KR20100018618A - 칼륨 채널 조절제로서의 4-(ｎ-아자시클로알킬) 아닐리드의 유도체 - Google Patents
칼륨 채널 조절제로서의 4-(ｎ-아자시클로알킬) 아닐리드의 유도체 Download PDFInfo
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- KR20100018618A KR20100018618A KR1020107000706A KR20107000706A KR20100018618A KR 20100018618 A KR20100018618 A KR 20100018618A KR 1020107000706 A KR1020107000706 A KR 1020107000706A KR 20107000706 A KR20107000706 A KR 20107000706A KR 20100018618 A KR20100018618 A KR 20100018618A
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- compound
- alkyl
- cycloalkyl
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- 102000004257 Potassium Channel Human genes 0.000 title claims abstract description 13
- 108020001213 potassium channel Proteins 0.000 title claims abstract description 13
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 title 1
- 150000003931 anilides Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 315
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 6
- 208000035475 disorder Diseases 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 claims abstract description 5
- 150000002148 esters Chemical class 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 4
- 239000000651 prodrug Substances 0.000 claims abstract description 4
- 229940002612 prodrug Drugs 0.000 claims abstract description 4
- 239000003937 drug carrier Substances 0.000 claims abstract description 3
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 104
- 229910052736 halogen Inorganic materials 0.000 claims description 69
- 150000002367 halogens Chemical class 0.000 claims description 69
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 29
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 17
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000005412 pyrazyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 239000000126 substance Substances 0.000 claims 2
- 241000219098 Parthenocissus Species 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 62
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 20
- 238000003786 synthesis reaction Methods 0.000 description 20
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- -1 methoxy, methylthio Chemical group 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical group CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001412 amines Chemical group 0.000 description 6
- 229910052786 argon Inorganic materials 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
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- NBZLULAOPCARMB-UHFFFAOYSA-N 1,3-dichloro-4-phenylbut-3-en-2-one Chemical compound ClCC(=O)C(Cl)=CC1=CC=CC=C1 NBZLULAOPCARMB-UHFFFAOYSA-N 0.000 description 5
- 108091006146 Channels Proteins 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003999 initiator Substances 0.000 description 5
- 230000028161 membrane depolarization Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000005855 radiation Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- BUTKIHRNYUEGKB-UHFFFAOYSA-N 3,3-dimethylbutanoyl chloride Chemical compound CC(C)(C)CC(Cl)=O BUTKIHRNYUEGKB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010015037 epilepsy Diseases 0.000 description 4
