HRP980003A2 - Tricyclic benzo/e/ isoindoles and benzo/h/isoquinolines - Google Patents

Tricyclic benzo/e/ isoindoles and benzo/h/isoquinolines

Info

Publication number: HRP980003A2
Authority: HR; Croatia
Prior art keywords: methyl; benzo; hexahydro; isoquinolin; cis
Prior art date: 1997-01-08

Application number

HR97100172.2A

Other languages

English (en)

Croatian (hr)

Inventor

Juergen Wichmann

Original Assignee

Juergen Wichmann

Priority date (The priority date 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 date listed.)

1997-01-08

Filing date

1998-01-07

Publication date

1998-10-31

1998-01-07 Application filed by Juergen Wichmann filed Critical Juergen Wichmann

1998-10-31 Publication of HRP980003A2 publication Critical patent/HRP980003A2/hr

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
UPHJGZJJEWHCKJ-RISCZKNCSA-N (4ar,10bs)-2,8-dimethyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6-one Chemical compound C1C(=O)C2=CC(C)=CC=C2[C@@H]2[C@@H]1CCN(C)C2 UPHJGZJJEWHCKJ-RISCZKNCSA-N 0.000 description 2
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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)

HR97100172.2A 1997-01-08 1998-01-07 Tricyclic benzo/e/ isoindoles and benzo/h/isoquinolines HRP980003A2 (en)

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 (fr)
KR (1)	KR100433609B1 (fr)
CN (1)	CN1113872C (fr)
AR (1)	AR011358A1 (fr)
CO (1)	CO4930268A1 (fr)
ES (1)	ES2212264T3 (fr)
HR (1)	HRP980003A2 (fr)
MA (1)	MA26461A1 (fr)
PE (1)	PE44199A1 (fr)
PT (1)	PT958285E (fr)
TR (1)	TR199901586T2 (fr)
ZA (1)	ZA9817B (fr)

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EP1792629A4 (fr)	2004-08-25	2010-08-25	Takeda Pharmaceutical	Agents preventifs/remedes pour l'incontinence de stress et procede de selecetion de ceux-ci
EP2727585A1 (fr)	2006-05-16	2014-05-07	Takeda Pharmaceutical Company Limited	Méthode de dépistage in-vivo
EP2216023A4 (fr)	2007-11-15	2013-03-13	Takeda Pharmaceutical	Dérivé de pyridine condensé et son utilisation
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 (fr) *	2010-02-10	2011-08-18	Peng Jinlian	Dérivé d'un polyacide phénol-acrylique, sa préparation et son utilisation dans la préparation de médicaments
JPWO2019131902A1 (ja)	2017-12-27	2020-12-10	武田薬品工業株式会社	腹圧性尿失禁および便失禁の治療薬
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 (fr) *	2021-04-16	2022-10-20	Eleusis Therapeutics Us, Inc.	3-phénylazétidines à substitution aryle et leur utilisation dans des procédés de traitement d'affections sensibles à 5-ht2

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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 ZA ZA9817A patent/ZA9817B/xx unknown
- 1998-01-02 MA MA24916A patent/MA26461A1/fr unknown
- 1998-01-05 AR ARP980100025A patent/AR011358A1/es unknown
- 1998-01-05 PE PE1998000005A patent/PE44199A1/es not_active Application Discontinuation
- 1998-01-06 US US09/003,446 patent/US6310208B1/en not_active Expired - Fee Related
- 1998-01-07 PT PT98902982T patent/PT958285E/pt 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 Expired - Fee Related
- 1998-01-07 TR TR1999/01586T patent/TR199901586T2/xx unknown
- 1998-01-07 ES ES98902982T patent/ES2212264T3/es not_active Expired - Lifetime
- 1998-01-07 CO CO98000437A patent/CO4930268A1/es unknown
- 1998-01-07 HR HR97100172.2A patent/HRP980003A2/hr not_active Application Discontinuation

Also Published As

Publication number	Publication date
TR199901586T2 (xx)	1999-10-21
CO4930268A1 (es)	2000-06-27
KR100433609B1 (ko)	2004-05-31
US6310208B1 (en)	2001-10-30
KR20000069962A (ko)	2000-11-25
MA26461A1 (fr)	2004-12-20
PE44199A1 (es)	1999-05-06
PT958285E (pt)	2004-05-31
AR011358A1 (es)	2000-08-16
CN1243510A (zh)	2000-02-02
ZA9817B (en)	1998-07-08
CN1113872C (zh)	2003-07-09
ES2212264T3 (es)	2004-07-16

Legal Events

Date	Code	Title
1998-10-31	A1OB	Publication of a patent application
1999-04-12	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2000-05-24	OBST	Application withdrawn

Publication	Publication Date	Title
US5561150A (en)	1996-10-01	Tricyclic pyrazole derivatives
EP0362695B1 (fr)	1991-04-03	Dérivés de pyrrolocarbazole, procédés de leur préparation et leur application comme médicaments
CA1330661C (fr)	1994-07-12	Les n-(pyridynyl)-1h-indol-1-amines, procede pour leur preparation et leur utilisation comme medicaments
SK148298A3 (en)	2000-02-14	Substituted indazole derivatives and their use as inhibitors phosphodiesterase (pde) type iv and the production of tumor necrosis factor (tnf)
EP0958285B1 (fr)	2004-01-07	BENZO[e]ISOINDOLES ET BENZO[h]ISOQUINOLEINES TRICYCLIQUES
EP0370236B1 (fr)	1991-12-27	Dérivés de l'indolocarbazole, procédés pour leur préparation et leur utilisation comme médicaments
CN103180312B (zh)	2016-01-20	用于治疗或预防因血清素、去甲肾上腺素或多巴胺的神经传导的降低所导致的紊乱的杂环化合物
US6310208B1 (en)	2001-10-30	Serotonin receptor binding benzo[e]isoindoles and benzo[h]isoquinolines
IL309951A (en)	2024-03-01	Histone deacetylase inhibitors
US5486611A (en)	1996-01-23	Carboxamido-(1,2N)-carbocyclic-2-aminotetralin derivatives
JP2008521780A (ja)	2008-06-26	２−アルコキシ−３，４，５−トリヒドロキシアルキルアミド系化合物、この調製、これを含有する組成物、および、この使用
DE69126612T2 (de)	1997-10-02	Carbamate des indan-pyrrolidins
EP1565421B1 (fr)	2008-07-23	Procede de preparation d'acide indan-1,3-dicarboxylique
Bös et al.	1998	Syntheses of O‐Methylasparvenone‐Derived Serotonin‐Receptor Antagonists
PL184412B1 (pl)	2002-10-31	Nowe pochodne 3,3a,4,5-tetrahydro-1H-oksazolo [3,4-a] chinolin-1-onu, sposób ich wytwarzania i preparat farmaceutyczny
WO2006016715A1 (fr)	2006-02-16	DÉRIVÉ DE LA PYRAZOLO[1,5-a]PYRIMIDINE
US3503990A (en)	1970-03-31	6-aryl-4,5,6,7-tetrahydro-4-oxoindole derivatives
US6057340A (en)	2000-05-02	Oxazole derivatives as serotonin-1A receptor agonists
MXPA99006173A (en)	2000-02-02	TRICYCLIC BENZO[e]ISOINDOLES AND BENZO[h]ISOQUINOLINES
Abd El-Aal et al.	2013	Friedel-Crafts chemistry. Part 40. An expedient novel synthesis of some dibenz-azepines,-azocines, 11H-benzo [f] pyrido [2, 3-b] azepines and 6H-benzo [g] pyrido [2, 3-c] azocines.
JP4655276B2 (ja)	2011-03-23	ピラゾロピリミジン化合物のメタンスルホン酸塩、その結晶およびその製造方法
Naik et al.	2015	Beckmann rearrangement for the synthesis of derivatives of β-and γ-carbolinones, dihydropyrrolopyridinone and tetrahydroisoquinolinone.
JP2003513969A (ja)	2003-04-15	５−ｈｔトランスポーターとしてのｎ−アリル−（ホモピペラジニル）−シクロヘキシルアミン
DE69219121T2 (de)	1997-08-28	Karboxamido-(1,2n)-karbocyclo-2-aminotetralinderivate
JP2002533447A (ja)	2002-10-08	神経疾患の治療に有用な１，４−ジアザシクロヘプタン誘導体