CN103987696B - 作为因子xia抑制剂的取代的四氢异喹啉化合物 - Google Patents
作为因子xia抑制剂的取代的四氢异喹啉化合物 Download PDFInfo
- Publication number
- CN103987696B CN103987696B CN201280061628.1A CN201280061628A CN103987696B CN 103987696 B CN103987696 B CN 103987696B CN 201280061628 A CN201280061628 A CN 201280061628A CN 103987696 B CN103987696 B CN 103987696B
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- Prior art keywords
- alkyl
- occurrence
- substituted
- conh
- phenyl
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 0 CC(C([C@](C1F)C=CC(O)=O)=CC=C1Cl)=* Chemical compound CC(C([C@](C1F)C=CC(O)=O)=CC=C1Cl)=* 0.000 description 7
- JZDAEMFHMRJBET-SFQUDFHCSA-N CC(C)(C1)C(C(c(cc2)ccc2C(N)=O)=CCC2)=C2C(C(Nc(cc2)ccc2C(O)=O)=O)N1C(/C=C/C(C(C=C1)[n]2nnnc2)C=C1Cl)=O Chemical compound CC(C)(C1)C(C(c(cc2)ccc2C(N)=O)=CCC2)=C2C(C(Nc(cc2)ccc2C(O)=O)=O)N1C(/C=C/C(C(C=C1)[n]2nnnc2)C=C1Cl)=O JZDAEMFHMRJBET-SFQUDFHCSA-N 0.000 description 1
- JBGIHUBDSGFFHF-FBMGVBCBSA-N CC(c(c(/C=C/C(N(CC1)C(C(Nc(cc2)ccc2C(O)=O)=O)c2c1c(-c(cc1)ccc1C(NCCN(C)C)=O)ccc2)=O)c1F)ccc1Cl)=O Chemical compound CC(c(c(/C=C/C(N(CC1)C(C(Nc(cc2)ccc2C(O)=O)=O)c2c1c(-c(cc1)ccc1C(NCCN(C)C)=O)ccc2)=O)c1F)ccc1Cl)=O JBGIHUBDSGFFHF-FBMGVBCBSA-N 0.000 description 1
- JLSSWDFCYXSLQX-UHFFFAOYSA-N CCOC(c(cc1)ccc1C#N)=O Chemical compound CCOC(c(cc1)ccc1C#N)=O JLSSWDFCYXSLQX-UHFFFAOYSA-N 0.000 description 1
- WYSMEGUVKCVXQV-MDWZMJQESA-N CN(C)c1cccc(C2C(Nc(cc3)ccc3C(O)=O)=O)c1CCN2C(/C=C/c(cc(cc1)Cl)c1-[n]1nnnc1)=O Chemical compound CN(C)c1cccc(C2C(Nc(cc3)ccc3C(O)=O)=O)c1CCN2C(/C=C/c(cc(cc1)Cl)c1-[n]1nnnc1)=O WYSMEGUVKCVXQV-MDWZMJQESA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6524—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having four or more nitrogen atoms as the only ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547301P | 2011-10-14 | 2011-10-14 | |
| US61/547,301 | 2011-10-14 | ||
| US61/547301 | 2011-10-14 | ||
| PCT/US2012/059932 WO2013056034A1 (en) | 2011-10-14 | 2012-10-12 | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103987696A CN103987696A (zh) | 2014-08-13 |
| CN103987696B true CN103987696B (zh) | 2016-12-21 |
Family
ID=47116434
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280061628.1A Expired - Fee Related CN103987696B (zh) | 2011-10-14 | 2012-10-12 | 作为因子xia抑制剂的取代的四氢异喹啉化合物 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9079929B2 (https=) |
| EP (1) | EP2766347B1 (https=) |
| JP (1) | JP6033318B2 (https=) |
| CN (1) | CN103987696B (https=) |
| ES (1) | ES2579832T3 (https=) |
| IN (1) | IN2014CN02805A (https=) |
| WO (1) | WO2013056034A1 (https=) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ602266A (en) | 2010-02-11 | 2014-05-30 | Bristol Myers Squibb Co | Macrocycles as factor xia inhibitors |
| TW201319068A (zh) | 2011-08-05 | 2013-05-16 | 必治妥美雅史谷比公司 | 作為xia因子抑制劑之環狀p1接合劑 |
| TW201311689A (zh) | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子xia抑制劑之新穎巨環化合物 |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| JP6033319B2 (ja) | 2011-10-14 | 2016-11-30 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 第XIa因子阻害剤としての置換テトラヒドロイソキノリン化合物 |
| WO2013055984A1 (en) | 2011-10-14 | 2013-04-18 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| CN104640843A (zh) | 2012-07-19 | 2015-05-20 | 大日本住友制药株式会社 | 1-(环烷基羰基)脯氨酸衍生物 |
| AU2013296259A1 (en) | 2012-08-03 | 2015-03-19 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| US9376444B2 (en) | 2012-08-03 | 2016-06-28 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Bristol Myers Squibb Co | Bir faktör XIa inhibitörünün kristalli formları. |
| EP2906552B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014135468A1 (en) * | 2013-03-05 | 2014-09-12 | Bayer Cropscience Ag | Use of acylsulfonamides for improving plant yield |
| WO2014160668A1 (en) * | 2013-03-25 | 2014-10-02 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| WO2015054087A1 (en) | 2013-10-07 | 2015-04-16 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| NO2760821T3 (https=) | 2014-01-31 | 2018-03-10 | ||
| SG10201908467RA (en) | 2014-01-31 | 2019-10-30 | Bristol Myers Squibb Co | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
| WO2015123091A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| WO2015123093A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| EP3134408B1 (en) | 2014-04-22 | 2020-08-12 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| MA40060A (fr) * | 2014-07-01 | 2016-01-07 | Takeda Pharmaceuticals Co | Composés hétérocycliques et leur utilisation en tant qu'inhibiteurs gamma-t du récepteur orphelin apparenté aux récepteurs des rétinoïdes (ror) ) |
| WO2016015593A1 (en) | 2014-07-28 | 2016-02-04 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| US10414731B2 (en) | 2014-09-24 | 2019-09-17 | Bayer Pharma Aktiengesellschaft | Substituted oxopyridine derivatives |
| EP3197872B1 (de) * | 2014-09-24 | 2019-01-30 | Bayer Pharma Aktiengesellschaft | (2h)-2-oxopyridine als faktor xia-inhibitoren zur behandlung von thrombotischen erkrankungen |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| ES2762987T3 (es) | 2015-06-19 | 2020-05-26 | Bristol Myers Squibb Co | Macrociclos de diamida como inhibidores del factor XIA |
| JO3703B1 (ar) | 2015-07-09 | 2021-01-31 | Bayer Pharma AG | مشتقات أوكسوبيريدين مستبدلة |
| CN114874222B (zh) | 2015-07-29 | 2025-06-06 | 百时美施贵宝公司 | 携带非芳族p2,基团的因子xia新大环 |
| JP6629958B2 (ja) | 2015-07-29 | 2020-01-15 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | アルキルまたはシクロアルキルP2’基を担持する大員環の第XIa因子阻害剤 |
| KR102697816B1 (ko) | 2015-08-05 | 2024-08-21 | 브리스톨-마이어스 스큅 컴퍼니 | 신규 치환된 글리신 유도된 fxia 억제제 |
| EP3371162B1 (en) | 2015-10-29 | 2022-01-26 | Merck Sharp & Dohme Corp. | Macrocyclic spirocarbamate derivatives as factor xia inhibitors, pharmaceutically acceptable compositions and their use |
| EP3368036B1 (en) | 2015-10-29 | 2022-07-20 | Merck Sharp & Dohme LLC | Macrocyclic pyridine-n-oxide derivatives as factor xia inhibitors |
| WO2017123518A1 (en) * | 2016-01-11 | 2017-07-20 | The Rockefeller University | Aminotriazole immunomodulators for treating autoimmune diseases |
| WO2017160116A2 (ko) * | 2016-03-17 | 2017-09-21 | 연세대학교 산학협력단 | 니코틴아미드 포스포리보실트랜스퍼라제 억제용 신규 화합물 및 이를 포함하는 조성물 |
| WO2018039094A1 (en) | 2016-08-22 | 2018-03-01 | Merck Sharp & Dohme Corp. | Pyridine-1-oxide derivatives and their use as factor xia inhibitors |
| BR112019003557A2 (pt) | 2016-08-31 | 2019-05-21 | Jiangsu Hengrui Medicine Co., Ltd. | derivados de oxopicolinamida, método de preparação dos mesmos e uso farmacêutico dos mesmos |
| CN109721539B (zh) * | 2017-10-27 | 2021-07-09 | 天津药物研究院有限公司 | 吡唑酰胺类衍生物及其制备方法和用途 |
| CN109867660A (zh) * | 2017-12-01 | 2019-06-11 | 四川科伦博泰生物医药股份有限公司 | 含季铵离子的四氢异喹啉酰胺化合物及其药物用途 |
| EP3778597B1 (en) | 2018-03-28 | 2025-05-28 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Tetrahydroisoquinoline derivative, preparation method therefor and uses thereof |
| US12304899B2 (en) | 2019-05-30 | 2025-05-20 | Merck Sharp & Dohme Llc | Factor XI activation inhibitors |
| US12492187B2 (en) | 2020-04-01 | 2025-12-09 | Merck Sharp & Dohme Llc | Factor XI activation inhibitors |
| EP4149917B1 (en) * | 2020-05-12 | 2025-07-30 | Merck Sharp & Dohme LLC | Factor xi activation inhibitors |
| EP3978487A1 (en) | 2020-09-30 | 2022-04-06 | Origo Biopharma, S.L. | 2-(3-pyridin-2-yl-4-quinolin-4-yl-pyrazol-1-yl)-acetamide derivatives as inhibitors of transforming growth factor-beta receptor i/alk5 |
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- 2012-10-12 US US14/350,411 patent/US9079929B2/en active Active
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- 2012-10-12 JP JP2014535916A patent/JP6033318B2/ja not_active Expired - Fee Related
- 2012-10-12 CN CN201280061628.1A patent/CN103987696B/zh not_active Expired - Fee Related
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| US20140274960A1 (en) | 2014-09-18 |
| WO2013056034A1 (en) | 2013-04-18 |
| ES2579832T3 (es) | 2016-08-17 |
| JP2014530240A (ja) | 2014-11-17 |
| IN2014CN02805A (https=) | 2015-07-03 |
| US9079929B2 (en) | 2015-07-14 |
| CN103987696A (zh) | 2014-08-13 |
| EP2766347A1 (en) | 2014-08-20 |
| EP2766347B1 (en) | 2016-05-04 |
| JP6033318B2 (ja) | 2016-11-30 |
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