KR102184246B1 - Atr 키나제의 억제제로서 유용한 화합물의 제조 방법 - Google Patents
Atr 키나제의 억제제로서 유용한 화합물의 제조 방법 Download PDFInfo
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- KR102184246B1 KR102184246B1 KR1020197023926A KR20197023926A KR102184246B1 KR 102184246 B1 KR102184246 B1 KR 102184246B1 KR 1020197023926 A KR1020197023926 A KR 1020197023926A KR 20197023926 A KR20197023926 A KR 20197023926A KR 102184246 B1 KR102184246 B1 KR 102184246B1
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- South Korea
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- methyl
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- 0 *NCCc1ccc(C(O*)O*)cc1 Chemical compound *NCCc1ccc(C(O*)O*)cc1 0.000 description 14
- PWBNBKBFANDLDZ-UHFFFAOYSA-N CC(C)(C)OC(NC1CCOCC1)=O Chemical compound CC(C)(C)OC(NC1CCOCC1)=O PWBNBKBFANDLDZ-UHFFFAOYSA-N 0.000 description 2
- FKUJZOLEACHYMJ-UHFFFAOYSA-N C=NC1CCOCC1 Chemical compound C=NC1CCOCC1 FKUJZOLEACHYMJ-UHFFFAOYSA-N 0.000 description 1
- WKSRJEIRMWCSMS-OQLLNIDSSA-N CC(C)(C)OC(N(C)Cc1ccc(/C=N/O)cc1)=O Chemical compound CC(C)(C)OC(N(C)Cc1ccc(/C=N/O)cc1)=O WKSRJEIRMWCSMS-OQLLNIDSSA-N 0.000 description 1
- DSWMAIALMFRTSA-UHFFFAOYSA-N CC(C)(C)OC(N(Cc(cc1)ccc1-c1n[o]c(-c2nc(Br)cnc2N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)c1)C1CCOCC1)=O Chemical compound CC(C)(C)OC(N(Cc(cc1)ccc1-c1n[o]c(-c2nc(Br)cnc2N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)c1)C1CCOCC1)=O DSWMAIALMFRTSA-UHFFFAOYSA-N 0.000 description 1
- WDBDEGJVFVJPGG-SILNSSARSA-N CC(C)(C)OC(N(Cc(cc1)ccc1/C(/Cl)=N/O)C1CCOCC1)=O Chemical compound CC(C)(C)OC(N(Cc(cc1)ccc1/C(/Cl)=N/O)C1CCOCC1)=O WDBDEGJVFVJPGG-SILNSSARSA-N 0.000 description 1
- BQZZINJDNSOQMW-XDHOZWIPSA-N CC(C)(C)OC(N(Cc1ccc(/C=N/O)cc1)C1CCOCC1)=O Chemical compound CC(C)(C)OC(N(Cc1ccc(/C=N/O)cc1)C1CCOCC1)=O BQZZINJDNSOQMW-XDHOZWIPSA-N 0.000 description 1
- HTMXMFARWHNJDW-UHFFFAOYSA-N CCOC(c1ccc(C=O)cc1)OCC Chemical compound CCOC(c1ccc(C=O)cc1)OCC HTMXMFARWHNJDW-UHFFFAOYSA-N 0.000 description 1
- YCKYJMVABHGLAD-UHFFFAOYSA-N CCOC(c1ccc(CN(C2CCOCC2)C(OC(C)(C)C)=O)cc1)OCC Chemical compound CCOC(c1ccc(CN(C2CCOCC2)C(OC(C)(C)C)=O)cc1)OCC YCKYJMVABHGLAD-UHFFFAOYSA-N 0.000 description 1
- IRMGNFFWKWLUBR-UHFFFAOYSA-N CCOC(c1ccc(CNC)cc1)OCC Chemical compound CCOC(c1ccc(CNC)cc1)OCC IRMGNFFWKWLUBR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161541865P | 2011-09-30 | 2011-09-30 | |
| US61/541,865 | 2011-09-30 | ||
| PCT/US2012/058127 WO2013049726A2 (en) | 2011-09-30 | 2012-09-28 | Processes for making compounds useful as inhibitors of atr kinase |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147011924A Division KR102013133B1 (ko) | 2011-09-30 | 2012-09-28 | Atr 키나제의 억제제로서 유용한 화합물의 제조 방법 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190099346A KR20190099346A (ko) | 2019-08-26 |
| KR102184246B1 true KR102184246B1 (ko) | 2020-12-01 |
Family
ID=47019163
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147011924A Expired - Fee Related KR102013133B1 (ko) | 2011-09-30 | 2012-09-28 | Atr 키나제의 억제제로서 유용한 화합물의 제조 방법 |
