JP5269766B2 - インスリン誘導体 - Google Patents
インスリン誘導体 Download PDFInfo
- Publication number
- JP5269766B2 JP5269766B2 JP2009508372A JP2009508372A JP5269766B2 JP 5269766 B2 JP5269766 B2 JP 5269766B2 JP 2009508372 A JP2009508372 A JP 2009508372A JP 2009508372 A JP2009508372 A JP 2009508372A JP 5269766 B2 JP5269766 B2 JP 5269766B2
- Authority
- JP
- Japan
- Prior art keywords
- insulin
- group
- cooh
- amide
- glu
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 title claims description 675
- 239000004026 insulin derivative Substances 0.000 title claims description 283
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- 108090001061 Insulin Proteins 0.000 claims description 176
- 229940125396 insulin Drugs 0.000 claims description 175
- 229910052739 hydrogen Inorganic materials 0.000 claims description 150
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 144
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 136
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 133
- -1 or H 2 - aryl Chemical group 0.000 claims description 114
- 235000001014 amino acid Nutrition 0.000 claims description 68
- 150000001413 amino acids Chemical class 0.000 claims description 67
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 66
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 54
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 48
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 47
- 125000001424 substituent group Chemical group 0.000 claims description 46
- 125000000539 amino acid group Chemical group 0.000 claims description 45
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- 206010012601 diabetes mellitus Diseases 0.000 claims description 16
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 15
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 14
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 8
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 8
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 230000002685 pulmonary effect Effects 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 6
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- 238000000034 method Methods 0.000 description 111
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 72
- 229940024606 amino acid Drugs 0.000 description 64
- 229910052717 sulfur Chemical group 0.000 description 63
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 54
- 229910052760 oxygen Inorganic materials 0.000 description 52
- 229920000728 polyester Polymers 0.000 description 46
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- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 42
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 42
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 39
- 239000011593 sulfur Chemical group 0.000 description 39
- 125000000732 arylene group Chemical group 0.000 description 38
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 36
- 239000001301 oxygen Chemical group 0.000 description 36
- 150000001875 compounds Chemical class 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 125000005549 heteroarylene group Chemical group 0.000 description 30
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 23
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- 125000005842 heteroatom Chemical group 0.000 description 22
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
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- 239000000654 additive Substances 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 17
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- 125000001931 aliphatic group Chemical group 0.000 description 16
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- 150000003536 tetrazoles Chemical class 0.000 description 16
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
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- 108091028043 Nucleic acid sequence Proteins 0.000 description 14
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- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 13
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- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 12
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- 239000002243 precursor Substances 0.000 description 1
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- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
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- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229940099315 rimadyl Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
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- 238000013222 sprague-dawley male rat Methods 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
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- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LOUXKPQFYICXOW-UHFFFAOYSA-N tert-butyl 3-(12-methoxy-12-oxododecyl)benzoate Chemical compound COC(=O)CCCCCCCCCCCC1=CC=CC(C(=O)OC(C)(C)C)=C1 LOUXKPQFYICXOW-UHFFFAOYSA-N 0.000 description 1
- UOEYILQHHVNJIV-UHFFFAOYSA-N tert-butyl 3-(4-iodophenyl)propanoate Chemical compound CC(C)(C)OC(=O)CCC1=CC=C(I)C=C1 UOEYILQHHVNJIV-UHFFFAOYSA-N 0.000 description 1
- XZUWLKIILSZGIR-UHFFFAOYSA-N tert-butyl 3-iodobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC(I)=C1 XZUWLKIILSZGIR-UHFFFAOYSA-N 0.000 description 1
- PZNFBLINFISYQI-UHFFFAOYSA-N tert-butyl 4-(11-methoxy-11-oxoundecyl)benzoate Chemical compound COC(=O)CCCCCCCCCCC1=CC=C(C(=O)OC(C)(C)C)C=C1 PZNFBLINFISYQI-UHFFFAOYSA-N 0.000 description 1
- WFIZBWFDAQDFTQ-UHFFFAOYSA-N tert-butyl 4-(12-methoxy-12-oxododecyl)benzoate Chemical compound COC(=O)CCCCCCCCCCCC1=CC=C(C(=O)OC(C)(C)C)C=C1 WFIZBWFDAQDFTQ-UHFFFAOYSA-N 0.000 description 1
- JSIJRSPZKINIJP-UHFFFAOYSA-N tert-butyl 4-[11-(2,5-dioxopyrrolidin-1-yl)oxy-11-oxoundecyl]benzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=CC=C1CCCCCCCCCCC(=O)ON1C(=O)CCC1=O JSIJRSPZKINIJP-UHFFFAOYSA-N 0.000 description 1
- XSABNZGBISTKMV-UHFFFAOYSA-N tert-butyl 4-[11-(2,5-dioxopyrrolidin-1-yl)oxy-11-oxoundecyl]benzoate;4-[11-[4-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]undecanoylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)C1=CC=C(CCCCCCCCCCC(=O)NCCCC(O)=O)C=C1.C1=CC(C(=O)OC(C)(C)C)=CC=C1CCCCCCCCCCC(=O)ON1C(=O)CCC1=O XSABNZGBISTKMV-UHFFFAOYSA-N 0.000 description 1
- AADOOEAGINMNLL-UHFFFAOYSA-N tert-butyl 4-[11-[[4-(2,5-dioxopyrrolidin-1-yl)oxy-4-oxobutyl]amino]-11-oxoundecyl]benzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=CC=C1CCCCCCCCCCC(=O)NCCCC(=O)ON1C(=O)CCC1=O AADOOEAGINMNLL-UHFFFAOYSA-N 0.000 description 1
- ZOWWWIQWPNUCMF-UHFFFAOYSA-N tert-butyl 4-iodobenzoate 4-iodobenzoic acid Chemical compound IC1=CC=C(C(=O)O)C=C1.C(C)(C)(C)OC(C1=CC=C(C=C1)I)=O ZOWWWIQWPNUCMF-UHFFFAOYSA-N 0.000 description 1
- KJHXSOOIOVLNPZ-UHFFFAOYSA-N tert-butyl thiophene-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CS1 KJHXSOOIOVLNPZ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 229940070384 ventolin Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- 238000001262 western blot Methods 0.000 description 1
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- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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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
- C07K14/62—Insulins
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06113711 | 2006-05-09 | ||
| EP06113711.3 | 2006-05-09 | ||
| EP06118254 | 2006-08-01 | ||
| EP06118254.9 | 2006-08-01 | ||
| PCT/EP2007/054439 WO2007128815A1 (en) | 2006-05-09 | 2007-05-08 | Insulin derivative |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009536178A JP2009536178A (ja) | 2009-10-08 |
| JP2009536178A5 JP2009536178A5 (enExample) | 2010-06-17 |
| JP5269766B2 true JP5269766B2 (ja) | 2013-08-21 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009508372A Expired - Fee Related JP5269766B2 (ja) | 2006-05-09 | 2007-05-08 | インスリン誘導体 |
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| Country | Link |
|---|---|
| US (1) | US8796205B2 (enExample) |
| EP (1) | EP2024390B1 (enExample) |
| JP (1) | JP5269766B2 (enExample) |
| ES (1) | ES2553154T3 (enExample) |
| WO (1) | WO2007128815A1 (enExample) |
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| ES2438145T3 (es) | 2005-02-02 | 2014-01-16 | Novo Nordisk A/S | Nuevos derivados de insulina |
| ES2490243T3 (es) | 2005-02-02 | 2014-09-03 | Novo Nordisk A/S | Derivados de insulina |
| JP4808785B2 (ja) | 2005-12-28 | 2011-11-02 | ノボ・ノルデイスク・エー／エス | インスリン組成物および組成物の製造方法 |
| JP5202338B2 (ja) * | 2006-02-27 | 2013-06-05 | ノボ・ノルデイスク・エー／エス | 新規インシュリン誘導体 |
| AU2007247109B2 (en) | 2006-05-09 | 2012-03-15 | Novo Nordisk A/S | Insulin derivative |
| US9018161B2 (en) | 2006-09-22 | 2015-04-28 | Novo Nordisk A/S | Protease resistant insulin analogues |
| US9387176B2 (en) | 2007-04-30 | 2016-07-12 | Novo Nordisk A/S | Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein |
| ES2744384T3 (es) | 2007-06-13 | 2020-02-24 | Novo Nordisk As | Formulación farmacéutica que comprende un derivado de insulina |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| JP5715418B2 (ja) | 2007-11-08 | 2015-05-07 | ノボ・ノルデイスク・エー／エス | インスリン誘導体 |
| ES2618073T3 (es) | 2008-03-14 | 2017-06-20 | Novo Nordisk A/S | Análogos de insulina estabilizados frente a proteasas |
| HUE032284T2 (en) | 2008-03-18 | 2017-09-28 | Novo Nordisk As | Protease-stabilized, acylated insulin analogues |
| EP2352513B1 (en) | 2008-10-30 | 2016-09-14 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| WO2011080102A2 (en) | 2009-12-16 | 2011-07-07 | Novo Nordisk A/S | Glp-1 analogues and derivatives |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| DE102010015123A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi-Aventis Deutschland Gmbh | Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| HRP20191793T1 (hr) | 2010-10-27 | 2019-12-27 | Novo Nordisk A/S | Liječenje dijabetesa melitusa injekcijama inzulina koje se primijenjuje u različitim intervalima injiciranja |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2836508B1 (en) | 2012-04-11 | 2016-06-29 | Novo Nordisk A/S | Insulin formulations |
| CN107312039B (zh) | 2012-08-30 | 2019-06-25 | 江苏豪森药业集团有限公司 | 一种替诺福韦前药的制备方法 |
| EP2991672A1 (en) | 2013-04-30 | 2016-03-09 | Novo Nordisk A/S | Novel administration regime |
| JP6499184B2 (ja) * | 2013-10-07 | 2019-04-10 | ノヴォ ノルディスク アー／エス | インスリン類似体の新規な誘導体 |
| AR099569A1 (es) | 2014-02-28 | 2016-08-03 | Novo Nordisk As | Derivados de insulina y los usos médicos de estos |
| EP3821905B1 (en) | 2016-12-16 | 2022-10-12 | Novo Nordisk A/S | Insulin containing pharmaceutical compositions |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| SG11202106168VA (en) | 2018-12-11 | 2021-07-29 | Sanofi Sa | Insulin analogs having reduced insulin receptor binding affinity |
| WO2021009027A1 (en) | 2019-07-12 | 2021-01-21 | Novo Nordisk A/S | High concentration insulin formulation |
| CN113651796A (zh) * | 2021-07-20 | 2021-11-16 | 海南海神同洲制药有限公司 | 一种硝酸舍他康唑中间体的制备方法 |
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| US3528960A (en) | 1968-10-07 | 1970-09-15 | Lilly Co Eli | N-carboxyaroyl insulins |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| PH25772A (en) | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| NZ222907A (en) | 1986-12-16 | 1990-08-28 | Novo Industri As | Preparation for intranasal administration containing a phospholipid absorption enhancing system |
