JPS61176573A - 新規なアミノ酸誘導体 - Google Patents
新規なアミノ酸誘導体Info
- Publication number
- JPS61176573A JPS61176573A JP60017563A JP1756385A JPS61176573A JP S61176573 A JPS61176573 A JP S61176573A JP 60017563 A JP60017563 A JP 60017563A JP 1756385 A JP1756385 A JP 1756385A JP S61176573 A JPS61176573 A JP S61176573A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- amino acid
- acid
- 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.)
- Granted
Links
- 150000003862 amino acid derivatives Chemical class 0.000 title claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 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 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 23
- 230000002401 inhibitory effect Effects 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 14
- 108091005804 Peptidases Proteins 0.000 abstract description 6
- 231100000053 low toxicity Toxicity 0.000 abstract description 5
- 206010020772 Hypertension Diseases 0.000 abstract description 4
- 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 abstract description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004365 Protease Substances 0.000 abstract 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 239000011347 resin Substances 0.000 abstract 1
- 229920005989 resin Polymers 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- 108090000783 Renin Proteins 0.000 description 19
- 102100028255 Renin Human genes 0.000 description 19
- -1 L-ynleucyl group Chemical group 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000013078 crystal Substances 0.000 description 15
- 238000002844 melting Methods 0.000 description 14
- 230000008018 melting Effects 0.000 description 14
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 102000004881 Angiotensinogen Human genes 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 239000012156 elution solvent Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 241000288950 Callithrix jacchus Species 0.000 description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 235000019260 propionic acid Nutrition 0.000 description 5
- 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 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 101800000734 Angiotensin-1 Proteins 0.000 description 4
- 102400000344 Angiotensin-1 Human genes 0.000 description 4
- 108090001067 Angiotensinogen Proteins 0.000 description 4
- 108010064733 Angiotensins Proteins 0.000 description 4
- 102000015427 Angiotensins Human genes 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 150000001540 azides Chemical class 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 210000001715 carotid artery Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229960002885 histidine Drugs 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
- 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
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 2
- CVKMFSAVYPAZTQ-UHFFFAOYSA-N 2-methylhexanoic acid Chemical compound CCCCC(C)C(O)=O CVKMFSAVYPAZTQ-UHFFFAOYSA-N 0.000 description 2
- 101800000733 Angiotensin-2 Proteins 0.000 description 2
- 102400000345 Angiotensin-2 Human genes 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
- 101000579218 Homo sapiens Renin Proteins 0.000 description 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II 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-])=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 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
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- YTAJBIBEHBLEOH-UHFFFAOYSA-N amino 2-hydroxy-5-methylhexanoate Chemical compound CC(C)CCC(O)C(=O)ON YTAJBIBEHBLEOH-UHFFFAOYSA-N 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 241001515942 marmosets Species 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229940048084 pyrophosphate Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 2
- 229940014800 succinic anhydride Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- GZLMFCWSEKVVGO-UHFFFAOYSA-N (2R,3R)-3-Amino-2-hydroxy-5-methylhexanoic acid Natural products CC(C)CC(N)C(O)C(O)=O GZLMFCWSEKVVGO-UHFFFAOYSA-N 0.000 description 1
- GZLMFCWSEKVVGO-NTSWFWBYSA-N (2r,3s)-3-amino-2-hydroxy-5-methylhexanoic acid Chemical compound CC(C)C[C@H](N)[C@@H](O)C(O)=O GZLMFCWSEKVVGO-NTSWFWBYSA-N 0.000 description 1
- HAMRIBBQVJPIBF-NASUQTAISA-N (2s)-3-(1h-imidazol-5-yl)-2-[[2-(naphthalen-1-ylmethyl)-4-oxo-4-(2-phenylethylamino)butanoyl]amino]propanoyl azide Chemical compound C([C@@H](C(=O)N=[N+]=[N-])NC(=O)C(CC(=O)NCCC=1C=CC=CC=1)CC=1C2=CC=CC=C2C=CC=1)C1=CN=CN1 HAMRIBBQVJPIBF-NASUQTAISA-N 0.000 description 1
- 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 1
- XTDHJNGGUYRMLH-UHFFFAOYSA-N 2-(naphthalen-1-ylmethyl)-4-oxo-4-(2-phenylethylamino)butanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(C(=O)O)CC(=O)NCCC1=CC=CC=C1 XTDHJNGGUYRMLH-UHFFFAOYSA-N 0.000 description 1
- LLJIDEXGXUFMCT-UHFFFAOYSA-N 2-(naphthalen-1-ylmethylidene)-4-oxo-4-(2-phenylethylamino)butanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1C=C(C(=O)O)CC(=O)NCCC1=CC=CC=C1 LLJIDEXGXUFMCT-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
- BUJCVBRLTBAYCW-UHFFFAOYSA-N 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propan-1-one Chemical compound COC1=CC=CC=C1OC(CO)C(=O)C1=CC=C(O)C(OC)=C1 BUJCVBRLTBAYCW-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- OVHDZBAFUMEXCX-UHFFFAOYSA-N benzyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1=CC=CC=C1 OVHDZBAFUMEXCX-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 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
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical class C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- NUKZAGXMHTUAFE-UHFFFAOYSA-N hexanoic acid methyl ester Natural products CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- YSKXFBIGECRRMS-UHFFFAOYSA-N methyl 2-hydroxy-5-methylhexanoate Chemical compound COC(=O)C(O)CCC(C)C YSKXFBIGECRRMS-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 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
- 239000007858 starting material Substances 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
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000035488 systolic blood pressure Effects 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
- 238000012360 testing method Methods 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60017563A JPS61176573A (ja) | 1985-01-31 | 1985-01-31 | 新規なアミノ酸誘導体 |
| EP86300666A EP0190891A3 (en) | 1985-01-31 | 1986-01-31 | Novel amino acid derivatives |
| US07/233,962 US4841067A (en) | 1985-01-31 | 1988-08-19 | Novel amino acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60017563A JPS61176573A (ja) | 1985-01-31 | 1985-01-31 | 新規なアミノ酸誘導体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61176573A true JPS61176573A (ja) | 1986-08-08 |
| JPH0559907B2 JPH0559907B2 (ko) | 1993-09-01 |
Family
ID=11947377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60017563A Granted JPS61176573A (ja) | 1985-01-31 | 1985-01-31 | 新規なアミノ酸誘導体 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61176573A (ko) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6329502B1 (en) | 1990-12-11 | 2001-12-11 | Japan Energy Corporation | β-amino-α-hydroxycarboxylic acid derivatives and HIV protease inhibitors |
-
1985
- 1985-01-31 JP JP60017563A patent/JPS61176573A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6329502B1 (en) | 1990-12-11 | 2001-12-11 | Japan Energy Corporation | β-amino-α-hydroxycarboxylic acid derivatives and HIV protease inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0559907B2 (ko) | 1993-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS61236770A (ja) | 新規なアミノ酸誘導体 | |
| JPS6256458A (ja) | 新規なアミノ酸誘導体 | |
| JPS61263998A (ja) | 新規なｎ−（アシルジペプチジル）−アミノグリコ−ル化合物 | |
| US4841067A (en) | Novel amino acid derivatives | |
| RU2107062C1 (ru) | N-замещенные производные имидазола или их соли, способ их получения, промежуточное соединение и фармацевтическая композиция, являющаяся антагонистом ангиотенсина ii | |
| HU200191B (en) | Process for production of new dipeptides | |
| JPH01113364A (ja) | 非ペプチジルα−コハク酸アミドアシルアミノジオール抗高血圧剤 | |
| US4857650A (en) | Novel renin inhibitory amino acid derivatives | |
| JPWO2009001730A1 (ja) | βセクレターゼ阻害活性を有する新規化合物 | |
| JPH10316662A (ja) | 置換された６−および７−アミノテトラヒドロイソキノリンカルボン酸 | |
| WO1992018488A1 (fr) | Nouveau derive d'oxazinone | |
| JPS61176573A (ja) | 新規なアミノ酸誘導体 | |
| JPH03505583A (ja) | 抗高血圧剤としてのアミノアルキルアミノカルボニルアミノジオールアミノ酸誘導体 | |
| US5166154A (en) | Imidazo[1,2-a]piperazines | |
| JPH06172288A (ja) | 新規なフェニルアラニン誘導体またはその塩 | |
| JPS62120370A (ja) | 新規なアミノ酸誘導体 | |
| JPS61200970A (ja) | 新規なアミノ酸誘導体 | |
| HUT51292A (en) | Process for production of amin-methil-peptides and medical compositions containinh them as active substance | |
| JPH01113357A (ja) | 抗高血圧剤としての非ペプチジルβ−アミノアシルアミノジオールカルバメート化合物 | |
| US4853463A (en) | Amino acid derivatives | |
| JPH0559908B2 (ko) | ||
| JPS62234071A (ja) | 新規なアミノ酸誘導体 | |
| JPS61137896A (ja) | 新規なジペプチド誘導体 | |
| JPH0378863B2 (ko) | ||
| JPS6133197A (ja) | ジヒドロオロツト酸誘導体およびその製法 |