FI68245C - Foerfarande foer framstaellning av terapeutiskt aktiva polypeptidderivat eller syraadditionssalter daerav - Google Patents

Foerfarande foer framstaellning av terapeutiskt aktiva polypeptidderivat eller syraadditionssalter daerav Download PDF

Info

Publication number: FI68245C
Authority: FI; Finland
Prior art keywords: arg; ser; asp; formula; ala
Prior art date: 1978-09-28

Application number

FI793002A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI68245B (fi

FI793002A7 (fi

Inventor

Hans Kofod

Original Assignee

Nordisk Insulinlab

Priority date (The priority date 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 date listed.)

1978-09-28

Filing date

1979-09-26

Publication date

1985-08-12

1979-09-26 Application filed by Nordisk Insulinlab filed Critical Nordisk Insulinlab

1980-03-29 Publication of FI793002A7 publication Critical patent/FI793002A7/fi

1985-04-30 Publication of FI68245B publication Critical patent/FI68245B/fi

1985-08-12 Application granted granted Critical

1985-08-12 Publication of FI68245C publication Critical patent/FI68245C/fi

Links

108090000765 processed proteins & peptides Proteins 0.000 claims description 50
102000004196 processed proteins & peptides Human genes 0.000 claims description 21
238000006243 chemical reaction Methods 0.000 claims description 17
OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical group C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 claims description 14
VGALFAWDSNRXJK-VIFPVBQESA-N L-aspartic acid beta-benzyl ester Chemical compound OC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 VGALFAWDSNRXJK-VIFPVBQESA-N 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
150000001413 amino acids Chemical group 0.000 claims description 11
150000001875 compounds Chemical class 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
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 claims description 9
239000008103 glucose Substances 0.000 claims description 9
238000000034 method Methods 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
230000015572 biosynthetic process Effects 0.000 claims description 5
230000004153 glucose metabolism Effects 0.000 claims description 5
229920001184 polypeptide Polymers 0.000 claims description 5
238000003786 synthesis reaction Methods 0.000 claims description 5
150000001483 arginine derivatives Chemical class 0.000 claims description 4
125000000524 functional group Chemical group 0.000 claims description 4
XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 claims description 4
230000003914 insulin secretion Effects 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
XGDCYUQSFDQISZ-BQBZGAKWSA-N Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O XGDCYUQSFDQISZ-BQBZGAKWSA-N 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
XMAUFHMAAVTODF-STQMWFEESA-N His-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CN=CN1 XMAUFHMAAVTODF-STQMWFEESA-N 0.000 claims description 2
SSJMZMUVNKEENT-IMJSIDKUSA-N Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CO SSJMZMUVNKEENT-IMJSIDKUSA-N 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
108010067216 glycyl-glycyl-glycine Proteins 0.000 claims description 2
108010092114 histidylphenylalanine Proteins 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
239000007795 chemical reaction product Substances 0.000 claims 2
238000003776 cleavage reaction Methods 0.000 claims 2
230000007017 scission Effects 0.000 claims 2
WMLFFCRUSPNENW-ZLUOBGJFSA-N Asp-Ser-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O WMLFFCRUSPNENW-ZLUOBGJFSA-N 0.000 claims 1
YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 47
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
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 34
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
239000000047 product Substances 0.000 description 19
102000004877 Insulin Human genes 0.000 description 18
108090001061 Insulin Proteins 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
229940125396 insulin Drugs 0.000 description 17
239000002244 precipitate Substances 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
235000001014 amino acid Nutrition 0.000 description 10
230000000694 effects Effects 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
108010086019 Secretin Proteins 0.000 description 9
102100037505 Secretin Human genes 0.000 description 9
239000000203 mixture Substances 0.000 description 9
239000012071 phase Substances 0.000 description 9
229960002101 secretin Drugs 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
239000000243 solution Substances 0.000 description 7
-1 t-butyloxycarbonyl Chemical group 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
238000004458 analytical method Methods 0.000 description 5
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical group OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
238000011282 treatment Methods 0.000 description 4
IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
210000004153 islets of langerhan Anatomy 0.000 description 3
IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000700198 Cavia Species 0.000 description 2
YBAFDPFAUTYYRW-YUMQZZPRSA-N Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O YBAFDPFAUTYYRW-YUMQZZPRSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
210000001789 adipocyte Anatomy 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
210000003020 exocrine pancreas Anatomy 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000003629 gastrointestinal hormone Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
230000028327 secretion Effects 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
QRDZSRWEULKVNW-UHFFFAOYSA-N 6-hydroxy-2-oxo-1h-quinoline-4-carboxylic acid Chemical group C1=C(O)C=C2C(C(=O)O)=CC(=O)NC2=C1 QRDZSRWEULKVNW-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
102000029816 Collagenase Human genes 0.000 description 1
108060005980 Collagenase Proteins 0.000 description 1
101001012217 Conus geographus Con-Ins G3 Proteins 0.000 description 1
101001012221 Conus tulipa Con-Ins T3 Proteins 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
238000003556 assay Methods 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
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
229960002424 collagenase Drugs 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000007515 enzymatic degradation Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000012812 general test Methods 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000004026 insulin derivative Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000463 material Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
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229910002027 silica gel Inorganic materials 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- C07K5/0825—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp and Glp-amino acid; Derivatives thereof
- 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
- 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
- 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
- C07K14/645—Secretins
- 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
- C07K14/66—Thymopoietins
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0819—Tripeptides with the first amino acid being acidic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1021—Tetrapeptides with the first amino acid being acidic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/14—Angiotensins: Related peptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Toxicology (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

