CN1444477A - 血小板生成素模拟物 - Google Patents
血小板生成素模拟物 Download PDFInfo
- Publication number
- CN1444477A CN1444477A CN01813340A CN01813340A CN1444477A CN 1444477 A CN1444477 A CN 1444477A CN 01813340 A CN01813340 A CN 01813340A CN 01813340 A CN01813340 A CN 01813340A CN 1444477 A CN1444477 A CN 1444477A
- Authority
- CN
- China
- Prior art keywords
- dihydropyrazol
- oxo
- ylidene
- hydrazino
- carboxylic acid
- 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.)
- Granted
Links
- 102000036693 Thrombopoietin Human genes 0.000 title description 57
- 108010041111 Thrombopoietin Proteins 0.000 title description 57
- 150000001875 compounds Chemical class 0.000 claims abstract description 644
- 238000000034 method Methods 0.000 claims abstract description 278
- 206010043554 thrombocytopenia Diseases 0.000 claims abstract description 32
- 238000002360 preparation method Methods 0.000 claims abstract description 19
- 241000124008 Mammalia Species 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 3
- -1 N-acylamino Chemical group 0.000 claims description 155
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 68
- 239000000203 mixture Substances 0.000 claims description 61
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 39
- 150000002367 halogens Chemical class 0.000 claims description 39
- ZXLYSSHNDUXXIN-UHFFFAOYSA-N 3-(3-amino-2-hydroxyphenyl)benzoic acid Chemical compound NC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O ZXLYSSHNDUXXIN-UHFFFAOYSA-N 0.000 claims description 38
- 210000001772 blood platelet Anatomy 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000005842 heteroatom Chemical group 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 210000004027 cell Anatomy 0.000 claims description 26
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 210000003593 megakaryocyte Anatomy 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 150000002148 esters Chemical class 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 210000000130 stem cell Anatomy 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000003107 substituted aryl group Chemical group 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 15
- 150000004677 hydrates Chemical class 0.000 claims description 14
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- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- SVOQIEJWJCQGDQ-UHFFFAOYSA-N 3-[3-[[2-(3,4-dimethylphenyl)-5-methyl-3-oxo-1H-pyrazol-4-yl]diazenyl]-2-hydroxyphenyl]benzoic acid Chemical compound CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)N=NC3=CC=CC(=C3O)C4=CC(=CC=C4)C(=O)O)C SVOQIEJWJCQGDQ-UHFFFAOYSA-N 0.000 claims description 10
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- JCFPSTQCDAZKJN-UHFFFAOYSA-N 3-(2-hydroxy-3-nitrophenyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C(=C(C=CC=2)[N+]([O-])=O)O)=C1 JCFPSTQCDAZKJN-UHFFFAOYSA-N 0.000 claims description 8
- IRVUPFHZGHFIJJ-UHFFFAOYSA-N 6-(5-chloro-2-hydroxyphenyl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(C=2C(=CC=C(Cl)C=2)O)=N1 IRVUPFHZGHFIJJ-UHFFFAOYSA-N 0.000 claims description 8
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- 125000004423 acyloxy group Chemical group 0.000 claims description 8
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- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 8
- 125000003367 polycyclic group Chemical group 0.000 claims description 8
