CA2520323C - Tie-2 modulators and methods of use - Google Patents
Tie-2 modulators and methods of use Download PDFInfo
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- CA2520323C CA2520323C CA2520323A CA2520323A CA2520323C CA 2520323 C CA2520323 C CA 2520323C CA 2520323 A CA2520323 A CA 2520323A CA 2520323 A CA2520323 A CA 2520323A CA 2520323 C CA2520323 C CA 2520323C
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- Prior art keywords
- optionally substituted
- pyridin
- ring
- ylquinazolin
- c6alkyl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- 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
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46144603P | 2003-04-09 | 2003-04-09 | |
| US60/461,446 | 2003-04-09 | ||
| PCT/US2004/010858 WO2004092196A2 (en) | 2003-04-09 | 2004-04-08 | Tie-2 modulators and methods of use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2520323A1 CA2520323A1 (en) | 2004-10-28 |
| CA2520323C true CA2520323C (en) | 2013-07-09 |
Family
ID=33299811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2520323A Expired - Fee Related CA2520323C (en) | 2003-04-09 | 2004-04-08 | Tie-2 modulators and methods of use |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7763627B2 (https=) |
| EP (1) | EP1610774A4 (https=) |
| JP (1) | JP4895806B2 (https=) |
| AU (2) | AU2004230928B2 (https=) |
| CA (1) | CA2520323C (https=) |
| WO (1) | WO2004092196A2 (https=) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2564355C (en) | 2004-05-07 | 2012-07-03 | Amgen Inc. | Protein kinase modulators and method of use |
| WO2006045010A2 (en) | 2004-10-20 | 2006-04-27 | Resverlogix Corp. | Stilbenes and chalcones for the prevention and treatment of cardiovascular diseases |
| KR20060079121A (ko) * | 2004-12-31 | 2006-07-05 | 에스케이케미칼주식회사 | 당뇨 및 비만 치료예방에 유효한 퀴나졸린 유도체 |
| US8410109B2 (en) | 2005-07-29 | 2013-04-02 | Resverlogix Corp. | Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices |
| PT2118074E (pt) | 2007-02-01 | 2014-03-20 | Resverlogix Corp | Compostos para a prevenção e tratamento de doenças cardiovasculares |
| SI2346837T1 (sl) | 2008-06-26 | 2015-05-29 | Resverlogix Corporation | Postopki pripravljanja kinazolinonskih derivatov |
| EP2307456B1 (en) | 2008-06-27 | 2014-10-15 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| ES2599458T3 (es) * | 2008-10-14 | 2017-02-01 | Sunshine Lake Pharma Co., Ltd. | Compuestos y métodos de uso |
| US8952021B2 (en) | 2009-01-08 | 2015-02-10 | Resverlogix Corp. | Compounds for the prevention and treatment of cardiovascular disease |
| KR101913109B1 (ko) | 2009-03-18 | 2018-10-31 | 리스버로직스 코퍼레이션 | 신규한 소염제 |
| EP2408300B1 (en) | 2009-03-21 | 2016-05-11 | Sunshine Lake Pharma Co., Ltd. | Amino ester derivatives, salts thereof and methods of use |
| US9757368B2 (en) | 2009-04-22 | 2017-09-12 | Resverlogix Corp. | Anti-inflammatory agents |
| WO2011036074A1 (en) | 2009-09-24 | 2011-03-31 | Basf Se | Aminoquinazoline compounds for combating invertebrate pests |
| AR079814A1 (es) * | 2009-12-31 | 2012-02-22 | Otsuka Pharma Co Ltd | Compuestos heterociclicos, composiciones farmaceuticas que los contienen y sus usos |
| BR112014007310A2 (pt) | 2011-09-27 | 2017-04-04 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inibidores de idh mutante |
| CA2851996C (en) | 2011-11-01 | 2020-01-07 | Resverlogix Corp. | Pharmaceutical compositions for substituted quinazolinones |
