NO305368B1 - AnalogifremgangsmÕte for fremstilling av et terapeutisk aktivt fosfolipidbundet glykosaminglykan - Google Patents
AnalogifremgangsmÕte for fremstilling av et terapeutisk aktivt fosfolipidbundet glykosaminglykan Download PDFInfo
- Publication number
- NO305368B1 NO305368B1 NO921083A NO921083A NO305368B1 NO 305368 B1 NO305368 B1 NO 305368B1 NO 921083 A NO921083 A NO 921083A NO 921083 A NO921083 A NO 921083A NO 305368 B1 NO305368 B1 NO 305368B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- gag
- phospholipid
- formula
- reducing terminal
- Prior art date
Links
- -1 Glycosamine Glycan Chemical class 0.000 title claims description 109
- 238000000034 method Methods 0.000 title claims description 69
- 238000002360 preparation method Methods 0.000 title claims description 44
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 135
- 150000002632 lipids Chemical class 0.000 claims abstract description 68
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 46
- 229920002683 Glycosaminoglycan Polymers 0.000 claims abstract description 9
- 230000007717 exclusion Effects 0.000 claims description 59
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 40
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 39
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 39
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 39
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 claims description 35
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 claims description 35
- 229920002567 Chondroitin Polymers 0.000 claims description 34
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 claims description 34
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 31
- 229920002674 hyaluronan Polymers 0.000 claims description 31
- 229960003160 hyaluronic acid Drugs 0.000 claims description 31
- 229920000045 Dermatan sulfate Polymers 0.000 claims description 23
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 claims description 23
- 229940051593 dermatan sulfate Drugs 0.000 claims description 23
- 230000002829 reductive effect Effects 0.000 claims description 23
- 150000008273 hexosamines Chemical group 0.000 claims description 21
- 229920002971 Heparan sulfate Polymers 0.000 claims description 20
- 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 claims description 19
- 229920000288 Keratan sulfate Polymers 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 238000007254 oxidation reaction Methods 0.000 claims description 18
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical group O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 claims description 17
- 229960002897 heparin Drugs 0.000 claims description 17
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 14
- 230000003647 oxidation Effects 0.000 claims description 14
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 229920000669 heparin Polymers 0.000 claims description 10
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 8
- 125000003172 aldehyde group Chemical group 0.000 claims description 8
- 229910004727 OSO3H Inorganic materials 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 6
- 125000005263 alkylenediamine group Chemical group 0.000 claims description 6
- 238000003776 cleavage reaction Methods 0.000 claims description 6
- 230000007017 scission Effects 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 150000002596 lactones Chemical class 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- CDAISMWEOUEBRE-UHFFFAOYSA-N inositol Chemical group OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 2
- IAJILQKETJEXLJ-LECHCGJUSA-N iduronic acid Chemical group O=C[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-LECHCGJUSA-N 0.000 claims 4
- 230000001225 therapeutic effect Effects 0.000 claims 3
- 210000004027 cell Anatomy 0.000 abstract description 54
- 150000001875 compounds Chemical class 0.000 abstract description 32
