JP5139797B2 - 硫酸化オリゴ糖誘導体 - Google Patents
硫酸化オリゴ糖誘導体 Download PDFInfo
- Publication number
- JP5139797B2 JP5139797B2 JP2007501068A JP2007501068A JP5139797B2 JP 5139797 B2 JP5139797 B2 JP 5139797B2 JP 2007501068 A JP2007501068 A JP 2007501068A JP 2007501068 A JP2007501068 A JP 2007501068A JP 5139797 B2 JP5139797 B2 JP 5139797B2
- Authority
- JP
- Japan
- Prior art keywords
- sulfono
- tri
- mannopyranosyl
- aryl
- peg
- 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.)
- Expired - Fee Related
Links
- 229920001542 oligosaccharide Polymers 0.000 title description 17
- 150000002482 oligosaccharides Chemical class 0.000 title description 13
- 239000000203 mixture Substances 0.000 claims description 95
- 150000001875 compounds Chemical class 0.000 claims description 85
- -1 n-octyl Chemical group 0.000 claims description 74
- 238000000034 method Methods 0.000 claims description 36
- 229920001223 polyethylene glycol Chemical group 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 17
- 150000002772 monosaccharides Chemical class 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 208000035475 disorder Diseases 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000003435 aroyl group Chemical group 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 230000033115 angiogenesis Effects 0.000 claims description 12
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 12
- 206010027476 Metastases Diseases 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 230000009401 metastasis Effects 0.000 claims description 11
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 11
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 208000007536 Thrombosis Diseases 0.000 claims description 10
- 230000004054 inflammatory process Effects 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 230000000813 microbial effect Effects 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 159000000000 sodium salts Chemical class 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 230000015271 coagulation Effects 0.000 claims description 8
- 238000005345 coagulation Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000001768 cations Chemical class 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 125000003107 substituted aryl group Chemical class 0.000 claims description 6
- 150000003536 tetrazoles Chemical class 0.000 claims description 6
- 150000003852 triazoles Chemical class 0.000 claims description 6
- 241000282414 Homo sapiens Species 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002347 octyl group Chemical group [H]C([*])([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 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 206010053567 Coagulopathies Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 230000035602 clotting Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 241000282412 Homo Species 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000003755 preservative agent Substances 0.000 claims description 2
- 230000002335 preservative effect Effects 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 5
- 241000124008 Mammalia Species 0.000 claims 4
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 206010003178 Arterial thrombosis Diseases 0.000 claims 1
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 208000010378 Pulmonary Embolism Diseases 0.000 claims 1
- 206010038934 Retinopathy proliferative Diseases 0.000 claims 1
- 206010043647 Thrombotic Stroke Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 206010047249 Venous thrombosis Diseases 0.000 claims 1
