CN114072396A - 作为dna-pk抑制剂的喹啉和噌啉衍生物 - Google Patents
作为dna-pk抑制剂的喹啉和噌啉衍生物 Download PDFInfo
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- CN114072396A CN114072396A CN202080045905.4A CN202080045905A CN114072396A CN 114072396 A CN114072396 A CN 114072396A CN 202080045905 A CN202080045905 A CN 202080045905A CN 114072396 A CN114072396 A CN 114072396A
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- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
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- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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- 238000011127 radiochemotherapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
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- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- ZGNPLWZYVAFUNZ-UHFFFAOYSA-N tert-butylphosphane Chemical compound CC(C)(C)P ZGNPLWZYVAFUNZ-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 231100000419 toxicity Toxicity 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- BFDBKMOZYNOTPK-UHFFFAOYSA-N vonoprazan Chemical compound C=1C=CN=CC=1S(=O)(=O)N1C=C(CNC)C=C1C1=CC=CC=C1F BFDBKMOZYNOTPK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D401/10—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 linked by a carbon chain containing aromatic 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/28—Cinnolines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明公开了式(I)所示化合物、其异构体或其药学上可接受的盐，并公开了其在制备治疗与DNA‑PK激酶抑制剂相关疾病药物中的应用。
Description
PCT国内申请，说明书已公开。
Claims (18)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019105687380 | 2019-06-27 | ||
| CN201910568738 | 2019-06-27 | ||
| CN202010076183 | 2020-01-23 | ||
| CN2020100761830 | 2020-01-23 | ||
| CN202010209372 | 2020-03-23 | ||
| CN2020102093720 | 2020-03-23 | ||
| PCT/CN2020/098198 WO2020259613A1 (zh) | 2019-06-27 | 2020-06-24 | 作为dna-pk抑制剂的喹啉和噌啉衍生物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114072396A true CN114072396A (zh) | 2022-02-18 |
| CN114072396B CN114072396B (zh) | 2024-02-02 |
Family
ID=74059859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080045905.4A Active CN114072396B (zh) | 2019-06-27 | 2020-06-24 | 作为dna-pk抑制剂的喹啉和噌啉衍生物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20220267310A1 (zh) |
| EP (1) | EP3992189A4 (zh) |
| JP (1) | JP7313492B2 (zh) |
| KR (1) | KR20220027183A (zh) |
| CN (1) | CN114072396B (zh) |
| WO (1) | WO2020259613A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116670128A (zh) * | 2020-12-28 | 2023-08-29 | 南京明德新药研发有限公司 | 吗啉取代的苯并嘧啶类化合物的晶型及其制备方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105358552A (zh) * | 2013-05-11 | 2016-02-24 | 默克专利股份公司 | 芳基喹唑啉 |
| WO2018114776A1 (en) * | 2016-12-19 | 2018-06-28 | Merck Patent Gmbh | Combination of a protein kinase inhibitor and an additional chemotherapeutic agent |
| WO2018178133A1 (en) * | 2017-03-30 | 2018-10-04 | Merck Patent Gmbh | Solid form of (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxy-pyridazin-3-yl)methanol |
| CN111909144A (zh) * | 2019-05-10 | 2020-11-10 | 山东轩竹医药科技有限公司 | 喹唑啉类dna-pk抑制剂 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI3601277T3 (fi) * | 2017-03-30 | 2024-01-09 | Merck Patent Gmbh | Farmaseuttinen formulaatio |
| IL269718B2 (en) * | 2017-03-30 | 2024-10-01 | Merck Patent Gmbh | Combination of anti-PD-L1 antibody and DNA-PK inhibitor for cancer treatment |
| EP3601271B1 (en) * | 2017-03-30 | 2022-06-08 | Merck Patent GmbH | Crystalline form of (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxy-pyridazin-3-yl)-methanol |
-
2020
- 2020-06-24 KR KR1020227002871A patent/KR20220027183A/ko not_active Application Discontinuation
- 2020-06-24 JP JP2021577645A patent/JP7313492B2/ja active Active
- 2020-06-24 WO PCT/CN2020/098198 patent/WO2020259613A1/zh unknown
- 2020-06-24 US US17/622,522 patent/US20220267310A1/en active Pending
- 2020-06-24 CN CN202080045905.4A patent/CN114072396B/zh active Active
- 2020-06-24 EP EP20831428.6A patent/EP3992189A4/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105358552A (zh) * | 2013-05-11 | 2016-02-24 | 默克专利股份公司 | 芳基喹唑啉 |
| WO2018114776A1 (en) * | 2016-12-19 | 2018-06-28 | Merck Patent Gmbh | Combination of a protein kinase inhibitor and an additional chemotherapeutic agent |
| WO2018178133A1 (en) * | 2017-03-30 | 2018-10-04 | Merck Patent Gmbh | Solid form of (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxy-pyridazin-3-yl)methanol |
| CN111909144A (zh) * | 2019-05-10 | 2020-11-10 | 山东轩竹医药科技有限公司 | 喹唑啉类dna-pk抑制剂 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2022540360A (ja) | 2022-09-15 |
| WO2020259613A1 (zh) | 2020-12-30 |
| EP3992189A1 (en) | 2022-05-04 |
| US20220267310A1 (en) | 2022-08-25 |
| JP7313492B2 (ja) | 2023-07-24 |
| KR20220027183A (ko) | 2022-03-07 |
| EP3992189A4 (en) | 2022-12-07 |
| CN114072396B (zh) | 2024-02-02 |
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