NO310976B1 - 5,11-dihydrobenzo[b,e][1,4]oksazepinderivater og farmasoytiske sammensetninger inneholdende de samme - Google Patents
5,11-dihydrobenzo[b,e][1,4]oksazepinderivater og farmasoytiske sammensetninger inneholdende de samme Download PDFInfo
- Publication number
- NO310976B1 NO310976B1 NO19984162A NO984162A NO310976B1 NO 310976 B1 NO310976 B1 NO 310976B1 NO 19984162 A NO19984162 A NO 19984162A NO 984162 A NO984162 A NO 984162A NO 310976 B1 NO310976 B1 NO 310976B1
- Authority
- NO
- Norway
- Prior art keywords
- oxazepine
- hydrogen atom
- mmol
- dihydro
- hydrates
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 19
- WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical class O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 58
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 150000004677 hydrates Chemical class 0.000 claims abstract description 20
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 17
- CJKPKVLFYAXEBS-UHFFFAOYSA-N 2,3,6,7-tetrahydrooxazepine Chemical class C1CC=CCNO1 CJKPKVLFYAXEBS-UHFFFAOYSA-N 0.000 claims description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- REUFESBNLHXVHN-HSZRJFAPSA-N 11-[[(2r)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-2-yl]methyl]-6h-benzo[c][1,5]benzoxazepine Chemical group C1=CC(OC)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)CCC1 REUFESBNLHXVHN-HSZRJFAPSA-N 0.000 claims description 5
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- UKPCNMUHCSROLE-HSZRJFAPSA-N 11-[[(2r)-1-[2-(4-fluorophenyl)ethyl]pyrrolidin-2-yl]methyl]-6h-benzo[c][1,5]benzoxazepine Chemical compound C1=CC(F)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)CCC1 UKPCNMUHCSROLE-HSZRJFAPSA-N 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 52
- 230000000694 effects Effects 0.000 abstract description 17
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 230000002411 adverse Effects 0.000 abstract 1
- 230000007659 motor function Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- 239000000243 solution Substances 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000012046 mixed solvent Substances 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000011780 sodium chloride Substances 0.000 description 23
- 238000000921 elemental analysis Methods 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- -1 methoxy, ethoxy Chemical group 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 238000004440 column chromatography Methods 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- SLGIBJWUMUWIFH-UHFFFAOYSA-N 6,11-dihydrobenzo[c][1,5]benzoxazepine Chemical compound C1OC2=CC=CC=C2NC2=CC=CC=C12 SLGIBJWUMUWIFH-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 229940127291 Calcium channel antagonist Drugs 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000000480 calcium channel blocker Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 208000002551 irritable bowel syndrome Diseases 0.000 description 7