- HIWPGCMGAMJNRG-UHFFFAOYSA-N beta-sophorose Natural products OC1C(O)C(CO)OC(O)C1OC1C(O)C(O)C(O)C(CO)O1 HIWPGCMGAMJNRG-UHFFFAOYSA-N 0.000 claims 1
- 208000023819 chronic asthma Diseases 0.000 claims 1
- XEKSTYNIJLDDAZ-JASSWCPGSA-F fondaparinux sodium Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].O[C@@H]1[C@@H](NS([O-])(=O)=O)[C@@H](OC)O[C@H](COS([O-])(=O)=O)[C@H]1O[C@H]1[C@H](OS([O-])(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS([O-])(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS([O-])(=O)=O)O4)NS([O-])(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS([O-])(=O)=O)O2)NS([O-])(=O)=O)[C@H](C(O)=O)O1 XEKSTYNIJLDDAZ-JASSWCPGSA-F 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 229920001427 mPEG Polymers 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- IPOGMIXXMPIMID-RIWCUPLTSA-N [(2r,3r,4s,5s,6r)-6-[(2r,3s,4s,5r,6r)-2-[(2r,3s,4s,5r,6r)-2-[(2r,3r,4s,5s,6r)-3,5-disulfooxy-2-(sulfooxymethyl)-6-[(2r,3s,4r,5r,6r)-2,4,5-trisulfooxy-6-(sulfooxymethyl)oxan-3-yl]oxyoxan-4-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl]oxy-3,5-disulfoox Chemical compound OS(=O)(=O)O[C@H]1[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@@H](COP(O)(=O)O)O[C@@H]1O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](O[C@@H]2[C@@H]([C@@H](O[C@@H]3[C@@H]([C@@H](O[C@H]4[C@H]([C@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O[C@@H]4OS(O)(=O)=O)OS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@H]3OS(O)(=O)=O)OS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@H]2OS(O)(=O)=O)OS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@H]1OS(O)(=O)=O IPOGMIXXMPIMID-RIWCUPLTSA-N 0.000 description 25
- 238000012360 testing method Methods 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000843 powder Substances 0.000 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 description 18
- 239000012230 colorless oil Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 16
- 230000027455 binding Effects 0.000 description 16
- 229920002971 Heparan sulfate Polymers 0.000 description 15
- 235000000346 sugar Nutrition 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 108010037536 heparanase Proteins 0.000 description 14
- 150000001540 azides Chemical class 0.000 description 13
- 239000003102 growth factor Substances 0.000 description 13
- 102100024025 Heparanase Human genes 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229930182470 glycoside Natural products 0.000 description 11
- 229920005862 polyol Polymers 0.000 description 11
- 239000000463 material Substances 0.000 description 10
- 239000002808 molecular sieve Substances 0.000 description 10
- 150000003077 polyols Chemical class 0.000 description 10
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 241000700584 Simplexvirus Species 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000002016 disaccharides Chemical class 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 0 *C1[C@@](OC(C2OCc3ccccc3)[C@](*)OC(COCc3ccccc3)[C@]2OCc2ccccc2)OC(COC(c2ccccc2)=O)[C@@](*)C1O[C@](C(C1O)OC(c2ccccc2)=O)OC(COC(c2ccccc2)=O)[C@]1OC(c1ccccc1)=O Chemical compound *C1[C@@](OC(C2OCc3ccccc3)[C@](*)OC(COCc3ccccc3)[C@]2OCc2ccccc2)OC(COC(c2ccccc2)=O)[C@@](*)C1O[C@](C(C1O)OC(c2ccccc2)=O)OC(COC(c2ccccc2)=O)[C@]1OC(c1ccccc1)=O 0.000 description 5
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 101150003085 Pdcl gene Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 150000001720 carbohydrates Chemical group 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000002744 extracellular matrix Anatomy 0.000 description 5
- 229920000669 heparin Polymers 0.000 description 5
- 229960002897 heparin Drugs 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- ZVQXQPNJHRNGID-UHFFFAOYSA-N tetramethylsuccinonitrile Chemical compound N#CC(C)(C)C(C)(C)C#N ZVQXQPNJHRNGID-UHFFFAOYSA-N 0.000 description 5
- 150000004044 tetrasaccharides Chemical class 0.000 description 5
- 150000004043 trisaccharides Chemical class 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
- 241000235648 Pichia Species 0.000 description 4
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000001212 derivatisation Methods 0.000 description 4
- NPNDNSLXOKGVJH-ZDTQQCKLSA-N diazonio-[[(2r,3r,4s,5s,6r)-3,4,5-tribenzoyloxy-6-(2,2,2-trichloroethanimidoyl)oxyoxan-2-yl]methyl]azanide Chemical compound O([C@@H]1[C@@H](CN=[N+]=[N-])O[C@@H]([C@H]([C@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)OC(=N)C(Cl)(Cl)Cl)C(=O)C1=CC=CC=C1 NPNDNSLXOKGVJH-ZDTQQCKLSA-N 0.000 description 4
- 210000003608 fece Anatomy 0.000 description 4
- 150000002338 glycosides Chemical class 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000001542 size-exclusion chromatography Methods 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 3
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 3
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- IBUZGVQIKARDAF-PEBLQZBPSA-N [(2r,3r,4s,5s,6r)-3,4,5-triacetyloxy-6-(2,2,2-trichloroethanimidoyl)oxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1O[C@H](OC(=N)C(Cl)(Cl)Cl)[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O IBUZGVQIKARDAF-PEBLQZBPSA-N 0.000 description 3
- FAZUIGXOWOIOEH-AEQXRQRWSA-N [(2r,3s,4s,5s,6s)-3,5-dibenzoyloxy-4-hydroxy-6-methoxyoxan-2-yl]methyl benzoate Chemical compound C([C@H]1O[C@@H]([C@H]([C@@H](O)[C@@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)OC)OC(=O)C1=CC=CC=C1 FAZUIGXOWOIOEH-AEQXRQRWSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000001772 anti-angiogenic effect Effects 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 230000019635 sulfation Effects 0.000 description 3
- 238000005670 sulfation reaction Methods 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- AFHZEIVSXDXEMO-OHBKMZHCSA-N (2s,3s,4r,5r,6r)-2,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-3-ol Chemical compound O([C@@H]1[C@H]([C@H]([C@H](OCC=2C=CC=CC=2)[C@@H](COCC=2C=CC=CC=2)O1)OCC=1C=CC=CC=1)O)CC1=CC=CC=C1 AFHZEIVSXDXEMO-OHBKMZHCSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 125000005916 2-methylpentyl group Chemical group 0.000 description 2
- 125000005917 3-methylpentyl group Chemical group 0.000 description 2
- 108090000935 Antithrombin III Proteins 0.000 description 2
- 102100022977 Antithrombin-III Human genes 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229930182475 S-glycoside Natural products 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HHSSHLYHLBYJQM-VLOJJGDQSA-N [(2R,3S,4S,5S,6R)-3,5-dibenzoyloxy-6-[(2R,3R,4S,5S,6R)-3,5-dibenzoyloxy-2-(benzoyloxymethyl)-6-[(2R,3R,4S,5S,6S)-3,5-dibenzoyloxy-2-(benzoyloxymethyl)-6-methoxyoxan-4-yl]oxyoxan-4-yl]oxy-4-hydroxyoxan-2-yl]methyl benzoate Chemical compound C([C@H]1O[C@@H]([C@H]([C@@H](O[C@@H]2[C@H]([C@@H](O[C@@H]3[C@H]([C@@H](O)[C@H](OC(=O)C=4C=CC=CC=4)[C@@H](COC(=O)C=4C=CC=CC=4)O3)OC(=O)C=3C=CC=CC=3)[C@H](OC(=O)C=3C=CC=CC=3)[C@@H](COC(=O)C=3C=CC=CC=3)O2)OC(=O)C=2C=CC=CC=2)[C@@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)OC)OC(=O)C1=CC=CC=C1 HHSSHLYHLBYJQM-VLOJJGDQSA-N 0.000 description 2
