NO313753B1 - Anti-konvulsive isokinolyl-benzamid-derivater, farmasöytiske preparater inneholdende dem, anvendelse av dem og fremgangsmåtefor fremstilling av dem - Google Patents

Anti-konvulsive isokinolyl-benzamid-derivater, farmasöytiske preparater inneholdende dem, anvendelse av dem og fremgangsmåtefor fremstilling av dem Download PDF

Info

Publication number: NO313753B1
Authority: NO; Norway
Prior art keywords: alkyl; hydrogen; disorders; formula; dimethyl
Prior art date: 1997-03-18

Application number

NO19994504A

Other languages

English (en)

Norwegian (no)

Other versions

NO994504D0 (no

NO994504L (no

Inventor

John David Harling

Barry Sidney Orlek

Mervyn Thompson

Original Assignee

Smithkline Beecham Plc

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.)

1997-03-18

Filing date

1999-09-17

Publication date

2002-11-25

1997-03-18 Priority claimed from GBGB9705620.4A external-priority patent/GB9705620D0/en

1997-12-17 Priority claimed from GBGB9726660.5A external-priority patent/GB9726660D0/en

1999-09-17 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

1999-09-17 Publication of NO994504D0 publication Critical patent/NO994504D0/no

1999-09-17 Publication of NO994504L publication Critical patent/NO994504L/no

2002-11-25 Publication of NO313753B1 publication Critical patent/NO313753B1/no

Links

238000000034 method Methods 0.000 title description 36
230000002082 anti-convulsion Effects 0.000 title 1
OMLUWEHKCFFWOP-UHFFFAOYSA-N n-isoquinolin-1-ylbenzamide Chemical class N=1C=CC2=CC=CC=C2C=1NC(=O)C1=CC=CC=C1 OMLUWEHKCFFWOP-UHFFFAOYSA-N 0.000 title 1
239000008194 pharmaceutical composition Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 99
229910052739 hydrogen Inorganic materials 0.000 claims description 31
239000001257 hydrogen Substances 0.000 claims description 31
238000002360 preparation method Methods 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
150000002431 hydrogen Chemical class 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
208000035475 disorder Diseases 0.000 claims description 15
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
-1 (±) N-(1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-chloro-4-ethoxy -2-methoxy-benzamide N-(1,2-dimethyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-bromo-2,4-dimethoxy-benzamide Chemical compound 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
229910052736 halogen Inorganic materials 0.000 claims description 13
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 12
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 12
ZPUCINDJVBIVPJ-LJISPDSOSA-N ***e Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 12
201000006417 multiple sclerosis Diseases 0.000 claims description 12
208000004296 neuralgia Diseases 0.000 claims description 12
230000001537 neural effect Effects 0.000 claims description 11
239000001961 anticonvulsive agent Substances 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
230000035939 shock Effects 0.000 claims description 8
208000019901 Anxiety disease Diseases 0.000 claims description 7
206010026749 Mania Diseases 0.000 claims description 7
229940125681 anticonvulsant agent Drugs 0.000 claims description 7
230000036506 anxiety Effects 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 6
208000030507 AIDS Diseases 0.000 claims description 6
208000024827 Alzheimer disease Diseases 0.000 claims description 6
206010003591 Ataxia Diseases 0.000 claims description 6
206010058019 Cancer Pain Diseases 0.000 claims description 6
206010008120 Cerebral ischaemia Diseases 0.000 claims description 6
208000017164 Chronobiology disease Diseases 0.000 claims description 6
208000023105 Huntington disease Diseases 0.000 claims description 6
208000019695 Migraine disease Diseases 0.000 claims description 6
208000026072 Motor neurone disease Diseases 0.000 claims description 6
206010028347 Muscle twitching Diseases 0.000 claims description 6
208000012902 Nervous system disease Diseases 0.000 claims description 6
208000002193 Pain Diseases 0.000 claims description 6
208000018737 Parkinson disease Diseases 0.000 claims description 6
206010036312 Post-traumatic epilepsy Diseases 0.000 claims description 6
208000028017 Psychotic disease Diseases 0.000 claims description 6
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 6
208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 6
206010043220 Temporomandibular joint syndrome Diseases 0.000 claims description 6
208000009205 Tinnitus Diseases 0.000 claims description 6
208000000323 Tourette Syndrome Diseases 0.000 claims description 6
208000016620 Tourette disease Diseases 0.000 claims description 6
208000030886 Traumatic Brain injury Diseases 0.000 claims description 6
230000016571 aggressive behavior Effects 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
229940049706 benzodiazepine Drugs 0.000 claims description 6
229960003920 ***e Drugs 0.000 claims description 6
206010012601 diabetes mellitus Diseases 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
206010015037 epilepsy Diseases 0.000 claims description 6
239000012458 free base Substances 0.000 claims description 6
206010022437 insomnia Diseases 0.000 claims description 6
206010027599 migraine Diseases 0.000 claims description 6
230000003387 muscular Effects 0.000 claims description 6
201000003631 narcolepsy Diseases 0.000 claims description 6
208000015122 neurodegenerative disease Diseases 0.000 claims description 6
208000021722 neuropathic pain Diseases 0.000 claims description 6
229960002715 nicotine Drugs 0.000 claims description 6
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 6
208000019906 panic disease Diseases 0.000 claims description 6
201000000980 schizophrenia Diseases 0.000 claims description 6
208000019116 sleep disease Diseases 0.000 claims description 6
231100000886 tinnitus Toxicity 0.000 claims description 6
230000009529 traumatic brain injury Effects 0.000 claims description 6
206010044652 trigeminal neuralgia Diseases 0.000 claims description 6
208000008238 Muscle Spasticity Diseases 0.000 claims description 5
208000005264 motor neuron disease Diseases 0.000 claims description 5
208000018198 spasticity Diseases 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
DOLKPFPCQQAQRD-UHFFFAOYSA-N 3-bromo-4-ethoxy-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)benzamide Chemical compound C1=C(Br)C(OCC)=CC=C1C(=O)NC1=CC=C2C(C)(C)CN(C)CC2=C1 DOLKPFPCQQAQRD-UHFFFAOYSA-N 0.000 claims description 2
UZOGCWQTUIIRKJ-UHFFFAOYSA-N 3-bromo-n-(1,2-dimethyl-3,4-dihydro-1h-isoquinolin-7-yl)-4-ethoxybenzamide Chemical compound C1=C(Br)C(OCC)=CC=C1C(=O)NC1=CC=C(CCN(C)C2C)C2=C1 UZOGCWQTUIIRKJ-UHFFFAOYSA-N 0.000 claims description 2
AMTIQANOOBNZPV-UHFFFAOYSA-N 5-chloro-n-(1,2-dimethyl-3,4-dihydro-1h-isoquinolin-5-yl)-4-ethoxy-2-methoxybenzamide Chemical compound C1=C(Cl)C(OCC)=CC(OC)=C1C(=O)NC1=CC=CC2=C1CCN(C)C2C AMTIQANOOBNZPV-UHFFFAOYSA-N 0.000 claims description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
KLSVMERGLCFVBL-UHFFFAOYSA-N n-(1,2-dimethyl-3,4-dihydro-1h-isoquinolin-6-yl)benzamide Chemical compound C=1C=C2C(C)N(C)CCC2=CC=1NC(=O)C1=CC=CC=C1 KLSVMERGLCFVBL-UHFFFAOYSA-N 0.000 claims description 2
XLJVEZLNTFVGIH-UHFFFAOYSA-N n-(1-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)benzamide Chemical compound C=1C=C2C(C)NCCC2=CC=1NC(=O)C1=CC=CC=C1 XLJVEZLNTFVGIH-UHFFFAOYSA-N 0.000 claims description 2
238000000926 separation method Methods 0.000 claims description 2
150000001557 benzodiazepines Chemical class 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
239000000203 mixture Substances 0.000 description 28
239000000243 solution Substances 0.000 description 28
238000005481 NMR spectroscopy Methods 0.000 description 27
239000000047 product Substances 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
239000007787 solid Substances 0.000 description 20
239000008186 active pharmaceutical agent Substances 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
229940126062 Compound A Drugs 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
235000019198 oils Nutrition 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
235000019441 ethanol Nutrition 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
238000005160 1H NMR spectroscopy Methods 0.000 description 7
206010010904 Convulsion Diseases 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
239000002244 precipitate 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 6
229910021529 ammonia Inorganic materials 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
239000000470 constituent Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
239000012453 solvate Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
239000007818 Grignard reagent Substances 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000001773 anti-convulsant effect Effects 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000006260 foam Substances 0.000 description 4
150000004795 grignard reagents Chemical class 0.000 description 4
239000013067 intermediate product Substances 0.000 description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 4
239000008188 pellet Substances 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000002243 precursor Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
PBKYPTQBAQQVPT-UHFFFAOYSA-N 4-methoxy-3-(trifluoromethyl)benzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1C(F)(F)F PBKYPTQBAQQVPT-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
206010043994 Tonic convulsion Diseases 0.000 description 3
239000002253 acid Substances 0.000 description 3
239000000654 additive Substances 0.000 description 3
229960003965 antiepileptics Drugs 0.000 description 3
239000012267 brine Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000000945 filler Substances 0.000 description 3
238000011049 filling Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
229920000609 methyl cellulose Polymers 0.000 description 3
239000001923 methylcellulose Substances 0.000 description 3
235000010981 methylcellulose Nutrition 0.000 description 3
238000002156 mixing Methods 0.000 description 3
238000000746 purification Methods 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 3
239000000080 wetting agent Substances 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
OGHSMOUGIDUPFX-UHFFFAOYSA-N 1,2-dimethyl-3,4-dihydro-1h-isoquinolin-5-amine Chemical compound C1=CC=C2C(C)N(C)CCC2=C1N OGHSMOUGIDUPFX-UHFFFAOYSA-N 0.000 description 2
VGWAQMUVFWPCLM-UHFFFAOYSA-M 1,2-dimethyl-3,4-dihydroisoquinolin-2-ium-7-amine;iodide Chemical compound [I-].C1=C(N)C=C2C(C)=[N+](C)CCC2=C1 VGWAQMUVFWPCLM-UHFFFAOYSA-M 0.000 description 2
JBXUYMPSEDWNSW-UHFFFAOYSA-N 1-methyl-3,4-dihydroisoquinolin-7-amine Chemical compound C1=C(N)C=C2C(C)=NCCC2=C1 JBXUYMPSEDWNSW-UHFFFAOYSA-N 0.000 description 2
JVXQHSHEHLIEPE-UHFFFAOYSA-N 2,4,4-trimethyl-7-nitroisoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC=C2C(C)(C)C(=O)N(C)C(=O)C2=C1 JVXQHSHEHLIEPE-UHFFFAOYSA-N 0.000 description 2
GPVDHNVGGIAOQT-UHFFFAOYSA-N 2,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 description 2
NVCUKQLXOGOZPZ-UHFFFAOYSA-N 2-benzyl-1-methyl-1h-isoquinolin-5-amine Chemical compound C1=CC2=C(N)C=CC=C2C(C)N1CC1=CC=CC=C1 NVCUKQLXOGOZPZ-UHFFFAOYSA-N 0.000 description 2
BANZVKGLDQDFDV-UHFFFAOYSA-N 2-propan-2-ylbenzoic acid Chemical compound CC(C)C1=CC=CC=C1C(O)=O BANZVKGLDQDFDV-UHFFFAOYSA-N 0.000 description 2
ICDBZRYXNCPKRM-UHFFFAOYSA-N 3,4-dihydroisoquinolin-7-amine Chemical compound C1CN=CC2=CC(N)=CC=C21 ICDBZRYXNCPKRM-UHFFFAOYSA-N 0.000 description 2
LQFMXKIGVFPAGJ-UHFFFAOYSA-N 3-bromo-4-ethoxybenzoyl chloride Chemical compound CCOC1=CC=C(C(Cl)=O)C=C1Br LQFMXKIGVFPAGJ-UHFFFAOYSA-N 0.000 description 2
HXDRDQKKWREBNN-UHFFFAOYSA-N 3-bromo-4-ethylbenzoyl chloride Chemical compound CCC1=CC=C(C(Cl)=O)C=C1Br HXDRDQKKWREBNN-UHFFFAOYSA-N 0.000 description 2
QPDMEVCCQAQDQE-UHFFFAOYSA-N 3-bromo-n-(1,2-dimethyl-3,4-dihydro-1h-isoquinolin-7-yl)-4-ethylbenzamide Chemical compound C1=C(Br)C(CC)=CC=C1C(=O)NC1=CC=C(CCN(C)C2C)C2=C1 QPDMEVCCQAQDQE-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
QHQFQDKUACTCCJ-UHFFFAOYSA-N 4-methoxy-3-(trifluoromethyl)-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)benzamide Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C(=O)NC1=CC=C2C(C)(C)CN(C)CC2=C1 QHQFQDKUACTCCJ-UHFFFAOYSA-N 0.000 description 2
VNWUPESTVBTYJM-UHFFFAOYSA-N 4-methoxy-3-(trifluoromethyl)benzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1C(F)(F)F VNWUPESTVBTYJM-UHFFFAOYSA-N 0.000 description 2
DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 2
WOPJFSQYDOHZMK-UHFFFAOYSA-N 5-bromo-2,4-dimethoxybenzoic acid Chemical compound COC1=CC(OC)=C(C(O)=O)C=C1Br WOPJFSQYDOHZMK-UHFFFAOYSA-N 0.000 description 2
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239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000000691 measurement method Methods 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
ZSBIMTDWIGWJPW-UHFFFAOYSA-N methyl 3-chloro-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(Cl)=C1 ZSBIMTDWIGWJPW-UHFFFAOYSA-N 0.000 description 1
VJROGSBBDLIEMZ-UHFFFAOYSA-N methyl 5-bromo-2,4-dimethoxybenzoate Chemical compound COC(=O)C1=CC(Br)=C(OC)C=C1OC VJROGSBBDLIEMZ-UHFFFAOYSA-N 0.000 description 1
JQJJGBDRZOUEAL-UHFFFAOYSA-N methyl 5-cyano-2-methoxy-4-propan-2-ylbenzoate Chemical compound COC(=O)C1=CC(C#N)=C(C(C)C)C=C1OC JQJJGBDRZOUEAL-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
230000036651 mood Effects 0.000 description 1
ZANGENJVDPXYQH-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-1-yl)benzamide Chemical class N1CCC2=CC=CC=C2C1NC(=O)C1=CC=CC=C1 ZANGENJVDPXYQH-UHFFFAOYSA-N 0.000 description 1
SNLMALWZNRCFBB-UHFFFAOYSA-N n-(1,2-dimethyl-3,4-dihydro-1h-isoquinolin-5-yl)-2-methoxy-4-methyl-5-(trifluoromethyl)benzamide Chemical compound COC1=CC(C)=C(C(F)(F)F)C=C1C(=O)NC1=CC=CC2=C1CCN(C)C2C SNLMALWZNRCFBB-UHFFFAOYSA-N 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
239000004323 potassium nitrate Substances 0.000 description 1
230000000216 proconvulsive effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
238000003653 radioligand binding assay Methods 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
229940032147 starch Drugs 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008221 sterile excipient Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
201000009032 substance abuse Diseases 0.000 description 1
231100000736 substance abuse Toxicity 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
KKXRPHONDRYDRT-UHFFFAOYSA-N tert-butyl 5-amino-1-methyl-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=CC=C2C(C)N(C(=O)OC(C)(C)C)CCC2=C1N KKXRPHONDRYDRT-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/28—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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Psychology (AREA)
Addiction (AREA)
Hospice & Palliative Care (AREA)
Anesthesiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO19994504A 1997-03-18 1999-09-17 Anti-konvulsive isokinolyl-benzamid-derivater, farmasöytiske preparater inneholdende dem, anvendelse av dem og fremgangsmåtefor fremstilling av dem NO313753B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9705620.4A GB9705620D0 (en)	1997-03-18	1997-03-18	Novel compounds
GBGB9726660.5A GB9726660D0 (en)	1997-12-17	1997-12-17	Novel compounds
PCT/GB1998/000781 WO1998041507A1 (fr)	1997-03-18	1998-03-16	Derives anticonvulsivants d'isoquinolyl-benzamide

Publications (3)

Publication Number	Publication Date
NO994504D0 NO994504D0 (no)	1999-09-17
NO994504L NO994504L (no)	1999-09-17
NO313753B1 true NO313753B1 (no)	2002-11-25

Family

ID=26311216

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19994504A NO313753B1 (no)	1997-03-18	1999-09-17	Anti-konvulsive isokinolyl-benzamid-derivater, farmasöytiske preparater inneholdende dem, anvendelse av dem og fremgangsmåtefor fremstilling av dem

Country Status (26)

Country	Link
US (1)	US6277861B1 (fr)
EP (1)	EP0971897A1 (fr)
JP (1)	JP2001516357A (fr)
KR (1)	KR20000076343A (fr)
CN (1)	CN1255917A (fr)
AP (1)	AP9901635A0 (fr)
AR (1)	AR012078A1 (fr)
AU (1)	AU732162B2 (fr)
BG (1)	BG103807A (fr)
BR (1)	BR9809048A (fr)
CA (1)	CA2283682A1 (fr)
CO (1)	CO4950554A1 (fr)
DZ (1)	DZ2446A1 (fr)
EA (1)	EA199900836A1 (fr)
ID (1)	ID22730A (fr)
IL (1)	IL131958A0 (fr)
MA (1)	MA24499A1 (fr)
NO (1)	NO313753B1 (fr)
NZ (1)	NZ337579A (fr)
OA (1)	OA11390A (fr)
PE (1)	PE62199A1 (fr)
PL (1)	PL335675A1 (fr)
SK (1)	SK126799A3 (fr)
TR (1)	TR199902282T2 (fr)
TW (1)	TW509679B (fr)
WO (1)	WO1998041507A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1999016752A1 (fr) *	1997-09-30	1999-04-08	Molecular Designs International, Inc.	AGONISTES DE β3-ADRENORECEPTEURS, COMPOSITIONS D'AGONISTES ET PROCEDES D'UTILISATION
GB9817424D0 (en) *	1998-08-11	1998-10-07	Smithkline Beecham Plc	Novel compounds
GB9915589D0 (en)	1999-07-02	1999-09-01	Smithkline Beecham Plc	Novel compounds
US6593341B2 (en)	2001-03-29	2003-07-15	Molecular Design International, Inc.	β3-adrenoreceptor agonists, agonist compositions and methods of making and using the same
US6596734B1 (en)	2002-10-11	2003-07-22	Molecular Design International, Inc.	Tetrahydroisoquinoline compounds for use as β3-adrenoreceptor agonists
CN109608325A (zh) *	2018-12-27	2019-04-12	先尼科化工（上海）有限公司	一种卤代苯甲酸衍生物的工业化合成方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4022900A (en) *	1970-09-09	1977-05-10	Marion Laboratories, Inc.	Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents
DE3766472D1 (de) *	1986-10-28	1991-01-10	Smith Kline French Lab	Tetrahydroisochinolin-2-yl-derivate von carbonsaeuren als thromboxan a2-antagonisten.
GB8807922D0 (en) *	1988-04-05	1988-05-05	Fujisawa Pharmaceutical Co	Isoquinoline compound & process for preparation thereof
US4883593A (en) *	1988-10-27	1989-11-28	Bend Research, Inc.	Ultrathin-skinned asymmetric membranes by immiscible solvents treatment
GB9112721D0 (en) *	1991-06-13	1991-07-31	Smithkline Beecham Plc	Novel treatment
BR9709906A (pt) *	1996-06-17	1999-08-10	Smithkline Beecham Plc	Derivados de benzamida substituídos e o uso dos mesmos como anticonvulsivantes

1998
- 1998-03-07 DZ DZ980056A patent/DZ2446A1/fr active
- 1998-03-16 TR TR1999/02282T patent/TR199902282T2/xx unknown
- 1998-03-16 BR BR9809048-8A patent/BR9809048A/pt not_active IP Right Cessation
- 1998-03-16 EA EA199900836A patent/EA199900836A1/ru unknown
- 1998-03-16 CN CN98805128A patent/CN1255917A/zh active Pending
- 1998-03-16 MA MA25000A patent/MA24499A1/fr unknown
- 1998-03-16 US US09/381,369 patent/US6277861B1/en not_active Expired - Fee Related
- 1998-03-16 AP APAP/P/1999/001635A patent/AP9901635A0/en unknown
- 1998-03-16 KR KR1019997008444A patent/KR20000076343A/ko not_active Application Discontinuation
- 1998-03-16 SK SK1267-99A patent/SK126799A3/sk unknown
- 1998-03-16 ID IDW991041D patent/ID22730A/id unknown
- 1998-03-16 AU AU64127/98A patent/AU732162B2/en not_active Ceased
- 1998-03-16 IL IL13195898A patent/IL131958A0/xx unknown
- 1998-03-16 NZ NZ337579A patent/NZ337579A/en unknown
- 1998-03-16 CA CA002283682A patent/CA2283682A1/fr not_active Abandoned
- 1998-03-16 AR ARP980101173A patent/AR012078A1/es not_active Application Discontinuation
- 1998-03-16 JP JP54024798A patent/JP2001516357A/ja not_active Withdrawn
- 1998-03-16 PL PL98335675A patent/PL335675A1/xx unknown
- 1998-03-16 WO PCT/GB1998/000781 patent/WO1998041507A1/fr not_active Application Discontinuation
- 1998-03-16 EP EP98909646A patent/EP0971897A1/fr not_active Withdrawn
- 1998-03-16 CO CO98014463A patent/CO4950554A1/es unknown
- 1998-03-17 PE PE1998000190A patent/PE62199A1/es not_active Application Discontinuation
- 1998-03-20 TW TW087104134A patent/TW509679B/zh not_active IP Right Cessation
1999
- 1999-09-17 OA OA9900210A patent/OA11390A/en unknown
- 1999-09-17 NO NO19994504A patent/NO313753B1/no not_active IP Right Cessation
- 1999-10-13 BG BG103807A patent/BG103807A/bg unknown

Also Published As

Publication number	Publication date
KR20000076343A (ko)	2000-12-26
EA199900836A1 (ru)	2000-04-24
OA11390A (en)	2004-04-14
MA24499A1 (fr)	1998-10-01
US6277861B1 (en)	2001-08-21
CA2283682A1 (fr)	1998-09-24
DZ2446A1 (fr)	2003-01-11
PE62199A1 (es)	1999-09-10
IL131958A0 (en)	2001-03-19
SK126799A3 (en)	2000-05-16
PL335675A1 (en)	2000-05-08
AU732162B2 (en)	2001-04-12
AR012078A1 (es)	2000-09-27
TR199902282T2 (en)	2000-07-21
TW509679B (en)	2002-11-11
NO994504D0 (no)	1999-09-17
AP9901635A0 (en)	1999-09-30
EP0971897A1 (fr)	2000-01-19
CO4950554A1 (es)	2000-09-01
BG103807A (bg)	2001-05-31
WO1998041507A1 (fr)	1998-09-24
CN1255917A (zh)	2000-06-07
ID22730A (id)	1999-12-09
AU6412798A (en)	1998-10-12
NZ337579A (en)	2001-04-27
NO994504L (no)	1999-09-17
BR9809048A (pt)	2000-08-01
JP2001516357A (ja)	2001-09-25

Legal Events

Date	Code	Title	Description
2004-12-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
KR100568654B1 (ko)	2006-04-07	치환된 이소퀴놀린 유도체 및 진경제로서의 그의 용도
WO2000007993A1 (fr)	2000-02-17	Isoquinoleines substituees et leur utilisation en tant qu'anticonvulsifs
CZ416498A3 (cs)	1999-06-16	Substituovaný benzamidový derivát a jeho použití jako antikonvulsantu
EP1042296B1 (fr)	2004-02-25	Derives d'isoquinoline substituee et utilisation de ces derniers comme anticonvulsifs
NO313753B1 (no)	2002-11-25	Anti-konvulsive isokinolyl-benzamid-derivater, farmasöytiske preparater inneholdende dem, anvendelse av dem og fremgangsmåtefor fremstilling av dem
JP2007145862A (ja)	2007-06-14	置換イソキノリン誘導体および抗痙攣剤としてのその使用
US6274594B1 (en)	2001-08-14	Isoquinoline derivatives and their therapeutical use
US6492378B1 (en)	2002-12-10	Substituted isoquinoline derivatives and their use as anticonvulsivants
MXPA99008627A (en)	2000-02-02	Anti-convulsant isoquinolyl-benzamide derivatives
CZ326299A3 (cs)	2000-05-17	Antikonvulsivní isochinolylbenzamidové deriváty
MXPA99008583A (en)	2000-02-02	Substituted isoquinoline derivatives and their use as anticonvulsants
KR20000016715A (ko)	2000-03-25	치환된 벤즈아미드 유도체 및 항경련제로서의그의 용도ㅔ