FI793002A 1978-09-28 1979-09-26 Foerfarande foer framstaellning av terapeutiskt aktiva polypeptidderivat eller syraadditionssalter daerav FI68245C (fi)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DK430478		1978-09-28
DK430478		1978-09-28

Publications (3)

Publication Number	Publication Date
FI793002A7 FI793002A7 (fi)	1980-03-29
FI68245B FI68245B (fi)	1985-04-30
FI68245C true FI68245C (fi)	1985-08-12

Family

ID=8132257

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
FI793002A FI68245C (fi)	1978-09-28	1979-09-26	Foerfarande foer framstaellning av terapeutiskt aktiva polypeptidderivat eller syraadditionssalter daerav
FI793001A FI68244C (fi)	1978-09-28	1979-09-26	Foerfarande foer framstaellning av terapeutiskt aktiva polypeptidderivat eller syraadditionssalter daerav

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
FI793001A FI68244C (fi)	1978-09-28	1979-09-26	Foerfarande foer framstaellning av terapeutiskt aktiva polypeptidderivat eller syraadditionssalter daerav

Country Status (16)

Country	Link
US (1)	US4356119A (fr)
JP (2)	JPS5569550A (fr)
AT (1)	AT375338B (fr)
AU (2)	AU526149B2 (fr)
BE (2)	BE879087A (fr)
CA (2)	CA1140116A (fr)
CH (2)	CH648567A5 (fr)
DE (2)	DE2939109A1 (fr)
ES (2)	ES484928A1 (fr)
FI (2)	FI68245C (fr)
FR (2)	FR2437399A1 (fr)
GB (2)	GB2031436B (fr)
IT (2)	IT1125421B (fr)
NL (2)	NL7907188A (fr)
NO (2)	NO148923C (fr)
SE (2)	SE7907938L (fr)