- MIDYHNIEIYNZAO-JMRLDLRKSA-N [(2r,3s,4s,5s,6r)-3,5-dibenzoyloxy-4-hydroxy-6-[(2s,3s,4s,5r,6r)-2,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl benzoate Chemical compound O([C@H]1[C@@H]([C@@H]([C@@H](O[C@H]2[C@H]([C@H](OCC=3C=CC=CC=3)[C@@H](COCC=3C=CC=CC=3)O[C@@H]2OCC=2C=CC=CC=2)OCC=2C=CC=CC=2)O[C@@H]1COC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 MIDYHNIEIYNZAO-JMRLDLRKSA-N 0.000 description 2
- IBBMMRZSEKYPJV-QFMDFWGDSA-N [(2r,3s,4s,5s,6r)-3,5-dibenzoyloxy-6-[(2r,3r,4s,5s,6s)-3,5-dibenzoyloxy-2-(benzoyloxymethyl)-6-methoxyoxan-4-yl]oxy-4-hydroxyoxan-2-yl]methyl benzoate Chemical compound C([C@H]1O[C@@H]([C@H]([C@@H](O[C@@H]2[C@H]([C@@H](O)[C@H](OC(=O)C=3C=CC=CC=3)[C@@H](COC(=O)C=3C=CC=CC=3)O2)OC(=O)C=2C=CC=CC=2)[C@@H]1OC(=O)C=1C=CC=CC=1)OC(=O)C=1C=CC=CC=1)OC)OC(=O)C1=CC=CC=C1 IBBMMRZSEKYPJV-QFMDFWGDSA-N 0.000 description 2
- MJOQJPYNENPSSS-XQHKEYJVSA-N [(3r,4s,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O MJOQJPYNENPSSS-XQHKEYJVSA-N 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000002001 anti-metastasis Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 239000002257 antimetastatic agent Substances 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 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 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 150000002402 hexoses Chemical class 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 150000002972 pentoses Chemical class 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229910052711 selenium Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 238000006277 sulfonation reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 150000003569 thioglycosides Chemical class 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 description 1
- 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 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- UZGKAASZIMOAMU-UHFFFAOYSA-N 124177-85-1 Chemical class NP(=O)=O UZGKAASZIMOAMU-UHFFFAOYSA-N 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-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
- UDTQSJGIFBAXRT-UHFFFAOYSA-N 2-bromohexan-1-ol Chemical compound CCCCC(Br)CO UDTQSJGIFBAXRT-UHFFFAOYSA-N 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- PKUPAJQAJXVUEK-UHFFFAOYSA-N 2-phenoxyacetyl chloride Chemical compound ClC(=O)COC1=CC=CC=C1 PKUPAJQAJXVUEK-UHFFFAOYSA-N 0.000 description 1
- 125000004336 3,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical class O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- FCMCSZXRVWDVAW-UHFFFAOYSA-N 6-bromo-1-hexanol Chemical compound OCCCCCCBr FCMCSZXRVWDVAW-UHFFFAOYSA-N 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 229930182476 C-glycoside Natural products 0.000 description 1
- 150000000700 C-glycosides Chemical class 0.000 description 1
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 1
- WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-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
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229940122588 Heparanase inhibitor Drugs 0.000 description 1
- 108090000481 Heparin Cofactor II Proteins 0.000 description 1
- 102000004032 Heparin Cofactor II Human genes 0.000 description 1
- 102100023920 Histone H1t Human genes 0.000 description 1
- 101000905044 Homo sapiens Histone H1t Proteins 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
- WTXSEYFOBJQKMW-UHFFFAOYSA-N NC(COC1C=CC=CC1)=O Chemical compound NC(COC1C=CC=CC1)=O WTXSEYFOBJQKMW-UHFFFAOYSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101710188371 Sulfate-binding protein Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 238000006058 Ugi-reaction Methods 0.000 description 1
- 206010072810 Vascular wall hypertrophy Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- YFHNDHXQDJQEEE-UHFFFAOYSA-N acetic acid;hydrazine Chemical compound NN.CC(O)=O YFHNDHXQDJQEEE-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
- OCIBBXPLUVYKCH-QXVNYKTNSA-N alpha-maltohexaose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](O[C@@H]2[C@H](O[C@H](O[C@@H]3[C@H](O[C@H](O[C@@H]4[C@H](O[C@H](O[C@@H]5[C@H](O[C@H](O)[C@H](O)[C@H]5O)CO)[C@H](O)[C@H]4O)CO)[C@H](O)[C@H]3O)CO)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O OCIBBXPLUVYKCH-QXVNYKTNSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000001858 anti-Xa Effects 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 238000002832 anti-viral assay Methods 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 125000001124 arachidoyl 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])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 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 1
- XFLVBMBRLSCJAI-UHFFFAOYSA-N biotin amide Natural products N1C(=O)NC2C(CCCCC(=O)N)SCC21 XFLVBMBRLSCJAI-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- 125000002676 chrysenyl group Chemical group C1(=CC=CC=2C3=CC=C4C=CC=CC4=C3C=CC12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 1
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000003074 decanoyl group Chemical group [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(*)=O 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [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])* 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 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 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [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])* 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000001641 gel filtration chromatography Methods 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
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- 102000036064 heparan sulfate binding proteins Human genes 0.000 description 1
- 108091000314 heparan sulfate binding proteins Proteins 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002454 idoses Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 125000000400 lauroyl 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])[H] 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- DJMVHSOAUQHPSN-UHFFFAOYSA-N malto-hexaose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(OC4C(C(O)C(O)C(CO)O4)O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 DJMVHSOAUQHPSN-UHFFFAOYSA-N 0.000 description 1
- 125000000628 margaroyl 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])[H] 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- YAHRDLICUYEDAU-UHFFFAOYSA-N methylhexaneamine Chemical compound CCC(C)CC(C)N YAHRDLICUYEDAU-UHFFFAOYSA-N 0.000 description 1
- 229950000752 methylhexaneamine Drugs 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 125000001419 myristoyl 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])[H] 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical compound CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 125000001402 nonanoyl 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])[H] 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([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
- 210000001331 nose Anatomy 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001991 scapula Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000011581 secondary neoplasm Diseases 0.000 description 1
