CS202568B2 - Process for preparing polypeptides - Google Patents
Process for preparing polypeptides Download PDFInfo
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- CS202568B2 CS202568B2 CS772289A CS228977A CS202568B2 CS 202568 B2 CS202568 B2 CS 202568B2 CS 772289 A CS772289 A CS 772289A CS 228977 A CS228977 A CS 228977A CS 202568 B2 CS202568 B2 CS 202568B2
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- Czechoslovakia
- Prior art keywords
- formula
- group
- carbon atoms
- radical
- gly
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 42
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 34
- 229920001184 polypeptide Polymers 0.000 title claims description 25
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 238000000034 method Methods 0.000 claims description 82
- 125000004432 carbon atom Chemical group C* 0.000 claims description 76
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 43
- 150000003254 radicals Chemical class 0.000 claims description 33
- -1 D-Lys amino acids Chemical class 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 24
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 22
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 20
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 12
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 235000001014 amino acid Nutrition 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical group CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 8
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Chemical group OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 6
- 125000000030 D-alanine group Chemical group [H]N([H])[C@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims description 6
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical group OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 6
- 125000000734 D-serino group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical group C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 claims description 5
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims description 5
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 5
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 4
- AGPKZVBTJJNPAG-RFZPGFLSSA-N D-Isoleucine Chemical compound CC[C@@H](C)[C@@H](N)C(O)=O AGPKZVBTJJNPAG-RFZPGFLSSA-N 0.000 claims description 4
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 3
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims 5
- LSPKYLAFTPBWIL-BYPYZUCNSA-N Glu-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(O)=O LSPKYLAFTPBWIL-BYPYZUCNSA-N 0.000 claims 4
- FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 claims 2
- 108010040443 aspartyl-aspartic acid Proteins 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical compound O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 claims 1
- KLAONOISLHWJEE-QWRGUYRKSA-N Phe-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 KLAONOISLHWJEE-QWRGUYRKSA-N 0.000 claims 1
- 150000001371 alpha-amino acids Chemical class 0.000 claims 1
- 235000008206 alpha-amino acids Nutrition 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 239000000203 mixture Substances 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 238000001704 evaporation Methods 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 21
- 239000003208 petroleum Substances 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- 239000000126 substance Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 230000008020 evaporation Effects 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- 229960001701 chloroform Drugs 0.000 description 15
- 239000012429 reaction media Substances 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 150000002148 esters Chemical group 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000002808 molecular sieve Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 8
- 230000000202 analgesic effect Effects 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 229920005654 Sephadex Polymers 0.000 description 6
- 239000012507 Sephadex™ Substances 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical class C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 239000005909 Kieselgur Substances 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 150000004702 methyl esters Chemical group 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
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- 239000003054 catalyst Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
- 239000011736 potassium bicarbonate Substances 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
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- MCRMUCXATQAAMN-HNNXBMFYSA-N (2s)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=C(O)C=C1 MCRMUCXATQAAMN-HNNXBMFYSA-N 0.000 description 3
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- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 3
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- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 3
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
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- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
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- 210000004556 brain Anatomy 0.000 description 2
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- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
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- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- ZGONRPXUNVTWTA-UHFFFAOYSA-N methyl 2-isocyanatoacetate Chemical compound COC(=O)CN=C=O ZGONRPXUNVTWTA-UHFFFAOYSA-N 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 1
- YKOQQFDCCBKROY-UHFFFAOYSA-N n,n-diethylpropanamide Chemical compound CCN(CC)C(=O)CC YKOQQFDCCBKROY-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 229960003893 phenacetin Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 1
