KR102651029B1 - 헥소스 유도체, 그의 제제 및 용도 - Google Patents
헥소스 유도체, 그의 제제 및 용도 Download PDFInfo
- Publication number
- KR102651029B1 KR102651029B1 KR1020227017066A KR20227017066A KR102651029B1 KR 102651029 B1 KR102651029 B1 KR 102651029B1 KR 1020227017066 A KR1020227017066 A KR 1020227017066A KR 20227017066 A KR20227017066 A KR 20227017066A KR 102651029 B1 KR102651029 B1 KR 102651029B1
- Authority
- KR
- South Korea
- Prior art keywords
- composition
- compound
- mmol
- experiment
- delete delete
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title description 3
- 150000002401 hexose derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 239000000203 mixture Substances 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 72
- 150000003839 salts Chemical class 0.000 claims description 36
- 230000008018 melting Effects 0.000 claims description 28
- 238000002844 melting Methods 0.000 claims description 28
- 230000006641 stabilisation Effects 0.000 claims description 26
- 238000011105 stabilization Methods 0.000 claims description 26
- -1 tissues Substances 0.000 claims description 25
- 229920001184 polypeptide Polymers 0.000 claims description 19
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 19
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 150000007523 nucleic acids Chemical class 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 9
- 238000004925 denaturation Methods 0.000 claims description 8
- 230000036425 denaturation Effects 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 241000700605 Viruses Species 0.000 claims description 7
- 210000000170 cell membrane Anatomy 0.000 claims description 7
- 230000001413 cellular effect Effects 0.000 claims description 7
- 239000002502 liposome Substances 0.000 claims description 7
- 239000002537 cosmetic Substances 0.000 claims description 6
- 230000002776 aggregation Effects 0.000 claims description 4
- 238000004220 aggregation Methods 0.000 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- 230000008014 freezing Effects 0.000 claims description 3
- 238000007710 freezing Methods 0.000 claims description 3
- 108091034117 Oligonucleotide Proteins 0.000 claims description 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 2
- 239000006172 buffering agent Substances 0.000 claims description 2
- 108020004999 messenger RNA Proteins 0.000 claims description 2
- 238000001694 spray drying Methods 0.000 claims description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 5
- 229910052698 phosphorus Inorganic materials 0.000 claims 5
- 239000011574 phosphorus Substances 0.000 claims 5
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 1
- 238000005054 agglomeration Methods 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
- 238000002474 experimental method Methods 0.000 description 98
- 238000003786 synthesis reaction Methods 0.000 description 55
- 230000015572 biosynthetic process Effects 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 48
- 239000000243 solution Substances 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- 239000012620 biological material Substances 0.000 description 35
- 238000003818 flash chromatography Methods 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
- 239000000047 product Substances 0.000 description 31
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 30
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 230000000087 stabilizing effect Effects 0.000 description 25
- 239000006260 foam Substances 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 24
- 102000016943 Muramidase Human genes 0.000 description 22
- 108010014251 Muramidase Proteins 0.000 description 22
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 22
- 238000006206 glycosylation reaction Methods 0.000 description 22
- 230000007062 hydrolysis Effects 0.000 description 22
- 238000006460 hydrolysis reaction Methods 0.000 description 22
- 239000004325 lysozyme Substances 0.000 description 22
- 229960000274 lysozyme Drugs 0.000 description 22
- 235000010335 lysozyme Nutrition 0.000 description 22
- 239000013058 crude material Substances 0.000 description 21
- 150000008505 β-D-glucopyranosides Chemical class 0.000 description 21
- 239000000386 donor Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 150000004702 methyl esters Chemical class 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 14
- 239000000370 acceptor Substances 0.000 description 14
- 238000006140 methanolysis reaction Methods 0.000 description 14
- 229910052700 potassium Inorganic materials 0.000 description 14
- 239000011591 potassium Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 108010059724 Micrococcal Nuclease Proteins 0.000 description 10
- 239000003381 stabilizer Substances 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- DDXCFDOPXBPUJC-UHFFFAOYSA-N Digeneaside Natural products OCC(C(O)=O)OC1OC(CO)C(O)C(O)C1O DDXCFDOPXBPUJC-UHFFFAOYSA-N 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 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 7
- 229940088598 enzyme Drugs 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 150000008146 mannosides Chemical class 0.000 description 7
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 7
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- 239000000937 glycosyl acceptor Substances 0.000 description 6
- 229940049920 malate Drugs 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 5
- 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 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002256 galaktoses Chemical class 0.000 description 5
- 150000008195 galaktosides Chemical class 0.000 description 5
- 229960001031 glucose Drugs 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 229930182478 glucoside Natural products 0.000 description 5
- 150000008131 glucosides Chemical class 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- RBNPOMFGQQGHHO-UWTATZPHSA-M D-glycerate Chemical compound OC[C@@H](O)C([O-])=O RBNPOMFGQQGHHO-UWTATZPHSA-M 0.000 description 4
- 108010005991 Pork Regular Insulin Proteins 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 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 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- OMSUIQOIVADKIM-UHFFFAOYSA-N ethyl 3-hydroxybutyrate Chemical compound CCOC(=O)CC(C)O OMSUIQOIVADKIM-UHFFFAOYSA-N 0.000 description 4
- 229930182830 galactose Natural products 0.000 description 4
- 150000002402 hexoses Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229930182475 S-glycoside Natural products 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
- 238000003556 assay Methods 0.000 description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- 125000001488 beta-D-galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 3
- YSEKNCXYRGKTBJ-BYPYZUCNSA-N dimethyl (2s)-2-hydroxybutanedioate Chemical compound COC(=O)C[C@H](O)C(=O)OC YSEKNCXYRGKTBJ-BYPYZUCNSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229960002442 glucosamine Drugs 0.000 description 3
- 150000002301 glucosamine derivatives Chemical class 0.000 description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 3
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 150000003569 thioglycosides Chemical class 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 2
- RGKVWQOMMIBSTE-NOASMPFISA-N (2s)-6-amino-5-hydroxy-2-[[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]amino]hexanoic acid Chemical compound NCC(O)CC[C@@H](C(O)=O)N[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O RGKVWQOMMIBSTE-NOASMPFISA-N 0.000 description 2
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 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
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- RBNPOMFGQQGHHO-REOHCLBHSA-N L-glyceric acid Chemical compound OC[C@H](O)C(O)=O RBNPOMFGQQGHHO-REOHCLBHSA-N 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical class CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241000797947 Paria Species 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-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
- AEEOGDIDWVOYEU-DLFCCZSRSA-M [K+].C[C@@H]([C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C([O-])=O Chemical compound [K+].C[C@@H]([C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C([O-])=O AEEOGDIDWVOYEU-DLFCCZSRSA-M 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- UHNHELGKNQMNGF-AOQKXWSCSA-N bacillithiol Chemical compound SC[C@H](N)C(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H](CC(O)=O)C(O)=O UHNHELGKNQMNGF-AOQKXWSCSA-N 0.000 description 2
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 2
- 229960002246 beta-d-glucopyranose Drugs 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- WQXNXVUDBPYKBA-YFKPBYRVSA-N ectoine Chemical compound CC1=[NH+][C@H](C([O-])=O)CCN1 WQXNXVUDBPYKBA-YFKPBYRVSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000005558 fluorometry Methods 0.000 description 2
