NO830011L - Fremgangsmaate for fremstilling av farmakologisk aktive n-acyl-peptider. - Google Patents
Fremgangsmaate for fremstilling av farmakologisk aktive n-acyl-peptider.Info
- Publication number
- NO830011L NO830011L NO830011A NO830011A NO830011L NO 830011 L NO830011 L NO 830011L NO 830011 A NO830011 A NO 830011A NO 830011 A NO830011 A NO 830011A NO 830011 L NO830011 L NO 830011L
- Authority
- NO
- Norway
- Prior art keywords
- lower alkyl
- carboxy
- hexadecanoyloxyoctadecanoyl
- valyl
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 67
- 238000002360 preparation method Methods 0.000 title claims description 33
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 110
- 150000001875 compounds Chemical class 0.000 claims abstract description 88
- 150000003839 salts Chemical class 0.000 claims abstract description 61
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 9
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- 230000003171 anti-complementary effect Effects 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 12
- -1 3-hexadecanoyloxyoctadecanoyl Chemical group 0.000 claims description 121
- 229960002989 glutamic acid Drugs 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 239000004473 Threonine Substances 0.000 claims description 16
- 229960002898 threonine Drugs 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 8
- IHSNQUNHINYDDN-JTQLQIEISA-N (2s)-2-(benzylamino)pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NCC1=CC=CC=C1 IHSNQUNHINYDDN-JTQLQIEISA-N 0.000 claims description 6
- 229960005261 aspartic acid Drugs 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 229960003080 taurine Drugs 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 3
- SELLFVRARCGIDX-UHFFFAOYSA-N 2-[[2-(3-hexadecanoyloxyoctadecanoylamino)acetyl]amino]ethanesulfonic acid Chemical compound CCCCCCCCCCCCCCCC(CC(=O)NCC(=O)NCCS(O)(=O)=O)OC(=O)CCCCCCCCCCCCCCC SELLFVRARCGIDX-UHFFFAOYSA-N 0.000 claims description 2
- OJTJKAUNOLVMDX-LBPRGKRZSA-N (2s)-6-amino-2-(phenylmethoxycarbonylamino)hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 OJTJKAUNOLVMDX-LBPRGKRZSA-N 0.000 claims 1
- 238000007257 deesterification reaction Methods 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 abstract description 2
- 206010052895 Coronary artery insufficiency Diseases 0.000 abstract description 2
- 208000024781 Immune Complex disease Diseases 0.000 abstract description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 abstract description 2
- 208000025747 Rheumatic disease Diseases 0.000 abstract description 2
- 208000006011 Stroke Diseases 0.000 abstract description 2
- 230000002490 cerebral effect Effects 0.000 abstract description 2
- 201000008383 nephritis Diseases 0.000 abstract description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 230000001567 anti-fibrinolytic effect Effects 0.000 abstract 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 239000000203 mixture Substances 0.000 description 75
- 239000000243 solution Substances 0.000 description 70
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 61
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 54
- 238000002329 infrared spectrum Methods 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 38
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 239000002904 solvent Substances 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- 239000000843 powder Substances 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- 239000013078 crystal Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 238000004519 manufacturing process Methods 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- UKZPVOXSOKDEQO-UHFFFAOYSA-N 3-hexadecanoyloxyoctadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(CC(O)=O)OC(=O)CCCCCCCCCCCCCCC UKZPVOXSOKDEQO-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 238000006722 reduction reaction Methods 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 11
- 125000005907 alkyl ester group Chemical group 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 150000002148 esters Chemical group 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 9
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 6
- 235000011054 acetic acid Nutrition 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000001589 carboacyl group Chemical group 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