| UY34632A (es) | 2012-02-24 | 2013-05-31 | Novartis Ag | Compuestos de oxazolidin- 2- ona y usos de los mismos |
| KR102215272B1 (ko) * | 2012-09-28 | 2021-02-15 | 이그니타, 인코포레이티드 | 비정형 단백질 키나제 c의 아자퀴나졸린 억제제 |
| US9296733B2 (en) | 2012-11-12 | 2016-03-29 | Novartis Ag | Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| JP2016507496A (ja) | 2012-12-21 | 2016-03-10 | ゼニス・エピジェネティクス・コーポレイションＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｃｏｒｐ． | ブロモドメイン阻害剤としての新規複素環式化合物 |
| JP6387360B2 (ja) | 2013-03-14 | 2018-09-05 | ノバルティス アーゲー | 変異ｉｄｈの阻害薬としての３−ピリミジン−４−イル−オキサゾリジン−２−オン |
| WO2015112739A1 (en) * | 2014-01-22 | 2015-07-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Compounds and method for treating parp1-deficient cancers |
| EP3226868A4 (en) | 2014-12-05 | 2018-08-15 | Subramaniam Ananthan | Novel quinazolines as biogenic amine transport modulators |
| CA2969839A1 (en) * | 2014-12-05 | 2016-06-09 | Subramaniam Ananthan | Heterocyclic compounds as biogenic amine transport modulators |
| US10111885B2 (en) | 2015-03-13 | 2018-10-30 | Resverlogix Corp. | Compositions and therapeutic methods for the treatment of complement-associated diseases |
| CN108290855A (zh) * | 2015-07-01 | 2018-07-17 | 西北大学 | 被取代的喹唑啉化合物及其调节葡糖脑苷脂酶活性的用途 |
| WO2017216726A1 (en) | 2016-06-13 | 2017-12-21 | Glaxosmithkline Intellectual Property Development Limited | Substituted pyridines as inhibitors of dnmt1 |
| MX2019012431A (es) | 2017-04-21 | 2020-08-03 | Ikena Oncology Inc | Inhibidores del receptor de hidrocarburos de arilo (ahr) de indol y usos de los mismos. |
| US11254654B2 (en) * | 2017-06-30 | 2022-02-22 | The University Of North Carolina At Chapel Hill | Heterochromatin gene repression inhibitors |
| EP3867253A4 (en) * | 2018-10-16 | 2022-05-18 | Ikena Oncology, Inc. | Indole ahr inhibitors and uses thereof |
| AU2020394424A1 (en) | 2019-11-26 | 2022-06-16 | Ikena Oncology, Inc. | Polymorphic carbazole derivatives and uses thereof |
| US20230339866A1 (en) * | 2020-02-04 | 2023-10-26 | TroBio Therapeutics Pty Ltd | Quinazoline compounds and the use thereof in the treatment of cancer |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3340260A (en) | 1962-12-03 | 1967-09-05 | Ciba Geigy Corp | 4-amino-pyrimidines |
| FR2263750A1 (en) * | 1974-03-12 | 1975-10-10 | Delalande Sa | N-phenyl-N-(2-aryl-6-methyl-pyrimidin-4-yl)amino acid derivs. - useful e.g. as analeptics, hypotensives, analgesics, etc. |
| US4306065A (en) * | 1979-12-19 | 1981-12-15 | A. H. Robins Company, Incorporated | 2-Aryl-4-substituted quinazolines |
| JP2657760B2 (ja) * | 1992-07-15 | 1997-09-24 | 小野薬品工業株式会社 | ４−アミノキナゾリン誘導体およびそれを含有する医薬品 |
| GB2295387A (en) * | 1994-11-23 | 1996-05-29 | Glaxo Inc | Quinazoline antagonists of alpha 1c adrenergic receptors |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| DE19904710A1 (de) * | 1999-02-05 | 2000-08-10 | Aventis Pharma Gmbh | Substituierte 4-Amino-2-aryl-tetrahydrochinazoline, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| WO2001036392A1 (en) * | 1999-11-17 | 2001-05-25 | Dainippon Pharmaceutical Co., Ltd. | [5-chloro-6-phenyl-2-(4-trifluoromethylphenyl)-4-pyrimidinylamino]acetamide derivatives, process for producing the same, medicinal compositions containing the same and intermediate of these compounds |
