JPH0427213B2 - - Google Patents

Info

Publication number: JPH0427213B2
Authority: JP; Japan
Prior art keywords: group; methoxyphenyl; benzothiazepine; lower alkyl; hydroxy
Prior art date: 1984-03-10
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

Application number

JP3254690A

Other languages

English (en)

Japanese (ja)

Other versions

JPH02288828A (ja

Inventor

Mikio Takeda

Atsuo Ooishi

Hiromichi Nakajima

Hiroshi Nagao

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.)

Tanabe Seiyaku Co Ltd

Original Assignee

Tanabe Seiyaku Co 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.)

1984-03-10

Filing date

1990-02-15

Publication date

1992-05-11

1990-02-15 Application filed by Tanabe Seiyaku Co Ltd filed Critical Tanabe Seiyaku Co Ltd

1990-11-28 Publication of JPH02288828A publication Critical patent/JPH02288828A/ja

1992-05-11 Publication of JPH0427213B2 publication Critical patent/JPH0427213B2/ja

Status Granted legal-status Critical Current

Links

150000003839 salts Chemical class 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 15
KJFRSZASZNLCDF-UHFFFAOYSA-N 1,5-benzothiazepine Chemical class S1C=CC=NC2=CC=CC=C12 KJFRSZASZNLCDF-UHFFFAOYSA-N 0.000 claims description 12
239000004480 active ingredient Substances 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000002252 acyl group Chemical group 0.000 claims description 8
230000002490 cerebral effect Effects 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
239000003218 coronary vasodilator agent Substances 0.000 claims description 5
101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 claims description 3
101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 claims description 3
229940127218 antiplatelet drug Drugs 0.000 claims description 3
239000000106 platelet aggregation inhibitor Substances 0.000 claims description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
150000001875 compounds Chemical class 0.000 description 39
239000000203 mixture Substances 0.000 description 32
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
239000002904 solvent Substances 0.000 description 22
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
238000004519 manufacturing process Methods 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
-1 methoxy, ethoxy Chemical group 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
239000002994 raw material Substances 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000013078 crystal Substances 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
238000001816 cooling Methods 0.000 description 8
239000012452 mother liquor Substances 0.000 description 7
239000008194 pharmaceutical composition Substances 0.000 description 7
208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
230000003276 anti-hypertensive effect Effects 0.000 description 6
230000017531 blood circulation Effects 0.000 description 6
235000014113 dietary fatty acids Nutrition 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
239000000194 fatty acid Substances 0.000 description 6
229930195729 fatty acid Natural products 0.000 description 6
150000004665 fatty acids Chemical class 0.000 description 6
238000000034 method Methods 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000006482 condensation reaction Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
239000000523 sample Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
150000007657 benzothiazepines Chemical class 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
229940085242 benzothiazepine derivative selective calcium channel blockers with direct cardiac effects Drugs 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
239000008103 glucose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
235000019260 propionic acid Nutrition 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group 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 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
230000000304 vasodilatating effect Effects 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ZKAFCDWKAHKZJG-UHFFFAOYSA-N 1,5-benzothiazepin-3-ol Chemical class N1=CC(O)=CSC2=CC=CC=C21 ZKAFCDWKAHKZJG-UHFFFAOYSA-N 0.000 description 2
BVABFIZTUSTDDW-UHFFFAOYSA-N 5h-1,2-benzothiazepin-4-one Chemical compound S1N=CC(=O)CC2=CC=CC=C21 BVABFIZTUSTDDW-UHFFFAOYSA-N 0.000 description 2
229930008281 A03AD01 - Papaverine Natural products 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
229960001789 papaverine Drugs 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
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239000002244 precipitate Substances 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-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
210000002385 vertebral artery Anatomy 0.000 description 2
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JHVKQEXNQYGGOH-AWEZNQCLSA-N (2s)-1-naphthalen-2-ylsulfonylpyrrolidine-2-carbonyl chloride Chemical compound ClC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 JHVKQEXNQYGGOH-AWEZNQCLSA-N 0.000 description 1
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125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
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QCLMTLDABHUUBC-UHFFFAOYSA-N 2-amino-4-methylbenzenethiol Chemical compound CC1=CC=C(S)C(N)=C1 QCLMTLDABHUUBC-UHFFFAOYSA-N 0.000 description 1
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LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
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150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
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230000001430 anti-depressive effect Effects 0.000 description 1
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MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
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239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
230000034994 death Effects 0.000 description 1
231100000517 death Toxicity 0.000 description 1
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Substances CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
239000007789 gas Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
208000001286 intracranial vasospasm Diseases 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
239000008101 lactose Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
235000019359 magnesium stearate Nutrition 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
QRNDDJXJUHBGSG-UHFFFAOYSA-N methoxyethyne Chemical group COC#C QRNDDJXJUHBGSG-UHFFFAOYSA-N 0.000 description 1
DKLZRLRMFNWRFB-UHFFFAOYSA-N methyl 2-(4-hydroxyanilino)acetate Chemical class COC(=O)CNC1=CC=C(O)C=C1 DKLZRLRMFNWRFB-UHFFFAOYSA-N 0.000 description 1
ARQVRCKIVSELCG-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(OC)C=C1 ARQVRCKIVSELCG-UHFFFAOYSA-N 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical class COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
239000012488 sample solution Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000011699 spontaneously hypertensive rat Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
208000023516 stroke disease Diseases 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
VSWLXYAZJZQIKA-UHFFFAOYSA-N tetrachloromethane;triphenylphosphane Chemical compound ClC(Cl)(Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VSWLXYAZJZQIKA-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000002936 tranquilizing effect Effects 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
235000019263 trisodium citrate Nutrition 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1

Landscapes

Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

JP3254690A 1984-03-10 1990-02-15 医薬組成物 Granted JPH02288828A (ja)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB8406318		1984-03-10
GB848406318A GB8406318D0 (en)	1984-03-10	1984-03-10	1 5-benzothiazepine derivatives

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
JP4423985A Division JPH0228594B2 (ja)	1984-03-10	1985-03-05	1*55benzochiazepinjudotai

Publications (2)

Publication Number	Publication Date
JPH02288828A JPH02288828A (ja)	1990-11-28
JPH0427213B2 true JPH0427213B2 (ko)	1992-05-11

Family

ID=10557882

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
JP4423985A Expired - Lifetime JPH0228594B2 (ja)	1984-03-10	1985-03-05	1*55benzochiazepinjudotai
JP3254690A Granted JPH02288828A (ja)	1984-03-10	1990-02-15	医薬組成物
JP3254790A Granted JPH02288871A (ja)	1984-03-10	1990-02-15	１，５‐ベンゾチアゼピン誘導体

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
JP4423985A Expired - Lifetime JPH0228594B2 (ja)	1984-03-10	1985-03-05	1*55benzochiazepinjudotai

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
JP3254790A Granted JPH02288871A (ja)	1984-03-10	1990-02-15	１，５‐ベンゾチアゼピン誘導体

Country Status (2)

Country	Link
JP (3)	JPH0228594B2 (ko)
GB (1)	GB8406318D0 (ko)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS649981A (en) *	1987-06-29	1989-01-13	Tanabe Seiyaku Co	1,5-benzothiazepine derivative
JPS649982A (en) *	1987-06-30	1989-01-13	Tanabe Seiyaku Co	1,5-benzothiazepine derivative
JP2703564B2 (ja) *	1987-07-31	1998-01-26	田辺製薬株式会社	１，５−ベンゾチアゼピン誘導体
JPS6450872A (en) *	1987-08-21	1989-02-27	Tanabe Seiyaku Co	Production of 1,5-benzothiazepine derivative
JPS6445376A (en) *	1987-08-12	1989-02-17	Tanabe Seiyaku Co	Production of 1,5-benzothiazepine derivative
JPH01128974A (ja) *	1987-11-13	1989-05-22	Tanabe Seiyaku Co Ltd	１，５−ベンゾチアゼピン誘導体の製法
JP2863534B2 (ja) *	1988-10-24	1999-03-03	マリオンラボラトリーズ，インコーポレイティド	医薬組成物
FR2641535B1 (fr) *	1989-01-11	1991-03-15	Synthelabo	Procede de preparation de (+) - (2s, 3s)-hydroxy-3 (methoxy-4 phenyl)-2 dihydro-2,3 5h-benzothiazepine-1,5 one-4
JPH0699409B2 (ja) *	1989-04-28	1994-12-07	田辺製薬株式会社	１，５―ベンゾチアゼピン誘導体の製法
JP2674232B2 (ja) *	1989-08-31	1997-11-12	田辺製薬株式会社	１，５―ベンゾチアゼピン誘導体
JPH0779706B2 (ja) *	1990-03-22	1995-08-30	田辺製薬株式会社	２―クロロ―３―ヒドロキシ―３―フエニルプロピオン酸エステル類の製法
JPH078798B2 (ja) *	1990-09-17	1995-02-01	田辺製薬株式会社	血小板凝集抑制組成物
JPH078799B2 (ja) *	1990-09-17	1995-02-01	田辺製薬株式会社	血小板凝集抑制組成物
JP2643798B2 (ja) *	1992-10-23	1997-08-20	田辺製薬株式会社	末梢動脈血流増加剤
IL123352A0 (en)	1997-02-27	1998-09-24	Tanabe Seiyaku Co	Process for preparing an optically active trans-3-substituted glycidic acid ester

1984
- 1984-03-10 GB GB848406318A patent/GB8406318D0/en active Pending
1985
- 1985-03-05 JP JP4423985A patent/JPH0228594B2/ja not_active Expired - Lifetime
1990
- 1990-02-15 JP JP3254690A patent/JPH02288828A/ja active Granted
- 1990-02-15 JP JP3254790A patent/JPH02288871A/ja active Granted

Also Published As

Publication number	Publication date
JPH02288871A (ja)	1990-11-28
JPH02288828A (ja)	1990-11-28
JPH0228594B2 (ja)	1990-06-25
GB8406318D0 (en)	1984-04-11
JPH0376307B2 (ko)	1991-12-05
JPS60202871A (ja)	1985-10-14

Legal Events

Date	Code	Title	Description
2004-06-01	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2005-03-05	EXPY	Cancellation because of completion of term

Publication	Publication Date	Title
KR900005697B1 (ko)	1990-08-06	8-클로로-1,5-벤조티아제핀 유도체의 제조방법
EP0154838B1 (en)	1988-07-06	Novel 1,5-benzothiazepine derivatives, processes for preparing the same and pharmaceutical compositions
JPH0427213B2 (ko)	1992-05-11
US4585768A (en)	1986-04-29	1,5-benzothiazepine derivatives and processes for preparing the same
US4665068A (en)	1987-05-12	Novel 9-chloro-1,5-benzothiazepine derivatives and their pharmaceutical use
JPS6313994B2 (ko)	1988-03-29
EP0158340B1 (en)	1989-01-18	Novel 1,5-benzothiazepine derivative, processes for preparing the same and pharmaceutical compositions
JPS60231669A (ja)	1985-11-18	１，５―ベンゾチアゼピン誘導体
FI85976B (fi)	1992-03-13	Foerfarande foer framstaellning av farmakologiskt vaerdefullt naftotiazepinderivat.
JPH0421667B2 (ko)	1992-04-13
JPH0421668B2 (ko)	1992-04-13
JPS62174019A (ja)	1987-07-30	血小板凝集抑制剤
JPS60226867A (ja)	1985-11-12	１，５―ベンゾチアゼピン誘導体
JPH0240372A (ja)	1990-02-09	ナフトチアゼピン誘導体
JPH0376290B2 (ko)	1991-12-05
JPS61103828A (ja)	1986-05-22	医薬組成物
JPS6281316A (ja)	1987-04-14	血小板凝集抑制剤
JPH05239042A (ja)	1993-09-17	１，５−ベンゾチアゼピン誘導体及びその合成中間体