- 125000004970 halomethyl group Chemical group 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- VURSUSFXXYBXGZ-UHFFFAOYSA-N n-[2-(3,4-dihydro-1h-isoquinolin-2-yl)-4,6-dimethoxypyrimidin-5-yl]-3,3-dimethylbutanamide Chemical compound COC1=C(NC(=O)CC(C)(C)C)C(OC)=NC(N2CC3=CC=CC=C3CC2)=N1 VURSUSFXXYBXGZ-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 0 CC(CC(*c1nc(N(CC2F)Cc3c2cccc3C)n2)=Nc1c2OC)C1CCC1 Chemical compound CC(CC(*c1nc(N(CC2F)Cc3c2cccc3C)n2)=Nc1c2OC)C1CCC1 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 238000007872 degassing Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- DGHSLOHHVSPBIK-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4,6-dimethoxypyrimidin-5-amine Chemical compound COC1=C(N)C(OC)=NC(N2CC3=CC=CC=C3CC2)=N1 DGHSLOHHVSPBIK-UHFFFAOYSA-N 0.000 description 2
- WOTVKLYMZOREFJ-UHFFFAOYSA-N 6-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=CC(C(F)(F)F)=CC=C21 WOTVKLYMZOREFJ-UHFFFAOYSA-N 0.000 description 2
- IGFFEMNFESMQQW-UHFFFAOYSA-N 6-fluoro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=CC(F)=CC=C21 IGFFEMNFESMQQW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 102100034354 Potassium voltage-gated channel subfamily KQT member 2 Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- PBOIRYABEXSZSY-UHFFFAOYSA-N n-[2,4-dimethyl-6-[2-(trifluoromethyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-6-yl]pyridin-3-yl]-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=CC(N2CC3=CN=C(N=C3CC2)C(F)(F)F)=N1 PBOIRYABEXSZSY-UHFFFAOYSA-N 0.000 description 2
- XLOPSBBUBVXOIL-UHFFFAOYSA-N n-[6-(3,4-dihydro-1h-isoquinolin-2-yl)-2,4-dimethylpyridin-3-yl]-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=CC(N2CC3=CC=CC=C3CC2)=N1 XLOPSBBUBVXOIL-UHFFFAOYSA-N 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification 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
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 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 description 1
- FSYHJEBPLDNXAM-UHFFFAOYSA-N 2,4-dimethylpyridin-3-amine Chemical compound CC1=CC=NC(C)=C1N FSYHJEBPLDNXAM-UHFFFAOYSA-N 0.000 description 1
- XSZKVKMGSAAAJZ-UHFFFAOYSA-N 2,4-dimethylpyridine-3-carboxylic acid Chemical compound CC1=CC=NC(C)=C1C(O)=O XSZKVKMGSAAAJZ-UHFFFAOYSA-N 0.000 description 1
- OZJZCCMIOZPPIT-UHFFFAOYSA-N 2-(2-methoxyethoxy)acetyl chloride Chemical compound COCCOCC(Cl)=O OZJZCCMIOZPPIT-UHFFFAOYSA-N 0.000 description 1
- CPCHRVAFINZGOY-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4,6-dimethylpyrimidin-5-amine Chemical compound CC1=C(N)C(C)=NC(N2CC3=CC=CC=C3CC2)=N1 CPCHRVAFINZGOY-UHFFFAOYSA-N 0.000 description 1
- RUEFAABHFWICOC-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4,6-dimethylpyrimidine-5-carboxylic acid Chemical compound CC1=C(C(O)=O)C(C)=NC(N2CC3=CC=CC=C3CC2)=N1 RUEFAABHFWICOC-UHFFFAOYSA-N 0.000 description 1
- RXLJXPPVVNGJCS-UHFFFAOYSA-N 2-(4,6-dimethoxy-5-nitropyrimidin-2-yl)-3,4-dihydro-1h-isoquinoline Chemical compound COC1=C([N+]([O-])=O)C(OC)=NC(N2CC3=CC=CC=C3CC2)=N1 RXLJXPPVVNGJCS-UHFFFAOYSA-N 0.000 description 1
