JP2012526766A - 腫瘍性及び線維性疾患の処置における新規な併用療法 - Google Patents
腫瘍性及び線維性疾患の処置における新規な併用療法 Download PDFInfo
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09160203.7 | 2009-05-14 | ||
| EP09160203 | 2009-05-14 | ||
| PCT/EP2010/056503 WO2010130757A1 (en) | 2009-05-14 | 2010-05-11 | New combination therapy in treatment of oncological and fibrotic diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012526766A true JP2012526766A (ja) | 2012-11-01 |
| JP2012526766A5 JP2012526766A5 (enExample) | 2013-06-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2012510279A Pending JP2012526766A (ja) | 2009-05-14 | 2010-05-11 | 腫瘍性及び線維性疾患の処置における新規な併用療法 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US20120142703A1 (enExample) |
| EP (2) | EP2429520A1 (enExample) |
| JP (1) | JP2012526766A (enExample) |
| WO (1) | WO2010130757A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012526767A (ja) * | 2009-05-14 | 2012-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌及び線維性疾患の処置における新規な併用療法 |
| JP2015524826A (ja) * | 2012-08-17 | 2015-08-27 | キャンサー・セラピューティクス・シーアールシー・ピーティーワイ・リミテッド | Ｖｅｇｆｒ３阻害剤 |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA107560C2 (uk) * | 2008-06-06 | 2015-01-26 | Фармацевтична лікарська форма для негайного вивільнення похідної індолінону | |
| US20170065529A1 (en) | 2015-09-09 | 2017-03-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical dosage form for immediate release of an indolinone derivative |
| EP2299987B1 (en) | 2008-06-06 | 2018-02-21 | Boehringer Ingelheim International GmbH | Capsule pharmaceutical dosage form comprising a suspension formulation of an indolinone derivative |
| CN102649778A (zh) * | 2011-02-23 | 2012-08-29 | 苏州波锐生物医药科技有限公司 | 喹唑啉衍生物及其在制备抗恶性肿瘤药物中的用途 |
| CN103102352B (zh) * | 2011-11-15 | 2015-08-12 | 山东亨利医药科技有限责任公司 | 酪氨酸激酶抑制剂吲哚满酮衍生物 |
| CN103130775B (zh) * | 2011-11-22 | 2015-09-30 | 山东亨利医药科技有限责任公司 | 作为酪氨酸激酶抑制剂的吲哚满酮衍生物 |
| CA2882270A1 (en) * | 2012-08-17 | 2014-02-20 | Cancer Therapeutics Crc Pty Limited | Vegfr3 inhibitors |
| CN103768067A (zh) * | 2012-10-23 | 2014-05-07 | 杨子娇 | 一类治疗房角狭窄的化合物及其用途 |
| WO2014138727A1 (en) * | 2013-03-08 | 2014-09-12 | Board Of Regents, The University Of Texas System | Suppression of malignant mesothelioma by overexpression or stimulation of endothelial protein c receptors (epcr) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006524634A (ja) * | 2003-04-29 | 2006-11-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ミエローマ細胞の細胞増殖、移動もしくはアポトーシス、又は血管形成と関係する疾患の治療用の組み合わせ |
| WO2008009639A2 (en) * | 2006-07-17 | 2008-01-24 | Boehringer Ingelheim International Gmbh | New indications for direct thrombin inhibitors |
| JP2008525370A (ja) * | 2004-12-24 | 2008-07-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 線維症の治療又は予防のための薬物 |
| JP2012526767A (ja) * | 2009-05-14 | 2012-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌及び線維性疾患の処置における新規な併用療法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE121699A1 (es) | 1997-02-18 | 1999-12-08 | Boehringer Ingelheim Pharma | Heterociclos biciclicos disustituidos como inhibidores de la trombina |
| UA75054C2 (uk) | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
| DE10063435A1 (de) | 2000-12-20 | 2002-07-04 | Boehringer Ingelheim Pharma | Chinazolinderviate,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DK1485094T4 (da) | 2002-03-07 | 2020-06-22 | Boehringer Ingelheim Int | Doseringsform til oral indgivelse af 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1h-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsyre-ethylester eller dets salte |
| DE10233500A1 (de) | 2002-07-24 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 3-Z-[1-(4-(N-((4-Methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylen]-6-methoxycarbonyl-2-indolinon-Monoethansulfonat und dessen Verwendung als Arzneimittel |
| DE10237423A1 (de) | 2002-08-16 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von LCK-Inhibitoren für die Behandlung von immunologischen Erkrankungen |
| DE10339862A1 (de) | 2003-08-29 | 2005-03-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 3-[(2-{[4-(Hexyloxycarbonylamino-imino-methyl)- phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsäure-ethylester-Methansulfonat und dessen Verwendung als Arzneimittel |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| JP5688877B2 (ja) | 2005-11-11 | 2015-03-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌疾患の治療用キナゾリン誘導体 |
| PT1948180E (pt) * | 2005-11-11 | 2013-05-10 | Boehringer Ingelheim Int | Tratamento de combinação de cancro compreendendo inibidores de egfr/her2 |
| WO2007057397A1 (en) * | 2005-11-15 | 2007-05-24 | Boehringer Ingelheim International Gmbh | Treatment of cancer |
| EP1870400A1 (en) | 2006-06-08 | 2007-12-26 | Boehringer Ingelheim Pharma GmbH & Co. KG | Salts and crystalline salt forms of an 2-indolinone derivative |
-
2010
- 2010-05-11 JP JP2012510279A patent/JP2012526766A/ja active Pending
- 2010-05-11 US US13/318,289 patent/US20120142703A1/en not_active Abandoned
- 2010-05-11 EP EP10721441A patent/EP2429520A1/en not_active Ceased
- 2010-05-11 WO PCT/EP2010/056503 patent/WO2010130757A1/en not_active Ceased
- 2010-05-11 EP EP13174888.1A patent/EP2647375A1/en not_active Withdrawn
-
2014
- 2014-03-06 US US14/198,726 patent/US20140187563A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006524634A (ja) * | 2003-04-29 | 2006-11-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ミエローマ細胞の細胞増殖、移動もしくはアポトーシス、又は血管形成と関係する疾患の治療用の組み合わせ |
| JP2008525370A (ja) * | 2004-12-24 | 2008-07-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 線維症の治療又は予防のための薬物 |
| WO2008009639A2 (en) * | 2006-07-17 | 2008-01-24 | Boehringer Ingelheim International Gmbh | New indications for direct thrombin inhibitors |
| JP2012526767A (ja) * | 2009-05-14 | 2012-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌及び線維性疾患の処置における新規な併用療法 |
Non-Patent Citations (5)
| Title |
|---|
| JPN6014021985; 小櫃由樹生ら: 癌と化学療法 ｖｏｌ．３６， Ｎｏ．４, 200904, ｐ．５３５-５３９ * |
| JPN6014021988; Ｍ．Ｂｅｎｅｄｅｔｔａ ｅｔ ａｌ．: Ｂｅｓｔ Ｐｒａｃｔｉｃｅ ＆ Ｒｅｓｅａｒｃｈ Ｃｌｉｎｉｃａｌ Ｈａｅｍａｔｏｌｏｇｙ ｖｏｌ．２２， Ｎｏ．１, 200903, ｐ．３-８ * |
| JPN6014021991; Ｌ．Ｈ．Ｅｉｎｈｏｒｎ ｅｔ ａｌ．: Ｊｏｕｒｎａｌ ｏｆ Ｔｈｏｒａｃｉｃ Ｏｎｃｏｌｏｇｙ ｖｏｌ．３， Ｎｏ．５, 2008, ｐ．５４５-５５５ * |
| JPN6014021994; Ｄ．Ｌ．Ｔ．Ｈｕｏｎｇ ｅｔ ａｌ．: Ａｎｎａｌｓ ｏｆ Ｒｈｅｕｍａｔｉｃ Ｄｉｓｅａｓｅｓ ｖｏｌ．５６, 1997, ｐ．２０５-２０８ * |
| JPN6014021996; Ｄ．Ｃ．Ｖａｌｌａ: Ｈｅｐａｔｏｌｏｇｙ ｖｏｌ．４７， Ｎｏ．４, 2008, ｐ．１３８４-１３９３ * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012526767A (ja) * | 2009-05-14 | 2012-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌及び線維性疾患の処置における新規な併用療法 |
| JP2015524826A (ja) * | 2012-08-17 | 2015-08-27 | キャンサー・セラピューティクス・シーアールシー・ピーティーワイ・リミテッド | Ｖｅｇｆｒ３阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010130757A1 (en) | 2010-11-18 |
| EP2429520A1 (en) | 2012-03-21 |
| US20120142703A1 (en) | 2012-06-07 |
| US20140187563A1 (en) | 2014-07-03 |
| EP2647375A1 (en) | 2013-10-09 |
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