JP2003506387A - カリウムチャンネルオープナーとしてのベンズアニリド - Google Patents
カリウムチャンネルオープナーとしてのベンズアニリドInfo
- Publication number
- JP2003506387A JP2003506387A JP2001514905A JP2001514905A JP2003506387A JP 2003506387 A JP2003506387 A JP 2003506387A JP 2001514905 A JP2001514905 A JP 2001514905A JP 2001514905 A JP2001514905 A JP 2001514905A JP 2003506387 A JP2003506387 A JP 2003506387A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- alkyl
- aryl
- heteroaryl
- group
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- ZVSKZLHKADLHSD-UHFFFAOYSA-N benzanilide Chemical compound C=1C=CC=CC=1C(=O)NC1=CC=CC=C1 ZVSKZLHKADLHSD-UHFFFAOYSA-N 0.000 title abstract description 15
- 239000004036 potassium channel stimulating agent Substances 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 238000000034 method Methods 0.000 claims abstract description 79
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 claims abstract description 18
- 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 206010010904 Convulsion Diseases 0.000 claims abstract description 9
- 208000035475 disorder Diseases 0.000 claims abstract description 9
- 206010015037 epilepsy Diseases 0.000 claims abstract description 9
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 7
- 208000016354 hearing loss disease Diseases 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 206010003591 Ataxia Diseases 0.000 claims abstract description 5
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 5
- 208000003174 Brain Neoplasms Diseases 0.000 claims abstract description 5
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 5
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 5
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 5
- 206010027599 migraine Diseases 0.000 claims abstract description 5
- 208000005264 motor neuron disease Diseases 0.000 claims abstract description 5
- 208000029257 vision disease Diseases 0.000 claims abstract description 5
- 230000004393 visual impairment Effects 0.000 claims abstract description 5
- 208000008238 Muscle Spasticity Diseases 0.000 claims abstract description 4
- 208000018198 spasticity Diseases 0.000 claims abstract description 4
- 206010047571 Visual impairment Diseases 0.000 claims abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 84
- -1 2-indolyl Chemical group 0.000 claims description 70
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 125000003107 substituted aryl group Chemical group 0.000 claims description 48
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 210000004027 cell Anatomy 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 239000000126 substance Substances 0.000 claims description 22
- 150000002500 ions Chemical class 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 230000033228 biological regulation Effects 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 208000019022 Mood disease Diseases 0.000 claims description 3
- 201000003723 learning disability Diseases 0.000 claims description 3
- 208000020358 Learning disease Diseases 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims 6
- 206010011878 Deafness Diseases 0.000 claims 2
- 231100000895 deafness Toxicity 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 125000002877 alkyl aryl group Chemical group 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 208000028329 epileptic seizure Diseases 0.000 claims 1
- 208000027232 peripheral nervous system disease Diseases 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 8
- 210000001428 peripheral nervous system Anatomy 0.000 abstract description 6
- 239000004090 neuroprotective agent Substances 0.000 abstract description 4
- 229910001414 potassium ion Inorganic materials 0.000 abstract description 4
- 208000019901 Anxiety disease Diseases 0.000 abstract description 2
- 208000020401 Depressive disease Diseases 0.000 abstract description 2
- 230000036506 anxiety Effects 0.000 abstract description 2
- 230000007812 deficiency Effects 0.000 abstract description 2
- 206010027175 memory impairment Diseases 0.000 abstract description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 abstract description 2
- 208000026072 Motor neurone disease Diseases 0.000 abstract 1
- 208000018360 neuromuscular disease Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 42
- 108020001213 potassium channel Proteins 0.000 description 38
- 102000004257 Potassium Channel Human genes 0.000 description 37
- 108091006146 Channels Proteins 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 description 23
- 102000005453 KCNQ2 Potassium Channel Human genes 0.000 description 23
- 238000002360 preparation method Methods 0.000 description 22
- 150000003839 salts Chemical class 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 150000003927 aminopyridines Chemical class 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 239000011591 potassium Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
- 239000012594 Earle’s Balanced Salt Solution Substances 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 208000002854 epidermolysis bullosa simplex superficialis Diseases 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 108010038888 KCNQ3 Potassium Channel Proteins 0.000 description 6
- 102000015686 KCNQ3 Potassium Channel Human genes 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000004907 flux Effects 0.000 description 6
- 150000002540 isothiocyanates Chemical class 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- OHCGBIHRHBBCSP-UHFFFAOYSA-N n-(6-chloropyridin-3-yl)-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NC=2C=NC(Cl)=CC=2)=C1 OHCGBIHRHBBCSP-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 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 description 6
- 229940127315 Potassium Channel Openers Drugs 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- RBVJTGOILWNECX-UHFFFAOYSA-N 3-chloro-n-(6-chloropyridin-3-yl)benzamide Chemical compound ClC1=CC=CC(C(=O)NC=2C=NC(Cl)=CC=2)=C1 RBVJTGOILWNECX-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- 102000004310 Ion Channels Human genes 0.000 description 4
- 108090000862 Ion Channels Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 229940124530 sulfonamide Drugs 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- KLGQWSOYKYFBTR-UHFFFAOYSA-N 2-nitrobenzamide Chemical compound NC(=O)C1=CC=CC=C1[N+]([O-])=O KLGQWSOYKYFBTR-UHFFFAOYSA-N 0.000 description 3
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 3
- YIFKMNQYIAKKJF-UHFFFAOYSA-N 3,4-dichloro-n-pyridin-3-ylbenzamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(=O)NC1=CC=CN=C1 YIFKMNQYIAKKJF-UHFFFAOYSA-N 0.000 description 3
- FZUWJYYLDIKCHR-UHFFFAOYSA-N 3,4-difluoro-n-(6-methylpyridin-3-yl)benzamide Chemical compound C1=NC(C)=CC=C1NC(=O)C1=CC=C(F)C(F)=C1 FZUWJYYLDIKCHR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 108010039918 Polylysine Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000460 chlorine 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
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- 230000003834 intracellular effect Effects 0.000 description 3
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- GDGUOCFTHNGPBK-UHFFFAOYSA-N n-(6-chloropyridin-3-yl)-3,4-difluorobenzamide Chemical compound C1=C(F)C(F)=CC=C1C(=O)NC1=CC=C(Cl)N=C1 GDGUOCFTHNGPBK-UHFFFAOYSA-N 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
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- 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
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- 230000008569 process Effects 0.000 description 3
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- 229910052708 sodium Inorganic materials 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
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- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- XOZAJNLUAODXSP-UHFFFAOYSA-N 2-fluoro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(F)N=C1 XOZAJNLUAODXSP-UHFFFAOYSA-N 0.000 description 2
- 150000005749 2-halopyridines Chemical class 0.000 description 2
- GTWNJFURQAZUTH-UHFFFAOYSA-N 3,4-dichloro-n-(6-chloropyridin-3-yl)benzamide Chemical compound C1=NC(Cl)=CC=C1NC(=O)C1=CC=C(Cl)C(Cl)=C1 GTWNJFURQAZUTH-UHFFFAOYSA-N 0.000 description 2
- HVSVOOJNAOXHRN-UHFFFAOYSA-N 3,4-difluoro-n-[6-(trifluoromethyl)pyridin-3-yl]benzamide Chemical compound C1=C(F)C(F)=CC=C1C(=O)NC1=CC=C(C(F)(F)F)N=C1 HVSVOOJNAOXHRN-UHFFFAOYSA-N 0.000 description 2
- CKJLMDNPUIQPTG-UHFFFAOYSA-N 3-chloro-n-(6-chloropyridin-3-yl)-4-fluorobenzamide Chemical compound C1=C(Cl)C(F)=CC=C1C(=O)NC1=CC=C(Cl)N=C1 CKJLMDNPUIQPTG-UHFFFAOYSA-N 0.000 description 2
- PQBWRWMVDMCZBY-UHFFFAOYSA-N 4,5-dichloro-n-(6-chloropyridin-3-yl)-1,2-thiazole-3-carboxamide Chemical compound ClC1=C(Cl)SN=C1C(=O)NC1=CC=C(Cl)N=C1 PQBWRWMVDMCZBY-UHFFFAOYSA-N 0.000 description 2
- IXPUJQKKUDICDE-UHFFFAOYSA-N 4-amino-n-(6-chloropyridin-3-yl)-3-fluorobenzamide Chemical compound C1=C(F)C(N)=CC=C1C(=O)NC1=CC=C(Cl)N=C1 IXPUJQKKUDICDE-UHFFFAOYSA-N 0.000 description 2
- SIPXSGCLAFNEJU-UHFFFAOYSA-N 5,6-difluoro-n-(6-fluoropyridin-3-yl)pyridine-3-carboxamide Chemical compound C1=NC(F)=CC=C1NC(=O)C1=CN=C(F)C(F)=C1 SIPXSGCLAFNEJU-UHFFFAOYSA-N 0.000 description 2
- XJSBCTASFJNPCG-UHFFFAOYSA-N 5-chloro-n-(6-chloropyridin-3-yl)-1-benzofuran-2-carboxamide Chemical compound C=1C2=CC(Cl)=CC=C2OC=1C(=O)NC1=CC=C(Cl)N=C1 XJSBCTASFJNPCG-UHFFFAOYSA-N 0.000 description 2
- MZEFYXQBJYCQDR-UHFFFAOYSA-N 5-chloro-n-(6-chloropyridin-3-yl)-1h-indole-2-carboxamide Chemical compound C=1C2=CC(Cl)=CC=C2NC=1C(=O)NC1=CC=C(Cl)N=C1 MZEFYXQBJYCQDR-UHFFFAOYSA-N 0.000 description 2
- OJPFTXAQFBMFPE-UHFFFAOYSA-N 5-chloro-n-(6-chloropyridin-3-yl)furan-2-carboxamide Chemical compound O1C(Cl)=CC=C1C(=O)NC1=CC=C(Cl)N=C1 OJPFTXAQFBMFPE-UHFFFAOYSA-N 0.000 description 2
- VMQLBADITVKEER-UHFFFAOYSA-N 5-chloro-n-(6-chloropyridin-3-yl)thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC1=CC=C(Cl)N=C1 VMQLBADITVKEER-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
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- Neurosurgery (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14722199P | 1999-08-04 | 1999-08-04 | |
| US60/147,221 | 1999-08-04 | ||
| PCT/US2000/021308 WO2001010380A2 (en) | 1999-08-04 | 2000-08-04 | Benzanilides as potassium channel openers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003506387A true JP2003506387A (ja) | 2003-02-18 |
| JP2003506387A5 JP2003506387A5 (https=) | 2006-01-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2001514905A Pending JP2003506387A (ja) | 1999-08-04 | 2000-08-04 | カリウムチャンネルオープナーとしてのベンズアニリド |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US6372767B1 (https=) |
| EP (1) | EP1208085B1 (https=) |
| JP (1) | JP2003506387A (https=) |
| AT (1) | ATE380176T1 (https=) |
| AU (1) | AU779034B2 (https=) |
| CA (1) | CA2378241A1 (https=) |
| DE (2) | DE60037321T4 (https=) |
| NZ (1) | NZ516610A (https=) |
| WO (1) | WO2001010380A2 (https=) |
| ZA (1) | ZA200200502B (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008531609A (ja) * | 2005-03-03 | 2008-08-14 | ハー・ルンドベック・アクチエゼルスカベット | 置換されたピリジン誘導体 |
| JP2010535172A (ja) * | 2007-08-02 | 2010-11-18 | エフ.ホフマン−ラ ロシュ アーゲー | Cns障害の処置のためのベンズアミド誘導体の使用 |
| JP2022528562A (ja) * | 2019-04-05 | 2022-06-14 | ストーム・セラピューティクス・リミテッド | Mettl3阻害化合物 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002238023B2 (en) * | 1999-08-04 | 2008-03-13 | Icagen, Inc | Pyridine-substituted benzanilides as potassium ion channel openers |
| NZ516610A (en) | 1999-08-04 | 2004-05-28 | Icagen Inc | Benzanilides as potassium channel openers |
| US6495550B2 (en) * | 1999-08-04 | 2002-12-17 | Icagen, Inc. | Pyridine-substituted benzanilides as potassium ion channel openers |
| NZ527771A (en) * | 1999-08-04 | 2005-04-29 | Icagen Inc | Methods for treating or preventing anxiety |
| US6589986B2 (en) | 2000-12-20 | 2003-07-08 | Wyeth | Methods of treating anxiety disorders |
| HUP0400063A2 (hu) * | 2001-02-20 | 2004-04-28 | Bristol-Myers Squibb Company | Fluor-oxo-indolszármazékok mint KCNQ káliumcsatorna modulátorok, alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények |
| CA2438868A1 (en) * | 2001-02-20 | 2002-09-19 | Valentin K. Gribkoff | Modulators of kcnq potassium channels and use thereof in treating migraine and mechanistically related diseases |
| JP2004535413A (ja) | 2001-05-31 | 2004-11-25 | ブリストル−マイヤーズ スクイブ カンパニー | Kcnqカリウムチャンネルモジュレーターとしてのシンナミド誘導体 |
| US7205307B2 (en) * | 2002-02-14 | 2007-04-17 | Icagen, Inc. | Pyrimidines as novel openers of potassium ion channels |
| US7442519B2 (en) * | 2002-06-25 | 2008-10-28 | Serono Genetics Institute, S.A. | KCNQ2-15 potassium channel |
| EP1539802B1 (en) * | 2002-06-25 | 2007-09-05 | Serono Genetics Institute S.A. | Novel kcnq polypeptides and their uses in the diagnosis of mental disorders |
| EP1565190A4 (en) | 2002-11-22 | 2006-04-26 | Bristol Myers Squibb Co | ARYLCYCLOPROPYLCARBOXYLIC ACID AMIDE AS A KALIUM CHANNEL OPENER |
| AU2003295782A1 (en) | 2002-11-22 | 2004-06-18 | Bristol-Myers Squibb Company | Pyridinyl, pyrimidinyl and pyrazinyl amides as potassium channel openers |
| US7087609B2 (en) | 2002-11-22 | 2006-08-08 | Bristol-Myers Squibb Company | 3-(pyridinyl-piperazin-1-yl)-phenylethyl amides as potassium channel openers |
| EP1581510A4 (en) | 2002-11-22 | 2006-08-30 | Bristol Myers Squibb Co | 1-ARYL-2-HYDROXYETHYLAMIDEALS CALIUM CHANNEL OPENER |
| AU2003294442A1 (en) | 2002-11-22 | 2004-06-18 | Bristol-Myers Squibb Company | 3-heterocyclic benzylamide derivatives as potassium channel openers |
| EP1603858A2 (en) * | 2003-03-11 | 2005-12-14 | NeuroSearch A/S | Kcnq channel modulating compounds and their pharmaceutical use |
| BRPI0415179A (pt) | 2003-10-07 | 2006-11-28 | Renovis Inc | derivados de amida como ligandos de canal de ìon e composições farmacêuticas e métodos de empregar as mesmas |
| US20050089559A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
| CA2571717A1 (en) * | 2004-06-23 | 2006-01-05 | Josette-Nicole Mahy Gehenne | Compounds for the treatment of inflammation of the central nervous system |
| UA89503C2 (uk) | 2004-09-13 | 2010-02-10 | Х. Луннбек А/С | Заміщені похідні аніліну |
| EP1838690A2 (en) * | 2004-12-21 | 2007-10-03 | Devgen N.V. | Compounds with kv4 ion channel activity |
| US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| UA92340C2 (en) * | 2005-03-03 | 2010-10-25 | Х. Луннбек А/С | Substituted pyridine derivatives |
| US7960436B2 (en) * | 2006-06-05 | 2011-06-14 | Valeant Pharmaceuticals International | Substituted arylamino-1,2,3,4-tetrahydro naphthalenes and-2,3-dihydro-1H-indenes as potassium channel modulators |
| US20080045534A1 (en) * | 2006-08-18 | 2008-02-21 | Valeant Pharmaceuticals North America | Derivatives of 1,3-diamino benzene as potassium channel modulators |
| US8993593B2 (en) * | 2006-08-23 | 2015-03-31 | Valeant Pharmaceuticals International | N-(4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2,6-dimethylphenyl)-3,3-dimethylbutanamide as potassium channel modulators |
| BRPI0716715B1 (pt) * | 2006-08-23 | 2021-07-06 | Xenon Pharmaceuticals, Inc | Derivados de 4-(n-azacicloalquil) anilidas como moduladores de canal de potássio, seus usos, produto, composição, comprimido e cápsula |
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| CA2670966A1 (en) * | 2006-11-28 | 2008-06-05 | Valeant Pharmaceuticals International | 1,4 diamino bicyclic retigabine analogues as potassium channel modulators |
| JP2010520875A (ja) | 2007-03-09 | 2010-06-17 | レノビス, インコーポレイテッド | P2x7調節因子としてのビシクロヘテロアリール化合物およびその使用 |
| US8367684B2 (en) * | 2007-06-13 | 2013-02-05 | Valeant Pharmaceuticals International | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
| US8563566B2 (en) | 2007-08-01 | 2013-10-22 | Valeant Pharmaceuticals International | Naphthyridine derivatives as potassium channel modulators |
| CN101790374A (zh) * | 2007-08-01 | 2010-07-28 | H.隆德贝克有限公司 | Kcnq钾通道开放剂用于减轻多巴胺能系统受到干扰的障碍或病症的症状或治疗这种障碍或病症的用途 |
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| US20120053165A1 (en) * | 2009-03-03 | 2012-03-01 | Pfizer Inc. | Novel Phenyl Imidazoles and Phenyl Triazoles As Gamma-Secretase Modulators |
| TWI504395B (zh) | 2009-03-10 | 2015-10-21 | Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier | |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
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| TWI461197B (zh) | 2009-03-12 | 2014-11-21 | 2-mercaptoquinoline-3-carboxamide as a KCNQ2 / 3 modifier | |
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- 2000-08-04 CA CA002378241A patent/CA2378241A1/en not_active Abandoned
- 2000-08-04 US US09/632,576 patent/US6372767B1/en not_active Expired - Fee Related
- 2000-08-04 AT AT00955367T patent/ATE380176T1/de not_active IP Right Cessation
- 2000-08-04 EP EP00955367A patent/EP1208085B1/en not_active Expired - Lifetime
- 2000-08-04 JP JP2001514905A patent/JP2003506387A/ja active Pending
- 2000-08-04 WO PCT/US2000/021308 patent/WO2001010380A2/en not_active Ceased
- 2000-08-04 AU AU67585/00A patent/AU779034B2/en not_active Ceased
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- 2001-12-06 US US10/004,122 patent/US6737422B2/en not_active Expired - Fee Related
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008531609A (ja) * | 2005-03-03 | 2008-08-14 | ハー・ルンドベック・アクチエゼルスカベット | 置換されたピリジン誘導体 |
| JP2013136613A (ja) * | 2005-03-03 | 2013-07-11 | H Lundbeck As | 置換されたピリジン誘導体 |
| JP2010535172A (ja) * | 2007-08-02 | 2010-11-18 | エフ.ホフマン−ラ ロシュ アーゲー | Cns障害の処置のためのベンズアミド誘導体の使用 |
| JP2022528562A (ja) * | 2019-04-05 | 2022-06-14 | ストーム・セラピューティクス・リミテッド | Mettl3阻害化合物 |
| JP7762957B2 (ja) | 2019-04-05 | 2025-10-31 | ストーム・セラピューティクス・リミテッド | Mettl3阻害化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20020091122A1 (en) | 2002-07-11 |
| DE60037321T2 (de) | 2008-11-27 |
| EP1208085A2 (en) | 2002-05-29 |
| US6372767B1 (en) | 2002-04-16 |
| AU779034B2 (en) | 2005-01-06 |
| US20040157829A1 (en) | 2004-08-12 |
| US6605725B2 (en) | 2003-08-12 |
| ZA200200502B (en) | 2003-04-30 |
| WO2001010380A3 (en) | 2001-08-16 |
| DE60037321D1 (de) | 2008-01-17 |
| US20020052393A1 (en) | 2002-05-02 |
| DE60037321T4 (de) | 2010-01-07 |
| US6989398B2 (en) | 2006-01-24 |
| US6737422B2 (en) | 2004-05-18 |
| WO2001010380A2 (en) | 2001-02-15 |
| NZ516610A (en) | 2004-05-28 |
| AU6758500A (en) | 2001-03-05 |
| EP1208085A4 (en) | 2003-05-02 |
| ATE380176T1 (de) | 2007-12-15 |
| EP1208085B1 (en) | 2007-12-05 |
| CA2378241A1 (en) | 2001-02-15 |
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