NO834441L

NO834441L - Substituerte tetrapeptider

Substituerte tetrapeptider

Info

Publication number: NO834441L
Authority: NO; Norway
Prior art keywords: compound; formula; group; acid; free
Prior art date: 1982-12-03

Application number

NO834441A

Other languages

English (en)

Norwegian (no)

Inventor

Bernhard Riniker

Peter Buehlmayer

Walter Fuhrer

Original Assignee

Ciba Geigy Ag

Priority date

1982-12-03

Filing date

1983-12-02

Publication date

1984-06-04

1983-12-02 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1984-06-04 Publication of NO834441L publication Critical patent/NO834441L/no

Links

150000001875 compounds Chemical class 0.000 claims abstract description 171
238000000034 method Methods 0.000 claims abstract description 86
150000003839 salts Chemical class 0.000 claims abstract description 74
125000000217 alkyl group Chemical group 0.000 claims abstract description 62
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 58
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 38
125000002252 acyl group Chemical group 0.000 claims abstract description 34
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 29
238000002360 preparation method Methods 0.000 claims abstract description 26
239000001257 hydrogen Substances 0.000 claims abstract description 16
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
230000008569 process Effects 0.000 claims abstract description 12
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 9
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 6
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract description 5
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 5
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract description 5
-1 N-substituted amide group Chemical group 0.000 claims description 202
239000002253 acid Substances 0.000 claims description 101
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 93
150000001413 amino acids Chemical class 0.000 claims description 73
238000006243 chemical reaction Methods 0.000 claims description 50
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 44
125000000524 functional group Chemical group 0.000 claims description 42
125000006239 protecting group Chemical group 0.000 claims description 37
125000001424 substituent group Chemical group 0.000 claims description 37
125000003277 amino group Chemical group 0.000 claims description 35
239000000203 mixture Substances 0.000 claims description 35
229910052736 halogen Inorganic materials 0.000 claims description 25
150000002367 halogens Chemical class 0.000 claims description 25
239000007858 starting material Substances 0.000 claims description 25
108090000765 processed proteins & peptides Proteins 0.000 claims description 19
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 16
239000003153 chemical reaction reagent Substances 0.000 claims description 16
108010085325 histidylproline Proteins 0.000 claims description 16
125000003396 thiol group Chemical group [H]S* 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
239000012634 fragment Substances 0.000 claims description 12
125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 10
239000003638 chemical reducing agent Substances 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 9
108010016626 Dipeptides Proteins 0.000 claims description 8
230000000295 complement effect Effects 0.000 claims description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
230000002829 reductive effect Effects 0.000 claims description 7
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
125000000539 amino acid group Chemical group 0.000 claims description 6
125000000468 ketone group Chemical group 0.000 claims description 6
230000000269 nucleophilic effect Effects 0.000 claims description 6
229910052725 zinc Inorganic materials 0.000 claims description 6
239000011701 zinc Substances 0.000 claims description 6
150000002118 epoxides Chemical class 0.000 claims description 5
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
238000006680 Reformatsky reaction Methods 0.000 claims description 3
125000003172 aldehyde group Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000003700 epoxy group Chemical group 0.000 claims description 3
230000004913 activation Effects 0.000 claims description 2
150000002596 lactones Chemical class 0.000 claims description 2
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 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 claims 1
108090000783 Renin Proteins 0.000 abstract description 4
230000009471 action Effects 0.000 abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 3
206010019280 Heart failures Diseases 0.000 abstract description 2
229940030600 antihypertensive agent Drugs 0.000 abstract description 2
239000002220 antihypertensive agent Substances 0.000 abstract description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 101
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 84
239000000243 solution Substances 0.000 description 80
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
235000002639 sodium chloride Nutrition 0.000 description 73
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
229910001868 water Inorganic materials 0.000 description 70
235000001014 amino acid Nutrition 0.000 description 63
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
125000004432 carbon atom Chemical group C* 0.000 description 41
239000000706 filtrate Substances 0.000 description 40
125000003118 aryl group Chemical group 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
150000007513 acids Chemical class 0.000 description 31
239000003054 catalyst Substances 0.000 description 29
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 28
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000003795 chemical substances by application Substances 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
229960000583 acetic acid Drugs 0.000 description 24
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
239000000843 powder Substances 0.000 description 23
239000002904 solvent Substances 0.000 description 22
150000008064 anhydrides Chemical class 0.000 description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 21
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 19
125000001931 aliphatic group Chemical group 0.000 description 19
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
238000001816 cooling Methods 0.000 description 18
238000010521 absorption reaction Methods 0.000 description 17
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 17
229910052763 palladium Inorganic materials 0.000 description 17
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 16
150000002148 esters Chemical class 0.000 description 16
238000010438 heat treatment Methods 0.000 description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 15
239000003921 oil Substances 0.000 description 15
235000019198 oils Nutrition 0.000 description 15
239000000741 silica gel Substances 0.000 description 15
229910002027 silica gel Inorganic materials 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 11
125000003545 alkoxy group Chemical group 0.000 description 11
238000009826 distribution Methods 0.000 description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 11
238000006722 reduction reaction Methods 0.000 description 11
239000000725 suspension Substances 0.000 description 11
JXGVXCZADZNAMJ-NSHDSACASA-N (2s)-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 JXGVXCZADZNAMJ-NSHDSACASA-N 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
235000011114 ammonium hydroxide Nutrition 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
239000012043 crude product Substances 0.000 description 10
238000001035 drying Methods 0.000 description 10
239000012442 inert solvent Substances 0.000 description 10
150000002500 ions Chemical class 0.000 description 10
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000013543 active substance Substances 0.000 description 9
229910052783 alkali metal Inorganic materials 0.000 description 9
125000005907 alkyl ester group Chemical group 0.000 description 9
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 9
229910052801 chlorine Inorganic materials 0.000 description 9
238000009833 condensation Methods 0.000 description 9
230000005494 condensation Effects 0.000 description 9
239000012362 glacial acetic acid Substances 0.000 description 9
239000011261 inert gas Substances 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000000825 pharmaceutical preparation Substances 0.000 description 9
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
230000009467 reduction Effects 0.000 description 9
235000011121 sodium hydroxide Nutrition 0.000 description 9
238000003756 stirring Methods 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 8
150000004945 aromatic hydrocarbons Chemical group 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
239000003480 eluent Substances 0.000 description 8
KVOCLJKQNJNTDY-KBPBESRZSA-N (3S,4S)-3-hydroxy-6-methyl-4-(phenylmethoxycarbonylamino)heptanoic acid Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 KVOCLJKQNJNTDY-KBPBESRZSA-N 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
150000001718 carbodiimides Chemical class 0.000 description 7
239000013078 crystal Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
150000007522 mineralic acids Chemical class 0.000 description 7
150000007524 organic acids Chemical class 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 7
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
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 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
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 6
102000015636 Oligopeptides Human genes 0.000 description 6
108010038807 Oligopeptides Proteins 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
150000001340 alkali metals Chemical class 0.000 description 6
150000003973 alkyl amines Chemical class 0.000 description 6
125000003368 amide group Chemical group 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
230000032050 esterification Effects 0.000 description 6
238000005886 esterification reaction Methods 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
229910052731 fluorine Inorganic materials 0.000 description 6
239000011737 fluorine Substances 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
229910052500 inorganic mineral Inorganic materials 0.000 description 6
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
229910052751 metal Inorganic materials 0.000 description 6
239000002184 metal Substances 0.000 description 6
235000010755 mineral Nutrition 0.000 description 6
239000011707 mineral Substances 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
101800000734 Angiotensin-1 Proteins 0.000 description 5
102400000344 Angiotensin-1 Human genes 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
102000004142 Trypsin Human genes 0.000 description 5
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230000002378 acidificating effect Effects 0.000 description 5
125000004423 acyloxy group Chemical group 0.000 description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I 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](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)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 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
235000011089 carbon dioxide Nutrition 0.000 description 5
150000001735 carboxylic acids Chemical class 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
125000004494 ethyl ester group Chemical group 0.000 description 5
UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 5
239000006260 foam Substances 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
150000007530 organic bases Chemical class 0.000 description 5
239000012071 phase Substances 0.000 description 5
230000007017 scission Effects 0.000 description 5
235000015424 sodium Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
239000007787 solid Substances 0.000 description 5
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
238000012360 testing method Methods 0.000 description 5
239000012588 trypsin Substances 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
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