HRP980003A2 - Tricyclic benzo/e/ isoindoles and benzo/h/isoquinolines - Google Patents
Tricyclic benzo/e/ isoindoles and benzo/h/isoquinolinesInfo
- Publication number
- HRP980003A2 HRP980003A2 HR97100172.2A HRP980003A HRP980003A2 HR P980003 A2 HRP980003 A2 HR P980003A2 HR P980003 A HRP980003 A HR P980003A HR P980003 A2 HRP980003 A2 HR P980003A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- benzo
- hexahydro
- isoquinolin
- cis
- Prior art date
Links
- 125000005605 benzo group Chemical group 0.000 title 2
- 125000000904 isoindolyl group Chemical class C=1(NC=C2C=CC=CC12)* 0.000 title 1
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- RVPHFBXESBBWKH-TZMCWYRMSA-N (4ar,10br)-2,7,9-trimethyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C1C(=O)C2=C(C)C=C(C)C=C2[C@H]2[C@@H]1CCN(C)C2 RVPHFBXESBBWKH-TZMCWYRMSA-N 0.000 claims description 11
- XKPFAVXGYLJDLN-MFKMUULPSA-N (4ar,10bs)-8-ethyl-7-hydroxy-9-methoxy-2-methyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C([C@@H]1CC2=O)CN(C)C[C@@H]1C1=C2C(O)=C(CC)C(OC)=C1 XKPFAVXGYLJDLN-MFKMUULPSA-N 0.000 claims description 11
- HCMDHUBCQLZYCM-ZYHUDNBSSA-N COC1=CC=CC2=C1C(C[C@H]1CCN(C[C@@H]21)C)=O Chemical compound COC1=CC=CC2=C1C(C[C@H]1CCN(C[C@@H]21)C)=O HCMDHUBCQLZYCM-ZYHUDNBSSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- GGJZYMHJKNTZJJ-ZWNOBZJWSA-N CN1C[C@H]2C3=C(C(C[C@H]2CC1)=O)C=CC=C3 Chemical compound CN1C[C@H]2C3=C(C(C[C@H]2CC1)=O)C=CC=C3 GGJZYMHJKNTZJJ-ZWNOBZJWSA-N 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 208000014674 injury Diseases 0.000 claims description 7
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- OHYAVVSABRKZPS-DGCLKSJQSA-N CN1C[C@H]2C3=C(C(C[C@H]2CC1)=O)C(=CC=C3)C Chemical compound CN1C[C@H]2C3=C(C(C[C@H]2CC1)=O)C(=CC=C3)C OHYAVVSABRKZPS-DGCLKSJQSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- GGJZYMHJKNTZJJ-UHFFFAOYSA-N 2-methyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C1C(=O)C2=CC=CC=C2C2C1CCN(C)C2 GGJZYMHJKNTZJJ-UHFFFAOYSA-N 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000032841 Bulimia Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010012335 Dependence Diseases 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 206010019233 Headaches Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 208000026139 Memory disease Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 206010041250 Social phobia Diseases 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 230000003542 behavioural effect Effects 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- 231100000869 headache Toxicity 0.000 claims description 4
- 230000036541 health Effects 0.000 claims description 4
- 230000003340 mental effect Effects 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000022821 personality disease Diseases 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 208000020016 psychiatric disease Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 4
- 208000015891 sexual disease Diseases 0.000 claims description 4
- 208000019116 sleep disease Diseases 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- UMEJOQOCVLDBPF-MWLCHTKSSA-N ClC1=CC=CC2=C1C(C[C@H]1CCN(C[C@@H]21)C)=O Chemical compound ClC1=CC=CC2=C1C(C[C@H]1CCN(C[C@@H]21)C)=O UMEJOQOCVLDBPF-MWLCHTKSSA-N 0.000 claims description 3
- LBOWASZHBVMBNJ-MWLCHTKSSA-N FC1=CC=CC2=C1C(C[C@H]1CCN(C[C@@H]21)C)=O Chemical compound FC1=CC=CC2=C1C(C[C@H]1CCN(C[C@@H]21)C)=O LBOWASZHBVMBNJ-MWLCHTKSSA-N 0.000 claims description 3
- 206010033664 Panic attack Diseases 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- 238000005574 benzylation reaction Methods 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 230000020335 dealkylation Effects 0.000 claims description 3
- 238000006900 dealkylation reaction Methods 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000005176 gastrointestinal motility Effects 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 208000019906 panic disease Diseases 0.000 claims description 3
- IUFDZLGEYYAUNN-BXUZGUMPSA-N CN1C[C@H]2C3=C(C(C[C@H]2CC1)=O)C=CC(=C3)C Chemical compound CN1C[C@H]2C3=C(C(C[C@H]2CC1)=O)C=CC(=C3)C IUFDZLGEYYAUNN-BXUZGUMPSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
- 125000001424 substituent group Chemical group 0.000 claims 2
- SQTYUBLJSDIHTH-QMTHXVAHSA-N COC=1C=CC2=C(C(C[C@H]3CCN(C[C@@H]23)C)=O)C1 Chemical compound COC=1C=CC2=C(C(C[C@H]3CCN(C[C@@H]23)C)=O)C1 SQTYUBLJSDIHTH-QMTHXVAHSA-N 0.000 claims 1
- 208000001738 Nervous System Trauma Diseases 0.000 claims 1
- 239000012876 carrier material Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 98
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 74
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 238000002844 melting Methods 0.000 description 60
- 230000008018 melting Effects 0.000 description 60
- 239000000203 mixture Substances 0.000 description 46
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 17
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
- 235000011114 ammonium hydroxide Nutrition 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 15
- 239000001530 fumaric acid Substances 0.000 description 14
- -1 methoxy, ethoxy, propoxy, isopropoxy Chemical group 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000012230 colorless oil Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- GPVPDRHTRGTSIH-UHFFFAOYSA-N isoquinolin-6-ol Chemical compound C1=NC=CC2=CC(O)=CC=C21 GPVPDRHTRGTSIH-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- HCMDHUBCQLZYCM-PWSUYJOCSA-N (4ar,10bs)-7-methoxy-2-methyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C([C@@H]12)N(C)CC[C@@H]1CC(=O)C1=C2C=CC=C1OC HCMDHUBCQLZYCM-PWSUYJOCSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- SOWOYMBNJVLWGP-UHFFFAOYSA-N isoindol-5-one Chemical compound O=C1C=CC2=CN=CC2=C1 SOWOYMBNJVLWGP-UHFFFAOYSA-N 0.000 description 5
- 239000001993 wax Substances 0.000 description 5
- XEXZQNTXIFYNOW-MFKMUULPSA-N (3as,9bs)-7-ethyl-6,8-dimethoxy-2-methyl-3,3a,4,9b-tetrahydro-1h-benzo[e]isoindol-5-one Chemical compound C1C(=O)C2=C(OC)C(CC)=C(OC)C=C2[C@H]2CN(C)C[C@H]21 XEXZQNTXIFYNOW-MFKMUULPSA-N 0.000 description 4
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- WOYFITDPZZERSY-UHFFFAOYSA-N methyl 2-(2-methylphenyl)prop-2-enoate Chemical compound COC(=O)C(=C)C1=CC=CC=C1C WOYFITDPZZERSY-UHFFFAOYSA-N 0.000 description 4
- NEIHGJSIKMRCBN-UHFFFAOYSA-N methyl 2-(4-ethyl-3,5-dimethoxyphenyl)prop-2-enoate Chemical compound CCC1=C(OC)C=C(C(=C)C(=O)OC)C=C1OC NEIHGJSIKMRCBN-UHFFFAOYSA-N 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229920000137 polyphosphoric acid Polymers 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 3
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 3
- 239000003054 catalyst 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
- 238000001816 cooling Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- ZIIBRVLOWGITIM-ACCUITESSA-N methyl (2e)-2-[3-(4-ethyl-3,5-dimethoxyphenyl)-1-methylpiperidin-4-ylidene]acetate Chemical compound C1=C(OC)C(CC)=C(OC)C=C1C1C(=C/C(=O)OC)/CCN(C)C1 ZIIBRVLOWGITIM-ACCUITESSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 2
- HZLZDBIDHYLBBP-SKDRFNHKSA-N (3as,9bs)-7-ethyl-6-hydroxy-8-methoxy-2-methyl-3,3a,4,9b-tetrahydro-1h-benzo[e]isoindol-5-one Chemical compound O=C1C[C@@H]2CN(C)C[C@@H]2C2=C1C(O)=C(CC)C(OC)=C2 HZLZDBIDHYLBBP-SKDRFNHKSA-N 0.000 description 2
- KSZNUQAOFKMJFH-RNSJEMGCSA-N (4aR,10bR)-2,7-dimethyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1C(=O)C2=C(C)C=CC=C2[C@H]2[C@@H]1CCN(C)C2 KSZNUQAOFKMJFH-RNSJEMGCSA-N 0.000 description 2
- VAVATSWPLAZFSF-DNVCBOLYSA-N (4ar,10br)-2-benzyl-8-fluoro-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C([C@H]1C2=CC=C(C=C2C(=O)C[C@H]1CC1)F)N1CC1=CC=CC=C1 VAVATSWPLAZFSF-DNVCBOLYSA-N 0.000 description 2
- BOSKYPCQKURRJL-QMTHXVAHSA-N (4ar,10br)-2-ethyl-8-fluoro-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C1C(=O)C2=CC(F)=CC=C2[C@H]2[C@@H]1CCN(CC)C2 BOSKYPCQKURRJL-QMTHXVAHSA-N 0.000 description 2
- VNLVXNKNDNAGOX-IAQYHMDHSA-N (4ar,10br)-8-fluoro-2-propyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C1C(=O)C2=CC(F)=CC=C2[C@H]2[C@@H]1CCN(CCC)C2 VNLVXNKNDNAGOX-IAQYHMDHSA-N 0.000 description 2
- IFOPSZCDYMWANQ-PWSUYJOCSA-N (4ar,10bs)-10-methoxy-2-methyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C([C@@H]1CC2=O)CN(C)C[C@@H]1C1=C2C=CC=C1OC IFOPSZCDYMWANQ-PWSUYJOCSA-N 0.000 description 2
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- 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
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- LOMVENUNSWAXEN-UHFFFAOYSA-N Methyl oxalate Chemical compound COC(=O)C(=O)OC LOMVENUNSWAXEN-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 235000021355 Stearic acid Nutrition 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
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- FZICDBOJOMQACG-UHFFFAOYSA-N benzo[h]isoquinoline Chemical class C1=NC=C2C3=CC=CC=C3C=CC2=C1 FZICDBOJOMQACG-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 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
- 230000009519 contusion Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- ULWHQCBEIJAXRS-UHFFFAOYSA-N dimethyl 2-(4-ethyl-3,5-dimethoxyphenyl)-3-oxobutanedioate Chemical compound CCC1=C(OC)C=C(C(C(=O)OC)C(=O)C(=O)OC)C=C1OC ULWHQCBEIJAXRS-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- ROEZPXRDTJGAAN-VOTSOKGWSA-N ethyl (e)-3-(3-chlorophenyl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC=CC(Cl)=C1 ROEZPXRDTJGAAN-VOTSOKGWSA-N 0.000 description 1
- WMXMFJJIJKZOGZ-UHFFFAOYSA-N ethyl 2-(3,5-dichlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC(Cl)=CC(Cl)=C1 WMXMFJJIJKZOGZ-UHFFFAOYSA-N 0.000 description 1
- APLWZHGFNHJFEK-UHFFFAOYSA-N ethyl 2-(4-ethyl-3,5-dimethoxyphenyl)prop-2-enoate Chemical compound CCOC(=O)C(=C)C1=CC(OC)=C(CC)C(OC)=C1 APLWZHGFNHJFEK-UHFFFAOYSA-N 0.000 description 1
- QQRJPDCUZPIHFK-UHFFFAOYSA-N ethyl 3-(3-methylphenyl)prop-2-enoate Chemical compound CCOC(=O)C=CC1=CC=CC(C)=C1 QQRJPDCUZPIHFK-UHFFFAOYSA-N 0.000 description 1
- MOXPNVNOLURPGE-UHFFFAOYSA-N ethyl 3-(4-ethyl-3,5-dimethoxyphenyl)prop-2-enoate Chemical compound CCOC(=O)C=CC1=CC(OC)=C(CC)C(OC)=C1 MOXPNVNOLURPGE-UHFFFAOYSA-N 0.000 description 1
- XVIJMHJTEHBUJI-UHFFFAOYSA-N ethyl 3-(methylamino)propanoate Chemical compound CCOC(=O)CCNC XVIJMHJTEHBUJI-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WAERXXDJZGITQU-UHFFFAOYSA-N methyl 2-(2-methoxyphenyl)prop-2-enoate Chemical compound COC(=O)C(=C)C1=CC=CC=C1OC WAERXXDJZGITQU-UHFFFAOYSA-N 0.000 description 1
- WXOJCEHMQHERFQ-UHFFFAOYSA-N methyl 2-(3,4-difluorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C(F)=C1 WXOJCEHMQHERFQ-UHFFFAOYSA-N 0.000 description 1
- XLIWHBWGBRQLQH-UHFFFAOYSA-N methyl 2-(3-chlorophenyl)prop-2-enoate Chemical compound COC(=O)C(=C)C1=CC=CC(Cl)=C1 XLIWHBWGBRQLQH-UHFFFAOYSA-N 0.000 description 1
- GGWJRBUNCHKWAF-UHFFFAOYSA-N methyl 2-(4-ethylphenyl)prop-2-enoate Chemical compound CCC1=CC=C(C(=C)C(=O)OC)C=C1 GGWJRBUNCHKWAF-UHFFFAOYSA-N 0.000 description 1
- PJRUCFSXULIYLQ-XJKSGUPXSA-N methyl 2-[(3r,4s)-3-(4-ethyl-3,5-dimethoxyphenyl)-1-methylpiperidin-4-yl]acetate Chemical compound C1=C(OC)C(CC)=C(OC)C=C1[C@H]1[C@H](CC(=O)OC)CCN(C)C1 PJRUCFSXULIYLQ-XJKSGUPXSA-N 0.000 description 1
- MXQHPPHJMXTMOZ-UHFFFAOYSA-N methyl 2-[3-(4-bromo-3,5-dimethoxyphenyl)-1-methylpiperidin-4-yl]acetate Chemical compound COC(=O)CC1CCN(C)CC1C1=CC(OC)=C(Br)C(OC)=C1 MXQHPPHJMXTMOZ-UHFFFAOYSA-N 0.000 description 1
- PJRUCFSXULIYLQ-UHFFFAOYSA-N methyl 2-[3-(4-ethyl-3,5-dimethoxyphenyl)-1-methylpiperidin-4-yl]acetate Chemical compound C1=C(OC)C(CC)=C(OC)C=C1C1C(CC(=O)OC)CCN(C)C1 PJRUCFSXULIYLQ-UHFFFAOYSA-N 0.000 description 1
- SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- 229940076279 serotonin Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97100172 | 1997-01-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP980003A2 true HRP980003A2 (en) | 1998-10-31 |
Family
ID=8226353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR97100172.2A HRP980003A2 (en) | 1997-01-08 | 1998-01-07 | Tricyclic benzo/e/ isoindoles and benzo/h/isoquinolines |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6310208B1 (zh) |
| KR (1) | KR100433609B1 (zh) |
| CN (1) | CN1113872C (zh) |
| AR (1) | AR011358A1 (zh) |
| CO (1) | CO4930268A1 (zh) |
| ES (1) | ES2212264T3 (zh) |
| HR (1) | HRP980003A2 (zh) |
| MA (1) | MA26461A1 (zh) |
| PE (1) | PE44199A1 (zh) |
| PT (1) | PT958285E (zh) |
| TR (1) | TR199901586T2 (zh) |
| ZA (1) | ZA9817B (zh) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2400300A1 (en) | 2004-08-25 | 2011-12-28 | Takeda Pharmaceutical Company Limited | Method of screening preventives/remedies for stress urinary incontinence |
| US8158617B2 (en) | 2006-05-16 | 2012-04-17 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound and use thereof |
| WO2009063992A1 (ja) | 2007-11-15 | 2009-05-22 | Takeda Pharmaceutical Company Limited | 縮合ピリジン誘導体およびその用途 |
| CN101648865B (zh) * | 2008-08-16 | 2013-03-20 | 重庆市科学技术研究院 | 多酚丙烯酸衍生物及其在药物中的应用 |
| JPWO2011071136A1 (ja) | 2009-12-11 | 2013-04-22 | アステラス製薬株式会社 | 線維筋痛症治療剤 |
| WO2011097797A1 (zh) * | 2010-02-10 | 2011-08-18 | Peng Jinlian | 多酚丙烯酸衍生物，其制备方法以及在制备药物中的应用 |
| EP3733204A4 (en) | 2017-12-27 | 2021-09-15 | Takeda Pharmaceutical Company Limited | THERAPEUTIC FOR EXERCISE INCONTINENCE AND STAIR INCONTINENCE |
| CN112028878A (zh) * | 2020-09-11 | 2020-12-04 | 江阴迈康升华医药科技有限公司 | 一种多氢异喹啉衍生物及其制备方法和医疗用途 |
| WO2022221774A1 (en) * | 2021-04-16 | 2022-10-20 | Eleusis Therapeutics Us, Inc. | Aryl-ring-substituted 3-phenylazetidines and their use in methods for treating 5-ht2 responsive conditions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH504438A (de) | 1968-05-27 | 1971-03-15 | Sandoz Ag | Verfahren zur Herstellung von 1,2,3,4,4a,5,6,10b-Octahydrobenz(h)isochinolin-6-on |
| US4678791A (en) | 1985-05-07 | 1987-07-07 | Pennwalt Corporation | 6-phenyl-1,2-3,4,4a,5-6,10b-octahydrobenz(h)isoquinolines useful for treating depression |
| JPH03101658A (ja) * | 1989-09-13 | 1991-04-26 | Nippon Chemiphar Co Ltd | ピロリジン酢酸誘導体 |
| US5180733A (en) | 1990-03-30 | 1993-01-19 | Abbott Laboratories | Biogenic amine uptake inhibitors |
-
1998
- 1998-01-02 MA MA24916A patent/MA26461A1/fr unknown
- 1998-01-02 ZA ZA9817A patent/ZA9817B/xx unknown
- 1998-01-05 PE PE1998000005A patent/PE44199A1/es not_active Application Discontinuation
- 1998-01-05 AR ARP980100025A patent/AR011358A1/es unknown
- 1998-01-06 US US09/003,446 patent/US6310208B1/en not_active Expired - Fee Related
- 1998-01-07 ES ES98902982T patent/ES2212264T3/es not_active Expired - Lifetime
- 1998-01-07 CO CO98000437A patent/CO4930268A1/es unknown
- 1998-01-07 CN CN98801734A patent/CN1113872C/zh not_active Expired - Fee Related
- 1998-01-07 KR KR10-1999-7006175A patent/KR100433609B1/ko not_active IP Right Cessation
- 1998-01-07 HR HR97100172.2A patent/HRP980003A2/hr not_active Application Discontinuation
- 1998-01-07 TR TR1999/01586T patent/TR199901586T2/xx unknown
- 1998-01-07 PT PT98902982T patent/PT958285E/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MA26461A1 (fr) | 2004-12-20 |
| CO4930268A1 (es) | 2000-06-27 |
| CN1243510A (zh) | 2000-02-02 |
| ZA9817B (en) | 1998-07-08 |
| PE44199A1 (es) | 1999-05-06 |
| ES2212264T3 (es) | 2004-07-16 |
| TR199901586T2 (xx) | 1999-10-21 |
| KR20000069962A (ko) | 2000-11-25 |
| AR011358A1 (es) | 2000-08-16 |
| CN1113872C (zh) | 2003-07-09 |
| US6310208B1 (en) | 2001-10-30 |
| KR100433609B1 (ko) | 2004-05-31 |
| PT958285E (pt) | 2004-05-31 |
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