| HK1050319B (en) * | 1999-12-02 | 2007-04-04 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine a1, a2a, and a3 receptor and uses thereof |
| KR100774855B1 (ko) * | 2000-04-27 | 2007-11-08 | 아스텔라스세이야쿠 가부시키가이샤 | 축합 헤테로아릴 유도체 |
| WO2002022605A1 (en) * | 2000-09-15 | 2002-03-21 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| JP2004509876A (ja) * | 2000-09-20 | 2004-04-02 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | ４−アミノ−キナゾリン |
| EP1351691A4 (en) * | 2000-12-12 | 2005-06-22 | Cytovia Inc | SUBSTITUTED 2-ARYL-4-ARYLAMINOPYRIMIDINES AND ANALOGUES AS ACTIVATORS OF CASPASES AND APOPTOSIS INDUCERS, AND USE THEREOF |
| CA2433090A1 (en) * | 2000-12-27 | 2002-07-04 | Kyowa Hakko Kogyo Co., Ltd. | Dipeptidyl peptidase iv inhibitor |
| US20040102455A1 (en) * | 2001-01-30 | 2004-05-27 | Burns Christopher John | Method of inhibiting kinases |
| WO2002062767A1 (en) * | 2001-02-07 | 2002-08-15 | Sumitomo Pharmaceuticals Company, Limited | Novel quinazoline derivatives |
| UY27224A1 (es) * | 2001-03-23 | 2002-10-31 | Bayer Corp | Inhibidores de la rho-quinasa |
| WO2003026661A1 (fr) * | 2001-09-14 | 2003-04-03 | Yamanouchi Pharmaceutical Co., Ltd. | Accelerateur de secretion de l'insuline et nouveau derive de pyrimidine |
| ATE466581T1 (de) * | 2001-12-07 | 2010-05-15 | Vertex Pharma | Verbindungen auf pyrimidin-basis als gsk-3-hemmer |
| WO2004030672A1 (en) * | 2002-10-02 | 2004-04-15 | Merck Patent Gmbh | Use of 4 amino-quinazolines as anti cancer agents |
| GB0301016D0 (en) * | 2003-01-16 | 2003-02-19 | Univ London | Treatment of benign prostatic hyperplasia |
| ES2217956B1 (es) * | 2003-01-23 | 2006-04-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de 4-aminotieno(2,3-d)pirimidin-6-carbonitrilo. |
| WO2004065392A1 (en) * | 2003-01-24 | 2004-08-05 | Smithkline Beecham Corporation | Condensed pyridines and pyrimidines and their use as alk-5 receptor ligands |
| CL2004000409A1 (es) * | 2003-03-03 | 2005-01-07 | Vertex Pharma | Compuestos derivados de 2-(cilo sustituido)-1-(amino u oxi sustituido)-quinazolina, inhibidores de canales ionicos de sodio y calcio dependientes de voltaje; composicion farmaceutica; y uso del compuesto en el tratamiento de dolor agudo, cronico, neu |
| DE602004014347D1 (de) * | 2003-03-12 | 2008-07-24 | Millennium Pharm Inc | Chinazolin-derivate als tgf-beta-inhibitoren |
-
2004
- 2004-04-08 JP JP2006509820A patent/JP4895806B2/ja not_active Expired - Fee Related
- 2004-04-08 CA CA2520323A patent/CA2520323C/en not_active Expired - Fee Related
- 2004-04-08 US US10/552,426 patent/US7763627B2/en not_active Expired - Fee Related
- 2004-04-08 AU AU2004230928A patent/AU2004230928B2/en not_active Ceased
- 2004-04-08 EP EP04749893A patent/EP1610774A4/en not_active Withdrawn
- 2004-04-08 WO PCT/US2004/010858 patent/WO2004092196A2/en not_active Ceased
-
2010
- 2010-11-04 AU AU2010241235A patent/AU2010241235A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004230928B2 (en) | 2010-12-02 |
| US7763627B2 (en) | 2010-07-27 |
| WO2004092196A3 (en) | 2005-03-17 |
| CA2520323A1 (en) | 2004-10-28 |
| US20070161651A1 (en) | 2007-07-12 |
| JP4895806B2 (ja) | 2012-03-14 |
| AU2010241235A1 (en) | 2010-11-25 |
| EP1610774A2 (en) | 2006-01-04 |
| EP1610774A4 (en) | 2008-07-16 |
| AU2004230928A1 (en) | 2004-10-28 |
| WO2004092196A2 (en) | 2004-10-28 |
| JP2006523238A (ja) | 2006-10-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160408 |