JP2010077131A - アゾリル基を有するキノリン誘導体およびキナゾリン誘導体 - Google Patents
アゾリル基を有するキノリン誘導体およびキナゾリン誘導体 Download PDFInfo
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- JP2010077131A JP2010077131A JP2009242477A JP2009242477A JP2010077131A JP 2010077131 A JP2010077131 A JP 2010077131A JP 2009242477 A JP2009242477 A JP 2009242477A JP 2009242477 A JP2009242477 A JP 2009242477A JP 2010077131 A JP2010077131 A JP 2010077131A
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- 125000003943 azolyl group Chemical group 0.000 title claims description 13
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
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- 239000012453 solvate Substances 0.000 claims abstract description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 587
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 59
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 49
- 125000003277 amino group Chemical group 0.000 claims description 49
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- 125000005843 halogen group Chemical group 0.000 claims description 31
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
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- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 10
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- SPMVMDHWKHCIDT-UHFFFAOYSA-N 1-[2-chloro-4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-3-(5-methyl-3-isoxazolyl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC=1C=C(C)ON=1 SPMVMDHWKHCIDT-UHFFFAOYSA-N 0.000 claims description 3
- ZIYRESLEDFVZIW-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-(1,3-thiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=NC=CS1 ZIYRESLEDFVZIW-UHFFFAOYSA-N 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
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- GNOMMUQGOOPKSZ-UHFFFAOYSA-N 1-[2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-(1,3-thiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC(C=C1Cl)=CC=C1NC(=O)NC1=NC=CS1 GNOMMUQGOOPKSZ-UHFFFAOYSA-N 0.000 claims description 2
- KDDTWIVRCCWDFL-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-(4-methyl-1,3-thiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=NC(C)=CS1 KDDTWIVRCCWDFL-UHFFFAOYSA-N 0.000 claims description 2
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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 48
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
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- 229910052739 hydrogen Inorganic materials 0.000 description 13
- -1 methoxy, ethoxy, n- propoxy, i- propoxy, n- butoxy, i- butoxy, s- butoxy, t- butoxy Chemical group 0.000 description 13
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- QXTRPGAMVIONMK-UHFFFAOYSA-N 2-amino-5-ethyl-1,3,4-thiadiazole Chemical compound CCC1=NN=C(N)S1 QXTRPGAMVIONMK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
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- XMXLBDNVSIHRRA-UHFFFAOYSA-N 2-amino-4,5-dimethyl-thiazole Natural products CC=1N=C(N)SC=1C XMXLBDNVSIHRRA-UHFFFAOYSA-N 0.000 description 7
- FNXYWHTZDAVRTB-UHFFFAOYSA-N 3-methyl-1,2-oxazol-5-amine Chemical compound CC=1C=C(N)ON=1 FNXYWHTZDAVRTB-UHFFFAOYSA-N 0.000 description 7