- 238000001816 cooling Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 229960004295 valine Drugs 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 238000010531 catalytic reduction reaction Methods 0.000 description 4
- DHQUQYYPAWHGAR-KRWDZBQOSA-N dibenzyl (2s)-2-aminopentanedioate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)CC(=O)OCC1=CC=CC=C1 DHQUQYYPAWHGAR-KRWDZBQOSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000003480 fibrinolytic effect Effects 0.000 description 4
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 229960005190 phenylalanine Drugs 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- BHJZMWAQZFQIDO-UHFFFAOYSA-N 3-octadec-9-enoyloxyicos-11-enoic acid Chemical compound CCCCCCCCC=CCCCCCCCC(CC(O)=O)OC(=O)CCCCCCCC=CCCCCCCCC BHJZMWAQZFQIDO-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910017052 cobalt Inorganic materials 0.000 description 3
- 239000010941 cobalt Substances 0.000 description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 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 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YSFFMBPFDFKWQL-XZEQTHJSSA-N (2s)-2-(2-hexadecanoyloxyhexadecanoylamino)-3-methylbutanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C(=O)N[C@@H](C(C)C)C(O)=O)CCCCCCCCCCCCCC YSFFMBPFDFKWQL-XZEQTHJSSA-N 0.000 description 2
- CNEBDXSTDGRJEC-SHXCFHCCSA-N (2s)-2-(3-hexadecanoyloxyoctadecanoylamino)-3-methylbutanoic acid Chemical compound CCCCCCCCCCCCCCCC(CC(=O)N[C@@H](C(C)C)C(O)=O)OC(=O)CCCCCCCCCCCCCCC CNEBDXSTDGRJEC-SHXCFHCCSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- JKUQUGBLNYRQLK-UHFFFAOYSA-N 15-methyl-3-(13-methyltetradecanoyloxy)hexadecanoic acid Chemical compound CC(C)CCCCCCCCCCCC(CC(O)=O)OC(=O)CCCCCCCCCCCC(C)C JKUQUGBLNYRQLK-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- JVGHMUKTIXAQFE-UHFFFAOYSA-N 2-(3-hexadecanoyloxyoctadecanoylamino)acetic acid Chemical compound CCCCCCCCCCCCCCCC(CC(=O)NCC(O)=O)OC(=O)CCCCCCCCCCCCCCC JVGHMUKTIXAQFE-UHFFFAOYSA-N 0.000 description 2
- KLBCBDGSFYFOEK-UHFFFAOYSA-N 2-hexadecanoyloxyhexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C(O)=O)CCCCCCCCCCCCCC KLBCBDGSFYFOEK-UHFFFAOYSA-N 0.000 description 2
- JGHSBPIZNUXPLA-UHFFFAOYSA-N 2-hydroxyhexadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)C(O)=O JGHSBPIZNUXPLA-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
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- 125000001312 palmitoyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002460 pentacosyl group Chemical group [H]C([*])([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])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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010268 sodium methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000003696 stearoyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- WORJEOGGNQDSOE-ASTXPPQBSA-N trichloro(deuterio)methane;trideuterio(deuteriooxy)methane Chemical compound [2H]C(Cl)(Cl)Cl.[2H]OC([2H])([2H])[2H] WORJEOGGNQDSOE-ASTXPPQBSA-N 0.000 description 1
- 125000002469 tricosyl group Chemical group [H]C([*])([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])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])C([H])([H])[H] 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([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 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8200212 | 1982-01-05 | ||
| GB8215910 | 1982-06-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO830011L true NO830011L (no) | 1983-07-06 |
Family
ID=26281659
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO830011A NO830011L (no) | 1982-01-05 | 1983-01-04 | Fremgangsmaate for fremstilling av farmakologisk aktive n-acyl-peptider. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4643990A (fr) |
| EP (1) | EP0085255B1 (fr) |
| KR (1) | KR840003235A (fr) |
| AT (1) | ATE22087T1 (fr) |
| AU (1) | AU9173582A (fr) |
| DE (1) | DE3273256D1 (fr) |
| DK (1) | DK579682A (fr) |
| ES (1) | ES518771A0 (fr) |
| FI (1) | FI824453L (fr) |
| GR (1) | GR77060B (fr) |
| NO (1) | NO830011L (fr) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0099709A3 (fr) * | 1982-07-19 | 1985-11-13 | Imperial Chemical Industries Plc | Dérivés d'amide |
| EP0136879A3 (fr) * | 1983-09-30 | 1987-01-07 | Yamanouchi Pharmaceutical Co., Ltd. | Dérivés d'acides gras et procédés de leur préparation |
| DE3423582A1 (de) * | 1984-06-27 | 1986-01-09 | Bayer Ag, 5090 Leverkusen | Substituierte 5-acylamino-1-phenylpyrazole |
