CA2853439A1 - Benzenesulfonamide compounds and their use as therapeutic agents - Google Patents
Benzenesulfonamide compounds and their use as therapeutic agents Download PDFInfo
- Publication number
- CA2853439A1 CA2853439A1 CA2853439A CA2853439A CA2853439A1 CA 2853439 A1 CA2853439 A1 CA 2853439A1 CA 2853439 A CA2853439 A CA 2853439A CA 2853439 A CA2853439 A CA 2853439A CA 2853439 A1 CA2853439 A1 CA 2853439A1
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- Prior art keywords
- optionally substituted
- haloalkyl
- alkyl
- independently hydrogen
- halo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 239000003814 drug Substances 0.000 title description 31
- 229940124597 therapeutic agent Drugs 0.000 title description 13
- 150000008331 benzenesulfonamides Chemical class 0.000 title description 4
- 208000002193 Pain Diseases 0.000 claims abstract description 127
- 230000036407 pain Effects 0.000 claims abstract description 119
- 239000000203 mixture Substances 0.000 claims abstract description 110
- 150000003839 salts Chemical class 0.000 claims abstract description 86
- 229940002612 prodrug Drugs 0.000 claims abstract description 82
- 239000000651 prodrug Substances 0.000 claims abstract description 82
- -1 as stereoisomers Chemical class 0.000 claims abstract description 80
- 102000018674 Sodium Channels Human genes 0.000 claims abstract description 77
- 108010052164 Sodium Channels Proteins 0.000 claims abstract description 77
- 239000012453 solvate Substances 0.000 claims abstract description 72
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 58
- 201000010099 disease Diseases 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 41
- 230000001404 mediated effect Effects 0.000 claims abstract description 27
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 485
- 239000001257 hydrogen Substances 0.000 claims description 485
- 125000001188 haloalkyl group Chemical group 0.000 claims description 411
- 125000000217 alkyl group Chemical group 0.000 claims description 363
- 150000001875 compounds Chemical class 0.000 claims description 344
- 125000005843 halogen group Chemical group 0.000 claims description 299
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 276
- 125000001072 heteroaryl group Chemical group 0.000 claims description 144
- 125000000623 heterocyclic group Chemical group 0.000 claims description 143
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 137
- 125000003107 substituted aryl group Chemical group 0.000 claims description 105
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 88
- 238000000034 method Methods 0.000 claims description 86
- 241000124008 Mammalia Species 0.000 claims description 81
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 74
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 73
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 73
- 239000008194 pharmaceutical composition Substances 0.000 claims description 61
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 59
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 51
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 50
- 125000002947 alkylene group Chemical group 0.000 claims description 43
- 208000003251 Pruritus Diseases 0.000 claims description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 30
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- 239000011734 sodium Substances 0.000 claims description 19
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- 125000004076 pyridyl group Chemical group 0.000 claims description 17
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- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 16
- 150000002500 ions Chemical class 0.000 claims description 16
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 16
- 208000004296 neuralgia Diseases 0.000 claims description 16
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 16
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 16
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- 239000003053 toxin Substances 0.000 claims description 7
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- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 7
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
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- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- HOGWTQOFGYMNOK-ZFWWWQNUSA-N 2,5-difluoro-4-[[(3s,4r)-4-(4-fluorophenyl)piperidin-3-yl]methoxy]-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2SN=CN=2)F)CNCC1 HOGWTQOFGYMNOK-ZFWWWQNUSA-N 0.000 claims description 5
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- OCGIYHGXHMLCPX-ZFWWWQNUSA-N 4-[[(3s,4r)-4-(4-chlorophenyl)piperidin-3-yl]methoxy]-2,5-difluoro-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1([C@@H]2CCNC[C@H]2COC2=CC(F)=C(C=C2F)S(=O)(=O)NC=2SN=CN=2)=CC=C(Cl)C=C1 OCGIYHGXHMLCPX-ZFWWWQNUSA-N 0.000 claims description 4
- ZTRJPVQOMYOPKN-WMZOPIPTSA-N 4-[[(3s,4r)-4-(4-chlorophenyl)piperidin-3-yl]methoxy]-2,5-difluoro-n-pyridin-2-ylbenzenesulfonamide Chemical compound C1([C@@H]2CCNC[C@H]2COC2=CC(F)=C(C=C2F)S(=O)(=O)NC=2N=CC=CC=2)=CC=C(Cl)C=C1 ZTRJPVQOMYOPKN-WMZOPIPTSA-N 0.000 claims description 4
- GUJMFDUXYXYBIE-RDJZCZTQSA-N 4-[[(3s,4r)-4-(4-chlorophenyl)piperidin-3-yl]methoxy]-2,5-difluoro-n-pyrimidin-2-ylbenzenesulfonamide Chemical compound C1([C@@H]2CCNC[C@H]2COC2=CC(F)=C(C=C2F)S(=O)(=O)NC=2N=CC=CN=2)=CC=C(Cl)C=C1 GUJMFDUXYXYBIE-RDJZCZTQSA-N 0.000 claims description 4
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- 230000002917 arthritic effect Effects 0.000 claims description 4
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 4
- 208000020016 psychiatric disease Diseases 0.000 claims description 4
- 238000013160 medical therapy Methods 0.000 claims description 3
- ALTZYACGMJLFNX-RDJZCZTQSA-N 1-[4-[[(3s,4r)-4-(4-chlorophenyl)piperidin-3-yl]methoxy]-2,5-difluorophenyl]sulfonyl-3-propan-2-ylurea Chemical compound C1=C(F)C(S(=O)(=O)NC(=O)NC(C)C)=CC(F)=C1OC[C@H]1[C@H](C=2C=CC(Cl)=CC=2)CCNC1 ALTZYACGMJLFNX-RDJZCZTQSA-N 0.000 claims description 2
- JPRPSPOHVXPDGZ-SUMWQHHRSA-N 2,5-difluoro-4-[(3s,4s)-4-(4-fluorophenyl)piperidin-3-yl]oxy-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](OC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2SN=CN=2)F)CNCC1 JPRPSPOHVXPDGZ-SUMWQHHRSA-N 0.000 claims description 2
- ONEVOOWUJAOPSN-HOCLYGCPSA-N 2,5-difluoro-4-[[(1r,2r)-2-(4-fluorophenyl)cyclohexyl]methoxy]-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2SN=CN=2)F)CCCC1 ONEVOOWUJAOPSN-HOCLYGCPSA-N 0.000 claims description 2
- XSBUZAIFXFCWIN-ZFWWWQNUSA-N 2,5-difluoro-4-[[(3r,4r)-3-(4-fluorophenyl)piperidin-4-yl]methoxy]-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2SN=CN=2)F)CCNC1 XSBUZAIFXFCWIN-ZFWWWQNUSA-N 0.000 claims description 2
- INAUGWMDRRSLLX-ZFWWWQNUSA-N 2,5-difluoro-4-[[(3s,4r)-4-(4-fluorophenyl)oxan-3-yl]methoxy]-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2SN=CN=2)F)COCC1 INAUGWMDRRSLLX-ZFWWWQNUSA-N 0.000 claims description 2
- AIZOGXUDMVUJRT-HOCLYGCPSA-N 2,5-difluoro-4-[[(3s,4r)-4-(4-methoxyphenyl)piperidin-3-yl]methoxy]-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@H](COC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2SN=CN=2)F)CNCC1 AIZOGXUDMVUJRT-HOCLYGCPSA-N 0.000 claims description 2
- KWJVTJCHNOYEQA-STQMWFEESA-N 2,5-difluoro-4-[[(3s,4r)-4-[4-fluoro-3-(trifluoromethyl)phenyl]piperidin-3-yl]methoxy]-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C1([C@@H]2CCNC[C@H]2COC2=CC(F)=C(C=C2F)S(=O)(=O)NC=2SN=CN=2)=CC=C(F)C(C(F)(F)F)=C1 KWJVTJCHNOYEQA-STQMWFEESA-N 0.000 claims description 2
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- HMUCIANDUAOOLC-RDJZCZTQSA-N 4-[[(3s,4r)-4-(4-chlorophenyl)piperidin-3-yl]methoxy]-2,5-difluoro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(OC[C@H]3[C@@H](CCNC3)C=3C=CC(Cl)=CC=3)=C(F)C=2)F)=N1 HMUCIANDUAOOLC-RDJZCZTQSA-N 0.000 claims description 2
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- RNYFDCRWQGEXOU-HOCLYGCPSA-N 4-[[(3s,4r)-4-(4-chlorophenyl)piperidin-3-yl]methoxy]-2,5-difluoro-n-methyl-n-(1,2,4-thiadiazol-5-yl)benzenesulfonamide Chemical compound C=1C(F)=C(OC[C@H]2[C@@H](CCNC2)C=2C=CC(Cl)=CC=2)C=C(F)C=1S(=O)(=O)N(C)C1=NC=NS1 RNYFDCRWQGEXOU-HOCLYGCPSA-N 0.000 claims description 2
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| Application Number | Priority Date | Filing Date | Title |
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| US201161553616P | 2011-10-31 | 2011-10-31 | |
| US61/553,616 | 2011-10-31 | ||
| PCT/IB2012/056031 WO2013064983A1 (en) | 2011-10-31 | 2012-10-30 | Benzenesulfonamide compounds and their use as therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2853439A1 true CA2853439A1 (en) | 2013-05-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2853439A Abandoned CA2853439A1 (en) | 2011-10-31 | 2012-10-30 | Benzenesulfonamide compounds and their use as therapeutic agents |
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| US (1) | US9630929B2 (enExample) |
| EP (1) | EP2773637B1 (enExample) |
| JP (1) | JP6014154B2 (enExample) |
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| MX (1) | MX2014005297A (enExample) |
| RU (1) | RU2014121984A (enExample) |
| WO (1) | WO2013064983A1 (enExample) |
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| CN104024251B (zh) | 2017-08-11 |
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| US9630929B2 (en) | 2017-04-25 |
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| EP2773637A4 (en) | 2015-03-11 |
| RU2014121984A (ru) | 2015-12-10 |
| KR20140091022A (ko) | 2014-07-18 |
| US20140296245A1 (en) | 2014-10-02 |
| JP2014532640A (ja) | 2014-12-08 |
| MX2014005297A (es) | 2014-09-11 |
| ES2586213T3 (es) | 2016-10-13 |
| EP2773637A1 (en) | 2014-09-10 |
| BR112014010271A2 (pt) | 2017-04-18 |
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