PT1732929E - Composto de benzopirano tricíclico enquanto agentes antiarrítmicos - Google Patents
Composto de benzopirano tricíclico enquanto agentes antiarrítmicos Download PDFInfo
- Publication number
- PT1732929E PT1732929E PT05727581T PT05727581T PT1732929E PT 1732929 E PT1732929 E PT 1732929E PT 05727581 T PT05727581 T PT 05727581T PT 05727581 T PT05727581 T PT 05727581T PT 1732929 E PT1732929 E PT 1732929E
- Authority
- PT
- Portugal
- Prior art keywords
- amino
- dihydro
- group
- pyrano
- trimethyl
- Prior art date
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- -1 benzopyran compound Chemical class 0.000 title claims description 226
- 239000003416 antiarrhythmic agent Substances 0.000 title abstract description 8
- 150000001562 benzopyrans Chemical class 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000003277 amino group Chemical group 0.000 claims abstract 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 86
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 65
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 63
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 49
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical compound C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- IQQDNMHUOLMLNJ-UHFFFAOYSA-N quinolin-3-ol Chemical compound C1=CC=CC2=CC(O)=CN=C21 IQQDNMHUOLMLNJ-UHFFFAOYSA-N 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 206010003119 arrhythmia Diseases 0.000 claims description 14
- 230000006793 arrhythmia Effects 0.000 claims description 14
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- OZMHIFNNCZPJFS-UHFFFAOYSA-N quinoline-7-carbonitrile Chemical compound C1=CC=NC2=CC(C#N)=CC=C21 OZMHIFNNCZPJFS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- CHIOVPNYOWEUJW-UHFFFAOYSA-N 2,2,7-trimethyl-4-(2-phenylethylamino)-3,4-dihydropyrano[2,3-g]quinolin-3-ol Chemical compound C12=CC3=NC(C)=CC=C3C=C2OC(C)(C)C(O)C1NCCC1=CC=CC=C1 CHIOVPNYOWEUJW-UHFFFAOYSA-N 0.000 claims 1
- IDLTUNKJYAGSFN-UHFFFAOYSA-N 2,2-dimethyl-4-(2-phenylethylamino)-3,4-dihydropyrano[2,3-g]quinolin-3-ol Chemical compound OC1C(C)(C)OC2=CC3=CC=CN=C3C=C2C1NCCC1=CC=CC=C1 IDLTUNKJYAGSFN-UHFFFAOYSA-N 0.000 claims 1
- GGBFTFYRWHXKLX-UHFFFAOYSA-N 2,2-dimethyl-N-(2-phenylethyl)-3,4-dihydropyran-4-amine Chemical compound CC1(C)CC(NCCC2=CC=CC=C2)C=CO1 GGBFTFYRWHXKLX-UHFFFAOYSA-N 0.000 claims 1
- KCHOBYCFOXAKNM-UHFFFAOYSA-N 7-chloro-4-(2-cyclohexylethylamino)-2,2,9-trimethyl-3,4-dihydropyrano[2,3-g]quinolin-3-ol Chemical compound OC1C(C)(C)OC=2C=C3C(C)=CC(Cl)=NC3=CC=2C1NCCC1CCCCC1 KCHOBYCFOXAKNM-UHFFFAOYSA-N 0.000 claims 1
- HZUJFGLZSGYMQT-UHFFFAOYSA-N 8-hydroxy-7,7-dimethyl-9-(2-phenylethylamino)-8,9-dihydro-1h-pyrano[3,2-g][1,4]benzoxazin-2-one Chemical compound OC1C(C)(C)OC2=CC=3OCC(=O)NC=3C=C2C1NCCC1=CC=CC=C1 HZUJFGLZSGYMQT-UHFFFAOYSA-N 0.000 claims 1
- KOCXCSREADKFMD-UHFFFAOYSA-N 8-hydroxy-7,7-dimethyl-9-(2-phenylethylamino)-8,9-dihydro-4h-pyrano[2,3-g][1,4]benzoxazin-3-one Chemical compound OC1C(C)(C)OC2=CC=3NC(=O)COC=3C=C2C1NCCC1=CC=CC=C1 KOCXCSREADKFMD-UHFFFAOYSA-N 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- ZUQDDQFXSNXEOD-UHFFFAOYSA-N quinoxalin-5-ol Chemical compound C1=CN=C2C(O)=CC=CC2=N1 ZUQDDQFXSNXEOD-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 141
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 4
- 125000004429 atom Chemical group 0.000 abstract description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
- 125000004434 sulfur atom Chemical group 0.000 abstract description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 abstract 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 239000000470 constituent Substances 0.000 abstract 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 363
- 239000000243 solution Substances 0.000 description 259
- 238000003786 synthesis reaction Methods 0.000 description 174
- 230000015572 biosynthetic process Effects 0.000 description 173
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 159
- 239000000047 product Substances 0.000 description 141
- 238000005160 1H NMR spectroscopy Methods 0.000 description 134
- 239000000203 mixture Substances 0.000 description 121
