SK9142000A3 - Tetrahydro isoquinolinyl carboxamide compounds, preparation thereof, pharmaceutical composition containing them and their use - Google Patents

Tetrahydro isoquinolinyl carboxamide compounds, preparation thereof, pharmaceutical composition containing them and their use Download PDF

Info

Publication number: SK9142000A3
Authority: SK; Slovakia
Prior art keywords: disorders; methoxy; tetraisoquinolin; chloro; alkyl
Prior art date: 1997-12-17

Application number

SK914-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Steven Coulton

Roderick Alan Porter

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.)

1997-12-17

Filing date

1998-12-16

Publication date

2000-11-07

1998-12-16 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

2000-11-07 Publication of SK9142000A3 publication Critical patent/SK9142000A3/sk

Links

-1 Tetrahydro isoquinolinyl carboxamide compounds Chemical class 0.000 title claims abstract description 30
238000002360 preparation method Methods 0.000 title claims description 19
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 75
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 58
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
208000035475 disorder Diseases 0.000 claims abstract description 32
239000001257 hydrogen Substances 0.000 claims abstract description 31
230000001537 neural effect Effects 0.000 claims abstract description 27
201000010099 disease Diseases 0.000 claims abstract description 26
239000000126 substance Substances 0.000 claims abstract description 26
208000004296 neuralgia Diseases 0.000 claims abstract description 23
150000003839 salts Chemical class 0.000 claims abstract description 23
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine 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 abstract description 20
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 19
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 19
201000006417 multiple sclerosis Diseases 0.000 claims abstract description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
150000002431 hydrogen Chemical class 0.000 claims abstract description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
150000002367 halogens Chemical class 0.000 claims abstract description 13
238000011282 treatment Methods 0.000 claims abstract description 13
239000001961 anticonvulsive agent Substances 0.000 claims abstract description 12
229910052736 halogen Inorganic materials 0.000 claims abstract description 12
230000035939 shock Effects 0.000 claims abstract description 12
239000012453 solvate Substances 0.000 claims abstract description 12
208000019901 Anxiety disease Diseases 0.000 claims abstract description 11
206010026749 Mania Diseases 0.000 claims abstract description 11
230000036506 anxiety Effects 0.000 claims abstract description 11
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims abstract description 10
208000030507 AIDS Diseases 0.000 claims abstract description 10
206010003591 Ataxia Diseases 0.000 claims abstract description 10
206010058019 Cancer Pain Diseases 0.000 claims abstract description 10
206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 10
208000019695 Migraine disease Diseases 0.000 claims abstract description 10
208000002740 Muscle Rigidity Diseases 0.000 claims abstract description 10
208000008238 Muscle Spasticity Diseases 0.000 claims abstract description 10
208000002193 Pain Diseases 0.000 claims abstract description 10
208000018737 Parkinson disease Diseases 0.000 claims abstract description 10
206010036312 Post-traumatic epilepsy Diseases 0.000 claims abstract description 10
208000028017 Psychotic disease Diseases 0.000 claims abstract description 10
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims abstract description 10
208000009205 Tinnitus Diseases 0.000 claims abstract description 10
230000016571 aggressive behavior Effects 0.000 claims abstract description 10
229940049706 benzodiazepine Drugs 0.000 claims abstract description 10
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims abstract description 10
229960003920 cocaine Drugs 0.000 claims abstract description 10
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
230000000694 effects Effects 0.000 claims abstract description 10
206010015037 epilepsy Diseases 0.000 claims abstract description 10
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 10
206010022437 insomnia Diseases 0.000 claims abstract description 10
206010027599 migraine Diseases 0.000 claims abstract description 10
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 10
230000007971 neurological deficit Effects 0.000 claims abstract description 10
229960002715 nicotine Drugs 0.000 claims abstract description 10
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims abstract description 10
208000019906 panic disease Diseases 0.000 claims abstract description 10
201000000980 schizophrenia Diseases 0.000 claims abstract description 10
208000019116 sleep disease Diseases 0.000 claims abstract description 10
208000018198 spasticity Diseases 0.000 claims abstract description 10
231100000886 tinnitus Toxicity 0.000 claims abstract description 10
208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims abstract description 9
208000000323 Tourette Syndrome Diseases 0.000 claims abstract description 9
208000016620 Tourette disease Diseases 0.000 claims abstract description 9
208000030886 Traumatic Brain injury Diseases 0.000 claims abstract description 9
201000003631 narcolepsy Diseases 0.000 claims abstract description 9
208000021722 neuropathic pain Diseases 0.000 claims abstract description 9
230000009529 traumatic brain injury Effects 0.000 claims abstract description 9
206010043220 Temporomandibular joint syndrome Diseases 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 8
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
206010044652 trigeminal neuralgia Diseases 0.000 claims abstract description 6
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 4
229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
208000026072 Motor neurone disease Diseases 0.000 claims abstract description 3
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims abstract description 3
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract 2
125000000217 alkyl group Chemical group 0.000 claims description 37
238000000034 method Methods 0.000 claims description 30
125000000304 alkynyl group Chemical group 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
SWXSODIZVQALAJ-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-1-carboxamide Chemical class C1=CC=C2C(C(=O)N)NCCC2=C1 SWXSODIZVQALAJ-UHFFFAOYSA-N 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
201000006474 Brain Ischemia Diseases 0.000 claims description 9
230000001773 anti-convulsant effect Effects 0.000 claims description 9
229940125681 anticonvulsant agent Drugs 0.000 claims description 9
206010008118 cerebral infarction Diseases 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
230000002265 prevention Effects 0.000 claims description 9
230000033764 rhythmic process Effects 0.000 claims description 9
201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 7
125000006124 n-propyl sulfonyl group Chemical group 0.000 claims description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
239000012458 free base Substances 0.000 claims description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Chemical group 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 4
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
229910004013 NO 2 Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
229940124597 therapeutic agent Drugs 0.000 claims description 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
BGTOWKSIORTVQH-HOSYLAQJSA-N cyclopentanone Chemical group O=[13C]1CCCC1 BGTOWKSIORTVQH-HOSYLAQJSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
230000004064 dysfunction Effects 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
208000005264 motor neuron disease Diseases 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
210000003901 trigeminal nerve Anatomy 0.000 claims description 2
DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical group CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 claims 1
235000005544 Acinos arvensis Nutrition 0.000 claims 1
244000207178 Acinos arvensis Species 0.000 claims 1
241000282465 Canis Species 0.000 claims 1
208000034189 Sclerosis Diseases 0.000 claims 1
125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
PAMCRRDMORMCSM-UHFFFAOYSA-N n-(trifluoromethyl)benzamide Chemical compound FC(F)(F)NC(=O)C1=CC=CC=C1 PAMCRRDMORMCSM-UHFFFAOYSA-N 0.000 claims 1
239000004081 narcotic agent Substances 0.000 claims 1
230000002981 neuropathic effect Effects 0.000 claims 1
125000005010 perfluoroalkyl group Chemical group 0.000 claims 1
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 abstract description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
206010008748 Chorea Diseases 0.000 abstract 1
208000017164 Chronobiology disease Diseases 0.000 abstract 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
208000012601 choreatic disease Diseases 0.000 abstract 1
238000011321 prophylaxis Methods 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
239000000203 mixture Substances 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
239000008186 active pharmaceutical agent Substances 0.000 description 24
239000002904 solvent Substances 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
239000007787 solid Substances 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
150000001408 amides Chemical class 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
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210000001519 tissue Anatomy 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
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150000001412 amines Chemical class 0.000 description 7
239000003480 eluent Substances 0.000 description 7
235000019441 ethanol Nutrition 0.000 description 7
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
UCJQSGHEAGPXKG-UHFFFAOYSA-N n-(8-chloro-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-methoxy-3-(trifluoromethyl)benzamide Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C(=O)NC1=CC=C(CCNC2)C2=C1Cl UCJQSGHEAGPXKG-UHFFFAOYSA-N 0.000 description 5
DUJFIXJYRUOLAR-UHFFFAOYSA-N n-[8-bromo-2-(2,2,2-trifluoroacetyl)-3,4-dihydro-1h-isoquinolin-7-yl]-4-methoxy-3-(trifluoromethyl)benzamide Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C(=O)NC1=CC=C(CCN(C2)C(=O)C(F)(F)F)C2=C1Br DUJFIXJYRUOLAR-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
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241000699670 Mus sp. Species 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
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KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
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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 3
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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
238000004440 column chromatography Methods 0.000 description 3
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000000080 wetting agent Substances 0.000 description 3
LZXQFYUUMWVPQK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-1-amine Chemical compound C1=CC=C2C(N)NCCC2=C1 LZXQFYUUMWVPQK-UHFFFAOYSA-N 0.000 description 2
HQRZUWHVVHWAOS-UHFFFAOYSA-N 1-(7-amino-8-chloro-3,4-dihydro-1h-isoquinolin-2-yl)-2,2,2-trifluoroethanone Chemical compound C1CN(C(=O)C(F)(F)F)CC2=C(Cl)C(N)=CC=C21 HQRZUWHVVHWAOS-UHFFFAOYSA-N 0.000 description 2
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Classifications

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- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
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- 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
- 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
- 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
- C07D217/06—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 the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
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Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
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Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Biomedical Technology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
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Psychology (AREA)
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Urology & Nephrology (AREA)
Vascular Medicine (AREA)
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Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
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SK914-2000A 1997-12-17 1998-12-16 Tetrahydro isoquinolinyl carboxamide compounds, preparation thereof, pharmaceutical composition containing them and their use SK9142000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9726695.1A GB9726695D0 (en)	1997-12-17	1997-12-17	Novel compounds
PCT/GB1998/003785 WO1999031068A1 (en)	1997-12-17	1998-12-16	Substituted isoquinoline derivatives and their use as anticonvulsants

Publications (1)

Publication Number	Publication Date
SK9142000A3 true SK9142000A3 (en)	2000-11-07

Family

ID=10823780

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK914-2000A SK9142000A3 (en)	1997-12-17	1998-12-16	Tetrahydro isoquinolinyl carboxamide compounds, preparation thereof, pharmaceutical composition containing them and their use

Country Status (30)

Country	Link
US (1)	US6248754B1 (de)
EP (1)	EP1042296B1 (de)
JP (1)	JP2002508360A (de)
KR (1)	KR20010033194A (de)
CN (1)	CN1125052C (de)
AP (1)	AP2000001832A0 (de)
AR (1)	AR014942A1 (de)
AT (1)	ATE260258T1 (de)
AU (1)	AU744451B2 (de)
BG (1)	BG104607A (de)
BR (1)	BR9813642A (de)
CA (1)	CA2315079A1 (de)
CO (1)	CO5080731A1 (de)
DE (1)	DE69821988T2 (de)
EA (1)	EA200000657A1 (de)
ES (1)	ES2216333T3 (de)
GB (1)	GB9726695D0 (de)
HU (2)	HUP0000987A3 (de)
ID (1)	ID24810A (de)
IL (1)	IL136382A0 (de)
MA (1)	MA26583A1 (de)
NO (1)	NO315649B1 (de)
NZ (1)	NZ504706A (de)
OA (1)	OA11526A (de)
PE (1)	PE20000006A1 (de)
PL (1)	PL341222A1 (de)
SK (1)	SK9142000A3 (de)
TR (1)	TR200001791T2 (de)
WO (1)	WO1999031068A1 (de)
ZA (1)	ZA9811503B (de)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20010016657A1 (en) *	1997-03-18	2001-08-23	Smithkline Beecham P.L.C.	Substituted isoquinoline derivatives and their use as anticonvulsants
EP1023269A4 (de) *	1997-09-30	2001-06-27	Molecular Design Int	Beta3-adrenoreceptor-agonisten, agonist-zubereitungen und verfahren zu ihrer verwendung
GB9915589D0 (en) *	1999-07-02	1999-09-01	Smithkline Beecham Plc	Novel compounds
AU1734401A (en) *	1999-12-09	2001-06-18	Mitsubishi Pharma Corporation	Carboxyamido derivatives
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
US7173032B2 (en)	2001-09-21	2007-02-06	Reddy Us Therapeutics, Inc.	Methods and compositions of novel triazine compounds
US6596734B1 (en)	2002-10-11	2003-07-22	Molecular Design International, Inc.	Tetrahydroisoquinoline compounds for use as β3-adrenoreceptor agonists
US7119214B2 (en) *	2004-04-13	2006-10-10	Cephalon France	Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives
GB0619176D0 (en) *	2006-09-29	2006-11-08	Lectus Therapeutics Ltd	Ion channel modulators & uses thereof
TWI459947B (zh)	2007-06-26	2014-11-11	Otsuka Pharma Co Ltd	苯并氮呯化合物及藥學製劑
CN118908892B (zh) *	2024-07-18	2025-10-31	武汉大学	氨基异喹啉类衍生物及其在制备抗病毒药物中的应用

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* 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
NZ332757A (en) *	1996-06-17	1999-06-29	Smithkline Beecham Plc	Substituted tetrahydroisoquinoline benzamide derivatives and their use as anticonvulsants and psycho-active agents
IL131756A0 (en) *	1997-03-18	2001-03-19	Smithkline Beecham Plc	Substituted isoquinoline derivatives and their use as anticonvulsants

1997
- 1997-12-17 GB GBGB9726695.1A patent/GB9726695D0/en not_active Ceased
1998
- 1998-03-16 HU HU0000987A patent/HUP0000987A3/hu unknown
- 1998-12-15 MA MA25393A patent/MA26583A1/fr unknown
- 1998-12-15 ZA ZA9811503A patent/ZA9811503B/xx unknown
- 1998-12-16 US US09/581,647 patent/US6248754B1/en not_active Expired - Fee Related
- 1998-12-16 CN CN98813570A patent/CN1125052C/zh not_active Expired - Fee Related
- 1998-12-16 OA OA1200000180A patent/OA11526A/en unknown
- 1998-12-16 EA EA200000657A patent/EA200000657A1/ru unknown
- 1998-12-16 PL PL98341222A patent/PL341222A1/xx unknown
- 1998-12-16 EP EP98960040A patent/EP1042296B1/de not_active Expired - Lifetime
- 1998-12-16 AR ARP980106398A patent/AR014942A1/es not_active Application Discontinuation
- 1998-12-16 AT AT98960040T patent/ATE260258T1/de not_active IP Right Cessation
- 1998-12-16 JP JP2000538995A patent/JP2002508360A/ja active Pending
- 1998-12-16 PE PE1998001234A patent/PE20000006A1/es not_active Application Discontinuation
- 1998-12-16 NZ NZ504706A patent/NZ504706A/xx unknown
- 1998-12-16 IL IL13638298A patent/IL136382A0/xx unknown
- 1998-12-16 TR TR2000/01791T patent/TR200001791T2/xx unknown
- 1998-12-16 KR KR1020007006579A patent/KR20010033194A/ko not_active Withdrawn
- 1998-12-16 HU HU0004663A patent/HUP0004663A3/hu unknown
- 1998-12-16 ID IDW20001157A patent/ID24810A/id unknown
- 1998-12-16 ES ES98960040T patent/ES2216333T3/es not_active Expired - Lifetime
- 1998-12-16 AU AU15724/99A patent/AU744451B2/en not_active Ceased
- 1998-12-16 BR BR9813642-9A patent/BR9813642A/pt not_active Application Discontinuation
- 1998-12-16 WO PCT/GB1998/003785 patent/WO1999031068A1/en not_active Ceased
- 1998-12-16 AP APAP/P/2000/001832A patent/AP2000001832A0/en unknown
- 1998-12-16 SK SK914-2000A patent/SK9142000A3/sk unknown
- 1998-12-16 CA CA002315079A patent/CA2315079A1/en not_active Abandoned
- 1998-12-16 DE DE69821988T patent/DE69821988T2/de not_active Expired - Fee Related
- 1998-12-17 CO CO98075174A patent/CO5080731A1/es unknown
2000
- 2000-06-16 NO NO20003142A patent/NO315649B1/no not_active IP Right Cessation
- 2000-07-13 BG BG104607A patent/BG104607A/bg unknown

Also Published As

Publication number	Publication date
EA200000657A1 (ru)	2000-12-25
DE69821988T2 (de)	2005-01-05
ES2216333T3 (es)	2004-10-16
CA2315079A1 (en)	1999-06-24
BR9813642A (pt)	2000-10-17
WO1999031068A1 (en)	1999-06-24
ZA9811503B (en)	2000-06-15
KR20010033194A (ko)	2001-04-25
NO315649B1 (no)	2003-10-06
ID24810A (id)	2000-08-24
EP1042296B1 (de)	2004-02-25
HUP0000987A3 (en)	2000-10-30
AU1572499A (en)	1999-07-05
ATE260258T1 (de)	2004-03-15
NZ504706A (en)	2002-11-26
HUP0000987A2 (hu)	2000-09-28
CN1284946A (zh)	2001-02-21
CN1125052C (zh)	2003-10-22
TR200001791T2 (tr)	2000-12-21
US6248754B1 (en)	2001-06-19
AU744451B2 (en)	2002-02-21
GB9726695D0 (en)	1998-02-18
IL136382A0 (en)	2001-06-14
DE69821988D1 (de)	2004-04-01
JP2002508360A (ja)	2002-03-19
BG104607A (bg)	2001-02-28
HUP0004663A2 (hu)	2001-05-28
EP1042296A1 (de)	2000-10-11
AR014942A1 (es)	2001-04-11
AP2000001832A0 (en)	2000-06-30
NO20003142L (no)	2000-06-16
OA11526A (en)	2004-02-09
PE20000006A1 (es)	2000-03-01
NO20003142D0 (no)	2000-06-16
CO5080731A1 (es)	2001-09-25
MA26583A1 (fr)	2004-12-20
HUP0004663A3 (en)	2002-10-28
PL341222A1 (en)	2001-03-26

Publication	Publication Date	Title
JP3690423B2 (ja)	2005-08-31	置換イソキノリン誘導体およびその抗痙攣薬としての使用
US20030144320A1 (en)	2003-07-31	Substituted isoquinoline derivatives and their use as anticonvulsants
CZ416498A3 (cs)	1999-06-16	Substituovaný benzamidový derivát a jeho použití jako antikonvulsantu
AU744451B2 (en)	2002-02-21	Substituted isoquinoline derivatives and their use as anticonvulsants
SK126799A3 (en)	2000-05-16	Isoquinolyl-benzamide derivatives, process for their production, pharmaceutical composition containing them and their use
EP1200409B1 (de)	2004-02-25	Substituierte isochinolinderivate und ihre verwendung als anticonvulsiva
JP2001523678A (ja)	2001-11-27	イソキノリン誘導体およびその治療用途
CZ2001436A3 (cs)	2001-08-15	Nové sloučeniny
US6410555B1 (en)	2002-06-25	Tetrahydronaphthyridinyl-carboxamides having anti-convulsant activity
US6492378B1 (en)	2002-12-10	Substituted isoquinoline derivatives and their use as anticonvulsivants
CZ20002221A3 (cs)	2000-11-15	Substituované deriváty isochinolinu a jejich použití jako antikonvulziva
WO2000008022A1 (en)	2000-02-17	Urea derivatives
MXPA99008583A (en)	2000-02-02	Substituted isoquinoline derivatives and their use as anticonvulsants
KR20000016715A (ko)	2000-03-25	치환된 벤즈아미드 유도체 및 항경련제로서의그의 용도ㅔ