JP2015535252A - 電位作動型ナトリウムチャネルにおいて選択的活性を有するn−置換インダゾールスルホンアミド化合物 - Google Patents
電位作動型ナトリウムチャネルにおいて選択的活性を有するn−置換インダゾールスルホンアミド化合物 Download PDFInfo
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- JP2015535252A JP2015535252A JP2015539755A JP2015539755A JP2015535252A JP 2015535252 A JP2015535252 A JP 2015535252A JP 2015539755 A JP2015539755 A JP 2015539755A JP 2015539755 A JP2015539755 A JP 2015539755A JP 2015535252 A JP2015535252 A JP 2015535252A
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- Prior art keywords
- indazole
- sulfonamide
- fluoro
- alkyl
- ethyl
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- -1 N-substituted indazolesulfonamide compounds Chemical class 0.000 title claims description 84
- 230000000694 effects Effects 0.000 title description 33
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 title description 4
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 186
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 35
- 208000004296 neuralgia Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 15
- 208000035475 disorder Diseases 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 91
- 125000001424 substituent group Chemical group 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 125000001072 heteroaryl group Chemical group 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000006413 ring segment Chemical group 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 16
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- GKUPWDSSECKUDV-UHFFFAOYSA-N 6-fluoro-1-(1,2,3,4-tetrahydroisoquinolin-8-ylmethyl)-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound FC1=CC=2N(CC=3C=4CNCCC=4C=CC=3)N=CC=2C=C1S(=O)(=O)NC1=NC=NS1 GKUPWDSSECKUDV-UHFFFAOYSA-N 0.000 claims description 7
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 6
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 6
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 6
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- XCWJYPNQTOFDRK-ZZXKWVIFSA-N 1-[[2-[(e)-3-aminoprop-1-enyl]phenyl]methyl]-6-fluoro-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound NC\C=C\C1=CC=CC=C1CN1C2=CC(F)=C(S(=O)(=O)NC=3SN=CN=3)C=C2C=N1 XCWJYPNQTOFDRK-ZZXKWVIFSA-N 0.000 claims description 5
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 5
- CSCJDGKSKWJIBP-MRXNPFEDSA-N n-(6-fluoropyridin-2-yl)-6-methyl-1-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]indazole-5-sulfonamide Chemical compound CC=1C=C2N([C@@H](C=3C=4CNCCC=4C=CC=3)C)N=CC2=CC=1S(=O)(=O)NC1=CC=CC(F)=N1 CSCJDGKSKWJIBP-MRXNPFEDSA-N 0.000 claims description 5
- 125000005021 aminoalkenyl group Chemical group 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- YFNMRKXDKJUPQG-UHFFFAOYSA-N 2-[(7-amino-5,6,7,8-tetrahydronaphthalen-1-yl)methyl]-n-(5-chloro-1,3-thiazol-2-yl)-6-fluoroindazole-5-sulfonamide Chemical compound C=12CC(N)CCC2=CC=CC=1CN(N=C1C=C2F)C=C1C=C2S(=O)(=O)NC1=NC=C(Cl)S1 YFNMRKXDKJUPQG-UHFFFAOYSA-N 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims 5
- HLIFNQCITGTXJX-DRMXPCRNSA-N 1-[(1r)-1-[2-[2-[(1r,2r)-2-aminocyclohexyl]ethynyl]phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2N=C(F)C=CC=2)=CC=CC=C1C#C[C@H]1CCCC[C@H]1N HLIFNQCITGTXJX-DRMXPCRNSA-N 0.000 claims 3
- CAIALQMFYYGXBJ-OAHLLOKOSA-N 1-[(1r)-1-[2-(3-aminopropyl)phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2N=C(F)C=CC=2)=CC=CC=C1CCCN CAIALQMFYYGXBJ-OAHLLOKOSA-N 0.000 claims 2
- WCWKMFXFWHIFGR-CQSZACIVSA-N 1-[(1r)-1-[2-(azetidin-3-yl)phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2N=C(F)C=CC=2)=CC=CC=C1C1CNC1 WCWKMFXFWHIFGR-CQSZACIVSA-N 0.000 claims 2
- HLIFNQCITGTXJX-WWEVIYMKSA-N 1-[(1r)-1-[2-[2-[(1s,2s)-2-aminocyclohexyl]ethynyl]phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2N=C(F)C=CC=2)=CC=CC=C1C#C[C@@H]1CCCC[C@@H]1N HLIFNQCITGTXJX-WWEVIYMKSA-N 0.000 claims 2
- HLIFNQCITGTXJX-UHFFFAOYSA-N 1-[1-[2-[2-(2-aminocyclohexyl)ethynyl]phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound N1=CC2=CC(S(=O)(=O)NC=3N=C(F)C=CC=3)=C(F)C=C2N1C(C)C1=CC=CC=C1C#CC1CCCCC1N HLIFNQCITGTXJX-UHFFFAOYSA-N 0.000 claims 2
- DBZJNIHBDORRII-OAHLLOKOSA-N 1-[[(7r)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-6-fluoro-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound C([C@H](CC1=2)N)CC1=CC=CC=2CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=NS1 DBZJNIHBDORRII-OAHLLOKOSA-N 0.000 claims 2
- RHZYYEZFTCJSBE-GFCCVEGCSA-N 6-fluoro-1-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound FC=1C=C2N([C@@H](C=3C=4CNCCC=4C=CC=3)C)N=CC2=CC=1S(=O)(=O)NC1=NC=NS1 RHZYYEZFTCJSBE-GFCCVEGCSA-N 0.000 claims 2
- YCZYLEYBYBXZRB-CYBMUJFWSA-N 6-fluoro-1-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]-n-(1,3-thiazol-2-yl)indazole-5-sulfonamide Chemical compound FC=1C=C2N([C@@H](C=3C=4CNCCC=4C=CC=3)C)N=CC2=CC=1S(=O)(=O)NC1=NC=CS1 YCZYLEYBYBXZRB-CYBMUJFWSA-N 0.000 claims 2
- ZQLOTXCADLUPOP-LLVKDONJSA-N 6-fluoro-1-[(1r)-1-phenylethyl]-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2SN=CN=2)=CC=CC=C1 ZQLOTXCADLUPOP-LLVKDONJSA-N 0.000 claims 2
- MTXZEXIUQKVXSK-CQSZACIVSA-N 6-fluoro-n-(5-fluoropyridin-2-yl)-1-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]indazole-5-sulfonamide Chemical compound FC=1C=C2N([C@@H](C=3C=4CNCCC=4C=CC=3)C)N=CC2=CC=1S(=O)(=O)NC1=CC=C(F)C=N1 MTXZEXIUQKVXSK-CQSZACIVSA-N 0.000 claims 2
- BDXVDLWUWAYQKL-CQSZACIVSA-N 6-fluoro-n-(6-fluoropyridin-2-yl)-1-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]indazole-5-sulfonamide Chemical compound FC=1C=C2N([C@@H](C=3C=4CNCCC=4C=CC=3)C)N=CC2=CC=1S(=O)(=O)NC1=CC=CC(F)=N1 BDXVDLWUWAYQKL-CQSZACIVSA-N 0.000 claims 2
- QMJIVIHONRHYGL-MRXNPFEDSA-N 6-fluoro-n-(6-fluoropyridin-2-yl)-1-[(1r)-1-(2-piperidin-4-ylphenyl)ethyl]indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2N=C(F)C=CC=2)=CC=CC=C1C1CCNCC1 QMJIVIHONRHYGL-MRXNPFEDSA-N 0.000 claims 2
- SRBXSJAKGQJETP-MRXNPFEDSA-N 6-fluoro-n-(6-fluoropyridin-2-yl)-1-[(1r)-1-[2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]ethyl]indazole-5-sulfonamide Chemical compound C1([C@@H](C)N2C3=CC(F)=C(C=C3C=N2)S(=O)(=O)NC=2N=C(F)C=CC=2)=CC=CC=C1C1=CCNCC1 SRBXSJAKGQJETP-MRXNPFEDSA-N 0.000 claims 2
- KVCFFRVMHFWXRQ-GFCCVEGCSA-N n-(5-chloro-1,3-thiazol-2-yl)-6-fluoro-1-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]indazole-5-sulfonamide Chemical compound FC=1C=C2N([C@@H](C=3C=4CNCCC=4C=CC=3)C)N=CC2=CC=1S(=O)(=O)NC1=NC=C(Cl)S1 KVCFFRVMHFWXRQ-GFCCVEGCSA-N 0.000 claims 2
- JXVAEAWLORTHQW-GFCCVEGCSA-N n-(5-chloro-1,3-thiazol-2-yl)-6-fluoro-2-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]indazole-5-sulfonamide Chemical compound FC1=CC2=NN([C@@H](C=3C=4CNCCC=4C=CC=3)C)C=C2C=C1S(=O)(=O)NC1=NC=C(Cl)S1 JXVAEAWLORTHQW-GFCCVEGCSA-N 0.000 claims 2
- BJAWBFPYZRHYLC-UHFFFAOYSA-N 1-(2,3-dihydro-1h-isoindol-4-ylmethyl)-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound FC1=CC=CC(NS(=O)(=O)C=2C(=CC=3N(CC=4C=5CNCC=5C=CC=4)N=CC=3C=2)F)=N1 BJAWBFPYZRHYLC-UHFFFAOYSA-N 0.000 claims 1
- AYFXUDMBPRBAPJ-UHFFFAOYSA-N 1-[(2-amino-2,3-dihydro-1h-inden-4-yl)methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C=12CC(N)CC2=CC=CC=1CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=CC=CC(F)=N1 AYFXUDMBPRBAPJ-UHFFFAOYSA-N 0.000 claims 1
- DBZJNIHBDORRII-UHFFFAOYSA-N 1-[(7-amino-5,6,7,8-tetrahydronaphthalen-1-yl)methyl]-6-fluoro-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound C=12CC(N)CCC2=CC=CC=1CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=NS1 DBZJNIHBDORRII-UHFFFAOYSA-N 0.000 claims 1
- UKZBXRYSYXZVOR-UHFFFAOYSA-N 1-[(7-amino-5,6,7,8-tetrahydronaphthalen-1-yl)methyl]-6-fluoro-n-(1,3-thiazol-2-yl)indazole-5-sulfonamide Chemical compound C=12CC(N)CCC2=CC=CC=1CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=CS1 UKZBXRYSYXZVOR-UHFFFAOYSA-N 0.000 claims 1
- GQZRFXWUYDBETK-UHFFFAOYSA-N 1-[(7-amino-5,6,7,8-tetrahydronaphthalen-1-yl)methyl]-6-methyl-n-(1,3-thiazol-2-yl)indazole-5-sulfonamide Chemical compound CC1=CC=2N(CC=3C=4CC(N)CCC=4C=CC=3)N=CC=2C=C1S(=O)(=O)NC1=NC=CS1 GQZRFXWUYDBETK-UHFFFAOYSA-N 0.000 claims 1
- PXUKNVBPQYBNED-UHFFFAOYSA-N 1-[(7-amino-5,6,7,8-tetrahydronaphthalen-1-yl)methyl]-n-(5-chloro-1,3-thiazol-2-yl)-6-fluoroindazole-5-sulfonamide Chemical compound C=12CC(N)CCC2=CC=CC=1CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=C(Cl)S1 PXUKNVBPQYBNED-UHFFFAOYSA-N 0.000 claims 1
- CAIALQMFYYGXBJ-UHFFFAOYSA-N 1-[1-[2-(3-aminopropyl)phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound N1=CC2=CC(S(=O)(=O)NC=3N=C(F)C=CC=3)=C(F)C=C2N1C(C)C1=CC=CC=C1CCCN CAIALQMFYYGXBJ-UHFFFAOYSA-N 0.000 claims 1
- WCWKMFXFWHIFGR-UHFFFAOYSA-N 1-[1-[2-(azetidin-3-yl)phenyl]ethyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound N1=CC2=CC(S(=O)(=O)NC=3N=C(F)C=CC=3)=C(F)C=C2N1C(C)C1=CC=CC=C1C1CNC1 WCWKMFXFWHIFGR-UHFFFAOYSA-N 0.000 claims 1
- UKZBXRYSYXZVOR-MRXNPFEDSA-N 1-[[(7r)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-6-fluoro-n-(1,3-thiazol-2-yl)indazole-5-sulfonamide Chemical compound C([C@H](CC1=2)N)CC1=CC=CC=2CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=CS1 UKZBXRYSYXZVOR-MRXNPFEDSA-N 0.000 claims 1
- MNUGLDCSCOZYSQ-QGZVFWFLSA-N 1-[[(7r)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C([C@H](CC1=2)N)CC1=CC=CC=2CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=CC=CC(F)=N1 MNUGLDCSCOZYSQ-QGZVFWFLSA-N 0.000 claims 1
- DBZJNIHBDORRII-HNNXBMFYSA-N 1-[[(7s)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-6-fluoro-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound C([C@@H](CC1=2)N)CC1=CC=CC=2CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=NS1 DBZJNIHBDORRII-HNNXBMFYSA-N 0.000 claims 1
- UKZBXRYSYXZVOR-INIZCTEOSA-N 1-[[(7s)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-6-fluoro-n-(1,3-thiazol-2-yl)indazole-5-sulfonamide Chemical compound C([C@@H](CC1=2)N)CC1=CC=CC=2CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=NC=CS1 UKZBXRYSYXZVOR-INIZCTEOSA-N 0.000 claims 1
- MNUGLDCSCOZYSQ-KRWDZBQOSA-N 1-[[(7s)-7-amino-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound C([C@@H](CC1=2)N)CC1=CC=CC=2CN(C1=CC=2F)N=CC1=CC=2S(=O)(=O)NC1=CC=CC(F)=N1 MNUGLDCSCOZYSQ-KRWDZBQOSA-N 0.000 claims 1
- HCYBVAJMNZELNV-UHFFFAOYSA-N 1-[[2-(1,2,3,4-tetrahydroisoquinolin-5-yl)phenyl]methyl]-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound C=1C=C2N(CC=3C(=CC=CC=3)C=3C=4CCNCC=4C=CC=3)N=CC2=CC=1S(=O)(=O)NC1=NC=NS1 HCYBVAJMNZELNV-UHFFFAOYSA-N 0.000 claims 1
- KPEIQQYVHAGHIA-UHFFFAOYSA-N 1-[[2-(2,3,4,7-tetrahydro-1h-azepin-5-yl)phenyl]methyl]-n-(1,2,4-thiadiazol-5-yl)indazole-5-sulfonamide Chemical compound C=1C=C2N(CC=3C(=CC=CC=3)C=3CCCNCC=3)N=CC2=CC=1S(=O)(=O)NC1=NC=NS1 KPEIQQYVHAGHIA-UHFFFAOYSA-N 0.000 claims 1
- IZQQSZDILYAADY-UHFFFAOYSA-N 1-[[2-(2-amino-1-fluoroethyl)phenyl]methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound NCC(F)C1=CC=CC=C1CN1C2=CC(F)=C(S(=O)(=O)NC=3N=C(F)C=CC=3)C=C2C=N1 IZQQSZDILYAADY-UHFFFAOYSA-N 0.000 claims 1
- KJXORRSVLNZSBG-UHFFFAOYSA-N 1-[[2-(2-aminoethyl)phenyl]methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound NCCC1=CC=CC=C1CN1C2=CC(F)=C(S(=O)(=O)NC=3N=C(F)C=CC=3)C=C2C=N1 KJXORRSVLNZSBG-UHFFFAOYSA-N 0.000 claims 1
- DJUDLAQQIDCWFL-UHFFFAOYSA-N 1-[[2-(3-aminoprop-1-ynyl)phenyl]methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound NCC#CC1=CC=CC=C1CN1C2=CC(F)=C(S(=O)(=O)NC=3N=C(F)C=CC=3)C=C2C=N1 DJUDLAQQIDCWFL-UHFFFAOYSA-N 0.000 claims 1
- DTUSTJJVJJTMGW-UHFFFAOYSA-N 1-[[2-(3-aminopropyl)phenyl]methyl]-6-fluoro-n-(1,3-thiazol-2-yl)indazole-5-sulfonamide Chemical compound NCCCC1=CC=CC=C1CN1C2=CC(F)=C(S(=O)(=O)NC=3SC=CN=3)C=C2C=N1 DTUSTJJVJJTMGW-UHFFFAOYSA-N 0.000 claims 1
- IOCLELURYWJHAP-UHFFFAOYSA-N 1-[[2-(3-aminopropyl)phenyl]methyl]-6-fluoro-n-(6-fluoropyridin-2-yl)indazole-5-sulfonamide Chemical compound NCCCC1=CC=CC=C1CN1C2=CC(F)=C(S(=O)(=O)NC=3N=C(F)C=CC=3)C=C2C=N1 IOCLELURYWJHAP-UHFFFAOYSA-N 0.000 claims 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
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- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
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- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D471/08—Bridged systems
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
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US201261719118P | 2012-10-26 | 2012-10-26 | |
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PCT/US2013/066360 WO2014066491A1 (en) | 2012-10-26 | 2013-10-23 | N-substituted indazole sulfonamide compounds with selective activity in voltage-gated sodium channels |
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JP2015535252A true JP2015535252A (ja) | 2015-12-10 |
JP2015535252A5 JP2015535252A5 (US07794700-20100914-C00152.png) | 2016-12-08 |
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JP2015539755A Pending JP2015535252A (ja) | 2012-10-26 | 2013-10-23 | 電位作動型ナトリウムチャネルにおいて選択的活性を有するn−置換インダゾールスルホンアミド化合物 |
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RU2014121983A (ru) | 2011-10-31 | 2015-12-10 | Ксенон Фармасьютикалз Инк. | Биарильные простоэфирные сульфонамиды и их применение в качестве терапевтических средств |
US9630929B2 (en) | 2011-10-31 | 2017-04-25 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
US8952169B2 (en) | 2012-05-22 | 2015-02-10 | Xenon Pharmaceuticals Inc. | N-substituted benzamides and methods of use thereof |
EP2870138B1 (en) | 2012-07-06 | 2018-08-22 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
CA2898679A1 (en) | 2013-03-14 | 2014-09-25 | Xenon Pharmaceuticals Inc. | Substituted triazolopyridines and methods of use thereof |
EP2970156B1 (en) | 2013-03-15 | 2018-07-25 | Genentech, Inc. | Substituted benzoxazoles and methods of use thereof |
CN105793238B (zh) | 2013-11-27 | 2019-12-24 | 基因泰克公司 | 经取代的苯甲酰胺及其使用方法 |
US10005724B2 (en) | 2014-07-07 | 2018-06-26 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US9783527B2 (en) * | 2014-09-16 | 2017-10-10 | Abbvie Inc. | Indazole ureas and method of use |
JP2018507900A (ja) * | 2015-03-13 | 2018-03-22 | アッヴィ・インコーポレイテッド | (インダゾール−4−イル)ヘキサヒドロピロロピロロン及び使用方法 |
MX2017014715A (es) | 2015-05-22 | 2018-03-16 | Genentech Inc | Benzamidas sustituidas y metodos para utilizarlas. |
WO2017035271A1 (en) | 2015-08-27 | 2017-03-02 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
EP3356360A1 (en) | 2015-09-28 | 2018-08-08 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10899732B2 (en) | 2015-11-25 | 2021-01-26 | Genentech, Inc. | Substituted benzamides useful as sodium channel blockers |
TW201726637A (zh) | 2015-12-18 | 2017-08-01 | 默沙東藥廠 | 對電位閘控鈉通道具選擇活性之羥基烷基胺-及羥基環烷基胺-取代之二胺-芳基磺胺化合物 |
CN109071426A (zh) | 2016-03-30 | 2018-12-21 | 基因泰克公司 | 取代的苯甲酰胺及其使用方法 |
JP6938545B2 (ja) | 2016-05-20 | 2021-09-22 | ゼノン・ファーマシューティカルズ・インコーポレイテッドXenon Pharmaceuticals Inc. | ベンゼンスルホンアミド化合物および治療剤としてのそれらの使用 |
RU2019114964A (ru) | 2016-10-17 | 2020-11-17 | Дженентек, Инк. | Терапевтические средства и способы их применения |
KR20190086772A (ko) | 2016-12-09 | 2019-07-23 | 제논 파마슈티칼스 인크. | 벤젠술폰아미드 화합물 및 치료제로서의 그의 용도 |
JP2020511511A (ja) | 2017-03-24 | 2020-04-16 | ジェネンテック, インコーポレイテッド | ナトリウムチャネル阻害剤としての4−ピペリジン−n−(ピリミジン−4−イル)クロマン−7−スルホンアミド誘導体 |
CN107247885B (zh) * | 2017-07-06 | 2020-07-03 | 中国水产科学研究院黄海水产研究所 | 一种电压-门控钠离子通道的结构预测方法 |
US11028075B2 (en) | 2018-02-26 | 2021-06-08 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
EP3774801A1 (en) | 2018-03-30 | 2021-02-17 | F. Hoffmann-La Roche AG | Fused ring hydro-pyrido compounds as sodium channel inhibitors |
WO2019241533A1 (en) | 2018-06-13 | 2019-12-19 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
US10752623B2 (en) | 2018-08-31 | 2020-08-25 | Xenon Pharmaceuticals Inc. | Heteroaryl-substituted sulfonamide compounds and their use as sodium channel inhibitors |
EP3844150A1 (en) | 2018-08-31 | 2021-07-07 | Xenon Pharmaceuticals Inc. | Heteroaryl-substituted sulfonamide compounds and their use as therapeutic agents |
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- 2013-10-23 KR KR1020157013297A patent/KR20150074123A/ko not_active Application Discontinuation
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EP2911663A1 (en) | 2015-09-02 |
EP2911663B1 (en) | 2020-03-18 |
US9388179B2 (en) | 2016-07-12 |
AU2013334664A1 (en) | 2015-05-07 |
CA2891056A1 (en) | 2014-05-01 |
KR20150074123A (ko) | 2015-07-01 |
WO2014066491A1 (en) | 2014-05-01 |
US20150284389A1 (en) | 2015-10-08 |
CN104869992A (zh) | 2015-08-26 |
RU2015119640A (ru) | 2016-12-20 |
BR112015008987A2 (pt) | 2017-07-04 |
EP2911663A4 (en) | 2016-04-13 |
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