- UOGPJRCEIZZIAO-UHFFFAOYSA-N 2-(4,6-dimethoxy-5-nitropyrimidin-2-yl)-6-(trifluoromethyl)-3,4-dihydro-1h-isoquinoline Chemical compound COC1=C([N+]([O-])=O)C(OC)=NC(N2CC3=CC=C(C=C3CC2)C(F)(F)F)=N1 UOGPJRCEIZZIAO-UHFFFAOYSA-N 0.000 description 1
- CKMCVIMYBWEVKX-UHFFFAOYSA-N 2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1NCCC2=NC(C(F)(F)F)=NC=C21 CKMCVIMYBWEVKX-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
- KUCWUAFNGCMZDB-UHFFFAOYSA-N 2-amino-3-nitrophenol Chemical compound NC1=C(O)C=CC=C1[N+]([O-])=O KUCWUAFNGCMZDB-UHFFFAOYSA-N 0.000 description 1
- FETZNGVNMWWJPO-UHFFFAOYSA-N 2-chloro-4,6-dimethoxy-5-nitropyrimidine Chemical compound COC1=NC(Cl)=NC(OC)=C1[N+]([O-])=O FETZNGVNMWWJPO-UHFFFAOYSA-N 0.000 description 1
- PBEKEFWBLFBSGQ-UHFFFAOYSA-N 2-chloro-4,6-dimethoxypyrimidine Chemical compound COC1=CC(OC)=NC(Cl)=N1 PBEKEFWBLFBSGQ-UHFFFAOYSA-N 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- YVKYZZSGAOUFGK-UHFFFAOYSA-N 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine Chemical compound C1CNCC2=CC(C(F)(F)F)=CN=C21 YVKYZZSGAOUFGK-UHFFFAOYSA-N 0.000 description 1
- PAUMLQOQTZUUGQ-UHFFFAOYSA-N 4,6-dimethoxy-2-[6-(trifluoromethyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyrimidin-5-amine Chemical compound COC1=C(N)C(OC)=NC(N2CC3=CC=C(C=C3CC2)C(F)(F)F)=N1 PAUMLQOQTZUUGQ-UHFFFAOYSA-N 0.000 description 1
- STXKJIIHKFGUCY-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical compound C1=NC=C2CNCCC2=N1 STXKJIIHKFGUCY-UHFFFAOYSA-N 0.000 description 1
- FLDDNTAAWZHAOT-UHFFFAOYSA-N 6-bromo-2,4-dimethylpyridin-3-amine Chemical compound CC1=CC(Br)=NC(C)=C1N FLDDNTAAWZHAOT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- HPGPGROIZDQSSL-UHFFFAOYSA-N CC(C)(C)CC(Nc(c(C)c1)c(C)nc1N(CC1)Cc(cc2)c1cc2F)=O Chemical compound CC(C)(C)CC(Nc(c(C)c1)c(C)nc1N(CC1)Cc(cc2)c1cc2F)=O HPGPGROIZDQSSL-UHFFFAOYSA-N 0.000 description 1
- SGEACAMHETYOIB-UHFFFAOYSA-N CC1C(C)CN(C)CC1 Chemical compound CC1C(C)CN(C)CC1 SGEACAMHETYOIB-UHFFFAOYSA-N 0.000 description 1
- REFKOFLQDAREIK-UHFFFAOYSA-N Cc(c(CC1)c2CN1c(nc1C)nc(C)c1NC(CC1CCCC1)=O)ncc2F Chemical compound Cc(c(CC1)c2CN1c(nc1C)nc(C)c1NC(CC1CCCC1)=O)ncc2F REFKOFLQDAREIK-UHFFFAOYSA-N 0.000 description 1
- CWSTZTCAUNEQAL-UHFFFAOYSA-N Cc(cc(N(CC1)Cc(cn2)c1cc2Cl)nc1C)c1NC(CC(CCN1)C1=O)=O Chemical compound Cc(cc(N(CC1)Cc(cn2)c1cc2Cl)nc1C)c1NC(CC(CCN1)C1=O)=O CWSTZTCAUNEQAL-UHFFFAOYSA-N 0.000 description 1
- YKVTYCJYCRCZDS-UHFFFAOYSA-N Cc(nc(N(CC1)Cc2c1nccc2F)nc1C)c1NC(CC1CCCC1)=O Chemical compound Cc(nc(N(CC1)Cc2c1nccc2F)nc1C)c1NC(CC1CCCC1)=O YKVTYCJYCRCZDS-UHFFFAOYSA-N 0.000 description 1
- MWNFMTXOJWLRJV-UHFFFAOYSA-N Cc1cc(CCN(C2)c(nc3C)cc(C(F)(F)F)c3NC(CC(CCO3)C3=O)=O)c2cc1 Chemical compound Cc1cc(CCN(C2)c(nc3C)cc(C(F)(F)F)c3NC(CC(CCO3)C3=O)=O)c2cc1 MWNFMTXOJWLRJV-UHFFFAOYSA-N 0.000 description 1
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- PKIAAUFRJKZATO-UHFFFAOYSA-N Cc1ccc(CF)c(CC2)c1CN2c(nc1C)nc(C)c1NC(CC1CCCC1)=O Chemical compound Cc1ccc(CF)c(CC2)c1CN2c(nc1C)nc(C)c1NC(CC1CCCC1)=O PKIAAUFRJKZATO-UHFFFAOYSA-N 0.000 description 1