- 150000003347 selenoglycosides Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 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
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- HYWCXWRMUZYRPH-UHFFFAOYSA-N trimethyl(prop-2-enyl)silane Chemical compound C[Si](C)(C)CC=C HYWCXWRMUZYRPH-UHFFFAOYSA-N 0.000 description 1
- 125000000297 undecanoyl 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])[H] 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([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
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
-
- 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
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/04—Disaccharides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Virology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2004901103A AU2004901103A0 (en) | 2004-03-04 | Sulfated Oligosaccharide Derivatives | |
| AU2004901103 | 2004-03-04 | ||
| PCT/AU2005/000314 WO2005085264A1 (en) | 2004-03-04 | 2005-03-04 | Sulfated oligosaccharide derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007526257A JP2007526257A (ja) | 2007-09-13 |
| JP2007526257A5 JP2007526257A5 (enExample) | 2008-04-17 |
| JP5139797B2 true JP5139797B2 (ja) | 2013-02-06 |
Family
ID=34916868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007501068A Expired - Fee Related JP5139797B2 (ja) | 2004-03-04 | 2005-03-04 | 硫酸化オリゴ糖誘導体 |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US7875592B2 (enExample) |
| EP (1) | EP1720889B1 (enExample) |
| JP (1) | JP5139797B2 (enExample) |
| KR (1) | KR101156273B1 (enExample) |
| CN (3) | CN1989146A (enExample) |
| AU (1) | AU2005219456B2 (enExample) |
| BR (1) | BRPI0508144A (enExample) |
| CA (1) | CA2557989C (enExample) |
| ES (1) | ES2531880T3 (enExample) |
| HK (1) | HK1199263A1 (enExample) |
| IL (1) | IL177870A (enExample) |
| MX (1) | MXPA06010049A (enExample) |
| NO (1) | NO338461B1 (enExample) |
| RU (1) | RU2392281C2 (enExample) |
| TW (1) | TWI426080B (enExample) |
| WO (1) | WO2005085264A1 (enExample) |
| ZA (1) | ZA200607057B (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2392281C2 (ru) * | 2004-03-04 | 2010-06-20 | Проджен Фармасьютикалз Лимитед | Сульфатированные производные олигосахаридов |
| JP2008534519A (ja) * | 2005-04-01 | 2008-08-28 | クリストファー・リチャード・パリッシュ | グルコサミンオリゴ糖などのｎｏｄ因子を用いる血管新生の調節 |
| ES2584927T7 (es) * | 2007-10-16 | 2020-11-05 | Progen Pg500 Series Pty Ltd | Derivados de oligosacáridos sulfatados novedosos |
| JP2011526925A (ja) * | 2008-07-01 | 2011-10-20 | ザカロン ファーマシューティカルズ，インク． | ヘパラン硫酸阻害剤 |
| EP2149580A1 (en) | 2008-07-15 | 2010-02-03 | Istituto Scientifico di Chimica E Biochimica "G Ronzoni | Mimetics of sulfated oligosaccharides |
| CN101591401A (zh) * | 2009-02-27 | 2009-12-02 | 江南大学 | 一种制备高活性低分子量肝素的方法 |
| JP5701498B2 (ja) * | 2009-12-01 | 2015-04-15 | 公益財団法人微生物化学研究会 | 炎症性細胞からのヘパラナーゼの放出抑制剤、抗炎症剤、及び薬用組成物 |
| CN107362168A (zh) * | 2011-06-09 | 2017-11-21 | 基亚生物科技股份有限公司 | 用于抑制肝癌复发、恶化或转移之医药组成物 |
| EP3116887B1 (en) | 2014-03-13 | 2021-02-17 | Universität Basel | Carbohydrate ligands that bind to igm antibodies against myelin-associated glycoprotein |
| CN105017341B (zh) * | 2014-04-22 | 2018-05-15 | 华东师范大学 | 硫酸化岩藻-半乳四糖及其制备方法和应用 |
| CN105001278B (zh) * | 2015-06-19 | 2018-07-06 | 天津红日药业股份有限公司 | 一种磺达肝癸钠二糖中间体片段的合成方法 |
| CN104876979B (zh) * | 2015-06-19 | 2018-10-09 | 天津红日药业股份有限公司 | 一种具有抗Xa因子活性的磺酸化五糖化合物 |
| JP6849667B2 (ja) | 2015-09-16 | 2021-03-24 | ウニヴェルズィテート バーゼル | スフィンゴ糖脂質の糖鎖エピトープに対する抗体に結合する炭水化物リガンド |
