CN101343250A - 血小板生成素模拟物 - Google Patents
血小板生成素模拟物 Download PDFInfo
- Publication number
- CN101343250A CN101343250A CNA200810129758XA CN200810129758A CN101343250A CN 101343250 A CN101343250 A CN 101343250A CN A200810129758X A CNA200810129758X A CN A200810129758XA CN 200810129758 A CN200810129758 A CN 200810129758A CN 101343250 A CN101343250 A CN 101343250A
- Authority
- CN
- China
- Prior art keywords
- xenol
- carboxylic acid
- pyrazoline
- chloro
- oxo
- 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 69
- 108010041111 Thrombopoietin Proteins 0.000 title description 69
- 150000001875 compounds Chemical class 0.000 claims abstract description 705
- 238000000034 method Methods 0.000 claims abstract description 270
- 238000002360 preparation method Methods 0.000 claims abstract description 31
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 166
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 239000004305 biphenyl Substances 0.000 claims description 83
- 235000010290 biphenyl Nutrition 0.000 claims description 83
- 239000001257 hydrogen Substances 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- -1 replacement Chemical group 0.000 claims description 59
- 150000003839 salts Chemical class 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- RCFKEIREOSXLET-UHFFFAOYSA-N disulfamide Chemical compound CC1=CC(Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O RCFKEIREOSXLET-UHFFFAOYSA-N 0.000 claims description 26
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 22
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 22
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical class OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 150000003009 phosphonic acids Chemical class 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 229960003512 nicotinic acid Drugs 0.000 claims description 16
- 239000011664 nicotinic acid Substances 0.000 claims description 16
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 12
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 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 9
- IRVUPFHZGHFIJJ-UHFFFAOYSA-N 6-(5-chloro-2-hydroxyphenyl)pyridine-2-carboxylic acid Chemical class OC(=O)C1=CC=CC(C=2C(=CC=C(Cl)C=2)O)=N1 IRVUPFHZGHFIJJ-UHFFFAOYSA-N 0.000 claims description 9
- PQSXHCBSEMTPTA-UHFFFAOYSA-N 6-(5-chloro-2-hydroxy-3-nitrophenyl)pyridine-2-carboxylic acid Chemical class 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 7
- FEWLQEHDQSJYAI-UHFFFAOYSA-N 4-(3-hydroxy-4-nitrophenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C([N+]([O-])=O)C(O)=C1 FEWLQEHDQSJYAI-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- ZQGHXZXYOLVJOY-UHFFFAOYSA-N 3-(3-hydroxy-4-nitrophenyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=C(O)C(=CC=2)[N+]([O-])=O)=C1 ZQGHXZXYOLVJOY-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- YZVZTVKKEUKEJR-UHFFFAOYSA-N 3-(5-chloro-2-methoxyphenyl)benzenesulfonic acid Chemical compound COC1=CC=C(Cl)C=C1C1=CC=CC(S(O)(=O)=O)=C1 YZVZTVKKEUKEJR-UHFFFAOYSA-N 0.000 claims description 4