- YLGBFNIRIRSORT-UHFFFAOYSA-N Cc1nc(N(CC2)Cc(c(Cl)c3)c2cc3Cl)cc(C(F)(F)F)c1NC(CC(CCN1)C1=O)=O Chemical compound Cc1nc(N(CC2)Cc(c(Cl)c3)c2cc3Cl)cc(C(F)(F)F)c1NC(CC(CCN1)C1=O)=O YLGBFNIRIRSORT-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 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
- 239000006144 Dulbecco’s modified Eagle's medium Substances 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
- 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
- 241000534944 Thia Species 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- YVYBOBCEEPIDJV-UHFFFAOYSA-N [2-amino-4-[(4-fluorophenyl)methylamino]phenyl]carbamic acid Chemical compound C1=C(NC(O)=O)C(N)=CC(NCC=2C=CC(F)=CC=2)=C1 YVYBOBCEEPIDJV-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- DIZHKKYVLBSXAW-UHFFFAOYSA-N ethyl 2,4-dimethylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)C=CN=C1C DIZHKKYVLBSXAW-UHFFFAOYSA-N 0.000 description 1
- TYHAINZSDRJUNN-UHFFFAOYSA-N ethyl 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4,6-dimethylpyrimidine-5-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=C(C)N=C1N1CC2=CC=CC=C2CC1 TYHAINZSDRJUNN-UHFFFAOYSA-N 0.000 description 1
- YMCDYRGMTRCAPZ-UHFFFAOYSA-N ethyl 2-acetyl-3-oxobutanoate Chemical compound CCOC(=O)C(C(C)=O)C(C)=O YMCDYRGMTRCAPZ-UHFFFAOYSA-N 0.000 description 1
- QWWCHVHQVYFMJU-UHFFFAOYSA-N ethyl 2-chloro-4,6-dimethylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(Cl)N=C1C QWWCHVHQVYFMJU-UHFFFAOYSA-N 0.000 description 1
- KJWOQDPSBKFTPF-UHFFFAOYSA-N ethyl 4,6-dimethyl-2-oxo-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(O)N=C1C KJWOQDPSBKFTPF-UHFFFAOYSA-N 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration 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
- 239000008187 granular material Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- UCXZIVSAIVTKNT-UHFFFAOYSA-N n-(6-bromo-2,4-dimethylpyridin-3-yl)-2-(2-methoxyethoxy)acetamide Chemical compound COCCOCC(=O)NC1=C(C)C=C(Br)N=C1C UCXZIVSAIVTKNT-UHFFFAOYSA-N 0.000 description 1
- ANOAORXOYSFENG-UHFFFAOYSA-N n-(6-bromo-2,4-dimethylpyridin-3-yl)-3,3-dimethylbutanamide Chemical compound CC1=CC(Br)=NC(C)=C1NC(=O)CC(C)(C)C ANOAORXOYSFENG-UHFFFAOYSA-N 0.000 description 1
- GBFYNQFQYQWOSP-UHFFFAOYSA-N n-[2,4-dimethyl-6-[6-(trifluoromethyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridin-3-yl]-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=CC(N2CC3=CC=C(C=C3CC2)C(F)(F)F)=N1 GBFYNQFQYQWOSP-UHFFFAOYSA-N 0.000 description 1
- OOLWEKXOJCPGBH-UHFFFAOYSA-N n-[2,4-dimethyl-6-[7-(trifluoromethyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyridin-3-yl]-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=CC(N2CC3=CC(=CC=C3CC2)C(F)(F)F)=N1 OOLWEKXOJCPGBH-UHFFFAOYSA-N 0.000 description 1
- PWQDNLQJTIZBLA-UHFFFAOYSA-N n-[2-(3,4-dihydro-1h-isoquinolin-2-yl)-4,6-dimethylpyrimidin-5-yl]-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=NC(N2CC3=CC=CC=C3CC2)=N1 PWQDNLQJTIZBLA-UHFFFAOYSA-N 0.000 description 1
- MWLAWFJNXCNHPL-UHFFFAOYSA-N n-[4,6-dimethoxy-2-[6-(trifluoromethyl)-3,4-dihydro-1h-isoquinolin-2-yl]pyrimidin-5-yl]-3,3-dimethylbutanamide Chemical compound COC1=C(NC(=O)CC(C)(C)C)C(OC)=NC(N2CC3=CC=C(C=C3CC2)C(F)(F)F)=N1 MWLAWFJNXCNHPL-UHFFFAOYSA-N 0.000 description 1