- 206010028980 Neoplasm Diseases 0.000 abstract description 15
- 201000011510 cancer Diseases 0.000 abstract description 15
- 206010027476 Metastases Diseases 0.000 abstract description 13
- 210000002744 extracellular matrix Anatomy 0.000 abstract description 12
- 230000009401 metastasis Effects 0.000 abstract description 10
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 239000002257 antimetastatic agent Substances 0.000 abstract description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- 125000000686 lactone group Chemical group 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
- 239000002244 precipitate Substances 0.000 description 32
- 150000002337 glycosamines Chemical class 0.000 description 31
- 239000000047 product Substances 0.000 description 30
- 235000002639 sodium chloride Nutrition 0.000 description 29
- 239000000203 mixture Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 18
- 150000002148 esters Chemical class 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- 230000021164 cell adhesion Effects 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 230000002209 hydrophobic effect Effects 0.000 description 10
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000001632 sodium acetate Substances 0.000 description 9
- 235000017281 sodium acetate Nutrition 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 8
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 8
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000009833 condensation Methods 0.000 description 8
- 230000005494 condensation Effects 0.000 description 8
- 210000002889 endothelial cell Anatomy 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- 108010067306 Fibronectins Proteins 0.000 description 7
- 102000016359 Fibronectins Human genes 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000006285 cell suspension Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 208000037819 metastatic cancer Diseases 0.000 description 6
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 5
- AEMOLEFTQBMNLQ-HNFCZKTMSA-N L-idopyranuronic acid Chemical group OC1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-HNFCZKTMSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 229930182830 galactose Natural products 0.000 description 5
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 5
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical class O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 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 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102000012422 Collagen Type I Human genes 0.000 description 3
- 108010022452 Collagen Type I Proteins 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108010031318 Vitronectin Proteins 0.000 description 3
- 102100035140 Vitronectin Human genes 0.000 description 3
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000001030 gas--liquid chromatography Methods 0.000 description 3
- 108010034892 glycyl-arginyl-glycyl-aspartyl-serine Proteins 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- AEMOLEFTQBMNLQ-CLQWQSTFSA-N l-iduronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O AEMOLEFTQBMNLQ-CLQWQSTFSA-N 0.000 description 3
- 238000007273 lactonization reaction Methods 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000005932 reductive alkylation reaction Methods 0.000 description 3
- 229940014800 succinic anhydride Drugs 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- RGNVSYKVCGAEHK-GUBZILKMSA-N (3s)-3-[[2-[[(2s)-2-[(2-aminoacetyl)amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-4-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-oxobutanoic acid Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O RGNVSYKVCGAEHK-GUBZILKMSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000251730 Chondrichthyes Species 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 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 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 210000003292 kidney cell Anatomy 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