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- FKPXGNGUVSHWQQ-UHFFFAOYSA-N 5-methyl-1,2-oxazol-3-amine Chemical compound CC1=CC(N)=NO1 FKPXGNGUVSHWQQ-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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Families Citing this family (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3519368B2 (ja) * | 1999-01-22 | 2004-04-12 | 麒麟麦酒株式会社 | キノリン誘導体およびキナゾリン誘導体 |
| TWI281915B (en) * | 1999-12-24 | 2007-06-01 | Kirin Brewery | Quinoline and quinazoline derivatives and drugs containing the same |
| US7879840B2 (en) | 2005-08-25 | 2011-02-01 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7718644B2 (en) | 2004-01-22 | 2010-05-18 | The Trustees Of Columbia University In The City Of New York | Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US6489125B1 (en) * | 2000-05-10 | 2002-12-03 | The Trustees Of Columbia University In The City Of New York | Methods for identifying chemical compounds that inhibit dissociation of FKBP12.6 binding protein from type 2 ryanodine receptor |
| US7393652B2 (en) | 2000-05-10 | 2008-07-01 | The Trustees Of Columbia University In The City Of New York | Methods for identifying a chemical compound that directly enhances binding of FKBP12.6 to PKA-phosphorylated type 2 ryanodine receptor (RyR2) |
| US20040229781A1 (en) * | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US20040048780A1 (en) * | 2000-05-10 | 2004-03-11 | The Trustees Of Columbia University In The City Of New York | Method for treating and preventing cardiac arrhythmia |
| US20060293266A1 (en) * | 2000-05-10 | 2006-12-28 | The Trustees Of Columbia | Phosphodiesterase 4D in the ryanodine receptor complex protects against heart failure |
| ATE419239T1 (de) | 2000-10-20 | 2009-01-15 | Eisai R&D Man Co Ltd | Verfahren zur herstellung von 4-phenoxy chinolin derivaten |
| AU2002255284B2 (en) | 2001-04-27 | 2007-10-04 | Kyowa Kirin Co., Ltd. | Quinoline derivative having azolyl group and quinazoline derivative |
| EP2088141A3 (en) * | 2001-06-22 | 2009-11-18 | Kirin Pharma Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives capable of inhibiting autophosphorylation of hepatocyte growth factor receptors, and pharmaceutical composition comprising the same |
| WO2003033472A1 (en) * | 2001-10-17 | 2003-04-24 | Kirin Beer Kabushiki Kaisha | Quinoline or quinazoline derivatives inhibiting auto- phosphorylation of fibroblast growth factor receptors |
| WO2003093238A1 (en) * | 2002-05-01 | 2003-11-13 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of macrophage colony stimulating factor receptor |
| EP2280003B1 (en) | 2002-07-15 | 2014-04-02 | Symphony Evolution, Inc. | Process for preparing receptor-type kinase modulators |
| WO2004035572A1 (ja) * | 2002-10-21 | 2004-04-29 | Kirin Beer Kabushiki Kaisha | Ｎ−｛２−クロロ−４−［（６，７−ジメトキシ−４−キノリル）オキシ］フェニル｝−ｎ’−（５−メチル−３−イソキサゾリル）ウレアの塩の結晶形 |
| US20080207617A1 (en) * | 2002-10-29 | 2008-08-28 | Kirin Beer Kabushiki Kaisha | Quinoline Derivatives and Quinazoline Derivatives Inhibiting Autophosphrylation of Flt3 and Medicinal Compositions Containing the Same |
| US7544678B2 (en) | 2002-11-05 | 2009-06-09 | The Trustees Of Columbia University In The City Of New York | Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| AU2003292838A1 (en) * | 2002-12-27 | 2004-07-29 | Kirin Beer Kabushiki Kaisha | Therapeutic agent for wet age-related macular degeneration |