- BLCXFSUTKOZWLS-UHFFFAOYSA-N 3-(5-chloro-2-methoxyphenyl)benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C1=CC=CC(C(O)=O)=C1 BLCXFSUTKOZWLS-UHFFFAOYSA-N 0.000 claims description 4
- KXHUUTFANFEZQQ-UHFFFAOYSA-N 5-(5-chloro-2-hydroxy-3-nitrophenyl)-2-hydroxybenzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=C(C=C(Cl)C=2)[N+]([O-])=O)O)=C1 KXHUUTFANFEZQQ-UHFFFAOYSA-N 0.000 claims description 4
- SCTHJPTVHRSKIA-UHFFFAOYSA-N 5-(5-chloro-2-hydroxyphenyl)-2-hydroxybenzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC=C(Cl)C=2)O)=C1 SCTHJPTVHRSKIA-UHFFFAOYSA-N 0.000 claims description 4
- QDCFGKSNLGLTPP-UHFFFAOYSA-N [3-(5-chloro-2-hydroxy-3-nitrophenyl)phenyl]phosphonic acid Chemical class C1=C(Cl)C=C([N+]([O-])=O)C(O)=C1C1=CC=CC(P(O)(O)=O)=C1 QDCFGKSNLGLTPP-UHFFFAOYSA-N 0.000 claims description 4
- KSRSVWSBHDNHMQ-UHFFFAOYSA-N [3-(5-chloro-2-methoxyphenyl)phenyl]phosphonic acid Chemical class COC1=CC=C(Cl)C=C1C1=CC=CC(P(O)(O)=O)=C1 KSRSVWSBHDNHMQ-UHFFFAOYSA-N 0.000 claims description 4
- ABINNOJEIVUZDE-UHFFFAOYSA-N 2-amino-4-chloro-6-[4-(2H-tetrazol-5-yl)phenyl]phenol Chemical group NC1=CC(Cl)=CC(C=2C=CC(=CC=2)C=2NN=NN=2)=C1O ABINNOJEIVUZDE-UHFFFAOYSA-N 0.000 claims description 3
- SWSCKLXUQFVPPN-UHFFFAOYSA-N 2-amino-6-[3-(2H-tetrazol-5-yl)phenyl]phenol Chemical group NC1=CC=CC(C=2C=C(C=CC=2)C=2NN=NN=2)=C1O SWSCKLXUQFVPPN-UHFFFAOYSA-N 0.000 claims description 3
- BDALNVGNAVIXHN-UHFFFAOYSA-N 2-amino-6-[4-(2H-tetrazol-5-yl)phenyl]phenol Chemical group NC1=CC=CC(C=2C=CC(=CC=2)C=2NN=NN=2)=C1O BDALNVGNAVIXHN-UHFFFAOYSA-N 0.000 claims description 3
- SXOLAPGRTRIDKB-UHFFFAOYSA-N 3-(5-chloro-2-hydroxy-3-nitrophenyl)benzenesulfonic acid Chemical compound C1=C(Cl)C=C([N+]([O-])=O)C(O)=C1C1=CC=CC(S(O)(=O)=O)=C1 SXOLAPGRTRIDKB-UHFFFAOYSA-N 0.000 claims description 3
- PGNTVCRTPYDGRN-UHFFFAOYSA-N 376592-58-4 Chemical compound OC(=O)C1=CC=CC(C=2C(=C(C=C(Cl)C=2)[N+]([O-])=O)O)=C1 PGNTVCRTPYDGRN-UHFFFAOYSA-N 0.000 claims description 3
- VHJSPQHJTZAUOJ-UHFFFAOYSA-N 4-(2-hydroxy-3-nitrophenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC([N+]([O-])=O)=C1O VHJSPQHJTZAUOJ-UHFFFAOYSA-N 0.000 claims description 3
- KYABISRBNXIXFV-UHFFFAOYSA-N 4-chloro-2-[3-(2h-tetrazol-5-yl)phenyl]phenol Chemical group OC1=CC=C(Cl)C=C1C1=CC=CC(C=2NN=NN=2)=C1 KYABISRBNXIXFV-UHFFFAOYSA-N 0.000 claims description 3
- RZSZAYIFNLVQLJ-UHFFFAOYSA-N 4-chloro-2-[4-(2H-tetrazol-5-yl)phenyl]phenol Chemical group OC1=CC=C(Cl)C=C1C1=CC=C(C=2NN=NN=2)C=C1 RZSZAYIFNLVQLJ-UHFFFAOYSA-N 0.000 claims description 3
- KGQQOCHJQGARLF-UHFFFAOYSA-N 4-chloro-2-nitro-6-[3-(2h-tetrazol-5-yl)phenyl]phenol Chemical group C1=C(Cl)C=C([N+]([O-])=O)C(O)=C1C1=CC=CC(C=2NN=NN=2)=C1 KGQQOCHJQGARLF-UHFFFAOYSA-N 0.000 claims description 3
- ZKIXGUNDRDDYTE-UHFFFAOYSA-N 4-chloro-2-nitro-6-[4-(2H-tetrazol-5-yl)phenyl]phenol Chemical group C1=C(Cl)C=C([N+]([O-])=O)C(O)=C1C1=CC=C(C=2NN=NN=2)C=C1 ZKIXGUNDRDDYTE-UHFFFAOYSA-N 0.000 claims description 3