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 2
- HOGDNTQCSIKEEV-UHFFFAOYSA-N n'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical class O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 150000003443 succinic acid derivatives Chemical class 0.000 description 2
- 150000003900 succinic acid esters Chemical class 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- MLIWQXBKMZNZNF-KUHOPJCQSA-N (2e)-2,6-bis[(4-azidophenyl)methylidene]-4-methylcyclohexan-1-one Chemical compound O=C1\C(=C\C=2C=CC(=CC=2)N=[N+]=[N-])CC(C)CC1=CC1=CC=C(N=[N+]=[N-])C=C1 MLIWQXBKMZNZNF-KUHOPJCQSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- BOSWPVRACYJBSJ-UHFFFAOYSA-N 1,3-di(p-tolyl)carbodiimide Chemical compound C1=CC(C)=CC=C1N=C=NC1=CC=C(C)C=C1 BOSWPVRACYJBSJ-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- GBLFCJFNRZFNIW-UHFFFAOYSA-N 3-(tert-butyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=NC(C)(C)C GBLFCJFNRZFNIW-UHFFFAOYSA-N 0.000 description 1
- FNEHAOQZWPHONV-UHFFFAOYSA-N 9h-carbazole;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC=C2C3=CC=CC=C3NC2=C1 FNEHAOQZWPHONV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000009331 Experimental Sarcoma Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 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 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
- 239000004166 Lanolin Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102100029469 WD repeat and HMG-box DNA-binding protein 1 Human genes 0.000 description 1
- 101710097421 WD repeat and HMG-box DNA-binding protein 1 Proteins 0.000 description 1
- 229960001413 acetanilide Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 description 1
- 210000002403 aortic endothelial cell Anatomy 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000010370 cell cloning Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- HCFPRFJJTHMING-UHFFFAOYSA-N ethane-1,2-diamine;hydron;chloride Chemical compound [Cl-].NCC[NH3+] HCFPRFJJTHMING-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 125000003981 glycosaminyl group Chemical group 0.000 description 1
- SELIRUAKCBWGGE-UHFFFAOYSA-N hexadecanoic acid;octadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O SELIRUAKCBWGGE-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- UOXRPRZMAROFPH-IESLQMLBSA-N lysophosphatidylinositol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP(O)(=O)OC1[C@H](O)[C@@H](O)C(O)[C@@H](O)[C@H]1O UOXRPRZMAROFPH-IESLQMLBSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000002032 methanolic fraction Substances 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 150000002759 monoacylglycerols Chemical class 0.000 description 1
- KSVMTHKYDGMXFJ-UHFFFAOYSA-N n,n'-bis(trimethylsilyl)methanediimine Chemical compound C[Si](C)(C)N=C=N[Si](C)(C)C KSVMTHKYDGMXFJ-UHFFFAOYSA-N 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- CMESPBFFDMPSIY-UHFFFAOYSA-N n,n'-diphenylmethanediimine Chemical compound C1=CC=CC=C1N=C=NC1=CC=CC=C1 CMESPBFFDMPSIY-UHFFFAOYSA-N 0.000 description 1
- QXHKSZBIXVHRNF-UHFFFAOYSA-N n-methyl-n'-propylmethanediimine Chemical compound CCCN=C=NC QXHKSZBIXVHRNF-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Substances [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 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
- 238000012360 testing method Methods 0.000 description 1
- 150000004044 tetrasaccharides Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
- A61K47/544—Phospholipids
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2193817A JP2997018B2 (ja) | 1990-07-24 | 1990-07-24 | 燐脂質又は脂質結合グリコサミノグリカン |
| JP2193818A JP2986519B2 (ja) | 1990-07-24 | 1990-07-24 | 燐脂質結合グリコサミノグリカン |
| JP2193816A JP2986518B2 (ja) | 1990-07-24 | 1990-07-24 | 癌転移抑制剤 |
| PCT/JP1991/000995 WO1992001720A1 (en) | 1990-07-24 | 1991-07-24 | Phospholipid- or lipid-combining glycosaminoglycan, production thereof, and cancer metastasis inhibitor |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO921083D0 NO921083D0 (no) | 1992-03-19 |
| NO921083L NO921083L (no) | 1992-05-21 |
| NO305368B1 true NO305368B1 (no) | 1999-05-18 |
Family
ID=27326820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO921083A NO305368B1 (no) | 1990-07-24 | 1992-03-19 | AnalogifremgangsmÕte for fremstilling av et terapeutisk aktivt fosfolipidbundet glykosaminglykan |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5464942A (fi) |
| EP (1) | EP0493622B1 (fi) |
| KR (1) | KR0181295B1 (fi) |
| AT (1) | ATE148713T1 (fi) |
| AU (1) | AU647814B2 (fi) |
| CA (1) | CA2067211C (fi) |
| DE (1) | DE69124590T2 (fi) |
| FI (1) | FI103279B1 (fi) |
| NO (1) | NO305368B1 (fi) |
| WO (1) | WO1992001720A1 (fi) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3199405B2 (ja) * | 1991-08-30 | 2001-08-20 | 生化学工業株式会社 | 肝細胞球状集塊化剤及び球状集塊化肝細胞の製造方法 |
| IT1260137B (it) * | 1992-04-17 | 1996-03-28 | Alfa Wassermann Spa | Glicosaminoglicani semisintetici a struttura eparinica od eparanica modificati nella posizione 2 dell'acido alfa-l-iduronico-2-0-solfato |
| CA2118586A1 (en) * | 1992-07-13 | 1994-01-20 | Bernard Malfroy-Camine | Transvascular and intracellular delivery of lipidized proteins |
| JP3714683B2 (ja) * | 1992-07-30 | 2005-11-09 | 生化学工業株式会社 | 抗リウマチ剤 |
| JP2787279B2 (ja) * | 1994-05-17 | 1998-08-13 | 雪印乳業株式会社 | 糖リン脂質及びその調製法 |
| US6228998B1 (en) | 1994-07-22 | 2001-05-08 | Seikagaku Kogyo Kabushiki Kaisha | Amino spacered glycosaminoglycan derivatives and their use in copolymerization with acrylamide |
| FR2725622A1 (fr) * | 1994-10-14 | 1996-04-19 | Fabre Pierre Dermo Cosmetique | Ceramide greffee anti-elastase |
| CA2175282A1 (en) * | 1996-04-29 | 1997-10-30 | Rudolf Edgar Falk | Use of forms of hyaluronic acid (ha) for the treatment of cancer |
| WO2000040253A1 (en) * | 1999-01-08 | 2000-07-13 | The Board Of Trustees Of The University Of Arkansas | Synthetic, highly charged molecules and uses thereof |
| JP3032824B1 (ja) * | 1999-01-28 | 2000-04-17 | 東京医科歯科大学長 | 骨誘導促進剤 |
| AU6472900A (en) * | 1999-08-10 | 2001-03-13 | Seikagaku Corporation | Glycosaminoglycan derivatives and utilization thereof |
| US7608598B2 (en) | 2000-01-10 | 2009-10-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of conjunctivitis |
| US8076312B2 (en) * | 2000-01-10 | 2011-12-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Use of lipid conjugates in the treatment of disease |
| US7772196B2 (en) * | 2000-01-10 | 2010-08-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases |
| US8916539B2 (en) * | 2000-01-10 | 2014-12-23 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of disease |
| US7893226B2 (en) * | 2004-09-29 | 2011-02-22 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Use of lipid conjugates in the treatment of diseases |
| US7101859B2 (en) * | 2000-01-10 | 2006-09-05 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases |
| US20090325876A1 (en) * | 2004-09-29 | 2009-12-31 | Saul Yedgar | Use of lipid conjugates in the treatment of diseases associated with vasculature |
| US7141552B2 (en) * | 2000-01-10 | 2006-11-28 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases |
| US7393938B2 (en) * | 2000-01-10 | 2008-07-01 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases |
| US7811999B2 (en) * | 2000-01-10 | 2010-10-12 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Use of lipid conjugates in the treatment of diseases |
| US20060189568A1 (en) * | 2000-01-10 | 2006-08-24 | Saul Yedgar | Use of lipid conjugates in the treatment of infection |
| US8304395B2 (en) * | 2000-01-10 | 2012-11-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Lipid conjugates in the treatment of disease |
