CH672792A5 - - Google Patents

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Info

Publication number: CH672792A5
Authority: CH; Switzerland
Prior art keywords: peptide; formula; group; residue; compound
Prior art date: 1985-02-19

Application number

CH537/86A

Other languages

German (de)

English (en)

Inventor

Robert H Abeles

Michael H Gelb

Original Assignee

Sandoz Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1985-02-19

Filing date

1986-02-11

Publication date

1989-12-29

1986-02-11 Application filed by Sandoz Ag filed Critical Sandoz Ag

1989-12-29 Publication of CH672792A5 publication Critical patent/CH672792A5/de

Links

150000001875 compounds Chemical class 0.000 claims description 70
108090000765 processed proteins & peptides Proteins 0.000 claims description 69
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
150000003839 salts Chemical group 0.000 claims description 15
238000000034 method Methods 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 10
239000011737 fluorine Substances 0.000 claims description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 9
230000008878 coupling Effects 0.000 claims description 8
238000010168 coupling process Methods 0.000 claims description 8
238000005859 coupling reaction Methods 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 3
150000001450 anions Chemical class 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims 2
206010007558 Cardiac failure chronic Diseases 0.000 claims 1
230000036772 blood pressure Effects 0.000 claims 1
125000004432 carbon atom Chemical group C* 0.000 description 57
-1 (S) -amino-3 (S) -hydroxy-6-methylheptanoyl Chemical group 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
125000000539 amino acid group Chemical group 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
230000000694 effects Effects 0.000 description 6
229940088598 enzyme Drugs 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000002243 precursor Substances 0.000 description 5
108090000284 Pepsin A Proteins 0.000 description 4
102000057297 Pepsin A Human genes 0.000 description 4
108090000783 Renin Proteins 0.000 description 4
102100028255 Renin Human genes 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
125000003282 alkyl amino group Chemical group 0.000 description 4
125000003435 aroyl group Chemical group 0.000 description 4
125000001589 carboacyl group Chemical group 0.000 description 4
125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
229940111202 pepsin Drugs 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000011321 prophylaxis Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000002461 renin inhibitor Substances 0.000 description 4
229940086526 renin-inhibitors Drugs 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
238000011282 treatment Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
239000004365 Protease Substances 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
229940024606 amino acid Drugs 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000002532 enzyme inhibitor Substances 0.000 description 3
239000000203 mixture Substances 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000000047 product Substances 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
239000000758 substrate Substances 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
DFVFTMTWCUHJBL-UHFFFAOYSA-N 4-azaniumyl-3-hydroxy-6-methylheptanoate Chemical compound CC(C)CC(N)C(O)CC(O)=O DFVFTMTWCUHJBL-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
206010007559 Cardiac failure congestive Diseases 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
102000035195 Peptidases Human genes 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
125000003884 phenylalkyl group Chemical group 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
UOUKEYVAKRKVQA-UHFFFAOYSA-N 3-methylbutyl 2,2,2-trifluoroacetate Chemical compound CC(C)CCOC(=O)C(F)(F)F UOUKEYVAKRKVQA-UHFFFAOYSA-N 0.000 description 1
GRMIYECWLRTQIT-UHFFFAOYSA-N 4-amino-6-methyl-3-oxoheptanoic acid Chemical compound CC(C)CC(N)C(=O)CC(O)=O GRMIYECWLRTQIT-UHFFFAOYSA-N 0.000 description 1
102000012440 Acetylcholinesterase Human genes 0.000 description 1
108010022752 Acetylcholinesterase Proteins 0.000 description 1
102000004400 Aminopeptidases Human genes 0.000 description 1
108090000915 Aminopeptidases Proteins 0.000 description 1
102000004881 Angiotensinogen Human genes 0.000 description 1
108090001067 Angiotensinogen Proteins 0.000 description 1
102000015427 Angiotensins Human genes 0.000 description 1
108010064733 Angiotensins Proteins 0.000 description 1
108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
HBGJBXQJQLOVBD-UHFFFAOYSA-N C1=CC=NC=C1.C1=CC=NC=C1.[O-2].[O-2].O.[Cr+4] Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.[O-2].[O-2].O.[Cr+4] HBGJBXQJQLOVBD-UHFFFAOYSA-N 0.000 description 1
UVRXVMIEBRLVSP-FJXQXJEOSA-N CC(C)CCNC([C@H](C)N)=O.CC(O)=O Chemical compound CC(C)CCNC([C@H](C)N)=O.CC(O)=O UVRXVMIEBRLVSP-FJXQXJEOSA-N 0.000 description 1
108090000087 Carboxypeptidase B Proteins 0.000 description 1
102000003670 Carboxypeptidase B Human genes 0.000 description 1
102000000496 Carboxypeptidases A Human genes 0.000 description 1
108010080937 Carboxypeptidases A Proteins 0.000 description 1
108090000746 Chymosin Proteins 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
206010014561 Emphysema Diseases 0.000 description 1
108090000371 Esterases Proteins 0.000 description 1
YKZYYMLLFMSURI-UHFFFAOYSA-N FCC(=O)O.C(C)Br Chemical compound FCC(=O)O.C(C)Br YKZYYMLLFMSURI-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
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 1
206010061218 Inflammation Diseases 0.000 description 1
235000019766 L-Lysine Nutrition 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
229930182844 L-isoleucine Natural products 0.000 description 1
229930182821 L-proline Natural products 0.000 description 1
102000002704 Leucyl aminopeptidase Human genes 0.000 description 1
108010004098 Leucyl aminopeptidase Proteins 0.000 description 1
239000004367 Lipase Substances 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
102100037611 Lysophospholipase Human genes 0.000 description 1
PHXQIAWFIIMOKG-UHFFFAOYSA-N NClO Chemical compound NClO PHXQIAWFIIMOKG-UHFFFAOYSA-N 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
102000016387 Pancreatic elastase Human genes 0.000 description 1
108010067372 Pancreatic elastase Proteins 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
108010058864 Phospholipases A2 Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
102000012479 Serine Proteases Human genes 0.000 description 1
108010022999 Serine Proteases Proteins 0.000 description 1
101710097834 Thiol protease Proteins 0.000 description 1
229940022698 acetylcholinesterase Drugs 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000012491 analyte Substances 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
BBEVLOCJABUASK-NBFOIZRFSA-N benzyl N-[(2S)-2-amino-6-methyl-3-oxoheptan-4-yl]carbamate Chemical compound C[C@@H](C(=O)C(CC(C)C)NC(=O)OCC1=CC=CC=C1)N BBEVLOCJABUASK-NBFOIZRFSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
239000000969 carrier Substances 0.000 description 1
229940080701 chymosin Drugs 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003602 elastase inhibitor Substances 0.000 description 1
210000004177 elastic tissue Anatomy 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
PQGVTLQEKCJXKF-RGMNGODLSA-N ethyl (2s)-2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.CCOC(=O)[C@@H](N)C(C)C PQGVTLQEKCJXKF-RGMNGODLSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
229960002885 histidine Drugs 0.000 description 1
108010092114 histidylphenylalanine Proteins 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
BRHPBVXVOVMTIQ-ZLELNMGESA-N l-leucine l-leucine Chemical compound CC(C)C[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O BRHPBVXVOVMTIQ-ZLELNMGESA-N 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical compound COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
GNOLWGAJQVLBSM-UHFFFAOYSA-N n,n,5,7-tetramethyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=C(C)C=C2C(N(C)C)CCCC2=C1C GNOLWGAJQVLBSM-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
229940055729 papain Drugs 0.000 description 1
235000019834 papain Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960005190 phenylalanine Drugs 0.000 description 1
108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960002429 proline Drugs 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007858 starting material Substances 0.000 description 1
210000001913 submandibular gland Anatomy 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
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 1
RQSBRFZHUKLKNO-VIFPVBQESA-N tert-butyl n-[(2s)-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C=O)NC(=O)OC(C)(C)C RQSBRFZHUKLKNO-VIFPVBQESA-N 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
238000001926 trapping method Methods 0.000 description 1
229960004441 tyrosine Drugs 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0227—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the (partial) peptide sequence -Phe-His-NH-(X)2-C(=0)-, e.g. Renin-inhibitors with n = 2 - 6; for n > 6 see C07K5/06 - C07K5/10
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Heart & Thoracic Surgery (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Cardiology (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)

CH537/86A 1985-02-19 1986-02-11 CH672792A5 (pl)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US70265185A	1985-02-19	1985-02-19

Publications (1)

Publication Number	Publication Date
CH672792A5 true CH672792A5 (pl)	1989-12-29

Family

ID=24822094

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH537/86A CH672792A5 (pl)	1985-02-19	1986-02-11

Country Status (7)

Country	Link
JP (1)	JPS61194097A (pl)
BE (1)	BE904233A (pl)
CH (1)	CH672792A5 (pl)
DE (1)	DE3604510A1 (pl)
FR (1)	FR2577557B1 (pl)
GB (1)	GB2171103B (pl)
IT (1)	IT1203743B (pl)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8600263D0 (en) *	1985-01-22	1986-02-12	Ici America Inc	Peptide derivatives
US5055450A (en) *	1985-01-22	1991-10-08	Ici Americas Inc.	Peptide derivatives
US5194588A (en) *	1985-01-22	1993-03-16	Ici Americas Inc.	Aminoalcohol intermediates for peptide derivatives
US5496927A (en) *	1985-02-04	1996-03-05	Merrell Pharmaceuticals Inc.	Peptidase inhibitors
US4882420A (en) *	1985-04-19	1989-11-21	The Upjohn Company	Dihalo-statine substituted renin inhibitors
GB8613704D0 (en) *	1986-06-05	1986-07-09	Ici America Inc	Difluoro keto compounds
GB8613703D0 (en) *	1986-06-05	1986-07-09	Ici America Inc	Difluoro peptide compounds
GB8619182D0 (en) *	1986-08-06	1986-09-17	Sandoz Ltd	Peptides & derivatives
NZ223148A (en) *	1987-01-16	1989-10-27	Merrell Dow Pharma	Peptide derivatives having peptidase inhibition activity
US4855303A (en) *	1987-07-01	1989-08-08	Pfizer Inc.	Fluorine containing renin inhibitors
US5071837A (en) *	1990-11-28	1991-12-10	Warner-Lambert Company	Novel renin inhibiting peptides
NZ241099A (en) *	1991-01-02	1994-08-26	Merrell Dow Pharma	Difluorostatone analogues and derivatives and pharmaceutical compositions
US5559140A (en) *	1991-01-02	1996-09-24	Merrell Pharmaceuticals Inc.	Difluoro statone analogs
IL108031A0 (en) *	1992-12-22	1994-04-12	Procter & Gamble	Difluoro pentapeptide derivatives and pharmaceutical compositions containing them
AU667995B2 (en) *	1993-02-15	1996-04-18	Bayer Aktiengesellschaft	New pseudopeptides having an antiviral action
WO1995001958A1 (en) *	1993-07-08	1995-01-19	Merrell Pharmaceuticals Inc.	Difluoro statone analogs
KR100308839B1 (ko) *	1993-09-09	2002-10-04	메렐 파마슈티칼스 인크.	디플루오로 스타톤 항바이러스성 유사체
EP0742791B1 (en) *	1994-02-04	2001-01-10	Merrell Pharmaceuticals Inc.	Macrocyclic difluorostatone derivatives useful as antiviral agents
GB9502152D0 (en) *	1995-02-03	1995-03-29	Zeneca Ltd	Proline derivatives
US6114380A (en) *	1995-12-18	2000-09-05	Merrell Pharmaceuticals Inc.	Difluoro statone analogs
US8324347B2 (en) *	2009-02-24	2012-12-04	Institute For Systems Biology	Methods of using halogenated peptides as internal standards for liquid chromatography-mass spectrometry

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
GR75019B (pl) *	1980-09-17	1984-07-12	Univ Miami
EP0218688B1 (en) *	1985-04-19	1990-09-12	The Upjohn Company	Dihalo-statine substituted renin inhibitors

1986
- 1986-02-11 CH CH537/86A patent/CH672792A5/de not_active IP Right Cessation
- 1986-02-13 DE DE19863604510 patent/DE3604510A1/de not_active Withdrawn
- 1986-02-17 BE BE1/011438A patent/BE904233A/fr not_active IP Right Cessation
- 1986-02-17 GB GB08603835A patent/GB2171103B/en not_active Expired
- 1986-02-17 FR FR868602218A patent/FR2577557B1/fr not_active Expired - Lifetime
- 1986-02-18 IT IT47666/86A patent/IT1203743B/it active
- 1986-02-18 JP JP61034930A patent/JPS61194097A/ja active Pending

Also Published As

Publication number	Publication date
BE904233A (fr)	1986-08-18
JPS61194097A (ja)	1986-08-28
GB2171103A (en)	1986-08-20
DE3604510A1 (de)	1986-08-21
FR2577557A1 (fr)	1986-08-22
GB8603835D0 (en)	1986-03-26
FR2577557B1 (fr)	1990-05-11
IT8647666A0 (it)	1986-02-18
IT1203743B (it)	1989-02-23
GB2171103B (en)	1989-01-25

Publication	Publication Date	Title
CH672792A5 (pl)	1989-12-29
US5066643A (en)	1991-11-19	Fluorine and chlorine statine or statone containing peptides and method of use
EP0236872B1 (de)	1992-11-25	Hydroxylaminderivate, deren Herstellung und Verwendung für Heilmittel
AU600226B2 (en)	1990-08-09	Novel peptidase inhibitors
EP0054862B1 (en)	1985-11-27	Substituted dipeptides, processes for their preparation and pharmaceutical compositions containing them and their use in the inhibition of enkephalinase
US5496927A (en)	1996-03-05	Peptidase inhibitors
EP0412350A2 (de)	1991-02-13	Renininhibitoren, Verfahren zur Herstellung und ihre Verwendung in Arzneimitteln
NZ260675A (en)	1996-04-26	Phosphinyloxymethyl ketones containing 1-3 amino acids as enzyme inhibitors; medicaments
EP0441192A2 (de)	1991-08-14	Retroisostere Dipeptide, Verfahren zu ihrer Herstellung und ihre Verwendung als Renininhibitoren in Arzneimitteln
DE3000628C2 (pl)	1988-09-08
DE69431359T2 (de)	2003-07-31	Prolyl-endopeptidaseinhibitoren
EP0236874A2 (de)	1987-09-16	Renininhibitoren, deren Herstellung und Verwendung sowie Aminosäure- und Aminoaldehyd-Derivate
DE69531459T2 (de)	2004-06-24	Elatase-inhibitoren
EP0394853A1 (de)	1990-10-31	Dipeptid-Derivate mit enzym-inhibitorischer Wirkung
DE4443390A1 (de)	1996-06-13	Neue dipeptidische p-Amidinobenzylamide mit N-terminalen Sulfonyl- bzw. Aminosulfonylresten
EP0144290A2 (de)	1985-06-12	Substituierte Aethylendiaminderivate
DE3884145T2 (de)	1994-01-13	4h-3,1-benzoxazin-4-on-verbindungen und serin protease-inhibierende arzneimittel.
EP0437729A2 (de)	1991-07-24	Neue Peptide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel, insbesondere als Arzneimittel gegen Retroviren
EP0403828A1 (de)	1990-12-27	Renininhibitorische Peptide, Verfahren zur ihrer Herstellung und ihre Verwendung in Arzneimitteln
AT390619B (de)	1990-06-11	Verfahren zur herstellung von neuen prolinderivaten
DE69913996T2 (de)	2004-12-09	Depsipeptide, die nicht-natürliche Aminosäuren enthalten
EP0058567A1 (en)	1982-08-25	Substituted acyl derivatives of octahydro-1H-isoindole-1-carboxylic acids and esters
DE69606552T2 (de)	2000-09-14	Acylierte enolderivate von alpha-ketoestern und alpha-ketoamiden
DE69522940T2 (de)	2002-04-04	Acylierte enolderivate als vorläufdrogen von elastaseinhibitoren
EP0203450B1 (de)	1992-04-01	Neue Derivate bicyclischer Aminosäuren, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung

Legal Events

Date	Code	Title	Description
1993-10-29	PL	Patent ceased
2024-10-31	PL	Patent ceased