- 229960003111 prochlorperazine Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- FNNIAKKPBXJGNJ-UHFFFAOYSA-N pyrazolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCN1 FNNIAKKPBXJGNJ-UHFFFAOYSA-N 0.000 description 1
- 238000013102 re-test Methods 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012260 resinous material Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- 238000005507 spraying Methods 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
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- 238000004809 thin layer chromatography Methods 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
- C07K14/665—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- C07K14/70—Enkephalins
- C07K14/702—Enkephalins with at least 1 amino acid in D-form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB14362/76A GB1523812A (en) | 1976-04-08 | 1976-04-08 | Polypeptide |
| GB2106376 | 1976-05-21 | ||
| GB2205576 | 1976-05-27 | ||
| GB2929876 | 1976-07-14 | ||
| GB4483876 | 1976-10-28 | ||
| GB4483776 | 1976-10-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS202568B2 true CS202568B2 (en) | 1981-01-30 |
Family
ID=27546664
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS772289A CS202568B2 (en) | 1976-04-08 | 1977-04-06 | Process for preparing polypeptides |
Country Status (13)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ303858B6 (cs) * | 2012-05-11 | 2013-05-29 | Zetor Tractors A.S. | Usporádání reverzacní dvoutoké prevodovky, zejména pro motorová vozidla a stavební stroje, s dvema vetvemi toku výkonu |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2730851A1 (de) * | 1976-07-19 | 1978-01-26 | Sandoz Ag | Neu polypeptidderivate, ihre herstellung und verwendung |
| FR2359817A1 (fr) * | 1976-07-27 | 1978-02-24 | Reckitt & Colmann Prod Ltd | Nouveaux peptides, leur procede de preparation et composition therapeutique les contenant |
| PT66982B (en) * | 1976-09-01 | 1979-02-13 | Coy David Howard | Process for preparing novel methionine enkephalin derivatives |
| HU178001B (en) * | 1976-09-16 | 1982-02-28 | Gyogyszekutato Intezet | Process for preparing new pentapeptides with morphine-like activity and derivatives thereof |
| US4259234A (en) * | 1976-09-27 | 1981-03-31 | Eli Lilly And Company | Analgesic compounds |
| DE2752341A1 (de) * | 1976-11-23 | 1978-05-24 | Wellcome Found | Biologisch wirksame amide, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische formulierungen |
| DE2862327D1 (en) * | 1977-07-22 | 1983-11-10 | Wellcome Found | Pentapeptide-n-alkylamides and their acid addition salts, methods for preparation of these compounds and pharmaceutical formulations containing them |
| GB1604850A (en) * | 1977-11-24 | 1981-12-16 | Wellcome Found | Biologically active peptides |
| US4178371A (en) * | 1977-12-15 | 1979-12-11 | Reckitt & Colman Products Limited | Tetrapeptide derivatives |
| FR2424253A1 (fr) * | 1978-04-27 | 1979-11-23 | Brun Lab Sa Le | Nouveaux derives de peptides analogues des enkephalines, leur procede de preparation et leur application therapeutique |
| US4278596A (en) * | 1978-08-08 | 1981-07-14 | American Home Products Corporation | Analgesic pentapeptides |
| CA1175810A (en) * | 1979-03-30 | 1984-10-09 | Frank A. Momany | Synthetic peptides having pituitary growth hormone releasing activity |
| DE2933947A1 (de) * | 1979-08-22 | 1981-03-12 | Hoechst Ag, 6000 Frankfurt | Neue peptidamide und verfahren zu ihrer herstellung. |
| JPS5692846A (en) * | 1979-12-27 | 1981-07-27 | Takeda Chem Ind Ltd | Tetrapeptide derivative and its preparation |
| FR2488253A1 (fr) * | 1980-08-08 | 1982-02-12 | Roques Bernard | Nouveaux peptides et leur application en therapeutique |
| US4495178A (en) * | 1983-10-06 | 1985-01-22 | G. D. Searle & Co. | Enkephalin analogs |
| JP2604268B2 (ja) * | 1990-04-09 | 1997-04-30 | 富士写真フイルム株式会社 | ペプチド誘導体両親媒性化合物、その中間体、ペプチド誘導体両親媒性化合物を用いたリポソームおよび薄膜 |
| EP1975153A3 (en) * | 2003-05-30 | 2010-03-31 | Prozymex A/S | Protease inhibitors |
| JP6149279B2 (ja) * | 2011-02-09 | 2017-06-21 | オーガノバランス ゲーエムベーハー | 皮膚状態の治療に使用するためのペプチド |
| JP2013043885A (ja) * | 2011-08-26 | 2013-03-04 | Kansai Bunri Sogo Gakuen | デヒドロアミノ酸含有グリセロール誘導体 |
| CA3082827A1 (en) | 2017-11-17 | 2019-05-23 | Cytogel Pharma, Llc | Polymer agonists of mu opioid receptors |
-
1977
- 1977-03-28 NZ NZ183712A patent/NZ183712A/xx unknown
- 1977-03-31 AU AU23819/77A patent/AU510760B2/en not_active Expired
- 1977-04-04 FI FI771049A patent/FI771049A7/fi not_active Application Discontinuation
- 1977-04-06 DK DK158077A patent/DK158077A/da not_active IP Right Cessation
- 1977-04-06 SE SE7704043A patent/SE7704043L/ not_active Application Discontinuation
- 1977-04-06 HU HU77IE774A patent/HU176260B/hu unknown
- 1977-04-06 CS CS772289A patent/CS202568B2/cs unknown
- 1977-04-07 DE DE19772715803 patent/DE2715803A1/de not_active Withdrawn
- 1977-04-07 DD DD7700198316A patent/DD130348A5/xx unknown
- 1977-04-07 FR FR7710668A patent/FR2347336A1/fr active Granted
- 1977-04-08 SU SU772470259A patent/SU904518A3/ru active
- 1977-04-08 PL PL1977197302A patent/PL106210B1/pl unknown
- 1977-04-08 JP JP4023077A patent/JPS52139039A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ303858B6 (cs) * | 2012-05-11 | 2013-05-29 | Zetor Tractors A.S. | Usporádání reverzacní dvoutoké prevodovky, zejména pro motorová vozidla a stavební stroje, s dvema vetvemi toku výkonu |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2347336B1 (enrdf_load_stackoverflow) | 1980-07-18 |
| NZ183712A (en) | 1979-10-25 |
| AU510760B2 (en) | 1980-07-10 |
| PL197302A1 (pl) | 1978-02-13 |
| JPS52139039A (en) | 1977-11-19 |
| PL106210B1 (pl) | 1979-12-31 |
| DE2715803A1 (de) | 1977-10-27 |
| FR2347336A1 (fr) | 1977-11-04 |
| DK158077A (da) | 1977-10-09 |
| DD130348A5 (de) | 1978-03-22 |
| FI771049A7 (enrdf_load_stackoverflow) | 1977-10-09 |
| HU176260B (en) | 1981-01-28 |
| SU904518A3 (ru) | 1982-02-07 |
| SE7704043L (sv) | 1977-10-09 |
| AU2381977A (en) | 1978-10-05 |
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