UA75579C2 - Process for synthesis of oligosaccharides mixture - Google Patents
Process for synthesis of oligosaccharides mixture Download PDFInfo
- Publication number
- UA75579C2 UA75579C2 UA2002021613A UA2002021613A UA75579C2 UA 75579 C2 UA75579 C2 UA 75579C2 UA 2002021613 A UA2002021613 A UA 2002021613A UA 2002021613 A UA2002021613 A UA 2002021613A UA 75579 C2 UA75579 C2 UA 75579C2
- Authority
- UA
- Ukraine
- Prior art keywords
- benzyl
- ribitol
- tri
- disaccharide
- spacer
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 78
- 150000002482 oligosaccharides Chemical class 0.000 title claims abstract description 64
- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title claims abstract description 58
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 55
- 230000015572 biosynthetic process Effects 0.000 title claims description 44
- 230000008569 process Effects 0.000 title claims description 22
- 125000006850 spacer group Chemical group 0.000 claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- KRBIJIBTUCNJGU-BLADHDKVSA-N OP(O)(O)=O.OC[C@H](O)[C@H](O)[C@H](O)CO.OC[C@@H](O)[C@@H](O)[C@@H](O)C=O Chemical compound OP(O)(O)=O.OC[C@H](O)[C@H](O)[C@H](O)CO.OC[C@@H](O)[C@@H](O)[C@@H](O)C=O KRBIJIBTUCNJGU-BLADHDKVSA-N 0.000 claims abstract description 3
- 150000002016 disaccharides Chemical class 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 34
- 239000013461 intermediate chemical Substances 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical group CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims description 11
- 230000007062 hydrolysis Effects 0.000 claims description 11
- 238000006460 hydrolysis reaction Methods 0.000 claims description 11
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 10
- 238000006384 oligomerization reaction Methods 0.000 claims description 10
- 238000006068 polycondensation reaction Methods 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 9
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 7
- 229940073608 benzyl chloride Drugs 0.000 claims description 7
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- -1 for example Substances 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- JVWLUVNSQYXYBE-UHFFFAOYSA-N Ribitol Natural products OCC(C)C(O)C(O)CO JVWLUVNSQYXYBE-UHFFFAOYSA-N 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 5
- 230000006196 deacetylation Effects 0.000 claims description 5
- 238000003381 deacetylation reaction Methods 0.000 claims description 5
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- CGJFKQFYZOARRV-UHFFFAOYSA-N 2-(2-azidoethoxy)ethanol Chemical group OCCOCCN=[N+]=[N-] CGJFKQFYZOARRV-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 238000005954 phosphonylation reaction Methods 0.000 claims description 3
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 3
- 230000021736 acetylation Effects 0.000 claims description 2
- 238000006640 acetylation reaction Methods 0.000 claims description 2
- MIBQYWIOHFTKHD-UHFFFAOYSA-N adamantane-1-carbonyl chloride Chemical compound C1C(C2)CC3CC2CC1(C(=O)Cl)C3 MIBQYWIOHFTKHD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001743 benzylic group Chemical group 0.000 claims description 2
- 238000003795 desorption Methods 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 238000006317 isomerization reaction Methods 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- VSYPNDQPNLIBBD-UHFFFAOYSA-N 1h-imidazole;trichlorophosphane Chemical compound ClP(Cl)Cl.C1=CNC=N1 VSYPNDQPNLIBBD-UHFFFAOYSA-N 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- AFINAILKDBCXMX-PBHICJAKSA-N (2s,3r)-2-amino-3-hydroxy-n-(4-octylphenyl)butanamide Chemical compound CCCCCCCCC1=CC=C(NC(=O)[C@@H](N)[C@@H](C)O)C=C1 AFINAILKDBCXMX-PBHICJAKSA-N 0.000 claims 1
- OZNXTQSXSHODFR-UHFFFAOYSA-N 1-chloroadamantane Chemical compound C1C(C2)CC3CC2CC1(Cl)C3 OZNXTQSXSHODFR-UHFFFAOYSA-N 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- 229960005486 vaccine Drugs 0.000 abstract description 42
- 150000004676 glycans Chemical class 0.000 abstract description 30
- 229920001282 polysaccharide Polymers 0.000 abstract description 27
- 239000005017 polysaccharide Substances 0.000 abstract description 27
- 230000021615 conjugation Effects 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 5
- 208000015181 infectious disease Diseases 0.000 abstract description 5
- 229960005030 other vaccine in atc Drugs 0.000 abstract description 4
- 241000606768 Haemophilus influenzae Species 0.000 abstract 3
- 229940045808 haemophilus influenzae type b Drugs 0.000 abstract 3
- 230000002265 prevention Effects 0.000 abstract 2
- 230000003252 repetitive effect Effects 0.000 abstract 2
- 239000000243 solution Substances 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 25
- 239000000427 antigen Substances 0.000 description 22
- 102000036639 antigens Human genes 0.000 description 22
- 108091007433 antigens Proteins 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000012634 fragment Substances 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000006188 syrup Substances 0.000 description 13
- 235000020357 syrup Nutrition 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 239000007790 solid phase Substances 0.000 description 12
- 108010060123 Conjugate Vaccines Proteins 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 229940031670 conjugate vaccine Drugs 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000000108 ultra-filtration Methods 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 101710116435 Outer membrane protein Proteins 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000002096 anti-tetanic effect Effects 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 238000005574 benzylation reaction Methods 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 238000011210 chromatographic step Methods 0.000 description 5
- 206010013023 diphtheria Diseases 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 230000028996 humoral immune response Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- OENLEHTYJXMVBG-UHFFFAOYSA-N pyridine;hydrate Chemical compound [OH-].C1=CC=[NH+]C=C1 OENLEHTYJXMVBG-UHFFFAOYSA-N 0.000 description 5
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 201000005702 Pertussis Diseases 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 206010043376 Tetanus Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
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- 238000005119 centrifugation Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 description 4
- 235000019800 disodium phosphate Nutrition 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 229960004906 thiomersal Drugs 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- MQEJSDYKOPLIDV-UHFFFAOYSA-N 2-[2,3-bis(2-aminoethyl)pyridin-4-yl]ethanamine Chemical compound NCCC1=CC=NC(CCN)=C1CCN MQEJSDYKOPLIDV-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
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- 239000000706 filtrate Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
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- 150000004804 polysaccharides Polymers 0.000 description 3
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- 238000012360 testing method Methods 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
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- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 201000009906 Meningitis Diseases 0.000 description 2
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- KOZCGIRYBYLSKC-UHFFFAOYSA-N nonatriacontane-19,20,21-triol Chemical compound CCCCCCCCCCCCCCCCCCC(O)C(O)C(O)CCCCCCCCCCCCCCCCCC KOZCGIRYBYLSKC-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
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- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
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- NRTLTGGGUQIRRT-UHFFFAOYSA-N triethylazanium;bromide Chemical compound [Br-].CC[NH+](CC)CC NRTLTGGGUQIRRT-UHFFFAOYSA-N 0.000 description 2
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- VJMRKWPMFQGIPI-UHFFFAOYSA-N n-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide Chemical group OCC1=C(C(=O)NCCO)C(C)=NN1C1=CC=CC2=C1SC(CC=1C=C(C=CC=1)C(F)(F)F)=C2 VJMRKWPMFQGIPI-UHFFFAOYSA-N 0.000 description 1
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000002743 phosphorus functional group Chemical group 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
- KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical compound CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
- C07H15/08—Polyoxyalkylene derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/18—Acyclic radicals, substituted by carbocyclic rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CU1999121A CU22904A1 (es) | 1999-08-30 | 1999-08-30 | Oligosacáridos derivados de ribosa- ribitol-fosfato, métodos para prepararlos, inmunógenos que los comprenden y vacunas que comprenden dichos inmunógenos |
| PCT/CU2000/000003 WO2001016146A1 (es) | 1999-08-30 | 2000-08-15 | Oligosacáridos derivados de ribosa-ribitol-fosfato y vacunas que los contienen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA75579C2 true UA75579C2 (en) | 2006-05-15 |
Family
ID=5459405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2002021613A UA75579C2 (en) | 1999-08-30 | 2000-08-15 | Process for synthesis of oligosaccharides mixture |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6765091B1 (ru) |
| EP (1) | EP1212334B1 (ru) |
| JP (1) | JP4850377B2 (ru) |
| KR (1) | KR100818163B1 (ru) |
| CN (1) | CN1205217C (ru) |
| AR (1) | AR025435A1 (ru) |
| AT (1) | ATE308551T1 (ru) |
| AU (1) | AU780816B2 (ru) |
| BR (1) | BRPI0013686B8 (ru) |
| CA (1) | CA2382602C (ru) |
| CO (1) | CO5180646A1 (ru) |
| CU (1) | CU22904A1 (ru) |
| CZ (1) | CZ2002721A3 (ru) |
| DE (1) | DE60023722T2 (ru) |
| DK (1) | DK1212334T3 (ru) |
| EA (1) | EA005381B1 (ru) |
| ES (1) | ES2252045T3 (ru) |
| HK (1) | HK1050693A1 (ru) |
| MX (1) | MXPA02002066A (ru) |
| NZ (1) | NZ517464A (ru) |
| SI (1) | SI1212334T1 (ru) |
| UA (1) | UA75579C2 (ru) |
| WO (1) | WO2001016146A1 (ru) |
| ZA (1) | ZA200201667B (ru) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050169941A1 (en) * | 2004-01-29 | 2005-08-04 | Andrew Lees | Use of amino-oxy functional groups in the preparation of protein-polysaccharide conjugate vaccines |
| WO2011017101A2 (en) | 2009-07-27 | 2011-02-10 | Fina Biosolutions, Llc | Method for producing protein-carbohydrate vaccines reduced in free carbohydrate |
| US9085610B2 (en) | 2009-07-31 | 2015-07-21 | National Research Council Of Canada | H. pylori lipopolysaccharide outer core epitope |
| CA2836140C (en) | 2009-12-17 | 2016-06-21 | Fina Biosolutions, Llc | Chemical reagents for the activation of polysaccharides in the preparation of conjugate vaccines |
| AU2010351576B2 (en) * | 2010-04-23 | 2014-08-14 | FinaBioSolutions, LLC | Simple method for simultaneous removal of multiple impurities from culture supernatants to ultralow levels |
| SG11201811350QA (en) | 2016-07-28 | 2019-01-30 | Max Planck Gesellschaft | Stable hydrolysis-resistant synthetic polyribosylribitolphosphate derivatives as vaccines against haemophilus influenzae type b |
