet of Pit-1 Proteins 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
208000010378 Pulmonary Embolism Diseases 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
101100514477 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MSI1 gene Proteins 0.000 description 1
239000005708 Sodium hypochlorite Substances 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
244000299461 Theobroma cacao Species 0.000 description 1
235000009470 Theobroma cacao Nutrition 0.000 description 1
108010000499 Thromboplastin Proteins 0.000 description 1
102000002262 Thromboplastin Human genes 0.000 description 1
244000111306 Torreya nucifera Species 0.000 description 1
235000006732 Torreya nucifera Nutrition 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
208000007814 Unstable Angina Diseases 0.000 description 1
206010047249 Venous thrombosis Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
240000000038 Ziziphus mauritiana Species 0.000 description 1
235000006545 Ziziphus mauritiana Nutrition 0.000 description 1
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
MWOZJZDNRDLJMG-UHFFFAOYSA-N [Si].O=C=O Chemical compound [Si].O=C=O MWOZJZDNRDLJMG-UHFFFAOYSA-N 0.000 description 1
WBXQXRXMGCOVHA-UHFFFAOYSA-N [methyl(nitroso)amino]methyl acetate Chemical compound O=NN(C)COC(C)=O WBXQXRXMGCOVHA-UHFFFAOYSA-N 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
238000005852 acetolysis reaction Methods 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
238000002399 angioplasty Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000002744 anti-aggregatory effect Effects 0.000 description 1
229940127090 anticoagulant agent Drugs 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 1
WDODWFPDZYSKIA-UHFFFAOYSA-N benzeneselenol Chemical compound [SeH]C1=CC=CC=C1 WDODWFPDZYSKIA-UHFFFAOYSA-N 0.000 description 1
CENQUTVRMPTFCN-UHFFFAOYSA-N benzotriazol-1-yl benzoate Chemical compound N1=NC2=CC=CC=C2N1OC(=O)C1=CC=CC=C1 CENQUTVRMPTFCN-UHFFFAOYSA-N 0.000 description 1
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
208000015294 blood coagulation disease Diseases 0.000 description 1
239000003114 blood coagulation factor Substances 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
210000001715 carotid artery Anatomy 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
229960003009 clopidogrel Drugs 0.000 description 1
230000009852 coagulant defect Effects 0.000 description 1
238000010276 construction Methods 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000005828 desilylation reaction Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 1
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
229960002768 dipyridamole Drugs 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
230000035622 drinking Effects 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940097043 glucuronic acid Drugs 0.000 description 1
BCDGQXUMWHRQCB-UHFFFAOYSA-N glycine methyl ketone Natural products CC(=O)CN BCDGQXUMWHRQCB-UHFFFAOYSA-N 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
238000001631 haemodialysis Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000004970 halomethyl group Chemical group 0.000 description 1
230000036541 health Effects 0.000 description 1
230000000322 hemodialysis Effects 0.000 description 1
230000023597 hemostasis Effects 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
229920001477 hydrophilic polymer Polymers 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
230000003027 hypercoagulation Effects 0.000 description 1
150000002453 idose derivatives Chemical class 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
201000004332 intermediate coronary syndrome Diseases 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
FYGDTMLNYKFZSV-UHFFFAOYSA-N mannotriose Natural products OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(OC2C(OC(O)C(O)C2O)CO)C(O)C1O FYGDTMLNYKFZSV-UHFFFAOYSA-N 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
229960002523 mercuric chloride Drugs 0.000 description 1
229940101209 mercuric oxide Drugs 0.000 description 1
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
230000014508 negative regulation of coagulation Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000005022 packaging material Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
ORQWTLCYLDRDHK-UHFFFAOYSA-N phenylselanylbenzene Chemical compound C=1C=CC=CC=1[Se]C1=CC=CC=C1 ORQWTLCYLDRDHK-UHFFFAOYSA-N 0.000 description 1
229910052699 polonium Inorganic materials 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
150000003138 primary alcohols Chemical group 0.000 description 1
230000008569 process Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
238000007348 radical reaction Methods 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
238000000926 separation method Methods 0.000 description 1
208000013220 shortness of breath Diseases 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000002910 solid waste Substances 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
230000001732 thrombotic effect Effects 0.000 description 1
PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
229960005001 ticlopidine Drugs 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
238000000844 transformation Methods 0.000 description 1
IMRYETFJNLKUHK-UHFFFAOYSA-N traseolide Chemical compound CC1=C(C(C)=O)C=C2C(C(C)C)C(C)C(C)(C)C2=C1 IMRYETFJNLKUHK-UHFFFAOYSA-N 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
201000002282 venous insufficiency Diseases 0.000 description 1
229920006163 vinyl copolymer Polymers 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000012991 xanthate Substances 0.000 description 1
FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H](CO)O[C@@H](O[C@@H]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 description 1

