JPH0365342B2 - - Google Patents
Info
- Publication number
- JPH0365342B2 JPH0365342B2 JP58104343A JP10434383A JPH0365342B2 JP H0365342 B2 JPH0365342 B2 JP H0365342B2 JP 58104343 A JP58104343 A JP 58104343A JP 10434383 A JP10434383 A JP 10434383A JP H0365342 B2 JPH0365342 B2 JP H0365342B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- hydrogen
- alkyl
- benzazepine
- tetrahydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 144
- 239000001257 hydrogen Substances 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 239000002253 acid Substances 0.000 claims abstract description 54
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 25
- 150000002367 halogens Chemical group 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims description 89
- 238000000034 method Methods 0.000 claims description 37
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 14
- 238000007796 conventional method Methods 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
- 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 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 7
- 235000019253 formic acid Nutrition 0.000 claims description 7
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 6
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052796 boron Inorganic materials 0.000 claims description 3
- 238000007344 nucleophilic reaction Methods 0.000 claims description 3
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims description 2
- 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 1
- 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 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
- 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 1
- -1 alkylene amine Chemical class 0.000 abstract description 18
- 125000000217 alkyl group Chemical group 0.000 abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 8
- 125000002947 alkylene group Chemical group 0.000 abstract description 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 178
- 239000000243 solution Substances 0.000 description 157
- 239000003921 oil Substances 0.000 description 143
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 135
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 127
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 239000000203 mixture Substances 0.000 description 93
- 238000002844 melting Methods 0.000 description 91
- 230000008018 melting Effects 0.000 description 91
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 75
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 74
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- 238000003756 stirring Methods 0.000 description 63
- 238000000921 elemental analysis Methods 0.000 description 60
- 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 49
- 239000011541 reaction mixture Substances 0.000 description 46
- 239000000126 substance Substances 0.000 description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 39
- 238000000354 decomposition reaction Methods 0.000 description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- 229910052757 nitrogen Inorganic materials 0.000 description 36
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 32
- 239000000284 extract Substances 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000725 suspension Substances 0.000 description 28
- 235000008504 concentrate Nutrition 0.000 description 25
- 239000012141 concentrate Substances 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000007788 liquid Substances 0.000 description 18
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 18
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 229910010082 LiAlH Inorganic materials 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 13
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 13
- 239000002904 solvent Substances 0.000 description 12
- 238000009835 boiling Methods 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- 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 8
- 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 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241000220324 Pyrus Species 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000010791 quenching Methods 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 5
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000011976 maleic acid Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000052 vinegar Substances 0.000 description 5
- 235000021419 vinegar Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 239000012259 ether extract Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 150000002688 maleic acid derivatives Chemical class 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- UNNNAIWPDLRVRN-UHFFFAOYSA-N 1-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C(F)(F)F)C=C1 UNNNAIWPDLRVRN-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
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 235000014443 Pyrus communis Nutrition 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000008098 formaldehyde solution Substances 0.000 description 3
- 235000021017 pears Nutrition 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-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-IWFBPKFRSA-N 0.000 description 2
- 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 description 2
- USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 2
- VZHJIJZEOCBKRA-UHFFFAOYSA-N 1-chloro-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1 VZHJIJZEOCBKRA-UHFFFAOYSA-N 0.000 description 2
- GBOWGKOVMBDPJF-UHFFFAOYSA-N 1-fluoro-3-(trifluoromethyl)benzene Chemical compound FC1=CC=CC(C(F)(F)F)=C1 GBOWGKOVMBDPJF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- YNHJTOGHZXHDOG-UHFFFAOYSA-N 3-methyl-5-phenoxy-1,2,4,5-tetrahydro-3-benzazepine;hydrochloride Chemical compound Cl.C1N(C)CCC2=CC=CC=C2C1OC1=CC=CC=C1 YNHJTOGHZXHDOG-UHFFFAOYSA-N 0.000 description 2
- YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 description 2
- YOVGFADJMWAQJG-UHFFFAOYSA-N 3h-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CNC=CC2=CC=CC=C21 YOVGFADJMWAQJG-UHFFFAOYSA-N 0.000 description 2
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 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 description 2
- 235000001674 Agaricus brunnescens Nutrition 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 206010015995 Eyelid ptosis Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000407193 Pindis Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000005881 detosylation reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 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 2
- 238000000605 extraction Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000314 lubricant Substances 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
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 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
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 235000006408 oxalic acid Nutrition 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
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 201000003004 ptosis Diseases 0.000 description 2
- 238000012289 standard assay Methods 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 229960005333 tetrabenazine Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
- YWVGLZQJRXEUTE-BTJKTKAUSA-N (z)-but-2-enedioic acid;5-(4-chlorophenoxy)-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(Cl)C=C1 YWVGLZQJRXEUTE-BTJKTKAUSA-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
- 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
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- NUMXHEUHHRTBQT-AATRIKPKSA-N 2,4-dimethoxy-1-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C(OC)=C1 NUMXHEUHHRTBQT-AATRIKPKSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OEZPDHRXGCLGKB-UHFFFAOYSA-N 2-chloropropanamide Chemical compound CC(Cl)C(N)=O OEZPDHRXGCLGKB-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
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
- 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 1
- 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 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
- CHKGRHVKBPQKQZ-UHFFFAOYSA-N 3-methyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine;hydrochloride Chemical compound Cl.C1N(C)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 CHKGRHVKBPQKQZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 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
- 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 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
- DSQIFHJPKDUDMQ-UHFFFAOYSA-N 5-(3-chlorophenoxy)-3-(cyclopropylmethyl)-1,2,4,5-tetrahydro-3-benzazepine;oxalic acid Chemical compound OC(=O)C(O)=O.ClC1=CC=CC(OC2C3=CC=CC=C3CCN(CC3CC3)C2)=C1 DSQIFHJPKDUDMQ-UHFFFAOYSA-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
- 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 description 1
- 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 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
- CELRYVDTFOSENW-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine;hydrochloride Chemical compound Cl.C1=2C=C(OC)C(OC)=CC=2CCN(C)CC1OC1=CC=C(C(F)(F)F)C=C1 CELRYVDTFOSENW-UHFFFAOYSA-N 0.000 description 1
- 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 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-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
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- YNUYSRGKOICQEU-UHFFFAOYSA-N C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.NCCN1CCC2=C(C(C1)OC1=CC=C(C=C1)C(F)(F)F)C=CC=C2 Chemical compound C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.NCCN1CCC2=C(C(C1)OC1=CC=C(C=C1)C(F)(F)F)C=CC=C2 YNUYSRGKOICQEU-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 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
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 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
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000750004 Nestor meridionalis Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- 241000384512 Trachichthyidae Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- 150000003973 alkyl amines Chemical class 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 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
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 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
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 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
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- ZVTQWXCKQTUVPY-UHFFFAOYSA-N chloromethylcyclopropane Chemical compound ClCC1CC1 ZVTQWXCKQTUVPY-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 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
- 125000004093 cyano group Chemical group *C#N 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
- 239000002027 dichloromethane extract Substances 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 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
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
- IMORGMGAXWQYDB-UHFFFAOYSA-N ethyl 5-[4-(trifluoromethyl)phenoxy]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate Chemical compound C1N(C(=O)OCC)CCC2=CC=CC=C2C1OC1=CC=C(C(F)(F)F)C=C1 IMORGMGAXWQYDB-UHFFFAOYSA-N 0.000 description 1
- VYSYZMNJHYOXGN-UHFFFAOYSA-N ethyl n-aminocarbamate Chemical compound CCOC(=O)NN VYSYZMNJHYOXGN-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229950004696 flusalan Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229960003602 guanethidine Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- RTWNYYOXLSILQN-UHFFFAOYSA-N methanediamine Chemical compound NCN RTWNYYOXLSILQN-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- JAMNOLUZQIBPRL-UHFFFAOYSA-N n,n-dimethyl-2-[5-[4-(trifluoromethyl)phenoxy]-3-benzazepin-3-yl]ethanamine;dihydrochloride Chemical compound Cl.Cl.C=1N(CCN(C)C)C=CC2=CC=CC=C2C=1OC1=CC=C(C(F)(F)F)C=C1 JAMNOLUZQIBPRL-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
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 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 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
- 239000003208 petroleum Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000376 reactant Substances 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
- 229930195734 saturated hydrocarbon Natural products 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
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000007070 tosylation reaction Methods 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
- 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 |
|---|---|---|---|
| US387916 | 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 (2)
| Publication Number | Publication Date |
|---|---|
| JPS595165A JPS595165A (ja) | 1984-01-12 |
| JPH0365342B2 true JPH0365342B2 (en:Method) | 1991-10-11 |
Family
ID=23531838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58104343A Granted JPS595165A (ja) | 1982-06-14 | 1983-06-13 | １−アリ−ルオキシ−２，３，４，５−テトラヒドロ−３−ベンズアゼピンおよびその製法 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4988690A (en:Method) |
| EP (1) | EP0096838B1 (en:Method) |
| JP (1) | JPS595165A (en:Method) |
| KR (1) | KR900001214B1 (en:Method) |
| AT (1) | ATE26263T1 (en:Method) |
| AU (1) | AU570920B2 (en:Method) |
| CA (1) | CA1214460A (en:Method) |
| DE (1) | DE3370621D1 (en:Method) |
| DK (1) | DK270983A (en:Method) |
| ES (1) | ES8503666A1 (en:Method) |
| FI (1) | FI78473C (en:Method) |
| GR (1) | GR78291B (en:Method) |
| HU (1) | HU190902B (en:Method) |
| IE (1) | IE55404B1 (en:Method) |
| IL (1) | IL68964A (en:Method) |
| PT (1) | PT76864B (en:Method) |
| ZA (1) | ZA834309B (en:Method) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH27337A (en) * | 1987-03-27 | 1993-06-08 | 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 |
| 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 |
| 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 |
| NZ578503A (en) * | 2003-06-17 | 2011-02-25 | Arena Pharm Inc | Benzazepine derivatives useful for the treatment of 5HT2C receptor associated diseases |
| EP2332921B1 (en) | 2003-06-17 | 2016-03-02 | Arena Pharmaceuticals, Inc. | 8-Chloro-1 -methyl-2,3,4,5-tetrahydro-1 H-3benzazapine Hydrochloride |
| WO2005042491A1 (en) * | 2003-10-22 | 2005-05-12 | Arena Pharmaceuticals, Inc. | Benzazepine derivatives and methods of prophylaxis or treatment of 5ht2c receptor associated diseases |
| US20070275949A1 (en) * | 2003-10-22 | 2007-11-29 | Arena Pharmaceuticals, Inc. | Benzazepine Derivatives and Methods of Prophylaxis or Treatment of 5Ht2C Receptor Associated Diseases |
| CN101084193B (zh) | 2004-12-21 | 2011-12-07 | 艾尼纳制药公司 | (r)-8-氯-1-甲基-2,3,4,5-四氢-1h-3-苯并氮杂卓盐酸盐的晶型 |
| 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 |
| NZ580802A (en) | 2007-05-10 | 2012-09-28 | Albany Molecular Res Inc | Aryloxy-and heteroaryloxy-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| JP5491421B2 (ja) | 2008-03-04 | 2014-05-14 | 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 | ５−ｈｔ２ｃアゴニストである（ｒ）−８−クロロ−１−メチル−２，３，４，５−テトラヒドロ−１ｈ−３−ベンゾアゼピンに関連する中間体の調製のためのプロセス |
| EP2443080A2 (en) | 2009-06-18 | 2012-04-25 | Arena Pharmaceuticals, Inc. | Process for the preparation of 5-ht2c receptor agonists |
| KR20130112848A (ko) | 2010-06-02 | 2013-10-14 | 아레나 파마슈티칼스, 인크. | 5-ｈｔ2ｃ 수용체 아고니스트의 제조 방법 |
| KR20130101524A (ko) | 2010-09-01 | 2013-09-13 | 아레나 파마슈티칼스, 인크. | 5-ｈｔ2ｃ 아고니스트의 비-흡습성 염 |
| NZ608266A (en) | 2010-09-01 | 2015-09-25 | Arena Pharm Inc | Administration of lorcaserin to individuals with renal impairment |
| CA2808909A1 (en) | 2010-09-01 | 2012-03-08 | Arena Pharmaceuticals, Inc. | Salts of lorcaserin with optically active acids |
| CA2808912C (en) | 2010-09-01 | 2019-09-17 | Zezhi Jesse Shao | Modified-release dosage forms of 5-ht2c agonists useful for weight management |
| KR20150070249A (ko) | 2012-10-09 | 2015-06-24 | 아레나 파마슈티칼스, 인크. | 체중 관리 방법 |
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 AT AT83105610T patent/ATE26263T1/de not_active IP Right Cessation
- 1983-06-08 EP EP83105610A patent/EP0096838B1/en not_active Expired
- 1983-06-08 DE DE8383105610T patent/DE3370621D1/de 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 GR GR71648A patent/GR78291B/el unknown
- 1983-06-13 ES ES523191A patent/ES8503666A1/es not_active Expired
- 1983-06-13 DK DK270983A patent/DK270983A/da not_active Application Discontinuation
- 1983-06-13 ZA ZA834309A patent/ZA834309B/xx unknown
- 1983-06-13 CA CA000430280A patent/CA1214460A/en not_active Expired
- 1983-06-13 IE IE1384/83A patent/IE55404B1/en unknown
- 1983-06-13 JP JP58104343A patent/JPS595165A/ja active Granted
- 1983-06-13 HU HU832096A patent/HU190902B/hu not_active IP Right Cessation
- 1983-06-13 IL IL68964A patent/IL68964A/xx 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 |
|---|---|
| KR900001214B1 (ko) | 1990-02-28 |
| HU190902B (en) | 1986-12-28 |
| ATE26263T1 (de) | 1987-04-15 |
| FI78473C (fi) | 1989-08-10 |
| CA1214460A (en) | 1986-11-25 |
| DK270983A (da) | 1983-12-15 |
| FI832092A0 (fi) | 1983-06-10 |
| US4988690A (en) | 1991-01-29 |
| AU570920B2 (en) | 1988-03-31 |
| ES523191A0 (es) | 1985-03-01 |
| IE831384L (en) | 1983-12-14 |
| PT76864A (en) | 1983-07-01 |
| IL68964A0 (en) | 1983-10-31 |
| IL68964A (en) | 1988-03-31 |
| GR78291B (en:Method) | 1984-09-26 |
| JPS595165A (ja) | 1984-01-12 |
| FI78473B (fi) | 1989-04-28 |
| ZA834309B (en) | 1984-03-28 |
| AU1576483A (en) | 1983-12-22 |
| KR840005103A (ko) | 1984-11-03 |
| FI832092L (fi) | 1983-12-15 |
| DE3370621D1 (en) | 1987-05-07 |
| ES8503666A1 (es) | 1985-03-01 |
| DK270983D0 (da) | 1983-06-13 |
| IE55404B1 (en) | 1990-09-12 |
| PT76864B (en) | 1986-02-27 |
| EP0096838A1 (en) | 1983-12-28 |
| EP0096838B1 (en) | 1987-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH0365342B2 (en:Method) | ||
| RU2079493C1 (ru) | Способ получения 4-амино-2-(4-метилпиперазин-1-ил)-5-(2,3,5-трихлорфенил) пиримидина или его кислой аддитивной соли | |
| JPH0819065B2 (ja) | ベンゾ融合シクロアルカンおよびオキサ‐およびチア‐シクロアルカントランス‐１，２‐ジアミン誘導体 | |
| JP2637737B2 (ja) | 新規な薬剤 | |
| US5250571A (en) | (S)-norfluoxetine in method of inhibiting serotonin uptake | |
| JP2776919B2 (ja) | フルオキセチン類似体 | |
| US5095039A (en) | Diphenylsulfide compound and use | |
| HU185523B (en) | Method for producing a phenyl-alkyl-aminoethyl-salicylamide | |
| EP0411912B1 (en) | Coumarin derivatives, their preparation and their use in the treatment of cerebrovascular disorders | |
| FR2663328A1 (fr) | Derives d'hexahydroazepines, un procede pour leur preparation et compositions pharmaceutiques les contenant. | |
| EP0345056A2 (en) | Improvements in and relating to serotonin antagonists | |
| EP0279633B1 (en) | Anticonvulsant agents | |
| CA1042905A (fr) | Procede de preparation de nouveaux azabicycloalcanes disubstitues | |
| US4705807A (en) | Amine derivatives | |
| JPS648621B2 (en:Method) | ||
| CA1057753A (en) | 1-(aminoalkoxyphenyl) derivatives of 2-oxohexahydro-indole | |
| JPH04221310A (ja) | セロトニン受容体に作用する化合物の改良 | |
| US6417222B1 (en) | [2-substituted-5-[3-thienyl)-benzyl]-2- ([2-isopropoxy-5-fluoro]-phenyoxy)-ethyl]-amine derivatives, method for the production and use thereof as medicaments | |
| EP0444855A1 (en) | Improvements in and relating to (S)-norfluoxetine | |
| US4868315A (en) | Novel aryloxycycloalkanolaminoalkylene aryl ketones | |
| JPH02236A (ja) | 選択的セロトニン摂取抑制剤 | |
| US20060264471A1 (en) | 3-(cyclopenten-1-yl)-benzyl-or 3-(cyclopenten-1-yl)-heteroarylmethyl-amine derviatives and use thereof as medicines for treating schizophrenia | |
| CH665842A5 (fr) | Derives de la pyridine, procede pour leur preparation et compositions therapeutiques les contenant. | |
| FR2505825A1 (fr) | Derives d'isoprenylamine et leur utilisation dans des compositions pharmaceutiques | |
| JPH0819061B2 (ja) | アミノアルコ−ル類 |