JPH045040B2 - - Google Patents
Info
- Publication number
- JPH045040B2 JPH045040B2 JP58177001A JP17700183A JPH045040B2 JP H045040 B2 JPH045040 B2 JP H045040B2 JP 58177001 A JP58177001 A JP 58177001A JP 17700183 A JP17700183 A JP 17700183A JP H045040 B2 JPH045040 B2 JP H045040B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl group
- compound
- lower alkyl
- general formula
- hydrogen
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VNSQOGASPXGGIR-UHFFFAOYSA-N 3-amino-2-phenyl-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound S1C2=CC=CC=C2NC(=O)C(N)C1C1=CC=CC=C1 VNSQOGASPXGGIR-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- -1 diborane Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- YYTRDFCSGHGANU-UHFFFAOYSA-N 2-[3-[(1-ethoxy-1-oxodecan-2-yl)amino]-4-oxo-2-phenyl-2,3-dihydro-1,5-benzothiazepin-5-yl]acetic acid Chemical compound S1C2=CC=CC=C2N(CC(O)=O)C(=O)C(NC(CCCCCCCC)C(=O)OCC)C1C1=CC=CC=C1 YYTRDFCSGHGANU-UHFFFAOYSA-N 0.000 description 1
- YXDNZWJCGLEGSZ-UHFFFAOYSA-N 2-[[5-(carboxymethyl)-4-oxo-2-phenyl-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]-4-phenylbutanoic acid Chemical compound O=C1N(CC(=O)O)C2=CC=CC=C2SC(C=2C=CC=CC=2)C1NC(C(O)=O)CCC1=CC=CC=C1 YXDNZWJCGLEGSZ-UHFFFAOYSA-N 0.000 description 1
- VRPJZSGYGXYOGP-UHFFFAOYSA-N 2-[[5-(carboxymethyl)-4-oxo-2-phenyl-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]acetic acid Chemical compound S1C2=CC=CC=C2N(CC(O)=O)C(=O)C(NCC(=O)O)C1C1=CC=CC=C1 VRPJZSGYGXYOGP-UHFFFAOYSA-N 0.000 description 1
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 1
- VNUDPFLTWOKTKQ-UHFFFAOYSA-N 3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound N1C(=O)CCSC2=CC=CC=C21 VNUDPFLTWOKTKQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BVABFIZTUSTDDW-UHFFFAOYSA-N 5h-1,2-benzothiazepin-4-one Chemical compound S1N=CC(=O)CC2=CC=CC=C21 BVABFIZTUSTDDW-UHFFFAOYSA-N 0.000 description 1
- PPQXADXGECUTFI-UHFFFAOYSA-N 5h-1,5-benzothiazepin-4-one Chemical compound S1C=CC(=O)NC2=CC=CC=C21 PPQXADXGECUTFI-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 150000007657 benzothiazepines Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012351 deprotecting agent Substances 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- DBXIOQSYFYLOSJ-UHFFFAOYSA-N ethyl 2-[[5-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-4-oxo-2-phenyl-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]decanoate Chemical compound S1C2=CC=CC=C2N(CC(=O)OC(C)(C)C)C(=O)C(NC(CCCCCCCC)C(=O)OCC)C1C1=CC=CC=C1 DBXIOQSYFYLOSJ-UHFFFAOYSA-N 0.000 description 1
- OCUDNGDEJLEQFG-UHFFFAOYSA-N ethyl 2-oxodecanoate Chemical compound CCCCCCCCC(=O)C(=O)OCC OCUDNGDEJLEQFG-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- ORCWEBYKGQVCRA-UHFFFAOYSA-N tert-butyl 2-(3-amino-4-oxo-2-phenyl-2,3-dihydro-1,5-benzothiazepin-5-yl)acetate Chemical compound NC1C(=O)N(CC(=O)OC(C)(C)C)C2=CC=CC=C2SC1C1=CC=CC=C1 ORCWEBYKGQVCRA-UHFFFAOYSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58177001A JPS6069076A (ja) | 1983-09-27 | 1983-09-27 | ベンゾチアゼピン誘導体およびその製造法 |
| US06/625,656 US4539150A (en) | 1983-06-29 | 1984-06-28 | Benzothiazepine derivatives and their methods of preparation |
| DE19843423743 DE3423743A1 (de) | 1983-06-29 | 1984-06-28 | Benzothiazepin-derivate und verfahren zu ihrer herstellung |
| GB08416421A GB2143816A (en) | 1983-06-29 | 1984-06-28 | Benzothiazepine derivatives |
| IT21645/84A IT1176345B (it) | 1983-06-29 | 1984-06-28 | Derivati benzotiazepinici e loro metodo di preparazione |
| FR8410370A FR2548184A1 (enrdf_load_stackoverflow) | 1983-06-29 | 1984-06-29 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58177001A JPS6069076A (ja) | 1983-09-27 | 1983-09-27 | ベンゾチアゼピン誘導体およびその製造法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6069076A JPS6069076A (ja) | 1985-04-19 |
| JPH045040B2 true JPH045040B2 (enrdf_load_stackoverflow) | 1992-01-30 |
Family
ID=16023435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58177001A Granted JPS6069076A (ja) | 1983-06-29 | 1983-09-27 | ベンゾチアゼピン誘導体およびその製造法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6069076A (enrdf_load_stackoverflow) |
-
1983
- 1983-09-27 JP JP58177001A patent/JPS6069076A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6069076A (ja) | 1985-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH07304770A (ja) | 新規ベンゾアゼピノン誘導体 | |
| EP0309324B1 (fr) | Procédé de synthèse d'alpha amino N alkyles et de leurs esters. Application à la synthèse de carboxyalkyl dipeptides | |
| KR100520700B1 (ko) | Ｎ-[(ｓ)-1-카르복시부틸]-(ｓ)-알라닌 에스테르의 합성방법 및 페린도프릴 합성에서의 용도 | |
| EP1603558B1 (en) | Process for preparation of perindopril and salts thereof | |
| KR100498869B1 (ko) | Ｎ-[(ｓ）-１-카르복시부틸]-（ｓ）-알라닌 에스테르 및페린도프릴의 합성에서의 용도 | |
| EP0169300B1 (en) | Process for preparation of alpha-alkyl amino acids | |
| EP0267098B1 (fr) | Procédé de préparation de dérivés de l'octahydroindole et intermédiaires de préparation | |
| JP3247696B2 (ja) | 〔１ｓ−（１ｒ＊，２ｓ＊，３ｒ＊）〕−ｎ−（４−モルホリニルスルホニル）−ｌ−フェニルアラニル−３−（２−アミノ−４−チアゾリル）−ｎ−〔（１−シクロヘキシルメチル）−２，３−ジヒドロキシ−５−メチルヘキシル〕−ｌ−アラニンアミドの改良された製法 | |
| JPH0432063B2 (enrdf_load_stackoverflow) | ||
| US4325886A (en) | Optical resolution of acylthiopropionic acid | |
| IE47073B1 (en) | Alpha amino-acids, compositions and process for preparing said compounds | |
| JPH045040B2 (enrdf_load_stackoverflow) | ||
| JPH08109173A (ja) | ４−置換された光学活性（ｓ）−２−オキサゾリジノンの製法、新規の（ｓ）−２−オキサゾリジノンおよび新規の光学活性（ｓ）−アミノアルコール | |
| JP3811885B2 (ja) | ４−チアゾリルメチル誘導体の製造方法 | |
| JPS6317077B2 (enrdf_load_stackoverflow) | ||
| HU194857B (en) | Process for production of 4-amin-6-fluor-cromane-4-carbonic acid and its 2/r/ methilesther | |
| JP2714447B2 (ja) | Ｌ―アラニル―ｌ―プロリン誘導体の製造方法 | |
| HU214086B (en) | Process for producing 3-isoxazolecarboxylic acid and intermediates thereof | |
| JPH1059947A (ja) | キラルで、非ラセミの（４−アリール−２，５−ジオキソイミダゾリジン−１−イル）酢酸の製造方法 | |
| JPS62132846A (ja) | ４−アミノブタン酸誘導体及びその製法 | |
| SK568590A3 (en) | Glutaric acid derivatives and method for the preparation thereof, and intermediate product of said method | |
| JPH07304746A (ja) | 新規ベンゾアゼピンカルボン酸誘導体 | |
| JPH11152282A (ja) | 新規なカルボン酸誘導体およびその製造方法 | |
| JPH07121916B2 (ja) | 光学活性３−アシル−２−オキソイミダゾリジン−４−カルボン酸誘導体及びその製法 | |
| HU194912B (en) | Process for producing alkylamino-furanone-dipeptide derivatives and acid additional salts thereof |