Classifications

- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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

UA99020967A 1996-07-19 1997-07-18 Синтетичні полісахариди, спосіб їх виготовлення та фармацевтичні композиції, які їх містять UA61921C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR9609116A FR2751334B1 (fr)	1996-07-19	1996-07-19	Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant
PCT/FR1997/001344 WO1998003554A1 (fr)	1996-07-19	1997-07-18	Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant

Publications (1)

Publication Number	Publication Date
UA61921C2 true UA61921C2 (uk)	2003-12-15

Family

ID=9494266

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA99020967A UA61921C2 (uk)	1996-07-19	1997-07-18	Синтетичні полісахариди, спосіб їх виготовлення та фармацевтичні композиції, які їх містять

Country Status (36)

Country	Link
US (1)	US6534481B1 (id)
EP (1)	EP0912613B1 (id)
JP (1)	JP3345020B2 (id)
KR (1)	KR100311857B1 (id)
CN (1)	CN1200003C (id)
AR (1)	AR008068A1 (id)
AT (1)	ATE224917T1 (id)
AU (1)	AU726679B2 (id)
BR (1)	BR9710739B1 (id)
CA (1)	CA2261597C (id)
CZ (1)	CZ301009B6 (id)
DE (1)	DE69715866T2 (id)
DK (1)	DK0912613T3 (id)
EE (1)	EE03929B1 (id)
ES (1)	ES2184123T3 (id)
FR (1)	FR2751334B1 (id)
HK (1)	HK1019757A1 (id)
HU (1)	HU223691B1 (id)
ID (1)	ID20604A (id)
IL (2)	IL128018A0 (id)
IS (1)	IS1968B (id)
MY (1)	MY124548A (id)
NO (1)	NO319682B1 (id)
NZ (1)	NZ333721A (id)
PL (1)	PL190397B1 (id)
PT (1)	PT912613E (id)
RU (1)	RU2167163C2 (id)
SA (1)	SA99200037B1 (id)
SI (1)	SI0912613T1 (id)
SK (1)	SK284881B6 (id)
TR (1)	TR199900114T2 (id)
TW (1)	TW520376B (id)
UA (1)	UA61921C2 (id)
WO (1)	WO1998003554A1 (id)
YU (1)	YU49247B (id)
ZA (1)	ZA976340B (id)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2773801B1 (fr)	1998-01-19	2000-05-12	Sanofi Sa	Nouveaux pentasaccharides, procedes pour leurs preparations et compositions pharmaceutiques les contenant
FR2814463B1 (fr) *	2000-09-22	2002-11-15	Sanofi Synthelabo	Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine
US7138531B2 (en) *	2001-10-15	2006-11-21	Kemin Pharma B.V.B.A.	Preparation and use of carbohydrate-based bicyclic ring structures with antimicrobial and cytostatic activity
EP1574516A1 (en) *	2004-03-05	2005-09-14	Sanofi-Aventis	Antithrombotic compound
US7563780B1 (en) *	2004-06-18	2009-07-21	Advanced Cardiovascular Systems, Inc.	Heparin prodrugs and drug delivery stents formed therefrom
FR2874924B1 (fr) *	2004-09-09	2006-12-01	Sanofi Aventis Sa	Hexadecasaccharides biotinyles, leur preparation et leur utilisation therapeutique
TWI403334B (zh) *	2004-12-23	2013-08-01	Merck Sharp & Dohme	包含生物素殘基之抗血栓雙重抑制劑
TWI376234B (en) *	2005-02-01	2012-11-11	Msd Oss Bv	Conjugates of a polypeptide and an oligosaccharide
IL181431A0 (en) *	2007-02-19	2007-07-04	Micha Shemer	Fruit juice and puree with a lowered amount of available sugars
CN101874035B (zh)	2007-10-16	2014-12-03	普罗吉恩制药有限公司	新的硫酸化寡糖衍生物
CN102046781A (zh)	2008-05-30	2011-05-04	动量制药公司	糖结构以及制造和使用此类结构的方法
FR2935386B1 (fr) *	2008-08-26	2010-09-10	Sanofi Aventis	Nouveaux polysaccharides a activite antithrombotique comprenant une liaion covalente avec une chaine amine
EP3666786A1 (en) *	2009-07-31	2020-06-17	Reliable Biopharmaceutical Corporation	Process for preparing fondaparinux sodium and intermediates useful in the synthesis thereof
FR2949114B1 (fr)	2009-08-14	2011-08-26	Sanofi Aventis	OCTASACCHARIDES N-ACYLES ACTIVATEURS DES RECEPTEURS DES FGFs, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
FR2949115B1 (fr)	2009-08-14	2012-11-02	Sanofi Aventis	OLIGOSACCHARIDES N-SULFATES ACTIVATEURS DES RECEPTEURS DES FGFs, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
US8420790B2 (en)	2009-10-30	2013-04-16	Reliable Biopharmaceutical Corporation	Efficient and scalable process for the manufacture of Fondaparinux sodium
KR101682466B1 (ko) *	2010-02-01	2016-12-05	롯데정밀화학 주식회사	아세틸화 셀룰로오스 에테르 및 이를 포함하는 물품
JP2013537181A (ja)	2010-09-10	2013-09-30	サノフイ	抗血栓活性及び改善された代謝安定性を有するビオチン化多糖類
FR2970969B1 (fr)	2011-01-27	2013-10-18	Sanofi Aventis	Oligosaccharides 3-o-alkyles activateurs des recepteurs des fgfs, leur preparation et leur application en therapeutique
CN109134555B (zh) *	2017-06-15	2021-09-28	南京正大天晴制药有限公司	抗凝血的五糖类化合物及其制备方法和医药用途
CN109134554B (zh) *	2017-06-15	2021-09-28	南京正大天晴制药有限公司	抗凝血的五糖类化合物及其制备方法和医药用途
CN109134553B (zh) *	2017-06-15	2021-09-28	南京正大天晴制药有限公司	抗凝血的五糖类化合物及其制备方法和医药用途

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4801583A (en)	1982-01-15	1989-01-31	Choay S.A.	Oligosaccharides and their biological applications
EP0300099A1 (en)	1987-07-20	1989-01-25	Akzo N.V.	New pentasaccharides
US5378829A (en)	1990-04-23	1995-01-03	Akzo N.V.	Sulfated glycosaminoglycanoid derivatives of the heparin and heparan sulfate type
US5382570A (en)	1990-04-23	1995-01-17	Akzo, N.V.	Sulfated glycosaminoglycanoid derivatives of the dermatan sulfate and chondroitin sulfate type
IL102758A (en)	1991-08-23	1997-03-18	Akzo Nv	Glycosaminoglycanoid derivatives, their preparation and pharmaceutical compositions comprising them
FR2704226B1 (fr)	1993-04-22	1995-07-21	Sanofi Elf	3-desoxy oligosaccharides, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
ES2147216T3 (es)	1993-09-01	2000-09-01	Akzo Nobel Nv	Bisconjugados que comprenden dos sacaridos y un grupo de union.
FR2749849B1 (fr) *	1996-06-14	1998-09-04	Sanofi Sa	Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant

1996
- 1996-07-19 FR FR9609116A patent/FR2751334B1/fr not_active Expired - Lifetime
1997
- 1997-07-08 US US09/230,139 patent/US6534481B1/en not_active Expired - Lifetime
- 1997-07-17 ZA ZA976340A patent/ZA976340B/xx unknown
- 1997-07-17 AR ARP970103200A patent/AR008068A1/es unknown
- 1997-07-18 WO PCT/FR1997/001344 patent/WO1998003554A1/fr active IP Right Grant
- 1997-07-18 EP EP97934596A patent/EP0912613B1/fr not_active Expired - Lifetime
- 1997-07-18 JP JP50665198A patent/JP3345020B2/ja not_active Expired - Lifetime
- 1997-07-18 NZ NZ333721A patent/NZ333721A/xx not_active IP Right Cessation
- 1997-07-18 IL IL12801897A patent/IL128018A0/xx active IP Right Grant
- 1997-07-18 AU AU37747/97A patent/AU726679B2/en not_active Expired
- 1997-07-18 DK DK97934596T patent/DK0912613T3/da active
- 1997-07-18 CN CNB971976171A patent/CN1200003C/zh not_active Expired - Lifetime
- 1997-07-18 EE EEP199900015A patent/EE03929B1/xx unknown
- 1997-07-18 HU HU9902287A patent/HU223691B1/hu active IP Right Grant
- 1997-07-18 CA CA002261597A patent/CA2261597C/fr not_active Expired - Lifetime
- 1997-07-18 RU RU99103646/04A patent/RU2167163C2/ru active
- 1997-07-18 SI SI9730424T patent/SI0912613T1/xx unknown
- 1997-07-18 DE DE69715866T patent/DE69715866T2/de not_active Expired - Lifetime
- 1997-07-18 ES ES97934596T patent/ES2184123T3/es not_active Expired - Lifetime
- 1997-07-18 MY MYPI97003269A patent/MY124548A/en unknown
- 1997-07-18 YU YU1999A patent/YU49247B/sh unknown
- 1997-07-18 AT AT97934596T patent/ATE224917T1/de active
- 1997-07-18 BR BRPI9710739-5A patent/BR9710739B1/pt not_active IP Right Cessation
- 1997-07-18 PT PT97934596T patent/PT912613E/pt unknown
- 1997-07-18 UA UA99020967A patent/UA61921C2/uk unknown
- 1997-07-18 CZ CZ0016099A patent/CZ301009B6/cs not_active IP Right Cessation
- 1997-07-18 PL PL97331259A patent/PL190397B1/pl unknown
- 1997-07-18 TR TR1999/00114T patent/TR199900114T2/xx unknown