- HGFNQMVYAFROEK-UHFFFAOYSA-N n-[6-(7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-6-yl)-2,4-dimethylpyridin-3-yl]-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=CC(N2CC3=CN=CN=C3CC2)=N1 HGFNQMVYAFROEK-UHFFFAOYSA-N 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 125000006413 ring segment Chemical group 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
- 229960005322 streptomycin Drugs 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
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| US93439607P | 2007-06-13 | 2007-06-13 | |
| US60/934,396 | 2007-06-13 | ||
| US12/138,251 US8367684B2 (en) | 2007-06-13 | 2008-06-12 | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
| US12/138,251 | 2008-06-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20100018618A true KR20100018618A (ko) | 2010-02-17 |
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| KR1020107000706A Withdrawn KR20100018618A (ko) | 2007-06-13 | 2008-06-13 | 칼륨 채널 조절제로서의 4-(ｎ-아자시클로알킬) 아닐리드의 유도체 |
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| Country | Link |
|---|---|
| US (1) | US8367684B2 (enExample) |
| EP (1) | EP2170861B1 (enExample) |
| JP (1) | JP2010530002A (enExample) |
| KR (1) | KR20100018618A (enExample) |
| CN (1) | CN101868451A (enExample) |
| AU (1) | AU2008266009B2 (enExample) |
| BR (1) | BRPI0812564A2 (enExample) |
| CA (1) | CA2689208A1 (enExample) |
| DK (1) | DK2170861T3 (enExample) |
| ES (1) | ES2392774T3 (enExample) |
| HR (1) | HRP20120857T1 (enExample) |
| MX (1) | MX2009013581A (enExample) |
| PL (1) | PL2170861T3 (enExample) |
| PT (1) | PT2170861E (enExample) |
| RU (1) | RU2010100893A (enExample) |
| SI (1) | SI2170861T1 (enExample) |
| TW (1) | TW200914452A (enExample) |
| WO (1) | WO2008157404A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO2010122064A1 (en) | 2009-04-21 | 2010-10-28 | Neurosearch A/S | Substituted naphthyridine derivatives and their medical use |
| EP2590961A1 (en) | 2010-07-08 | 2013-05-15 | Pfizer Inc | Piperidinyl pyrimidine amides as kv7 potassium channel openers |
| RU2014144951A (ru) | 2012-04-10 | 2016-06-10 | Сумитомо Дайниппон Фарма Ко., Лтд. | Новое 1-замещенное производное индазола |
| CN108250128A (zh) * | 2012-09-27 | 2018-07-06 | 江苏先声药业有限公司 | 作为钾通道调节剂的化合物 |
| WO2017004791A1 (en) | 2015-07-07 | 2017-01-12 | Colgate-Palmolive Company | Oral care implement and monofilament bristle for use with the same |
| CN110511220B (zh) | 2018-05-22 | 2022-04-01 | 上海挚盟医药科技有限公司 | 作为钾通道调节剂的对二氨基苯衍生物、其制备方法及其在医药上的应用 |
| WO2023125935A1 (zh) * | 2021-12-31 | 2023-07-06 | 上海翰森生物医药科技有限公司 | 苯并哌啶衍生物调节剂、其制备方法和应用 |
| CN116535353A (zh) * | 2022-01-25 | 2023-08-04 | 上海挚盟医药科技有限公司 | 作为钾通道调节剂的酰胺类化合物及其制备和应用 |
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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 |
| ATE46265T1 (de) | 1985-01-23 | 1989-09-15 | Asta Pharma Ag | 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 |
| IN172468B (enExample) | 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 |
