CN113906026A - 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 - Google Patents
作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 Download PDFInfo
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- CN113906026A CN113906026A CN202080040989.2A CN202080040989A CN113906026A CN 113906026 A CN113906026 A CN 113906026A CN 202080040989 A CN202080040989 A CN 202080040989A CN 113906026 A CN113906026 A CN 113906026A
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Classifications
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- 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)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
通式(A)化合物,它们可用于治疗ATR激酶介导的疾病,例如增生性疾病,例如癌症。还提供通式(A)化合物的药物组合物、其用于治疗ATR激酶介导的疾病的用途、及其制备。
Description
PCT国内申请,说明书已公开。
Claims (26)
- PCT国内申请,权利要求书已公开。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN202410650691.3A CN118619944A (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
Applications Claiming Priority (7)
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CN201910490080 | 2019-06-06 | ||
CN2019104900806 | 2019-06-06 | ||
CN201910876919X | 2019-09-17 | ||
CN201910876919 | 2019-09-17 | ||
CN202010441539 | 2020-05-22 | ||
CN2020104415396 | 2020-05-22 | ||
PCT/CN2020/094532 WO2020244613A1 (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
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CN202410650691.3A Division CN118619944A (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
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CN113906026A true CN113906026A (zh) | 2022-01-07 |
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CN202010503909.4A Active CN112047938B (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
CN202410650691.3A Pending CN118619944A (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
CN202080040989.2A Pending CN113906026A (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
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CN202010503909.4A Active CN112047938B (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
CN202410650691.3A Pending CN118619944A (zh) | 2019-06-06 | 2020-06-05 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20220378799A1 (zh) |
EP (1) | EP3967694A4 (zh) |
JP (1) | JP7485701B2 (zh) |
KR (1) | KR20220016225A (zh) |
CN (3) | CN112047938B (zh) |
TW (1) | TWI778366B (zh) |
WO (1) | WO2020244613A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115043770A (zh) * | 2022-07-21 | 2022-09-13 | 南京大学 | 一种吲哚/氮杂吲哚类化合物的光诱导合成方法 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115551860A (zh) * | 2020-05-20 | 2022-12-30 | 北京泰德制药股份有限公司 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
CN114213424B (zh) * | 2021-12-30 | 2023-05-26 | 杭州高光制药有限公司 | 一种呋喃[3,2-b]并吡啶衍生物的合成方法 |
CN115745995B (zh) * | 2022-01-10 | 2024-09-03 | 苏州浦合医药科技有限公司 | Atr抑制剂及其用途 |
WO2023215133A1 (en) * | 2022-05-02 | 2023-11-09 | AcuraStem Incorporated | Pikfyve kinase inhibitors |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6251900B1 (en) * | 1997-07-24 | 2001-06-26 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compounds and antitumor agent containing the same as active ingredient |
WO2008032077A1 (en) * | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | Pyrimidine derivatives |
WO2009093981A1 (en) * | 2008-01-23 | 2009-07-30 | S Bio Pte Ltd | Triazine compounds as kinase inhibitors |
CN101535296A (zh) * | 2006-09-14 | 2009-09-16 | 阿斯利康(瑞典)有限公司 | 作为p13k和mtor抑制剂用于治疗增殖性疾病的2-苯并咪唑基-6-吗啉代-4-苯基嘧啶衍生物 |
US20110009405A1 (en) * | 2009-07-07 | 2011-01-13 | Pathway Therapeutics Limited | Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy |
WO2019050889A1 (en) * | 2017-09-08 | 2019-03-14 | Bluevalley Pharmaceutical Llc | SUBSTITUTED PYRROLOPYRIDINES AS ATR INHIBITORS |
WO2019154365A1 (zh) * | 2018-02-07 | 2019-08-15 | 南京明德新药研发有限公司 | 一种atr抑制剂及其应用 |
CN110467610A (zh) * | 2018-05-10 | 2019-11-19 | 四川科伦博泰生物医药股份有限公司 | 一种取代嘧啶化合物、其制备方法和用途 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5376645A (en) | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