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229940126062 Compound A Drugs 0.000 description 6
- 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 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 230000036760 body temperature Effects 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 208000028774 intestinal disease Diseases 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- 108090000312 Calcium Channels Proteins 0.000 description 4
- 102000003922 Calcium Channels Human genes 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 230000001078 anti-cholinergic effect Effects 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 230000029142 excretion Effects 0.000 description 4
- 210000003405 ileum Anatomy 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 231100000053 low toxicity Toxicity 0.000 description 3
- 230000004899 motility Effects 0.000 description 3
- 229960001783 nicardipine Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- MALUIDUWVBGDMU-IVMQYODDSA-N (3s)-3-chloro-1-[2-(4-methoxyphenyl)-2-(oxan-2-yl)ethyl]piperidine Chemical compound C1=CC(OC)=CC=C1C(C1OCCCC1)CN1C[C@@H](Cl)CCC1 MALUIDUWVBGDMU-IVMQYODDSA-N 0.000 description 2
- LPPSBNUFSWTGSA-GOEBONIOSA-N (3s,5r)-3-chloro-5-(methoxymethoxy)-1-[2-(4-methoxyphenyl)ethyl]piperidine Chemical compound C1[C@H](OCOC)C[C@H](Cl)CN1CCC1=CC=C(OC)C=C1 LPPSBNUFSWTGSA-GOEBONIOSA-N 0.000 description 2
- FZTPYHFHQJQQFN-PKTZIBPZSA-N (3s,5r)-5-(6h-benzo[c][1,5]benzoxazepin-11-ylmethyl)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-3-ol Chemical compound C1=CC(OC)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)C[C@H](O)C1 FZTPYHFHQJQQFN-PKTZIBPZSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 2
- JJLBVKRIOOBGPP-UHFFFAOYSA-N 2-bromo-1-(4-methoxyphenyl)ethanol Chemical compound COC1=CC=C(C(O)CBr)C=C1 JJLBVKRIOOBGPP-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 208000006550 Mydriasis Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- FSFDCELVHDUMKA-IPJUCJBFSA-N [(2r)-1-[2-(4-methoxyphenyl)-2-(oxan-2-yloxy)ethyl]pyrrolidin-2-yl]methanol Chemical compound C1=CC(OC)=CC=C1C(OC1OCCCC1)CN1[C@@H](CO)CCC1 FSFDCELVHDUMKA-IPJUCJBFSA-N 0.000 description 2
- VOANNDWYHVZRDA-GDBMZVCRSA-N [(2r,4r)-4-(methoxymethoxy)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-2-yl]methanol Chemical compound C1[C@H](OCOC)C[C@H](CO)N1CCC1=CC=C(OC)C=C1 VOANNDWYHVZRDA-GDBMZVCRSA-N 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- GJEUABUMSODXMH-IAGOWNOFSA-N ethyl (2r,4r)-4-(methoxymethoxy)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1C[C@@H](OCOC)CN1CCC1=CC=C(OC)C=C1 GJEUABUMSODXMH-IAGOWNOFSA-N 0.000 description 2
- LFPIXDUFBCSWLX-UKRRQHHQSA-N ethyl (2r,4r)-4-hydroxy-1-[2-(4-methoxyphenyl)ethyl]pyrrolidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1C[C@@H](O)CN1CCC1=CC=C(OC)C=C1 LFPIXDUFBCSWLX-UKRRQHHQSA-N 0.000 description 2