- ZSCIIJRZMGRZAW-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)-2-hydroxybenzoic acid Chemical compound NC1=CC=CC(C=2C=C(C(O)=CC=2)C(O)=O)=C1O ZSCIIJRZMGRZAW-UHFFFAOYSA-N 0.000 claims description 3
- RMGYXHYQEZZNIL-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)pyridine-3-carboxylic acid Chemical compound NC1=CC=CC(C=2C=C(C=NC=2)C(O)=O)=C1O RMGYXHYQEZZNIL-UHFFFAOYSA-N 0.000 claims description 3
- ZJNUQVSSGXNKQQ-UHFFFAOYSA-N 5-(5-chloro-2-hydroxy-3-nitrophenyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(C=2C(=C(C=C(Cl)C=2)[N+]([O-])=O)O)=C1 ZJNUQVSSGXNKQQ-UHFFFAOYSA-N 0.000 claims description 3
- JOSDFDUFCGZDKO-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-2-hydroxybenzoic acid Chemical compound COC1=CC=C(Cl)C=C1C1=CC=C(O)C(C(O)=O)=C1 JOSDFDUFCGZDKO-UHFFFAOYSA-N 0.000 claims description 3
- NBUAXZAMRXNROL-UHFFFAOYSA-N 6-(3-amino-2-hydroxyphenyl)pyridine-2-carboxylic acid Chemical class NC1=CC=CC(C=2N=C(C=CC=2)C(O)=O)=C1O NBUAXZAMRXNROL-UHFFFAOYSA-N 0.000 claims description 3
- DYCFNJNPLIGHQS-UHFFFAOYSA-N 6-(3-amino-5-chloro-2-hydroxyphenyl)pyridine-2-carboxylic acid Chemical class NC1=CC(Cl)=CC(C=2N=C(C=CC=2)C(O)=O)=C1O DYCFNJNPLIGHQS-UHFFFAOYSA-N 0.000 claims description 3
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- 238000003419 tautomerization reaction Methods 0.000 claims description 3
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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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- 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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- 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
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- 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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Abstract
Description
Claims (2)
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US20708400P | 2000-05-25 | 2000-05-25 | |
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US60/228,929 | 2000-08-30 |
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CNB018133401A Expired - Lifetime CN100423721C (zh) | 2000-05-25 | 2001-05-24 | 血小板生成素模拟物 |
CN2008101297594A Expired - Fee Related CN101343251B (zh) | 2000-05-25 | 2001-05-24 | 血小板生成素模拟物 |
CN200810129758XA Expired - Fee Related CN101343250B (zh) | 2000-05-25 | 2001-05-24 | 血小板生成素模拟物 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103819406A (zh) * | 2014-03-17 | 2014-05-28 | 苏州明锐医药科技有限公司 | 艾曲波帕的制备方法 |
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CN105085276A (zh) * | 2014-05-12 | 2015-11-25 | 上海医药工业研究院 | 艾曲波帕中间体及其制备方法和应用 |
Families Citing this family (104)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001066553A2 (en) | 2000-03-08 | 2001-09-13 | Metabasis Therapeutics, Inc. | Novel aryl fructose-1,6-bisphosphatase inhibitors |
CY2010012I2 (el) * | 2000-05-25 | 2020-05-29 | Novartis Ag | Μιμητικα θρομβοποιητινης |
US20110212054A1 (en) * | 2000-05-25 | 2011-09-01 | Glaxosmithkline Llc. | Thrombopoietin mimetics |
EP1370252A4 (en) * | 2001-03-01 | 2006-04-05 | Smithkline Beecham Corp | Thrombopoietin mimetics |
US7659409B2 (en) | 2002-03-19 | 2010-02-09 | Mitsubishi Chemical Corporation | 3-Hydroxy-3-(2-thienyl) propionamides and production method thereof, and production method of 3-amino-1-(2-thienyl)-1-propanols using the same |
MY142390A (en) * | 2002-05-22 | 2010-11-30 | Glaxosmithkline Llc | 3' - [(2z)-[1-(3,4-dimethylphenyl)-1,5- dihydro-3- methyl-5-0xo-4h-pyrazol-4- ylidene]hydrazino]-2' -hydroxy -[1,1' -biphenyl]-3-carboxylic acid bis-(monoethanolamine) |
AU2003248630A1 (en) * | 2002-06-06 | 2003-12-22 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
JP4412173B2 (ja) | 2002-08-14 | 2010-02-10 | 日産化学工業株式会社 | トロンボポエチンレセプター活性化剤ならびにそれらの製造方法 |
TWI324593B (en) | 2002-10-09 | 2010-05-11 | Nissan Chemical Ind Ltd | Pyrazolone compounds and thrombopoietin receptor activator |
US20090143453A1 (en) * | 2003-04-29 | 2009-06-04 | Connie Erickson-Miller | Methods for treating degenerative diseases/injuries |
US20090048318A1 (en) * | 2003-04-29 | 2009-02-19 | Connie Erickson-Miller | Methods for treating degenerative diseases/injuries |
JP4895807B2 (ja) * | 2003-04-29 | 2012-03-14 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 変性疾患/損傷の治療方法 |
US20100004302A1 (en) * | 2003-04-29 | 2010-01-07 | Connie Erickson-Miller | Methods for Treating Degenerative Diseases/Injuries |
US20090298179A1 (en) * | 2003-04-29 | 2009-12-03 | Connie Erickson-Miller | Methods For Treating Degenerative Diseases/Injuries |
US7753958B2 (en) * | 2003-08-05 | 2010-07-13 | Gordon Charles R | Expandable intervertebral implant |
SE0302486D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
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 |
EP1796673A2 (en) * | 2004-09-23 | 2007-06-20 | Reddy US Therapeutics, Inc. | Novel pyrimidine compounds, process for their preparation and compositions containing them |
DE602005024599D1 (de) * | 2004-10-25 | 2010-12-16 | Ligand Pharm Inc | Verbindungen modulierende thrombopoietinaktivität und verfahren |
RU2395505C2 (ru) | 2004-12-08 | 2010-07-27 | Ниссан Кемикал Индастриз, ЛТД | 3-этилиденгидразино-замещенные гетероциклические соединения в качестве активаторов рецептора тромбопоэтина |
EP1845090A4 (en) | 2004-12-14 | 2009-11-11 | Nissan Chemical Ind Ltd | AMIDE COMPOUND AND THROMBOPOIETINE RECEPTOR ACTIVATOR |
TW200716580A (en) | 2005-06-08 | 2007-05-01 | Smithkline Beecham Corp | (5Z)-5-(6-quinoxalinylmethylidene)-2-[(2,6-dichlorophenyl)amino]-1,3-thiazol-4(5H)-one |
WO2007010954A1 (en) | 2005-07-15 | 2007-01-25 | Nissan Chemical Industries, Ltd. | Thiophene compounds and thrombopoietin receptor activators |
KR101290484B1 (ko) | 2005-07-20 | 2013-07-26 | 닛산 가가쿠 고교 가부시키 가이샤 | 피라졸 화합물 및 트롬보포이에틴 수용체 활성화제 |
EP1942906A2 (en) * | 2005-10-13 | 2008-07-16 | SmithKline Beecham Corporation | Methods for the preservation of platelet efficacy during storage |
WO2007052808A1 (ja) | 2005-11-07 | 2007-05-10 | Nissan Chemical Industries, Ltd. | ヒドラジド化合物及びトロンボポエチンレセプター活性化剤 |
EP2025671A4 (en) | 2006-06-07 | 2011-04-06 | Nissan Chemical Ind Ltd | NITROGENIC HETEROCYCLIC COMPOUND AND THROMBOPOIETIN RECEPTOR ACTIVATOR |
EP2086551A4 (en) * | 2006-12-01 | 2011-06-08 | Stategics Inc | Thrombopoietin mimetics |
US20110160130A1 (en) * | 2007-02-16 | 2011-06-30 | Connie Erickson-Miller | Cancer treatment method |
UY30915A1 (es) * | 2007-02-16 | 2008-09-02 | Smithkline Beecham Corp | Método de tratamiento de canceres |
US20110129550A1 (en) * | 2007-02-16 | 2011-06-02 | Connie Erickson-Miller | Cancer treatment method |
WO2008134338A1 (en) * | 2007-04-24 | 2008-11-06 | Smithkline Beecham Corporation | Novel processes of making hydroxy-1-azo-derivatives as tpo mimetics |
ECSP077628A (es) | 2007-05-03 | 2008-12-30 | Smithkline Beechman Corp | Nueva composición farmacéutica |
EA022915B1 (ru) * | 2007-10-09 | 2016-03-31 | Дзе Трастиз Оф Дзе Юниверсити Оф Пенсильвания | Способы лечения острого миелоидного лейкоза и миелодиспластического синдрома |
CN101481352A (zh) * | 2008-01-10 | 2009-07-15 | 上海恒瑞医药有限公司 | 双环取代吡唑酮偶氮类衍生物、其制备方法及其在医药上的应用 |
EP2278879B1 (en) | 2008-04-21 | 2016-06-15 | PATH Drug Solutions | Compounds, compositions and methods comprising oxadiazole derivatives |
US8236838B2 (en) | 2008-04-21 | 2012-08-07 | Institute For Oneworld Health | Compounds, compositions and methods comprising isoxazole derivatives |
WO2009151862A1 (en) * | 2008-05-15 | 2009-12-17 | Smithkline Beecham Corporation | Method of treatment |
WO2010045310A1 (en) * | 2008-10-16 | 2010-04-22 | Glaxosmithkline Llc | Method of treating thrombocytopenia |
PE20100362A1 (es) | 2008-10-30 | 2010-05-27 | Irm Llc | Derivados de purina que expanden las celulas madre hematopoyeticas |
JP2012522792A (ja) | 2009-04-01 | 2012-09-27 | プリバ フルバトゥスカ ドゥ.オ.オ. | エルトロンボパグ及びエルトロンボパグ塩の多形体、並びにその調製方法 |
US8343976B2 (en) | 2009-04-20 | 2013-01-01 | Institute For Oneworld Health | Compounds, compositions and methods comprising pyrazole derivatives |
US8476249B2 (en) | 2009-05-07 | 2013-07-02 | Glaxosmithkline Llc | Method of treating thrombocytopenia |
WO2010129738A1 (en) * | 2009-05-07 | 2010-11-11 | Glaxosmithkline Llc | Method of treating thrombocytopenia |
US8680150B2 (en) * | 2009-05-28 | 2014-03-25 | Ligand Pharmaceuticals, Inc. | Small molecule hematopoietic growth factor mimetic compounds that activate hematopoietic growth factor receptors |
HUE049075T2 (hu) * | 2009-05-29 | 2020-08-28 | Novartis Ag | Eljárás thrombopoietin-agonista vegyületek beadására |
CN101921232A (zh) * | 2009-06-11 | 2010-12-22 | 上海恒瑞医药有限公司 | 双环取代吡唑酮偶氮类衍生物的盐,其制备方法及其在医药上的应用 |
CN102639314B (zh) | 2009-12-01 | 2015-04-29 | 巴斯夫欧洲公司 | 基于聚氨酯的拉挤成型树脂体系 |
CN101805291A (zh) * | 2010-04-26 | 2010-08-18 | 西北大学 | 1-(4-异丙苯基)-3-甲基-5-吡唑啉酮及其制备方法和应用 |
AU2011296047A1 (en) | 2010-09-01 | 2013-03-21 | Novartis Ag | Combination of HDAC inhibitors with thrombocytopenia drugs |
WO2012102937A2 (en) | 2011-01-25 | 2012-08-02 | Irm Llc | Compounds that expand hematopoietic stem cells |
WO2012121958A2 (en) * | 2011-03-08 | 2012-09-13 | Glaxosmithkline Llc | Combination |
WO2012121957A1 (en) * | 2011-03-08 | 2012-09-13 | Glaxosmithkline Llc | Combination |
US20120309796A1 (en) | 2011-06-06 | 2012-12-06 | Fariborz Firooznia | Benzocycloheptene acetic acids |
EP2729560A4 (en) * | 2011-07-06 | 2014-12-03 | Cellerant Therapeutics Inc | MEGAKARYOCYTE PRE-PROVIDER CELLS FOR THE PRODUCTION OF BLOOD PLATES |
BR112014004741B1 (pt) | 2011-08-30 | 2021-10-13 | Chdi Foundation, Inc | Entidade química, seu uso e composição farmacêutica compreendendo a mesma |
US9440927B2 (en) | 2011-09-13 | 2016-09-13 | Glenmark Pharmaceuticals Limited | Process for preparation of substituted 3'-hydroazino-diphenyl-3-carboxylic acid compounds |
WO2013049605A1 (en) | 2011-09-28 | 2013-04-04 | Assia Chemical Industries Ltd. | Processes for the preparation of an intermediate in the synthesis of eltrombopag |
CA2851788C (en) | 2011-10-11 | 2022-11-29 | Dana-Farber Cancer Institute, Inc. | Pyrazol-3-ones that activate pro-apoptotic bax |
CN104039761A (zh) | 2011-11-14 | 2014-09-10 | 利亘制药公司 | 与粒细胞集落刺激因子受体相关的方法和组合物 |
AU2012347534B2 (en) | 2011-12-08 | 2018-01-25 | Fred Hutchinson Cancer Research Center | Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells |
US9409906B2 (en) | 2012-01-27 | 2016-08-09 | Universite De Montreal | Pyrimido[4,5-B]indole derivatives and use thereof in the expansion of hematopoietic stem cells |
CN103360317B (zh) * | 2012-04-11 | 2016-12-14 | 齐鲁制药有限公司 | 双环取代吡唑酮偶氮类衍生物、其制备方法及用途 |
JP2015154715A (ja) * | 2012-05-22 | 2015-08-27 | 国立大学法人旭川医科大学 | ヒト単核球由来の新規血管再生細胞群及びその分化誘導法 |
US20140047572A1 (en) * | 2012-08-13 | 2014-02-13 | University Of Rochester | Thrombopoietin mimetics for the treatment of radiation or chemical induced bone marrow injury |
WO2014150252A1 (en) | 2013-03-15 | 2014-09-25 | Ligand Pharmaceuticals Incorporated | Methods of treatment associated with the granulocyte colony-stimulating factor receptor |
EP2799425A1 (en) | 2013-04-29 | 2014-11-05 | Esteve Química, S.A. | Preparation process of an agonist of the thrombopoietin receptor |
EP3041511B1 (en) | 2013-09-02 | 2021-06-02 | Hetero Research Foundation | Compositions of eltrombopag |
ITMI20131782A1 (it) | 2013-10-25 | 2015-04-26 | Dipharma Francis Srl | Procedimento per la preparazione di un agonista della trombopoietina |
CN104628647A (zh) * | 2013-11-12 | 2015-05-20 | 上海医药工业研究院 | 3-甲基-1-(3,4-二甲基苯基)-2-吡唑啉-5-酮的制备方法 |
CN104725318A (zh) * | 2013-12-20 | 2015-06-24 | 北京蓝贝望生物医药科技股份有限公司 | 一种爱曲伯帕的合成方法 |
WO2015111085A2 (en) | 2014-01-27 | 2015-07-30 | Cadila Healthcare Limited | Processes for the preparation of eltrombopag and pharmaceutically acceptable salts, solvates and intermediates thereof |
CN106414445B (zh) | 2014-04-22 | 2020-07-03 | 蒙特利尔大学 | 化合物及其在扩增造血干细胞和/或造血祖细胞中的应用 |
SG11201700341PA (en) | 2014-07-17 | 2017-02-27 | Chdi Foundation Inc | Methods and compositions for treating hiv-related disorders |
EP3188737A4 (en) | 2014-09-05 | 2018-05-02 | Hetero Research Foundation | Crystalline form of eltrombopag free acid |
WO2016055935A1 (en) | 2014-10-06 | 2016-04-14 | Glaxosmithkline Intellectual Property (No.2) Limited | Combination of lysine-specific demethylase 1 inhibitor and thrombopoietin agonist |
EP3214209B1 (en) | 2014-10-31 | 2020-01-29 | Nissan Chemical Corporation | Ligand-binding fiber and cell culture substrate using said fiber |
CN104829593B (zh) * | 2015-03-26 | 2017-08-25 | 苏州福来兹检测科技有限公司 | 一种用于检测溶液中金属离子含量的有机化合物及其应用 |
WO2017042839A1 (en) | 2015-09-08 | 2017-03-16 | Actavis Group Ptc Ehf. | Novel eltrombopag salt and preparation thereof |
EP3445571B1 (de) | 2016-04-21 | 2020-02-26 | Basf Se | Verfahren zur herstellung von pultrudaten auf basis von polyurethan |
EP3474834A1 (en) | 2016-06-27 | 2019-05-01 | The General Hospital Corporation Dba Massachusetts General Hospital | Stimulating platelet generation by activating mitochondrial biogenesis |
US20200079958A1 (en) | 2017-03-09 | 2020-03-12 | Basf Se | Polyurethane formulations for the production of composite elements |
CN107021928B (zh) * | 2017-04-01 | 2022-11-18 | 常州制药厂有限公司 | 艾曲波帕新的中间体及其制备方法和应用 |
EP3395331B1 (en) | 2017-04-26 | 2019-08-21 | Alfred E. Tiefenbacher (GmbH & Co. KG) | Pharmaceutical tablet composition comprising eltrombopag olamine |
WO2019071111A1 (en) | 2017-10-06 | 2019-04-11 | Teva Pharmaceuticals Usa, Inc. | FORMS IN THE STRONG STATE 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 |
CN110467531B (zh) * | 2018-05-09 | 2022-04-19 | 新发药业有限公司 | 一种3’-硝基-2’-羟基联苯-3-甲酸的制备方法 |
WO2019229572A1 (en) * | 2018-06-01 | 2019-12-05 | Aurobindo Pharma Ltd | An improved process for the preparation of eltrombopag olamine and its intermediates |
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 |
US20220071961A1 (en) * | 2019-01-08 | 2022-03-10 | Jiangsu Hengrui Medicine Co., Ltd. | Dosing Regimen of Bicyclic Substituted Pyrazolone Azo Derivative |
US20220298116A1 (en) | 2019-07-04 | 2022-09-22 | F.l.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 |
CN114341112A (zh) * | 2019-10-21 | 2022-04-12 | 广东东阳光药业有限公司 | 乙酰化艾曲波帕的新晶型及其制备方法 |
CN114341113A (zh) * | 2019-10-21 | 2022-04-12 | 广东东阳光药业有限公司 | 乙酰化艾曲波帕的新晶型及其制备方法 |
AU2020397233A1 (en) | 2019-12-06 | 2022-06-30 | Synthon B.V. | Pharmaceutical composition comprising eltrombopag bis(monoethanolamine) |
WO2021110942A1 (en) | 2019-12-06 | 2021-06-10 | 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 |
CN113336704B (zh) * | 2021-06-11 | 2022-10-11 | 上海大学 | 丹参素衍生物及其制备方法和医药用途 |
CN114507186A (zh) * | 2021-12-02 | 2022-05-17 | 天津力生制药股份有限公司 | 一种艾曲波帕的制备方法 |
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 |
ES8503669A1 (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 |
EP0854052B1 (en) * | 1993-12-28 | 2000-03-22 | Dai Nippon Printing Co., Ltd. | Thermal-transfer recording sheet using a specific dye |
GB2285446B (en) * | 1994-01-03 | 1999-07-28 | Genentech Inc | Thrombopoietin |
HUT75359A (en) | 1994-02-14 | 1997-05-28 | Univ Washington | 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 |