| JPH04502465A (ja) | 1988-12-23 | 1992-05-07 | ノボ ノルディスク アクティーゼルスカブ | ヒトインシュリン類似物質 |
| PT93057B (pt) | 1989-02-09 | 1995-12-29 | Lilly Co Eli | Processo para a preparacao de analogos da insulina |
| KR930001305B1 (ko) | 1989-10-19 | 1993-02-25 | 니뽕 유우시 가부시끼가이샤 | 당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type) |
| JP3018463B2 (ja) | 1989-10-19 | 2000-03-13 | 日本油脂株式会社 | グルコース応答性薬物放出複合体 |
| DK10191D0 (da) | 1991-01-22 | 1991-01-22 | Novo Nordisk As | Hidtil ukendte peptider |
| US6869930B1 (en) | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| BR9407508A (pt) | 1993-09-17 | 1997-01-07 | Novo Nordisk As | Derivado de insulina composição farmaceutica e processo para o tratamento de diabete em um paciente com necessidade deste tratamento |
| US6011007A (en) | 1993-09-17 | 2000-01-04 | Novo Nordisk A/S | Acylated insulin |
| US5905140A (en) | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
| US5898067A (en) | 1997-02-07 | 1999-04-27 | Novo Nordisk A/S | Crystallization of proteins |
| WO1999034821A1 (en) | 1998-01-09 | 1999-07-15 | Novo Nordisk A/S | Stabilised insulin compositions |
| WO2003075950A1 (en) | 2002-03-13 | 2003-09-18 | Novo Nordisk A/S | Minimising body weight gain in insulin treatment |
| US20040138099A1 (en) | 2002-11-29 | 2004-07-15 | Draeger Eberhard Kurt | Insulin administration regimens for the treatment of subjects with diabetes |
| EP1644411A2 (en) | 2003-07-11 | 2006-04-12 | Novo Nordisk A/S | Stabilised insulin compositions |
| US20060183667A1 (en) | 2003-07-11 | 2006-08-17 | Novo Nordisk A/S | Stabilised insulin compositions |
| CA2531988C (en) | 2003-08-05 | 2016-06-28 | Novo Nordisk A/S | Novel insulin derivatives |
| JP2007532096A (ja) | 2003-11-14 | 2007-11-15 | ノボ ノルディスク アクティーゼルスカブ | アシル化されたインスリンの製造方法 |
| WO2006008238A1 (en) | 2004-07-16 | 2006-01-26 | Novo Nordisk A/S | Method for selective acylation |
| ES2490243T3 (es) | 2005-02-02 | 2014-09-03 | Novo Nordisk A/S | Derivados de insulina |
| ES2438145T3 (es) * | 2005-02-02 | 2014-01-16 | Novo Nordisk A/S | Nuevos derivados de insulina |
| JP4808785B2 (ja) | 2005-12-28 | 2011-11-02 | ノボ・ノルデイスク・エー／エス | インスリン組成物および組成物の製造方法 |
| JP5202338B2 (ja) | 2006-02-27 | 2013-06-05 | ノボ・ノルデイスク・エー／エス | 新規インシュリン誘導体 |
| US20090069215A1 (en) | 2006-03-13 | 2009-03-12 | Novo Nordisk A/S | Acylated Single Chain Insulin |
| AU2007247109B2 (en) | 2006-05-09 | 2012-03-15 | Novo Nordisk A/S | Insulin derivative |
| ES2744384T3 (es) | 2007-06-13 | 2020-02-24 | Novo Nordisk As | Formulación farmacéutica que comprende un derivado de insulina |
| JP5715418B2 (ja) | 2007-11-08 | 2015-05-07 | ノボ・ノルデイスク・エー／エス | インスリン誘導体 |
| EP2352513B1 (en) | 2008-10-30 | 2016-09-14 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| WO2011141407A1 (en) | 2010-05-10 | 2011-11-17 | Novo Nordisk A/S | Process for the preparation of insulin-zinc complexes |
-
2007
- 2007-05-08 EP EP07728892.6A patent/EP2024390B1/en not_active Not-in-force
- 2007-05-08 JP JP2009508372A patent/JP5269766B2/ja not_active Expired - Fee Related
- 2007-05-08 US US12/297,914 patent/US8796205B2/en not_active Expired - Fee Related
- 2007-05-08 ES ES07728892.6T patent/ES2553154T3/es active Active
- 2007-05-08 WO PCT/EP2007/054439 patent/WO2007128815A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007128815A1 (en) | 2007-11-15 |
| US20090105121A1 (en) | 2009-04-23 |
| JP2009536178A (ja) | 2009-10-08 |
| ES2553154T3 (es) | 2015-12-04 |
| EP2024390B1 (en) | 2015-08-19 |
| EP2024390A1 (en) | 2009-02-18 |
| US8796205B2 (en) | 2014-08-05 |
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