| US9040078B2 (en) * | 2000-01-10 | 2015-05-26 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases of the nervous system |
| US8501701B2 (en) * | 2000-01-10 | 2013-08-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Use of lipid conjugates in the treatment of disease |
| US7259152B2 (en) | 2000-06-07 | 2007-08-21 | Alfa Wasserman, Inc. | Methods and compositions using sulodexide for the treatment of diabetic nephropathy |
| US8883761B2 (en) * | 2001-01-10 | 2014-11-11 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases associated with vasculature |
| US7280612B2 (en) * | 2003-07-25 | 2007-10-09 | Zarbana Digital Fund Llc | Digital branch calibrator for an RF transmitter |
| EP1681306B1 (en) * | 2003-10-29 | 2013-02-20 | Teijin Limited | Hyaluronic acid compound, hydrogel thereof and material for treating joint |
| CA2617484A1 (en) * | 2005-08-03 | 2007-02-15 | Morria Biopharmaceuticals | Use of lipid conjugates in cystic fibrosis and applications thereof |
| JP4744973B2 (ja) * | 2005-08-05 | 2011-08-10 | 株式会社トプコン | 眼底カメラ |
| US8475694B2 (en) | 2005-10-25 | 2013-07-02 | Zephyros, Inc. | Shaped expandable material |
| US8906882B2 (en) | 2005-11-17 | 2014-12-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Lipid conjugates in the treatment of allergic rhinitis |
| US8859524B2 (en) | 2005-11-17 | 2014-10-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Lipid conjugates in the treatment of chronic rhinosinusitis |
| US20080183282A1 (en) * | 2006-03-09 | 2008-07-31 | Saul Yedgar | Use of lipid conjugates for the coating of stents and catheters |
| AU2007320737B2 (en) * | 2006-11-14 | 2014-04-03 | Celsus Therapeutics Plc | Contact lens compositions |
| CA2705785A1 (en) * | 2006-11-14 | 2008-05-22 | Saul Yedgar | Use of lipid conjugates in the treatment of diseases or disorders of the eye |
| EP2429532A4 (en) * | 2009-05-11 | 2015-05-27 | Yissum Res Dev Co | LIPID / POLYMER CONJUGATES, THEIR PREPARATION AND USES THEREOF |
| GB0916205D0 (en) | 2009-09-15 | 2009-10-28 | Zephyros Inc | Improvements in or relating to cavity filling |
| US20130012473A1 (en) * | 2010-03-17 | 2013-01-10 | Ktb Tumorforschungsgesellschaft Mbh | Combined use of phospholipid and sulfate groups-carrying polysaccharides for inhibiting metastatic spread |
| CA2703532C (en) * | 2010-05-10 | 2018-05-01 | Eva Turley | Topically administered, skin-penetrating glycosaminoglycan formulations suitable for use in cosmetic and pharmaceutical applications |
| JP2022530253A (ja) * | 2019-04-29 | 2022-06-28 | ボシュ・アンド・ロム・インコーポレイテッド | 糖リン脂質ポリマーネットワーク及びその使用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2374910A1 (fr) * | 1976-10-23 | 1978-07-21 | Choay Sa | Preparation a base d'heparine, comprenant des liposomes, procede pour l'obtenir et medicaments contenant de telles preparations |
| FR2492259A1 (fr) * | 1980-10-21 | 1982-04-23 | Idinvex Sa | Formulation d'heparine |
| US4362737A (en) * | 1981-04-13 | 1982-12-07 | Schaefer Rolf | Transdermal carrier materials |
| US4654327A (en) * | 1982-04-21 | 1987-03-31 | Research Corp. | Quaternary ammonium complexes of heparin |
| US4604376A (en) * | 1982-04-21 | 1986-08-05 | Research Corporation | Enteric compounds and complexes |
| EP0114589B1 (en) * | 1982-12-20 | 1987-09-23 | The President And Fellows Of Harvard College | Inhibition of angiogenesis |
| JPS6117A (ja) * | 1984-06-11 | 1986-01-06 | Seikagaku Kogyo Co Ltd | ムコ多糖系癌転移抑制剤 |
| CA1291423C (en) * | 1985-10-24 | 1991-10-29 | Ping W. Tang | Biochemical reagent |
| IL79255A0 (en) * | 1986-06-26 | 1986-09-30 | Hadassah Med Org | Composition for metastasis prevention |
| IT1203515B (it) * | 1987-02-26 | 1989-02-15 | Indena Spa | Complessi di saponine con fosfolipidi e composizioni farmaceutiche e cosmetiche che li contengono |
| US5169636A (en) * | 1988-03-17 | 1992-12-08 | Nippon Fine Chemical Co., Ltd. | Liposomes |
| JPH0219393A (ja) * | 1988-07-08 | 1990-01-23 | Higeta Shoyu Kk | Ｎ‐アセチルガラクトサミノオリゴ糖及びその製造方法 |