| JP2016199579A (ja) * | 2016-07-08 | 2016-12-01 | 基亜生物科技股▲ふん▼有限公司Ｍｅｄｉｇｅｎ Ｂｉｏｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐ． | 肝癌の再発、悪化または転移の抑制に用いる医薬組成物 |
| WO2018103680A1 (zh) * | 2016-12-10 | 2018-06-14 | 扬州蓝色生物医药科技有限公司 | 甘露寡聚糖类化合物及其作为抗rna病毒药物的应用 |
| JP2020503377A (ja) | 2016-12-13 | 2020-01-30 | ベータ セラピューティクス プロプライアタリー リミティド | ヘパラナーゼ阻害剤及びそれの使用 |
| US11787783B2 (en) | 2016-12-13 | 2023-10-17 | Beta Therapeutics Pty Ltd | Heparanase inhibitors and use thereof |
| WO2018107244A1 (en) | 2016-12-15 | 2018-06-21 | Progen Pg500 Series Pty Ltd | Composition and uses thereof |
| US10842804B2 (en) * | 2017-03-01 | 2020-11-24 | Medigen Biotechnology Corporation | Muparfostat for use in treating patients with hepatitis virus-related hepatocellular carcinoma after surgical resection |
| KR102377358B1 (ko) | 2017-10-16 | 2022-03-23 | 삼성전자주식회사 | 반도체 메모리 소자 및 그 제조 방법 |
| JP7359396B2 (ja) * | 2017-12-15 | 2023-10-11 | ジ・オーストラリアン・ナショナル・ユニヴァーシティ | 細胞外ヒストンによって媒介される病理を処置及び予防するための化合物 |
| JP6619830B2 (ja) * | 2018-02-22 | 2019-12-11 | 基亜生物科技股▲ふん▼有限公司Ｍｅｄｉｇｅｎ Ｂｉｏｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐ． | 肝癌の再発、悪化または転移の抑制に用いる医薬組成物 |
| CN109762032A (zh) * | 2019-01-16 | 2019-05-17 | 天津科技大学 | 一种磺酸化路易斯x三糖及其合成方法和应用 |
| SG11202109032SA (en) * | 2019-02-25 | 2021-09-29 | Univ Australian National | Compounds for treating and preventing net associated complications |
| CN116813675B (zh) * | 2023-08-23 | 2023-11-24 | 北京远大九和药业有限公司 | 一种化合物晶型及其制备、组合物和用途 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989003684A1 (fr) | 1987-10-30 | 1989-05-05 | Chugai Seiyaku Kabushiki Kaisha | Agent anti-vih |
| FR2704226B1 (fr) * | 1993-04-22 | 1995-07-21 | Sanofi Elf | 3-desoxy oligosaccharides, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| US5739115A (en) | 1993-10-07 | 1998-04-14 | Glycomed Incorporated | Sulfated maltooligosaccharides with heparin-like properties |
| JPH09503510A (ja) * | 1993-10-07 | 1997-04-08 | グリコメド・インコーポレイテッド | ヘパリン様特性を有する高硫酸化マルトオリゴ糖 |
| AUPN261895A0 (en) | 1995-04-28 | 1995-05-18 | Australian National University, The | Preparation and use of sulfated oligosaccharides |
| RU2193039C2 (ru) * | 1995-04-28 | 2002-11-20 | Такара Сузо Ко., Лтд. | Соединение сахара |
| JPH09183789A (ja) * | 1995-10-31 | 1997-07-15 | Sanwa Kagaku Kenkyusho Co Ltd | 新規な硫酸化及び燐酸化糖誘導体、その製法及び用途 |
| IL120722A (en) * | 1996-05-08 | 1999-07-14 | Akzo Nobel Nv | Polysulfated tetrasaccharide derivatives and pharmaceutical compositions containing them |
| AUPO556297A0 (en) | 1997-03-11 | 1997-04-10 | Australian National University, The | Sulfated oligosaccharides having anticoagulant/ antithrombotic activity |
| IL126893A (en) * | 1997-11-19 | 2003-05-29 | Akzo Nobel Nv | Sulfated pentasaccharide derivatives and pharmaceutical compositions containing them |
| FR2773801B1 (fr) * | 1998-01-19 | 2000-05-12 | Sanofi Sa | Nouveaux pentasaccharides, procedes pour leurs preparations et compositions pharmaceutiques les contenant |
| CN1450075A (zh) * | 2002-04-11 | 2003-10-22 | 中国科学院生态环境研究中心 | 一类寡糖及其硫酸化产物和它们的制备方法及含该寡糖的药物组合物 |
| RU2392281C2 (ru) * | 2004-03-04 | 2010-06-20 | Проджен Фармасьютикалз Лимитед | Сульфатированные производные олигосахаридов |
-
2005
- 2005-03-04 RU RU2006134972/04A patent/RU2392281C2/ru not_active IP Right Cessation
- 2005-03-04 CA CA2557989A patent/CA2557989C/en not_active Expired - Fee Related
- 2005-03-04 EP EP05706346.3A patent/EP1720889B1/en not_active Expired - Lifetime
- 2005-03-04 TW TW094106609A patent/TWI426080B/zh not_active IP Right Cessation
- 2005-03-04 CN CNA2005800068338A patent/CN1989146A/zh active Pending
- 2005-03-04 WO PCT/AU2005/000314 patent/WO2005085264A1/en not_active Ceased
