KR20080056267A - 보호된 아민 염을 이용하는 말단 아민기를 갖는 중합체의제조방법 - Google Patents
보호된 아민 염을 이용하는 말단 아민기를 갖는 중합체의제조방법 Download PDFInfo
- Publication number
- KR20080056267A KR20080056267A KR1020087010397A KR20087010397A KR20080056267A KR 20080056267 A KR20080056267 A KR 20080056267A KR 1020087010397 A KR1020087010397 A KR 1020087010397A KR 20087010397 A KR20087010397 A KR 20087010397A KR 20080056267 A KR20080056267 A KR 20080056267A
- Authority
- KR
- South Korea
- Prior art keywords
- polymer
- terminal
- group
- peg
- substituted
- 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.)
- Withdrawn
Links
- 229920000642 polymer Polymers 0.000 title claims abstract description 85
- -1 amine salts Chemical class 0.000 title claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 title claims description 18
- 125000003277 amino group Chemical group 0.000 title description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 50
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 42
- 150000001412 amines Chemical group 0.000 claims abstract description 38
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims abstract description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 15
- 230000000890 antigenic effect Effects 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical group CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 229920013730 reactive polymer Polymers 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 claims description 4
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- XCAQIUOFDMREBA-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)OC(C)(C)C XCAQIUOFDMREBA-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 229910003002 lithium salt Inorganic materials 0.000 claims description 3
- 159000000002 lithium salts Chemical class 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 229960005215 dichloroacetic acid Drugs 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229920001451 polypropylene glycol Polymers 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 1
- 229940077388 benzenesulfonate Drugs 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000000999 tert-butyl group Chemical class [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000005490 tosylate group Chemical group 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- PVVTWNMXEHROIA-UHFFFAOYSA-N 2-(3-hydroxypropyl)-1h-quinazolin-4-one Chemical compound C1=CC=C2NC(CCCO)=NC(=O)C2=C1 PVVTWNMXEHROIA-UHFFFAOYSA-N 0.000 description 15
- 239000012265 solid product Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 229920001427 mPEG Polymers 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 238000009739 binding Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 238000005576 amination reaction Methods 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 159000000001 potassium salts Chemical class 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- YSFGBPCBPNVLOK-UHFFFAOYSA-N 6-hydroxy-2-methylhex-2-enamide Chemical compound NC(=O)C(C)=CCCCO YSFGBPCBPNVLOK-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 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 2
- 125000005647 linker group Chemical group 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- GODZNYBQGNSJJN-UHFFFAOYSA-N 1-aminoethane-1,2-diol Chemical compound NC(O)CO GODZNYBQGNSJJN-UHFFFAOYSA-N 0.000 description 1
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- TZXJJSAQSRHKCZ-UHFFFAOYSA-N 2-methoxyethyl 4-methylbenzenesulfonate Chemical compound COCCOS(=O)(=O)C1=CC=C(C)C=C1 TZXJJSAQSRHKCZ-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229940013688 formic acid Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910052751 metal Chemical group 0.000 description 1
