CA1102317A - Traduction non-disponible - Google Patents
Traduction non-disponibleInfo
- Publication number
- CA1102317A CA1102317A CA314,012A CA314012A CA1102317A CA 1102317 A CA1102317 A CA 1102317A CA 314012 A CA314012 A CA 314012A CA 1102317 A CA1102317 A CA 1102317A
- Authority
- CA
- Canada
- Prior art keywords
- solution
- added
- amino acid
- followed
- dissolved
- 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
Links
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 title claims 8
- 108010077895 Sarcosine Proteins 0.000 title claims 4
- 229940043230 sarcosine Drugs 0.000 title claims 4
- UQBOJOOOTLPNST-UHFFFAOYSA-N Dehydroalanine Chemical compound NC(=C)C(O)=O UQBOJOOOTLPNST-UHFFFAOYSA-N 0.000 title description 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 title 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 87
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 238000010168 coupling process Methods 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 230000008878 coupling Effects 0.000 claims description 12
- 238000005859 coupling reaction Methods 0.000 claims description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 229920000642 polymer Polymers 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
- HMWKLMZSMUXKKM-JLBKCEDKSA-N (2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid hydrochloride Chemical compound Cl.C(C)(C)(C)OC(=O)N(C)CC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O HMWKLMZSMUXKKM-JLBKCEDKSA-N 0.000 claims description 2
- WBNHVLKWIWGFDZ-ONTIZHBOSA-N (2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetyl]-nitroamino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound CC(C)(C)OC(=O)N(C)CC(=O)N([N+]([O-])=O)[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WBNHVLKWIWGFDZ-ONTIZHBOSA-N 0.000 claims description 2
- 101800000021 N-terminal protease Proteins 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 238000006356 dehydrogenation reaction Methods 0.000 claims 2
- 239000003586 protic polar solvent Substances 0.000 claims 2
- 101800001415 Bri23 peptide Proteins 0.000 claims 1
- 101800000655 C-terminal peptide Proteins 0.000 claims 1
- 102400000107 C-terminal peptide Human genes 0.000 claims 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- PCAVRLKFMDMZTO-ZBKXOXPVSA-N methyl (2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-amino-3-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoate;hydrochloride Chemical compound Cl.C([C@H](NC(=O)[C@@H](N)[C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)OC)C1=CNC=N1 PCAVRLKFMDMZTO-ZBKXOXPVSA-N 0.000 claims 1
- KWSCYXZCGOKREW-KDDLROOKSA-N methyl 2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylprop-2-enoate dihydrochloride Chemical compound Cl.Cl.COC(C(NC([C@H]1N(CCC1)C([C@@H](NC([C@@H](N)[C@@H](C)CC)=O)CC1=CNC=N1)=O)=O)=CC1=CC=CC=C1)=O KWSCYXZCGOKREW-KDDLROOKSA-N 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 1
- 108010064733 Angiotensins Proteins 0.000 abstract description 3
- 102000015427 Angiotensins Human genes 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 39
- 239000000047 product Substances 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- -1 e-thyl Chemical group 0.000 description 20
- 239000011347 resin Substances 0.000 description 17
- 229920005989 resin Polymers 0.000 description 17
- 238000003756 stirring Methods 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 7
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 7
- 102400000345 Angiotensin-2 Human genes 0.000 description 7
- 101800000733 Angiotensin-2 Proteins 0.000 description 7
- 229950006323 angiotensin ii Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 7
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 229960004132 diethyl ether Drugs 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- WRSXLBCDXHDOBF-VHJJOGJUSA-N (2s)-3-(1h-imidazol-5-yl)-2-[[(2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]propanoic acid;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 WRSXLBCDXHDOBF-VHJJOGJUSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- VEYJKJORLPYVLO-RYUDHWBXSA-N Val-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 VEYJKJORLPYVLO-RYUDHWBXSA-N 0.000 description 2
- 229940022682 acetone Drugs 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000011067 equilibration Methods 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- VXYFARNRGZWHTJ-FVGYRXGTSA-N methyl (2s)-2-amino-3-(4-hydroxyphenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VXYFARNRGZWHTJ-FVGYRXGTSA-N 0.000 description 2
- JHRYVLCEDDXLLX-HOTGVXAUSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[[(2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C=C1 JHRYVLCEDDXLLX-HOTGVXAUSA-N 0.000 description 2
- QDXNCFQXVVJHOC-FUTPGTCUSA-N methyl 2-[[(2S)-1-[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S,3S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylprop-2-enoate Chemical compound COC(C(NC([C@H]1N(CCC1)C([C@@H](NC([C@@H](NC(=O)OC(C)(C)C)[C@@H](C)CC)=O)CC1=CNC=N1)=O)=O)=CC1=CC=CC=C1)=O QDXNCFQXVVJHOC-FUTPGTCUSA-N 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 2
- 239000002511 suppository base Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- KNXAIVLYDJENKJ-UWVGGRQHSA-N tert-butyl (2s)-2-[[(2s)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound COC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C KNXAIVLYDJENKJ-UWVGGRQHSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 108010009962 valyltyrosine Proteins 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/14—Angiotensins: Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84499977A | 1977-10-25 | 1977-10-25 | |
| US844,999 | 1977-10-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1102317A true CA1102317A (fr) | 1981-06-02 |
Family
ID=25294159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA314,012A Expired CA1102317A (fr) | 1977-10-25 | 1978-10-24 | Traduction non-disponible |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JPS5484574A (fr) |
| AU (1) | AU4098978A (fr) |
| CA (1) | CA1102317A (fr) |
| DE (1) | DE2846200A1 (fr) |
| DK (1) | DK471978A (fr) |
| FR (1) | FR2407199A1 (fr) |
| GB (1) | GB2008122B (fr) |
| IT (1) | IT1106137B (fr) |
| SE (1) | SE7811035L (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0105509B8 (pt) * | 2001-11-05 | 2021-05-25 | Univ Minas Gerais | formulações do peptídeo angiotensina-(1-7) usando as ciclodextrinas, lipossomas e o polímero plga |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1320104A (en) * | 1971-05-20 | 1973-06-13 | Norwich Pharma Co | Hepta-and octapeptides |
-
1978
- 1978-10-24 DE DE19782846200 patent/DE2846200A1/de not_active Withdrawn
- 1978-10-24 SE SE7811035A patent/SE7811035L/xx unknown
- 1978-10-24 CA CA314,012A patent/CA1102317A/fr not_active Expired
- 1978-10-24 JP JP13011078A patent/JPS5484574A/ja active Pending
- 1978-10-24 GB GB7841664A patent/GB2008122B/en not_active Expired
- 1978-10-24 IT IT51630/78A patent/IT1106137B/it active
- 1978-10-24 AU AU40989/78A patent/AU4098978A/en active Pending
- 1978-10-24 DK DK471978A patent/DK471978A/da not_active Application Discontinuation
- 1978-10-25 FR FR7830367A patent/FR2407199A1/fr not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| DE2846200A1 (de) | 1979-04-26 |
| JPS5484574A (en) | 1979-07-05 |
| SE7811035L (sv) | 1979-04-26 |
| IT1106137B (it) | 1985-11-11 |
| FR2407199A1 (fr) | 1979-05-25 |
| IT7851630A0 (it) | 1978-10-24 |
| AU4098978A (en) | 1980-05-01 |
| DK471978A (da) | 1979-04-26 |
| GB2008122B (en) | 1982-03-24 |
| GB2008122A (en) | 1979-05-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry | ||
| MKEX | Expiry |
Effective date: 19980602 |