KR20100075436A - 칼륨 채널 조절제로서의 5-아미노-4,6-이치환된 인돌 및 5-아미노-4,6-이치환된 인돌린의 유도체 - Google Patents
칼륨 채널 조절제로서의 5-아미노-4,6-이치환된 인돌 및 5-아미노-4,6-이치환된 인돌린의 유도체 Download PDFInfo
- Publication number
- KR20100075436A KR20100075436A KR1020107005508A KR20107005508A KR20100075436A KR 20100075436 A KR20100075436 A KR 20100075436A KR 1020107005508 A KR1020107005508 A KR 1020107005508A KR 20107005508 A KR20107005508 A KR 20107005508A KR 20100075436 A KR20100075436 A KR 20100075436A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- dimethyl
- formula
- pharmaceutically acceptable
- alkyl
- Prior art date
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- 102000004257 Potassium Channel Human genes 0.000 title claims abstract description 18
- 108020001213 potassium channel Proteins 0.000 title claims abstract description 18
- -1 5-amino-4,6-disubstituted indole Chemical class 0.000 title claims description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 154
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 9
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 7
- 125000002541 furyl group Chemical group 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims abstract description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
- 125000005412 pyrazyl group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- SXZMIGFFCOLZGM-UHFFFAOYSA-N n-[1-[(3,4-difluorophenyl)methyl]-4,6-dimethyl-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=C(F)C(F)=C1 SXZMIGFFCOLZGM-UHFFFAOYSA-N 0.000 claims description 4
- GJSUFXHZBNCHQM-UHFFFAOYSA-N n-[1-[(4-fluorophenyl)methyl]-4,6-dimethyl-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=C(F)C=C1 GJSUFXHZBNCHQM-UHFFFAOYSA-N 0.000 claims description 4
- KTIHIEQTTWYZBI-UHFFFAOYSA-N n-[4,6-dimethyl-1-(pyridin-3-ylmethyl)-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=CN=C1 KTIHIEQTTWYZBI-UHFFFAOYSA-N 0.000 claims description 4
- QHDSASIBTYDMFN-UHFFFAOYSA-N n-[4,6-dimethyl-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=C(C(F)(F)F)C=C1 QHDSASIBTYDMFN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- JCERMRWXGCGRHU-UHFFFAOYSA-N n-[1-[(3-chlorophenyl)methyl]-4,6-dimethyl-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=CC(Cl)=C1 JCERMRWXGCGRHU-UHFFFAOYSA-N 0.000 claims description 3
- CQSSTSHZSMWLIZ-UHFFFAOYSA-N n-[1-[(4-bromophenyl)methyl]-4,6-dimethyl-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=C(Br)C=C1 CQSSTSHZSMWLIZ-UHFFFAOYSA-N 0.000 claims description 3
- KRKHXCLSAITASC-UHFFFAOYSA-N n-[4,6-dimethyl-1-(naphthalen-2-ylmethyl)-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1=CC=CC2=CC(CN3C=4C=C(C(=C(C)C=4CC3)NC(=O)CC(C)(C)C)C)=CC=C21 KRKHXCLSAITASC-UHFFFAOYSA-N 0.000 claims description 3
- UHZXSJAJAGVFPE-UHFFFAOYSA-N n-[4,6-dimethyl-1-(pyridin-4-ylmethyl)-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=NC=C1 UHZXSJAJAGVFPE-UHFFFAOYSA-N 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- PIEXCQIOSMOEOU-UHFFFAOYSA-N 1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Br)C(=O)N(Cl)C1=O PIEXCQIOSMOEOU-UHFFFAOYSA-N 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- 125000004970 halomethyl group Chemical group 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- PCOBBVZJEWWZFR-UHFFFAOYSA-N ezogabine Chemical compound C1=C(N)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1 PCOBBVZJEWWZFR-UHFFFAOYSA-N 0.000 description 15
- 229960003312 retigabine Drugs 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 206010015037 epilepsy Diseases 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 108091006146 Channels Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000028161 membrane depolarization Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- QANCFDUNZQXJAE-UHFFFAOYSA-N 1-(4,6-dimethyl-2,3-dihydroindol-1-yl)ethanone Chemical compound C1=C(C)C=C(C)C2=C1N(C(=O)C)CC2 QANCFDUNZQXJAE-UHFFFAOYSA-N 0.000 description 4
- RQWIBRCENFYWQC-UHFFFAOYSA-N 4,6-dimethyl-5-nitro-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroindole Chemical compound C1CC=2C(C)=C([N+]([O-])=O)C(C)=CC=2N1CC1=CC=C(C(F)(F)F)C=C1 RQWIBRCENFYWQC-UHFFFAOYSA-N 0.000 description 4
- YMYWWTVHGWHXOJ-UHFFFAOYSA-N 4,6-dimethyl-5-nitro-2,3-dihydro-1h-indole Chemical compound CC1=C([N+]([O-])=O)C(C)=CC2=C1CCN2 YMYWWTVHGWHXOJ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 4
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- ZIUACFJAEUJLGL-UHFFFAOYSA-N 1-(4,6-dimethyl-5-nitro-2,3-dihydroindol-1-yl)ethanone Chemical compound C1=C(C)C([N+]([O-])=O)=C(C)C2=C1N(C(=O)C)CC2 ZIUACFJAEUJLGL-UHFFFAOYSA-N 0.000 description 3
- BEKMBBQDMNMRGD-UHFFFAOYSA-N 4,6-dimethyl-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroindol-5-amine Chemical compound C1CC=2C(C)=C(N)C(C)=CC=2N1CC1=CC=C(C(F)(F)F)C=C1 BEKMBBQDMNMRGD-UHFFFAOYSA-N 0.000 description 3
- WUCQJZHJZJSFLU-UHFFFAOYSA-N 4,6-dimethyl-1h-indole Chemical compound CC1=CC(C)=C2C=CNC2=C1 WUCQJZHJZJSFLU-UHFFFAOYSA-N 0.000 description 3
- HRHYVQGVACIBPS-UHFFFAOYSA-N 4,6-dimethyl-1h-indole-2-carboxylic acid Chemical compound CC1=CC(C)=C2C=C(C(O)=O)NC2=C1 HRHYVQGVACIBPS-UHFFFAOYSA-N 0.000 description 3
- ZDTVMIZTUFHUPF-UHFFFAOYSA-N 4,6-dimethyl-2,3-dihydro-1h-indole Chemical compound CC1=CC(C)=CC2=C1CCN2 ZDTVMIZTUFHUPF-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 description 3
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- 102100034354 Potassium voltage-gated channel subfamily KQT member 2 Human genes 0.000 description 3
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- MMFBMAHZFBCFMJ-UHFFFAOYSA-N ethyl 4,6-dimethyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2NC(C(=O)OCC)=CC2=C1C MMFBMAHZFBCFMJ-UHFFFAOYSA-N 0.000 description 3
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- CABLELNEBGCTMD-UHFFFAOYSA-N 1-[(3,4-difluorophenyl)methyl]-4,6-dimethyl-2,3-dihydroindol-5-amine Chemical compound C1CC=2C(C)=C(N)C(C)=CC=2N1CC1=CC=C(F)C(F)=C1 CABLELNEBGCTMD-UHFFFAOYSA-N 0.000 description 1
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- RYNJYDPDOBVGOU-UHFFFAOYSA-N n-[1-[(3,5-difluorophenyl)methyl]-4,6-dimethylindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1=CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC(F)=CC(F)=C1 RYNJYDPDOBVGOU-UHFFFAOYSA-N 0.000 description 1
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- HPSMWDMAJCOPRR-UHFFFAOYSA-N n-[1-[(4-bromophenyl)methyl]-4,6-dimethylindol-5-yl]-3,3-dimethylbutanamide Chemical compound C1=CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=C(Br)C=C1 HPSMWDMAJCOPRR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| US96452607P | 2007-08-13 | 2007-08-13 | |
| US60/964,526 | 2007-08-13 | ||
| US12/189,709 US7786146B2 (en) | 2007-08-13 | 2008-08-11 | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
| US12/189,709 | 2008-08-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20100075436A true KR20100075436A (ko) | 2010-07-02 |
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| KR1020107005508A Withdrawn KR20100075436A (ko) | 2007-08-13 | 2008-08-12 | 칼륨 채널 조절제로서의 5-아미노-4,6-이치환된 인돌 및 5-아미노-4,6-이치환된 인돌린의 유도체 |
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|---|---|
| US (2) | US7786146B2 (enExample) |
| EP (1) | EP2190534B1 (enExample) |
| JP (1) | JP2010536771A (enExample) |
| KR (1) | KR20100075436A (enExample) |
| CN (1) | CN101795727A (enExample) |
| AU (1) | AU2008286919B2 (enExample) |
| BR (1) | BRPI0815210A2 (enExample) |
| CA (1) | CA2696012C (enExample) |
| ES (1) | ES2531335T3 (enExample) |
| HU (1) | HUE025928T2 (enExample) |
| MX (1) | MX2010001712A (enExample) |
| PL (1) | PL2190534T3 (enExample) |
| RU (1) | RU2483060C2 (enExample) |
| SG (1) | SG183725A1 (enExample) |
| TW (1) | TW200927096A (enExample) |
| WO (1) | WO2009023677A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| US8722929B2 (en) * | 2006-10-10 | 2014-05-13 | Valeant Pharmaceuticals International | N-[2-amino-4-(phenylmethoxy)phenyl] amides and related compounds as potassium channel modulators |
| US8563566B2 (en) * | 2007-08-01 | 2013-10-22 | Valeant Pharmaceuticals International | Naphthyridine derivatives as potassium channel modulators |
| US7786146B2 (en) * | 2007-08-13 | 2010-08-31 | Valeant Pharmaceuticals International | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
| CN102241608A (zh) * | 2011-05-12 | 2011-11-16 | 天津市汉康医药生物技术有限公司 | 瑞替加滨化合物及其组合物 |
| US9321750B2 (en) * | 2012-04-20 | 2016-04-26 | Innov17 Llc | ROR modulators and their uses |
| CN103508960B (zh) * | 2012-06-29 | 2017-12-12 | 江苏先声药业有限公司 | 苯并杂环衍生物 |
| CN107098844B (zh) * | 2017-05-17 | 2019-07-30 | 许昌学院 | 一种c-5位硝基取代的酰基吲哚啉类化合物的合成方法 |
| CN112010808B (zh) * | 2019-05-31 | 2021-11-30 | 上海挚盟医药科技有限公司 | 作为钾通道调节剂的四氢-1h-苯氮杂卓类化合物及其制备和应用 |
| CN114539120A (zh) * | 2022-03-09 | 2022-05-27 | 台州学院 | 一种吲哚类钾离子通道激动剂的制备方法 |
| TW202604508A (zh) * | 2024-05-03 | 2026-02-01 | 加拿大商再諾製藥公司 | 氮雜吲哚及氮雜吲哚啉化合物及其用途 |
| WO2025231323A1 (en) * | 2024-05-03 | 2025-11-06 | Xenon Pharmaceuticals Inc. | Bicyclic heteroaryl compounds and uses thereof |
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| US4181803A (en) * | 1973-12-14 | 1980-01-01 | Eisai Co., Ltd. | Propiophenone derivatives and preparation thereof |
| ATE25078T1 (de) * | 1982-10-27 | 1987-02-15 | Degussa | 2-amino-3-acylamino-6-benzylamino-pyridinderivate mit anti-epileptischer wirkung. |
| DE3337593A1 (de) | 1982-10-27 | 1984-05-03 | Degussa Ag, 6000 Frankfurt | 2-amino-3-acylamino-6-benzylamino-pyridin-derivate mit antiepileptischer wirkung |
| EP0189788B1 (de) * | 1985-01-23 | 1989-09-13 | ASTA Pharma Aktiengesellschaft | Synergistische Kombination von Flupirtin und nicht-steroidalen Antiphlogistika |
| EP0193056B1 (de) * | 1985-02-23 | 1989-06-07 | ASTA Pharma Aktiengesellschaft | Kombination von Flupirtin und anticholinergisch wirkenden Spasmolytika |
| DE3604575A1 (de) | 1985-02-23 | 1986-08-28 | Degussa Ag, 6000 Frankfurt | Kombination von flupirtin und anticholinergisch wirkenden spasmolytika |
| JP2583067B2 (ja) * | 1987-08-04 | 1997-02-19 | 住友化学工業株式会社 | モノアゾ化合物およびそれを用いて疎水性繊維材料を染色または捺染する方法 |
| GB8800199D0 (en) * | 1988-01-06 | 1988-02-10 | Beecham Group Plc | Pharmaceutical preparation |
| MC2029A1 (fr) * | 1988-05-16 | 1990-04-25 | Asta Pharma Ag | (n-heterocyclyl)-3 diamino-2,6 pyridines substituees et leurs n-oxydes,preparation de ces composes et leur application comme medicaments |
| US5629307A (en) * | 1989-10-20 | 1997-05-13 | Olney; John W. | Use of ibogaine in reducing excitotoxic brain damage |
| US6004945A (en) * | 1990-05-10 | 1999-12-21 | Fukunaga; Atsuo F. | Use of adenosine compounds to relieve pain |
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-
2008
- 2008-08-11 US US12/189,709 patent/US7786146B2/en not_active Expired - Fee Related
- 2008-08-12 HU HUE08827266A patent/HUE025928T2/en unknown
- 2008-08-12 WO PCT/US2008/072926 patent/WO2009023677A1/en not_active Ceased
- 2008-08-12 AU AU2008286919A patent/AU2008286919B2/en not_active Ceased
- 2008-08-12 BR BRPI0815210 patent/BRPI0815210A2/pt active Search and Examination
- 2008-08-12 SG SG2012059937A patent/SG183725A1/en unknown
- 2008-08-12 JP JP2010521125A patent/JP2010536771A/ja active Pending
- 2008-08-12 MX MX2010001712A patent/MX2010001712A/es active IP Right Grant
- 2008-08-12 EP EP08827266.1A patent/EP2190534B1/en not_active Not-in-force
- 2008-08-12 RU RU2010109388/04A patent/RU2483060C2/ru not_active IP Right Cessation
- 2008-08-12 CN CN200880103296A patent/CN101795727A/zh active Pending
- 2008-08-12 CA CA2696012A patent/CA2696012C/en not_active Expired - Fee Related
- 2008-08-12 ES ES08827266T patent/ES2531335T3/es active Active
- 2008-08-12 PL PL08827266T patent/PL2190534T3/pl unknown
- 2008-08-12 KR KR1020107005508A patent/KR20100075436A/ko not_active Withdrawn
- 2008-08-13 TW TW097130826A patent/TW200927096A/zh unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2696012A1 (en) | 2009-02-19 |
| TW200927096A (en) | 2009-07-01 |
| MX2010001712A (es) | 2010-07-28 |
| JP2010536771A (ja) | 2010-12-02 |
| US8211918B2 (en) | 2012-07-03 |
| RU2483060C2 (ru) | 2013-05-27 |
| AU2008286919A1 (en) | 2009-02-19 |
| HUE025928T2 (en) | 2016-05-30 |
| PL2190534T3 (pl) | 2015-11-30 |
| AU2008286919B2 (en) | 2014-05-29 |
| WO2009023677A1 (en) | 2009-02-19 |
| RU2010109388A (ru) | 2011-09-20 |
| EP2190534A1 (en) | 2010-06-02 |
| US20110118318A1 (en) | 2011-05-19 |
| BRPI0815210A2 (pt) | 2015-03-31 |
| CA2696012C (en) | 2017-10-31 |
| ES2531335T3 (es) | 2015-03-13 |
| EP2190534B1 (en) | 2015-02-18 |
| SG183725A1 (en) | 2012-09-27 |
| US20090137635A1 (en) | 2009-05-28 |
| CN101795727A (zh) | 2010-08-04 |
| US7786146B2 (en) | 2010-08-31 |
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