| DE3700173A1 (de) * | 1987-01-05 | 1988-07-14 | Hoechst Ag | Verfahren zur herstellung von lipophilen aminosaeurederivaten sowie lipophile aminosaeurederivate |
| FR2611205B1 (fr) * | 1987-02-20 | 1990-03-02 | Serbio | Dipeptides, procede de preparation et utilisation dans le dosage de proteases |
| US5464825A (en) * | 1991-03-14 | 1995-11-07 | Cornell Research Foundation, Inc. | Raising glutathione equivalent levels using N-acyl glutathione monoesters |
| WO1994025052A1 (fr) * | 1993-05-03 | 1994-11-10 | Cornell Research Foundation, Inc. | Utilisation de diesters de glutathione |
| US5627210A (en) * | 1995-02-06 | 1997-05-06 | Chiron Corporation | Branched combinatorial libraries |
| AU1180200A (en) * | 1999-11-12 | 2001-05-30 | Fujimoto Brothers Co., Ltd. | Antiinflammatory medicinal compositions |
| US7498309B2 (en) * | 2003-11-29 | 2009-03-03 | Sangstat Medical Corporation | Pharmaceutical compositions for bioactive peptide agents |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL109134C (fr) * | 1900-01-01 | |||
| NL279057A (fr) * | 1900-01-01 | |||
| FR2907E (fr) * | 1903-03-09 | 1904-07-12 | Brunet Loiseau Freres Soc | Interrupteur-vibreur pour bobine d'induction, en vue de l'allumage des moteurs |
| FR4629E (fr) * | 1904-04-21 | 1905-09-02 | Jean Victorin Poplawski | Générateur de vapeur à mèche |
| FR7648E (fr) * | 1906-02-26 | 1907-09-17 | Georges Clesse | Dispositif de changement de vitesse et de renversement de marche pour voitures automobiles |
| BE568629A (fr) * | 1957-07-11 | |||
| JPS4211925Y1 (fr) * | 1966-02-09 | 1967-07-05 | ||
| DE1593858A1 (de) * | 1967-03-02 | 1970-10-29 | Hoechst Ag | Verfahren zur Herstellung tyrosinhaltiger Peptide und deren Derivaten |
| JPS468685Y1 (fr) * | 1967-08-02 | 1971-03-27 | ||
| JPS46164Y1 (fr) * | 1967-09-05 | 1971-01-07 | ||
| US3893992A (en) * | 1970-11-19 | 1975-07-08 | Rohm & Haas | N-acylated peptides of amino aromatic sulfonic acids and their derivatives |
| FR2340983A1 (fr) * | 1976-02-10 | 1977-09-09 | Ugine Kuhlmann | Activateurs pour percomposes |
| LU78804A1 (de) * | 1977-12-30 | 1979-07-20 | Byk Gulden Lomberg Chem Fab | N-substituierte w-aminoalkanoyl-w-aminoalkansaeuren,ihre verwendung und verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel |
| US4205069A (en) * | 1978-09-29 | 1980-05-27 | American Home Products Corporation | Dipeptide narcotic antagonists |
| US4311640A (en) * | 1978-11-14 | 1982-01-19 | Fujisawa Pharmaceutical Co., Ltd. | Peptide, process for preparation thereof and use thereof |
| EP0011283B1 (fr) * | 1978-11-14 | 1982-07-28 | Fujisawa Pharmaceutical Co., Ltd. | Lactyl-tétrapeptide, procédé pour sa préparation et compositions pharmaceutiques le contenant |
| FR2460288A1 (fr) * | 1979-06-29 | 1981-01-23 | Rhone Poulenc Ind | Nouveaux dipeptides, leur preparation et les medicaments qui les contiennent |
| US4436726A (en) * | 1980-12-15 | 1984-03-13 | Fujisawa Pharmaceutical Co., Ltd. | N-Acylpeptide compound, processes for the preparation thereof and the pharmaceutical compositions |
-
1982
- 1982-12-21 AU AU91735/82A patent/AU9173582A/en not_active Abandoned
- 1982-12-22 GR GR70144A patent/GR77060B/el unknown
- 1982-12-23 DE DE8282306928T patent/DE3273256D1/de not_active Expired
- 1982-12-23 EP EP82306928A patent/EP0085255B1/fr not_active Expired
- 1982-12-23 US US06/452,827 patent/US4643990A/en not_active Expired - Fee Related
- 1982-12-23 AT AT82306928T patent/ATE22087T1/de active
- 1982-12-27 FI FI824453A patent/FI824453L/fi not_active Application Discontinuation
- 1982-12-30 DK DK579682A patent/DK579682A/da not_active Application Discontinuation
-
1983
- 1983-01-04 NO NO830011A patent/NO830011L/no unknown
- 1983-01-04 ES ES518771A patent/ES518771A0/es active Granted
- 1983-01-05 KR KR1019830000017A patent/KR840003235A/ko not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0085255A3 (en) | 1984-08-01 |
| DK579682A (da) | 1983-07-06 |
| EP0085255A2 (fr) | 1983-08-10 |
| GR77060B (fr) | 1984-09-05 |
| KR840003235A (ko) | 1984-08-20 |
| ES8500892A1 (es) | 1984-03-01 |
| US4643990A (en) | 1987-02-17 |
| EP0085255B1 (fr) | 1986-09-10 |
| FI824453A0 (fi) | 1982-12-27 |
| AU9173582A (en) | 1983-07-14 |
| ATE22087T1 (de) | 1986-09-15 |
| ES518771A0 (es) | 1984-03-01 |
| FI824453L (fi) | 1983-07-06 |
| DE3273256D1 (en) | 1986-10-16 |
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