CA1281718C - Derives de l'acide 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5- acetique - Google Patents

Derives de l'acide 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5- acetique

Info

Publication number: CA1281718C
Authority: CA; Canada
Prior art keywords: compound; formula; tetrahydro; oxo; group
Prior art date: 1984-03-22
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

CA000471650A

Other languages

English (en)

Inventor

Hirosada Sugihara

Katsumi Ito

Kohei Nishikawa

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.)

Takeda Pharmaceutical Co Ltd

Original Assignee

Takeda Chemical Industries Ltd

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.)

1984-03-22

Filing date

1985-01-08

Publication date

1991-03-19

1984-03-24 Priority claimed from PCT/JP1984/000119 external-priority patent/WO1985004402A1/fr

1984-04-06 Priority claimed from PCT/JP1984/000172 external-priority patent/WO1985004657A1/fr

1984-04-11 Priority claimed from US06/599,187 external-priority patent/US4564612A/en

1984-07-13 Priority claimed from PCT/JP1984/000363 external-priority patent/WO1986000618A1/fr

1985-01-08 Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd

1991-03-19 Application granted granted Critical

1991-03-19 Publication of CA1281718C publication Critical patent/CA1281718C/fr

2008-03-19 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

FKJMRSNUIRKFPA-UHFFFAOYSA-N 2-(3-amino-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl)acetic acid Chemical class OC(=O)CN1C(=O)C(N)CSC2=CC=CC=C21 FKJMRSNUIRKFPA-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 210
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
239000001257 hydrogen Substances 0.000 claims abstract description 49
125000000217 alkyl group Chemical group 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 33
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 26
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 22
229910052736 halogen Inorganic materials 0.000 claims abstract description 21
150000002367 halogens Chemical class 0.000 claims abstract description 21
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 16
125000002947 alkylene group Chemical group 0.000 claims abstract description 13
125000004429 atom Chemical group 0.000 claims abstract description 12
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims abstract description 3
-1 pyrrolldinyl Chemical group 0.000 claims description 187
230000002829 reductive effect Effects 0.000 claims description 142
238000000034 method Methods 0.000 claims description 35
239000002253 acid Substances 0.000 claims description 27
239000002585 base Substances 0.000 claims description 27
238000010531 catalytic reduction reaction Methods 0.000 claims description 22
230000008569 process Effects 0.000 claims description 19
229910052751 metal Inorganic materials 0.000 claims description 17
239000002184 metal Substances 0.000 claims description 17
150000002431 hydrogen Chemical class 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
125000001841 imino group Chemical group [H]N=* 0.000 claims description 11
238000006460 hydrolysis reaction Methods 0.000 claims description 10
125000002252 acyl group Chemical group 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
238000005804 alkylation reaction Methods 0.000 claims description 8
238000006482 condensation reaction Methods 0.000 claims description 8
230000007062 hydrolysis Effects 0.000 claims description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
125000005936 piperidyl group Chemical group 0.000 claims description 7
238000007363 ring formation reaction Methods 0.000 claims description 7
238000003379 elimination reaction Methods 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
238000003797 solvolysis reaction Methods 0.000 claims description 6
238000009833 condensation Methods 0.000 claims description 5
230000005494 condensation Effects 0.000 claims description 5
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 4
125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
125000005458 thianyl group Chemical group 0.000 claims description 4
125000002393 azetidinyl group Chemical group 0.000 claims description 3
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
125000000532 dioxanyl group Chemical group 0.000 claims description 3
125000005883 dithianyl group Chemical group 0.000 claims description 3
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 claims description 3
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 3
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 3
125000002757 morpholinyl group Chemical group 0.000 claims description 3
125000003551 oxepanyl group Chemical group 0.000 claims description 3
125000003566 oxetanyl group Chemical group 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 3
125000001583 thiepanyl group Chemical group 0.000 claims description 3
125000002053 thietanyl group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
230000008030 elimination Effects 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 24
229940126214 compound 3 Drugs 0.000 claims 8
125000001589 carboacyl group Chemical group 0.000 claims 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
125000001412 tetrahydropyranyl group Chemical group 0.000 claims 3
VGLXNWGVKZBOQS-IRXDYDNUSA-N (2s)-2-[[(3r)-5-(carboxymethyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]-6-piperidin-4-ylhexanoic acid Chemical compound C([C@H](N[C@H]1CSC2=CC=CC=C2N(C1=O)CC(=O)O)C(O)=O)CCCC1CCNCC1 VGLXNWGVKZBOQS-IRXDYDNUSA-N 0.000 claims 1
230000003276 anti-hypertensive effect Effects 0.000 claims 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 abstract description 10
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 abstract description 10
206010020772 Hypertension Diseases 0.000 abstract description 8
239000003795 chemical substances by application Substances 0.000 abstract description 7
230000002401 inhibitory effect Effects 0.000 abstract description 7
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 abstract description 4
125000003545 alkoxy group Chemical group 0.000 abstract description 4
201000010099 disease Diseases 0.000 abstract description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
230000002490 cerebral effect Effects 0.000 abstract description 3
238000003745 diagnosis Methods 0.000 abstract description 2
230000002265 prevention Effects 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 484
239000000243 solution Substances 0.000 description 283
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 261
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 207
239000000203 mixture Substances 0.000 description 203
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 189
229940093499 ethyl acetate Drugs 0.000 description 161
235000019439 ethyl acetate Nutrition 0.000 description 161
238000006243 chemical reaction Methods 0.000 description 154
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 142
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 137
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 114
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 112
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 81
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 75
238000003756 stirring Methods 0.000 description 73
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 71
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 71
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 67
239000000463 material Substances 0.000 description 67
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 60
238000001816 cooling Methods 0.000 description 52
239000010410 layer Substances 0.000 description 50
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
239000000843 powder Substances 0.000 description 45
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 40
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 38
238000001819 mass spectrum Methods 0.000 description 38
235000011121 sodium hydroxide Nutrition 0.000 description 37
238000010898 silica gel chromatography Methods 0.000 description 36
238000006722 reduction reaction Methods 0.000 description 34
229910000030 sodium bicarbonate Inorganic materials 0.000 description 34
235000017557 sodium bicarbonate Nutrition 0.000 description 34
238000000921 elemental analysis Methods 0.000 description 32
239000012230 colorless oil Substances 0.000 description 31
238000001914 filtration Methods 0.000 description 29
230000009467 reduction Effects 0.000 description 29
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
239000003208 petroleum Substances 0.000 description 24
239000000047 product Substances 0.000 description 24
239000003054 catalyst Substances 0.000 description 23
229940086542 triethylamine Drugs 0.000 description 23
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
239000002244 precipitate Substances 0.000 description 21
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 20
229910000027 potassium carbonate Inorganic materials 0.000 description 20
235000011181 potassium carbonates Nutrition 0.000 description 20
229910052708 sodium Inorganic materials 0.000 description 20
239000011734 sodium Substances 0.000 description 20
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 19
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 17
MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 16
238000002844 melting Methods 0.000 description 16
230000008018 melting Effects 0.000 description 16
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 16
239000002904 solvent Substances 0.000 description 16
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
229910000041 hydrogen chloride Inorganic materials 0.000 description 15
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
239000000460 chlorine Substances 0.000 description 14
238000004440 column chromatography Methods 0.000 description 14
239000003921 oil Substances 0.000 description 14
239000013078 crystal Substances 0.000 description 13
238000000605 extraction Methods 0.000 description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
239000003960 organic solvent Substances 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 12
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
239000000126 substance Substances 0.000 description 12
239000006228 supernatant Substances 0.000 description 12
HBBIPUCUTBNKJJ-JTQLQIEISA-N tert-butyl 2-[(3r)-3-amino-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetate Chemical compound S1C[C@H](N)C(=O)N(CC(=O)OC(C)(C)C)C2=CC=CC=C21 HBBIPUCUTBNKJJ-JTQLQIEISA-N 0.000 description 12
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
238000001228 spectrum Methods 0.000 description 11
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
230000002378 acidificating effect Effects 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
101150041968 CDC13 gene Proteins 0.000 description 9
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 9
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 9
239000007858 starting material Substances 0.000 description 9
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
238000002474 experimental method Methods 0.000 description 8
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 8
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
239000011345 viscous material Substances 0.000 description 8
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
229910000147 aluminium phosphate Inorganic materials 0.000 description 7
229940085242 benzothiazepine derivative selective calcium channel blockers with direct cardiac effects Drugs 0.000 description 7
150000007657 benzothiazepines Chemical class 0.000 description 7
229920001429 chelating resin Polymers 0.000 description 7
239000003480 eluent Substances 0.000 description 7
229910000042 hydrogen bromide Inorganic materials 0.000 description 7
239000007788 liquid Substances 0.000 description 7
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
238000012360 testing method Methods 0.000 description 7
239000011701 zinc Substances 0.000 description 7
229910052725 zinc Inorganic materials 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
239000012359 Methanesulfonyl chloride Substances 0.000 description 6
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical class C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 6
RKXUSINLWJIUOW-UHFFFAOYSA-N benzyl 4-(6-ethoxy-5-hydroxy-6-oxohexyl)piperidine-1-carboxylate Chemical compound C1CC(CCCCC(O)C(=O)OCC)CCN1C(=O)OCC1=CC=CC=C1 RKXUSINLWJIUOW-UHFFFAOYSA-N 0.000 description 6
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical class C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
230000001631 hypertensive effect Effects 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
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150000007942 carboxylates Chemical class 0.000 description 1
YBZSHUAKOJGWRT-UHFFFAOYSA-M cesium;propanoate Chemical compound [Cs+].CCC([O-])=O YBZSHUAKOJGWRT-UHFFFAOYSA-M 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
229940005991 chloric acid Drugs 0.000 description 1
238000004737 colorimetric analysis Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
JEFMUYDRUOHPIW-UHFFFAOYSA-N diethyl 2-[5-(1-phenylmethoxycarbonylpiperidin-4-yl)pentyl]propanedioate Chemical compound C1CC(CCCCCC(C(=O)OCC)C(=O)OCC)CCN1C(=O)OCC1=CC=CC=C1 JEFMUYDRUOHPIW-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
235000019797 dipotassium phosphate Nutrition 0.000 description 1
QNPCWVPCAXGWPL-UHFFFAOYSA-L disodium hydrogen carbonate acetate Chemical compound [Na+].[Na+].CC([O-])=O.OC([O-])=O QNPCWVPCAXGWPL-UHFFFAOYSA-L 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
238000001035 drying Methods 0.000 description 1
ABZPCWYIRGIXJP-ONEGZZNKSA-N ethyl (e)-3-pyridin-4-ylprop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC=NC=C1 ABZPCWYIRGIXJP-ONEGZZNKSA-N 0.000 description 1
PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
VIFLUHBPKXDMDY-UHFFFAOYSA-N ethyl 2-bromo-10-(1,3-dioxoisoindol-2-yl)decanoate Chemical compound C1=CC=C2C(=O)N(CCCCCCCCC(Br)C(=O)OCC)C(=O)C2=C1 VIFLUHBPKXDMDY-UHFFFAOYSA-N 0.000 description 1
DIOCWWLLFWNZJV-UHFFFAOYSA-N ethyl 2-bromo-7-(1,3-dioxoisoindol-2-yl)heptanoate Chemical compound C1=CC=C2C(=O)N(CCCCCC(Br)C(=O)OCC)C(=O)C2=C1 DIOCWWLLFWNZJV-UHFFFAOYSA-N 0.000 description 1
LLRZTGSOBOFVQO-UHFFFAOYSA-N ethyl 3-(oxan-4-yl)prop-2-enoate Chemical compound CCOC(=O)C=CC1CCOCC1 LLRZTGSOBOFVQO-UHFFFAOYSA-N 0.000 description 1
FGFHEEOMUOKGTG-UHFFFAOYSA-N ethyl 3-(thian-4-yl)prop-2-enoate Chemical compound CCOC(=O)C=CC1CCSCC1 FGFHEEOMUOKGTG-UHFFFAOYSA-N 0.000 description 1
YNDVVCULFWJREU-UHFFFAOYSA-N ethyl 3-(thian-4-yl)propanoate Chemical compound CCOC(=O)CCC1CCSCC1 YNDVVCULFWJREU-UHFFFAOYSA-N 0.000 description 1
XGABTHFOTUYVMO-UHFFFAOYSA-N ethyl 4-piperidin-4-ylbutanoate Chemical compound CCOC(=O)CCCC1CCNCC1 XGABTHFOTUYVMO-UHFFFAOYSA-N 0.000 description 1
ONWJGSSBCPCBCH-AWESVXIMSA-N ethyl 6-amino-2-[[(3r)-5-(2-ethoxy-2-oxoethyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]hexanoate;dihydrochloride Chemical compound Cl.Cl.S1C[C@H](NC(CCCCN)C(=O)OCC)C(=O)N(CC(=O)OCC)C2=CC=CC=C21 ONWJGSSBCPCBCH-AWESVXIMSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical class CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
238000005187 foaming Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000010575 fractional recrystallization Methods 0.000 description 1
238000005227 gel permeation chromatography Methods 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 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
KQPMFNHZHBLVRR-UHFFFAOYSA-N oxalic acid;hydrochloride Chemical compound Cl.OC(=O)C(O)=O KQPMFNHZHBLVRR-UHFFFAOYSA-N 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
229960002275 pentobarbital sodium Drugs 0.000 description 1
KOUCTZDKTJGHSS-UHFFFAOYSA-N pentyl 4-methylbenzenesulfonate Chemical compound CCCCCOS(=O)(=O)C1=CC=C(C)C=C1 KOUCTZDKTJGHSS-UHFFFAOYSA-N 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000012071 phase Substances 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229920000573 polyethylene Polymers 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
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical compound CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000005588 protonation Effects 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
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 1
229960001404 quinidine Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
206010038464 renal hypertension Diseases 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
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229960001866 silicon dioxide Drugs 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
238000005694 sulfonylation reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WYFDZUFBNKIQKX-BPARTEKVSA-N tert-butyl 2-[(3r)-3-[[1-cyano-5-(1,3-dioxoisoindol-2-yl)pentyl]amino]-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetate Chemical compound O=C1N(CC(=O)OC(C)(C)C)C2=CC=CC=C2SC[C@@H]1NC(C#N)CCCCN1C(=O)C2=CC=CC=C2C1=O WYFDZUFBNKIQKX-BPARTEKVSA-N 0.000 description 1
CVAWKJKISIPBOD-UHFFFAOYSA-N tert-butyl 2-bromopropanoate Chemical compound CC(Br)C(=O)OC(C)(C)C CVAWKJKISIPBOD-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
239000012085 test solution Substances 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
LMVCLDAMMNHILO-UHFFFAOYSA-N thian-4-ylmethanol Chemical compound OCC1CCSCC1 LMVCLDAMMNHILO-UHFFFAOYSA-N 0.000 description 1
QGVNJRROSLYGKF-UHFFFAOYSA-N thiobarbital Chemical compound CCC1(CC)C(=O)NC(=S)NC1=O QGVNJRROSLYGKF-UHFFFAOYSA-N 0.000 description 1
239000011135 tin Substances 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

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CA000471650A 1984-03-22 1985-01-08 Derives de l'acide 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5- acetique Expired - Lifetime CA1281718C (fr)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
JP84/00119		1984-03-22
PCT/JP1984/000119 WO1985004402A1 (fr)	1984-03-24	1984-03-24	Composes cycliques fusionnes a sept membres et leur procede de preparation
PCT/JP1984/000172 WO1985004657A1 (fr)	1984-04-06	1984-04-06	Composes cycliques a 7 elements fusionnes et leur procede de preparation
JP84/00172		1984-04-06
US599,187		1984-04-11
US06/599,187 US4564612A (en)	1983-04-22	1984-04-11	Condensed, seven-membered ring compounds and their use
JP84/00363		1984-07-13
PCT/JP1984/000363 WO1986000618A1 (fr)	1984-07-13	1984-07-13	Composes cycliques condenses a 7 membres et leur procede de preparation

Publications (1)

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CA1281718C true CA1281718C (fr)	1991-03-19

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CA000471650A Expired - Lifetime CA1281718C (fr)	1984-03-22	1985-01-08	Derives de l'acide 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5- acetique

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CA (1)	CA1281718C (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN115948751A (zh) *	2022-12-31	2023-04-11	广西师范大学	电催化n-芳基马来酰亚胺与醇的开环二氢烷氧基化反应方法
CN116396295A (zh) *	2023-04-04	2023-07-07	合肥工业大学	一种基于protac的plk1降解剂的合成方法

1985
- 1985-01-08 CA CA000471650A patent/CA1281718C/fr not_active Expired - Lifetime

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN115948751A (zh) *	2022-12-31	2023-04-11	广西师范大学	电催化n-芳基马来酰亚胺与醇的开环二氢烷氧基化反应方法
CN116396295A (zh) *	2023-04-04	2023-07-07	合肥工业大学	一种基于protac的plk1降解剂的合成方法

Legal Events

Date	Code	Title	Description
1993-09-21	MKLA	Lapsed

Publication	Publication Date	Title
US4591458A (en)	1986-05-27	3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine derivatives
FI76074B (fi)	1988-05-31	Foerfarande foer framstaellning av antihypertensiva 3-amino-/1/bensazepin-2-on-1-alkansyror.
EP0024852A1 (fr)	1981-03-11	Dérivés du dihydro-2,3 1H-indole et leurs intermédiaires, procédés pour leur préparation, compositions pharmaceutiques contenant lesdits dérivés et leur préparation
EP0125056B1 (fr)	1991-01-16	Composés contenant des cycles à sept chaînons condensés, leur préparation et leur utilisation
KR940009528B1 (ko)	1994-10-14	헤테로 고리 화합물의 제조 방법
JPH0826037B2 (ja)	1996-03-13	生理活性物質ｋ−２５２の誘導体
EP0187037A2 (fr)	1986-07-09	Dérivés de pipéridine, leur production et emploi
CA1281718C (fr)	1991-03-19	Derives de l'acide 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5- acetique
EP0061768B1 (fr)	1986-05-14	Dipeptides N-amido substitués
US7253162B2 (en)	2007-08-07	Benzothiazine and benzothiadiazine compounds
US4638000A (en)	1987-01-20	Condensed seven-membered ring compounds, their production and use
EP0156455A2 (fr)	1985-10-02	Composés contenant des anneaux à 7 membres condensés, leur production et leur emploi
US4739066A (en)	1988-04-19	Intermediates for the preparation of condensed seven-membered ring compounds
NZ210781A (en)	1988-01-08	Benzothiazepine derivatives and pharmaceutical compositions
JPH0566389B2 (fr)	1993-09-21
EP0059966B1 (fr)	1986-08-13	Analogues et dérivés de l'acide thiazolidine carboxylique substitué, comme antihypertenseurs
KR890001194B1 (ko)	1989-04-27	N-(3-메르캅토-2-알킬-1-옥소프로필)-2,3-디하이드로-1h-인돌-2-카복실산 유도체의 제조방법
AU598105B2 (en)	1990-06-14	4-piperidyl derivatives
US4595675A (en)	1986-06-17	Bicyclic α-iminocarboxylic acid compounds having hypotensive activity
FI81089B (fi)	1990-05-31	4-piperidyl-substituerade karboxylsyraderivat och foerfarande foer deras framstaellning.
WO1985004657A1 (fr)	1985-10-24	Composes cycliques a 7 elements fusionnes et leur procede de preparation
Kato et al.	1997	Asymmetric synthesis of (R)‐6‐amino‐1‐methyl‐4‐(3‐methyl‐benzyl) hexahydro‐1H‐1, 4‐diazepine from L‐asparagine
DK155666B (da)	1989-05-01	Analogifremgangsmaade til fremstilling af 1,3,4,5-tetrahydro 2h-3-benzazepin-2-on-derivater eller syreadditionssalte deraf

CA1281718C - Derives de l'acide 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5- acetique - Google Patents

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Applications Claiming Priority (8)

Publications (1)

Family

ID=26425037

Family Applications (1)

Country Status (1)

Cited By (2)

Cited By (2)

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