JPH0559105B2 - - Google Patents

Info

Publication number: JPH0559105B2
Authority: JP; Japan
Prior art keywords: formula; phenyl; hydrogen; compound; cis
Prior art date: 1981-11-05
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 - Lifetime

Application number

JP8690187A

Other languages

English (en)

Japanese (ja)

Other versions

JPS6251A (ja

Inventor

Teetsu Fuorukaa

Gaigaa Rorufu

Urubatsuha Hansuyoruku

Betsukaa Rainharuto

Sherukensu Berunuanto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Hoechst AG

Original Assignee

Hoechst 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.)

1981-11-05

Filing date

1986-04-21

Publication date

1993-08-30

1986-04-21 Application filed by Hoechst AG filed Critical Hoechst AG

1987-01-06 Publication of JPS6251A publication Critical patent/JPS6251A/ja

1993-08-30 Publication of JPH0559105B2 publication Critical patent/JPH0559105B2/ja

Status Granted legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims description 49
229910052739 hydrogen Inorganic materials 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 25
125000004432 carbon atom Chemical group C* 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 13
239000000203 mixture Substances 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical group C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 10
239000004472 Lysine Substances 0.000 claims description 8
125000002619 bicyclic group Chemical group 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
-1 Benzyl ester Chemical class 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
238000005481 NMR spectroscopy Methods 0.000 description 10
238000000921 elemental analysis Methods 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
239000012141 concentrate Substances 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
239000002904 solvent Substances 0.000 description 8
150000002168 ethanoic acid esters Chemical class 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
238000000034 method Methods 0.000 description 5
239000000047 product Substances 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
238000007327 hydrogenolysis reaction Methods 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
239000007787 solid Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229960003767 alanine Drugs 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
235000008206 alpha-amino acids Nutrition 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
239000002585 base Substances 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000002934 diuretic Substances 0.000 description 2
235000019439 ethyl acetate Nutrition 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000008103 glucose Substances 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
230000001077 hypotensive effect Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
ROVTUJRZGCDHDL-UHFFFAOYSA-N tert-butyl 2-ethylheptanoate Chemical compound CCCCCC(CC)C(=O)OC(C)(C)C ROVTUJRZGCDHDL-UHFFFAOYSA-N 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
239000011701 zinc Chemical class 0.000 description 2
OQHKEWIEKYQINX-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrol-1-ium-2-carboxylate Chemical class C1CCC2NC(C(=O)O)CC21 OQHKEWIEKYQINX-UHFFFAOYSA-N 0.000 description 1
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
KOFSFYBXUYHNJL-UHFFFAOYSA-N 1-(cyclopenten-1-yl)pyrrolidine Chemical compound C1CCCN1C1=CCCC1 KOFSFYBXUYHNJL-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
238000005160 1H NMR spectroscopy Methods 0.000 description 1
NWSUNZPPHJFQKX-UHFFFAOYSA-N 2-benzoylpent-2-enoic acid Chemical compound CCC=C(C(O)=O)C(=O)C1=CC=CC=C1 NWSUNZPPHJFQKX-UHFFFAOYSA-N 0.000 description 1
BSIKSEUHJFHNBU-UHFFFAOYSA-N 2-cyclooctylazocane-2-carboxylic acid Chemical compound C1CCCCCCC1C1(C(=O)O)CCCCCCN1 BSIKSEUHJFHNBU-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
VAPOFMGACKUWCI-UHFFFAOYSA-N 4-(cyclopenten-1-yl)morpholine Chemical compound C1CCC=C1N1CCOCC1 VAPOFMGACKUWCI-UHFFFAOYSA-N 0.000 description 1
ZPLCXHWYPWVJDL-UHFFFAOYSA-N 4-[(4-hydroxyphenyl)methyl]-1,3-oxazolidin-2-one Chemical compound C1=CC(O)=CC=C1CC1NC(=O)OC1 ZPLCXHWYPWVJDL-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
102100030988 Angiotensin-converting enzyme Human genes 0.000 description 1
108010064733 Angiotensins Proteins 0.000 description 1
102000015427 Angiotensins Human genes 0.000 description 1
KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
JKGZEHXJVWQUTK-UHFFFAOYSA-N C(C)OC(C(CC)=C=O)=O Chemical compound C(C)OC(C(CC)=C=O)=O JKGZEHXJVWQUTK-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxylic acid Natural products OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
101000632319 Homo sapiens Septin-7 Proteins 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
150000008534 L-alanines Chemical class 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
238000006845 Michael addition reaction Methods 0.000 description 1
KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
241000700159 Rattus Species 0.000 description 1
101100184046 Schizosaccharomyces pombe (strain 972 / ATCC 24843) mid1 gene Proteins 0.000 description 1
102100027981 Septin-7 Human genes 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
244000061458 Solanum melongena Species 0.000 description 1
235000002597 Solanum melongena Nutrition 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
150000001294 alanine derivatives Chemical class 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
239000010775 animal oil Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
XXAYGJGDVLSEML-LBPRGKRZSA-N benzyl (2s)-2,6-diaminohexanoate Chemical class NCCCC[C@H](N)C(=O)OCC1=CC=CC=C1 XXAYGJGDVLSEML-LBPRGKRZSA-N 0.000 description 1
HLXCXOQXUDRJLF-UHFFFAOYSA-N benzyl 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole-2-carboxylate;hydrochloride Chemical compound Cl.C1C2CCCC2NC1C(=O)OCC1=CC=CC=C1 HLXCXOQXUDRJLF-UHFFFAOYSA-N 0.000 description 1
JCUJFSWZBBGJFT-UHFFFAOYSA-N benzyl 2-ethylheptanoate;hydrochloride Chemical compound Cl.CCCCCC(CC)C(=O)OCC1=CC=CC=C1 JCUJFSWZBBGJFT-UHFFFAOYSA-N 0.000 description 1
TVWUWTZLQRMAKS-UHFFFAOYSA-N benzyl 2-oxoacetate Chemical compound O=CC(=O)OCC1=CC=CC=C1 TVWUWTZLQRMAKS-UHFFFAOYSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
229960003237 betaine Drugs 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
239000003026 cod liver oil Substances 0.000 description 1
235000012716 cod liver oil Nutrition 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000007859 condensation product Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclo-pentanone Natural products O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 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
125000004663 dialkyl amino group Chemical group 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000007908 dry granulation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
LJYCJYJAOWYANE-UHFFFAOYSA-N ethyl 2-benzoylprop-2-enoate Chemical compound CCOC(=O)C(=C)C(=O)C1=CC=CC=C1 LJYCJYJAOWYANE-UHFFFAOYSA-N 0.000 description 1
NHFIFGSTRSPHDN-UHFFFAOYSA-N ethyl 2-methylidene-4-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=C)CC(=O)C1=CC=CC=C1 NHFIFGSTRSPHDN-UHFFFAOYSA-N 0.000 description 1
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
208000021822 hypotensive Diseases 0.000 description 1
239000012535 impurity Substances 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000008101 lactose Substances 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
239000011777 magnesium Chemical class 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
XUKJQVOYXYEVSK-UHFFFAOYSA-N methyl 2-acetamido-3-(2-oxocyclopentyl)propanoate Chemical compound COC(=O)C(NC(C)=O)CC1CCCC1=O XUKJQVOYXYEVSK-UHFFFAOYSA-N 0.000 description 1
GIENHCGYXUYZFO-UHFFFAOYSA-N methyl 2-amino-2-(chloromethyl)-3-oxobutanoate Chemical compound COC(C(CCl)(C(C)=O)N)=O GIENHCGYXUYZFO-UHFFFAOYSA-N 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
POTQIHURRUDRCG-UHFFFAOYSA-N nonanoic acid;hydrochloride Chemical compound Cl.CCCCCCCCC(O)=O POTQIHURRUDRCG-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000011121 sodium hydroxide Nutrition 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000563 toxic property Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Landscapes

Peptides Or Proteins (AREA)
Indole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

JP61090187A 1981-11-05 1986-04-21 シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体およびその製法 Granted JPS6251A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE3143946		1981-11-05
DE3143946.2		1981-11-05
DE3226768.1		1982-07-17

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
JP3077209A Division JPH0694443B2 (ja)	1981-11-05	1991-03-18	アミノ酸誘導体

Publications (2)

Publication Number	Publication Date
JPS6251A JPS6251A (ja)	1987-01-06
JPH0559105B2 true JPH0559105B2 (de)	1993-08-30

Family

ID=6145696

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
JP19262282A Granted JPS58103364A (ja)	1981-11-05	1982-11-04	シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体
JP9018886A Granted JPS61293967A (ja)	1981-11-05	1986-04-21	シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体およびその製法
JP61090187A Granted JPS6251A (ja)	1981-11-05	1986-04-21	シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体およびその製法

Family Applications Before (2)

Application Number	Title	Priority Date	Filing Date
JP19262282A Granted JPS58103364A (ja)	1981-11-05	1982-11-04	シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体
JP9018886A Granted JPS61293967A (ja)	1981-11-05	1986-04-21	シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体およびその製法

Country Status (4)

Country	Link
JP (3)	JPS58103364A (de)
MX (1)	MX9217A (de)
SU (1)	SU1327787A3 (de)
ZA (1)	ZA828085B (de)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3324263A1 (de) *	1983-07-06	1985-01-17	Hoechst Ag, 6230 Frankfurt	Derivate der 2-azabicyclo(3.1.0)hexan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie 2-azabicyclo(3.1.0)hexan-derivate als zwischenprodukte und verfahren zu deren herstellung
DE3333455A1 (de) *	1983-09-16	1985-04-11	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung n-alkylierter dipeptide und deren estern
DE3413710A1 (de) *	1984-04-12	1985-10-24	Hoechst Ag, 6230 Frankfurt	Verfahren zur behandlung der herzinsuffizienz
US4925969A (en) *	1985-02-04	1990-05-15	Kanegafuchi Kagaku Kogyo Kabushiki Kaisha	Process for preparing ethyl-alpha-amino-gamma-oxo-gamma-phenybutyrate derivatives
DE3536687A1 (de) *	1985-10-15	1987-04-16	Hoechst Ag	Verfahren zur behandlung von atherosklerose, thrombose und der peripheren gefaesskrankheit
DE3633496A1 (de) *	1986-10-02	1988-04-14	Hoechst Ag	Kombination von angiotensin-converting-enzyme-hemmern mit calciumantagonisten sowie deren verwendung in arzneimitteln
JP2754010B2 (ja) *	1988-05-23	1998-05-20	株式会社リコー	画像形成装置に於ける像担持体のクリーニング方法
US4947750A (en) *	1988-08-19	1990-08-14	Presstek, Inc.	Printing member for a press with dampening
JP3316639B2 (ja) *	1993-03-05	2002-08-19	コニカ株式会社	高感度で安定性の優れたハロゲン化銀写真感光材料
JP3792777B2 (ja) *	1996-05-10	2006-07-05	株式会社カネカ	１−アルコキシカルボニル−３−フェニルプロピル誘導体の製造方法
AR033048A1 (es)	2001-03-19	2003-12-03	Kaneka Corp	Metodo para la purificacion de la n-(1(s)-etoxicarbonil-3-fenilpropil) -l-alanina
BRPI0506507A (pt) *	2004-01-19	2007-02-27	Lupin Ltd	processo para a purificação de ramipril, monohidrato de ramipril, processo para a preparação de monohidrato de ramipril e composição farmacêutica

Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5777672A (en) *	1980-08-30	1982-05-15	Hoechst Ag	Amino acid derivative and manufacture
JPS5791974A (en) *	1980-10-02	1982-06-08	Science Union & Cie	Imino diacid compound, manufacture and medicinal composition containing same as active component
JPS57112359A (en) *	1980-10-23	1982-07-13	Schering Plough Corp	Carboxylalkyl dipeptide, manufacture and medicinal composition
JPS63209625A (ja) *	1987-02-27	1988-08-31	オリンパス光学工業株式会社	内視鏡

1982
- 1982-11-03 SU SU823513217A patent/SU1327787A3/ru active
- 1982-11-04 JP JP19262282A patent/JPS58103364A/ja active Granted
- 1982-11-04 ZA ZA828085A patent/ZA828085B/xx unknown
1986
- 1986-04-21 JP JP9018886A patent/JPS61293967A/ja active Granted
- 1986-04-21 JP JP61090187A patent/JPS6251A/ja active Granted
1989
- 1989-01-05 MX MX921789A patent/MX9217A/es unknown

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5777672A (en) *	1980-08-30	1982-05-15	Hoechst Ag	Amino acid derivative and manufacture
JPS5791974A (en) *	1980-10-02	1982-06-08	Science Union & Cie	Imino diacid compound, manufacture and medicinal composition containing same as active component
JPS57112359A (en) *	1980-10-23	1982-07-13	Schering Plough Corp	Carboxylalkyl dipeptide, manufacture and medicinal composition
JPS63209625A (ja) *	1987-02-27	1988-08-31	オリンパス光学工業株式会社	内視鏡

Also Published As

Publication number	Publication date
ZA828085B (en)	1983-09-28
JPS6251A (ja)	1987-01-06
JPH0531544B2 (de)	1993-05-12
MX9217A (es)	1993-07-01
JPS58103364A (ja)	1983-06-20
JPH047741B2 (de)	1992-02-12
JPS61293967A (ja)	1986-12-24
SU1327787A3 (ru)	1987-07-30

Publication	Publication Date	Title
US4879403A (en)	1989-11-07	Process for the preparation of cis, endo-2-azabicyclo-[3.3.0]-octane-3-carboxylic acids
US4668797A (en)	1987-05-26	Bicyclic aminoacids as intermediates and processes for their preparation
US4714708A (en)	1987-12-22	Derivatives of cis, endo-2-azabicyclo[5.3.0]decane-3-carboxylic acid, and their use for treating hypertension
HU209413B (en)	1994-05-30	Method for producing 2-azabicyclo [3.1.0] hexane-3-carboxylic acid derivatives as well as their physiologically acceptable salts
EP0116276B1 (de)	1989-01-11	Neue spirocyclische Aminosäurederivate, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung sowie neue spirocyclische Aminosäuren als Zwischenprodukte und Verfahren zu deren Herstellung
EP0105102A1 (de)	1984-04-11	Neue Derivate der 2-Aza-bicyclo(2.2.2)octan-3-carbonsäure, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung sowie 2-Aza-bicyclo(2.2.2)octan-3-carbonsäure als Zwischenstufe und Verfahren zu deren Herstellung
JPH0559105B2 (de)	1993-08-30
KR910001438B1 (ko)	1991-03-07	광학적 활성 비시클릭 이미노-α-카복실산 에스테르 라세미체의 분할방법
EP0113880A2 (de)	1984-07-25	Neue 2-Azabicyclo(2.2.1)heptan-Derivate, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung sowie 2-Azabicyclo(2.2.1)heptan-Derivate als Zwischenprodukte und Verfahren zu deren Herstellung
EP0203450B1 (de)	1992-04-01	Neue Derivate bicyclischer Aminosäuren, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung
JPH0379339B2 (de)	1991-12-18