CA2959688C - Quinolone compounds and their use to treat diseases related to hypoxia inducible factor and/or erythropoietin - Google Patents
Quinolone compounds and their use to treat diseases related to hypoxia inducible factor and/or erythropoietin Download PDFInfo
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- CA2959688C CA2959688C CA2959688A CA2959688A CA2959688C CA 2959688 C CA2959688 C CA 2959688C CA 2959688 A CA2959688 A CA 2959688A CA 2959688 A CA2959688 A CA 2959688A CA 2959688 C CA2959688 C CA 2959688C
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 95
- 201000010099 disease Diseases 0.000 title claims abstract description 84
- 108090000394 Erythropoietin Proteins 0.000 title claims abstract description 47
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 229940105423 erythropoietin Drugs 0.000 title claims abstract description 46
- 206010021143 Hypoxia Diseases 0.000 title claims abstract description 29
- 230000007954 hypoxia Effects 0.000 title claims abstract description 21
- 230000001939 inductive effect Effects 0.000 title claims abstract description 19
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- 150000007660 quinolones Chemical class 0.000 title abstract description 3
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 32
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 32
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 32
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- 125000002757 morpholinyl group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
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- 239000011737 fluorine Substances 0.000 claims description 24
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 24
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 23
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 21
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- 125000001544 thienyl group Chemical group 0.000 claims description 18
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 17
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 208000028867 ischemia Diseases 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 14
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 150000001204 N-oxides Chemical class 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
- 208000010125 myocardial infarction Diseases 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 11
- 206010002383 Angina Pectoris Diseases 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
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- 208000030159 metabolic disease Diseases 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 9
- 125000005493 quinolyl group Chemical group 0.000 claims description 9
- 125000000466 oxiranyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 7
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 239000003981 vehicle Substances 0.000 claims description 7
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 101710138860 Hypoxia-inducible factor prolyl hydroxylase Proteins 0.000 claims description 4
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 3
- 241000756171 Hypoxis Species 0.000 claims 1
- 230000002107 myocardial effect Effects 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 14
- 238000002360 preparation method Methods 0.000 abstract description 6
- 102100031939 Erythropoietin Human genes 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 350
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 139
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- 150000004965 peroxy acids Chemical class 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
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- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 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
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
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- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- 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
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410442574.4 | 2014-09-02 | ||
| CN201410442574 | 2014-09-02 | ||
| PCT/CN2015/088799 WO2016034108A1 (zh) | 2014-09-02 | 2015-09-01 | 喹啉酮类化合物及其应用 |
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| CA2959688A1 CA2959688A1 (en) | 2016-03-10 |
| CA2959688C true CA2959688C (en) | 2024-02-27 |
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| CA2959688A Active CA2959688C (en) | 2014-09-02 | 2015-09-01 | Quinolone compounds and their use to treat diseases related to hypoxia inducible factor and/or erythropoietin |
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| EP (1) | EP3190104B1 (cg-RX-API-DMAC7.html) |
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| CN (1) | CN105384687B (cg-RX-API-DMAC7.html) |
| AU (1) | AU2015311333B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2959688C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2898476T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2016034108A1 (cg-RX-API-DMAC7.html) |
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| CN106146414A (zh) * | 2016-07-07 | 2016-11-23 | 浙江大学 | 喹唑啉二酮类衍生物及其制备方法和用途 |
| CN108069952B (zh) * | 2016-11-08 | 2022-09-27 | 广东东阳光药业有限公司 | 喹啉酮类化合物及其在药物中应用 |
| CN108069957B (zh) * | 2016-11-09 | 2022-11-04 | 广东东阳光药业有限公司 | 脯氨酰羟化酶抑制剂及其用途 |
| CN108285460A (zh) * | 2017-01-09 | 2018-07-17 | 南京圣和药业股份有限公司 | 一种egfr激酶抑制剂的药用盐及其制备方法与用途 |
| JP6999469B2 (ja) * | 2018-03-28 | 2022-01-18 | 東京応化工業株式会社 | 水素バリア剤、水素バリア膜形成用組成物、水素バリア膜、水素バリア膜の製造方法、及び電子素子 |
| CN111269177B (zh) * | 2019-11-28 | 2023-05-09 | 广东东阳光药业有限公司 | 喹啉酮类化合物的晶型 |
| CN111269178A (zh) * | 2019-11-28 | 2020-06-12 | 南北兄弟药业投资有限公司 | 喹啉酮类化合物的晶型 |
| CN111269176A (zh) * | 2019-11-28 | 2020-06-12 | 南北兄弟药业投资有限公司 | 喹啉酮类化合物的晶型 |
| WO2021104353A1 (zh) | 2019-11-28 | 2021-06-03 | 广东东阳光药业有限公司 | 喹啉酮类化合物的晶型及其用途 |
| CN115010662B (zh) * | 2021-03-05 | 2023-12-08 | 广东东阳光药业股份有限公司 | 喹啉酮类化合物的晶型及其用途 |
| CN115010663A (zh) * | 2021-03-05 | 2022-09-06 | 广东东阳光药业有限公司 | 喹啉酮类化合物的晶型及其用途 |
| CN115010664A (zh) * | 2021-03-05 | 2022-09-06 | 广东东阳光药业有限公司 | 喹啉酮类化合物的晶型及其用途 |
| CN114989085B (zh) * | 2022-05-23 | 2023-11-24 | 安徽医科大学 | 一种芳基内酰胺环类化合物、药物组合物及其应用 |
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| JPWO2006088246A1 (ja) * | 2005-02-18 | 2008-07-10 | 武田薬品工業株式会社 | Ｇｐｒ３４受容体機能調節剤 |
| US8703795B2 (en) | 2005-03-02 | 2014-04-22 | Fibrogen, Inc. | Thienopyridine compounds, and methods of use thereof |
| DE102005019712A1 (de) | 2005-04-28 | 2006-11-09 | Bayer Healthcare Ag | Dipyridyl-dihydropyrazolone und ihre Verwendung |
| WO2007038571A2 (en) * | 2005-09-26 | 2007-04-05 | Smithkline Beecham Corporation | Prolyl hydroxylase antagonists |
| ES2446416T3 (es) * | 2005-12-09 | 2014-03-07 | Amgen, Inc. | Compuestos basados en quinolona que presentan actividad inhibidora de prolil hidroxilasa, composiciones y usos de los mismos |
| AU2007211077B2 (en) | 2006-01-27 | 2012-09-20 | Fibrogen, Inc. | Cyanoisoquinoline compounds that stabilize hypoxia inducible factor (HIF) |
| AR059733A1 (es) * | 2006-03-07 | 2008-04-23 | Smithkline Beecham Corp | Compuesto derivado de glicina n- sustituida con heteroaromaticos bicicicos, composicion farmaceutica que lo comprende, uso para preparar un medicamento para tratar la anemia y proceso para su preparacion |
| MX2008012734A (es) | 2006-04-04 | 2009-01-29 | Fibrogen Inc | Compuestos pirrolo- y tiazolo-piridina como moduladores del factor inducible de hipoxia (hif). |
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| TWI394747B (zh) | 2006-06-23 | 2013-05-01 | Smithkline Beecham Corp | 脯胺醯基羥化酶抑制劑 |
| AU2007265460B2 (en) | 2006-06-26 | 2011-03-03 | Akebia Therapeutics Inc. | Prolyl hydroxylase inhibitors and methods of use |
| DE102006050516A1 (de) | 2006-10-26 | 2008-04-30 | Bayer Healthcare Ag | Substituierte Dihydropyrazolone und ihre Verwendung |
| WO2008076427A2 (en) | 2006-12-18 | 2008-06-26 | Amgen Inc. | Naphthalenone compounds exhibiting prolyl hydroxylase inhibitory activity, compositions, and uses thereof |
| AU2007334321B2 (en) | 2006-12-18 | 2012-03-08 | Amgen Inc. | Azaquinolone based compounds exhibiting prolyl hydroxylase inhibitory activity, compositions, and uses thereof |
| TW200845991A (en) | 2007-01-12 | 2008-12-01 | Smithkline Beecham Corp | N-substituted glycine derivatives: hydroxylase inhibitors |
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- 2015-09-01 CN CN201510557206.9A patent/CN105384687B/zh active Active
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| US20170247332A1 (en) | 2017-08-31 |
| CA2959688A1 (en) | 2016-03-10 |
| WO2016034108A1 (zh) | 2016-03-10 |
| US10065928B2 (en) | 2018-09-04 |
| EP3190104B1 (en) | 2021-10-27 |
| AU2015311333B2 (en) | 2017-11-16 |
| CN105384687B (zh) | 2018-05-01 |
| AU2015311333A1 (en) | 2017-02-16 |
| CN105384687A (zh) | 2016-03-09 |
| JP2017525737A (ja) | 2017-09-07 |
| JP6506390B2 (ja) | 2019-04-24 |
| ES2898476T3 (es) | 2022-03-07 |
| EP3190104A1 (en) | 2017-07-12 |
| EP3190104A4 (en) | 2018-04-11 |
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