- 238000006243 chemical reaction Methods 0.000 description 116
- 239000002904 solvent Substances 0.000 description 101
- 239000000460 chlorine Substances 0.000 description 93
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 74
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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 70
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
- 239000007864 aqueous solution Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 54
- 235000019253 formic acid Nutrition 0.000 description 54
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 51
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 48
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 47
- 239000013078 crystal Substances 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 229920006395 saturated elastomer Polymers 0.000 description 37
- 235000017557 sodium bicarbonate Nutrition 0.000 description 37
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- 238000004821 distillation Methods 0.000 description 34
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- 239000011780 sodium chloride Substances 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 235000019441 ethanol Nutrition 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 238000000354 decomposition reaction Methods 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 20
- 230000001746 atrial effect Effects 0.000 description 19
- 238000004440 column chromatography Methods 0.000 description 19
- 230000036279 refractory period Effects 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 16
- 235000019270 ammonium chloride Nutrition 0.000 description 16
- 125000000623 heterocyclic group Chemical group 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 210000003205 muscle Anatomy 0.000 description 15
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 230000002861 ventricular Effects 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 11
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 11
- 235000019345 sodium thiosulphate Nutrition 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 10
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 10
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 10
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000011976 maleic acid Substances 0.000 description 8
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 8
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- MYVQNEHWKNRZPD-UHFFFAOYSA-N 2,2,9-trimethylpyrano[2,3-g]quinoline Chemical compound C1=CC(C)(C)OC2=C1C=C1N=CC=C(C)C1=C2 MYVQNEHWKNRZPD-UHFFFAOYSA-N 0.000 description 6
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- 239000003377 acid catalyst Substances 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
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- 239000005708 Sodium hypochlorite Substances 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 244000309464 bull Species 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
- 230000037024 effective refractory period Effects 0.000 description 4
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- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
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- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical class C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- XTTGYFREQJCEML-UHFFFAOYSA-N tributyl phosphite Chemical compound CCCCOP(OCCCC)OCCCC XTTGYFREQJCEML-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 125000001874 trioxidanyl group Chemical group [*]OOO[H] 0.000 description 1
- BKHZQJRTFNFCTG-UHFFFAOYSA-N tris(2-methylphenyl) phosphite Chemical compound CC1=CC=CC=C1OP(OC=1C(=CC=CC=1)C)OC1=CC=CC=C1C BKHZQJRTFNFCTG-UHFFFAOYSA-N 0.000 description 1
- 230000001515 vagal effect Effects 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229910052727 yttrium Chemical group 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D515/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Dental Preparations (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004084605 | 2004-03-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1732929E true PT1732929E (pt) | 2010-12-21 |
Family
ID=34962589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT05727581T PT1732929E (pt) | 2004-03-23 | 2005-03-23 | Composto de benzopirano tricíclico enquanto agentes antiarrítmicos |
Country Status (30)
| Country | Link |
|---|---|
| US (2) | US7652008B2 (https=) |
| EP (1) | EP1732929B1 (https=) |
| JP (1) | JP4840594B2 (https=) |
| KR (2) | KR101085979B1 (https=) |
| CN (3) | CN102190661B (https=) |
| AT (1) | ATE485299T1 (https=) |
| AU (2) | AU2005223612B2 (https=) |
| BR (1) | BRPI0508768A (https=) |
| CA (1) | CA2558139C (https=) |
| CY (1) | CY1111250T1 (https=) |
| CZ (1) | CZ2006598A3 (https=) |
| DE (1) | DE602005024245D1 (https=) |
| DK (1) | DK1732929T3 (https=) |
| EG (1) | EG27163A (https=) |
| ES (1) | ES2353021T3 (https=) |
| HR (1) | HRP20110005T1 (https=) |
| IL (1) | IL177950A (https=) |
| MX (1) | MXPA06010880A (https=) |
| NO (1) | NO339495B1 (https=) |
| NZ (2) | NZ549570A (https=) |
| PL (1) | PL1732929T3 (https=) |
| PT (1) | PT1732929E (https=) |
| RS (1) | RS51742B (https=) |
| RU (1) | RU2380370C2 (https=) |
| SI (1) | SI1732929T1 (https=) |
| SK (1) | SK287994B6 (https=) |
| TW (1) | TWI352704B (https=) |
| UA (1) | UA91189C2 (https=) |
| WO (1) | WO2005090357A1 (https=) |
| ZA (1) | ZA200607388B (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2353021T3 (es) * | 2004-03-23 | 2011-02-24 | Nissan Chemical Industries, Ltd. | Compuesto de benzopirano tricíclico como agentes anti-arrítmicos. |
| RU2448112C2 (ru) | 2006-03-10 | 2012-04-20 | Ниссан Кемикал Индастриз, Лтд. | Способ получения оптически активного соединения оксида хромена |
| TW201022223A (en) * | 2008-08-14 | 2010-06-16 | Nissan Chemical Ind Ltd | Di-substituted benzopyrane compound |
| KR101703202B1 (ko) * | 2009-04-30 | 2017-02-06 | 닛산 가가쿠 고교 가부시키 가이샤 | 3환성 벤조피란 화합물의 신규한 결정형태 및 그 제조방법 |
| US8431576B2 (en) | 2009-06-25 | 2013-04-30 | Alkermes Pharma Ireland Limited | Heterocyclic compounds for the treatment of neurological and psychological disorders |
| JPWO2014051077A1 (ja) * | 2012-09-27 | 2016-08-25 | 日産化学工業株式会社 | 高純度の含窒素複素環化合物の製造方法 |
| JP6202280B2 (ja) * | 2012-09-27 | 2017-09-27 | 日産化学工業株式会社 | 含窒素複素環ｎ−オキシド化合物の製造方法 |
| JPWO2015012271A1 (ja) * | 2013-07-25 | 2017-03-02 | 日産化学工業株式会社 | 複素環化合物の製造方法 |
| US11168094B2 (en) | 2017-01-06 | 2021-11-09 | Azcuris Co., Ltd. | Quinolinone derivative and pharmaceutical composition for preventing or treating allergic diseases such as asthma or atopic dermatitis including the quinolinone derivative as active ingredient |
| EP3761983A1 (en) | 2018-03-05 | 2021-01-13 | Alkermes Pharma Ireland Limited | Aripiprazole dosing strategy |
| CN108727261B (zh) * | 2018-06-21 | 2021-09-24 | 济南大学 | 一种硝基取代喹那啶的制备方法 |
| US20220071951A1 (en) * | 2018-12-28 | 2022-03-10 | Osaka University | Therapeutic agent for inherited bradyarrhythmia |
| RU2754610C1 (ru) * | 2020-04-14 | 2021-09-03 | Георгий Викторович ТЕЦ | Препарат для лечения заболеваний, вызванных бактериями |
| CN115916201B (zh) * | 2020-06-26 | 2024-09-17 | 国立大学法人大阪大学 | 药剂诱发性心动过缓及心动过缓性心律失常治疗药 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZM7682A1 (en) | 1981-09-25 | 1983-05-23 | Beecham Group Plc | Active compounds |
| JPS5867683U (ja) | 1981-10-28 | 1983-05-09 | 株式会社ナムコ | 歩行ロボツト |
| JPH0699439B2 (ja) * | 1988-02-03 | 1994-12-07 | 日産化学工業株式会社 | ピラノベンゾオキサジアゾール誘導体 |
| JP2658198B2 (ja) * | 1988-06-23 | 1997-09-30 | 日産化学工業株式会社 | ピラノベンゾトリアゾール誘導体 |
| JP2876712B2 (ja) * | 1989-07-17 | 1999-03-31 | 日産化学工業株式会社 | 光学活性ピラノベンゾオキサジアゾール誘導体 |
| US5097037A (en) * | 1989-07-17 | 1992-03-17 | Nissan Chemical Industries, Ltd. | Process for the optical resolution of pyranobenzoxadiazole compounds |
| US5164509A (en) * | 1990-11-26 | 1992-11-17 | E. R. Squibb & Sons, Inc. | Benzodiazolo analogs |
| JPH07300414A (ja) * | 1993-04-02 | 1995-11-14 | Nissan Chem Ind Ltd | 心不全治療薬 |
| UA27973C2 (uk) * | 1993-04-02 | 2000-10-16 | Ніссан Кемікал Індастріз Лтд | Лікарський засіб для лікування серцевої недостатності |
| JP2734457B2 (ja) | 1994-02-23 | 1998-03-30 | 日産化学工業株式会社 | 不斉エポキシ化反応 |
| WO1995034547A1 (en) * | 1994-06-10 | 1995-12-21 | Smithkline Beecham Plc | C-4 amide substituted compounds and their use as therapeutic agents |