| JP2007525165A (ja) | 2003-03-07 | 2007-09-06 | トラスティーズ・オブ・コロンビア・ユニバーシティ・イン・ザ・シティ・オブ・ニューヨーク | タイプ１ライアノジン受容体に基づく方法 |
| JPWO2004080462A1 (ja) * | 2003-03-10 | 2006-06-08 | エーザイ株式会社 | ｃ−Ｋｉｔキナーゼ阻害剤 |
| EP2392565B1 (en) | 2003-09-26 | 2014-03-19 | Exelixis, Inc. | c-Met modulators and methods of use |
| CN101337930B (zh) | 2003-11-11 | 2010-09-08 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
| CA2545711A1 (en) * | 2003-11-13 | 2005-06-02 | Ambit Biosciences Corporation | Urea derivatives as kinase modulators |
| US8710045B2 (en) | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| WO2005073224A2 (en) * | 2004-01-23 | 2005-08-11 | Amgen Inc | Quinoline quinazoline pyridine and pyrimidine counds and their use in the treatment of inflammation angiogenesis and cancer |
| TW200530236A (en) | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
| JP4834553B2 (ja) | 2004-09-17 | 2011-12-14 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 医薬組成物 |
| CA2603748A1 (en) * | 2005-04-06 | 2006-10-12 | Exelixis, Inc. | C-met modulators and methods of use |
| TW200740820A (en) * | 2005-07-05 | 2007-11-01 | Takeda Pharmaceuticals Co | Fused heterocyclic derivatives and use thereof |
| WO2007015569A1 (ja) * | 2005-08-01 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を予測する方法 |
| EP1925676A4 (en) | 2005-08-02 | 2010-11-10 | Eisai R&D Man Co Ltd | TEST METHOD FOR THE EFFECT OF A VASCULARIZATION INHIBITOR |
| US7704990B2 (en) | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| EP1938842A4 (en) * | 2005-09-01 | 2013-01-09 | Eisai R&D Man Co Ltd | METHOD FOR PRODUCING A PHARMACEUTICAL COMPOSITION COMPRISING IMPROVED CRASHING CHARACTERISTICS |
| JPWO2007052849A1 (ja) * | 2005-11-07 | 2009-04-30 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質とｃ−ｋｉｔキナーゼ阻害物質との併用 |
| WO2007061127A1 (ja) * | 2005-11-22 | 2007-05-31 | Eisai R & D Management Co., Ltd. | 多発性骨髄腫に対する抗腫瘍剤 |
| RU2448708C3 (ru) * | 2006-05-18 | 2017-09-28 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое средство против рака щитовидной железы |
| EP2044939A1 (en) * | 2006-06-29 | 2009-04-08 | Eisai R&D Management Co., Ltd. | Therapeutic agent for liver fibrosis |
| US8865737B2 (en) | 2006-08-28 | 2014-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for undifferentiated gastric cancer |
| WO2008093855A1 (ja) | 2007-01-29 | 2008-08-07 | Eisai R & D Management Co., Ltd. | 未分化型胃癌治療用組成物 |
| ES2635131T3 (es) | 2007-08-29 | 2017-10-02 | Methylgene Inc. | Inhibidores de la actividad de la proteína tirosina cinasa |
| KR101513326B1 (ko) | 2007-11-09 | 2015-04-17 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 혈관 신생 저해 물질과 항종양성 백금 착물의 병용 |
| MX2010008187A (es) * | 2008-01-29 | 2010-08-10 | Eisai R&D Man Co Ltd | Uso combinado de inhibidor de angiogenesis y taxano. |
| HUE025197T2 (en) * | 2008-03-17 | 2016-02-29 | Ambit Biosciences Corp | Quinazoline derivatives as RAF kinase modulators and methods for their use |
| RS52754B2 (sr) | 2009-01-16 | 2022-08-31 | Exelixis Inc | Malat so n-(4- {[6,7-bis(metiloksi)hinolin-4-il]oksi}fenil-n'- (4-fluorofenil) ciklopropan-1,1-dikarboksamid-a, i njeni kristalni oblici za lečenje karcinoma |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| TH121482A (th) | 2009-08-19 | 2013-02-28 | นางสาวปัณณพัฒน์ เหลืองธาตุทอง | องค์ประกอบทางเภสัชกรรมที่ประกอบด้วยอนุพันธ์ของควิโนลีน |