EP2055712A1 (en) | 1995-06-07 | 2009-05-06 | 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 |
WO1999011262A1 (en) | 1997-09-02 | 1999-03-11 | Roche Diagnostics Gmbh | Mpl-receptor ligands, process for their preparation, medicaments containing them and 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 |
ES2284217T3 (es) * | 1997-10-31 | 2007-11-01 | Smithkline Beecham Corporation | Complejos metalicos novedosos. |
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 |
US7026334B1 (en) * | 1999-07-26 | 2006-04-11 | Shionogi & Co., Ltd. | Thiazolidine compounds and pharmaceutical compositions exhibiting thrombopoietin receptor agonism |
JP4488663B2 (ja) | 1999-09-10 | 2010-06-23 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | トロンボポイエチン模倣物 |
JP2003509462A (ja) | 1999-09-24 | 2003-03-11 | スミスクライン・ビーチャム・コーポレイション | トロンボポイエチン模倣物 |
AU1462201A (en) | 1999-11-05 | 2001-06-06 | 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 |
US7241783B2 (en) | 2000-12-19 | 2007-07-10 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
WO2002057300A1 (en) | 2000-12-21 | 2002-07-25 | Smithkline Beecham Corporation | Regulated activation of cell-membrane receptors by metal-chelating agonists |
CA2435143A1 (en) | 2001-01-26 | 2002-08-01 | Shionogi & Co., Ltd. | Halogen compounds having thrombopoietin receptor agonism |
US7169931B2 (en) | 2001-01-26 | 2007-01-30 | Shionogi & Co., Ltd. | Cyclic compounds exhibiting 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 |
EP1450791A1 (en) | 2001-11-30 | 2004-09-01 | Kinetek Pharmaceuticals, Inc. | Hydrazonopyrazole derivatives and their use as therapeutics |
WO2003074550A2 (en) | 2002-03-01 | 2003-09-12 | Pintex Pharmaceuticals, Inc. | Pin1-modulating compounds and methods of use thereof |
MY142390A (en) | 2002-05-22 | 2010-11-30 | Glaxosmithkline Llc | 3' - [(2z)-[1-(3,4-dimethylphenyl)-1,5- dihydro-3- methyl-5-0xo-4h-pyrazol-4- ylidene]hydrazino]-2' -hydroxy -[1,1' -biphenyl]-3-carboxylic acid bis-(monoethanolamine) |
AU2003248630A1 (en) | 2002-06-06 | 2003-12-22 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
TWI324593B (en) * | 2002-10-09 | 2010-05-11 | Nissan Chemical Ind Ltd | Pyrazolone compounds and thrombopoietin receptor activator |
WO2004054515A2 (en) | 2002-12-13 | 2004-07-01 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
US20090298179A1 (en) * | 2003-04-29 | 2009-12-03 | Connie Erickson-Miller | Methods For Treating Degenerative Diseases/Injuries |
JP4895807B2 (ja) * | 2003-04-29 | 2012-03-14 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 変性疾患/損傷の治療方法 |
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 |
DE602005024599D1 (de) * | 2004-10-25 | 2010-12-16 | Ligand Pharm Inc | Verbindungen modulierende thrombopoietinaktivität und verfahren |
EP1942906A2 (en) * | 2005-10-13 | 2008-07-16 | SmithKline Beecham Corporation | Methods for the preservation of platelet efficacy during storage |
EP2086551A4 (en) * | 2006-12-01 | 2011-06-08 | Stategics Inc | Thrombopoietin mimetics |
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