- 1997-07-18 SK SK53-99A patent/SK284881B6/sk not_active IP Right Cessation
- 1997-07-21 ID IDP972525A patent/ID20604A/id unknown
- 1997-08-20 TW TW086111937A patent/TW520376B/zh not_active IP Right Cessation
1999
- 1999-01-12 IL IL128018A patent/IL128018A/en not_active IP Right Cessation
- 1999-01-18 IS IS4945A patent/IS1968B/is unknown
- 1999-01-18 NO NO19990215A patent/NO319682B1/no not_active IP Right Cessation
- 1999-01-18 KR KR1019997000366A patent/KR100311857B1/ko not_active IP Right Cessation
- 1999-04-25 SA SA99200037A patent/SA99200037B1/ar unknown
- 1999-11-01 HK HK99104901A patent/HK1019757A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
YU49247B (sh)	2004-12-31
WO1998003554A1 (fr)	1998-01-29
US6534481B1 (en)	2003-03-18
SI0912613T1 (en)	2003-04-30
KR20000067909A (ko)	2000-11-25
CZ16099A3 (cs)	1999-06-16
HU223691B1 (hu)	2004-12-28
SK5399A3 (en)	2000-05-16
CN1228785A (zh)	1999-09-15
NZ333721A (en)	2000-08-25
ES2184123T3 (es)	2003-04-01
NO990215L (no)	1999-03-18
SK284881B6 (sk)	2006-02-02
AU726679B2 (en)	2000-11-16
IL128018A0 (en)	1999-11-30
SA99200037B1 (ar)	2006-08-23
EP0912613A1 (fr)	1999-05-06
ATE224917T1 (de)	2002-10-15
CA2261597C (fr)	2004-12-14
NO319682B1 (no)	2005-09-05
NO990215D0 (no)	1999-01-18
EE03929B1 (et)	2002-12-16
BR9710739A (pt)	1999-08-17
KR100311857B1 (ko)	2001-11-14
YU1999A (sh)	2000-03-21
BR9710739B1 (pt)	2008-11-18
IS4945A (is)	1999-01-18
CZ301009B6 (cs)	2009-10-14
ZA976340B (en)	1999-01-22
TW520376B (en)	2003-02-11
RU2167163C2 (ru)	2001-05-20
FR2751334A1 (fr)	1998-01-23
IL128018A (en)	2007-10-31
JP3345020B2 (ja)	2002-11-18
EP0912613B1 (fr)	2002-09-25
FR2751334B1 (fr)	1998-10-16
JP2000500807A (ja)	2000-01-25
PL331259A1 (en)	1999-07-05
IS1968B (is)	2004-12-15
EE9900015A (et)	1999-08-16
HUP9902287A1 (hu)	1999-10-28
DE69715866T2 (de)	2003-05-28
CN1200003C (zh)	2005-05-04
MY124548A (en)	2006-06-30
DE69715866D1 (de)	2002-10-31
HUP9902287A3 (en)	2001-09-28
CA2261597A1 (fr)	1998-01-29
HK1019757A1 (en)	2000-02-25
DK0912613T3 (da)	2003-01-27
TR199900114T2 (xx)	1999-03-22
PT912613E (pt)	2003-01-31
AU3774797A (en)	1998-02-10
AR008068A1 (es)	1999-12-09
ID20604A (id)	1999-01-21
PL190397B1 (pl)	2005-12-30

Publication	Publication Date	Title
UA61921C2 (uk)	2003-12-15	Синтетичні полісахариди, спосіб їх виготовлення та фармацевтичні композиції, які їх містять
AU2001291960C1 (en)	2009-10-08	Polysaccharides with antithrombotic activity comprising at least a covalent bond with biotin or a biotin derivative
TWI426080B (zh)	2014-02-11	硫酸化寡醣衍生物
AU741748B2 (en)	2001-12-06	Synthetic polysaccharides, their method of production and pharmaceutical compositions containing same
EP0801071A1 (en)	1997-10-15	Lewis x derivative and process for producing the same
AU2005284080B2 (en)	2011-10-13	Biotinylated hexadecasaccharides, preparation and use thereof
JPH09183789A (ja)	1997-07-15	新規な硫酸化及び燐酸化糖誘導体、その製法及び用途