CN107137402A - 用tor激酶抑制剂治疗癌症 - Google Patents
用tor激酶抑制剂治疗癌症 Download PDFInfo
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- CN107137402A CN107137402A CN201710422322.9A CN201710422322A CN107137402A CN 107137402 A CN107137402 A CN 107137402A CN 201710422322 A CN201710422322 A CN 201710422322A CN 107137402 A CN107137402 A CN 107137402A
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- Prior art keywords
- bases
- pyrazine
- substituted
- unsubstituted
- kinase inhibitors
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Classifications
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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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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
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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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261611370P | 2012-03-15 | 2012-03-15 | |
| US61/611,370 | 2012-03-15 | ||
| US201261715329P | 2012-10-18 | 2012-10-18 | |
| US61/715,329 | 2012-10-18 | ||
| CN201380025102.2A CN104302295B (zh) | 2012-03-15 | 2013-03-14 | 用tor 激酶抑制剂治疗癌症 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201380025102.2A Division CN104302295B (zh) | 2012-03-15 | 2013-03-14 | 用tor 激酶抑制剂治疗癌症 |
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|---|---|
| CN107137402A true CN107137402A (zh) | 2017-09-08 |
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| CN201710422322.9A Pending CN107137402A (zh) | 2012-03-15 | 2013-03-14 | 用tor激酶抑制剂治疗癌症 |
| CN201380025102.2A Active CN104302295B (zh) | 2012-03-15 | 2013-03-14 | 用tor 激酶抑制剂治疗癌症 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380025102.2A Active CN104302295B (zh) | 2012-03-15 | 2013-03-14 | 用tor 激酶抑制剂治疗癌症 |
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| Country | Link |
|---|---|
| US (1) | US20130245029A1 (enExample) |
| EP (1) | EP2825168B1 (enExample) |
| JP (2) | JP2015516375A (enExample) |
| KR (3) | KR20200034818A (enExample) |
| CN (2) | CN107137402A (enExample) |
| AU (1) | AU2013203156C1 (enExample) |
| BR (1) | BR112014022697A2 (enExample) |
| CA (1) | CA2867349A1 (enExample) |
| EA (1) | EA028434B1 (enExample) |
| ES (1) | ES2677908T3 (enExample) |
| IL (2) | IL234640B (enExample) |
| MX (1) | MX360877B (enExample) |
| MY (1) | MY182650A (enExample) |
| NI (1) | NI201400109A (enExample) |
| NZ (1) | NZ628421A (enExample) |
| PH (2) | PH12014502048B1 (enExample) |
| SG (1) | SG11201405706TA (enExample) |
| TW (2) | TWI600428B (enExample) |
| WO (1) | WO2013138556A1 (enExample) |
| ZA (1) | ZA201406709B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111095082A (zh) * | 2018-03-01 | 2020-05-01 | 依视路国际公司 | 镜片元件 |
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| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| EP2945636B1 (en) | 2013-01-16 | 2017-06-28 | Signal Pharmaceuticals, LLC | Substituted pyrrolopyrimidine compounds, compositions thereof, and methods of treatment therewith |
| BR112015026257B1 (pt) | 2013-04-17 | 2022-12-20 | Signal Pharmaceuticals, Llc | Uso de um composto dihidropirazino-pirazina e enzalutamida, composição farmacêutica que os compreende, e kit |
| SG11201508527VA (en) | 2013-04-17 | 2015-11-27 | Signal Pharm Llc | Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one |
| ES2944478T3 (es) | 2013-04-17 | 2023-06-21 | Signal Pharm Llc | 1-etil-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-ona para tratar el glioblastoma multiforme |
| NZ629411A (en) | 2013-04-17 | 2017-06-30 | Signal Pharm Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| AU2014254057A1 (en) | 2013-04-17 | 2015-11-05 | Signal Pharmaceuticals, Llc | Combination therapy comprising a TOR kinase inhibitor and N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer |
| MX368286B (es) | 2013-04-17 | 2019-09-27 | Signal Pharm Llc | Terapia de combinacion que comprende un inhibidor de tor cinasa y un compuesto de quinazolinona 5-sustituida para tratar cancer. |
| KR102242505B1 (ko) | 2013-04-17 | 2021-04-20 | 시그날 파마소티칼 엘엘씨 | 암 치료용 tor 키나제 억제제 및 시티딘 유사체를 포함하는 병용 요법 |
| JP6401250B2 (ja) | 2013-05-29 | 2018-10-10 | シグナル ファーマシューティカルズ,エルエルシー | 7−(6−(2−ヒドロキシプロパン−2−イル)ピリジン−3−イル)−1−((trans)−4−メトキシシクロヘキシル)−3,4−ジヒドロピラジノ[2,3−b]ピラジン−2(1H)−オン、その固体形態の医薬組成物、及びその使用方法 |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use |
| US9718824B2 (en) | 2014-04-16 | 2017-08-01 | Signal Pharmaceuticals, Llc | Solid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof |
| US9737535B2 (en) | 2014-04-16 | 2017-08-22 | Signal Pharmaceuticals, Llc | Methods for treating cancer using TOR kinase inhibitor combination therapy comprising administering substituted pyrazino[2,3-b]pyrazines |
| US9512129B2 (en) | 2014-04-16 | 2016-12-06 | Signal Pharmaceuticals, Llc | Solid forms comprising 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and a coformer |
| AU2015289929A1 (en) | 2014-07-14 | 2017-03-02 | Signal Pharmaceuticals, Llc | Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof |
| NZ629796A (en) | 2014-07-14 | 2015-12-24 | Signal Pharm Llc | Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use |
| HUE054548T2 (hu) * | 2016-12-20 | 2021-09-28 | Astrazeneca Ab | Amino-triazolopiridin vegyületek és azok alkalmazása rák kezelésében |
| EP3641772B1 (en) | 2017-06-22 | 2023-08-02 | Celgene Corporation | Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection |
| CN113493471B (zh) * | 2020-04-03 | 2024-06-11 | 山东轩竹医药科技有限公司 | 杂芳环类激酶抑制剂 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051494A1 (en) * | 2006-10-19 | 2008-05-02 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and use thereof as protein kinase inhibitors |
| WO2008051493A2 (en) * | 2006-10-19 | 2008-05-02 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors |
| WO2010062571A1 (en) * | 2008-10-27 | 2010-06-03 | Signal Pharmaceuticals, Llc | Mtor kinase inhibitors for oncology indications and diseases associated with the mtor/p13k/akt pathway |
| WO2011133668A2 (en) * | 2010-04-20 | 2011-10-27 | President And Fellows Of Harvard College | Methods and compositions for the treatment of cancer |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013508456A (ja) | 2009-10-26 | 2013-03-07 | シグナル ファーマシューティカルズ, エルエルシー | ヘテロアリール化合物の合成方法および精製方法 |
-
2013
- 2013-03-14 KR KR1020207008188A patent/KR20200034818A/ko not_active Ceased
- 2013-03-14 EP EP13712647.0A patent/EP2825168B1/en active Active
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- 2013-03-14 US US13/803,323 patent/US20130245029A1/en not_active Abandoned
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- 2013-03-14 ES ES13712647.0T patent/ES2677908T3/es active Active
- 2013-03-14 TW TW102109153A patent/TWI600428B/zh active
- 2013-03-14 KR KR1020147028710A patent/KR102057358B1/ko active Active
- 2013-03-14 CN CN201710422322.9A patent/CN107137402A/zh active Pending
- 2013-03-14 CA CA2867349A patent/CA2867349A1/en not_active Abandoned
- 2013-03-14 MX MX2014011117A patent/MX360877B/es active IP Right Grant
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- 2013-03-14 NZ NZ628421A patent/NZ628421A/en not_active IP Right Cessation
-
2014
- 2014-09-12 ZA ZA2014/06709A patent/ZA201406709B/en unknown
- 2014-09-12 NI NI201400109A patent/NI201400109A/es unknown
- 2014-09-14 IL IL234640A patent/IL234640B/en active IP Right Grant
- 2014-09-15 PH PH12014502048A patent/PH12014502048B1/en unknown
-
2017
- 2017-11-13 JP JP2017218364A patent/JP6470821B2/ja active Active
-
2018
- 2018-10-18 PH PH12018502234A patent/PH12018502234B1/en unknown
-
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- 2020-04-28 IL IL274318A patent/IL274318A/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051494A1 (en) * | 2006-10-19 | 2008-05-02 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and use thereof as protein kinase inhibitors |
| WO2008051493A2 (en) * | 2006-10-19 | 2008-05-02 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors |
| WO2010062571A1 (en) * | 2008-10-27 | 2010-06-03 | Signal Pharmaceuticals, Llc | Mtor kinase inhibitors for oncology indications and diseases associated with the mtor/p13k/akt pathway |
| CN102245611A (zh) * | 2008-10-27 | 2011-11-16 | 西格诺药品有限公司 | 用于与 mTOR/PI3K/AKT/途径相关的肿瘤适应症和疾病的 mTOR激酶抑制剂 |
| WO2011133668A2 (en) * | 2010-04-20 | 2011-10-27 | President And Fellows Of Harvard College | Methods and compositions for the treatment of cancer |
Non-Patent Citations (1)
| Title |
|---|
| MATEO-LOZANO, S.ET AL: "Rapamycin induces the fusion-type independent downregulation of the EWS/FLI-1 proteins and inhibits Ewing’s sarcoma cell proliferation", 《ONCOGENE》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111095082A (zh) * | 2018-03-01 | 2020-05-01 | 依视路国际公司 | 镜片元件 |
| US11067832B2 (en) | 2018-03-01 | 2021-07-20 | Essilor International | Lens element |
| CN111095082B (zh) * | 2018-03-01 | 2021-11-30 | 依视路国际公司 | 镜片元件 |
| US12158637B2 (en) | 2018-03-01 | 2024-12-03 | Essilor International | Lens element |
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