CA1214460A - 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines, a process for preparing the same and their use as medicaments - Google Patents
1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines, a process for preparing the same and their use as medicamentsInfo
- Publication number
- CA1214460A CA1214460A CA000430280A CA430280A CA1214460A CA 1214460 A CA1214460 A CA 1214460A CA 000430280 A CA000430280 A CA 000430280A CA 430280 A CA430280 A CA 430280A CA 1214460 A CA1214460 A CA 1214460A
- Authority
- CA
- Canada
- Prior art keywords
- tetrahydro
- benzazepine
- compound
- formula
- lower alkyl
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract 3
- 239000003814 drug Substances 0.000 title abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 114
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 62
- -1 alkylene amine Chemical class 0.000 claims abstract description 34
- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 23
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical group 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 9
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 55
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 16
- 229910010084 LiAlH4 Inorganic materials 0.000 claims description 15
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 15
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims description 15
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 11
- 150000004820 halides Chemical class 0.000 claims description 10
- 239000012442 inert solvent Substances 0.000 claims description 10
- JEJAWQBUJIIGHW-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenoxy]-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCNC1 JEJAWQBUJIIGHW-UHFFFAOYSA-N 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 8
- 229910052987 metal hydride Inorganic materials 0.000 claims description 7
- 150000004681 metal hydrides Chemical class 0.000 claims description 7
- CAOMJAMNASENBC-UHFFFAOYSA-N 7,8-dimethoxy-5-[4-(trifluoromethyl)phenoxy]-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(C(F)(F)F)C=C1 CAOMJAMNASENBC-UHFFFAOYSA-N 0.000 claims description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 5
- UNNNAIWPDLRVRN-UHFFFAOYSA-N 1-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C(F)(F)F)C=C1 UNNNAIWPDLRVRN-UHFFFAOYSA-N 0.000 claims description 4
- LUIGKSPQPMWPBD-UHFFFAOYSA-N 2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]acetonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCN(CC#N)C1 LUIGKSPQPMWPBD-UHFFFAOYSA-N 0.000 claims description 4
- DLBVOUHTERRKRW-UHFFFAOYSA-N 7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepin-5-ol Chemical compound C1CNCC(O)C2=C1C=C(OC)C(OC)=C2 DLBVOUHTERRKRW-UHFFFAOYSA-N 0.000 claims description 4
- MAIIKQNCBVQRBM-UHFFFAOYSA-N 7,8-dimethoxy-5-phenoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC=C1 MAIIKQNCBVQRBM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000007344 nucleophilic reaction Methods 0.000 claims description 3
- JHWVRHCUFLRKFZ-UHFFFAOYSA-N 2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethanamine Chemical compound C1N(CCN)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 JHWVRHCUFLRKFZ-UHFFFAOYSA-N 0.000 claims description 2
- SMKOBRGTXKBMEO-UHFFFAOYSA-N 5-(4-methoxyphenoxy)-3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(OC)=CC=C1OC1C2=CC=CC=C2CCN(S(=O)(=O)C=2C=CC(C)=CC=2)C1 SMKOBRGTXKBMEO-UHFFFAOYSA-N 0.000 claims description 2
- XBJOTFYSRVFFRV-UHFFFAOYSA-N 7,8-dimethoxy-5-(4-methoxyphenoxy)-3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(OC)=CC=C1OC1C2=CC(OC)=C(OC)C=C2CCN(S(=O)(=O)C=2C=CC(C)=CC=2)C1 XBJOTFYSRVFFRV-UHFFFAOYSA-N 0.000 claims description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- GFVKLWPPOMFGAK-UHFFFAOYSA-N ethyl 7,8-dimethoxy-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate Chemical compound C1N(C(=O)OCC)CCC2=CC(OC)=C(OC)C=C2C1OC1=CC=C(C(F)(F)F)C=C1 GFVKLWPPOMFGAK-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 14
- ZMOPIHQDPJYYKW-UHFFFAOYSA-N 5-(3-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC(Cl)=C1 ZMOPIHQDPJYYKW-UHFFFAOYSA-N 0.000 claims 2
- VOIFXRDZAJDFPB-UHFFFAOYSA-N 5-(4-methoxyphenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=CC(OC)=CC=C1OC1C2=CC=CC=C2CCNC1 VOIFXRDZAJDFPB-UHFFFAOYSA-N 0.000 claims 2
- ZUGSPVVYXXJHCM-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=CC=C1 ZUGSPVVYXXJHCM-UHFFFAOYSA-N 0.000 claims 2
- VZHJIJZEOCBKRA-UHFFFAOYSA-N 1-chloro-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1 VZHJIJZEOCBKRA-UHFFFAOYSA-N 0.000 claims 1
- OEZPDHRXGCLGKB-UHFFFAOYSA-N 2-chloropropanamide Chemical compound CC(Cl)C(N)=O OEZPDHRXGCLGKB-UHFFFAOYSA-N 0.000 claims 1
- UXKLWPPBHFSCIU-UHFFFAOYSA-N 3-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]propan-1-amine Chemical compound C1N(CCCN)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 UXKLWPPBHFSCIU-UHFFFAOYSA-N 0.000 claims 1
- ZRWVGJZKRRLXOG-UHFFFAOYSA-N 7,8-dimethoxy-3-(4-methylphenyl)sulfonyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1OC1=CC=CC=C1 ZRWVGJZKRRLXOG-UHFFFAOYSA-N 0.000 claims 1
- AOHFDDOIDVKIPT-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=C(C(F)(F)F)C=C1 AOHFDDOIDVKIPT-UHFFFAOYSA-N 0.000 claims 1
- WNBKEEWOYWFAIT-UHFFFAOYSA-N 7,8-dimethoxy-5-(4-methoxyphenoxy)-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(OC)=CC=C1OC1C2=CC(OC)=C(OC)C=C2CCN(C)C1 WNBKEEWOYWFAIT-UHFFFAOYSA-N 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 150000001350 alkyl halides Chemical class 0.000 claims 1
- 229910052796 boron Inorganic materials 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 206010015995 Eyelid ptosis Diseases 0.000 abstract description 4
- 241000124008 Mammalia Species 0.000 abstract description 4
- 241000699670 Mus sp. Species 0.000 abstract description 4
- 201000003004 ptosis Diseases 0.000 abstract description 4
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 abstract description 3
- 229960005333 tetrabenazine Drugs 0.000 abstract description 3
- 208000020401 Depressive disease Diseases 0.000 abstract description 2
- 239000003921 oil Substances 0.000 description 163
- 239000000243 solution Substances 0.000 description 163
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 159
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 126
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 115
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 107
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 90
- 229910052799 carbon Inorganic materials 0.000 description 84
- 239000000203 mixture Substances 0.000 description 76
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 74
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 62
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 48
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 46
- 238000007792 addition Methods 0.000 description 44
- 235000019341 magnesium sulphate Nutrition 0.000 description 44
- 238000004458 analytical method Methods 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
- 229940093499 ethyl acetate Drugs 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 229910052757 nitrogen Inorganic materials 0.000 description 30
- 239000000725 suspension Substances 0.000 description 30
- 239000000463 material Substances 0.000 description 29
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 25
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 229960001701 chloroform Drugs 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- 150000003891 oxalate salts Chemical class 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 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 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 239000012259 ether extract Substances 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000004533 oil dispersion Substances 0.000 description 8
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 8
- JXMLAPZRDDWRRV-UHFFFAOYSA-N ethyl n-(ethoxycarbonylamino)carbamate Chemical compound CCOC(=O)NNC(=O)OCC JXMLAPZRDDWRRV-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
- 150000002688 maleic acid derivatives Chemical class 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 description 6
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 6
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 6
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 6
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 5
- YNLHBGLBJHVNTK-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepin-5-ol Chemical class OC1CNCCC2=CC=CC=C12 YNLHBGLBJHVNTK-UHFFFAOYSA-N 0.000 description 5
- FLSBQILUUNXTLC-UHFFFAOYSA-N 5-(3-chlorophenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound ClC1=CC=CC(OC2C3=CC=CC=C3CCNC2)=C1 FLSBQILUUNXTLC-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 235000011087 fumaric acid Nutrition 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000008098 formaldehyde solution Substances 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- RJCGZNCCVKIBHO-UHFFFAOYSA-N 1-chloro-4-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1 RJCGZNCCVKIBHO-UHFFFAOYSA-N 0.000 description 3
- GBOWGKOVMBDPJF-UHFFFAOYSA-N 1-fluoro-3-(trifluoromethyl)benzene Chemical compound FC1=CC=CC(C(F)(F)F)=C1 GBOWGKOVMBDPJF-UHFFFAOYSA-N 0.000 description 3
- RXPDDRVCOCIHMI-UHFFFAOYSA-N 3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepin-5-ol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(O)C2=CC=CC=C2CC1 RXPDDRVCOCIHMI-UHFFFAOYSA-N 0.000 description 3
- ZOXUTHALVVFSOO-UHFFFAOYSA-N 3-(4-methylphenyl)sulfonyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(OC=2C=CC(=CC=2)C(F)(F)F)C2=CC=CC=C2CC1 ZOXUTHALVVFSOO-UHFFFAOYSA-N 0.000 description 3
- YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 description 3
- IDIYBOXGNAFJBP-UHFFFAOYSA-N 7,8-dimethoxy-3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepin-5-ol Chemical compound C1C(O)C=2C=C(OC)C(OC)=CC=2CCN1S(=O)(=O)C1=CC=C(C)C=C1 IDIYBOXGNAFJBP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- DLPAZJHBHBXCIR-UHFFFAOYSA-N 1-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 DLPAZJHBHBXCIR-UHFFFAOYSA-N 0.000 description 2
- HJXVUJRPTUQIAX-UHFFFAOYSA-N 2-[5-(3-chlorophenoxy)-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethanamine;oxalic acid Chemical compound OC(=O)C(O)=O.OC(=O)C(O)=O.C1N(CCN)CCC2=CC=CC=C2C1OC1=CC=CC(Cl)=C1 HJXVUJRPTUQIAX-UHFFFAOYSA-N 0.000 description 2
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
- JPVPKERTPABKLW-UHFFFAOYSA-N 3-(4-methylphenyl)sulfonyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(OC=2C=CC=CC=2)C2=CC=CC=C2CC1 JPVPKERTPABKLW-UHFFFAOYSA-N 0.000 description 2
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 2
- LLMQTQFMHREURJ-UHFFFAOYSA-N 5-(4-methoxyphenoxy)-3-methyl-1,2,4,5-tetrahydro-3-benzazepine;hydrobromide Chemical compound Br.C1=CC(OC)=CC=C1OC1C2=CC=CC=C2CCN(C)C1 LLMQTQFMHREURJ-UHFFFAOYSA-N 0.000 description 2
- JPCUJJSQPYABLA-UHFFFAOYSA-N 5-(4-methylphenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(C)=CC=C1OC1C2=CC=CC=C2CCNC1 JPCUJJSQPYABLA-UHFFFAOYSA-N 0.000 description 2
- HPHCTDCUNZGPQY-UHFFFAOYSA-N 5-phenoxy-2,3,4,5-tetrahydro-1h-3-benzazepine;hydrochloride Chemical compound Cl.C1NCCC2=CC=CC=C2C1OC1=CC=CC=C1 HPHCTDCUNZGPQY-UHFFFAOYSA-N 0.000 description 2
- OSGWADYCGIGOQO-UHFFFAOYSA-N 7,8-dimethoxy-5-(4-methoxyphenoxy)-3-methyl-1,2,4,5-tetrahydro-3-benzazepine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1OC1C2=CC(OC)=C(OC)C=C2CCN(C)C1 OSGWADYCGIGOQO-UHFFFAOYSA-N 0.000 description 2
- DBJFASJJLPLYEW-UHFFFAOYSA-N 7,8-dimethoxy-5-phenoxy-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC=C1 DBJFASJJLPLYEW-UHFFFAOYSA-N 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JEGQLESHHLGSIY-UHFFFAOYSA-N C(C=C/C(=O)O)(=O)O.C(C=C/C(=O)O)(=O)O.NCCCN1CCC2=C(C(C1)OC1=CC=C(C=C1)C(F)(F)F)C=CC=C2 Chemical compound C(C=C/C(=O)O)(=O)O.C(C=C/C(=O)O)(=O)O.NCCCN1CCC2=C(C(C1)OC1=CC=C(C=C1)C(F)(F)F)C=CC=C2 JEGQLESHHLGSIY-UHFFFAOYSA-N 0.000 description 2
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229910010199 LiAl Inorganic materials 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- DBZWGBVCLXHHGQ-UHFFFAOYSA-N oxalic acid;5-[4-(trifluoromethyl)phenoxy]-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound OC(=O)C(O)=O.C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCNC1 DBZWGBVCLXHHGQ-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000012289 standard assay Methods 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 1
- ATHNWODHOWZNEQ-BTJKTKAUSA-N (z)-but-2-enedioic acid;3-ethyl-7,8-dimethoxy-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine Chemical compound OC(=O)\C=C/C(O)=O.C1N(CC)CCC2=CC(OC)=C(OC)C=C2C1OC1=CC=CC=C1 ATHNWODHOWZNEQ-BTJKTKAUSA-N 0.000 description 1
- QDPLFWNTMBOORN-BTJKTKAUSA-N (z)-but-2-enedioic acid;5-(4-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound OC(=O)\C=C/C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(Cl)C=C1 QDPLFWNTMBOORN-BTJKTKAUSA-N 0.000 description 1
- LRFOCBQOZHJDFM-BTJKTKAUSA-N (z)-but-2-enedioic acid;5-(4-fluorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound OC(=O)\C=C/C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(F)C=C1 LRFOCBQOZHJDFM-BTJKTKAUSA-N 0.000 description 1
- KWQBGLQNYFNCSS-BTJKTKAUSA-N (z)-but-2-enedioic acid;5-(4-fluorophenoxy)-7,8-dimethoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound OC(=O)\C=C/C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=C(F)C=C1 KWQBGLQNYFNCSS-BTJKTKAUSA-N 0.000 description 1
- ANXOZOZWHNFHPZ-UHFFFAOYSA-N 1-(2,2-difluoro-1-phenylethenyl)-4-fluorobenzene Chemical compound C=1C=C(F)C=CC=1C(=C(F)F)C1=CC=CC=C1 ANXOZOZWHNFHPZ-UHFFFAOYSA-N 0.000 description 1
- NTURQZFFJDCTMZ-UHFFFAOYSA-N 1-(2-bromoethyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(CCBr)C=C1 NTURQZFFJDCTMZ-UHFFFAOYSA-N 0.000 description 1
- QDSFIYBVXMTQST-UHFFFAOYSA-N 1-(7,8-dimethoxy-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethanone Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(C)=O)CC1OC1=CC=CC=C1 QDSFIYBVXMTQST-UHFFFAOYSA-N 0.000 description 1
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- FXDKNAHANNRXOR-UHFFFAOYSA-N 1h-1-benzazepine;hydrobromide Chemical compound Br.N1C=CC=CC2=CC=CC=C12 FXDKNAHANNRXOR-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- YKLFBRXLEKRCRF-UHFFFAOYSA-N 2-[5-[3-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]acetonitrile Chemical compound FC(F)(F)C1=CC=CC(OC2C3=CC=CC=C3CCN(CC#N)C2)=C1 YKLFBRXLEKRCRF-UHFFFAOYSA-N 0.000 description 1
- CPBGRDXXGOTGSC-UHFFFAOYSA-N 2-[7,8-dimethoxy-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]acetonitrile Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(CC#N)CC1OC1=CC=C(C(F)(F)F)C=C1 CPBGRDXXGOTGSC-UHFFFAOYSA-N 0.000 description 1
- HMGSJZHTXRYLJW-UHFFFAOYSA-N 2-[7,8-dimethoxy-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethanamine oxalic acid Chemical compound OC(=O)C(O)=O.OC(=O)C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCN(CCN)CC1OC1=CC=C(C(F)(F)F)C=C1 HMGSJZHTXRYLJW-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- FMBJCYMWQLOHMT-UHFFFAOYSA-N 3-(4-methylphenyl)sulfonyl-5-[3-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(OC=2C=C(C=CC=2)C(F)(F)F)C2=CC=CC=C2CC1 FMBJCYMWQLOHMT-UHFFFAOYSA-N 0.000 description 1
- UMFLBCMPKRNKNC-UHFFFAOYSA-N 3-(cyclopropylmethyl)-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine;hydrobromide Chemical compound Br.C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCN(CC2CC2)C1 UMFLBCMPKRNKNC-UHFFFAOYSA-N 0.000 description 1
- MLZRILNPMOFNID-UHFFFAOYSA-N 3-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]propanenitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1OC1C2=CC=CC=C2CCN(CCC#N)C1 MLZRILNPMOFNID-UHFFFAOYSA-N 0.000 description 1
- GAWHPTWIXOPVFT-UHFFFAOYSA-N 3-methyl-5-[3-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1N(C)CCC2=CC=CC=C2C1OC1=CC=CC(C(F)(F)F)=C1 GAWHPTWIXOPVFT-UHFFFAOYSA-N 0.000 description 1
- ADFWSYOVSIPTLB-UHFFFAOYSA-N 3-methyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1N(C)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 ADFWSYOVSIPTLB-UHFFFAOYSA-N 0.000 description 1
- WMXVRWUSODRGFC-UHFFFAOYSA-N 3-propyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1CN(CCC)CCC2=CC=CC=C21 WMXVRWUSODRGFC-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- BMWLVLQEYWDPJI-UHFFFAOYSA-N 5-(2-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC=C1Cl BMWLVLQEYWDPJI-UHFFFAOYSA-N 0.000 description 1
- FPISAZWWUJERKI-UHFFFAOYSA-N 5-(2-chlorophenoxy)-7,8-dimethoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=CC=C1Cl FPISAZWWUJERKI-UHFFFAOYSA-N 0.000 description 1
- DNJSJAWZOMMPSI-UHFFFAOYSA-N 5-(3,4-dichlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(Cl)C(Cl)=C1 DNJSJAWZOMMPSI-UHFFFAOYSA-N 0.000 description 1
- LKZUYXSDKMVQCV-UHFFFAOYSA-N 5-(3-chlorophenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.ClC1=CC=CC(OC2C3=CC=CC=C3CCNC2)=C1 LKZUYXSDKMVQCV-UHFFFAOYSA-N 0.000 description 1
- DNXJMKZXHNYVLQ-UHFFFAOYSA-N 5-(3-chlorophenoxy)-3-(2-phenylethyl)-1,2,4,5-tetrahydro-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.ClC1=CC=CC(OC2C3=CC=CC=C3CCN(CCC=3C=CC=CC=3)C2)=C1 DNXJMKZXHNYVLQ-UHFFFAOYSA-N 0.000 description 1
- LZTGRANIEAXJAB-UHFFFAOYSA-N 5-(3-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=CC(Cl)=C1 LZTGRANIEAXJAB-UHFFFAOYSA-N 0.000 description 1
- WMDZCPRKKGXPBF-UHFFFAOYSA-N 5-(4-bromophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(Br)C=C1 WMDZCPRKKGXPBF-UHFFFAOYSA-N 0.000 description 1
- ZTYXSJCXMOIHOL-BTJKTKAUSA-N 5-(4-bromophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(Br)C=C1 ZTYXSJCXMOIHOL-BTJKTKAUSA-N 0.000 description 1
- OHCXTAABZDRATK-UHFFFAOYSA-N 5-(4-chlorophenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(Cl)=CC=C1OC1C2=CC=CC=C2CCNC1 OHCXTAABZDRATK-UHFFFAOYSA-N 0.000 description 1
- FSOFMYYSNVSUQP-UHFFFAOYSA-N 5-(4-chlorophenoxy)-3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(OC=2C=CC(Cl)=CC=2)C2=CC=CC=C2CC1 FSOFMYYSNVSUQP-UHFFFAOYSA-N 0.000 description 1
- UROGRNBSGRSUIY-UHFFFAOYSA-N 5-(4-chlorophenoxy)-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1N(C)CCC2=CC=CC=C2C1OC1=CC=C(Cl)C=C1 UROGRNBSGRSUIY-UHFFFAOYSA-N 0.000 description 1
- QEHXTTMFQCIOCQ-UHFFFAOYSA-N 5-(4-chlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCNCC1OC1=CC=C(Cl)C=C1 QEHXTTMFQCIOCQ-UHFFFAOYSA-N 0.000 description 1
- WLMILHZBHZYNII-UHFFFAOYSA-N 5-(4-chlorophenoxy)-7,8-dimethoxy-3-(4-methylphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1OC1=CC=C(Cl)C=C1 WLMILHZBHZYNII-UHFFFAOYSA-N 0.000 description 1
- MVBWEZWXISMURJ-UHFFFAOYSA-N 5-(4-fluorophenoxy)-7,8-dimethoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=C(F)C=C1 MVBWEZWXISMURJ-UHFFFAOYSA-N 0.000 description 1
- OYEXZZFAVRFXNZ-UHFFFAOYSA-N 5-(4-methoxyphenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(OC)=CC=C1OC1C2=CC=CC=C2CCNC1 OYEXZZFAVRFXNZ-UHFFFAOYSA-N 0.000 description 1
- BOYSQLJLJGQYKP-UHFFFAOYSA-N 5-(4-methylphenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=CC(C)=CC=C1OC1C2=CC=CC=C2CCNC1 BOYSQLJLJGQYKP-UHFFFAOYSA-N 0.000 description 1
- FVHARZUEEDVHOV-UHFFFAOYSA-N 5-(4-nitrophenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1C2=CC=CC=C2CCNC1 FVHARZUEEDVHOV-UHFFFAOYSA-N 0.000 description 1
- ILIKDGQVHKOXBB-UHFFFAOYSA-N 5-(4-nitrophenoxy)-2,3,4,5-tetrahydro-1h-3-benzazepine;hydrochloride Chemical compound Cl.C1=CC([N+](=O)[O-])=CC=C1OC1C2=CC=CC=C2CCNC1 ILIKDGQVHKOXBB-UHFFFAOYSA-N 0.000 description 1
- YPSCVOIRZZGNDZ-UHFFFAOYSA-N 5-phenoxy-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1NCCC2=CC=CC=C2C1OC1=CC=CC=C1 YPSCVOIRZZGNDZ-UHFFFAOYSA-N 0.000 description 1
- JUDHUJJPRAQLDC-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=CC=C1 JUDHUJJPRAQLDC-UHFFFAOYSA-N 0.000 description 1
- YIFHWENTMLFYOI-UHFFFAOYSA-N 7,8-dimethoxy-5-phenoxy-3-propyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound C1N(CCC)CCC2=CC(OC)=C(OC)C=C2C1OC1=CC=CC=C1 YIFHWENTMLFYOI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000406799 Deto Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 101000654298 Homo sapiens N-terminal kinase-like protein Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 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
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- HXXNUJBODGEODL-UHFFFAOYSA-N N-methyl-2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethanamine oxalic acid Chemical compound C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.CNCCN1CCC2=C(C(C1)OC1=CC=C(C=C1)C(F)(F)F)C=CC=C2 HXXNUJBODGEODL-UHFFFAOYSA-N 0.000 description 1
- 102100031703 N-terminal kinase-like protein Human genes 0.000 description 1
- SZYDTHRDYYQNFR-UHFFFAOYSA-N OC(=O)C=C/C(O)=O.N1C=CC=CC2=CC=CC=C12 Chemical compound OC(=O)C=C/C(O)=O.N1C=CC=CC2=CC=CC=C12 SZYDTHRDYYQNFR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000244317 Tillandsia usneoides Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 229910000091 aluminium hydride Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- 150000008038 benzoazepines Chemical class 0.000 description 1
- 235000019445 benzyl alcohol 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
- 239000011230 binding agent Substances 0.000 description 1
- OKUDBXZACZBZJE-UHFFFAOYSA-N bis(2-methoxyethoxy)aluminum;sodium Chemical compound [Na].COCCO[Al]OCCOC OKUDBXZACZBZJE-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
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- ZVTQWXCKQTUVPY-UHFFFAOYSA-N chloromethylcyclopropane Chemical compound ClCC1CC1 ZVTQWXCKQTUVPY-UHFFFAOYSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- SSOFTMBPQFNSRI-UHFFFAOYSA-N ethyl n-[2-[5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]ethyl]carbamate Chemical compound C1N(CCNC(=O)OCC)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 SSOFTMBPQFNSRI-UHFFFAOYSA-N 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 125000005441 o-toluyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/387,916 US4988690A (en) | 1982-06-14 | 1982-06-14 | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines and anti-depressant use thereof |
| US387,916 | 1982-06-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1214460A true CA1214460A (en) | 1986-11-25 |
Family
ID=23531838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000430280A Expired CA1214460A (en) | 1982-06-14 | 1983-06-13 | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines, a process for preparing the same and their use as medicaments |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4988690A (enExample) |
| EP (1) | EP0096838B1 (enExample) |
| JP (1) | JPS595165A (enExample) |
| KR (1) | KR900001214B1 (enExample) |
| AT (1) | ATE26263T1 (enExample) |
| AU (1) | AU570920B2 (enExample) |
| CA (1) | CA1214460A (enExample) |
| DE (1) | DE3370621D1 (enExample) |
| DK (1) | DK270983A (enExample) |
| ES (1) | ES8503666A1 (enExample) |
| FI (1) | FI78473C (enExample) |
| GR (1) | GR78291B (enExample) |
| HU (1) | HU190902B (enExample) |
| IE (1) | IE55404B1 (enExample) |
| IL (1) | IL68964A (enExample) |
| PT (1) | PT76864B (enExample) |
| ZA (1) | ZA834309B (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA882080B (en) * | 1987-03-27 | 1989-04-26 | Schering Corp | Substituted benzazepines,their preparation and pharmaceutical compositions containing them |
| US5015639A (en) * | 1987-03-27 | 1991-05-14 | Schering Corporation | Substituted benzazepines, their preparation and pharmaceutical compositions containing them |
| ZA885824B (en) * | 1987-08-14 | 1989-04-26 | Merrell Dow Pharma | Novel antidepressants |
| US5202319A (en) * | 1991-09-23 | 1993-04-13 | Hoechst-Roussel Pharmaceuticals Inc. | Substituted 3-amino-2,3,4,5-tetrahydro-1-aryloxy-3-benzazepines |
| US5639482A (en) * | 1993-11-10 | 1997-06-17 | Crary; Ely J. | Composition for control and prevention of diabetic retinopathy |
| US7115766B2 (en) * | 2000-11-30 | 2006-10-03 | Indiana University Research & Technology Corp. | Nucleophilic approach for preparing radiolabeled imaging agents and associated compounds |
| US6953787B2 (en) * | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| US8367657B2 (en) | 2003-06-17 | 2013-02-05 | Arena Pharmaceuticals, Inc. | Processes for preparing 3-benzazepines |
| CN1805938B (zh) * | 2003-06-17 | 2010-06-16 | 艾尼纳制药公司 | 用于治疗5ht2c受体相关疾病的苯并氮杂卓衍生物 |
| WO2005042491A1 (en) * | 2003-10-22 | 2005-05-12 | Arena Pharmaceuticals, Inc. | Benzazepine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases |
| WO2005042490A1 (en) * | 2003-10-22 | 2005-05-12 | Arena Pharmaceuticals, Inc. | Benzazepine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases |
| EP2149562A1 (en) | 2004-12-21 | 2010-02-03 | Arena Pharmaceuticals, Inc. | method of preparing (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate |
| NZ589951A (en) * | 2004-12-23 | 2012-11-30 | Arena Pharm Inc | 5HT2C receptor modulator compositions and methods of use |
| CA2646044A1 (en) | 2006-04-03 | 2007-10-25 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates related thereto |
| EP2099743B1 (en) * | 2006-12-05 | 2014-08-27 | Arena Pharmaceuticals, Inc. | Processes for preparing (r)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates thereof |
| KR20100017767A (ko) * | 2007-05-10 | 2010-02-16 | 에이엠알 테크놀로지, 인크. | 아릴옥시- 및 헤테로 아릴옥시-치환된 테트라히드로벤즈아제핀 및 도파민 및 세로토닌의 재흡수를 차단하기 위한 이의 용도 |
| US8822727B2 (en) | 2008-03-04 | 2014-09-02 | Arena Pharmaceuticals, Inc. | Processes for the preparation of intermediates related to the 5-HT2C agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine |
| WO2010148207A2 (en) | 2009-06-18 | 2010-12-23 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 5-ht2c receptor agonists |
| WO2011153206A1 (en) | 2010-06-02 | 2011-12-08 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 5-ht2c receptor agonists |
| JP2013539470A (ja) | 2010-09-01 | 2013-10-24 | アリーナ ファーマシューティカルズ， インコーポレイテッド | ロルカセリンと光学活性な酸との塩 |
| KR20180118801A (ko) | 2010-09-01 | 2018-10-31 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 체중 관리에 유용한 5-ｈｔ2ｃ 작동제의 변형-방출 투여 형태 |
| EA201390335A1 (ru) | 2010-09-01 | 2013-09-30 | Арена Фармасьютикалз, Инк. | Введение лоркасерина индивидуумам с почечной недостаточностью |
| KR20130101524A (ko) | 2010-09-01 | 2013-09-13 | 아레나 파마슈티칼스, 인크. | 5-ｈｔ2ｃ 아고니스트의 비-흡습성 염 |
| RU2674670C1 (ru) | 2012-10-09 | 2018-12-12 | Арена Фармасьютикалз, Инк. | Способ коррекции массы тела |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5233687A (en) * | 1975-09-11 | 1977-03-14 | Shionogi & Co Ltd | Process for preparation of 1,5-dihydro-2h-1,4-benzodiazepine-2-on deri vatives |
| JPS5481290A (en) * | 1977-11-17 | 1979-06-28 | Smithkline Corp | Benzazepin compound |
-
1982
- 1982-06-14 US US06/387,916 patent/US4988690A/en not_active Expired - Fee Related
-
1983
- 1983-06-08 DE DE8383105610T patent/DE3370621D1/de not_active Expired
- 1983-06-08 AT AT83105610T patent/ATE26263T1/de not_active IP Right Cessation
- 1983-06-08 EP EP83105610A patent/EP0096838B1/en not_active Expired
- 1983-06-10 FI FI832092A patent/FI78473C/fi not_active IP Right Cessation
- 1983-06-11 KR KR1019830002597A patent/KR900001214B1/ko not_active Expired
- 1983-06-13 IE IE1384/83A patent/IE55404B1/en unknown
- 1983-06-13 DK DK270983A patent/DK270983A/da not_active Application Discontinuation
- 1983-06-13 HU HU832096A patent/HU190902B/hu not_active IP Right Cessation
- 1983-06-13 ES ES523191A patent/ES8503666A1/es not_active Expired
- 1983-06-13 JP JP58104343A patent/JPS595165A/ja active Granted
- 1983-06-13 GR GR71648A patent/GR78291B/el unknown
- 1983-06-13 IL IL68964A patent/IL68964A/xx unknown
- 1983-06-13 ZA ZA834309A patent/ZA834309B/xx unknown
- 1983-06-13 CA CA000430280A patent/CA1214460A/en not_active Expired
- 1983-06-14 PT PT76864A patent/PT76864B/pt unknown
- 1983-06-14 AU AU15764/83A patent/AU570920B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| KR840005103A (ko) | 1984-11-03 |
| AU1576483A (en) | 1983-12-22 |
| FI832092A0 (fi) | 1983-06-10 |
| PT76864A (en) | 1983-07-01 |
| EP0096838A1 (en) | 1983-12-28 |
| KR900001214B1 (ko) | 1990-02-28 |
| ES523191A0 (es) | 1985-03-01 |
| JPH0365342B2 (enExample) | 1991-10-11 |
| FI832092L (fi) | 1983-12-15 |
| IE55404B1 (en) | 1990-09-12 |
| PT76864B (en) | 1986-02-27 |
| JPS595165A (ja) | 1984-01-12 |
| FI78473C (fi) | 1989-08-10 |
| AU570920B2 (en) | 1988-03-31 |
| ZA834309B (en) | 1984-03-28 |
| IL68964A (en) | 1988-03-31 |
| DK270983D0 (da) | 1983-06-13 |
| US4988690A (en) | 1991-01-29 |
| DK270983A (da) | 1983-12-15 |
| IL68964A0 (en) | 1983-10-31 |
| DE3370621D1 (en) | 1987-05-07 |
| IE831384L (en) | 1983-12-14 |
| HU190902B (en) | 1986-12-28 |
| EP0096838B1 (en) | 1987-04-01 |
| ATE26263T1 (de) | 1987-04-15 |
| ES8503666A1 (es) | 1985-03-01 |
| GR78291B (enExample) | 1984-09-26 |
| FI78473B (fi) | 1989-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0096838B1 (en) | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines, a process for preparing the same and their use as medicaments | |
| CA1148547A (en) | Amino-ether oxides | |
| EP0080779B1 (en) | 3-benzazepines as alpha-2 antagonists | |
| WO1993016997A1 (en) | 2,3,4,5-TETRAHYDRO-1H^_-3-BENZAZEPINES HAVING ANTI-PSYCHOTIC ACTIVITY, AND SYNTHESIS OF α-SUBSTITUTED-ARYLACETAMIDES | |
| HU214578B (hu) | Eljárás aril-acetamidok, valamint hatóanyagként ezen vegyületeket tartalmazó gyógyászati készítmények előállítására | |
| CA1053230A (en) | 4-arylpiperidine derivatives and processes for the production thereof | |
| US3483185A (en) | N-substituted 2,3,4,5-tetrahydro-1h-3-benzazepines | |
| AU592733B2 (en) | Substituted 1h-imidazoles | |
| US4888335A (en) | 3-alkoxy-2-aminopropyl heterocyclic amines and their use as cardiovascular agents | |
| EP0152236A2 (en) | Aryloxymethylpyrrolidinols and piperidinols having antidepressant, antiarhythmic or hypotensive activity | |
| IE49945B1 (en) | Production of methylene-cycloamines | |
| CA1271748A (en) | Benzazepine derivatives | |
| US4465677A (en) | Pharmaceutical compositions and method of producing alpha2 antagonism | |
| US5059688A (en) | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepine preparation | |
| CA1173833A (en) | 4-aryloxy-1,2,3,4-tetrahydroisoquinolines, and intermediates, a process for preparing the same, a pharmaceutical composition containing the same and their use as medicaments | |
| US3381000A (en) | Certain 11-basic substituted-5, 6-dihydromorphanthridine compounds | |
| US4752645A (en) | Benzazepine derivatives | |
| US4794181A (en) | 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines | |
| EP0033632B1 (en) | 7,8-amino, hydroxy-1-phenyl-2,3,4,5-tetrahydro-1h-3-benzazepines, process for their preparation and pharmaceutical compositions containing them | |
| EP0043729B1 (en) | New dopaminergic isoquinolines | |
| US4198418A (en) | Spiro[dibenz(b,f)oxepin-piperidine]s | |
| US4935418A (en) | Medical compositions of 1-aryloxy-2,3,4,5-tetrahydro-3-benzazepines and use thereof | |
| EP0508995B1 (en) | Muscarinic receptor antagonists | |
| US4477670A (en) | 4-Aryloxy-1,2,3,4-tetrahydroisoquinolines | |
| EP0369334A2 (en) | 1-Aminoalkyl-3-oxysubstituted-4-aryl-1,3,4,5-tetrahydro-2H-1,3-benzodiazepine-2-ones, a process for their preparation and their use as medicaments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |