IL99148A - Tetrahydrobenz [CD] 6-Induced Indulgent Pharmaceutical Preparations Including Their Use and Process for Their Preparation - Google Patents

Tetrahydrobenz [CD] 6-Induced Indulgent Pharmaceutical Preparations Including Their Use and Process for Their Preparation

Info

Publication number: IL99148A
Authority: IL; Israel
Prior art keywords: alkyl; substituted; aryl; hydrogen; compound
Prior art date: 1990-08-15

Application number

IL9914891A

Other languages

English (en)

Hebrew (he)

Original Assignee

Lilly Co Eli

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.)

1990-08-15

Filing date

1991-08-09

Publication date

1995-12-08

1991-08-09 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1995-12-08 Publication of IL99148A publication Critical patent/IL99148A/en

Links

-1 6-substituted-tetrahydrobenz (cd) indoles Chemical class 0.000 title claims abstract description 74
238000000034 method Methods 0.000 title claims description 50
238000002360 preparation method Methods 0.000 title claims description 28
230000008569 process Effects 0.000 title claims description 12
239000008194 pharmaceutical composition Substances 0.000 title claims description 6
150000001875 compounds Chemical class 0.000 claims description 100
125000000217 alkyl group Chemical group 0.000 claims description 97
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 70
239000001257 hydrogen Substances 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 48
125000003118 aryl group Chemical group 0.000 claims description 39
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 35
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 35
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 31
125000003107 substituted aryl group Chemical group 0.000 claims description 29
125000000753 cycloalkyl group Chemical group 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
230000000903 blocking effect Effects 0.000 claims description 17
125000003342 alkenyl group Chemical group 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 14
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 12
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
239000004480 active ingredient Substances 0.000 claims description 11
125000002496 methyl group Chemical class [H]C([H])([H])* 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 4
ZYVORBSWPVDTCX-UHFFFAOYSA-N 1,2,2a,3-tetrahydrobenzo[cd]indole Chemical compound C1=CCC2CNC3=CC=CC1=C32 ZYVORBSWPVDTCX-UHFFFAOYSA-N 0.000 claims description 3
XNFILRQULZRSHY-UHFFFAOYSA-N 1-[4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]-2-methoxyethanone Chemical compound C1=C(C(=O)COC)C(CC(N(CCC)CCC)C2)=C3C2=CNC3=C1 XNFILRQULZRSHY-UHFFFAOYSA-N 0.000 claims description 3
230000001590 oxidative effect Effects 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
KMHYGHPTAQAVCK-UHFFFAOYSA-N 1-[4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]-2-phenylethanone Chemical compound C12=C3CC(N(CCC)CCC)CC2=CNC1=CC=C3C(=O)CC1=CC=CC=C1 KMHYGHPTAQAVCK-UHFFFAOYSA-N 0.000 claims description 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 4
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
LUMYSYOJGVMVLA-UHFFFAOYSA-N 1-[4-[cyclopropylmethyl(propyl)amino]-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]propan-1-one Chemical compound C1C(C=23)=CNC3=CC=C(C(=O)CC)C=2CC1N(CCC)CC1CC1 LUMYSYOJGVMVLA-UHFFFAOYSA-N 0.000 claims 1
SGGSSSGDBMXLCZ-UHFFFAOYSA-N 2-methyl-1-[4-(propylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]propan-1-one Chemical compound C1=C(C(=O)C(C)C)C(CC(NCCC)C2)=C3C2=CNC3=C1 SGGSSSGDBMXLCZ-UHFFFAOYSA-N 0.000 claims 1
XKPVXWPYVFGSRF-UHFFFAOYSA-N [4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]-phenylmethanone Chemical compound C12=C3CC(N(CCC)CCC)CC2=CNC1=CC=C3C(=O)C1=CC=CC=C1 XKPVXWPYVFGSRF-UHFFFAOYSA-N 0.000 claims 1
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 111
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
239000000243 solution Substances 0.000 description 64
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 56
239000000203 mixture Substances 0.000 description 49
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
235000019439 ethyl acetate Nutrition 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
239000003921 oil Substances 0.000 description 34
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
239000000047 product Substances 0.000 description 23
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 19
239000002904 solvent Substances 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
238000004458 analytical method Methods 0.000 description 12
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 12
125000006519 CCH3 Chemical group 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
238000009472 formulation Methods 0.000 description 11
239000008279 sol Substances 0.000 description 11
DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
229920002472 Starch Polymers 0.000 description 10
150000001414 amino alcohols Chemical class 0.000 description 10
238000004587 chromatography analysis Methods 0.000 description 10
238000007327 hydrogenolysis reaction Methods 0.000 description 10
235000019698 starch Nutrition 0.000 description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
238000005481 NMR spectroscopy Methods 0.000 description 9
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 9
239000012528 membrane Substances 0.000 description 9
239000008107 starch Substances 0.000 description 9
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
238000000159 protein binding assay Methods 0.000 description 8
150000003335 secondary amines Chemical class 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
238000011282 treatment Methods 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
150000002118 epoxides Chemical class 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
229940076279 serotonin Drugs 0.000 description 7
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000000872 buffer Substances 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
230000006870 function Effects 0.000 description 6
150000002431 hydrogen Chemical group 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
238000007254 oxidation reaction Methods 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
238000003756 stirring Methods 0.000 description 6
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 6
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
239000003310 5-hydroxyindoleacetic acid Substances 0.000 description 5
RVWZUOPFHTYIEO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Natural products C1=C(O)C=C2C(C(=O)O)=CNC2=C1 RVWZUOPFHTYIEO-UHFFFAOYSA-N 0.000 description 5
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
241000700159 Rattus Species 0.000 description 5
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 5
239000002253 acid Substances 0.000 description 5
239000003929 acidic solution Substances 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
150000001541 aziridines Chemical class 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
235000010980 cellulose Nutrition 0.000 description 5
239000001913 cellulose Substances 0.000 description 5
229920002678 cellulose Polymers 0.000 description 5
229940125782 compound 2 Drugs 0.000 description 5
201000010099 disease Diseases 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
150000002576 ketones Chemical class 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
239000007800 oxidant agent Substances 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
230000000707 stereoselective effect Effects 0.000 description 5
239000000725 suspension Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
235000002906 tartaric acid Nutrition 0.000 description 5
239000011975 tartaric acid Substances 0.000 description 5
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 4
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 4
101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
239000007818 Grignard reagent Substances 0.000 description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
239000012043 crude product Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012039 electrophile Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
150000004795 grignard reagents Chemical class 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000008188 pellet Substances 0.000 description 4
239000000376 reactant Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
238000005303 weighing Methods 0.000 description 4
NFHCWFHJRBEWNC-UHFFFAOYSA-N 1-[4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]-2,2-dimethylpropan-1-one Chemical compound C1=C(C(=O)C(C)(C)C)C(CC(N(CCC)CCC)C2)=C3C2=CNC3=C1 NFHCWFHJRBEWNC-UHFFFAOYSA-N 0.000 description 3
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 3
VBHJUUAUIGGAPS-UHFFFAOYSA-N 2-[4-(4-bromophenyl)-1,3-thiazol-2-yl]acetonitrile Chemical compound C1=CC(Br)=CC=C1C1=CSC(CC#N)=N1 VBHJUUAUIGGAPS-UHFFFAOYSA-N 0.000 description 3
QZAYGJVTTNCVMB-PZFLKRBQSA-N 3-(2-amino-1,2-ditritioethyl)-1h-indol-5-ol Chemical compound C1=C(O)C=C2C(C([3H])C(N)[3H])=CNC2=C1 QZAYGJVTTNCVMB-PZFLKRBQSA-N 0.000 description 3
ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 3
OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 3
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 3
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
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 3
229930006000 Sucrose Natural products 0.000 description 3
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
230000004075 alteration Effects 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
230000036506 anxiety Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
150000002475 indoles Chemical class 0.000 description 3
150000002476 indolines Chemical class 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
235000019813 microcrystalline cellulose Nutrition 0.000 description 3
239000008108 microcrystalline cellulose Substances 0.000 description 3
229940016286 microcrystalline cellulose Drugs 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
239000000829 suppository Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
GCAZALMXGZXFKV-UHFFFAOYSA-N 1-[4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-6-yl]-2-methylpropan-1-one Chemical compound C1=C(C(=O)C(C)C)C(CC(N(CCC)CCC)C2)=C3C2=CNC3=C1 GCAZALMXGZXFKV-UHFFFAOYSA-N 0.000 description 2
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239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012058 sterile packaged powder Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
230000028016 temperature homeostasis Effects 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229940071104 xylenesulfonate Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- 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, ***e
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Addiction (AREA)
Heart & Thoracic Surgery (AREA)
Anesthesiology (AREA)
Pain & Pain Management (AREA)
Cardiology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Otolaryngology (AREA)
Urology & Nephrology (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)

IL9914891A 1990-08-15 1991-08-09 Tetrahydrobenz [CD] 6-Induced Indulgent Pharmaceutical Preparations Including Their Use and Process for Their Preparation IL99148A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US56799090A	1990-08-15	1990-08-15
US07/725,175 US5229409A (en)	1990-08-15	1991-07-03	6-substituted-tetrahydrobenz[cd]indoles

Publications (1)

Publication Number	Publication Date
IL99148A true IL99148A (en)	1995-12-08

Family

ID=27074632

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9914891A IL99148A (en)	1990-08-15	1991-08-09	Tetrahydrobenz [CD] 6-Induced Indulgent Pharmaceutical Preparations Including Their Use and Process for Their Preparation

Country Status (25)

Country	Link
US (1)	US5229409A (es)
EP (1)	EP0471576B1 (es)
JP (1)	JP3034085B2 (es)
KR (1)	KR100221159B1 (es)
CN (1)	CN1031999C (es)
AT (1)	ATE234285T1 (es)
AU (1)	AU648575B2 (es)
BR (1)	BR9103481A (es)
CA (1)	CA2049212C (es)
CZ (1)	CZ280605B6 (es)
DE (1)	DE69133212T2 (es)
DK (1)	DK0471576T3 (es)
ES (1)	ES2194007T3 (es)
FI (1)	FI102677B (es)
HU (1)	HU220757B1 (es)
IE (1)	IE912878A1 (es)
IL (1)	IL99148A (es)
MX (1)	MX9100646A (es)
MY (1)	MY106764A (es)
NO (1)	NO176020C (es)
NZ (1)	NZ239333A (es)
PT (1)	PT98640B (es)
RU (1)	RU2073672C1 (es)
TW (1)	TW197422B (es)
YU (1)	YU48058B (es)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5204340A (en) *	1989-04-11	1993-04-20	Eli Lilly And Company	Tetrahydrobenz(c,d)indole serotonin agonists
TW219933B (es) *	1990-02-26	1994-02-01	Lilly Co Eli
US5340838A (en) *	1990-05-04	1994-08-23	Eli Lilly And Company	Method of inhibiting gastric acid secretion with 2-phenylcyclopropylamines
US5089517A (en) *	1990-08-03	1992-02-18	The Board Of Trustees Of The Leland Stanford Junior University	Neuroprotection by indolactam v and derivatives thereof
US5229410A (en) *	1990-08-15	1993-07-20	Eli Lilly And Company	6-substituted-hexahydrobenz[cd]indoles
CZ285762B6 (cs) *	1993-06-10	1999-11-17	Eli Lilly And Company	Farmaceutický prostředek vhodný pro prevenci dávení a zvracení a pro ošetřování sexuální dysfunkce savců a jeho použití
US5385928A (en) *	1994-05-18	1995-01-31	Eli Lilly And Company	Tetrahydrobenz [CD] indazoles, compositions and use

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE517732C (de) *	1927-10-27	1931-02-09	Then Rudolf	Faerbekufe mit einem drehbaren, trommelartigen Rahmen fuer die auf aus-wechselbaren Faerbestoecken aufgehaengten Waren, insbesondere Struempfe
US3194811A (en) *	1963-09-05	1965-07-13	Merck & Co Inc	Aroyl-benzindolyl acids
BE755270A (fr) *	1969-08-27	1971-02-25	Sandoz Sa	Nouveaux derives du benzo(cd)indole, leur preparation et medicaments contenant ces derives
BE757879A (fr) *	1969-10-24	1971-04-22	Sandoz Sa	Derives du benzo(cd)indole, leur preparation et medicaments contenant ces derives
FI206974A (es) *	1973-07-16	1975-01-17	Sandoz Ag
US4110339A (en) *	1977-11-25	1978-08-29	Eli Lilly And Company	4-(Di-n-propyl)amino-1,3,4,5-tetrahydrobenz[cd]indole
ZA795239B (en) *	1978-10-12	1980-11-26	Glaxo Group Ltd	Heterocyclic compounds
US4282240A (en) *	1979-11-23	1981-08-04	Merck & Co., Inc.	Amino substituted tetrahydrobenzindoles
FR2510111A1 (fr) *	1981-07-24	1983-01-28	Roussel Uclaf	Nouveaux derives du piperidin-3-yl indole, leurs sels, leur procede de preparation, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant
FR2522658A1 (fr) *	1982-03-05	1983-09-09	Roussel Uclaf	Application a titre de medicaments de derives du trans 4-amino benz (c,d) indol-5-ol ainsi que de leurs sels, compositions les renfermant, nouveaux derives et leur procede de preparation
DE3346573A1 (de) *	1983-12-23	1985-07-04	Troponwerke GmbH & Co KG, 5000 Köln	1,3,4,5-tetrahydrobenz(c,d)indole, ein verfahren zu ihrer herstellung und ihre verwendung
IL74222A (en) *	1984-02-06	1988-07-31	Lilly Co Eli	6-substituted-4-dialkylamino tetrahydrobenz(c,d)indoles,their preparation and pharmaceutical compositions comprising them
US4983622A (en) *	1984-02-06	1991-01-08	Eli Lilly And Company	6-substituted-4-dialkylaminotetrahydrobenz(c,d)indoles
US4576959A (en) *	1984-02-06	1986-03-18	Eli Lilly And Company	6-Substituted-4-dialkylaminotetrahydrobenz[c,d]indoles
CA1266482A1 (en) *	1984-05-24	1990-03-06	Carl Kaiser	6-oxygenated-1,3,4,5-tetrahydrobenz(cd)indol-4-amines
DE3525564A1 (de) *	1985-07-15	1987-02-05	Schering Ag	Tricyclische verbindungen mit indolstruktur, verfahren zu ihrer herstellung und deren verwendung als arzneimittel
US4745126A (en) *	1987-03-12	1988-05-17	Eli Lilly And Company	Method of treating anxiety with tetrahydrobenz[c,d]indole-6-carboxamides
DE3809155A1 (de) *	1988-03-18	1989-09-28	Bayer Ag	1,3,4,5-tetrahydrobenz-(c,d)-indole
US5204340A (en) *	1989-04-11	1993-04-20	Eli Lilly And Company	Tetrahydrobenz(c,d)indole serotonin agonists
JPH07103105B2 (ja) *	1989-05-12	1995-11-08	杏林製薬株式会社	インドール誘導体及びその製造方法
US5039820A (en) *	1990-02-26	1991-08-13	Eli Lilly And Company	4-amino-6-iodo-hexahydrobenz(cd)indoles
US5096908A (en) *	1990-05-04	1992-03-17	Eli Lilly And Company	Method of inhibiting gastric acid secretion

1991
- 1991-07-03 US US07/725,175 patent/US5229409A/en not_active Expired - Lifetime
- 1991-08-09 IL IL9914891A patent/IL99148A/en not_active IP Right Cessation
- 1991-08-09 NZ NZ239333A patent/NZ239333A/xx not_active IP Right Cessation
- 1991-08-12 PT PT98640A patent/PT98640B/pt not_active IP Right Cessation
- 1991-08-12 CZ CS912494A patent/CZ280605B6/cs not_active IP Right Cessation
- 1991-08-13 MX MX9100646A patent/MX9100646A/es not_active IP Right Cessation
- 1991-08-13 FI FI913835A patent/FI102677B/fi not_active IP Right Cessation
- 1991-08-13 KR KR1019910013967A patent/KR100221159B1/ko not_active IP Right Cessation
- 1991-08-13 AU AU82406/91A patent/AU648575B2/en not_active Ceased
- 1991-08-13 MY MYPI91001471A patent/MY106764A/en unknown
- 1991-08-13 TW TW080106390A patent/TW197422B/zh active
- 1991-08-13 NO NO913159A patent/NO176020C/no unknown
- 1991-08-14 BR BR919103481A patent/BR9103481A/pt not_active Application Discontinuation
- 1991-08-14 IE IE287891A patent/IE912878A1/en not_active Application Discontinuation
- 1991-08-14 CA CA002049212A patent/CA2049212C/en not_active Expired - Fee Related
- 1991-08-14 JP JP3204237A patent/JP3034085B2/ja not_active Expired - Fee Related
- 1991-08-14 HU HU9102706A patent/HU220757B1/hu not_active IP Right Cessation
- 1991-08-14 AT AT91307531T patent/ATE234285T1/de not_active IP Right Cessation
- 1991-08-14 DE DE69133212T patent/DE69133212T2/de not_active Expired - Fee Related
- 1991-08-14 YU YU140491A patent/YU48058B/sh unknown
- 1991-08-14 ES ES91307531T patent/ES2194007T3/es not_active Expired - Lifetime
- 1991-08-14 CN CN91105624A patent/CN1031999C/zh not_active Expired - Fee Related
- 1991-08-14 DK DK91307531T patent/DK0471576T3/da active
- 1991-08-14 EP EP91307531A patent/EP0471576B1/en not_active Expired - Lifetime
1992
- 1992-09-30 RU SU925052704A patent/RU2073672C1/ru active

Also Published As

Publication number	Publication date
CN1058961A (zh)	1992-02-26
FI102677B1 (fi)	1999-01-29
NO176020B (no)	1994-10-10
RU2073672C1 (ru)	1997-02-20
DK0471576T3 (da)	2003-12-01
CN1031999C (zh)	1996-06-12
HU912706D0 (en)	1992-01-28
BR9103481A (pt)	1992-05-12
IE912878A1 (en)	1992-02-26
ES2194007T3 (es)	2003-11-16
FI102677B (fi)	1999-01-29
PT98640A (pt)	1992-06-30
YU140491A (sh)	1994-01-20
EP0471576A1 (en)	1992-02-19
EP0471576B1 (en)	2003-03-12
KR100221159B1 (ko)	1999-09-15
FI913835A0 (fi)	1991-08-13
ATE234285T1 (de)	2003-03-15
HU220757B1 (hu)	2002-05-28
CA2049212C (en)	2003-04-08
NZ239333A (en)	1993-05-26
HUT59094A (en)	1992-04-28
TW197422B (es)	1993-01-01
KR920004347A (ko)	1992-03-27
NO913159D0 (no)	1991-08-13
JPH04230663A (ja)	1992-08-19
MY106764A (en)	1995-07-31
AU648575B2 (en)	1994-04-28
CA2049212A1 (en)	1992-02-16
JP3034085B2 (ja)	2000-04-17
DE69133212T2 (de)	2003-11-20
YU48058B (sh)	1996-10-18
PT98640B (pt)	1999-01-29
NO176020C (no)	1995-01-18
NO913159L (no)	1992-02-17
US5229409A (en)	1993-07-20
MX9100646A (es)	1992-04-01
AU8240691A (en)	1992-02-27
CZ280605B6 (cs)	1996-03-13
DE69133212D1 (de)	2003-04-17
FI913835A (fi)	1992-02-16
CS249491A3 (en)	1992-03-18

Legal Events

Date	Code	Title
1996-06-18	FF	Patent granted
1998-01-04	KB	Patent renewed
2001-10-31	KB	Patent renewed
2005-09-25	KB	Patent renewed
2010-10-31	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
JP3159766B2 (ja)	2001-04-23	６−複素環−４−アミノ−１，３，４，５−テトラヒドロベンズ［ｃｄ］インドール類
JP3174382B2 (ja)	2001-06-11	６−複素環−４−アミノ−１，２，２ａ，３，４，５−ヘキサヒドロベンズ［ｃｄ］インドール類
US5229410A (en)	1993-07-20	6-substituted-hexahydrobenz[cd]indoles
US5470853A (en)	1995-11-28	6-substituted-hexahydrobenz [CD] indoles
IL99148A (en)	1995-12-08	Tetrahydrobenz [CD] 6-Induced Indulgent Pharmaceutical Preparations Including Their Use and Process for Their Preparation
JPH06211655A (ja)	1994-08-02	乗物酔いおよび嘔吐症の処置用６−ヘテロ環−４−アミノ−１，３，４，５−テトラヒドロベンズ［ｃｄ］インドール類
US5665744A (en)	1997-09-09	6-heterocyclic-4-amino-1,2,2A,3,4,5-hexahydrobenzn [cd] indoles
US5783590A (en)	1998-07-21	6-heterocyclic-4-amino-1,2,2A,3,4,5-hexahydrobenz CD!indoles
AU645779B2 (en)	1994-01-27	6-substituted hexahydrobenz(cd)indoles
CA2049176A1 (en)	1992-02-16	6-substituted-hexahydrobenz [cd] indoles
CA2037100C (en)	2003-10-21	6-substituted-hexahydrobenz ¢cd! indoles