KR20100036326A - 프람린타이드의 생산 방법 - Google Patents
프람린타이드의 생산 방법 Download PDFInfo
- Publication number
- KR20100036326A KR20100036326A KR1020107001183A KR20107001183A KR20100036326A KR 20100036326 A KR20100036326 A KR 20100036326A KR 1020107001183 A KR1020107001183 A KR 1020107001183A KR 20107001183 A KR20107001183 A KR 20107001183A KR 20100036326 A KR20100036326 A KR 20100036326A
- Authority
- KR
- South Korea
- Prior art keywords
- peptide
- side chain
- protected
- formula
- protecting group
- 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- Withdrawn
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- 238000000034 method Methods 0.000 title claims description 16
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 108010029667 pramlintide Proteins 0.000 title description 4
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 title description 4
- 229960003611 pramlintide Drugs 0.000 title description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 85
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 30
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 28
- 238000010168 coupling process Methods 0.000 claims description 30
- 238000005859 coupling reaction Methods 0.000 claims description 30
- 230000008878 coupling Effects 0.000 claims description 29
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 28
- 125000006239 protecting group Chemical group 0.000 claims description 27
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 16
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 14
- TZCYLJGNWDVJRA-UHFFFAOYSA-N 6-chloro-1-hydroxybenzotriazole Chemical compound C1=C(Cl)C=C2N(O)N=NC2=C1 TZCYLJGNWDVJRA-UHFFFAOYSA-N 0.000 claims description 11
- -1 Boc-protected amino Chemical group 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 102000007079 Peptide Fragments Human genes 0.000 claims description 6
- 108010033276 Peptide Fragments Proteins 0.000 claims description 6
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000012634 fragment Substances 0.000 abstract description 12
- 125000000539 amino acid group Chemical group 0.000 abstract description 3
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 229920005989 resin Polymers 0.000 description 30
- 239000011347 resin Substances 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 235000001014 amino acid Nutrition 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 108010016626 Dipeptides Proteins 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- VORIUEAZEKLUSJ-UHFFFAOYSA-M [(6-chlorobenzotriazol-1-yl)oxy-(dimethylamino)methylidene]-dimethylazanium;trifluoroborane;fluoride Chemical compound [F-].FB(F)F.C1=C(Cl)C=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 VORIUEAZEKLUSJ-UHFFFAOYSA-M 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
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- 238000011068 loading method Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- SHYYAQLDNVHPFT-DLOVCJGASA-N Ala-Asn-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SHYYAQLDNVHPFT-DLOVCJGASA-N 0.000 description 3
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 2
- NDKDFTQNXLHCGO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1=CC=C2C(COC(=O)NCC(=O)O)C3=CC=CC=C3C2=C1 NDKDFTQNXLHCGO-UHFFFAOYSA-N 0.000 description 2
- PPCORQFLAZWUNO-QWRGUYRKSA-N Asn-Phe-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)N)N PPCORQFLAZWUNO-QWRGUYRKSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- YFXFOZPXVFPBDH-VZFHVOOUSA-N Cys-Ala-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)CS)C(O)=O YFXFOZPXVFPBDH-VZFHVOOUSA-N 0.000 description 2
- PRBLYKYHAJEABA-SRVKXCTJSA-N Gln-Arg-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O PRBLYKYHAJEABA-SRVKXCTJSA-N 0.000 description 2
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 2
- LMDVGHQPPPLYAR-IHRRRGAJSA-N Leu-Val-His Chemical compound N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O LMDVGHQPPPLYAR-IHRRRGAJSA-N 0.000 description 2
- XTONYTDATVADQH-CIUDSAMLSA-N Lys-Cys-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O XTONYTDATVADQH-CIUDSAMLSA-N 0.000 description 2
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 2
- VZKBJNBZMZHKRC-XUXIUFHCSA-N Pro-Ile-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O VZKBJNBZMZHKRC-XUXIUFHCSA-N 0.000 description 2
- WVXQQUWOKUZIEG-VEVYYDQMSA-N Pro-Thr-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O WVXQQUWOKUZIEG-VEVYYDQMSA-N 0.000 description 2
- WLJPJRGQRNCIQS-ZLUOBGJFSA-N Ser-Ser-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O WLJPJRGQRNCIQS-ZLUOBGJFSA-N 0.000 description 2
- CAJFZCICSVBOJK-SHGPDSBTSA-N Thr-Ala-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAJFZCICSVBOJK-SHGPDSBTSA-N 0.000 description 2
- WRXWNQJYARAPLU-UHFFFAOYSA-F [(5-chloro-3-oxidobenzotriazol-3-ium-1-yl)-(dimethylamino)methylidene]-dimethylazanium fluoro-dioxido-oxo-lambda5-phosphane Chemical compound [O-]P([O-])(F)=O.[O-]P([O-])(F)=O.[O-]P([O-])(F)=O.[O-]P([O-])(F)=O.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1.ClC1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1 WRXWNQJYARAPLU-UHFFFAOYSA-F 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000004900 c-terminal fragment Anatomy 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
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- 238000004128 high performance liquid chromatography Methods 0.000 description 2
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- 108010018006 histidylserine Proteins 0.000 description 2
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 108010064486 phenylalanyl-leucyl-valine Proteins 0.000 description 2
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- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 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 2
- 238000005406 washing Methods 0.000 description 2
- CSMYOORPUGPKAP-IBGZPJMESA-N (2r)-3-(acetamidomethylsulfanyl)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CSCNC(=O)C)C(O)=O)C3=CC=CC=C3C2=C1 CSMYOORPUGPKAP-IBGZPJMESA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- OBOHMJWDFPBPKD-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 OBOHMJWDFPBPKD-UHFFFAOYSA-N 0.000 description 1
- VUTZFAOGDXUYEJ-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 VUTZFAOGDXUYEJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- KZYSHAMXEBPJBD-JRQIVUDYSA-N Asn-Thr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZYSHAMXEBPJBD-JRQIVUDYSA-N 0.000 description 1
- ZAESWDKAMDVHLL-RCOVLWMOSA-N Asn-Val-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O ZAESWDKAMDVHLL-RCOVLWMOSA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 1
- 101100315624 Caenorhabditis elegans tyr-1 gene Proteins 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- IALQAMYQJBZNSK-WHFBIAKZSA-N Gly-Ser-Asn Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O IALQAMYQJBZNSK-WHFBIAKZSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 101001081479 Homo sapiens Islet amyloid polypeptide Proteins 0.000 description 1
- PMMMQRVUMVURGJ-XUXIUFHCSA-N Ile-Leu-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O PMMMQRVUMVURGJ-XUXIUFHCSA-N 0.000 description 1
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- 229920001367 Merrifield resin Polymers 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- FBVSXKMMQOZUNU-NSHDSACASA-N N2,N6-Bis{[(2-methyl-2-propanyl)oxy]carbonyl}lysine Chemical compound CC(C)(C)OC(=O)NCCCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C FBVSXKMMQOZUNU-NSHDSACASA-N 0.000 description 1
- NPLGQVKZFGJWAI-QWHCGFSZSA-N Phe-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O NPLGQVKZFGJWAI-QWHCGFSZSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 1
- OOKCGAYXSNJBGQ-ZLUOBGJFSA-N Ser-Asn-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O OOKCGAYXSNJBGQ-ZLUOBGJFSA-N 0.000 description 1
- UGJRQLURDVGULT-LKXGYXEUSA-N Ser-Asn-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UGJRQLURDVGULT-LKXGYXEUSA-N 0.000 description 1
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 1
- HQYVQDRYODWONX-DCAQKATOSA-N Val-His-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CO)C(=O)O)N HQYVQDRYODWONX-DCAQKATOSA-N 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
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- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- UBLQIESZTDNNAO-UHFFFAOYSA-N n,n-diethylethanamine;phosphoric acid Chemical compound [O-]P([O-])([O-])=O.CC[NH+](CC)CC.CC[NH+](CC)CC.CC[NH+](CC)CC UBLQIESZTDNNAO-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 239000012071 phase Substances 0.000 description 1
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- 238000002360 preparation method Methods 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
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- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 229940099093 symlin Drugs 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07012806 | 2007-06-29 | ||
| EP07012806.1 | 2007-06-29 | ||
| EP07022380 | 2007-11-19 | ||
| EP07022380.5 | 2007-11-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20100036326A true KR20100036326A (ko) | 2010-04-07 |
Family
ID=39885153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020107001183A Withdrawn KR20100036326A (ko) | 2007-06-29 | 2008-06-30 | 프람린타이드의 생산 방법 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20100249370A1 (https=) |
| EP (1) | EP2181118A1 (https=) |
| JP (1) | JP2010531828A (https=) |
| KR (1) | KR20100036326A (https=) |
| CN (1) | CN101790535A (https=) |
| AU (1) | AU2008271608A1 (https=) |
| WO (1) | WO2009003666A1 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100081788A1 (en) * | 2008-09-03 | 2010-04-01 | Scinopharm Taiwan Ltd. | Process for the Preparation of Pramlintide |
| CN101747426B (zh) * | 2009-12-18 | 2013-01-16 | 深圳翰宇药业股份有限公司 | 一种合成普兰林肽的方法 |
| CN102180943A (zh) * | 2010-12-16 | 2011-09-14 | 深圳市健元医药科技有限公司 | 一种辅助降血糖多肽药物的生产工艺 |
| CN102250235A (zh) * | 2011-06-23 | 2011-11-23 | 成都圣诺科技发展有限公司 | 奈西立肽的制备方法 |
| US8846614B2 (en) * | 2011-08-25 | 2014-09-30 | Usv Limited | Process for the synthesis of 37-mer peptide pramlintide |
| CN102816213A (zh) * | 2012-05-29 | 2012-12-12 | 南京工业大学 | 使用固相和液相组合技术制备普兰林肽的方法 |
| US10450343B2 (en) | 2013-03-21 | 2019-10-22 | Sanofi-Aventis Deutschland Gmbh | Synthesis of cyclic imide containing peptide products |
| CA2907454C (en) | 2013-03-21 | 2021-05-04 | Sanofi-Aventis Deutschland Gmbh | Synthesis of hydantoin containing peptide products |
| DK3517543T3 (da) | 2018-01-30 | 2020-12-07 | Bachem Ag | Fremstilling af glucagonpeptider |
| CN111499719B (zh) * | 2020-03-19 | 2022-04-08 | 杭州固拓生物科技有限公司 | 一种合成普兰林肽的方法 |
| WO2024110477A2 (en) * | 2022-11-21 | 2024-05-30 | Janssen Pharmaceutica Nv | Synthesis of a cyclic peptide |
| CN118530332A (zh) * | 2024-07-26 | 2024-08-23 | 南京羚诺生物医药技术研究院有限公司 | 一种普兰林肽的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU222249B1 (hu) * | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására |
| WO1992015317A1 (en) * | 1991-03-08 | 1992-09-17 | Amylin Pharmaceuticals, Inc. | Synthetic preparation of amylin and amylin analogues |
| US7910548B2 (en) * | 1997-06-06 | 2011-03-22 | Amylin Pharmaceuticals, Inc. | Methods for treating obesity |
| US6281331B1 (en) * | 1998-03-23 | 2001-08-28 | Trimeris, Inc. | Methods and compositions for peptide synthesis |
| ATE469912T1 (de) * | 2004-10-04 | 2010-06-15 | Novetide Ltd | Gegenionenaustauschverfahren für peptide |
| TW200637872A (en) * | 2004-10-26 | 2006-11-01 | Lonza Ag | Thiol group protection and cyclization in solid-phase peptide synthesis |
| US20100081788A1 (en) * | 2008-09-03 | 2010-04-01 | Scinopharm Taiwan Ltd. | Process for the Preparation of Pramlintide |
-
2008
- 2008-06-30 KR KR1020107001183A patent/KR20100036326A/ko not_active Withdrawn
- 2008-06-30 EP EP08773766A patent/EP2181118A1/en not_active Withdrawn
- 2008-06-30 AU AU2008271608A patent/AU2008271608A1/en not_active Abandoned
- 2008-06-30 WO PCT/EP2008/005325 patent/WO2009003666A1/en not_active Ceased
- 2008-06-30 CN CN200880022433A patent/CN101790535A/zh active Pending
- 2008-06-30 US US12/665,844 patent/US20100249370A1/en not_active Abandoned
- 2008-06-30 JP JP2010513770A patent/JP2010531828A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP2181118A1 (en) | 2010-05-05 |
| CN101790535A (zh) | 2010-07-28 |
| AU2008271608A1 (en) | 2009-01-08 |
| JP2010531828A (ja) | 2010-09-30 |
| US20100249370A1 (en) | 2010-09-30 |
| WO2009003666A1 (en) | 2009-01-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20100119 Patent event code: PA01051R01D Comment text: International Patent Application |
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| 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 |