CA2834692A1 - Pyruvate kinase activators for use in therapy - Google Patents
Pyruvate kinase activators for use in therapy Download PDFInfo
- Publication number
- CA2834692A1 CA2834692A1 CA2834692A CA2834692A CA2834692A1 CA 2834692 A1 CA2834692 A1 CA 2834692A1 CA 2834692 A CA2834692 A CA 2834692A CA 2834692 A CA2834692 A CA 2834692A CA 2834692 A1 CA2834692 A1 CA 2834692A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- phenyl
- sulfonamide
- carbonyl
- nmr
- 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
Links
- 102000013009 Pyruvate Kinase Human genes 0.000 title abstract description 12
- 108020005115 Pyruvate Kinase Proteins 0.000 title abstract description 12
- 239000012190 activator Substances 0.000 title description 10
- 238000002560 therapeutic procedure Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 422
- 238000000034 method Methods 0.000 claims abstract description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 137
- 239000000203 mixture Substances 0.000 claims description 111
- -1 carbocycle Chemical group 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 210000003743 erythrocyte Anatomy 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 210000004369 blood Anatomy 0.000 claims description 17
- 239000008280 blood Substances 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 210000004027 cell Anatomy 0.000 claims description 16
- 239000003937 drug carrier Substances 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- XOHUEYCVLUUEJJ-UHFFFAOYSA-I 2,3-Diphosphoglycerate Chemical compound [O-]P(=O)([O-])OC(C(=O)[O-])COP([O-])([O-])=O XOHUEYCVLUUEJJ-UHFFFAOYSA-I 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 201000003922 congenital nonspherocytic hemolytic anemia Diseases 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 2
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 2
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 2
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- 208000007056 sickle cell anemia Diseases 0.000 claims description 2
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 2
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 2
- WTQLCJQZNSECQT-UHFFFAOYSA-N 2-oxo-n-[4-(4-phenylpiperazine-1-carbonyl)phenyl]-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=C3NC(=O)NC3=CC=2)C=CC=1C(=O)N(CC1)CCN1C1=CC=CC=C1 WTQLCJQZNSECQT-UHFFFAOYSA-N 0.000 claims 1
- GJUZEPDVPURTJO-UHFFFAOYSA-N 2-oxo-n-[4-(4-pyridin-2-ylpiperazine-1-carbonyl)phenyl]-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=C3NC(=O)NC3=CC=2)C=CC=1C(=O)N(CC1)CCN1C1=CC=CC=N1 GJUZEPDVPURTJO-UHFFFAOYSA-N 0.000 claims 1
- BFTCRVGGPSHTOJ-UHFFFAOYSA-N 2-oxo-n-[4-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]phenyl]-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C1CN(CC(F)(F)F)CCN1C(=O)C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(NC(=O)N2)C2=C1 BFTCRVGGPSHTOJ-UHFFFAOYSA-N 0.000 claims 1
- XLIKYSFZVYNBAP-UHFFFAOYSA-N 2-oxo-n-[4-[4-(thiophen-3-ylmethyl)piperazine-1-carbonyl]phenyl]-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=C3NC(=O)NC3=CC=2)C=CC=1C(=O)N(CC1)CCN1CC=1C=CSC=1 XLIKYSFZVYNBAP-UHFFFAOYSA-N 0.000 claims 1
- TXMXKWSHRLLINA-UHFFFAOYSA-N ethyl 4-[4-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)sulfonylamino]benzoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(NC(=O)N2)C2=C1 TXMXKWSHRLLINA-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- ZEZRSVCSJSRGLO-UHFFFAOYSA-N n-[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]-4-(4-methylpiperazine-1-carbonyl)benzenesulfonamide Chemical compound COC1=CC(OC)=CC(NC=2C(=NC3=CC=CC=C3N=2)NS(=O)(=O)C=2C=CC(=CC=2)C(=O)N2CCN(C)CC2)=C1 ZEZRSVCSJSRGLO-UHFFFAOYSA-N 0.000 claims 1
- SDPWIXFRKBOJHH-UHFFFAOYSA-N n-[4-(4-acetylpiperazine-1-carbonyl)phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C1CN(C(=O)C)CCN1C(=O)C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(NC(=O)N2)C2=C1 SDPWIXFRKBOJHH-UHFFFAOYSA-N 0.000 claims 1
- PKNOUYFGJZBGIQ-UHFFFAOYSA-N n-[4-[4-(2,3-dimethylphenyl)piperazine-1-carbonyl]phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound CC1=CC=CC(N2CCN(CC2)C(=O)C=2C=CC(NS(=O)(=O)C=3C=C4NC(=O)NC4=CC=3)=CC=2)=C1C PKNOUYFGJZBGIQ-UHFFFAOYSA-N 0.000 claims 1
- YOTDGZDZJATVAS-UHFFFAOYSA-N n-[4-[4-(2-ethoxyphenyl)piperazine-1-carbonyl]phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound CCOC1=CC=CC=C1N1CCN(C(=O)C=2C=CC(NS(=O)(=O)C=3C=C4NC(=O)NC4=CC=3)=CC=2)CC1 YOTDGZDZJATVAS-UHFFFAOYSA-N 0.000 claims 1
- QUTMWIBWVVIQIV-UHFFFAOYSA-N n-[4-[4-(2-hydroxyphenyl)piperazine-1-carbonyl]phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound OC1=CC=CC=C1N1CCN(C(=O)C=2C=CC(NS(=O)(=O)C=3C=C4NC(=O)NC4=CC=3)=CC=2)CC1 QUTMWIBWVVIQIV-UHFFFAOYSA-N 0.000 claims 1
- GHZZESYKWCBRJB-UHFFFAOYSA-N n-[4-[4-(4-fluorophenyl)piperazine-1-carbonyl]phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C1=CC(F)=CC=C1N1CCN(C(=O)C=2C=CC(NS(=O)(=O)C=3C=C4NC(=O)NC4=CC=3)=CC=2)CC1 GHZZESYKWCBRJB-UHFFFAOYSA-N 0.000 claims 1
- SLNRYAYGMZMYHV-UHFFFAOYSA-N n-[4-[4-(4-nitrophenyl)piperazine-1-carbonyl]phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCN(C(=O)C=2C=CC(NS(=O)(=O)C=3C=C4NC(=O)NC4=CC=3)=CC=2)CC1 SLNRYAYGMZMYHV-UHFFFAOYSA-N 0.000 claims 1
- MERGJCWMDMBTNS-UHFFFAOYSA-N n-[4-[4-(furan-2-ylmethyl)piperazine-1-carbonyl]phenyl]-2-oxo-1,3-dihydrobenzimidazole-5-sulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=C3NC(=O)NC3=CC=2)C=CC=1C(=O)N(CC1)CCN1CC1=CC=CO1 MERGJCWMDMBTNS-UHFFFAOYSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 282
- 238000004128 high performance liquid chromatography Methods 0.000 description 243
- 238000005481 NMR spectroscopy Methods 0.000 description 240
- ZTYZEUXZHGOXRT-UHFFFAOYSA-N quinoline-8-sulfonamide Chemical compound C1=CN=C2C(S(=O)(=O)N)=CC=CC2=C1 ZTYZEUXZHGOXRT-UHFFFAOYSA-N 0.000 description 139
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 107
- 239000000243 solution Substances 0.000 description 97
- 101150041968 CDC13 gene Proteins 0.000 description 87
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 87
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
- 238000003786 synthesis reaction Methods 0.000 description 70
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 60
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0641—Erythrocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- 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
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- C07D417/02—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
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161482166P | 2011-05-03 | 2011-05-03 | |
| US61/482,166 | 2011-05-03 | ||
| PCT/US2012/036413 WO2012151452A1 (en) | 2011-05-03 | 2012-05-03 | Pyruvate kinase activators for use in therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2834692A1 true CA2834692A1 (en) | 2012-11-08 |
Family
ID=46085224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2834692A Abandoned CA2834692A1 (en) | 2011-05-03 | 2012-05-03 | Pyruvate kinase activators for use in therapy |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US9404081B2 (enExample) |
| EP (1) | EP2704720B1 (enExample) |
| JP (2) | JP6267112B2 (enExample) |
| CN (1) | CN103608016A (enExample) |
| AU (1) | AU2012250690B2 (enExample) |
| CA (1) | CA2834692A1 (enExample) |
| ES (1) | ES2746558T3 (enExample) |
| WO (1) | WO2012151452A1 (enExample) |
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| CN108524505A (zh) | 2009-03-13 | 2018-09-14 | 安吉奥斯医药品有限公司 | 用于细胞增殖相关病症的方法和组合物 |
| CN102448951B (zh) | 2009-04-06 | 2017-05-10 | 安吉奥斯医药品有限公司 | 丙酮酸激酶m2调节剂、治疗组合物和相关使用方法 |
| PT2448582T (pt) | 2009-06-29 | 2017-07-10 | Agios Pharmaceuticals Inc | Compostos e composições terapêuticas |
| EP3561077B1 (en) | 2009-10-21 | 2022-12-21 | Les Laboratoires Servier | Methods for cell-proliferation-related disorders |
| US9328077B2 (en) | 2010-12-21 | 2016-05-03 | Agios Pharmaceuticals, Inc | Bicyclic PKM2 activators |
| TWI549947B (zh) * | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| CN108451955B (zh) | 2011-05-03 | 2022-02-01 | 安吉奥斯医药品有限公司 | 用于治疗的丙酮酸激酶活化剂 |
| WO2012151452A1 (en) * | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc | Pyruvate kinase activators for use in therapy |
| CN102827170A (zh) | 2011-06-17 | 2012-12-19 | 安吉奥斯医药品有限公司 | 治疗活性组合物和它们的使用方法 |
| CN102827073A (zh) | 2011-06-17 | 2012-12-19 | 安吉奥斯医药品有限公司 | 治疗活性组合物和它们的使用方法 |
| US9474779B2 (en) | 2012-01-19 | 2016-10-25 | Agios Pharmaceuticals, Inc. | Therapeutically active compositions and their methods of use |
| SG11201507486SA (en) | 2013-03-13 | 2015-10-29 | Forma Therapeutics Inc | Novel compounds and compositions for inhibition of fasn |
| WO2014139144A1 (en) * | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| US9579324B2 (en) | 2013-07-11 | 2017-02-28 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
| AU2014287121B2 (en) | 2013-07-11 | 2018-11-15 | Agios Pharmaceuticals, Inc. | 2,4- or 4,6-diaminopyrimidine compounds as IDH2 mutants inhibitors for the treatment of cancer |
| WO2015003360A2 (en) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
| WO2015003355A2 (en) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
| US20150031627A1 (en) | 2013-07-25 | 2015-01-29 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
| EA036325B1 (ru) | 2014-03-14 | 2020-10-27 | Аджиос Фармасьютикалз, Инк. | Фармацевтическая композиция на основе твердой дисперсии ингибитора idh1 |
| FR3030516B1 (fr) * | 2014-12-19 | 2019-12-27 | Galderma Research & Development | Derives sulfonamides bicycles en tant qu'agonistes inverses du recepteur gamma orphelin associe aux retinoides ror gamma (t) |
| SMT202300344T1 (it) * | 2015-06-11 | 2023-11-13 | Agios Pharmaceuticals Inc | Metodi di utilizzo degli attivatori della piruvato chinasi |
| ES2897959T3 (es) | 2015-10-15 | 2022-03-03 | Servier Lab | Terapia de combinación para tratar neoplasias malignas |
| UA123401C2 (uk) | 2015-10-15 | 2021-03-31 | Аджиос Фармасьютікалз, Інк. | Комбінована терапія для лікування злоякісних пухлин |
| US11014927B2 (en) * | 2017-03-20 | 2021-05-25 | Forma Therapeutics, Inc. | Pyrrolopyrrole compositions as pyruvate kinase (PKR) activators |
| MX2020001832A (es) | 2017-08-15 | 2020-07-22 | Agios Pharmaceuticals Inc | Activadores de piruvato quinasas para usar en el tratamiento de trastornos en la sangre. |
| US10980788B2 (en) | 2018-06-08 | 2021-04-20 | Agios Pharmaceuticals, Inc. | Therapy for treating malignancies |
| ES2989438T3 (es) | 2018-09-19 | 2024-11-26 | Novo Nordisk Healthcare Ag | Activación de la piruvato cinasa R |
| US12053458B2 (en) | 2018-09-19 | 2024-08-06 | Novo Nordisk Health Care Ag | Treating sickle cell disease with a pyruvate kinase R activating compound |
| TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
| CN113382633A (zh) | 2018-10-29 | 2021-09-10 | 福马治疗股份有限公司 | (4-(2-氟-4-(1-甲基-1H-苯并[d]咪唑-5-基)苯甲酰基)哌嗪-1-基)(1-羟基环丙基)甲酮的固体形式 |
| BR112021015996A2 (pt) * | 2019-02-13 | 2021-11-09 | Agios Pharmaceuticals Inc | Derivados de tieno[3,2-b]pirrol[3,2-d]piridazinona e seu uso como derivados de pkm2 para o tratamento de câncer, obesidade e distúrbios relacionados a diabetes |
| EP4031132A4 (en) | 2019-09-19 | 2023-09-13 | Forma Therapeutics, Inc. | Activating pyruvate kinase r |
| CN111892599B (zh) * | 2020-08-14 | 2023-01-13 | 黄芳 | 一种2,5-二氮杂双环[2.2.2]辛烷-2-羧酸叔丁酯的合成方法 |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
| EP4147700A1 (en) * | 2021-09-08 | 2023-03-15 | LQT Therapeutics Inc. | N-(4-(azaindazol-6-yl)-phenyl)-sulfonamides for use in the treatment of sickle cell disease |
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| IL115420A0 (en) | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
| IL117580A0 (en) | 1995-03-29 | 1996-07-23 | Merck & Co Inc | Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them |
| ES2100129B1 (es) | 1995-10-11 | 1998-02-16 | Medichem Sa | Nuevos compuestos aminopiridinicos policiclicos inhibidores de acetilcolinesterasa, procedimiento para su preparacion y su utilizacion. |
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| US5834485A (en) | 1996-05-20 | 1998-11-10 | Chiroscience Limited | Quinoline sulfonamides and their therapeutic use |
| US6214879B1 (en) | 1998-03-24 | 2001-04-10 | Virginia Commonwealth University | Allosteric inhibitors of pyruvate kinase |
| HUP0203954A2 (hu) | 1999-09-17 | 2003-03-28 | Millennium Pharmaceuticals, Inc. | Xa faktor inhibitorok |
| BR0014076A (pt) | 1999-09-17 | 2002-10-15 | Millennium Pharm Inc | Benzamidas e inibidores correlatos do fator xa |
| DK1259485T3 (da) | 2000-02-29 | 2006-04-10 | Millennium Pharm Inc | Benzamider og beslægtede inhibitorer for faktor Xa |
| AU2002256418A1 (en) | 2001-04-27 | 2002-11-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of bace |
| US7144883B2 (en) | 2001-06-11 | 2006-12-05 | Biovitrum Ab | Bicyclic sulfonamide compounds |
| EP1618090A1 (en) | 2003-04-11 | 2006-01-25 | Novo Nordisk A/S | 11ß-HYDROXYSTEROID DEHYDROGENASE TYPE 1 ACTIVE COMPOUNDS |
| GB0412526D0 (en) | 2004-06-05 | 2004-07-14 | Leuven K U Res & Dev | Type 2 diabetes |
| MX2007003319A (es) | 2004-09-20 | 2007-06-05 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como agentes terapeuticos. |
| WO2006038594A1 (ja) | 2004-10-04 | 2006-04-13 | Ono Pharmaceutical Co., Ltd. | Ｎ型カルシウムチャネル阻害薬 |
| GB0513702D0 (en) | 2005-07-04 | 2005-08-10 | Sterix Ltd | Compound |
| WO2007008143A1 (en) | 2005-07-08 | 2007-01-18 | Astrazeneca Ab | Heterocyclic sulfonamide derivatives as inhibitors of factor xa |
| WO2007023186A1 (en) | 2005-08-26 | 2007-03-01 | Laboratoires Serono S.A. | Pyrazine derivatives and use as pi3k inhibitors |
| US7906555B2 (en) | 2006-10-26 | 2011-03-15 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Aquaporin modulators and methods of using them for the treatment of edema and fluid imbalance |
| HUP0600810A3 (en) * | 2006-10-27 | 2008-09-29 | Richter Gedeon Nyrt | New sulfonamide derivatives as bradykinin antagonists, process and intermediates for their preparation and pharmaceutical compositions containing them |
| PT2101760E (pt) | 2006-12-08 | 2013-05-07 | Millennium Pharm Inc | Formulações de dose unitária e métodos de tratamento da trombose com um inibidor oral do fator xa |
| CN108524505A (zh) | 2009-03-13 | 2018-09-14 | 安吉奥斯医药品有限公司 | 用于细胞增殖相关病症的方法和组合物 |
| PL2427441T3 (pl) | 2009-05-04 | 2017-06-30 | Agios Pharmaceuticals, Inc. | Aktywatory PKM2 do stosowania w leczeniu raka |
| WO2010130638A1 (en) | 2009-05-14 | 2010-11-18 | Evotec Ag | Sulfonamide compounds, pharmaceutical compositions and uses thereof |
| PT2448582T (pt) | 2009-06-29 | 2017-07-10 | Agios Pharmaceuticals Inc | Compostos e composições terapêuticas |
| WO2011032169A2 (en) | 2009-09-14 | 2011-03-17 | Phusis Therapeutics Inc. | Pharmaceutical compositions and formulations including inhibitors of the pleckstrin homology domain and methods for using same |
| EP2491030B1 (en) | 2009-10-22 | 2015-07-15 | Fibrotech Therapeutics PTY LTD | Fused ring analogues of anti-fibrotic agents |
| EP2542086A4 (en) * | 2010-03-01 | 2013-09-04 | Myrexis Inc | COMPOUNDS AND ITS THERAPEUTIC USE |
| FR2967674B1 (fr) | 2010-11-23 | 2012-12-14 | Pf Medicament | Derives d'heteroarylsulfonamides, leur preparation et leur application en therapeutique humaine |
| TWI549947B (zh) | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| CN108451955B (zh) * | 2011-05-03 | 2022-02-01 | 安吉奥斯医药品有限公司 | 用于治疗的丙酮酸激酶活化剂 |
| WO2012151452A1 (en) | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc | Pyruvate kinase activators for use in therapy |
-
2012
- 2012-05-03 WO PCT/US2012/036413 patent/WO2012151452A1/en not_active Ceased
- 2012-05-03 ES ES12721111T patent/ES2746558T3/es active Active
- 2012-05-03 EP EP12721111.8A patent/EP2704720B1/en active Active
- 2012-05-03 CN CN201280028693.4A patent/CN103608016A/zh active Pending
- 2012-05-03 US US14/115,292 patent/US9404081B2/en not_active Expired - Fee Related
- 2012-05-03 JP JP2014509459A patent/JP6267112B2/ja not_active Expired - Fee Related
- 2012-05-03 AU AU2012250690A patent/AU2012250690B2/en not_active Ceased
- 2012-05-03 CA CA2834692A patent/CA2834692A1/en not_active Abandoned
-
2016
- 2016-09-05 JP JP2016173166A patent/JP6267299B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN103608016A (zh) | 2014-02-26 |
| EP2704720B1 (en) | 2019-08-07 |
| ES2746558T3 (es) | 2020-03-06 |
| WO2012151452A1 (en) | 2012-11-08 |
| JP6267112B2 (ja) | 2018-01-24 |
| EP2704720A1 (en) | 2014-03-12 |
| JP6267299B2 (ja) | 2018-01-24 |
| AU2012250690A1 (en) | 2013-11-14 |
| JP2016199597A (ja) | 2016-12-01 |
| US9404081B2 (en) | 2016-08-02 |
| JP2014513134A (ja) | 2014-05-29 |
| US20140155408A1 (en) | 2014-06-05 |
| AU2012250690B2 (en) | 2017-06-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20170503 |
|
| FZDE | Discontinued |
Effective date: 20210831 |
|
| FZDE | Discontinued |
Effective date: 20210831 |