| EP3768309A4 (en) * | 2018-03-23 | 2021-12-01 | Koranex Capital | PRECISION GLYCOCONJUGATES AS THERAPEUTIC TOOLS |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ223009A (en) * | 1986-12-31 | 1990-06-26 | Nl Rivm Of Thoven | Oligosaccharides containing d-ribose d-ribitol and phosphate units mimicing haemophilus influenzae type b antigens |
| EP0320942A3 (en) * | 1987-12-18 | 1989-10-04 | American Cyanamid Company | Novel polysaccharides novel macromolecular conjugates of the polysaccharides |
| US5843463A (en) * | 1990-12-21 | 1998-12-01 | Antexbiologics, Inc. | Adhesin-oligosaccharide conjugate vaccine for Haemophilus influenzae |
-
1999
- 1999-08-30 CU CU1999121A patent/CU22904A1/es unknown
-
2000
- 2000-08-15 ES ES00956040T patent/ES2252045T3/es not_active Expired - Lifetime
- 2000-08-15 DK DK00956040T patent/DK1212334T3/da active
- 2000-08-15 MX MXPA02002066A patent/MXPA02002066A/es active IP Right Grant
- 2000-08-15 BR BRPI0013686A patent/BRPI0013686B8/pt not_active IP Right Cessation
- 2000-08-15 KR KR1020027002706A patent/KR100818163B1/ko not_active IP Right Cessation
- 2000-08-15 EP EP00956040A patent/EP1212334B1/en not_active Expired - Lifetime
- 2000-08-15 JP JP2001519710A patent/JP4850377B2/ja not_active Expired - Fee Related
- 2000-08-15 AT AT00956040T patent/ATE308551T1/de active
- 2000-08-15 DE DE60023722T patent/DE60023722T2/de not_active Expired - Lifetime
- 2000-08-15 CZ CZ2002721A patent/CZ2002721A3/cs unknown
- 2000-08-15 US US10/070,101 patent/US6765091B1/en not_active Expired - Lifetime
- 2000-08-15 NZ NZ517464A patent/NZ517464A/en not_active IP Right Cessation
- 2000-08-15 SI SI200030780T patent/SI1212334T1/sl unknown
- 2000-08-15 CN CNB008134731A patent/CN1205217C/zh not_active Expired - Lifetime
- 2000-08-15 EA EA200200314A patent/EA005381B1/ru not_active IP Right Cessation
- 2000-08-15 WO PCT/CU2000/000003 patent/WO2001016146A1/es active IP Right Grant
- 2000-08-15 CA CA2382602A patent/CA2382602C/en not_active Expired - Fee Related
- 2000-08-15 AU AU68173/00A patent/AU780816B2/en not_active Ceased
- 2000-08-15 UA UA2002021613A patent/UA75579C2/uk unknown
- 2000-08-28 CO CO00064095A patent/CO5180646A1/es active IP Right Grant
- 2000-08-29 AR ARP000104496A patent/AR025435A1/es not_active Application Discontinuation
-
2002
- 2002-02-27 ZA ZA200201667A patent/ZA200201667B/en unknown
-
2003
- 2003-04-23 HK HK03102864A patent/HK1050693A1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2003528032A (ja) | 2003-09-24 |
| WO2001016146A1 (es) | 2001-03-08 |
| EA005381B1 (ru) | 2005-02-24 |
| CO5180646A1 (es) | 2002-07-30 |
| US6765091B1 (en) | 2004-07-20 |
| MXPA02002066A (es) | 2004-07-30 |
| CU22904A1 (es) | 2004-01-23 |
| CZ2002721A3 (cs) | 2002-07-17 |
| CN1376158A (zh) | 2002-10-23 |
| CA2382602C (en) | 2010-02-16 |
| CN1205217C (zh) | 2005-06-08 |
| BRPI0013686B8 (pt) | 2021-05-25 |
| AU780816B2 (en) | 2005-04-21 |
| DE60023722D1 (de) | 2005-12-08 |
| ATE308551T1 (de) | 2005-11-15 |
| EP1212334A1 (en) | 2002-06-12 |
| BR0013686A (pt) | 2002-08-13 |
| BRPI0013686B1 (pt) | 2016-07-26 |
| EP1212334B1 (en) | 2005-11-02 |
| AU6817300A (en) | 2001-03-26 |
| KR100818163B1 (ko) | 2008-03-31 |
| DE60023722T2 (de) | 2006-07-20 |
| DK1212334T3 (da) | 2006-03-20 |
| SI1212334T1 (sl) | 2006-04-30 |
| KR20020068501A (ko) | 2002-08-27 |
| EA200200314A1 (ru) | 2002-10-31 |
| AR025435A1 (es) | 2002-11-27 |
| ZA200201667B (en) | 2003-08-27 |
| CA2382602A1 (en) | 2001-03-08 |
| ES2252045T3 (es) | 2006-05-16 |
| JP4850377B2 (ja) | 2012-01-11 |
| NZ517464A (en) | 2004-03-26 |
| HK1050693A1 (en) | 2003-07-04 |
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