- HHXSZDXMSRXWJV-KGZKBUQUSA-N ethyl (2r,4r)-4-hydroxypyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)[C@H]1C[C@@H](O)CN1 HHXSZDXMSRXWJV-KGZKBUQUSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000002366 halogen compounds Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- YBWJSPRLFXEGPH-GFCCVEGCSA-N (3r)-1-[2-(1,3-benzodioxol-5-yl)ethyl]-3-chloropiperidine Chemical compound C1[C@H](Cl)CCCN1CCC1=CC=C(OCO2)C2=C1 YBWJSPRLFXEGPH-GFCCVEGCSA-N 0.000 description 1
- AHJLNVZKKDZTPA-CYBMUJFWSA-N (3r)-3-chloro-1-[2-(3,4-dimethoxyphenyl)ethyl]piperidine Chemical compound C1=C(OC)C(OC)=CC=C1CCN1C[C@H](Cl)CCC1 AHJLNVZKKDZTPA-CYBMUJFWSA-N 0.000 description 1
- RALPFGRFBVRXIW-CYBMUJFWSA-N (3r)-3-chloro-1-[2-(3-methoxyphenyl)ethyl]piperidine Chemical compound COC1=CC=CC(CCN2C[C@H](Cl)CCC2)=C1 RALPFGRFBVRXIW-CYBMUJFWSA-N 0.000 description 1
- FZTPYHFHQJQQFN-DHIUTWEWSA-N (3r,5r)-5-(6h-benzo[c][1,5]benzoxazepin-11-ylmethyl)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-3-ol Chemical compound C1=CC(OC)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)C[C@@H](O)C1 FZTPYHFHQJQQFN-DHIUTWEWSA-N 0.000 description 1
- AHJLNVZKKDZTPA-ZDUSSCGKSA-N (3s)-3-chloro-1-[2-(3,4-dimethoxyphenyl)ethyl]piperidine Chemical compound C1=C(OC)C(OC)=CC=C1CCN1C[C@@H](Cl)CCC1 AHJLNVZKKDZTPA-ZDUSSCGKSA-N 0.000 description 1
- UFQAXYFEDWTKOG-LBPRGKRZSA-N (3s)-3-chloro-1-[2-(4-fluorophenyl)ethyl]piperidine Chemical compound C1=CC(F)=CC=C1CCN1C[C@@H](Cl)CCC1 UFQAXYFEDWTKOG-LBPRGKRZSA-N 0.000 description 1
- RAUSLMRPEWXFMC-ZDUSSCGKSA-N (3s)-3-chloro-1-[2-(4-methoxyphenyl)ethyl]piperidine Chemical compound C1=CC(OC)=CC=C1CCN1C[C@@H](Cl)CCC1 RAUSLMRPEWXFMC-ZDUSSCGKSA-N 0.000 description 1
- VGCOHQLCGZMSBZ-RFPXDPOKSA-N (3s,5r)-5-(6h-benzo[c][1,5]benzoxazepin-11-ylmethyl)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-3-ol;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)C[C@H](O)C1 VGCOHQLCGZMSBZ-RFPXDPOKSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PZYCMDRUEIOZNN-UYSSGXRJSA-N 11-[(1R)-2-phenyl-1-pyrrolidin-2-ylpropyl]-6H-benzo[c][1,5]benzoxazepine Chemical compound C1(=CC=CC=C1)C(C)[C@@H](N1C2=C(OCC3=C1C=CC=C3)C=CC=C2)C1NCCC1 PZYCMDRUEIOZNN-UYSSGXRJSA-N 0.000 description 1
- QVEPWCHFXPHWJG-GNAFDRTKSA-N 11-[[(2r)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-2-yl]methyl]-6h-benzo[c][1,5]benzoxazepine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)CCC1 QVEPWCHFXPHWJG-GNAFDRTKSA-N 0.000 description 1
- UTYQKIGPDVPIGG-QHCPKHFHSA-N 11-[[(2s)-1-[2-(3-methoxyphenyl)ethyl]pyrrolidin-2-yl]methyl]-6h-benzo[c][1,5]benzoxazepine Chemical compound COC1=CC=CC(CCN2[C@@H](CCC2)CN2C3=CC=CC=C3OCC3=CC=CC=C32)=C1 UTYQKIGPDVPIGG-QHCPKHFHSA-N 0.000 description 1
- AOGQCSARSZSBQR-BQAIUKQQSA-N 11-[[(2s)-1-[2-(3-methoxyphenyl)ethyl]pyrrolidin-2-yl]methyl]-6h-benzo[c][1,5]benzoxazepine;hydrochloride Chemical compound Cl.COC1=CC=CC(CCN2[C@@H](CCC2)CN2C3=CC=CC=C3OCC3=CC=CC=C32)=C1 AOGQCSARSZSBQR-BQAIUKQQSA-N 0.000 description 1
- REUFESBNLHXVHN-QHCPKHFHSA-N 11-[[(2s)-1-[2-(4-methoxyphenyl)ethyl]pyrrolidin-2-yl]methyl]-6h-benzo[c][1,5]benzoxazepine Chemical compound C1=CC(OC)=CC=C1CCN1[C@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)CCC1 REUFESBNLHXVHN-QHCPKHFHSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- XQJAHBHCLXUGEP-UHFFFAOYSA-N 2-bromo-1-(4-methoxyphenyl)ethanone Chemical compound COC1=CC=C(C(=O)CBr)C=C1 XQJAHBHCLXUGEP-UHFFFAOYSA-N 0.000 description 1
- SSXYKBHZZRYLLY-UHFFFAOYSA-N 2-chloro-1,3-oxazole Chemical compound ClC1=NC=CO1 SSXYKBHZZRYLLY-UHFFFAOYSA-N 0.000 description 1
- MUGSKSNNEORSJG-UHFFFAOYSA-N 3174-74-1 Chemical compound C1CC=CCO1 MUGSKSNNEORSJG-UHFFFAOYSA-N 0.000 description 1
- ZHDIJFGLWLETJT-XMMPIXPASA-N 4-[2-[(2r)-2-(6h-benzo[c][1,5]benzoxazepin-11-ylmethyl)pyrrolidin-1-yl]ethyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)CCC1 ZHDIJFGLWLETJT-XMMPIXPASA-N 0.000 description 1
- AEFIJQVFCYGNQI-GJFSDDNBSA-N 4-[2-[(2r)-2-(6h-benzo[c][1,5]benzoxazepin-11-ylmethyl)pyrrolidin-1-yl]ethyl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(C#N)=CC=C1CCN1[C@@H](CN2C3=CC=CC=C3OCC3=CC=CC=C32)CCC1 AEFIJQVFCYGNQI-GJFSDDNBSA-N 0.000 description 1
- LDXYAPHWRRUNGC-AWEZNQCLSA-N 4-[2-[(3s)-3-chloropiperidin-1-yl]ethyl]benzonitrile Chemical compound C1[C@@H](Cl)CCCN1CCC1=CC=C(C#N)C=C1 LDXYAPHWRRUNGC-AWEZNQCLSA-N 0.000 description 1
- QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- CPLXJAQNEMZWPI-YUZLPWPTSA-N Cl[C@@H]1CN(CCC1)C(C)C1=CC=CC=C1 Chemical compound Cl[C@@H]1CN(CCC1)C(C)C1=CC=CC=C1 CPLXJAQNEMZWPI-YUZLPWPTSA-N 0.000 description 1
- CPLXJAQNEMZWPI-GLGOKHISSA-N Cl[C@H]1CN(CCC1)C(C)C1=CC=CC=C1 Chemical compound Cl[C@H]1CN(CCC1)C(C)C1=CC=CC=C1 CPLXJAQNEMZWPI-GLGOKHISSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940125714 antidiarrheal agent Drugs 0.000 description 1
- 239000003793 antidiarrheal agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 210000000467 autonomic pathway Anatomy 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008061 calcium-channel-blocking effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- PMMYEEVYMWASQN-QWWZWVQMSA-N cis-4-hydroxy-D-proline Chemical compound O[C@H]1C[NH2+][C@@H](C([O-])=O)C1 PMMYEEVYMWASQN-QWWZWVQMSA-N 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003871 intestinal function Effects 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 description 1
- 150000004912 thiazepines Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8310496 | 1996-03-11 | ||
| PCT/JP1997/000754 WO1997033885A1 (fr) | 1996-03-11 | 1997-03-11 | DERIVES DE 5,11-DIHYDRODIBENZ[b,e] [1,4]OXAZEPINE, ET COMPOSITIONS MEDICAMENTEUSES LES COMPORTANT |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO984162D0 NO984162D0 (no) | 1998-09-10 |
| NO984162L NO984162L (no) | 1998-11-05 |
| NO310976B1 true NO310976B1 (no) | 2001-09-24 |
Family
ID=13792896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19984162A NO310976B1 (no) | 1996-03-11 | 1998-09-10 | 5,11-dihydrobenzo[b,e][1,4]oksazepinderivater og farmasoytiske sammensetninger inneholdende de samme |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US6127361A (pt) |
| EP (1) | EP0889043B1 (pt) |
| JP (1) | JP3127469B2 (pt) |
| KR (1) | KR100344331B1 (pt) |
| CN (1) | CN1085209C (pt) |
| AT (1) | ATE204871T1 (pt) |
| AU (1) | AU704521B2 (pt) |
| BR (1) | BR9707962A (pt) |
| CA (1) | CA2261271C (pt) |
| DE (1) | DE69706406T2 (pt) |
| ES (1) | ES2159843T3 (pt) |
| NO (1) | NO310976B1 (pt) |
| PT (1) | PT889043E (pt) |
| TW (1) | TW479057B (pt) |
| WO (1) | WO1997033885A1 (pt) |
| ZA (1) | ZA972038B (pt) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69811520T2 (de) | 1997-09-10 | 2003-12-11 | Ajinomoto Kk | 5,11-DIHYDROBENZ[b,e][1,4]OXAZEPIN-DERIVATE UND DIESE ENTHALTENDE MEDIZINISCHE ZUBEREITUNGEN |
| EP1471060A1 (en) | 1999-01-08 | 2004-10-27 | Ajinomoto Co., Inc. | 5,11-Dihydrodibenzo[b,e][1,4]-oxazepine derivatives as calcium channel antagonists |
| AU6868900A (en) * | 1999-09-03 | 2001-04-10 | Ajinomoto Co., Inc. | Novel processes for preparing oxazepine derivatives |
| AU2001217359A1 (en) * | 2000-12-11 | 2002-06-24 | Ajinomoto Co., Inc. | Novel crystals of oxazepine derivatives and process for the production thereof |
| WO2002096891A1 (fr) | 2001-05-30 | 2002-12-05 | Ajinomoto Co.,Inc. | Derives de dihydrodiaryloxazepine, et medicaments contenant ces derives |
| JP2005343791A (ja) * | 2002-05-31 | 2005-12-15 | Ajinomoto Co Inc | 消化管疾患を治療するための医薬組成物 |
| JP2005343790A (ja) * | 2002-05-31 | 2005-12-15 | Ajinomoto Co Inc | カルシウムチャネル拮抗薬を含有する医薬組成物 |
| CN104016937B (zh) * | 2014-05-09 | 2016-12-07 | 中科院广州化学有限公司 | 一种n-芳基氧氮杂卓酮类化合物及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8912303D0 (en) * | 1989-05-27 | 1989-07-12 | Pfizer Ltd | Therapeutic agents |
| AU2669992A (en) * | 1991-11-05 | 1993-06-07 | G.D. Searle & Co. | 10-acyl-dibenz(b,f) (1,4)-oxazepines and their thiazepines analo gues useful as prostaglandin antagonists |
| EP1404359A2 (en) * | 2000-12-07 | 2004-04-07 | Board Of Regents, The University Of Texas System | Methods of treatment involving human mda-7 |
-
1997
- 1997-03-10 TW TW086102931A patent/TW479057B/zh not_active IP Right Cessation
- 1997-03-10 ZA ZA9702038A patent/ZA972038B/xx unknown
- 1997-03-11 PT PT97905478T patent/PT889043E/pt unknown
- 1997-03-11 EP EP97905478A patent/EP0889043B1/en not_active Expired - Lifetime
- 1997-03-11 CN CN97193005A patent/CN1085209C/zh not_active Expired - Fee Related
- 1997-03-11 DE DE69706406T patent/DE69706406T2/de not_active Expired - Fee Related
- 1997-03-11 JP JP09532434A patent/JP3127469B2/ja not_active Expired - Fee Related
- 1997-03-11 CA CA002261271A patent/CA2261271C/en not_active Expired - Fee Related
- 1997-03-11 WO PCT/JP1997/000754 patent/WO1997033885A1/ja active IP Right Grant
- 1997-03-11 ES ES97905478T patent/ES2159843T3/es not_active Expired - Lifetime
- 1997-03-11 US US09/147,012 patent/US6127361A/en not_active Expired - Fee Related
- 1997-03-11 AU AU22335/97A patent/AU704521B2/en not_active Ceased
- 1997-03-11 BR BR9707962A patent/BR9707962A/pt not_active IP Right Cessation
- 1997-03-11 KR KR1019980707117A patent/KR100344331B1/ko not_active IP Right Cessation
- 1997-03-11 AT AT97905478T patent/ATE204871T1/de not_active IP Right Cessation
-
1998
- 1998-09-10 NO NO19984162A patent/NO310976B1/no unknown
-
2000
- 2000-06-19 US US09/597,409 patent/US6436922B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR19990087655A (ko) | 1999-12-27 |
| ES2159843T3 (es) | 2001-10-16 |
| US6127361A (en) | 2000-10-03 |
| WO1997033885A1 (fr) | 1997-09-18 |
| TW479057B (en) | 2002-03-11 |
| AU704521B2 (en) | 1999-04-22 |
| KR100344331B1 (ko) | 2002-12-05 |
| DE69706406D1 (de) | 2001-10-04 |
| AU2233597A (en) | 1997-10-01 |
| EP0889043A4 (en) | 1999-07-21 |
| US6436922B1 (en) | 2002-08-20 |
| BR9707962A (pt) | 1999-07-27 |
| CN1085209C (zh) | 2002-05-22 |
| EP0889043B1 (en) | 2001-08-29 |
| NO984162D0 (no) | 1998-09-10 |
| JP3127469B2 (ja) | 2001-01-22 |
| CA2261271A1 (en) | 1997-09-18 |
| ATE204871T1 (de) | 2001-09-15 |
| CN1213371A (zh) | 1999-04-07 |
| CA2261271C (en) | 2003-09-16 |
| PT889043E (pt) | 2002-02-28 |
| NO984162L (no) | 1998-11-05 |
| DE69706406T2 (de) | 2002-04-18 |
| ZA972038B (en) | 1997-09-17 |
| EP0889043A1 (en) | 1999-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CZ129590A3 (en) | Substituted pyrrolidine derivative, process of its preparation, intermediates of such process and pharmaceutical composition containing thereof | |
| EP0583408A1 (en) | Substituted dibenzoxazepine compounds, pharmaceutical compositions and methods of use | |
| CA2828415A1 (en) | Substituted morpholines as modulators for the calcium sensing receptor | |
| JP2010521523A (ja) | 新規なベンズアミド誘導体およびその製造方法 | |
| WO2010137620A1 (ja) | フェノキシエチルアミン誘導体 | |
| NO310976B1 (no) | 5,11-dihydrobenzo[b,e][1,4]oksazepinderivater og farmasoytiske sammensetninger inneholdende de samme | |
| CA2017535C (en) | Antispasmodic agents | |
| KR20010041341A (ko) | 벤질피페라지닐 및 벤질피페리디닐 에탄온 유도체, 이의제조 방법 및 도파민 ｄ４ 수용체 길항제로서의 이의 용도 | |
| EP1020466B1 (en) | 5,11-DIHYDRODIBENZ[b,e][1,4]OXAZEPINE DERIVATIVES AND MEDICINAL COMPOSITION CONTAINING THE SAME | |
| EP0684237B1 (en) | Morpholine derivative | |
| US6528504B2 (en) | Oxazepine derivatives and medicine containing the same | |
| US7320973B2 (en) | Dihydrodiaryloxazepine derivative and pharmaceutical composition containing the same | |
| JP2000186091A (ja) | 縮合ベンズイソアゾ―ル誘導体、その製造法および用途 | |
| WO2004089936A1 (ja) | ヘテロアリールスルホン酸アニリド誘導体及びそれを含有する医薬組成物 | |
| JPH04210970A (ja) | ベンズアミド誘導体及びその中間体 | |
| NO171363B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive oksysalicylaminoderivater | |
| JP2005343790A (ja) | カルシウムチャネル拮抗薬を含有する医薬組成物 | |
| MX2007014441A (es) | Derivado de pirrolidina o una sal del mismo. |