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA685075A (en) *		1964-04-21	Schwyzer Robert	Polypeptides and process for their manufacture
CA798855A (en) *		1968-11-12	Bernardi Luigi	Process for preparing a new undecapeptide
CA616330A (en) *		1961-03-14	Schwyzer Robert	Polypeptide and derivatives thereof and process for their manfuacture
GB1064417A (en) *	1963-12-09	1967-04-05	Kyowa Hakko Kogyo Kk	Process for the preparation of copolypeptides
US3400118A (en) *	1966-05-27	1968-09-03	Squibb & Sons Inc	Intermediates in the preparation of secretin
US3832337A (en) *	1970-07-28	1974-08-27	Squibb & Sons Inc	Peptide enzyme inhibitors
US3856770A (en) *	1972-03-08	1974-12-24	Akzona Inc	Psychopharmacologically active tetra-, penta-, hexa-, and heptapeptides
NL175174C (nl) *	1972-03-31	1984-10-01	Akzo Nv	Werkwijze ter bereiding van een farmaceutisch preparaat met psychofarmacologische werking, dat een peptide of peptide-derivaat als actief bestanddeel bevat, alsmede een werkwijze ter bereiding van deze peptiden.
NL175988C (nl) *	1972-05-24	1985-02-01	Akzo Nv	Werkwijze ter bereiding van een farmaceutisch preparaat met psychofarmacologische werking, dat een peptide of peptide-derivaat dat afgeleid is van een de aminozuren 4-10 omvattend, fragment van adrenocorticotroop hormoon als actief bestanddeel bevat, alsmede een werkwijze ter bereiding van deze peptiden.
NL175618C (nl) *	1972-07-15	1984-12-03	Akzo Nv	Werkwijze ter bereiding van een farmaceutisch preparaat met psychofarmacologische werking, dat een peptide of peptide-derivaat bevat, alsmede een werkwijze ter bereiding van dergelijke peptiden.
DE2315271C3 (de) *	1973-03-27	1975-09-11	Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V., 3400 Goettingen	L- Norleucin-13-Motilin, Verfahren zu dessen Herstellung und dasselbe enthaltendes Mittel
GB1532211A (en) *	1974-10-25	1978-11-15	Wellcome Found	Lh-rh peptide analogues
US3975365A (en) *	1975-01-27	1976-08-17	G. D. Searle & Co.	Inhibitory octapeptides angiotensin II
US4171299A (en) *	1975-04-04	1979-10-16	The Regents Of The University Of California	Polypeptide agents for blocking the human allergic response
DE2602443A1 (de) *	1975-04-04	1976-10-21	Univ California	Biologisch aktive polypeptide
US4058512A (en) *	1975-04-28	1977-11-15	Ab Kabi	Synthetic peptides having growth promoting activity
US4024121A (en) *	1976-01-27	1977-05-17	Schally Andrew Victor	(Pyro)-Glu-His-Trp-D-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHR and intermediates
SE436645C (sv) *	1976-04-29	1996-07-22	Bonnierfoeretagen Ab	Antigeniskt aktiv polypeptid, som kan användas vid cancerdiagnosticering och vid framställning av antikroppar
US4110321A (en) *	1976-07-12	1978-08-29	Folkers Karl	Synthetic tridecapeptide [Gln4 ]-neurotensin having hormonal activity
US4086220A (en) *	1976-08-09	1978-04-25	G. D. Searle & Co.	Fragments of secretin

1979
- 1979-09-24 US US06/078,424 patent/US4356119A/en not_active Expired - Lifetime
- 1979-09-25 SE SE7907938A patent/SE7907938L/ not_active Application Discontinuation
- 1979-09-25 SE SE7907939A patent/SE7907939L/ not_active Application Discontinuation
- 1979-09-26 FI FI793002A patent/FI68245C/fi not_active IP Right Cessation
- 1979-09-26 AU AU51245/79A patent/AU526149B2/en not_active Ceased
- 1979-09-26 AU AU51246/79A patent/AU533684B2/en not_active Ceased
- 1979-09-26 FI FI793001A patent/FI68244C/fi not_active IP Right Cessation
- 1979-09-27 NL NL7907188A patent/NL7907188A/nl not_active Application Discontinuation
- 1979-09-27 AT AT0634679A patent/AT375338B/de not_active IP Right Cessation
- 1979-09-27 FR FR7924077A patent/FR2437399A1/fr active Granted
- 1979-09-27 NO NO793112A patent/NO148923C/no unknown
- 1979-09-27 DE DE19792939109 patent/DE2939109A1/de not_active Withdrawn
- 1979-09-27 FR FR7924078A patent/FR2437400A1/fr active Granted
- 1979-09-27 DE DE19792939135 patent/DE2939135A1/de not_active Withdrawn
- 1979-09-27 CH CH8714/79A patent/CH648567A5/de not_active IP Right Cessation
- 1979-09-27 CA CA000336681A patent/CA1140116A/fr not_active Expired
- 1979-09-27 NL NL7907187A patent/NL7907187A/nl not_active Application Discontinuation
- 1979-09-27 GB GB7933541A patent/GB2031436B/en not_active Expired
- 1979-09-27 NO NO793111A patent/NO148922C/no unknown
- 1979-09-27 CH CH8715/79A patent/CH648568A5/de not_active IP Right Cessation
- 1979-09-27 GB GB7933540A patent/GB2031435B/en not_active Expired
- 1979-09-27 CA CA000336694A patent/CA1158640A/fr not_active Expired
- 1979-09-28 JP JP12522079A patent/JPS5569550A/ja active Pending
- 1979-09-28 BE BE0/197392A patent/BE879087A/fr not_active IP Right Cessation
- 1979-09-28 ES ES484928A patent/ES484928A1/es not_active Expired
- 1979-09-28 ES ES484926A patent/ES484926A1/es not_active Expired
- 1979-09-28 IT IT26111/79A patent/IT1125421B/it active
- 1979-09-28 IT IT26112/79A patent/IT1125422B/it active
- 1979-09-28 JP JP12522179A patent/JPS5576849A/ja active Pending
- 1979-09-28 BE BE0/197391A patent/BE879086A/fr not_active IP Right Cessation