| US5965582A (en) * | 1994-08-03 | 1999-10-12 | Asta Medica Aktiengesellschaft | N-benzylindole and benzopyrazole derivatives with anti-asthmatic, anti-allergic, anti-inflammatory and immunemodulating effect |
| WO1996009044A1 (en) | 1994-09-22 | 1996-03-28 | Richard Alan Smith | Compositions useful for the preparation of medicines for treating a variety of intractable disorders |
| US5679706A (en) | 1994-09-30 | 1997-10-21 | Bristol-Myers Squibb Company | Combination of a potassium channel activator and an antiarrhythmic agent |
| MX9703988A (es) | 1994-12-12 | 1998-02-28 | Omeros Med Sys Inc | SOLUCIaN Y MÉTODO DE IRRIGACIaN PARA LA INHIBICIaN DEL DOLOR, LA INFLAMACIaN Y ES ESPASMO. |
| 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 |
| IN188411B (enExample) * | 1997-03-27 | 2002-09-21 | Yuhan Corp | |
| US5760007A (en) | 1997-07-16 | 1998-06-02 | Ortho Pharmaceutical Corporation | Anticonvulsant derivatives useful in treating neuropathic pain |
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-
2008
- 2008-06-12 US US12/138,251 patent/US8367684B2/en active Active
- 2008-06-13 KR KR1020107000706A patent/KR20100018618A/ko not_active Withdrawn
- 2008-06-13 PT PT08771077T patent/PT2170861E/pt unknown
- 2008-06-13 CN CN200880102338A patent/CN101868451A/zh active Pending
- 2008-06-13 SI SI200830745T patent/SI2170861T1/sl unknown
- 2008-06-13 CA CA002689208A patent/CA2689208A1/en not_active Abandoned
- 2008-06-13 BR BRPI0812564-3A2A patent/BRPI0812564A2/pt not_active Application Discontinuation
- 2008-06-13 HR HRP20120857AT patent/HRP20120857T1/hr unknown
- 2008-06-13 DK DK08771077.8T patent/DK2170861T3/da active
- 2008-06-13 ES ES08771077T patent/ES2392774T3/es active Active
- 2008-06-13 EP EP08771077A patent/EP2170861B1/en not_active Not-in-force
- 2008-06-13 JP JP2010512399A patent/JP2010530002A/ja active Pending
- 2008-06-13 MX MX2009013581A patent/MX2009013581A/es active IP Right Grant
- 2008-06-13 AU AU2008266009A patent/AU2008266009B2/en not_active Ceased
- 2008-06-13 RU RU2010100893/04A patent/RU2010100893A/ru not_active Application Discontinuation
- 2008-06-13 WO PCT/US2008/066984 patent/WO2008157404A2/en not_active Ceased
- 2008-06-13 PL PL08771077T patent/PL2170861T3/pl unknown
- 2008-06-13 TW TW097122339A patent/TW200914452A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SI2170861T1 (sl) | 2012-12-31 |
| PL2170861T3 (pl) | 2013-01-31 |
| TW200914452A (en) | 2009-04-01 |
| US20080318979A1 (en) | 2008-12-25 |
| JP2010530002A (ja) | 2010-09-02 |
| CA2689208A1 (en) | 2008-12-24 |
| PT2170861E (pt) | 2012-09-06 |
| AU2008266009A1 (en) | 2008-12-24 |
| RU2010100893A (ru) | 2011-07-20 |
| WO2008157404A3 (en) | 2009-02-19 |
| ES2392774T3 (es) | 2012-12-13 |
| DK2170861T3 (da) | 2012-11-26 |
| BRPI0812564A2 (pt) | 2015-02-10 |
| EP2170861A2 (en) | 2010-04-07 |
| US8367684B2 (en) | 2013-02-05 |
| AU2008266009B2 (en) | 2013-06-06 |
| WO2008157404A2 (en) | 2008-12-24 |
| CN101868451A (zh) | 2010-10-20 |
| HRP20120857T1 (hr) | 2012-11-30 |
| MX2009013581A (es) | 2010-01-26 |
| EP2170861B1 (en) | 2012-08-29 |
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