| HRP970255B1 (en) * | 1996-05-15 | 2003-10-31 | Hoechst Ag | Sulfonamido substituted chromane derivatives, method for their preparation, their use as medicaments or diagnostic agents as well as medicaments containing them |
| US6486178B1 (en) | 1998-06-03 | 2002-11-26 | Nissan Chemical Industries, Ltd. | Indane derivatives |
| AU5444499A (en) | 1998-09-01 | 2000-03-21 | Nissan Chemical Industries Ltd. | Benzoxazine derivatives |
| AU2830800A (en) | 1999-03-25 | 2000-10-16 | Nissan Chemical Industries Ltd. | Chroman derivatives |
| CA2383583C (en) * | 1999-09-17 | 2009-04-07 | Nissan Chemical Industries, Ltd. | Benzopyran derivative |
| EP1214307B1 (en) | 1999-09-24 | 2004-04-07 | Nissan Chemical Industries, Ltd. | 4-oxybenzopyran derivative |
| US6677371B1 (en) | 1999-10-05 | 2004-01-13 | Nissan Chemical Industries, Ltd. | 4-oxybenzopyran derivative |
| TW589305B (en) | 2001-02-14 | 2004-06-01 | Nissan Chemical Ind Ltd | 4-aminobenzopyran derivatives |
| EP1401823B1 (en) | 2001-06-25 | 2005-10-05 | Nissan Chemical Industries, Ltd. | Substituted benzopyran derivatives against arrhythmia |
| WO2003014113A1 (en) | 2001-08-06 | 2003-02-20 | Glenmark Pharmaceuticals Limited | Novel benzopyran compounds and process for their preparation and use |
| ES2353021T3 (es) * | 2004-03-23 | 2011-02-24 | Nissan Chemical Industries, Ltd. | Compuesto de benzopirano tricíclico como agentes anti-arrítmicos. |
-
2005
- 2005-03-23 ES ES05727581T patent/ES2353021T3/es not_active Expired - Lifetime
- 2005-03-23 SK SK5079-2006A patent/SK287994B6/sk not_active IP Right Cessation
- 2005-03-23 PT PT05727581T patent/PT1732929E/pt unknown
- 2005-03-23 TW TW094108962A patent/TWI352704B/zh not_active IP Right Cessation
- 2005-03-23 NZ NZ549570A patent/NZ549570A/en not_active IP Right Cessation
- 2005-03-23 SI SI200531171T patent/SI1732929T1/sl unknown
- 2005-03-23 DE DE602005024245T patent/DE602005024245D1/de not_active Expired - Lifetime
- 2005-03-23 US US10/590,975 patent/US7652008B2/en active Active
- 2005-03-23 CN CN2011100751168A patent/CN102190661B/zh not_active Expired - Fee Related
- 2005-03-23 UA UAA200611101A patent/UA91189C2/ru unknown
- 2005-03-23 ZA ZA200607388A patent/ZA200607388B/en unknown
- 2005-03-23 CN CN2008101707921A patent/CN101429200B/zh not_active Expired - Fee Related
- 2005-03-23 CN CN2005800090295A patent/CN1934116B/zh not_active Expired - Lifetime
- 2005-03-23 JP JP2006530022A patent/JP4840594B2/ja not_active Expired - Lifetime
- 2005-03-23 CA CA2558139A patent/CA2558139C/en not_active Expired - Fee Related
- 2005-03-23 DK DK05727581.0T patent/DK1732929T3/da active
- 2005-03-23 KR KR1020107027058A patent/KR101085979B1/ko not_active Expired - Fee Related
- 2005-03-23 RU RU2006137284/04A patent/RU2380370C2/ru not_active IP Right Cessation
- 2005-03-23 HR HR20110005T patent/HRP20110005T1/hr unknown
- 2005-03-23 AU AU2005223612A patent/AU2005223612B2/en not_active Ceased
- 2005-03-23 NZ NZ585606A patent/NZ585606A/en not_active IP Right Cessation
- 2005-03-23 PL PL05727581T patent/PL1732929T3/pl unknown
- 2005-03-23 MX MXPA06010880A patent/MXPA06010880A/es active IP Right Grant
- 2005-03-23 KR KR1020067021988A patent/KR101019402B1/ko not_active Expired - Lifetime
- 2005-03-23 WO PCT/JP2005/006004 patent/WO2005090357A1/en not_active Ceased
- 2005-03-23 BR BRPI0508768-6A patent/BRPI0508768A/pt not_active Application Discontinuation
- 2005-03-23 EP EP05727581A patent/EP1732929B1/en not_active Expired - Lifetime
- 2005-03-23 CZ CZ20060598A patent/CZ2006598A3/cs unknown
- 2005-03-23 AT AT05727581T patent/ATE485299T1/de active
- 2005-03-23 RS RS20110028A patent/RS51742B/sr unknown
-
2006
- 2006-09-02 EG EGNA2006000900 patent/EG27163A/xx active
- 2006-09-07 IL IL177950A patent/IL177950A/en not_active IP Right Cessation
- 2006-10-23 NO NO20064819A patent/NO339495B1/no not_active IP Right Cessation
-
2009
- 2009-11-17 US US12/591,353 patent/US7964623B2/en not_active Expired - Fee Related
-
2010
- 2010-07-08 AU AU2010202900A patent/AU2010202900B2/en not_active Ceased
-
2011
- 2011-01-19 CY CY20111100060T patent/CY1111250T1/el unknown
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