CA2898294C - Heteroaromatic compounds as pi3 kinase modulators - Google Patents
Heteroaromatic compounds as pi3 kinase modulators Download PDFInfo
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- CA2898294C CA2898294C CA2898294A CA2898294A CA2898294C CA 2898294 C CA2898294 C CA 2898294C CA 2898294 A CA2898294 A CA 2898294A CA 2898294 A CA2898294 A CA 2898294A CA 2898294 C CA2898294 C CA 2898294C
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- Prior art keywords
- cancer
- alkylene
- cycloalkyl
- alkyl
- compound
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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
- A61K31/435—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
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201361767721P | 2013-02-21 | 2013-02-21 | |
| US61/767,721 | 2013-02-21 | ||
| PCT/US2014/016643 WO2014130375A1 (en) | 2013-02-21 | 2014-02-15 | Heteroaromatic compounds as pi3 kinase modulators |
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| CA2898294A1 CA2898294A1 (en) | 2014-08-28 |
| CA2898294C true CA2898294C (en) | 2020-06-09 |
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| CA2995997A1 (en) | 2015-08-26 | 2017-03-02 | Blueprint Medicines Corporation | Compounds and compositions useful for treating disorders related to ntrk |
| KR20180081790A (ko) | 2015-11-19 | 2018-07-17 | 블루프린트 메디신즈 코포레이션 | Ntrk 관련 장애의 치료에 유용한 화합물 및 조성물 |
| JP7193460B2 (ja) * | 2016-12-23 | 2022-12-20 | プレキシコン インコーポレーテッド | Ｃｄｋ８調節およびその適応症のための化合物および方法 |
| AU2018209164B2 (en) | 2017-01-17 | 2021-11-04 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
| WO2018169700A1 (en) * | 2017-03-14 | 2018-09-20 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| CN109867671B (zh) * | 2017-12-02 | 2020-07-07 | 广东东阳光药业有限公司 | 一种吡唑[1,5-a]吡啶化合物的晶型及其药物组合物和用途 |
| CN109867672B (zh) * | 2017-12-02 | 2020-07-07 | 广东东阳光药业有限公司 | 吡唑[1,5-a]吡啶衍生物的盐及其用途 |
| CN109867670B (zh) * | 2017-12-02 | 2020-07-07 | 广东东阳光药业有限公司 | 一种吡唑[1,5-a]吡啶化合物的单钠盐及其医药用途 |
| CN109867669B (zh) * | 2017-12-02 | 2021-02-26 | 广东东阳光药业有限公司 | 一种吡唑[1,5-a]吡啶化合物的晶型及其药物组合物和用途 |
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| ES2222813B1 (es) * | 2003-07-24 | 2005-12-16 | Ferrer Internacional, S.A. | N-(3-(3-sustituidas-pirazolo(1,5-a)pirimidin-7-il)-fenil)-sulfonamidas y composiciones y metodos relacionados. |
| EP1663953A1 (en) | 2003-09-24 | 2006-06-07 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7329662B2 (en) | 2003-10-03 | 2008-02-12 | Hoffmann-La Roche Inc. | Pyrazolo-pyridine |
| KR101258504B1 (ko) | 2004-03-26 | 2013-04-26 | 메틸진 인코포레이티드 | 히스톤 데아세틸라제의 억제제 |
| WO2006010264A1 (en) | 2004-07-30 | 2006-02-02 | Methylgene, Inc. | Inhibitors of vegf receptor and hgf receptor signaling |
| EP1863818B1 (en) | 2005-03-23 | 2010-03-10 | F.Hoffmann-La Roche Ag | Acetylenyl-pyrazolo-pvrimidine derivatives as mglur2 antagonists |
| JP2011500823A (ja) * | 2007-10-22 | 2011-01-06 | 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 | Ｐｉ３キナーゼ阻害物質としてのピリドスルホンアミド誘導体 |
| US7820665B2 (en) | 2007-12-19 | 2010-10-26 | Amgen Inc. | Imidazopyridazine inhibitors of PI3 kinase for cancer treatment |
| EP2417138B1 (en) | 2009-04-09 | 2019-11-27 | Merck Sharp & Dohme Corp. | Pyrazolo[1, 5-a]pyrimidine derivatives as mtor inhibitors |
| UA111579C2 (uk) | 2009-08-17 | 2016-05-25 | Інтеллікіне Ллк | ГЕТЕРОЦИКЛІЧНІ ПОХІДНІ 2-АМІНОБЕНЗО[d]ОКСАЗОЛУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ НА ЇХ ОСНОВІ ТА ЇХ ЗАСТОСУВАННЯ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАННЯ, ПОВ'АНОГО З РІ3-КІНАЗОЮ |
| EP2608669B1 (en) * | 2010-08-23 | 2016-06-22 | Merck Sharp & Dohme Corp. | NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
| CN102675286B (zh) | 2011-03-07 | 2015-08-19 | 中国科学院上海药物研究所 | 一类吲唑类化合物及其制备方法、用途和药物组合物 |
| US9284334B2 (en) * | 2011-05-19 | 2016-03-15 | Fundación Centro Nacional De Investigaciones Oncologicas Carlos Iii | Macrocyclic compounds as protein kinase inhibitors |
| WO2012174312A2 (en) | 2011-06-15 | 2012-12-20 | Glaxosmithkline Llc | Benzimidazole derivatives as antiviral agents |
| KR101274986B1 (ko) | 2011-07-27 | 2013-06-17 | 한국과학기술원 | 이미다조피리딘 유도체, 이를 포함하는 ＰＩ3Ｋ 및/또는 ｍＴＯＲ 저해제용 약학 조성물 및 ＰＩ3Ｋ 및/또는 ｍＴＯＲ과 연관된 질환 치료용 약학 조성물 |
| GB201205669D0 (en) | 2012-03-30 | 2012-05-16 | Agency Science Tech & Res | Bicyclic heterocyclic derivatives as mnk2 and mnk2 modulators and uses thereof |
| CN102924450A (zh) | 2012-11-01 | 2013-02-13 | 西安交通大学 | 6-(5-吡啶基)-1,2,4-三唑并吡啶类化合物及其制备方法和用途 |
-
2014
- 2014-02-15 BR BR112015018318A patent/BR112015018318A2/pt not_active Application Discontinuation
- 2014-02-15 CA CA2898294A patent/CA2898294C/en active Active
- 2014-02-15 MY MYPI2015702491A patent/MY182036A/en unknown
- 2014-02-15 SG SG11201505493QA patent/SG11201505493QA/en unknown
- 2014-02-15 AU AU2014219256A patent/AU2014219256B2/en active Active
- 2014-02-15 EP EP14754663.4A patent/EP2958564B1/en active Active
- 2014-02-15 JP JP2015558892A patent/JP6389829B2/ja active Active
- 2014-02-15 MX MX2015010700A patent/MX2015010700A/es unknown
- 2014-02-15 ES ES14754663.4T patent/ES2674705T3/es active Active
- 2014-02-15 WO PCT/US2014/016643 patent/WO2014130375A1/en not_active Ceased
- 2014-02-15 RU RU2015131467A patent/RU2672910C9/ru active
- 2014-02-15 US US14/181,670 patent/US9573953B2/en active Active
- 2014-02-15 KR KR1020157019069A patent/KR102148681B1/ko active Active
- 2014-02-18 TW TW103105349A patent/TWI620749B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| MX2015010700A (es) | 2017-01-23 |
| EP2958564A1 (en) | 2015-12-30 |
| RU2015131467A (ru) | 2017-03-24 |
| WO2014130375A1 (en) | 2014-08-28 |
| EP2958564B1 (en) | 2018-05-09 |
| HK1218385A1 (en) | 2017-02-17 |
| TWI620749B (zh) | 2018-04-11 |
| RU2672910C2 (ru) | 2018-11-21 |
| AU2014219256A1 (en) | 2015-07-30 |
| RU2672910C9 (ru) | 2019-06-04 |
| EP2958564A4 (en) | 2016-10-26 |
| KR20150118102A (ko) | 2015-10-21 |
| AU2014219256B2 (en) | 2017-02-16 |
| SG11201505493QA (en) | 2015-08-28 |
| TW201443049A (zh) | 2014-11-16 |
| US20140234254A1 (en) | 2014-08-21 |
| CA2898294A1 (en) | 2014-08-28 |
| US9573953B2 (en) | 2017-02-21 |
| JP6389829B2 (ja) | 2018-09-12 |
| MY182036A (en) | 2021-01-18 |
| KR102148681B1 (ko) | 2020-08-27 |
| JP2016509056A (ja) | 2016-03-24 |
| ES2674705T3 (es) | 2018-07-03 |
| BR112015018318A2 (pt) | 2017-08-22 |
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