| KR1020197023926A Expired - Fee Related KR102184246B1 (ko) | 2011-09-30 | 2012-09-28 | Atr 키나제의 억제제로서 유용한 화합물의 제조 방법 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147011924A Expired - Fee Related KR102013133B1 (ko) | 2011-09-30 | 2012-09-28 | Atr 키나제의 억제제로서 유용한 화합물의 제조 방법 |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US9035053B2 (enExample) |
| EP (4) | EP3608316A1 (enExample) |
| JP (4) | JP6212045B2 (enExample) |
| KR (2) | KR102013133B1 (enExample) |
| CN (2) | CN106496173A (enExample) |
| AR (1) | AR088092A1 (enExample) |
| AU (3) | AU2012315615A1 (enExample) |
| BR (1) | BR112014007721B1 (enExample) |
| CA (2) | CA3124539A1 (enExample) |
| ES (1) | ES2751741T3 (enExample) |
| HR (1) | HRP20191641T1 (enExample) |
| HU (1) | HUE046429T2 (enExample) |
| IL (3) | IL231771A0 (enExample) |
| IN (1) | IN2014KN00929A (enExample) |
| MX (1) | MX353461B (enExample) |
| PL (1) | PL2940017T3 (enExample) |
| PT (1) | PT2940017T (enExample) |
| RS (1) | RS59337B1 (enExample) |
| RU (2) | RU2018147217A (enExample) |
| SG (2) | SG11201401093WA (enExample) |
| TW (3) | TWI625328B (enExample) |
| WO (1) | WO2013049726A2 (enExample) |
| ZA (1) | ZA201402625B (enExample) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2376485T3 (pl) | 2008-12-19 | 2018-05-30 | Vertex Pharmaceuticals Incorporated | Pochodne pirazyny użyteczne jako inhibitory kinazy ATR |
| WO2011143423A2 (en) | 2010-05-12 | 2011-11-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| US8969356B2 (en) | 2010-05-12 | 2015-03-03 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| EP2569287B1 (en) | 2010-05-12 | 2014-07-09 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| CA2798763A1 (en) | 2010-05-12 | 2011-11-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2011143419A1 (en) | 2010-05-12 | 2011-11-17 | Vertex Pharmaceuticals Incorporated | Pyrazines useful as inhibitors of atr kinase |
| MX2012013082A (es) | 2010-05-12 | 2013-05-09 | Vertex Pharma | Derivados de 2-aminopiridina utiles como iinhibidores de cinasa atr. |
| MX2013000103A (es) | 2010-06-23 | 2013-06-13 | Vertex Pharma | Derivados de pirrolo-pirazina utiles como inhibidores de cinasa art. |
| KR20140027974A (ko) | 2011-04-05 | 2014-03-07 | 버텍스 파마슈티칼스 인코포레이티드 | Tra 키나제의 억제제로서 유용한 아미노피라진 화합물 |
| JP2014517079A (ja) | 2011-06-22 | 2014-07-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | Atrキナーゼ阻害剤として有用な化合物 |
| JP2014520161A (ja) | 2011-06-22 | 2014-08-21 | バーテックス ファーマシューティカルズ インコーポレイテッド | Atrキナーゼ阻害剤として有用な化合物 |
| EP2723747A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| WO2013049719A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| MX392542B (es) | 2011-09-30 | 2025-03-24 | Vertex Pharma | Tratamiento del cancer de pancreas y del cancer de pulmon de celulas no pequeñas con inhibidores de atr. |
| US8853217B2 (en) | 2011-09-30 | 2014-10-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| JP2014528419A (ja) | 2011-09-30 | 2014-10-27 | バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated | Atrキナーゼ阻害剤として有用な化合物 |
| HUE046429T2 (hu) | 2011-09-30 | 2020-03-30 | Vertex Pharma | ATR kináz inhibítoraként használható vegyületek elõállítására szolgáló eljárás |
| EP2776422A1 (en) | 2011-11-09 | 2014-09-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013071088A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013071085A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Pyrazine compounds useful as inhibitors of atr kinase |
| EP2776420A1 (en) | 2011-11-09 | 2014-09-17 | Vertex Pharmaceuticals Incorporated | Pyrazine compounds useful as inhibitors of atr kinase |
| WO2013071094A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| CN108478577A (zh) | 2012-04-05 | 2018-09-04 | 沃泰克斯药物股份有限公司 | 可用作atr激酶抑制剂的化合物及其组合疗法 |
| US8999632B2 (en) | 2012-10-04 | 2015-04-07 | Vertex Pharmaceuticals Incorporated | Method for measuring ATR inhibition mediated increases in DNA damage |
| WO2014062604A1 (en) | 2012-10-16 | 2014-04-24 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| SMT202000713T1 (it) | 2012-12-07 | 2021-03-15 | Vertex Pharma | Pirazolo [1,5-a] pirimidine utili come inibitori dell'atr chinasi per il trattamento di malattie del cancro |
| US9663519B2 (en) | 2013-03-15 | 2017-05-30 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| ES2768678T3 (es) | 2013-12-06 | 2020-06-23 | Vertex Pharma | Compuesto de 2-amino-6-fluoro-N-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inhibidor de la ATR quinasa, su preparación, diferentes formas sólidas y derivados radiomarcados de las mismas |
| SG10201902206QA (en) | 2014-06-05 | 2019-04-29 | Vertex Pharma | Radiolabelled derivatives of a 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]- pyrazolo[1,5-a]pyrimidin-3-carboxamide compound useful as atr kinase inhibitor, the preparation of said compound and different solid forms thereof |
| AU2015277212B2 (en) | 2014-06-17 | 2020-07-02 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of Chk1 and ATR inhibitors |
| RU2768621C1 (ru) | 2015-09-30 | 2022-03-24 | Вертекс Фармасьютикалз Инкорпорейтед | Способ лечения рака с использованием комбинации повреждающих днк средств и ингибиторов atr |
| MA43870A (fr) | 2016-01-11 | 2021-05-26 | Celator Pharmaceuticals Inc | Inhibition de la protéine associée à l'ataxie télangiectasie et à rad3 (atr) |
| WO2017180723A1 (en) * | 2016-04-12 | 2017-10-19 | Atrin Pharmaceuticals LLC | Ataxia telengiectasia and rad3-related (atr) inhibitors and methods of their use |
| EA039513B1 (ru) * | 2017-01-09 | 2022-02-04 | Селатор Фармасьютикалз, Инк. | Ингибитор атаксии-телеангиэкстазии и rad3-родственного белка (atr) и содержащие его липосомные композиции |
| EP3461480A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer |
| EP3732301A4 (en) * | 2017-12-29 | 2022-02-09 | Vertex Pharmaceuticals Incorporated | METHOD OF TREATMENT OF CANCER USING AN ATR INHIBITOR |
| WO2019226213A2 (en) | 2018-03-08 | 2019-11-28 | Incyte Corporation | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
| CN113286614A (zh) | 2018-09-26 | 2021-08-20 | 默克专利股份有限公司 | 用于治疗癌症的pd-1拮抗剂、atr抑制剂和铂化物质的组合 |
| CA3116234A1 (en) | 2018-10-15 | 2020-04-23 | Merck Patent Gmbh | Combination therapy utilizing dna alkylating agents and atr inhibitors |
| EP4232037A1 (en) | 2020-10-26 | 2023-08-30 | Merck Patent GmbH | Atr inhibitors for use in the treatment of viral infections |
| CN115703768B (zh) * | 2021-08-13 | 2024-12-17 | 苏州爱科百发生物医药技术有限公司 | 用作atr激酶抑制剂的化合物 |
| TW202321230A (zh) * | 2021-08-13 | 2023-06-01 | 大陸商蘇州愛科百發生物醫藥技術有限公司 | 用作atr激酶抑制劑的化合物 |
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