CA2939501C - Isoquinoline derivatives and use thereof - Google Patents
Isoquinoline derivatives and use thereof Download PDFInfo
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- CA2939501C CA2939501C CA2939501A CA2939501A CA2939501C CA 2939501 C CA2939501 C CA 2939501C CA 2939501 A CA2939501 A CA 2939501A CA 2939501 A CA2939501 A CA 2939501A CA 2939501 C CA2939501 C CA 2939501C
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- alkyl
- amino
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- substituted
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- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 246
- 208000002193 Pain Diseases 0.000 claims abstract description 98
- 230000036407 pain Effects 0.000 claims abstract description 70
- 239000012453 solvate Substances 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 102000018674 Sodium Channels Human genes 0.000 claims abstract description 37
- 108010052164 Sodium Channels Proteins 0.000 claims abstract description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 32
- 208000035475 disorder Diseases 0.000 claims abstract description 28
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 352
- -1 ureido, guanidino Chemical class 0.000 claims description 131
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 99
- 125000000623 heterocyclic group Chemical class 0.000 claims description 83
- 125000003545 alkoxy group Chemical group 0.000 claims description 80
- 125000001072 heteroaryl group Chemical group 0.000 claims description 74
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 73
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 58
- 125000001424 substituent group Chemical group 0.000 claims description 55
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 125000005518 carboxamido group Chemical group 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 239000003814 drug Substances 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 35
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims description 25
- 125000005420 sulfonamido group Chemical class S(=O)(=O)(N*)* 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 208000004296 neuralgia Diseases 0.000 claims description 23
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 22
- 208000021722 neuropathic pain Diseases 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 206010015037 epilepsy Diseases 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 20
- 125000000304 alkynyl group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 206010065390 Inflammatory pain Diseases 0.000 claims description 17
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 17
- 208000000094 Chronic Pain Diseases 0.000 claims description 15
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 208000005298 acute pain Diseases 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 206010010904 Convulsion Diseases 0.000 claims description 12
- 206010003119 arrhythmia Diseases 0.000 claims description 12
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 206010061533 Myotonia Diseases 0.000 claims description 10
- 208000009205 Tinnitus Diseases 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical class 0.000 claims description 10
- 231100000886 tinnitus Toxicity 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 230000004770 neurodegeneration Effects 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- 208000019695 Migraine disease Diseases 0.000 claims description 8
- 208000016285 Movement disease Diseases 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 208000028867 ischemia Diseases 0.000 claims description 8
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 8
- 206010027599 migraine Diseases 0.000 claims description 8
- 208000019865 paroxysmal extreme pain disease Diseases 0.000 claims description 8
- 125000004076 pyridyl group Chemical class 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 206010008027 Cerebellar atrophy Diseases 0.000 claims description 7
- 206010019196 Head injury Diseases 0.000 claims description 7
- 208000036626 Mental retardation Diseases 0.000 claims description 7
- 208000028683 bipolar I disease Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 201000011384 erythromelalgia Diseases 0.000 claims description 7
- 238000002690 local anesthesia Methods 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 230000003961 neuronal insult Effects 0.000 claims description 7
- 206010003591 Ataxia Diseases 0.000 claims description 6
- 208000037674 Primary erythromelalgia Diseases 0.000 claims description 6
- 208000017692 primary erythermalgia Diseases 0.000 claims description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical class 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 230000027455 binding Effects 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000000596 cyclohexenyl group Chemical class C1(=CCCCC1)* 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 238000012216 screening Methods 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims description 3
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 229940126208 compound 22 Drugs 0.000 claims description 3
- 229940125877 compound 31 Drugs 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000004306 triazinyl group Chemical class 0.000 claims description 3
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims description 2
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 claims description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims description 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 claims description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims description 2
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims description 2
- 229940125833 compound 23 Drugs 0.000 claims description 2
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- 125000006413 ring segment Chemical group 0.000 claims description 2
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- FFFYSIINVOIAJZ-YADHBBJMSA-N (2S,3R)-2,3-dihydroxy-3-[6-[5-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyridin-2-yl]propanamide Chemical compound O[C@H](C(=O)N)[C@@H](C1=NC(=CC=C1)N1CC2=CC=CC(=C2CC1)C1=CC=C(C=C1)C(F)(F)F)O FFFYSIINVOIAJZ-YADHBBJMSA-N 0.000 claims 1
- BKZXMCAIWWDHSQ-QFIPXVFZSA-N 6-[(1R)-1,2-dihydroxyethyl]-4-[5-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyridine-2-carboxamide Chemical compound O[C@@H](CO)C1=CC(=CC(=N1)C(=O)N)N1CC2=CC=CC(=C2CC1)C1=CC=C(C=C1)C(F)(F)F BKZXMCAIWWDHSQ-QFIPXVFZSA-N 0.000 claims 1
- BKZXMCAIWWDHSQ-JOCHJYFZSA-N 6-[(1S)-1,2-dihydroxyethyl]-4-[5-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyridine-2-carboxamide Chemical compound O[C@H](CO)C1=CC(=CC(=N1)C(=O)N)N1CC2=CC=CC(=C2CC1)C1=CC=C(C=C1)C(F)(F)F BKZXMCAIWWDHSQ-JOCHJYFZSA-N 0.000 claims 1
- PDKJRCDTWHBSKE-UHFFFAOYSA-N 6-[5-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyridine-2-carboxamide Chemical compound FC(C1=CC=C(C=C1)C1=C2CCN(CC2=CC=C1)C1=CC=CC(=N1)C(=O)N)(F)F PDKJRCDTWHBSKE-UHFFFAOYSA-N 0.000 claims 1
- HHIDIFCNHJJOIJ-AWEZNQCLSA-N 6-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-(5-cyclohexyl-3,4-dihydro-1H-isoquinolin-2-yl)pyrimidine-4-carboxamide Chemical compound NC([C@H](C)NC1=CC(=NC(=N1)N1CC2=CC=CC(=C2CC1)C1CCCCC1)C(=O)N)=O HHIDIFCNHJJOIJ-AWEZNQCLSA-N 0.000 claims 1
- KQQNLKRRPXIPSA-AWEZNQCLSA-N 6-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-[5-(cyclohexen-1-yl)-3,4-dihydro-1H-isoquinolin-2-yl]pyrimidine-4-carboxamide Chemical compound NC([C@H](C)NC1=CC(=NC(=N1)N1CC2=CC=CC(=C2CC1)C1=CCCCC1)C(=O)N)=O KQQNLKRRPXIPSA-AWEZNQCLSA-N 0.000 claims 1
- ZSYCMPDGXVQBIO-ZDUSSCGKSA-N 6-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-[5-[2-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyrimidine-4-carboxamide Chemical compound NC([C@H](C)NC1=CC(=NC(=N1)N1CC2=CC=CC(=C2CC1)C1=C(C=CC=C1)C(F)(F)F)C(=O)N)=O ZSYCMPDGXVQBIO-ZDUSSCGKSA-N 0.000 claims 1
- IGZIEUGVWAHCSI-ZDUSSCGKSA-N 6-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-[5-[3-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyrimidine-4-carboxamide Chemical compound NC([C@H](C)NC1=CC(=NC(=N1)N1CC2=CC=CC(=C2CC1)C1=CC(=CC=C1)C(F)(F)F)C(=O)N)=O IGZIEUGVWAHCSI-ZDUSSCGKSA-N 0.000 claims 1
- RTJIPUIEDQRKRX-ZDUSSCGKSA-N 6-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-[5-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl]pyrimidine-4-carboxamide Chemical compound NC([C@H](C)NC1=CC(=NC(=N1)N1CC2=CC=CC(=C2CC1)C1=CC=C(C=C1)C(F)(F)F)C(=O)N)=O RTJIPUIEDQRKRX-ZDUSSCGKSA-N 0.000 claims 1
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Classifications
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- 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
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- 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
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Landscapes
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| CA3082427A1 (en) | 2013-03-15 | 2014-09-25 | Purdue Pharma L.P. | Carboxamide derivatives and use thereof |
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| US9828348B2 (en) | 2013-11-08 | 2017-11-28 | Purdue Pharma L.P. | Benzimidazole derivatives and use thereof |
| JP6337124B2 (ja) | 2013-12-23 | 2018-06-06 | パーデュー、ファーマ、リミテッド、パートナーシップ | インダゾール及びその使用 |
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| JP2017521373A (ja) | 2014-05-27 | 2017-08-03 | パーデュー、ファーマ、リミテッド、パートナーシップ | スピロ環モルフィナン及びその使用 |
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| CN110325516A (zh) | 2016-12-29 | 2019-10-11 | 米尼奥尔克斯治疗有限公司 | 杂芳基化合物和它们的用途 |
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| US9181185B2 (en) | 2011-10-31 | 2015-11-10 | Purdue Pharma L.P. | Heteroaryl compounds as sodium channel blockers |
| US9133131B2 (en) | 2011-11-15 | 2015-09-15 | Purdue Pharma L.P. | Pyrimidine diol amides as sodium channel blockers |
| AU2013203824A1 (en) | 2012-03-16 | 2013-10-03 | Purdue Pharma L.P. | Substituted pyridines and pryimidines as sodium channel blockers |
| US9714252B2 (en) | 2012-12-20 | 2017-07-25 | Purdue Pharma L.P. | Cyclic sulfonamides as sodium channel blockers |
| US9120786B2 (en) | 2013-03-04 | 2015-09-01 | Purdue Pharma, L.P. | Triazine carboxamides as sodium channel blockers |
| ES2680246T3 (es) | 2013-03-04 | 2018-09-05 | Purdue Pharma Lp | Pirimidincarboxamidas como bloqueantes de canal de sodio |
| CA3082427A1 (en) | 2013-03-15 | 2014-09-25 | Purdue Pharma L.P. | Carboxamide derivatives and use thereof |
| US9359330B2 (en) | 2013-08-26 | 2016-06-07 | Purdue Pharma L.P. | Substituted piperidines as sodium channel blockers |
| US9828348B2 (en) | 2013-11-08 | 2017-11-28 | Purdue Pharma L.P. | Benzimidazole derivatives and use thereof |
| US9340504B2 (en) | 2013-11-21 | 2016-05-17 | Purdue Pharma L.P. | Pyridine and piperidine derivatives as novel sodium channel blockers |
| US9695144B2 (en) | 2013-12-23 | 2017-07-04 | Purdue Pharma L.P. | Dibenzazepine derivatives and use thereof |
| US10730866B2 (en) | 2014-04-07 | 2020-08-04 | Purdue Pharma L.P. | Indole derivatives and use thereof |
-
2015
- 2015-02-12 JP JP2016551246A patent/JP6556154B2/ja active Active
- 2015-02-12 AU AU2015217185A patent/AU2015217185B2/en active Active
- 2015-02-12 US US15/118,563 patent/US10738026B2/en active Active
- 2015-02-12 WO PCT/US2015/015576 patent/WO2015123398A1/en not_active Ceased
- 2015-02-12 EP EP15748728.1A patent/EP3105217B1/en active Active
- 2015-02-12 CA CA2939501A patent/CA2939501C/en active Active
- 2015-02-12 CN CN201580015712.3A patent/CN106103422B/zh not_active Expired - Fee Related
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2016
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2020
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| CA2939501A1 (en) | 2015-08-20 |
| WO2015123398A1 (en) | 2015-08-20 |
| AU2015217185B2 (en) | 2018-04-05 |
| US11401258B2 (en) | 2022-08-02 |
| EP3105217A4 (en) | 2017-08-09 |
| JP2017511794A (ja) | 2017-04-27 |
| US20170057942A1 (en) | 2017-03-02 |
| CN106103422A (zh) | 2016-11-09 |
| JP6556154B2 (ja) | 2019-08-07 |
| IL247252A0 (en) | 2016-09-29 |
| US10738026B2 (en) | 2020-08-11 |
| CN106103422B (zh) | 2020-09-18 |
| IL247252B (en) | 2020-04-30 |
| EP3105217B1 (en) | 2019-05-29 |
| US20200407338A1 (en) | 2020-12-31 |
| EP3105217A1 (en) | 2016-12-21 |
| AU2015217185A1 (en) | 2016-09-01 |
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