JPH0378863B2 - - Google Patents
Info
- Publication number
- JPH0378863B2 JPH0378863B2 JP14359385A JP14359385A JPH0378863B2 JP H0378863 B2 JPH0378863 B2 JP H0378863B2 JP 14359385 A JP14359385 A JP 14359385A JP 14359385 A JP14359385 A JP 14359385A JP H0378863 B2 JPH0378863 B2 JP H0378863B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- group
- amino
- pharmacologically acceptable
- general formula
- 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
- 150000003839 salts Chemical class 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 24
- 150000003862 amino acid derivatives Chemical class 0.000 claims description 24
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000002904 solvent Substances 0.000 description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 150000001875 compounds Chemical class 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- -1 10,11-dihydro-5H-dibenzo[a,d]cycloheptenyl group Chemical group 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- 108090000783 Renin Proteins 0.000 description 25
- 102100028255 Renin Human genes 0.000 description 25
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 24
- 230000002401 inhibitory effect Effects 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 238000003756 stirring Methods 0.000 description 21
- 239000000843 powder Substances 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
- 230000000694 effects Effects 0.000 description 15
- 238000007792 addition Methods 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 235000019260 propionic acid Nutrition 0.000 description 12
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 12
- 102000015427 Angiotensins Human genes 0.000 description 11
- 108010064733 Angiotensins Proteins 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 108091005804 Peptidases Proteins 0.000 description 7
- 102000035195 Peptidases Human genes 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 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
- 238000007796 conventional method Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000012156 elution solvent Substances 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 102000004881 Angiotensinogen Human genes 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 231100000053 low toxicity Toxicity 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- 101000579218 Homo sapiens Renin Proteins 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000008194 pharmaceutical composition 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
- 239000007858 starting material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- DJZCWTDKDFJARG-IENPIDJESA-N (3s)-2-hydroxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)C[C@@H](C(O)C(O)=O)NC(=O)OC(C)(C)C DJZCWTDKDFJARG-IENPIDJESA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 2
- SONAPUPHFUHJDX-UHFFFAOYSA-N 3-(naphthalen-1-ylmethylidene)oxolane-2,5-dione Chemical compound O=C1OC(=O)CC1=CC1=CC=CC2=CC=CC=C12 SONAPUPHFUHJDX-UHFFFAOYSA-N 0.000 description 2
- GZLMFCWSEKVVGO-UHFFFAOYSA-N 3-azaniumyl-2-hydroxy-5-methylhexanoate Chemical compound CC(C)CC(N)C(O)C(O)=O GZLMFCWSEKVVGO-UHFFFAOYSA-N 0.000 description 2
- UKKVEWNSZYZRNZ-UHFFFAOYSA-N 4-(2-methoxycarbonylpyrrolidin-1-yl)-2-(naphthalen-1-ylmethyl)-4-oxobutanoic acid Chemical compound COC(=O)C1CCCN1C(=O)CC(C(O)=O)CC1=CC=CC2=CC=CC=C12 UKKVEWNSZYZRNZ-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 2
- 108090001067 Angiotensinogen Proteins 0.000 description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 101000579223 Ovis aries Renin Proteins 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 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
- 230000005764 inhibitory process Effects 0.000 description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
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- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- GZLMFCWSEKVVGO-ZBHICJROSA-N (3s)-3-amino-2-hydroxy-5-methylhexanoic acid Chemical compound CC(C)C[C@H](N)C(O)C(O)=O GZLMFCWSEKVVGO-ZBHICJROSA-N 0.000 description 1
- GDIPITMTJLOTPN-GNVLWMSISA-N (3s)-3-amino-2-hydroxy-5-methylhexanoic acid;hydrochloride Chemical compound Cl.CC(C)C[C@H](N)C(O)C(O)=O GDIPITMTJLOTPN-GNVLWMSISA-N 0.000 description 1
- NQBRFIXRZDTIRQ-UHFFFAOYSA-N (4-methoxyphenyl)methyl n-diazocarbamate Chemical compound COC1=CC=C(COC(=O)N=[N+]=[N-])C=C1 NQBRFIXRZDTIRQ-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- OCEJTXWZGWBSPX-UHFFFAOYSA-N 2-(naphthalen-1-ylmethylidene)butanedioic acid Chemical compound C1=CC=C2C(C=C(CC(=O)O)C(O)=O)=CC=CC2=C1 OCEJTXWZGWBSPX-UHFFFAOYSA-N 0.000 description 1
- UKKVEWNSZYZRNZ-UHUGOGIASA-N 4-[(2r)-2-methoxycarbonylpyrrolidin-1-yl]-2-(naphthalen-1-ylmethyl)-4-oxobutanoic acid Chemical compound COC(=O)[C@H]1CCCN1C(=O)CC(C(O)=O)CC1=CC=CC2=CC=CC=C12 UKKVEWNSZYZRNZ-UHUGOGIASA-N 0.000 description 1
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
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- BXRMEWOQUXOLDH-LURJTMIESA-N L-Histidine methyl ester Chemical compound COC(=O)[C@@H](N)CC1=CN=CN1 BXRMEWOQUXOLDH-LURJTMIESA-N 0.000 description 1
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- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- DWAYENIPKPKKMV-ILKKLZGPSA-N [(2s)-3-(1h-imidazol-3-ium-4-yl)-1-methoxy-1-oxopropan-2-yl]azanium;dichloride Chemical compound Cl.Cl.COC(=O)[C@@H](N)CC1=CN=CN1 DWAYENIPKPKKMV-ILKKLZGPSA-N 0.000 description 1
- CZCSLHYZEQSUNV-UHFFFAOYSA-N [Na].OB(O)O Chemical compound [Na].OB(O)O CZCSLHYZEQSUNV-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
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- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
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- FHYREDOQUFUFOO-UHFFFAOYSA-N benzyl n-(1-cyano-1-hydroxy-4-methylpentan-2-yl)carbamate Chemical compound CC(C)CC(C(O)C#N)NC(=O)OCC1=CC=CC=C1 FHYREDOQUFUFOO-UHFFFAOYSA-N 0.000 description 1
- SEWLQRPKYMZHDM-ZDUSSCGKSA-N benzyl n-[(2s)-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C=O)NC(=O)OCC1=CC=CC=C1 SEWLQRPKYMZHDM-ZDUSSCGKSA-N 0.000 description 1
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000012230 colorless oil Substances 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
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- JMQGGPRJQOQKRT-UHFFFAOYSA-N diphenyl hydrogen phosphate;azide Chemical compound [N-]=[N+]=[N-].C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 JMQGGPRJQOQKRT-UHFFFAOYSA-N 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960003136 leucine Drugs 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
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229940053050 neomycin sulfate Drugs 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14359385A JPS624286A (ja) | 1985-06-28 | 1985-06-28 | 新規なアミノ酸誘導体 |
| EP86304849A EP0206807A3 (fr) | 1985-06-28 | 1986-06-24 | Dérivés d'amino-acides |
| US06/879,741 US4857650A (en) | 1985-06-28 | 1986-06-27 | Novel renin inhibitory amino acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14359385A JPS624286A (ja) | 1985-06-28 | 1985-06-28 | 新規なアミノ酸誘導体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS624286A JPS624286A (ja) | 1987-01-10 |
| JPH0378863B2 true JPH0378863B2 (fr) | 1991-12-17 |
Family
ID=15342329
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14359385A Granted JPS624286A (ja) | 1985-06-28 | 1985-06-28 | 新規なアミノ酸誘導体 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS624286A (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6313094B1 (en) | 1990-12-11 | 2001-11-06 | Japan Energy Corporation | β-amino-α-hydroxycarboxylic acid derivatives and HIV protease inhibitors |
-
1985
- 1985-06-28 JP JP14359385A patent/JPS624286A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS624286A (ja) | 1987-01-10 |
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