GB0415364D0 (en) * | 2004-07-09 | 2004-08-11 | Astrazeneca Ab | Pyrimidine derivatives |
CN101765597A (zh) * | 2007-04-12 | 2010-06-30 | 霍夫曼-拉罗奇有限公司 | 作为磷脂酰肌醇-3-激酶抑制剂的嘧啶衍生物 |
JP2010523637A (ja) * | 2007-04-12 | 2010-07-15 | エフ.ホフマン−ラ ロシュ アーゲー | 医薬化合物 |
EP2411387B1 (en) * | 2009-03-27 | 2015-08-19 | VetDC, Inc. | Pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy |
WO2012044641A1 (en) * | 2010-09-29 | 2012-04-05 | Pathway Therapeutics Inc. | 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy |
MA40933A (fr) * | 2014-11-11 | 2017-09-19 | Piqur Therapeutics Ag | Difluorométhyl-aminopyridines et difluorométhyl-aminopyrimidines |
CN110818690B (zh) * | 2016-07-26 | 2021-08-10 | 深圳市塔吉瑞生物医药有限公司 | 用于抑制蛋白酪氨酸激酶活性的氨基嘧啶类化合物 |
CN111867590B (zh) * | 2017-07-13 | 2023-11-17 | 德州大学系统董事会 | Atr激酶的杂环抑制剂 |
JP7290627B2 (ja) * | 2017-08-17 | 2023-06-13 | ボード オブ レジェンツ,ザ ユニバーシティ オブ テキサス システム | Atrキナーゼの複素環式阻害剤 |
EP3715343B1 (en) * | 2017-12-21 | 2024-02-14 | Shenzhen TargetRx, Inc. | Diphenylaminopyrimidine compound for inhibiting kinase activity |
CN110343095A (zh) * | 2018-04-08 | 2019-10-18 | 中国科学院上海药物研究所 | 一类精氨酸甲基转移酶抑制剂及其药物组合物和用途 |
AU2020325416A1 (en) * | 2019-08-06 | 2022-02-03 | Wuxi Biocity Biopharmaceutics Co., Ltd. | Crystalline form of ATR inhibitor and use thereof |
CN115551860A (zh) * | 2020-05-20 | 2022-12-30 | 北京泰德制药股份有限公司 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
WO2021238999A1 (zh) * | 2020-05-29 | 2021-12-02 | 深圳市瓴方生物医药科技有限公司 | 氟代吡咯并吡啶类化合物及其应用 |
-
2020
- 2020-06-05 TW TW109118941A patent/TWI778366B/zh active
- 2020-06-05 CN CN202010503909.4A patent/CN112047938B/zh active Active
- 2020-06-05 JP JP2021572544A patent/JP7485701B2/ja active Active
- 2020-06-05 WO PCT/CN2020/094532 patent/WO2020244613A1/zh unknown
- 2020-06-05 EP EP20818265.9A patent/EP3967694A4/en active Pending
- 2020-06-05 KR KR1020217043346A patent/KR20220016225A/ko not_active Application Discontinuation
- 2020-06-05 US US17/616,571 patent/US20220378799A1/en active Pending
- 2020-06-05 CN CN202410650691.3A patent/CN118619944A/zh active Pending
- 2020-06-05 CN CN202080040989.2A patent/CN113906026A/zh active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6251900B1 (en) * | 1997-07-24 | 2001-06-26 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compounds and antitumor agent containing the same as active ingredient |
WO2008032077A1 (en) * | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | Pyrimidine derivatives |
CN101535296A (zh) * | 2006-09-14 | 2009-09-16 | 阿斯利康(瑞典)有限公司 | 作为p13k和mtor抑制剂用于治疗增殖性疾病的2-苯并咪唑基-6-吗啉代-4-苯基嘧啶衍生物 |
US20090325954A1 (en) * | 2006-09-14 | 2009-12-31 | Sam Butterworth | 2-benzimidazolyl-6-morpholino-4-phenylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
WO2009093981A1 (en) * | 2008-01-23 | 2009-07-30 | S Bio Pte Ltd | Triazine compounds as kinase inhibitors |
US20110009405A1 (en) * | 2009-07-07 | 2011-01-13 | Pathway Therapeutics Limited | Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy |
WO2019050889A1 (en) * | 2017-09-08 | 2019-03-14 | Bluevalley Pharmaceutical Llc | SUBSTITUTED PYRROLOPYRIDINES AS ATR INHIBITORS |
WO2019154365A1 (zh) * | 2018-02-07 | 2019-08-15 | 南京明德新药研发有限公司 | 一种atr抑制剂及其应用 |
CN110467610A (zh) * | 2018-05-10 | 2019-11-19 | 四川科伦博泰生物医药股份有限公司 | 一种取代嘧啶化合物、其制备方法和用途 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115043770A (zh) * | 2022-07-21 | 2022-09-13 | 南京大学 | 一种吲哚/氮杂吲哚类化合物的光诱导合成方法 |
CN115043770B (zh) * | 2022-07-21 | 2023-09-08 | 南京大学 | 一种吲哚/氮杂吲哚类化合物的光诱导合成方法 |
Also Published As
Publication number | Publication date |
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TW202112764A (zh) | 2021-04-01 |
KR20220016225A (ko) | 2022-02-08 |
CN112047938B (zh) | 2022-11-22 |
EP3967694A4 (en) | 2022-12-07 |
TWI778366B (zh) | 2022-09-21 |
JP2022536313A (ja) | 2022-08-15 |
EP3967694A1 (en) | 2022-03-16 |
WO2020244613A1 (zh) | 2020-12-10 |
CN112047938A (zh) | 2020-12-08 |
US20220378799A1 (en) | 2022-12-01 |
JP7485701B2 (ja) | 2024-05-16 |
CN118619944A (zh) | 2024-09-10 |
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