| US7998973B2 (en) * | 2009-11-13 | 2011-08-16 | Aveo Pharmaceuticals, Inc. | Tivozanib and temsirolimus in combination |
| AU2011270165B2 (en) | 2010-06-25 | 2015-12-24 | Eisai R&D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
| US20130225581A1 (en) * | 2010-07-16 | 2013-08-29 | Kyowa Hakko Kirin Co., Ltd | Nitrogen-containing aromatic heterocyclic derivative |
| EA022873B1 (ru) | 2010-10-27 | 2016-03-31 | Новартис Аг | Применение ингибитора vegf-r2 для лечения офтальмологического сосудистого заболевания |
| WO2012144463A1 (ja) | 2011-04-18 | 2012-10-26 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| CN102532116B (zh) * | 2011-08-09 | 2015-01-21 | 武汉迈德森医药科技有限公司 | 抗肿瘤靶向治疗药物tivozanib的合成方法 |
| CN102408411B (zh) * | 2011-09-19 | 2014-10-22 | 北京康辰药业股份有限公司 | 一种含喹啉基的羟肟酸类化合物及其制备方法、以及含有该化合物的药物组合物及其应用 |
| CN102408418A (zh) * | 2011-10-21 | 2012-04-11 | 武汉迈德森医药科技有限公司 | Tivozanib酸性盐及其制备方法和晶型 |
| EP2626073A1 (en) | 2012-02-13 | 2013-08-14 | Harmonic Pharma | Compound for use in the prevention and/or treatment of a neurogenerative disease or a disease involving an activation of phosphodiesterase-4 (PDE4) |
| RU2015115397A (ru) | 2012-12-21 | 2017-01-25 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Аморфная форма производного хинолина и способ его получения |
| ES2687968T3 (es) | 2013-05-14 | 2018-10-30 | Eisai R&D Management Co., Ltd. | Biomarcadores para pronosticar y evaluar la reactividad de sujetos con cáncer de endometrio a compuestos con lenvatinib |
| EA201690212A8 (ru) | 2013-07-12 | 2016-08-31 | Офтотек Корпорейшн | Способы лечения или профилактики офтальмологических патологических состояний |
| KR20230043234A (ko) | 2014-08-28 | 2023-03-30 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 고순도의 퀴놀린 유도체 및 이를 제조하는 방법 |
| SG11201705767PA (en) | 2015-01-13 | 2017-08-30 | Univ Kyoto | Agent for preventing and/or treating amyotrophic lateral sclerosis |
| LT3263106T (lt) | 2015-02-25 | 2024-01-10 | Eisai R&D Management Co., Ltd. | Chinolino darinių kartumo sumažinimo būdas |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| MX373231B (es) | 2015-06-16 | 2020-05-08 | Eisai R&D Man Co Ltd | Agente anticancerigeno. |
| CA2994925C (en) | 2015-08-20 | 2023-08-29 | Eisai R&D Management Co., Ltd. | Tumor therapeutic agent |
| WO2017062500A2 (en) | 2015-10-05 | 2017-04-13 | The Trustees Of Columbia University In The City Of New York | Activators of autophagic flux and phospholipase d and clearance of protein aggregates including tau and treatment of proteinopathies |
| CN107698562A (zh) * | 2016-08-09 | 2018-02-16 | 殷建明 | 一种喹啉衍生物及其用途 |
| CN106478621B (zh) * | 2016-09-30 | 2018-12-25 | 遵义医学院 | 喹啉或喹唑啉类衍生物、制备方法及其应用 |
| JP7105774B2 (ja) | 2016-12-01 | 2022-07-25 | イグナイタ インコーポレイテッド | がん治療のための方法 |
| CN108341813B (zh) * | 2017-01-24 | 2020-11-17 | 四川大学 | 取代的1-(异恶唑-3-基)-3-(3-氟-4-苯基)脲衍生物及其制备方法和用途 |
| US12303505B2 (en) | 2017-02-08 | 2025-05-20 | Eisai R&D Management Co., Ltd. | Tumor-treating pharmaceutical composition |
| CN108530455B (zh) | 2017-03-01 | 2021-01-12 | 北京赛特明强医药科技有限公司 | 脲取代的芳环连二噁烷并喹唑啉类化合物或药用盐或水合物及作为酪氨酸激酶抑制剂的应用 |
| WO2018197643A1 (en) * | 2017-04-27 | 2018-11-01 | Astrazeneca Ab | Phenoxyquinazoline compounds and their use in treating cancer |
| EP3615522B1 (en) | 2017-04-27 | 2021-08-04 | Astrazeneca AB | C5-anilinoquinazoline compounds and their use in treating cancer |
| BR112019023064A2 (pt) | 2017-05-16 | 2020-06-09 | Eisai R&D Man Co Ltd | tratamento de carcinoma hepatocelular |
| CN109553612B (zh) * | 2017-09-26 | 2021-09-03 | 广西梧州制药（集团）股份有限公司 | 一种吡唑并嘧啶衍生物及其制备方法和在药物制备中的用途 |
| EP3750894B1 (en) | 2018-02-11 | 2024-04-03 | Beijing Scitech-MQ Pharmaceuticals Limited | Urea-substituted aromatic ring-linked dioxazoline compound, preparation method therefor, and uses thereof |
| CA3118690A1 (en) | 2018-11-05 | 2020-05-14 | Aveo Pharmaceuticals, Inc. | Use of tivozanib to treat subjects with refractory cancer |
| US20220040324A1 (en) | 2018-12-21 | 2022-02-10 | Daiichi Sankyo Company, Limited | Combination of antibody-drug conjugate and kinase inhibitor |
| WO2023081923A1 (en) | 2021-11-08 | 2023-05-11 | Frequency Therapeutics, Inc. | Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof |
| WO2023096651A1 (en) | 2021-11-26 | 2023-06-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods for treating bile duct cancers with tivozanib |
| AU2023274540A1 (en) | 2022-05-24 | 2024-12-12 | Daiichi Sankyo Company, Limited | Dosage regimen of an anti-cdh6 antibody-drug conjugate |
| WO2024095127A1 (en) | 2022-10-31 | 2024-05-10 | Pliva Hrvatska D.O.O. | Solid state forms of tivozanib and process for preparation thereof |
| WO2024110606A1 (en) | 2022-11-25 | 2024-05-30 | Synthon B.V. | A process for preparation of cabozantinib or tivozanib |
| WO2025120654A1 (en) * | 2023-12-05 | 2025-06-12 | Natco Pharma Limited | An improved process for the preparation of tivozanib hydrochloride hydrate |
| WO2025253311A1 (en) | 2024-06-04 | 2025-12-11 | Hetero Labs Limited | 1,2-dicarboxamide compounds as kinase inhibitors |
Family Cites Families (11)
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| JP2728878B2 (ja) | 1987-12-15 | 1998-03-18 | 大倉工業株式会社 | 中空押出成形板 |
| GB9000644D0 (en) * | 1990-01-11 | 1990-03-14 | Erba Carlo Spa | New ureido derivatives of poly-4-amino-2-carboxy-1-methyl compounds |
| WO1997017329A1 (en) | 1995-11-07 | 1997-05-15 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of growth factor receptor originating in platelet and pharmaceutical compositions containing the same |
| JP4194678B2 (ja) | 1997-11-28 | 2008-12-10 | キリンファーマ株式会社 | キノリン誘導体およびそれを含む医薬組成物 |
| ES2154253T3 (es) | 1997-12-22 | 2012-01-27 | Bayer Healthcare Llc | Inhibición de la actividad de p38 cinasa usando ureas heterocíclicas sustituidas. |
| EP1047418B1 (en) * | 1997-12-22 | 2005-07-27 | Bayer Pharmaceuticals Corp. | Inhibition of raf kinase using substituted heterocyclic ureas |
| JP3519368B2 (ja) * | 1999-01-22 | 2004-04-12 | 麒麟麦酒株式会社 | キノリン誘導体およびキナゾリン誘導体 |
| TWI281915B (en) | 1999-12-24 | 2007-06-01 | Kirin Brewery | Quinoline and quinazoline derivatives and drugs containing the same |
| JP2002030083A (ja) | 2000-07-18 | 2002-01-29 | Kirin Brewery Co Ltd | Ｎ−（２−クロロ−４−｛［６−メトキシ−７−（３−ピリジルメトキシ）−４−キノリル］オキシ｝フェニル）−ｎ’−プロピルウレアの二塩酸塩 |
| ATE419239T1 (de) * | 2000-10-20 | 2009-01-15 | Eisai R&D Man Co Ltd | Verfahren zur herstellung von 4-phenoxy chinolin derivaten |
| AU2002255284B2 (en) * | 2001-04-27 | 2007-10-04 | Kyowa Kirin Co., Ltd. | Quinoline derivative having azolyl group and quinazoline derivative |
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