- SFMHOXZQBSSDPN-UHFFFAOYSA-N C1=C(C)C(C)=CC=C1N(N=C1)C(=O)C1=NNC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O Chemical compound C1=C(C)C(C)=CC=C1N(N=C1)C(=O)C1=NNC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O SFMHOXZQBSSDPN-UHFFFAOYSA-N 0.000 claims description 7
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- PQSXHCBSEMTPTA-UHFFFAOYSA-N 6-(5-chloro-2-hydroxy-3-nitrophenyl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(C=2C(=C(C=C(Cl)C=2)[N+]([O-])=O)O)=N1 PQSXHCBSEMTPTA-UHFFFAOYSA-N 0.000 claims description 6
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 claims description 6
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- AJSCIDJNLYWXMX-UHFFFAOYSA-N CC1=NN(C=2C=C(F)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C(F)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 AJSCIDJNLYWXMX-UHFFFAOYSA-N 0.000 claims description 6
- PVNVLZSJRDSWLN-UHFFFAOYSA-N CCC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CCC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 PVNVLZSJRDSWLN-UHFFFAOYSA-N 0.000 claims description 6
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- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 230000004083 survival effect Effects 0.000 claims description 6
- AAPGMCIBKOSNAL-UHFFFAOYSA-N 3-(2-methoxy-3-nitrophenyl)benzoic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC=CC(C(O)=O)=C1 AAPGMCIBKOSNAL-UHFFFAOYSA-N 0.000 claims description 5
- NFDGRVDJUBNISC-UHFFFAOYSA-N 3-(4-amino-3-hydroxyphenyl)benzoic acid Chemical compound C1=C(O)C(N)=CC=C1C1=CC=CC(C(O)=O)=C1 NFDGRVDJUBNISC-UHFFFAOYSA-N 0.000 claims description 5
- ODFAHRGJRYPTMU-UHFFFAOYSA-N 6-(2-hydroxy-5-methylphenyl)pyridine-2-carboxylic acid Chemical compound CC1=CC=C(O)C(C=2N=C(C=CC=2)C(O)=O)=C1 ODFAHRGJRYPTMU-UHFFFAOYSA-N 0.000 claims description 5
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 5
- NBCFNXHGRRXRAH-UHFFFAOYSA-N 2-(3-aminophenyl)-6-nitrophenol Chemical compound NC1=CC=CC(C=2C(=C(C=CC=2)[N+]([O-])=O)O)=C1 NBCFNXHGRRXRAH-UHFFFAOYSA-N 0.000 claims description 4
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- JXLLFYPMNIIERR-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)-4-[[2-hydroxy-3-[3-(1H-tetrazol-5-yl)phenyl]phenyl]hydrazinylidene]-5-pyridin-2-ylpyrazol-3-one Chemical group C1=C(C)C(C)=CC=C1N(N=C1C=2N=CC=CC=2)C(=O)C1=NNC1=CC=CC(C=2C=C(C=CC=2)C=2NN=NN=2)=C1O JXLLFYPMNIIERR-UHFFFAOYSA-N 0.000 claims description 3
- PQQHMKXDFRQSJC-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)-4-[[2-hydroxy-3-[3-(1H-tetrazol-5-yl)phenyl]phenyl]hydrazinylidene]-5-pyridin-4-ylpyrazol-3-one Chemical group C1=C(C)C(C)=CC=C1N(N=C1C=2C=CN=CC=2)C(=O)C1=NNC1=CC=CC(C=2C=C(C=CC=2)C=2NN=NN=2)=C1O PQQHMKXDFRQSJC-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
- C07D231/48—Oxygen atom in position 3 or 5 and nitrogen atom in position 4 with hydrocarbon radicals attached to said nitrogen atom
-
- 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
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D405/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
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Publication number | Priority date | Publication date | Assignee | Title |
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US11072586B2 (en) | 2017-10-06 | 2021-07-27 | Assia Chemical Industries Ltd. | Solid state forms of eltrombopag choline |
EP3409272B1 (en) * | 2018-03-07 | 2020-06-24 | Alfred E. Tiefenbacher (GmbH & Co. KG) | Pharmaceutical composition comprising eltrombopag olamine, reducing sugar, and polymeric binder |
EP3802651A4 (en) * | 2018-06-01 | 2022-05-04 | Aurobindo Pharma Limited | IMPROVED PROCESS FOR THE MANUFACTURE OF ELTROMBOPAG OLAMINE AND ITS INTERMEDIATE PRODUCTS |
EP3604284B1 (en) | 2018-08-02 | 2020-11-11 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Crystalline eltrombopag monoethanolamine salt form d |
EP3604285B1 (en) | 2018-08-02 | 2020-06-17 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Highly stable crystalline form d1 of the eltrombopag monoethanolamine salt |
EP3994126A1 (en) | 2019-07-04 | 2022-05-11 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Process for the preparation of key intermediates for the synthesis of eltrombopag or salt thereof |
JP7083793B2 (ja) * | 2019-09-10 | 2022-06-13 | Jfeケミカル株式会社 | パラターフェニルテトラカルボン酸およびパラターフェニルテトラカルボン酸二無水物の製造方法 |
US20210169854A1 (en) | 2019-09-20 | 2021-06-10 | Novartis Ag | 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid and its salts formulation |
WO2021110942A1 (en) | 2019-12-06 | 2021-06-10 | Synthon B.V. | Pharmaceutical composition comprising eltrombopag bis(monoethanolamine) |
US20230022228A1 (en) | 2019-12-06 | 2023-01-26 | Synthon B.V. | Pharmaceutical composition comprising eltrombopag bis(monoethanolamine) |
TR202014694A1 (tr) | 2020-09-16 | 2022-03-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Eltrombopag olami̇n i̇çeren bi̇r kati oral farmasöri̇k formülasyon |
WO2022201087A1 (en) | 2021-03-25 | 2022-09-29 | Novartis Ag | 3'-[(2z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4h-pyrazol-4-ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid and its salts formulation |
WO2023111187A1 (en) | 2021-12-15 | 2023-06-22 | Galenicum Health, S.L.U | Pharmaceutical compositions comprising eltrombopag |
Family Cites Families (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE193350C (zh) | ||||
US851444A (en) | 1905-11-13 | 1907-04-23 | Agfa Ag | Amido-oxy-sulfonic acid of phenylnaphthimidazol and process of making same. |
GB779880A (en) | 1953-02-27 | 1957-07-24 | Ciba Ltd | Functional derivatives of azo-dyestuffs containing sulphonic acid groups and processfor making them |
US2809963A (en) * | 1954-10-26 | 1957-10-15 | Ciba Ltd | Azo-dyestuffs |
DE1046220B (de) * | 1956-04-21 | 1958-12-11 | Bayer Ag | Verfahren zur Herstellung von Monoazofarbstoffen und deren Metallkomplexverbindungen |
GB826207A (en) | 1956-07-23 | 1959-12-31 | Bayer Ag | ú´-ú´-dihydroxy-monoazo dyestuffs containing pyrrolidonyl residues and their metal complex compounds |
US2950273A (en) | 1956-11-20 | 1960-08-23 | Agfa Ag | Process for the production of symmetrical and unsymmetrical azo compounds |
US3366619A (en) | 1965-04-09 | 1968-01-30 | Interchem Corp | Disazo pyrazolone pigments |
US4435417A (en) | 1981-02-20 | 1984-03-06 | Gruppo Lepetit S.P.A. | Antiinflammatory 3H-naphtho[1,2-d]imidazoles |
ES523609A0 (es) | 1982-07-05 | 1985-03-01 | Erba Farmitalia | Procedimiento para preparar derivados n-imidazolilicos de compuestos biciclicos. |
FR2559483B1 (fr) * | 1984-02-10 | 1986-12-05 | Sandoz Sa | Composes heterocycliques contenant des groupes basiques et/ou cationiques, leur preparation et leur utilisation comme colorants |
FI91869C (fi) | 1987-03-18 | 1994-08-25 | Tanabe Seiyaku Co | Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi |
US4880788A (en) | 1987-10-30 | 1989-11-14 | Baylor College Of Medicine | Method for preventing and treating thrombosis |
WO1993017681A1 (en) | 1992-03-02 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
IL109570A0 (en) | 1993-05-17 | 1994-08-26 | Fujisawa Pharmaceutical Co | Guanidine derivatives, pharmaceutical compositions containing the same and processes for the preparation thereof |
EP0638617A1 (de) | 1993-08-13 | 1995-02-15 | Ciba-Geigy Ag | Pigmentsalze |
DE69423661T2 (de) | 1993-12-28 | 2000-11-23 | Dai Nippon Printing Co., Ltd. | Thermische Übertragungsaufzeichnungsschicht, die einen bestimmten Farbstoff verwendet |
GB2285446B (en) * | 1994-01-03 | 1999-07-28 | Genentech Inc | Thrombopoietin |
CA2183266A1 (en) | 1994-02-14 | 1995-08-17 | Richard D. Holly | Hematopoietic protein and materials and methods for making it |
US5482546A (en) | 1994-03-30 | 1996-01-09 | Canon Kabushiki Kaisha | Dye, ink containing the same, and ink-jet recording method and instrument using the ink |
US5760038A (en) | 1995-02-06 | 1998-06-02 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
US5746821A (en) | 1995-02-13 | 1998-05-05 | Engelhard Corporation | Pigment compositions |
EP0885242B1 (en) | 1995-06-07 | 2008-03-26 | Glaxo Group Limited | Peptides and compounds that bind to a thrombopoietin receptor |
US5622818A (en) * | 1995-11-29 | 1997-04-22 | Eastman Kodak Company | Color photographic elements containing yellow colored magenta dye forming masking couplers |
US5669967A (en) | 1996-05-30 | 1997-09-23 | Engelhard Corporation | Pigment compositions |
US5932546A (en) | 1996-10-04 | 1999-08-03 | Glaxo Wellcome Inc. | Peptides and compounds that bind to the thrombopoietin receptor |
SE9701398D0 (sv) | 1997-04-15 | 1997-04-15 | Astra Pharma Prod | Novel compounds |
GB9715830D0 (en) | 1997-07-25 | 1997-10-01 | Basf Ag | Reactive dyes containing piperazine |
AU9265698A (en) | 1997-09-02 | 1999-03-22 | Boehringer Mannheim Gmbh | Mpl-receptor ligands, process for their preparation, medicaments containing themand their use for the treatment and prevention of thrombocytopaenia and anaemia |
GB9718913D0 (en) | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
DE69837279T2 (de) | 1997-10-31 | 2007-11-15 | Smithkline Beecham Corp. | Neue metall-komplexe |
DE19851389A1 (de) | 1998-11-07 | 2000-05-11 | Dystar Textilfarben Gmbh & Co | Gelbe Farbstoffmischungen von wasserlöslichen faserreaktiven Azofarbstoffen und ihre Verwendung |
GC0000177A (en) * | 1998-12-17 | 2006-03-29 | Smithkline Beecham | Thrombopoietin mimetics |
US6750342B1 (en) * | 1999-05-19 | 2004-06-15 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade |
CN1376150A (zh) * | 1999-07-26 | 2002-10-23 | 盐野义制药株式会社 | 具有血栓形成素受体拮抗作用的药物组合物 |
ATE315934T1 (de) * | 1999-09-10 | 2006-02-15 | Smithkline Beecham Corp | Thrombopoietin-mimetika |
US6552008B1 (en) * | 1999-09-24 | 2003-04-22 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
WO2001034585A1 (en) | 1999-11-05 | 2001-05-17 | Smithkline Beecham Corporation | Semicarbazone derivatives and their use as thrombopoietin mimetics |
ES2160560T1 (es) | 1999-11-10 | 2001-11-16 | Curacyte Ag | Colorantes o,o'-dihidroxi-azoicos como constituyentes de medicamentos para el tratamiento de trombopenias. |
TWI284639B (en) | 2000-01-24 | 2007-08-01 | Shionogi & Co | A compound having thrombopoietin receptor agonistic effect |
AR030273A1 (es) * | 2000-03-10 | 2003-08-20 | Smithkline Beecham Corp | Compuestos de hidroxifenil urea sustituidos con sulfonamidas, composiciones farmaceuticas que los comprenden, y uso de los mismos en la fabricacion de medicamentos para tratar una enfermedad mediada por una quimioquina |
US6214813B1 (en) | 2000-04-07 | 2001-04-10 | Kinetek Pharmaceuticals, Inc. | Pyrazole compounds |
US6436915B1 (en) | 2000-04-07 | 2002-08-20 | Kinetek Pharmaceuticals, Inc. | Pyrazole compounds |
CY2010012I2 (el) * | 2000-05-25 | 2020-05-29 | Novartis Ag | Μιμητικα θρομβοποιητινης |
US6642265B1 (en) * | 2000-09-08 | 2003-11-04 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
JP2004520302A (ja) | 2000-12-19 | 2004-07-08 | スミスクライン・ビーチャム・コーポレイション | トロンボポエチン模倣物 |
EP1351979B1 (en) | 2000-12-21 | 2008-01-16 | Smithkline Beecham Corporation | Regulated activation of cell-membrane receptors by metal-chelating agonists |
EP1361220A4 (en) | 2001-01-26 | 2005-09-07 | Shionogi & Co | CYCLIC COMPOUNDS WITH THROMBOPOIETIN RECEPTAGONISM |
CA2435143A1 (en) | 2001-01-26 | 2002-08-01 | Shionogi & Co., Ltd. | Halogen compounds having thrombopoietin receptor agonism |
EP1370252A4 (en) | 2001-03-01 | 2006-04-05 | Smithkline Beecham Corp | Thrombopoietin mimetics |
JP3927001B2 (ja) | 2001-06-15 | 2007-06-06 | 三菱化学株式会社 | 色素セット、インクセット並びに記録方法 |
US6560161B1 (en) * | 2001-08-30 | 2003-05-06 | Micron Technology, Inc. | Synchronous flash memory command sequence |
CA2468562C (en) | 2001-11-30 | 2011-12-20 | Zaihui Zhang | Hydrazonopyrazole derivatives and their use as therapeutics |
AU2003213673A1 (en) | 2002-03-01 | 2003-09-16 | Pintex Pharmaceuticals, Inc. | Pin1-modulating compounds and methods of use thereof |
TWI280128B (en) | 2002-05-22 | 2007-05-01 | Smithkline Beecham Corp | 3'-[(2Z)-[1-(3,4- dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine) |
WO2003103686A1 (en) | 2002-06-06 | 2003-12-18 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
TWI324593B (en) * | 2002-10-09 | 2010-05-11 | Nissan Chemical Ind Ltd | Pyrazolone compounds and thrombopoietin receptor activator |
AU2003297925A1 (en) | 2002-12-13 | 2004-07-09 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
US20090298179A1 (en) * | 2003-04-29 | 2009-12-03 | Connie Erickson-Miller | Methods For Treating Degenerative Diseases/Injuries |
EP2387998A1 (en) * | 2003-04-29 | 2011-11-23 | Glaxosmithkline LLC | Methods for treating degenerative diseases/injuries |
TW200526638A (en) * | 2003-10-22 | 2005-08-16 | Smithkline Beecham Corp | 2-(3,4-dimethylphenyl)-4-{[2-hydroxy-3'-(1H-tetrazol-5-yl)biphenyl-3-yl]-hydrazono}-5-methyl-2,4-dihydropyrazol-3-one choline |
WO2005118551A2 (en) * | 2004-05-28 | 2005-12-15 | Ligand Pharmaceuticals Inc. | Thrombopoietin activity modulating compounds and methods |
KR100958337B1 (ko) * | 2004-10-25 | 2010-05-17 | 리간드 파마슈티칼스 인코포레이티드 | 트롬보포이에틴 활성 조절 화합물 및 방법 |
EP1942906A2 (en) * | 2005-10-13 | 2008-07-16 | SmithKline Beecham Corporation | Methods for the preservation of platelet efficacy during storage |
US7786159B2 (en) * | 2006-12-01 | 2010-08-31 | Stategics, Inc. | Thrombopoietin mimetics |
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Publication number | Priority date | Publication date | Assignee | Title |
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