- 239000002184 metal Chemical group 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
- C08G65/33303—Polymers modified by chemical after-treatment with organic compounds containing nitrogen containing amino group
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/321—Polymers modified by chemical after-treatment with inorganic compounds
- C08G65/325—Polymers modified by chemical after-treatment with inorganic compounds containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/334—Polymers modified by chemical after-treatment with organic compounds containing sulfur
- C08G65/3348—Polymers modified by chemical after-treatment with organic compounds containing sulfur containing nitrogen in addition to sulfur
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
- C08L71/02—Polyalkylene oxides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Polyethers (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/242,656 US7601798B2 (en) | 2005-10-04 | 2005-10-04 | Methods of preparing polymers having terminal amine groups using protected amine salts |
| US11/242,656 | 2005-10-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080056267A true KR20080056267A (ko) | 2008-06-20 |
Family
ID=37902700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087010397A Withdrawn KR20080056267A (ko) | 2005-10-04 | 2006-09-29 | 보호된 아민 염을 이용하는 말단 아민기를 갖는 중합체의제조방법 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US7601798B2 (enExample) |
| EP (1) | EP1931313A4 (enExample) |
| JP (1) | JP2009510253A (enExample) |
| KR (1) | KR20080056267A (enExample) |
| CN (1) | CN101321516A (enExample) |
| AU (1) | AU2006302585A1 (enExample) |
| CA (1) | CA2623542A1 (enExample) |
| IL (1) | IL190415A0 (enExample) |
| TW (1) | TW200718730A (enExample) |
| WO (1) | WO2007044319A2 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7820765B2 (en) * | 2005-07-20 | 2010-10-26 | Bridgestone Corporation | Amine functionalized polymers |
| US8133707B2 (en) * | 2006-01-17 | 2012-03-13 | Enzon Pharmaceuticals, Inc. | Methods of preparing activated polymers having alpha nitrogen groups |
| US20090156629A1 (en) * | 2006-06-09 | 2009-06-18 | Enzon Pharmaceuticals, Inc. | Indenoisoquinoline-releasable polymer conjugates |
| JP2010515762A (ja) * | 2007-01-16 | 2010-05-13 | エンゾン ファーマスーティカルズ インコーポレイテッド | ポサコナゾール−ポリマー複合体、並びに、ポサコナゾールおよびそのポリマー複合体を使用した治療方法 |
| DK2147122T3 (da) * | 2007-04-20 | 2014-10-13 | Sigma Tau Rare Diseases S A | Enzymatisk kræftbehandling |
| AU2008242748B2 (en) * | 2007-04-20 | 2013-12-05 | Unikeris Limited | Stable recombinant adenosine deaminase |
| WO2009009712A1 (en) * | 2007-07-11 | 2009-01-15 | Enzon Pharmaceuticals, Inc. | Polymeric drug delivery system containing a multi-substituted aromatic moiety |
| JP6625627B2 (ja) | 2014-10-14 | 2019-12-25 | ハロザイム インコーポレイテッド | アデノシンデアミナーゼ−２（ａｄａ２）、その変異体の組成物およびそれを使用する方法 |
| PH12021552223A1 (en) | 2019-03-21 | 2022-05-30 | Codiak Biosciences Inc | Extracellular vesicles for vaccine delivery |
| US12233356B2 (en) | 2019-03-21 | 2025-02-25 | Lonza Sales Ag | Process for preparing extracellular vesicles |
| WO2022066934A2 (en) | 2020-09-23 | 2022-03-31 | Codiak Biosciences, Inc. | Process for preparing extracellular vesicles |
| US20240241020A1 (en) | 2020-09-23 | 2024-07-18 | Lonza Sales Ag | Process for preparing extracellular vesicles |
| CN114409890A (zh) * | 2022-02-28 | 2022-04-29 | 中国科学院长春应用化学研究所 | 一种氨基功能化的聚乙二醇衍生物及其制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US5643575A (en) * | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US6448369B1 (en) * | 1997-11-06 | 2002-09-10 | Shearwater Corporation | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
| US6824766B2 (en) * | 1998-04-17 | 2004-11-30 | Enzon, Inc. | Biodegradable high molecular weight polymeric linkers and their conjugates |
| KR20020022691A (ko) * | 1999-06-08 | 2002-03-27 | 와이즈먼 앤드루 | 아미노옥시기를 포함하는 원자가 플랫폼 분자 |
| US20030149307A1 (en) | 2001-10-24 | 2003-08-07 | Baxter International Inc. | Process for the preparation of polyethylene glycol bis amine |
| WO2004035657A1 (en) * | 2002-10-15 | 2004-04-29 | Baxter International Inc. | Process for the preparation of polyethylene glycol bis amine |
| US7332164B2 (en) * | 2003-03-21 | 2008-02-19 | Enzon Pharmaceuticals, Inc. | Heterobifunctional polymeric bioconjugates |
| KR100512483B1 (ko) * | 2003-05-07 | 2005-09-05 | 선바이오(주) | 신규한 폴리에틸렌글리콜-말레이미드 유도체의 합성방법 |
| EP1688150A1 (en) * | 2005-02-08 | 2006-08-09 | Novo Nordisk A/S | Process for the preparation of alkoxyamine functionalised poly ethylene glycols |
-
2005
- 2005-10-04 US US11/242,656 patent/US7601798B2/en not_active Expired - Fee Related
-
2006
- 2006-09-29 KR KR1020087010397A patent/KR20080056267A/ko not_active Withdrawn
- 2006-09-29 US US11/537,172 patent/US7569657B2/en not_active Expired - Fee Related
- 2006-09-29 AU AU2006302585A patent/AU2006302585A1/en not_active Abandoned
- 2006-09-29 WO PCT/US2006/038562 patent/WO2007044319A2/en not_active Ceased
- 2006-09-29 CN CNA2006800455829A patent/CN101321516A/zh active Pending
- 2006-09-29 CA CA002623542A patent/CA2623542A1/en not_active Abandoned
- 2006-09-29 EP EP06816091A patent/EP1931313A4/en not_active Withdrawn
- 2006-09-29 JP JP2008534615A patent/JP2009510253A/ja active Pending
- 2006-10-02 TW TW095136519A patent/TW200718730A/zh unknown
-
2008
- 2008-03-25 IL IL190415A patent/IL190415A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1931313A4 (en) | 2009-12-23 |
| WO2007044319A2 (en) | 2007-04-19 |
| IL190415A0 (en) | 2009-09-22 |
| US7601798B2 (en) | 2009-10-13 |
| WO2007044319A3 (en) | 2007-07-12 |
| AU2006302585A1 (en) | 2007-04-19 |
| CN101321516A (zh) | 2008-12-10 |
| JP2009510253A (ja) | 2009-03-12 |
| US20070078219A1 (en) | 2007-04-05 |
| EP1931313A2 (en) | 2008-06-18 |
| US20070078257A1 (en) | 2007-04-05 |
| TW200718730A (en) | 2007-05-16 |
| CA2623542A1 (en) | 2007-04-19 |
| US7569657B2 (en) | 2009-08-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4758608B2 (ja) | 分枝ポリマーおよびそれらの結合体 | |
| ES2404685T3 (es) | Derivados heterobifuncionales de poli(etilenglicol) y métodos para su preparación | |
| KR101918339B1 (ko) | 다중-아암 폴리에틸렌 글리콜 유도체, 그 유도체의 중간체, 및 그 유도체의 제조방법 | |
| WO1997014740A1 (en) | Discrete-length polyethylene glycols | |
| EP2010592A2 (en) | Method for preparing multi-arm poly(ethylene glycol) amines | |
| KR20080056267A (ko) | 보호된 아민 염을 이용하는 말단 아민기를 갖는 중합체의제조방법 | |
| EP1928934B1 (en) | Methods of preparing polymers having terminal amine groups | |
| JP7618380B2 (ja) | マルチアーム型ポリエチレングリコール誘導体の製造方法 | |
| JP5150297B2 (ja) | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 | |
| JP5953459B2 (ja) | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 | |
| MX2008004375A (en) | Methods of preparing polymers having terminal amine groups using protected amine salts | |
| CN101248107A (zh) | 制备含有末端胺基的聚合物的方法 | |
| JP6361083B2 (ja) | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 | |
| JP6184462B2 (ja) | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 | |
| AU2009249967B2 (en) | A method for preparing high-purity polyethyleneglycol aldehyde derivatives | |
| JP2018115338A (ja) | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20080429 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |