EA036208B1 - Замещенные производные оксопиридина - Google Patents
Замещенные производные оксопиридина Download PDFInfo
- Publication number
- EA036208B1 EA036208B1 EA201890111A EA201890111A EA036208B1 EA 036208 B1 EA036208 B1 EA 036208B1 EA 201890111 A EA201890111 A EA 201890111A EA 201890111 A EA201890111 A EA 201890111A EA 036208 B1 EA036208 B1 EA 036208B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- mmol
- mixture
- tert
- formula
- methoxy
- Prior art date
Links
- 238000000034 method Methods 0.000 claims abstract description 231
- 150000001875 compounds Chemical class 0.000 claims abstract description 196
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 230000009424 thromboembolic effect Effects 0.000 claims abstract description 26
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- 239000003814 drug Substances 0.000 claims abstract description 16
- 241001465754 Metazoa Species 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 29
- 239000000460 chlorine Substances 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 26
- 230000002265 prevention Effects 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 6
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 8
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
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- 238000004949 mass spectrometry Methods 0.000 description 288
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
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- -1 fenprocoumon Chemical compound 0.000 description 110
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 94
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 82
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- 238000000746 purification Methods 0.000 description 37
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- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 27
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- INQOMBQAUSQDDS-FIBGUPNXSA-N trideuterio(iodo)methane Chemical compound [2H]C([2H])([2H])I INQOMBQAUSQDDS-FIBGUPNXSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D401/14—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 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
- A61K31/435—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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- C07D413/02—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
- C07D413/10—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 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15176099 | 2015-07-09 | ||
| EP16157350 | 2016-02-25 | ||
| PCT/EP2016/065787 WO2017005725A1 (en) | 2015-07-09 | 2016-07-05 | Substituted oxopyridine derivatives |
Publications (2)
| Publication Number | Publication Date |
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| EA201890111A1 EA201890111A1 (ru) | 2018-06-29 |
| EA036208B1 true EA036208B1 (ru) | 2020-10-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201890111A EA036208B1 (ru) | 2015-07-09 | 2016-07-05 | Замещенные производные оксопиридина |
Country Status (39)
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| ES2722423T3 (es) * | 2014-09-24 | 2019-08-12 | Bayer Pharma AG | Derivados de oxopiridina sustituidos |
| US20190119213A1 (en) * | 2015-03-19 | 2019-04-25 | Bayer Pharma Aktiengesellschaft | Oxo-pyridine-derivatives as factor xia inhibitors for the treatment of thrombosis |
| JO3703B1 (ar) * | 2015-07-09 | 2021-01-31 | Bayer Pharma AG | مشتقات أوكسوبيريدين مستبدلة |
| WO2018041122A1 (zh) | 2016-08-31 | 2018-03-08 | 江苏恒瑞医药股份有限公司 | 氧代吡啶酰胺类衍生物、其制备方法及其在医药上的应用 |
| IL277240B2 (en) * | 2018-03-15 | 2024-01-01 | Bayer Ag | Preparative process of two 4-{[(2s)-2-{4-[5-chloro-2-(1h-1,2,3-triazol-1-yl)phenyl]-5-methoxy-2-oxopyridin-1(2h)-yl}butanoyl]amino}-2-fluorobenzamide derivatives |
| AU2019251699B2 (en) | 2018-04-10 | 2024-02-29 | Bayer Pharma Aktiengesellschaft | A substituted oxopyridine derivative |
| US11225462B2 (en) | 2018-07-02 | 2022-01-18 | Jiangsu Hengrui Medicine Co., Ltd. | Crystal forms of oxypyridine amide derivative and preparation method therefor |
| AR115870A1 (es) | 2018-07-31 | 2021-03-10 | Sumitomo Chemical Co | MÉTODO PARA CONTROLAR EL HONGO DE LA ROYA DE LA SOJA QUE TIENE RESISTENCIA AL INHIBIDOR DE SITIO Qₒ |
| CN113166099A (zh) * | 2018-12-17 | 2021-07-23 | 拜耳公司 | 用于治疗和/或预防血栓形成性或血栓栓塞性疾病和/或血栓形成性或血栓栓塞性并发症的取代的氧代吡啶衍生物 |
| WO2020127508A1 (en) | 2018-12-21 | 2020-06-25 | Bayer Aktiengesellschaft | Substituted oxopyridine derivatives |
| JOP20210161A1 (ar) | 2018-12-21 | 2023-01-30 | Bayer Ag | مشتقات أكسوبيريدين تحمل بدائل |
| CN116120240A (zh) | 2019-09-27 | 2023-05-16 | 深圳信立泰药业股份有限公司 | FXIa抑制剂化合物及其制备方法和医药用途 |
| JP7700218B2 (ja) | 2020-09-17 | 2025-06-30 | 浙江海正薬業股▲ふん▼有限公司 | ピペラジン誘導体、その製造方法、およびその使用 |
| CN114621140B (zh) * | 2020-12-10 | 2023-08-11 | 中国科学院上海药物研究所 | 芳基二氟乙酰胺化合物及其制备方法和用途 |
| WO2022189280A1 (en) | 2021-03-09 | 2022-09-15 | Bayer Aktiengesellschaft | Solvates of (4s)-24-chloro-4-ethyl-73-fluoro-35-methoxy-32,5-dioxo-14-(trifluoro-methyl)-32 h-6- aza-3(4,1)-pyridina-1(1)-[1,2,3]triazola-2(1,2),7(1)-dibenzenaheptaphane-74-carboxamide |
| GEAP202316370A (en) * | 2021-03-09 | 2023-11-27 | Bayer Ag | Pharmaceutical dosage forms comprising (4s)-24-chloro-4-ethyl-73-fluoro-35-methoxy-32,5-dioxo-14-(trifluoromethyl)-32h-6-aza-3(4,1)-pyridina-1(1)-[1,2,3] triazola-2(1,2),7(1)- dibenzenaheptaphane-74-carboxamide |
| JP2024508971A (ja) * | 2021-03-09 | 2024-02-28 | バイエル・アクチエンゲゼルシヤフト | （４ｓ）－２４－クロロ－４－エチル－７３－フルオロ－３５－メトキシ－３２，５－ジオキソ－１４－（トリフルオロメチル）－３２ｈ－６－アザ－３（４，１）－ピリジナ－１（１）－［１，２，３］トリアゾラ－２（１，２），７（１）－５ ジベンゼナヘプタファン－７４－カルボキサミドの結晶形態 |
| US11845748B2 (en) | 2021-03-18 | 2023-12-19 | Janssen Pharmaceutica Nv | Bicyclic pyridine N-oxide derivatives useful as a factor XIa inhibitors |
| US11814364B2 (en) | 2021-03-18 | 2023-11-14 | Janssen Pharmaceutica Nv | Pyridine N-oxide derivatives useful as factor XIa inhibitors |
| US11919881B2 (en) | 2021-03-18 | 2024-03-05 | Janssen Pharmaceutica Nv | Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors |
| CN113666826B (zh) * | 2021-07-30 | 2024-03-26 | 五邑大学 | 一种芳基或杂芳基甲氧基化反应的方法 |
| CN116199672A (zh) * | 2021-11-30 | 2023-06-02 | 成都泰和伟业生物科技有限公司 | 一种嘧啶酰胺类衍生物及其制备方法和用途 |
| WO2023174399A1 (zh) * | 2022-03-18 | 2023-09-21 | 苏州晶云药物科技股份有限公司 | 取代的氧代吡啶类衍生物的晶型及其制备方法 |
| CN116262735B (zh) * | 2022-11-18 | 2025-05-13 | 成都施贝康生物医药科技有限公司 | 新型氧代吡啶类化合物及其制备方法和用途 |
| CN116262734B (zh) * | 2022-11-18 | 2025-05-13 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物及其制备方法和用途 |
| CN116262740A (zh) * | 2022-11-18 | 2023-06-16 | 成都施贝康生物医药科技有限公司 | 新型氧代吡啶类化合物及其制备方法和用途 |
| CN116082303B (zh) * | 2022-12-21 | 2025-02-25 | 成都施贝康生物医药科技有限公司 | 新型氧代吡啶类化合物及其中间体和应用 |
| CN116262736B (zh) * | 2022-12-26 | 2025-05-13 | 成都施贝康生物医药科技有限公司 | 新型氧代吡啶类化合物及其制备方法和用途 |
| KR20250164210A (ko) | 2023-03-31 | 2025-11-24 | 바이엘 악티엔게젤샤프트 | (4s)-24-클로로-4-에틸-73-플루오로-35-메톡시-32,5-디옥소-14-(트리플루오로메틸)-32h-6-아자-3(4,1)-피리디나-1(1)-[1,2,3]트리아졸라-2(1,2),7(1)-디벤제나헵타판-74-카르복스아미드를포함하는 제약 투여 형태 |
| CN116535392B (zh) * | 2023-06-26 | 2023-09-05 | 成都施贝康生物医药科技有限公司 | 一种氧代吡啶类化合物的制备方法及中间体和应用 |
| CN116751136B (zh) * | 2023-06-21 | 2025-08-29 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物的新型制备方法及关键中间体 |
| CN116621728B (zh) * | 2023-06-09 | 2025-07-29 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物的新型制备方法及关键中间体 |
| CN116621742B (zh) * | 2023-06-09 | 2025-05-06 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物的新型制备方法及关键中间体 |
| WO2024251276A1 (zh) | 2023-06-09 | 2024-12-12 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物的新型制备方法及关键中间体和应用 |
| CN116874387B (zh) * | 2023-06-21 | 2025-08-26 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物的新型制备方法及关键中间体 |
| CN116730861A (zh) * | 2023-06-21 | 2023-09-12 | 成都施贝康生物医药科技有限公司 | 氧代吡啶类化合物的新型制备方法及关键中间体 |
| CN117164562B (zh) * | 2023-09-07 | 2025-06-13 | 成都施贝康生物医药科技有限公司 | 一种氧代哒嗪类化合物及其制备方法和用途 |
| CN117164566B (zh) * | 2023-09-07 | 2025-06-06 | 成都施贝康生物医药科技有限公司 | 一种氧代哒嗪类化合物及其制备方法和用途 |
| CN117164561A (zh) * | 2023-09-07 | 2023-12-05 | 成都施贝康生物医药科技有限公司 | 一种氧代嘧啶类化合物及其制备方法和用途 |
| CN117164565B (zh) * | 2023-09-07 | 2025-05-27 | 成都施贝康生物医药科技有限公司 | 一种氧代嘧啶类化合物及其制备方法和用途 |
| CN117164564B (zh) * | 2023-09-07 | 2025-07-08 | 成都施贝康生物医药科技有限公司 | 氧代哒嗪类化合物及其制备方法和用途 |
| CN117164563B (zh) * | 2023-09-07 | 2025-06-10 | 成都施贝康生物医药科技有限公司 | 氧代嘧啶类化合物及其制备方法和用途 |
| CN117186073B (zh) * | 2023-09-08 | 2025-06-06 | 成都施贝康生物医药科技有限公司 | 氧代嘧啶类化合物及其制备方法和用途 |
| CN118894814B (zh) * | 2024-07-15 | 2025-09-12 | 上海康鹏科技股份有限公司 | 1-(2-溴-4-氯苯基)-4-(三氟甲基)-1h-1，2，3-三唑的制备方法 |
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| WO2014154794A1 (de) * | 2013-03-28 | 2014-10-02 | Bayer Pharma Aktiengesellschaft | Substituierte oxopyridin-derivate und ihre verwendung bei der behandlung von herz-kreislauf-erkrankungen |
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| WO2014160592A2 (en) * | 2013-03-27 | 2014-10-02 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| WO2014154794A1 (de) * | 2013-03-28 | 2014-10-02 | Bayer Pharma Aktiengesellschaft | Substituierte oxopyridin-derivate und ihre verwendung bei der behandlung von herz-kreislauf-erkrankungen |
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