JP2004509902A5 - - Google Patents
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- Publication number
- JP2004509902A5 JP2004509902A5 JP2002529162A JP2002529162A JP2004509902A5 JP 2004509902 A5 JP2004509902 A5 JP 2004509902A5 JP 2002529162 A JP2002529162 A JP 2002529162A JP 2002529162 A JP2002529162 A JP 2002529162A JP 2004509902 A5 JP2004509902 A5 JP 2004509902A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- glucopyranosyl
- tri
- sulfonate
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
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- 239000000243 solution Substances 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000004519 manufacturing process Methods 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 229920005654 Sephadex Polymers 0.000 description 17
- 239000012507 Sephadex™ Substances 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000004108 freeze drying Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 9
- -1 2,3,6-tri-O-methyl-β-D-glucopyranosyl Chemical group 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 3
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 3
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- XFLVBMBRLSCJAI-ZKWXMUAHSA-N biotin amide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)N)SC[C@@H]21 XFLVBMBRLSCJAI-ZKWXMUAHSA-N 0.000 description 3
- XFLVBMBRLSCJAI-UHFFFAOYSA-N biotin amide Natural products N1C(=O)NC2C(CCCCC(=O)N)SCC21 XFLVBMBRLSCJAI-UHFFFAOYSA-N 0.000 description 3
- 229940125807 compound 37 Drugs 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 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 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
- YYHPEVZFVMVUNJ-UHFFFAOYSA-N n,n-diethylethanamine;sulfur trioxide Chemical compound O=S(=O)=O.CCN(CC)CC YYHPEVZFVMVUNJ-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 3
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 2
- 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
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 2
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 2
- OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 description 2
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 2
- 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 2
- BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 description 2
- 229940126639 Compound 33 Drugs 0.000 description 2
- 229940127007 Compound 39 Drugs 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 2
- 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 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229940125878 compound 36 Drugs 0.000 description 2
- 229940126540 compound 41 Drugs 0.000 description 2
- 229940125844 compound 46 Drugs 0.000 description 2
- 229940127271 compound 49 Drugs 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 1
- OFDPEKFHZNICPM-WYRLRVFGSA-N (2r,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol;2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl.OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O OFDPEKFHZNICPM-WYRLRVFGSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- DMDQHFMRRHKFOW-UFLZEWODSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoic acid;2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound OS(=O)(=O)C1CC(=O)NC1=O.N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 DMDQHFMRRHKFOW-UFLZEWODSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
- YFHNDHXQDJQEEE-UHFFFAOYSA-N acetic acid;hydrazine Chemical compound NN.CC(O)=O YFHNDHXQDJQEEE-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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
- 230000003472 neutralizing effect Effects 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000004044 tetrasaccharides Chemical class 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0012094A FR2814463B1 (fr) | 2000-09-22 | 2000-09-22 | Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine |
| FR00/12094 | 2000-09-22 | ||
| PCT/FR2001/002918 WO2002024754A1 (fr) | 2000-09-22 | 2001-09-20 | Polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine |
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| JP2012027377A Division JP2012131809A (ja) | 2000-09-22 | 2012-02-10 | ビオチンまたはビオチン誘導体との少なくとも一つの共有結合を含み抗血栓活性を有するポリサッカライド |
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| JP2004509902A JP2004509902A (ja) | 2004-04-02 |
| JP2004509902A5 true JP2004509902A5 (member.php) | 2012-03-29 |
| JP5016778B2 JP5016778B2 (ja) | 2012-09-05 |
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| JP2002529162A Expired - Fee Related JP5016778B2 (ja) | 2000-09-22 | 2001-09-20 | ビオチンまたはビオチン誘導体との少なくとも一つの共有結合を含み抗血栓活性を有するポリサッカライド |
| JP2012027377A Pending JP2012131809A (ja) | 2000-09-22 | 2012-02-10 | ビオチンまたはビオチン誘導体との少なくとも一つの共有結合を含み抗血栓活性を有するポリサッカライド |
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| JP2012027377A Pending JP2012131809A (ja) | 2000-09-22 | 2012-02-10 | ビオチンまたはビオチン誘導体との少なくとも一つの共有結合を含み抗血栓活性を有するポリサッカライド |
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Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| 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 |
| US8183228B2 (en) * | 2005-10-10 | 2012-05-22 | MSD OSS B.V. Netherlands | Anticoagulant antithrombotic dual inhibitors comprising a biotin label |
| ATE500849T1 (de) * | 2005-10-10 | 2011-03-15 | Organon Nv | Antikoagulans/antithrombose-dual-hemmer mit einem biotin-label |
| CN1317035C (zh) * | 2005-10-24 | 2007-05-23 | 天津大学 | 基于酰肼基的微粒表面多重生物功能因子组装方法 |
| EP1886696A1 (en) * | 2006-08-03 | 2008-02-13 | Endotis Pharma | Conjugates of antithrombin binding oligosaccharide derivatives and therapeutic proteins |
| FR2912409B1 (fr) * | 2007-02-14 | 2012-08-24 | Sanofi Aventis | Heparines de bas poids moleculaire comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine leur procede de preparation,leur utilisation |
| TW201006479A (en) * | 2008-07-18 | 2010-02-16 | Sanofi Aventis | Use of idrabiotaparinux for decreasing the incidence of bleedings during an antithrombotic treatment |
| EP2233143A1 (en) | 2009-03-24 | 2010-09-29 | Sanofi-Aventis | Use of idrabiotaparinux for decreasing the incidence of bleedings during an antithrombotic treatment |
| EP2145624A1 (en) | 2008-07-18 | 2010-01-20 | Sanofi-Aventis | Use of idrabiotaparinux for decreasing the incidence of bleedings during an antithrombotic treatment |
| FR2935386B1 (fr) * | 2008-08-26 | 2010-09-10 | Sanofi Aventis | Nouveaux polysaccharides a activite antithrombotique comprenant une liaion covalente avec une chaine amine |
| US20110150976A1 (en) * | 2008-09-10 | 2011-06-23 | Transpharma Medical Ltd. | Transdermal delivery of oligosaccharides |
| CA2746509C (en) | 2008-12-19 | 2018-11-20 | Supernus Pharmaceuticals, Inc. | Use of molindone for the treatment of impulsive agression |
| FR2952935B1 (fr) * | 2009-11-20 | 2011-12-02 | Sanofi Aventis | Procede de preparation du n-biotinyl-6-aminocaproate de n succinimidyle |
| CA2784529C (en) | 2009-12-18 | 2018-05-22 | Catalent France Beinheim Sa | Pharmaceutical oral dosage form containing a synthetic oligosaccharide |
| CZ302510B6 (cs) * | 2010-03-29 | 2011-06-22 | Univerzita Palackého v Olomouci | Efektivní zpusob biotinylace sloucenin s karboxylovou skupinou pomocí syntézy na pevné fázi pro potreby afinitní chromatografie |
| CZ302669B6 (cs) * | 2010-03-29 | 2011-08-24 | Univerzita Palackého v Olomouci | Efektivní zpusob biotinylace aminosloucenin pomocí syntézy na pevné fázi pro potreby afinitní chromatografie |
| US8748472B2 (en) | 2010-03-31 | 2014-06-10 | Supernus Pharmaceuticals, Inc. | Stabilized formulations of CNS compounds |
| WO2012042123A1 (fr) | 2010-09-10 | 2012-04-05 | Sanofi | Polysaccharides biotinyles a activite antithrombotique et presentant une stabilite metabolique amelioree |
| FR2964660B1 (fr) * | 2010-09-10 | 2012-09-28 | Sanofi Aventis | Nouveaux polysaccharides biotinyles a activite antithrombotique et presentant une stabilite metabolique amelioree |
| EP2484366A1 (en) | 2011-02-07 | 2012-08-08 | Sanofi | Idrabiotaparinux for the treatment of pulmonary embolism and for the secondary prevention of venous thromboembolic events |
| CN103917552B (zh) | 2011-06-17 | 2017-03-29 | 卡博梅麦特斯公司 | 具有短半衰期和高活性的合成五糖 |
| JP2015536999A (ja) * | 2012-11-13 | 2015-12-24 | スパーナス ファーマシューティカルズ インコーポレイテッド | 攻撃性の治療法 |
| WO2015195404A1 (en) | 2014-06-20 | 2015-12-23 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Methods for detection of an analyte by movement of tethered microparticles |
| WO2016205239A1 (en) | 2015-06-15 | 2016-12-22 | The United States Of America, As Represented By The Secretary Department Of Health And Human Services | Non-hormonal mammalian sperm decoy contraception based on the n-terminus of the zp2 protein |
| US11536719B2 (en) | 2016-10-21 | 2022-12-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Molecular nanotags |
| CN108976318B (zh) * | 2017-06-01 | 2021-03-30 | 首都医科大学 | 单-6-(生物素酰胺基)-6-脱氧-β-环糊精及其制备方法和应用 |
| WO2019133727A1 (en) | 2017-12-29 | 2019-07-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Universal influenza virus probe set for enrichment of any influenza virus nucleic acid |
| WO2021007429A1 (en) | 2019-07-09 | 2021-01-14 | Optimvia Llc | Methods for synthesizing anticoagulant polysaccharides |
| US20230047654A1 (en) * | 2019-10-17 | 2023-02-16 | Autonetworks Technologies, Ltd. | Wiring module |
| WO2022056078A1 (en) | 2020-09-11 | 2022-03-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Rnase h-assisted detection assay for rna (radar) |
| WO2024191684A1 (en) | 2023-03-10 | 2024-09-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Detection of hepatitis c virus ribonucleic acid from whole blood using reverse transcription loop-mediated isothermal amplification |
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| US3960884A (en) * | 1974-04-24 | 1976-06-01 | Sergei Ivanovich Zavyalov | Method of preparing racemic biotin |
| AU563351C (en) * | 1982-01-15 | 2003-06-19 | Glaxo Group Limited | Synthesis of oligosaccharides |
| IL102758A (en) * | 1991-08-23 | 1997-03-18 | Akzo Nv | Glycosaminoglycanoid derivatives, their preparation and pharmaceutical compositions comprising them |
| US20010023288A1 (en) * | 1999-07-07 | 2001-09-20 | Wilbur D. Scott | Trifunctional reagent for conjugation to a biomolecule |
| WO2000002050A1 (en) * | 1998-07-07 | 2000-01-13 | Department Of Radiation Oncology, University Of Washington | Trifunctional reagent for conjugation to a biomolecule |
| FR2751334B1 (fr) * | 1996-07-19 | 1998-10-16 | Sanofi Sa | Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant |
| FR2773804B1 (fr) * | 1998-01-19 | 2000-02-18 | Sanofi Sa | Polysaccharides de synthese, procede pour leur preparation et compositions pharmaceutiques le contenant |
| FR2773801B1 (fr) * | 1998-01-19 | 2000-05-12 | Sanofi Sa | Nouveaux pentasaccharides, procedes pour leurs preparations et compositions pharmaceutiques les contenant |
| GB2335490B (en) * | 1998-03-20 | 2003-05-14 | Ortho Clinical Diagnostics | An assay surface that permits an analyte releasiing step |
| CA2305619C (en) | 1998-07-31 | 2008-05-20 | Seikagaku Corporation | Novel glycosaminoglycan and pharmaceutical composition using the same as active ingredient |
| 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 |
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2000
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