| JPH0258501A (ja) * | 1988-08-25 | 1990-02-27 | Mitsubishi Gas Chem Co Inc | リポ多糖およびその用途 |
| JPH03220201A (ja) * | 1988-11-18 | 1991-09-27 | Eisai Co Ltd | プロスタグランジン類と多糖類の結合体 |
-
1991
- 1991-07-24 AT AT91913108T patent/ATE148713T1/de not_active IP Right Cessation
- 1991-07-24 EP EP91913108A patent/EP0493622B1/en not_active Expired - Lifetime
- 1991-07-24 KR KR1019920700665A patent/KR0181295B1/ko not_active IP Right Cessation
- 1991-07-24 US US07/847,065 patent/US5464942A/en not_active Expired - Lifetime
- 1991-07-24 AU AU82266/91A patent/AU647814B2/en not_active Ceased
- 1991-07-24 CA CA002067211A patent/CA2067211C/en not_active Expired - Fee Related
- 1991-07-24 WO PCT/JP1991/000995 patent/WO1992001720A1/ja active IP Right Grant
- 1991-07-24 DE DE69124590T patent/DE69124590T2/de not_active Expired - Fee Related
-
1992
- 1992-02-19 FI FI920717A patent/FI103279B1/fi active
- 1992-03-19 NO NO921083A patent/NO305368B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI103279B (fi) | 1999-05-31 |
| EP0493622A1 (en) | 1992-07-08 |
| AU8226691A (en) | 1992-02-18 |
| KR920702377A (ko) | 1992-09-03 |
| EP0493622B1 (en) | 1997-02-05 |
| NO921083D0 (no) | 1992-03-19 |
| ATE148713T1 (de) | 1997-02-15 |
| KR0181295B1 (ko) | 1999-04-01 |
| NO921083L (no) | 1992-05-21 |
| AU647814B2 (en) | 1994-03-31 |
| CA2067211A1 (en) | 1992-01-25 |
| WO1992001720A1 (en) | 1992-02-06 |
| DE69124590T2 (de) | 1997-06-12 |
| FI920717A0 (fi) | 1992-02-19 |
| EP0493622A4 (en) | 1993-10-27 |
| DE69124590D1 (de) | 1997-03-20 |
| US5464942A (en) | 1995-11-07 |
| FI103279B1 (fi) | 1999-05-31 |
| CA2067211C (en) | 2004-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO305368B1 (no) | AnalogifremgangsmÕte for fremstilling av et terapeutisk aktivt fosfolipidbundet glykosaminglykan | |
| US5733892A (en) | Metastasis inhibitor composition comprising a phospholipid-linked glycosaminoglycan and method for inhibiting metastasis employing the same | |
| US5470578A (en) | Antirheumatic composition | |
| EP3350193B1 (en) | Carbohydrate ligands that bind to antibodies against glycoepitopes of glycosphingolipids | |
| FI84074B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara gangliosidderivat. | |
| NO179452B (no) | Sulfaterte glukosamin-glukanoid-derivater | |
| PT91249B (pt) | Processo para a preparacao de glicosaminoglicanos selectivamente o-acilados | |
| AU2005284080B2 (en) | Biotinylated hexadecasaccharides, preparation and use thereof | |
| JP2986519B2 (ja) | 燐脂質結合グリコサミノグリカン | |
| EP1095657B1 (en) | Compositions for the regulation of cytokine activity | |
| JP2997018B2 (ja) | 燐脂質又は脂質結合グリコサミノグリカン | |
| CN108285498B (zh) | 一种抑制内源性凝血因子x酶复合物的寡糖化合物及其制备方法与用途 | |
| JP2986518B2 (ja) | 癌転移抑制剤 | |
| EA020485B1 (ru) | N-ацилированные октасахариды, активирующие рецепторы fgf, их получение и применение в терапии | |
| EP0561523A2 (en) | Sugar compound, sialic acid-containing sugar chains' biosynthesis inhibitor, production process thereof and intermediate | |
| HU198216B (en) | Process for producing sialosyl-cholesterin and pharmaceutical compositions containing them as active components | |
| NZ231624A (en) | Ganglioside derivatives, medicaments | |
| JPH02223525A (ja) | 血管新生阻害剤 | |
| WO2012160337A1 (en) | Sulfated oligosaccharides for use in treatment of neurodegenerative diseases | |
| US4425335A (en) | Ester derivatives of alkoxybenzoyldeoxyfluorouridine | |
| Chernyak et al. | Synthesis of carbohydrate-amino acid conjugates related to the capsular antigen K54 from Escherichia coli O6: K54: H10 and artificial antigens therefrom | |
| US5700918A (en) | Moranoline derivative | |
| WO2020114418A1 (zh) | 抗凝血的五糖类化合物、组合物及其制备方法和医药用途 | |
| Dhamale | New methods for the chemical synthesis of glycosaminoglycans | |
| AU2003207116A1 (en) | Anti-influenza virus compound comprising biflavonoid-sialic acid glycoside |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN JANUARY 2001 |