Also Published As

Publication number	Publication date
AU5124679A (en)	1980-04-03
JPS5576849A (en)	1980-06-10
GB2031435A (en)	1980-04-23
AU526149B2 (en)	1982-12-16
ES484928A1 (es)	1980-07-01
CH648567A5 (de)	1985-03-29
FI68245B (fi)	1985-04-30
NO793112L (no)	1980-03-31
DE2939135A1 (de)	1980-04-17
NO148922B (no)	1983-10-03
FR2437400B1 (fr)	1984-06-15
ES484926A1 (es)	1980-07-01
NL7907188A (nl)	1980-04-01
AU533684B2 (en)	1983-12-08
NL7907187A (nl)	1980-04-01
GB2031436B (en)	1982-10-20
US4356119A (en)	1982-10-26
FR2437399A1 (fr)	1980-04-25
FI68244C (fi)	1985-08-12
NO793111L (no)	1980-03-31
BE879086A (fr)	1980-03-28
NO148923C (no)	1984-01-11
FR2437400A1 (fr)	1980-04-25
IT1125421B (it)	1986-05-14
FR2437399B1 (fr)	1983-01-28
AU5124579A (en)	1980-04-03
GB2031435B (en)	1982-11-10
FI68244B (fi)	1985-04-30
CA1140116A (fr)	1983-01-25
SE7907939L (sv)	1980-03-29
JPS5569550A (en)	1980-05-26
ATA634679A (de)	1983-12-15
BE879087A (fr)	1980-03-28
NO148922C (no)	1984-01-11
NO148923B (no)	1983-10-03
IT7926112A0 (it)	1979-09-28
IT1125422B (it)	1986-05-14
SE7907938L (sv)	1980-03-29
AT375338B (de)	1984-07-25
DE2939109A1 (de)	1980-04-10
GB2031436A (en)	1980-04-23
CH648568A5 (de)	1985-03-29
CA1158640A (fr)	1983-12-13
FI793001A7 (fi)	1980-03-29
IT7926111A0 (it)	1979-09-28
FI793002A7 (fi)	1980-03-29

Legal Events

Date	Code	Title	Description
2004-08-31	MM	Patent lapsed	Owner name: NORDISK INSULINLABORATORIUM

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CN100540565C (zh)	2009-09-16	修饰的Exendins及其应用
JPH06501950A (ja)	1994-03-03	環状ペプチド、その調製法およびその薬理組成物としての使用
US4237046A (en)	1980-12-02	Polypeptides and methods of preparation
JPH0273100A (ja)	1990-03-13	医薬用化合物
AU641366B2 (en)	1993-09-23	Peptide compounds
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US4397842A (en)	1983-08-09	Peptides having thymopoietin-like activity
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