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
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Classifications
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- 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)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (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 |
|---|---|---|---|
| US387,916 | 1982-06-14 | ||
| 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 |
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 (OSRAM) |
| EP (1) | EP0096838B1 (OSRAM) |
| JP (1) | JPS595165A (OSRAM) |
| KR (1) | KR900001214B1 (OSRAM) |
| AT (1) | ATE26263T1 (OSRAM) |
| AU (1) | AU570920B2 (OSRAM) |
| CA (1) | CA1214460A (OSRAM) |
| DE (1) | DE3370621D1 (OSRAM) |
| DK (1) | DK270983A (OSRAM) |
| ES (1) | ES8503666A1 (OSRAM) |
| FI (1) | FI78473C (OSRAM) |
| GR (1) | GR78291B (OSRAM) |
| HU (1) | HU190902B (OSRAM) |
| IE (1) | IE55404B1 (OSRAM) |
| IL (1) | IL68964A (OSRAM) |
| PT (1) | PT76864B (OSRAM) |
| ZA (1) | ZA834309B (OSRAM) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5015639A (en) * | 1987-03-27 | 1991-05-14 | Schering Corporation | Substituted benzazepines, their preparation and pharmaceutical compositions containing them |
| ZA882080B (en) * | 1987-03-27 | 1989-04-26 | Schering Corp | Substituted benzazepines,their preparation and pharmaceutical compositions containing them |
| CA1327795C (en) * | 1987-08-14 | 1994-03-15 | Jules Freedman | Antidepressants which are aryloxy inadanamines |
| 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 |
| WO2002044144A2 (en) * | 2000-11-30 | 2002-06-06 | Advanced Research And Technology Institute, Inc. | Nucleophilic approach for preparing radiolabeled imaging agents and associated compounds |
| US6953787B2 (en) * | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| EP2189448B1 (en) | 2003-06-17 | 2014-01-29 | Arena Pharmaceuticals, Inc. | Processes for the Separation of 3-Benzazepine Racemates |
| JP4782003B2 (ja) * | 2003-06-17 | 2011-09-28 | 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 | ５ｈｔ２ｃレセプター関連疾患の処置に有用なベンズアゼピン誘導体 |
| US20080009478A1 (en) * | 2003-10-22 | 2008-01-10 | 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 |
| SI1838677T1 (sl) | 2004-12-21 | 2010-01-29 | Arena Pharm Inc | Kristalne oblike (R)-8-kloro-1-metil-2,3,4,5-tetrahidro-1H-3-benzazepin hidroklorida |
| AU2005322183B2 (en) | 2004-12-23 | 2012-03-29 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulator compositions and methods of use |
| JP5199997B2 (ja) * | 2006-04-03 | 2013-05-15 | 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 | ８−クロロ−１−メチル−２，３，４，５−テトラヒドロ−１ｈ−３−ベンズアゼピンおよびこれに関連する中間体を調製するためのプロセス |
| ES2522587T3 (es) * | 2006-12-05 | 2014-11-17 | Arena Pharmaceuticals, Inc. | Procesos para preparar (R)-8-cloro-1-metil-2,3,4,5-tetrahidro-1H-3-benzacepina e intermedios de la misma |
| WO2008141082A1 (en) | 2007-05-10 | 2008-11-20 | Amr Technology, Inc. | Aryloxy-and heteroaryloxy-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| EP2288585A1 (en) | 2008-03-04 | 2011-03-02 | 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 |
| CN102648170A (zh) | 2009-06-18 | 2012-08-22 | 艾尼纳制药公司 | 制备5-ht2c受体激动剂的方法 |
| US9045431B2 (en) | 2010-06-02 | 2015-06-02 | Arena Pharmaceuticals, Inc. | Processes for the preparation of 5-HT2C receptor agonists |
| CN103347523A (zh) | 2010-09-01 | 2013-10-09 | 艾尼纳制药公司 | 向具有肾损伤的个体给药氯卡色林 |
| EP2611782A1 (en) | 2010-09-01 | 2013-07-10 | Arena Pharmaceuticals, Inc. | Salts of lorcaserin with optically active acids |
| KR20130101524A (ko) | 2010-09-01 | 2013-09-13 | 아레나 파마슈티칼스, 인크. | 5-ｈｔ2ｃ 아고니스트의 비-흡습성 염 |
| CN103189053A (zh) | 2010-09-01 | 2013-07-03 | 艾尼纳制药公司 | 用于体重控制的5-ht2c激动剂的调节释放剂型 |
| CA2886875A1 (en) | 2012-10-09 | 2014-04-17 | Arena Pharmaceuticals, Inc. | Method of weight management |
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 CA CA000430280A patent/CA1214460A/en not_active Expired
- 1983-06-13 IL IL68964A patent/IL68964A/xx unknown
- 1983-06-13 ES ES523191A patent/ES8503666A1/es not_active Expired
- 1983-06-13 JP JP58104343A patent/JPS595165A/ja active Granted
- 1983-06-13 IE IE1384/83A patent/IE55404B1/en unknown
- 1983-06-13 ZA ZA834309A patent/ZA834309B/xx unknown
- 1983-06-13 HU HU832096A patent/HU190902B/hu not_active IP Right Cessation
- 1983-06-13 DK DK270983A patent/DK270983A/da not_active Application Discontinuation
- 1983-06-13 GR GR71648A patent/GR78291B/el unknown
- 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 |
|---|---|
| FI78473C (fi) | 1989-08-10 |
| GR78291B (OSRAM) | 1984-09-26 |
| EP0096838B1 (en) | 1987-04-01 |
| ES523191A0 (es) | 1985-03-01 |
| ES8503666A1 (es) | 1985-03-01 |
| FI832092A0 (fi) | 1983-06-10 |
| FI78473B (fi) | 1989-04-28 |
| PT76864B (en) | 1986-02-27 |
| KR840005103A (ko) | 1984-11-03 |
| IL68964A (en) | 1988-03-31 |
| IE831384L (en) | 1983-12-14 |
| IL68964A0 (en) | 1983-10-31 |
| PT76864A (en) | 1983-07-01 |
| US4988690A (en) | 1991-01-29 |
| DE3370621D1 (en) | 1987-05-07 |
| DK270983D0 (da) | 1983-06-13 |
| IE55404B1 (en) | 1990-09-12 |
| HU190902B (en) | 1986-12-28 |
| KR900001214B1 (ko) | 1990-02-28 |
| ATE26263T1 (de) | 1987-04-15 |
| JPS595165A (ja) | 1984-01-12 |
| DK270983A (da) | 1983-12-15 |
| AU1576483A (en) | 1983-12-22 |
| FI832092L (fi) | 1983-12-15 |
| ZA834309B (en) | 1984-03-28 |
| AU570920B2 (en) | 1988-03-31 |
| EP0096838A1 (en) | 1983-12-28 |
| JPH0365342B2 (OSRAM) | 1991-10-11 |
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Legal Events
| Date | Code | Title | Description |
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| MKEX | Expiry |