- 150000002303 glucose derivatives Chemical class 0.000 description 2
- 230000008642 heat stress Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 150000003893 lactate salts Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical group OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 150000004701 malic acid derivatives Chemical class 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000029983 protein stabilization Effects 0.000 description 2
- 230000006432 protein unfolding Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- GKHCBYYBLTXYEV-YMWOCUMHSA-N (2r,3r,4s,5r)-2-(hydroxymethyl)-6-phenylmethoxyoxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)OC1OCC1=CC=CC=C1 GKHCBYYBLTXYEV-YMWOCUMHSA-N 0.000 description 1
- RTSODCRZYKSCLO-VKHMYHEASA-N (3s)-3-hydroxy-4-methoxy-4-oxobutanoic acid Chemical compound COC(=O)[C@@H](O)CC(O)=O RTSODCRZYKSCLO-VKHMYHEASA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 1
- PHAJLQZMIYTPTH-MGHXQANLSA-N 2-hydroxy-2-[(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]acetic acid Chemical compound OC[C@H]1O[C@H](C(O)C(O)=O)[C@@H](O)[C@@H](O)[C@@H]1O PHAJLQZMIYTPTH-MGHXQANLSA-N 0.000 description 1
- YEBNQUQCOVQUKH-UHFFFAOYSA-N 4-[(1-phenylpiperidin-4-ylidene)methyl]naphthalene-1-carbonitrile Chemical compound C12=CC=CC=C2C(C#N)=CC=C1C=C(CC1)CCN1C1=CC=CC=C1 YEBNQUQCOVQUKH-UHFFFAOYSA-N 0.000 description 1
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
- IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- UKNDPWQFDLJVSJ-NFOVDCHBSA-N C(C(O)CO)(=O)OC1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O1)CO Chemical compound C(C(O)CO)(=O)OC1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O1)CO UKNDPWQFDLJVSJ-NFOVDCHBSA-N 0.000 description 1
- BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- 229930195711 D-Serine Natural products 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 241000228162 Rubrobacter xylanophilus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000003800 Staudinger reaction Methods 0.000 description 1
- 241000205180 Thermococcus litoralis Species 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 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 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229940077731 carbohydrate nutrients Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000003950 cyclic amides Chemical class 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960003082 galactose Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000000348 glycosyl donor Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229940041290 mannose Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- COFCNNXZXGCREM-UHFFFAOYSA-N methyl 2,3-dihydroxypropanoate Chemical class COC(=O)C(O)CO COFCNNXZXGCREM-UHFFFAOYSA-N 0.000 description 1
- HOVAGTYPODGVJG-PZRMXXKTSA-N methyl alpha-D-galactoside Chemical compound CO[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O HOVAGTYPODGVJG-PZRMXXKTSA-N 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000001048 orange dye Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- VWOFJCHHYLOZKH-UHFFFAOYSA-N phosphoric acid;propane-1,2,3-triol Chemical compound OP(O)(O)=O.OCC(O)CO.OCC(O)CO VWOFJCHHYLOZKH-UHFFFAOYSA-N 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
- C07H9/06—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing nitrogen as ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1136—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating or stabilising agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Crystallography & Structural Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Saccharide Compounds (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020247009385A KR102828884B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461953392P | 2014-03-14 | 2014-03-14 | |
| US61/953,392 | 2014-03-14 | ||
| PCT/PT2015/050001 WO2015137838A1 (en) | 2014-03-14 | 2015-03-13 | Hexose derivatives, preparation and uses thereof |
| KR1020167028609A KR102401853B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020167028609A Division KR102401853B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020247009385A Division KR102828884B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20220153571A KR20220153571A (ko) | 2022-11-18 |
| KR102651029B1 true KR102651029B1 (ko) | 2024-03-25 |
Family
ID=53264710
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020227017066A Active KR102651029B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
| KR1020247009385A Active KR102828884B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
| KR1020167028609A Active KR102401853B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020247009385A Active KR102828884B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
| KR1020167028609A Active KR102401853B1 (ko) | 2014-03-14 | 2015-03-13 | 헥소스 유도체, 그의 제제 및 용도 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US11708387B2 (https=) |
| EP (1) | EP3116886A1 (https=) |
| JP (2) | JP7067867B2 (https=) |
| KR (3) | KR102651029B1 (https=) |
| CN (2) | CN106573952A (https=) |
| BR (1) | BR112016021231B1 (https=) |
| CA (1) | CA2942635C (https=) |
| IL (1) | IL247531B (https=) |
| MX (1) | MX386787B (https=) |
| RU (1) | RU2731563C2 (https=) |
| SG (2) | SG10201807891UA (https=) |
| WO (1) | WO2015137838A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102651029B1 (ko) * | 2014-03-14 | 2024-03-25 | 파쿠우다지 지 씨엔씨아스 다 우니베르시다지 지 리스보아 | 헥소스 유도체, 그의 제제 및 용도 |
| FR3061013B1 (fr) * | 2016-12-22 | 2020-04-17 | Greenpharma | Composition contenant le digeneaside, son procede d'obtention et son utilisation cosmetique, veterinaire ou nutraceutique |
| US12098162B2 (en) * | 2017-11-13 | 2024-09-24 | Extremochem, Lda | Neutral glycosylated amides and dianionic glucuronidated acids as stabilizers for biological molecules |
| CN116251110B (zh) * | 2022-11-18 | 2025-02-14 | 广东药科大学 | β-D-吡喃葡萄糖基-乳酸及其衍生物在制备治疗代谢性疾病、炎症药物中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007097652A2 (en) | 2006-02-24 | 2007-08-30 | STAB VIDA, Investigação e Serviços em Ciências Biológicas, Lda | Synthetic mannosylglycerate derivatives for the stabilisation and preservation of biomaterials |
| US20130143787A1 (en) | 2010-07-27 | 2013-06-06 | Henkel Ag & Co. Kgaa | Stabilized liquid enzyme-containing surfactant preparation |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060099567A1 (en) * | 2004-04-08 | 2006-05-11 | Biomatrica, Inc. | Integration of sample storage and sample management for life science |
| DE102004031588A1 (de) * | 2004-06-30 | 2006-02-09 | Symrise Gmbh & Co. Kg | Verwendung von Äpfelsäureglucosiden als Geschmacksstoffe |
| PT103441A (pt) | 2006-02-24 | 2007-08-24 | Stab Vida Investigacao E Servi | Utilização de solutos compatíveis para melhorar o desempenho de técnicas utilizando materiais biológicos imobilizados |
| DE102011118027A1 (de) * | 2011-09-12 | 2013-03-14 | Henkel Ag & Co. Kgaa | Verfahren zur Anpassung eines Hydrolytischen Enzyms an eine das hydrolytische Enzym stabilisierende Komponente |
| KR102651029B1 (ko) | 2014-03-14 | 2024-03-25 | 파쿠우다지 지 씨엔씨아스 다 우니베르시다지 지 리스보아 | 헥소스 유도체, 그의 제제 및 용도 |
| JP2020097767A (ja) | 2018-12-18 | 2020-06-25 | 株式会社東芝 | 表面処理剤、これを用いた積層体、及び無電解めっき製品 |
-
2015
- 2015-03-13 KR KR1020227017066A patent/KR102651029B1/ko active Active
- 2015-03-13 JP JP2016575290A patent/JP7067867B2/ja active Active
- 2015-03-13 KR KR1020247009385A patent/KR102828884B1/ko active Active
- 2015-03-13 US US15/125,522 patent/US11708387B2/en active Active
- 2015-03-13 BR BR112016021231-2A patent/BR112016021231B1/pt active IP Right Grant
- 2015-03-13 KR KR1020167028609A patent/KR102401853B1/ko active Active
- 2015-03-13 SG SG10201807891UA patent/SG10201807891UA/en unknown
- 2015-03-13 MX MX2016011808A patent/MX386787B/es unknown
- 2015-03-13 CA CA2942635A patent/CA2942635C/en active Active
- 2015-03-13 CN CN201580014386.4A patent/CN106573952A/zh active Pending
- 2015-03-13 EP EP15724386.6A patent/EP3116886A1/en active Pending
- 2015-03-13 RU RU2016140337A patent/RU2731563C2/ru active
- 2015-03-13 CN CN202211044372.5A patent/CN115448964A/zh active Pending
- 2015-03-13 WO PCT/PT2015/050001 patent/WO2015137838A1/en not_active Ceased
- 2015-03-13 SG SG11201607530XA patent/SG11201607530XA/en unknown
-
2016
- 2016-08-29 IL IL247531A patent/IL247531B/en active IP Right Grant
-
2020
- 2020-06-04 JP JP2020097767A patent/JP7077361B2/ja active Active
-
2023
- 2023-06-09 US US18/332,157 patent/US12590117B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007097652A2 (en) | 2006-02-24 | 2007-08-30 | STAB VIDA, Investigação e Serviços em Ciências Biológicas, Lda | Synthetic mannosylglycerate derivatives for the stabilisation and preservation of biomaterials |
| US20130143787A1 (en) | 2010-07-27 | 2013-06-06 | Henkel Ag & Co. Kgaa | Stabilized liquid enzyme-containing surfactant preparation |
Non-Patent Citations (4)
| Title |
|---|
| A.I.Khodair et al., Synthesis, vol.2004 (2004) p.53-58.* |
| S.I.Ascencio et al., Carbohydrate Research, vol.341 (2006) p.677-682.* |
| T.Q.Faria et al., Carbohydrate Research, vol.343 (2008) p.3025-3033. |
| T.Sawangwan et al., Organic & Biomolecular Chem., vol.7 (2009) p.4267-4270.* |
Also Published As
| Publication number | Publication date |
|---|---|
| SG11201607530XA (en) | 2016-10-28 |
| BR112016021231B1 (pt) | 2021-07-27 |
| KR102401853B1 (ko) | 2022-05-25 |
| US12590117B2 (en) | 2026-03-31 |
| JP7077361B2 (ja) | 2022-05-30 |
| US20230357301A1 (en) | 2023-11-09 |
| IL247531A0 (en) | 2016-11-30 |
| CA2942635A1 (en) | 2015-09-17 |
| KR20220153571A (ko) | 2022-11-18 |
| KR20240045328A (ko) | 2024-04-05 |
| JP2017516838A (ja) | 2017-06-22 |
| SG10201807891UA (en) | 2018-10-30 |
| EP3116886A1 (en) | 2017-01-18 |
| MX386787B (es) | 2025-03-19 |
| US20180170955A1 (en) | 2018-06-21 |
| IL247531B (en) | 2021-04-29 |
| JP2020183383A (ja) | 2020-11-12 |
| CA2942635C (en) | 2022-12-06 |
| RU2016140337A3 (https=) | 2018-10-30 |
| CN106573952A (zh) | 2017-04-19 |
| KR20160145584A (ko) | 2016-12-20 |
| BR112016021231A2 (en) | 2018-07-10 |
| CN115448964A (zh) | 2022-12-09 |
| US11708387B2 (en) | 2023-07-25 |
| KR102828884B1 (ko) | 2025-07-02 |
| JP7067867B2 (ja) | 2022-05-16 |
| MX2016011808A (es) | 2017-05-09 |
| RU2016140337A (ru) | 2018-04-17 |
| RU2731563C2 (ru) | 2020-09-04 |
| WO2015137838A1 (en) | 2015-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12590117B2 (en) | Hexose derivatives, preparation and uses thereof | |
| AU2016303661B2 (en) | Multiligand agent for drug delivery | |
| WO2012155916A1 (en) | Manufacture of lacto-n-tetraose | |
| WO2017037719A1 (en) | Aminoglycoside derivatives and uses thereof in treating genetic disorders | |
| CA2689524C (fr) | Glycoconjugues et leur utilisation comme vaccin contre shigella flexneri de serotype 3a et x | |
| Chatterjee et al. | Stereoselective α-glycosidation using FeCl 3 as a Lewis acid catalyst | |
| EP1371733B1 (en) | Process for producing hyaluronic acid or its derivative | |
| WO2017118968A1 (en) | Aminoglycoside derivatives and uses thereof in treating genetic disorders | |
| Lourenço et al. | The synthesis of compatible solute analogues—solvent effects on selective glycosylation | |
| CA2355097A1 (en) | Inositol-containing hexasaccharides, their synthesis and their uses | |
| HK40084341A (en) | Hexose derivatives, preparation and uses thereof | |
| HK1236538A1 (en) | Hexose derivatives, preparation and uses thereof | |
| JP2007084484A (ja) | 皮膚外用剤 | |
| JP5438998B2 (ja) | 新規糖鎖プライマーとその利用 | |
| Le Guen et al. | Allyl 4, 6-O-benzylidene-2-deoxy-2-trichloroacetamido-β-d-glucopyranoside | |
| WO2025163383A1 (en) | Molecular surgery: cut-insert-stitch editing reaction (cister) technique | |
| Verhart | Some approaches to the innovative chemical use of sucrose and related monosaccharides | |
| Seo | The chemistry of unsaturated pyranosides and L-(–)-sucrose | |
| Tamura et al. | Synthesis of linear-type chondroitin clusters having a C8 spacer between disaccharide moieties and enzymatic transfer of d-glucuronic acid to the artificial glycans | |
| Lamosa et al. | A unique glyceryl diglycoside identified in the thermophilic, radiation-resistant bacterium Rubrobacter xylanophilus | |
| Martín-Lomas et al. | Inositol-containing hexasaccharides, their synthesis and their uses | |
| Me2S2 | 4.4 2-Iodoalkylidene Acetals as Tether | |
| JP2013032306A (ja) | 新規チオオリゴ糖の合成とそれを用いたセルラーゼの活性測定法 | |
| Raaijmakers | Some aspects of the synthesis and properties of carbohydrate-based amphiphiles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20220520 Application number text: 1020167028609 Filing date: 20161014 |
|
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20220617 Comment text: Request for Examination of Application |
|
| PG1501 | Laying open of application | ||
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20221205 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20231220 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20240320 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20240321 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration |