HUE025928T2 - Potassium channel modulator 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline derivatives - Google Patents
Potassium channel modulator 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline derivatives Download PDFInfo
- Publication number
- HUE025928T2 HUE025928T2 HUE08827266A HUE08827266A HUE025928T2 HU E025928 T2 HUE025928 T2 HU E025928T2 HU E08827266 A HUE08827266 A HU E08827266A HU E08827266 A HUE08827266 A HU E08827266A HU E025928 T2 HUE025928 T2 HU E025928T2
- Authority
- HU
- Hungary
- Prior art keywords
- dimethyl
- indol
- compound
- pharmaceutically acceptable
- formula
- Prior art date
Links
- 102000004257 Potassium Channel Human genes 0.000 title claims description 13
- 108020001213 potassium channel Proteins 0.000 title claims description 13
- -1 5-amino-4, 6-disubstituted indole Chemical class 0.000 title claims description 9
- 239000000203 mixture Substances 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims 2
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims 1
- RFPQEXNUIMCZDQ-UHFFFAOYSA-N ac1ne2g0 Chemical compound CCC[CH2-] RFPQEXNUIMCZDQ-UHFFFAOYSA-N 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 90
- 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 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 229910001419 rubidium ion Inorganic materials 0.000 description 18
- 125000000217 alkyl group Chemical group 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- NCCSSGKUIKYAJD-UHFFFAOYSA-N rubidium(1+) Chemical compound [Rb+] NCCSSGKUIKYAJD-UHFFFAOYSA-N 0.000 description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 238000002360 preparation method Methods 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
- 239000000872 buffer Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 206010015037 epilepsy Diseases 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 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
- 229910052736 halogen Inorganic materials 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000007787 solid Substances 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
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 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 6
- 229960003312 retigabine Drugs 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 230000028161 membrane depolarization Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 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 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- RLIZWHRMWRNQRJ-UHFFFAOYSA-N n-[1-[(3-chlorophenyl)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=CC(Cl)=C1 RLIZWHRMWRNQRJ-UHFFFAOYSA-N 0.000 description 4
- RGWMJZBSAUJOLD-UHFFFAOYSA-N n-[4,6-dimethyl-1-[[4-(trifluoromethyl)phenyl]methyl]indol-5-yl]-3,3-dimethylbutanamide Chemical compound C1=CC=2C(C)=C(NC(=O)CC(C)(C)C)C(C)=CC=2N1CC1=CC=C(C(F)(F)F)C=C1 RGWMJZBSAUJOLD-UHFFFAOYSA-N 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
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HYWYSZBKIYHZRW-UHFFFAOYSA-N BrC1=CC=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=C1.ClC=1C=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=CC1 Chemical compound BrC1=CC=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=C1.ClC=1C=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=CC1 HYWYSZBKIYHZRW-UHFFFAOYSA-N 0.000 description 3
- QPNTYLHOCHBOST-UHFFFAOYSA-N CC1=C2CCN(C2=CC(=C1NC(CC(C)(C)C)=O)C)CC=1C=NC=CC1.CC1=C2CCN(C2=CC(=C1NC(CC(C)(C)C)=O)C)CC1=CC=NC=C1 Chemical compound CC1=C2CCN(C2=CC(=C1NC(CC(C)(C)C)=O)C)CC=1C=NC=CC1.CC1=C2CCN(C2=CC(=C1NC(CC(C)(C)C)=O)C)CC1=CC=NC=C1 QPNTYLHOCHBOST-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- VLTJIYXWQWHVCZ-UHFFFAOYSA-N N-[4,6-dimethyl-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide N-[1-[(4-fluorophenyl)methyl]-4,6-dimethyl-2,3-dihydroindol-5-yl]-3,3-dimethylbutanamide Chemical compound FC1=CC=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=C1.FC(C1=CC=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=C1)(F)F VLTJIYXWQWHVCZ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 description 3
- 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000005059 halophenyl group Chemical group 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 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 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
- 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 2
- 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 2
- IKWXSNHOHZZEQS-UHFFFAOYSA-N CC1=C2CCN(C2=CC(=C1NC(CC(C)(C)C)=O)C)CC1=CC2=CC=CC=C2C=C1.FC=1C=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=CC1F Chemical compound CC1=C2CCN(C2=CC(=C1NC(CC(C)(C)C)=O)C)CC1=CC2=CC=CC=C2C=C1.FC=1C=C(CN2CCC3=C(C(=C(C=C23)C)NC(CC(C)(C)C)=O)C)C=CC1F IKWXSNHOHZZEQS-UHFFFAOYSA-N 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 description 2
- 102100034354 Potassium voltage-gated channel subfamily KQT member 2 Human genes 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000006377 halopyridyl group Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- IPRVHHUKCAJSJN-UHFFFAOYSA-N n-[1-[(3,4-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=C(F)C(F)=C1 IPRVHHUKCAJSJN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- RSBQANBNDXZFIY-UHFFFAOYSA-N (3,5-dimethylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC1=CC(C)=CC(N[NH3+])=C1 RSBQANBNDXZFIY-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WUCQJZHJZJSFLU-UHFFFAOYSA-N 4,6-dimethyl-1h-indole Chemical compound CC1=CC(C)=C2C=CNC2=C1 WUCQJZHJZJSFLU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000008882 Benign Neonatal Epilepsy Diseases 0.000 description 1
- 206010067866 Benign familial neonatal convulsions Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000004703 alkoxides Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000001479 atomic absorption spectroscopy Methods 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 201000003452 benign familial neonatal epilepsy Diseases 0.000 description 1
- 201000010295 benign neonatal seizures Diseases 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 125000004212 difluorophenyl group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 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 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 229940117360 ethyl pyruvate Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000005412 pyrazyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96452607P | 2007-08-13 | 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE025928T2 true HUE025928T2 (en) | 2016-05-30 |
Family
ID=40029251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE08827266A HUE025928T2 (en) | 2007-08-13 | 2008-08-12 | Potassium channel modulator 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline derivatives |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7786146B2 (https=) |
| EP (1) | EP2190534B1 (https=) |
| JP (1) | JP2010536771A (https=) |
| KR (1) | KR20100075436A (https=) |
| CN (1) | CN101795727A (https=) |
| AU (1) | AU2008286919B2 (https=) |
| BR (1) | BRPI0815210A2 (https=) |
| CA (1) | CA2696012C (https=) |
| ES (1) | ES2531335T3 (https=) |
| HU (1) | HUE025928T2 (https=) |
| MX (1) | MX2010001712A (https=) |
| PL (1) | PL2190534T3 (https=) |
| RU (1) | RU2483060C2 (https=) |
| SG (1) | SG183725A1 (https=) |
| TW (1) | TW200927096A (https=) |
| WO (1) | WO2009023677A1 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| EP2844247A4 (en) * | 2012-04-20 | 2015-11-25 | Anderson Gaweco | ROR MODULATORS AND ITS 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 |
| WO2025231323A1 (en) * | 2024-05-03 | 2025-11-06 | Xenon Pharmaceuticals Inc. | Bicyclic heteroaryl compounds and uses thereof |
| WO2025231340A1 (en) * | 2024-05-03 | 2025-11-06 | Xenon Pharmaceuticals Inc. | Azaindole and azaindoline compounds and uses thereof |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DE3665538D1 (en) * | 1985-01-23 | 1989-10-19 | Asta Pharma Ag | Synergistic combination of flupirtin and non-steroidal anti-phlogistics |
| DE3604575A1 (de) | 1985-02-23 | 1986-08-28 | Degussa Ag, 6000 Frankfurt | Kombination von flupirtin und anticholinergisch wirkenden spasmolytika |
| EP0193056B1 (de) * | 1985-02-23 | 1989-06-07 | ASTA Pharma Aktiengesellschaft | 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 |
| IN172468B (https=) * | 1990-07-14 | 1993-08-14 | Asta Medica Ag | |
| US5643921A (en) * | 1990-09-26 | 1997-07-01 | E.R. Squibb & Sons, Inc. | Cardiopulmonary bypass and organ transplant using a potassium channel activator |
| US5234947A (en) * | 1991-11-07 | 1993-08-10 | New York University | Potassium channel activating compounds and methods of use thereof |
| DE4200259A1 (de) * | 1992-01-08 | 1993-07-15 | Asta Medica Ag | Neue 1,2,4-triaminobenzol-derivate und verfahren zu deren herstellung |
| US5262419A (en) * | 1992-06-11 | 1993-11-16 | E. R. Squibb & Sons, Inc. | Method for the prophylaxis and/or treatment of ulcerative gastrointestinal conditions using a potassium channel activator |
| CA2115792C (en) * | 1993-03-05 | 2005-11-01 | David J. Mayer | Method for the treatment of pain |
| US5428039A (en) * | 1994-02-20 | 1995-06-27 | The Center For Innovative Technology | Method for electively achieving reversible hyperpolarized cardiac arrest |
| JPH10503501A (ja) * | 1994-08-03 | 1998-03-31 | アスタ メディカ アクチエンゲゼルシャフト | 抗喘息、抗アレルギー、抗炎症及び免疫修飾作用を有するインドール、インダゾール、ピリドピロール及びピリドピラゾール誘導体 |
| JP4097285B2 (ja) * | 1994-09-22 | 2008-06-11 | リチャード・アラン・スミス | 種々の頑固な疾患の治療のための医薬の製造に有用な組成物 |
| US5679706A (en) * | 1994-09-30 | 1997-10-21 | Bristol-Myers Squibb Company | Combination of a potassium channel activator and an antiarrhythmic agent |
| WO1996019233A2 (en) * | 1994-12-12 | 1996-06-27 | Omeros Medical Systems, Inc. | Irrigation solution and method for inhibition of pain, inflammation and spasm |
| DE19539861A1 (de) * | 1995-10-26 | 1997-04-30 | Asta Medica Ag | Verwendung von 4-Amino-4-(4-fluorbenzylamino)-1-ethoxy-carbonylaminobenzen zur Prophylaxe und Behandlung der Folgen der akuten und chronischen zerebralen Minderdurchblutung sowie neurodegenerativer Erkrankungen |
| DE19701694A1 (de) * | 1997-01-20 | 1998-07-23 | Asta Medica Ag | Neue Modifikationen des 2-Amino-4-(4-fluorbenzylamino)-l-ethoxycarbonyl-aminobenzen sowie Verfahren zu ihrer Herstellung |
| US5800285A (en) * | 1997-03-19 | 1998-09-01 | Sturm, Ruger & Company, Inc. | Method of fabricating golf club parts carrying artwork etched after fabrication and parts with such artwork |
| JP2002501502A (ja) | 1997-04-25 | 2002-01-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害物質 |
| US5760007A (en) * | 1997-07-16 | 1998-06-02 | Ortho Pharmaceutical Corporation | Anticonvulsant derivatives useful in treating neuropathic pain |
| AU8561298A (en) * | 1997-08-08 | 1999-03-01 | Chugai Seiyaku Kabushiki Kaisha | Remedies for complications of diabetes |
| US6593335B1 (en) * | 1997-12-18 | 2003-07-15 | Abbott Laboratories | Potassium channel openers |
| US6265417B1 (en) * | 1997-12-18 | 2001-07-24 | Abbott Laboratories | Potassium channel openers |
| US6211171B1 (en) * | 1998-05-19 | 2001-04-03 | Dalhousie University | Use of antidepressants for local analgesia |
| JP3441970B2 (ja) | 1998-06-30 | 2003-09-02 | 株式会社サミー | 豆腐の製造方法及び製造装置 |
| BR9916162A (pt) * | 1998-12-14 | 2001-09-04 | Cellegy Pharma Inc | Composição e método para o tratamento de um distúrbio anorretal e para controlar a dor associada com o mesmo |
| US6281211B1 (en) * | 1999-02-04 | 2001-08-28 | Euro-Celtique S.A. | Substituted semicarbazides and the use thereof |
| GB9903476D0 (en) * | 1999-02-17 | 1999-04-07 | Zeneca Ltd | Therapeutic agents |
| US6451857B1 (en) * | 1999-03-10 | 2002-09-17 | Warner-Lambert Company | Analgesic compositions comprising anti-epileptic compounds and methods of using same |
| AU766648B2 (en) | 1999-03-17 | 2003-10-23 | Axys Pharmaceuticals, Inc. | Compounds and methods for modulation of estrogen receptors |
| AT409083B (de) | 1999-04-01 | 2002-05-27 | Sanochemia Pharmazeutika Ag | Pharmazeutische, tolperison enthaltende zubereitung zur oralen verabreichung |
| GB9915414D0 (en) | 1999-07-01 | 1999-09-01 | Glaxo Group Ltd | Medical use |
| PT1200073E (pt) | 1999-07-06 | 2007-03-30 | Lilly Co Eli | Antagonistas selectivos do receptor de iglur5 para o tratamento de enxaqueca |
| US6472165B1 (en) | 1999-08-03 | 2002-10-29 | Arzneimittelwerk Dresden Gmbh | Modulatory binding site in potassium channels for screening and finding new active ingredients |
| ATE380176T1 (de) * | 1999-08-04 | 2007-12-15 | Icagen Inc | Benzanilide als öffner des kaliumkanals |
| EP1200086A4 (en) * | 1999-08-04 | 2009-05-27 | Icagen Inc | THERAPEUTIC OR PROPHYLACTIC METHODS OF PAIN AND ANXIETY |
| US6495550B2 (en) * | 1999-08-04 | 2002-12-17 | Icagen, Inc. | Pyridine-substituted benzanilides as potassium ion channel openers |
| US6117900A (en) * | 1999-09-27 | 2000-09-12 | Asta Medica Aktiengesellschaft | Use of retigabine for the treatment of neuropathic pain |
| US6383511B1 (en) * | 1999-10-25 | 2002-05-07 | Epicept Corporation | Local prevention or amelioration of pain from surgically closed wounds |
| US6538004B2 (en) * | 2000-03-03 | 2003-03-25 | Abbott Laboratories | Tricyclic dihydropyrazolone and tricyclic dihydroisoxazolone potassium channel openers |
| US20020015730A1 (en) * | 2000-03-09 | 2002-02-07 | Torsten Hoffmann | Pharmaceutical formulations and method for making |
| US6348486B1 (en) * | 2000-10-17 | 2002-02-19 | American Home Products Corporation | Methods for modulating bladder function |
| US6589986B2 (en) * | 2000-12-20 | 2003-07-08 | Wyeth | Methods of treating anxiety disorders |
| US6469042B1 (en) * | 2001-02-20 | 2002-10-22 | Bristol-Myers Squibb Company | Fluoro oxindole derivatives as modulators if KCNQ potassium channels |
| US20020183395A1 (en) * | 2001-04-04 | 2002-12-05 | Wyeth | Methods for treating hyperactive gastric motility |
| GB0121214D0 (en) * | 2001-08-31 | 2001-10-24 | Btg Int Ltd | Synthetic method |
| US6831087B2 (en) * | 2001-11-09 | 2004-12-14 | Hoffmann-La Roche Inc. | Pyridine substituted isoquinoline derivatives |
| PE20030762A1 (es) * | 2001-12-18 | 2003-09-05 | Schering Corp | Compuestos heterociclicos como antagonistas nk1 |
| WO2003068769A1 (en) | 2002-02-12 | 2003-08-21 | Pfizer Inc. | Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh) |
| WO2003097586A1 (en) | 2002-05-17 | 2003-11-27 | Janssen Pharmaceutica N.V. | Aminotetralin-derived urea modulators of vanilloid vr1 receptor |
| EP1511718B1 (en) * | 2002-05-29 | 2009-05-06 | F. Hoffmann-La Roche Ag | N-acylaminobenzene dervatives as selective monoamine oxidase b inhibitors |
| WO2003106454A1 (en) | 2002-06-12 | 2003-12-24 | Orchid Chemicals & Pharmaceuticals Ltd | 1h-isoquinoline-oxazolidinone derivaties and their use as antibacterial agents |
| AUPS312602A0 (en) * | 2002-06-21 | 2002-07-18 | James Cook University | Organ arrest, protection, preservation and recovery |
| US7419981B2 (en) * | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
| US7045551B2 (en) * | 2002-11-22 | 2006-05-16 | Bristol-Myers Squibb Company | 1-aryl-2-hydroxyethyl amides as potassium channel openers |
| ATE488231T1 (de) * | 2002-12-23 | 2010-12-15 | Icagen Inc | Quinazolinone als kaliumkanalmodulatoren |
| ES2282701T3 (es) | 2002-12-27 | 2007-10-16 | H. Lundbeck A/S | Derivados de 1,2,4-triaminobenceno utiles para tratar trastornos del sistema nervioso central. |
| EP1606247A1 (en) | 2003-03-14 | 2005-12-21 | H. Lundbeck A/S | Substituted aniline derivatives |
| AR043507A1 (es) * | 2003-03-14 | 2005-08-03 | Lundbeck & Co As H | Derivados de anilina sustituidos y composiciones farmaceuticas |
| WO2004082677A1 (en) | 2003-03-21 | 2004-09-30 | H. Lundbeck A/S | Substituted p-diaminobenzene derivatives |
| MXPA05010174A (es) * | 2003-04-25 | 2005-11-08 | Lundbeck & Co As H | Derivados de indol e indolina sustituidos. |
| WO2004105795A1 (en) | 2003-05-27 | 2004-12-09 | Altana Pharma Ag | Pharmaceutical combinations of a proton pump inhibitor and a compound which modifies gastrointestinal motility |
| JP4786147B2 (ja) * | 2003-06-26 | 2011-10-05 | 武田薬品工業株式会社 | カンナビノイド受容体調節剤 |
| WO2005007628A1 (en) * | 2003-07-11 | 2005-01-27 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives as cannabinoid receptor modulators |
| JP2007505142A (ja) * | 2003-09-10 | 2007-03-08 | セダーズ−シナイ メディカル センター | 血液脳関門を通過する薬剤のカリウムチャネル媒介性送達 |
| 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 |
| DE10359335A1 (de) | 2003-10-23 | 2005-05-25 | Viatris Gmbh & Co. Kg | Kombinationen aus Kaliumkanalöffnern und Natriumkanalinhibitoren oder Natriumkanal beeinflussenden Wirkstoffen zur Behandlung von Schmerzzuständen |
| ES2235626B1 (es) | 2003-11-10 | 2006-11-01 | Almirall Prodesfarma, S.A. | Formas de administracion masticables, no comprimidas dosificadas individualmente. |
| TWI349666B (en) | 2004-03-12 | 2011-10-01 | Lundbeck & Co As H | Substituted morpholine and thiomorpholine derivatives |
| AU2005233642A1 (en) | 2004-04-13 | 2005-10-27 | Astellas Pharma Inc. | Polycyclic pyridines as potassium ion channel modulators |
| RU2006139930A (ru) * | 2004-05-03 | 2008-06-10 | Дюк Юниверсити (Сша/Сша) (Us) | Составы для содействия снижению веса |
| UA89503C2 (uk) * | 2004-09-13 | 2010-02-10 | Х. Луннбек А/С | Заміщені похідні аніліну |
| CA2589001A1 (en) | 2004-11-19 | 2006-05-26 | Kissei Pharmaceutical Co., Ltd. | Preventive or therapeutic agent for neuropathic pain |
| EP1688141A1 (en) * | 2005-01-31 | 2006-08-09 | elbion AG | The use of flupirtine for the treatment of overactive bladder and associated diseases, and for the treatment of irritable bowel syndrome |
| EP1861394A1 (en) | 2005-03-03 | 2007-12-05 | H.Lundbeck A/S | Substituted pyridine derivatives |
| KR20080043314A (ko) * | 2005-09-09 | 2008-05-16 | 하. 룬트벡 아크티에 셀스카브 | 피리미딘 유도체 및 ｋｃｎｑ 포타슘 채널 개방제로서의그의 용도 |
| US7683058B2 (en) * | 2005-09-09 | 2010-03-23 | H. Lundbeck A/S | Substituted pyrimidine derivatives |
| JP2009256208A (ja) | 2006-08-17 | 2009-11-05 | Dainippon Sumitomo Pharma Co Ltd | フタリド誘導体またはその薬学的に許容される塩 |
| SG174095A1 (en) * | 2006-08-23 | 2011-09-29 | Valeant Pharmaceuticals Int | Derivatives of 4-(n-azacycloalkyl) anilides as potassium channel modulators |
| CN101578259A (zh) * | 2006-11-28 | 2009-11-11 | 威朗国际制药公司 | 作为钾通道调节剂的1,4-二氨基双环瑞替加滨类似物 |
| JP5414540B2 (ja) * | 2007-02-23 | 2014-02-12 | オプテイカル・エア・データ・システムズ，エルエルシー | 航空機の着陸及び離陸の間の航空機の位置及び情況を決定及び表示する光学システム |
| 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 |
| 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 |
| CA2765678A1 (en) * | 2009-06-22 | 2010-12-29 | Christopher Blackburn | Substituted hydroxamic acids and uses thereof |
-
2008
- 2008-08-11 US US12/189,709 patent/US7786146B2/en not_active Expired - Fee Related
- 2008-08-12 KR KR1020107005508A patent/KR20100075436A/ko not_active Withdrawn
- 2008-08-12 WO PCT/US2008/072926 patent/WO2009023677A1/en not_active Ceased
- 2008-08-12 EP EP08827266.1A patent/EP2190534B1/en not_active Not-in-force
- 2008-08-12 BR BRPI0815210 patent/BRPI0815210A2/pt active Search and Examination
- 2008-08-12 AU AU2008286919A patent/AU2008286919B2/en not_active Ceased
- 2008-08-12 CN CN200880103296A patent/CN101795727A/zh active Pending
- 2008-08-12 HU HUE08827266A patent/HUE025928T2/en unknown
- 2008-08-12 ES ES08827266T patent/ES2531335T3/es active Active
- 2008-08-12 RU RU2010109388/04A patent/RU2483060C2/ru not_active IP Right Cessation
- 2008-08-12 SG SG2012059937A patent/SG183725A1/en unknown
- 2008-08-12 JP JP2010521125A patent/JP2010536771A/ja active Pending
- 2008-08-12 PL PL08827266T patent/PL2190534T3/pl unknown
- 2008-08-12 MX MX2010001712A patent/MX2010001712A/es active IP Right Grant
- 2008-08-12 CA CA2696012A patent/CA2696012C/en not_active Expired - Fee Related
- 2008-08-13 TW TW097130826A patent/TW200927096A/zh unknown
-
2010
- 2010-08-13 US US12/856,514 patent/US8211918B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| RU2483060C2 (ru) | 2013-05-27 |
| US8211918B2 (en) | 2012-07-03 |
| US20090137635A1 (en) | 2009-05-28 |
| KR20100075436A (ko) | 2010-07-02 |
| PL2190534T3 (pl) | 2015-11-30 |
| MX2010001712A (es) | 2010-07-28 |
| CN101795727A (zh) | 2010-08-04 |
| EP2190534A1 (en) | 2010-06-02 |
| US7786146B2 (en) | 2010-08-31 |
| EP2190534B1 (en) | 2015-02-18 |
| BRPI0815210A2 (pt) | 2015-03-31 |
| ES2531335T3 (es) | 2015-03-13 |
| CA2696012A1 (en) | 2009-02-19 |
| CA2696012C (en) | 2017-10-31 |
| WO2009023677A1 (en) | 2009-02-19 |
| SG183725A1 (en) | 2012-09-27 |
| JP2010536771A (ja) | 2010-12-02 |
| TW200927096A (en) | 2009-07-01 |
| AU2008286919B2 (en) | 2014-05-29 |
| US20110118318A1 (en) | 2011-05-19 |
| RU2010109388A (ru) | 2011-09-20 |
| AU2008286919A1 (en) | 2009-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2190534B1 (en) | Derivatives of 5-amino-4, 6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators | |
| JP2010536771A5 (https=) | ||
| EP0708101B1 (fr) | Dérivés de pipéridine utiles comme antagonistes des récepteurs des neurokinines | |
| US8299092B2 (en) | Derivatives of 2-phenyl-3-hydroxyquinoline-4(1H)-one and methods of their preparation and utilization | |
| EP2183250B1 (en) | Naphthyridine derivatives as potassium channel modulators | |
| AU655840B2 (en) | 2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents | |
| US7384969B2 (en) | N-(1H-indolyl)-1H-indole-2-carboxamide derivatives, their preparation and their therapeutic use | |
| EP0509398B1 (de) | Chinoxaline, Verfahren zu ihrer Herstellung und ihre Verwendung | |
| US20080045534A1 (en) | Derivatives of 1,3-diamino benzene as potassium channel modulators | |
| WO2014000694A1 (zh) | 苯并杂环衍生物 | |
| EP0657166A1 (de) | Kombinationspräparate, enthaltend ein Chinoxalin und ein Nukleosid | |
| KR101522803B1 (ko) | Kat ii 억제제 | |
| JPH06508378A (ja) | 新規アミドアルキル−およびイミドアルキル−ピペラジン類 | |
| JP2003192659A (ja) | フェニル尿素誘導体 | |
| JP2008523154A (ja) | ６−［（５ｓ，９ｒ）−９−（４−シアノフェニル）−３−（３，５−ジクロロフェニル）−１−メチル−２，４−ジオキソ−１，３，７−トリアザスピロ［４．４］ノン−７−イル］ニコチン酸の結晶形 | |
| JP2011528335A (ja) | 神経変性疾患の治療において用いられる複素環誘導体 | |
| CN116249691B (zh) | 双环类衍生物调节剂、其制备方法和应用 | |
| US7449459B2 (en) | Inhibitors of soluble adenylate cyclase | |
| RS20060623A (sr) | Novi piperazinski derivati dialkil oksindola | |
| US6255322B1 (en) | 2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents | |
| Marinho et al. | The reaction of o-phenylenediamine with ethoxymethylene compounds and aromatic aldehydes. | |
| US20020147230A1 (en) | Aminal Diones as potassium channel openers |