- 2005-03-04 KR KR1020067020704A patent/KR101156273B1/ko not_active Expired - Fee Related
- 2005-03-04 US US10/591,577 patent/US7875592B2/en not_active Expired - Fee Related
- 2005-03-04 CN CN201410042932.2A patent/CN103788141B/zh not_active Expired - Fee Related
- 2005-03-04 CN CN201410353750.7A patent/CN104119404A/zh active Pending
- 2005-03-04 BR BRPI0508144-0A patent/BRPI0508144A/pt not_active Application Discontinuation
- 2005-03-04 MX MXPA06010049A patent/MXPA06010049A/es active IP Right Grant
- 2005-03-04 AU AU2005219456A patent/AU2005219456B2/en not_active Ceased
- 2005-03-04 ES ES05706346.3T patent/ES2531880T3/es not_active Expired - Lifetime
- 2005-03-04 JP JP2007501068A patent/JP5139797B2/ja not_active Expired - Fee Related
-
2006
- 2006-08-23 ZA ZA2006/07057A patent/ZA200607057B/en unknown
- 2006-09-03 IL IL177870A patent/IL177870A/en active IP Right Grant
- 2006-10-03 NO NO20064489A patent/NO338461B1/no not_active IP Right Cessation
-
2007
- 2007-12-19 HK HK14112830.3A patent/HK1199263A1/xx unknown
-
2010
- 2010-12-03 US US12/960,145 patent/US8173606B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7875592B2 (en) | 2011-01-25 |
| BRPI0508144A (pt) | 2007-07-24 |
| WO2005085264A1 (en) | 2005-09-15 |
| AU2005219456B2 (en) | 2011-04-07 |
| CA2557989C (en) | 2013-04-23 |
| HK1199263A1 (en) | 2015-06-26 |
| US20110130354A1 (en) | 2011-06-02 |
| KR101156273B1 (ko) | 2012-06-13 |
| EP1720889B1 (en) | 2014-11-26 |
| CN103788141A (zh) | 2014-05-14 |
| NO338461B1 (no) | 2016-08-15 |
| TW200602351A (en) | 2006-01-16 |
| AU2005219456A1 (en) | 2005-09-15 |
| CN104119404A (zh) | 2014-10-29 |
| CN1989146A (zh) | 2007-06-27 |
| IL177870A (en) | 2011-08-31 |
| ZA200607057B (en) | 2008-04-30 |
| MXPA06010049A (es) | 2007-04-10 |
| RU2006134972A (ru) | 2008-04-10 |
| US20070185037A1 (en) | 2007-08-09 |
| NO20064489L (no) | 2006-11-27 |
| US8173606B2 (en) | 2012-05-08 |
| CN103788141B (zh) | 2016-08-17 |
| CA2557989A1 (en) | 2005-09-15 |
| EP1720889A4 (en) | 2008-03-19 |
| EP1720889A1 (en) | 2006-11-15 |
| TWI426080B (zh) | 2014-02-11 |
| IL177870A0 (en) | 2006-12-31 |
| ES2531880T3 (es) | 2015-03-20 |
| RU2392281C2 (ru) | 2010-06-20 |
| JP2007526257A (ja) | 2007-09-13 |
| KR20070007815A (ko) | 2007-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5139797B2 (ja) | 硫酸化オリゴ糖誘導体 | |
| AU2008314505B2 (en) | Novel sulfated oligosaccharide derivatives | |
| JP3345020B2 (ja) | 合成ポリサッカライド、それらの製造法およびそれらを含む医薬組成物 | |
| CA2551181A1 (en) | Glycosaminoglycan (gag) mimetics | |
| WO2008041131A2 (en) | Anticoagulant compounds | |
| HK1197915A (en) | Sulfated oligosaccharide derivatives | |
| HK1197915B (en) | Sulfated oligosaccharide derivatives | |
| HK1108581A (en) | Sulfated oligosaccharide derivatives | |
| JPH09110903A (ja) | 硫酸化オリゴ糖の経口吸収性増加方法及び硫酸化オリゴ糖誘導体並びにこれを有効成分とする抗ウイルス剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080229 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080229 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110823 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111122 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111213 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120911 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121023 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121113 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121116 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5139797 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151122 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |