JPH0551588B2 - - Google Patents
Info
- Publication number
- JPH0551588B2 JPH0551588B2 JP86169847A JP16984786A JPH0551588B2 JP H0551588 B2 JPH0551588 B2 JP H0551588B2 JP 86169847 A JP86169847 A JP 86169847A JP 16984786 A JP16984786 A JP 16984786A JP H0551588 B2 JPH0551588 B2 JP H0551588B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- methyl
- dihydro
- oxo
- benzothiazine
- 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 60
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 238000002844 melting Methods 0.000 description 38
- 230000008018 melting Effects 0.000 description 38
- -1 phenyloxy group Chemical group 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 13
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 12
- 229940126062 Compound A Drugs 0.000 description 11
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 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 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000008101 lactose Substances 0.000 description 9
- FBOSKQVOIHEWAX-UHFFFAOYSA-N benzothiazine Chemical class C1=CC=C2N=CCSC2=C1 FBOSKQVOIHEWAX-UHFFFAOYSA-N 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- DIEJEELGDWGUCV-WLHGVMLRSA-N 2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCN(C)CCOC1=CC=C(OCO2)C2=C1 DIEJEELGDWGUCV-WLHGVMLRSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000000704 physical effect Effects 0.000 description 6
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 230000002213 calciumantagonistic effect Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- MWXZAALLSPVRIN-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[5-methoxy-2-[4-[methyl-[2-(3,4,5-trimethoxyphenoxy)ethyl]amino]butoxy]phenyl]-4-methyl-1,4-benzothiazin-3-one Chemical compound OC(=O)\C=C\C(O)=O.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCCN(C)CCOC1=CC(OC)=C(OC)C(OC)=C1 MWXZAALLSPVRIN-WLHGVMLRSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 3
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 3
- OSIHAUUUEFEAKY-UHFFFAOYSA-N 2-(2-hydroxy-5-methoxyphenyl)-4-methyl-1,4-benzothiazin-3-one Chemical compound COC1=CC=C(O)C(C2C(N(C)C3=CC=CC=C3S2)=O)=C1 OSIHAUUUEFEAKY-UHFFFAOYSA-N 0.000 description 3
- WEGYSJAJMPOKRI-UHFFFAOYSA-N 2-[2-[4-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]butoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;oxalic acid Chemical compound OC(=O)C(O)=O.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCCN(C)CCOC1=CC=C(OCO2)C2=C1 WEGYSJAJMPOKRI-UHFFFAOYSA-N 0.000 description 3
- 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 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 3
- 239000001087 glyceryl triacetate Substances 0.000 description 3
- 235000013773 glyceryl triacetate Nutrition 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 3
- 229920001592 potato starch Polymers 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 229960002622 triacetin Drugs 0.000 description 3
- URGNBHNOQDVJCG-UHFFFAOYSA-N 2-[2-(3-bromopropoxy)-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one Chemical compound COC1=CC=C(OCCCBr)C(C2C(N(C)C3=CC=CC=C3S2)=O)=C1 URGNBHNOQDVJCG-UHFFFAOYSA-N 0.000 description 2
- QJPHUNPOJNLVRG-UHFFFAOYSA-N 2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one 2-hydroxy-2-phenylacetic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCN(C)CCOC1=CC=C(OCO2)C2=C1 QJPHUNPOJNLVRG-UHFFFAOYSA-N 0.000 description 2
- BDXFBMWGPVJNQN-WLHGVMLRSA-N 2-[2-[4-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]butoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCCN(C)CCOC1=CC=C(OCO2)C2=C1 BDXFBMWGPVJNQN-WLHGVMLRSA-N 0.000 description 2
- IFXHQULCWYGQMV-UHFFFAOYSA-N 2-[4-[4-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]butoxy]phenyl]-4-methyl-1,4-benzothiazin-3-one;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2OCOC2=CC(OCCN(CCCCOC=2C=CC(=CC=2)C2C(N(C)C3=CC=CC=C3S2)=O)C)=C1 IFXHQULCWYGQMV-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002284 Cellulose triacetate Polymers 0.000 description 2
- 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 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- IWYDHOAUDWTVEP-ZETCQYMHSA-M (S)-mandelate Chemical compound [O-]C(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-M 0.000 description 1
- LDONSNUBBPBNHO-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[4-[4-[2-(2-chlorophenoxy)ethyl-methylamino]butoxy]phenyl]-4h-1,4-benzothiazin-3-one Chemical compound OC(=O)\C=C\C(O)=O.C=1C=C(C2C(NC3=CC=CC=C3S2)=O)C=CC=1OCCCCN(C)CCOC1=CC=CC=C1Cl LDONSNUBBPBNHO-WLHGVMLRSA-N 0.000 description 1
- PQDZYOUYROPJGN-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yloxy)-n-methylethanamine Chemical compound CNCCOC1=CC=C2OCOC2=C1 PQDZYOUYROPJGN-UHFFFAOYSA-N 0.000 description 1
- VNWRTGOGEXBNSD-UHFFFAOYSA-N 2-[2-(4-bromobutoxy)-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one Chemical compound COC1=CC=C(OCCCCBr)C(C2C(N(C)C3=CC=CC=C3S2)=O)=C1 VNWRTGOGEXBNSD-UHFFFAOYSA-N 0.000 description 1
- FXJRDRJPJJTIIR-UHFFFAOYSA-N 2-[2-[2-[3-(1,3-benzodioxol-5-yloxy)propyl-methylamino]ethoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;oxalic acid Chemical compound OC(=O)C(O)=O.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCN(C)CCCOC1=CC=C(OCO2)C2=C1 FXJRDRJPJJTIIR-UHFFFAOYSA-N 0.000 description 1
- QEXGSXDFQURHPC-UHFFFAOYSA-N 2-[2-[3-[(3,4-dimethoxyphenoxy)methyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;hydrochloride Chemical compound Cl.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCN(C)COC1=CC=C(OC)C(OC)=C1 QEXGSXDFQURHPC-UHFFFAOYSA-N 0.000 description 1
- KOVPTANETKJOOL-WLHGVMLRSA-N 2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-chlorophenyl]-4-methyl-1,4-benzothiazin-3-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C2OCOC2=CC(OCCN(CCCOC=2C(=CC(Cl)=CC=2)C2C(N(C)C3=CC=CC=C3S2)=O)C)=C1 KOVPTANETKJOOL-WLHGVMLRSA-N 0.000 description 1
- CVDVYIMDVZBYFJ-WLHGVMLRSA-N 2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-methylphenyl]-4-methyl-1,4-benzothiazin-3-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C2OCOC2=CC(OCCN(CCCOC=2C(=CC(C)=CC=2)C2C(N(C)C3=CC=CC=C3S2)=O)C)=C1 CVDVYIMDVZBYFJ-WLHGVMLRSA-N 0.000 description 1
- IXGYXWGGTYLBQH-WLHGVMLRSA-N 2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-nitrophenyl]-4-methyl-1,4-benzothiazin-3-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C2OCOC2=CC(OCCN(CCCOC=2C(=CC(=CC=2)[N+]([O-])=O)C2C(N(C)C3=CC=CC=C3S2)=O)C)=C1 IXGYXWGGTYLBQH-WLHGVMLRSA-N 0.000 description 1
- QTQVIVWOJIPZFB-UHFFFAOYSA-N 2-[2-[3-[2-(2,6-dimethoxyphenoxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;hydrochloride Chemical compound Cl.S1C2=CC=CC=C2N(C)C(=O)C1C1=CC(OC)=CC=C1OCCCN(C)CCOC1=C(OC)C=CC=C1OC QTQVIVWOJIPZFB-UHFFFAOYSA-N 0.000 description 1
- AQCNWTSEEJAUIY-UHFFFAOYSA-N 2-[2-[3-[2-(3,4-dimethoxyphenoxy)ethyl-methylamino]propoxy]-5-methoxy-4-nitrophenyl]-4-methyl-1,4-benzothiazin-3-one;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C(OC)C(OC)=CC=C1OCCN(C)CCCOC1=CC([N+]([O-])=O)=C(OC)C=C1C1C(=O)N(C)C2=CC=CC=C2S1 AQCNWTSEEJAUIY-UHFFFAOYSA-N 0.000 description 1
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
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- 229920001615 Tragacanth Polymers 0.000 description 1
- WRWYGOVGIGCDLE-UHFFFAOYSA-N [O]c1ccccc1F Chemical group [O]c1ccccc1F WRWYGOVGIGCDLE-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
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- 239000000739 antihistaminic agent Substances 0.000 description 1
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- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910010277 boron hydride Inorganic materials 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
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
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- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
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- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
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- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002917 insecticide Substances 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
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- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- 239000004014 plasticizer Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- 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
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP1985/000426 WO1987000837A1 (fr) | 1985-07-29 | 1985-07-29 | Nouveaux derives de benzothiazine |
| WO85/426 | 1985-07-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62123181A JPS62123181A (ja) | 1987-06-04 |
| JPH0551588B2 true JPH0551588B2 (fr) | 1993-08-03 |
Family
ID=13846537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61169847A Granted JPS62123181A (ja) | 1985-07-29 | 1986-07-21 | 新規ベンゾチアジン誘導体 |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS62123181A (fr) |
| WO (1) | WO1987000837A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002542283A (ja) * | 1999-04-22 | 2002-12-10 | グラクソ・スミスクライン株式会社 | 医薬処方物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4584300A (en) * | 1983-02-07 | 1986-04-22 | Santen Pharmaceutical Co., Ltd. | Platelet anti-aggregative- and calcium antagonistic -1,4-benzothiazin-3-one derivatives, compositions, and methods of use therefor |
-
1985
- 1985-07-29 WO PCT/JP1985/000426 patent/WO1987000837A1/fr unknown
-
1986
- 1986-07-21 JP JP61169847A patent/JPS62123181A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002542283A (ja) * | 1999-04-22 | 2002-12-10 | グラクソ・スミスクライン株式会社 | 医薬処方物 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62123181A (ja) | 1987-06-04 |
| WO1987000837A1 (fr) | 1987-02-12 |
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