CN103987697B - 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
- CN103987697B CN103987697B CN201280061670.3A CN201280061670A CN103987697B CN 103987697 B CN103987697 B CN 103987697B CN 201280061670 A CN201280061670 A CN 201280061670A CN 103987697 B CN103987697 B CN 103987697B
- Authority
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- China
- Prior art keywords
- phenyl
- bases
- alkyl
- chloro
- tetrazolium
- Prior art date
- 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
Links
- 0 CC1=CC2=CN(*)N=CC2C=C1 Chemical compound CC1=CC2=CN(*)N=CC2C=C1 0.000 description 6
- AYPLNGXIRFCAJC-DBXZZFOPSA-N CC(C)(Cc(c(/C=C/C(N(CC1)C(C(Nc(cc2)ccc2C(O)=O)=O)c2c1[n](Cc1ccccc1)nc2C)=O)c1F)ccc1Cl)/C=N\N=N Chemical compound CC(C)(Cc(c(/C=C/C(N(CC1)C(C(Nc(cc2)ccc2C(O)=O)=O)c2c1[n](Cc1ccccc1)nc2C)=O)c1F)ccc1Cl)/C=N\N=N AYPLNGXIRFCAJC-DBXZZFOPSA-N 0.000 description 1
- DHOZGVQOZATZGP-UHFFFAOYSA-N CC(CCN)C=C Chemical compound CC(CCN)C=C DHOZGVQOZATZGP-UHFFFAOYSA-N 0.000 description 1
- VUZKKQLAKICMKV-UHFFFAOYSA-N C[N]1(C2)(C2C1)#C Chemical compound C[N]1(C2)(C2C1)#C VUZKKQLAKICMKV-UHFFFAOYSA-N 0.000 description 1
- KQLSFTLKDUMXDM-RUDMXATFSA-N C[n]1nc(CCN(C2C(Nc(cc3)ccc3C(O)=O)=O)C(/C=C/c3cc(Cl)ccc3-[n]3nnnc3)=O)c2c1 Chemical compound C[n]1nc(CCN(C2C(Nc(cc3)ccc3C(O)=O)=O)C(/C=C/c3cc(Cl)ccc3-[n]3nnnc3)=O)c2c1 KQLSFTLKDUMXDM-RUDMXATFSA-N 0.000 description 1
- BIRRBRQQDQJKMQ-UHFFFAOYSA-N N#Cc1cc([n](C(OCc2ccccc2)=O)nc2)c2cc1 Chemical compound N#Cc1cc([n](C(OCc2ccccc2)=O)nc2)c2cc1 BIRRBRQQDQJKMQ-UHFFFAOYSA-N 0.000 description 1
- XCTSAVLSNJIQFA-MDWZMJQESA-N OC(c(cc1)ccc1NC(C(c1c[n](Cc2ccccc2)nc1CC1)[N-]1C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC(C(c1c[n](Cc2ccccc2)nc1CC1)[N-]1C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O XCTSAVLSNJIQFA-MDWZMJQESA-N 0.000 description 1
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- C07D401/12—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
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547305P | 2011-10-14 | 2011-10-14 | |
| US61/547305 | 2011-10-14 | ||
| PCT/US2012/059859 WO2013055984A1 (en) | 2011-10-14 | 2012-10-12 | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103987697A CN103987697A (zh) | 2014-08-13 |
| CN103987697B true CN103987697B (zh) | 2017-04-26 |
Family
ID=47080862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280061670.3A Expired - Fee Related CN103987697B (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 (5) | US9108951B2 (https=) |
| EP (2) | EP2766345B1 (https=) |
| JP (1) | JP6033317B2 (https=) |
| CN (1) | CN103987697B (https=) |
| ES (2) | ES2572908T3 (https=) |
| IN (1) | IN2014CN02806A (https=) |
| WO (1) | WO2013055984A1 (https=) |
Families Citing this family (54)
| 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 |
| 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 |
| 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 |
| 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 |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| 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 |
| EP2906552B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Bristol Myers Squibb Co | Bir faktör XIa inhibitörünün kristalli formları. |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2975031A4 (en) | 2013-03-14 | 2017-04-19 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| WO2014160668A1 (en) | 2013-03-25 | 2014-10-02 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| EP3018123B1 (en) | 2013-07-03 | 2023-05-10 | Takeda Pharmaceutical Company Limited | Amide compound |
| JP6427491B2 (ja) | 2013-07-03 | 2018-11-21 | 武田薬品工業株式会社 | 複素環化合物 |
| EP3049435A4 (en) * | 2013-09-27 | 2017-03-29 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| WO2015054087A1 (en) | 2013-10-07 | 2015-04-16 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| SG10201908467RA (en) | 2014-01-31 | 2019-10-30 | Bristol Myers Squibb Co | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
| NO2760821T3 (https=) | 2014-01-31 | 2018-03-10 | ||
| WO2015123093A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| WO2015123091A1 (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 |
| AU2015258805B2 (en) | 2014-05-16 | 2018-05-10 | Cumberland Pharmaceuticals, Inc. | Compositions and methods of treating cardiac fibrosis with ifetroban |
| 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 |
| JP6759514B2 (ja) * | 2014-08-01 | 2020-09-23 | ヌエヴォリューション・アクティーゼルスカブＮｕｅｖｏｌｕｔｉｏｎ Ａ／Ｓ | ブロモドメインに対して活性な化合物 |
| CN105461688B (zh) * | 2014-08-26 | 2017-12-29 | 上海医药工业研究院 | 苯并咪唑化合物k的合成方法 |
| ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| JP6799530B2 (ja) * | 2014-10-01 | 2020-12-16 | メディミューン リミテッド | チカグレロルに対する抗体および使用方法 |
| ES2762987T3 (es) | 2015-06-19 | 2020-05-26 | Bristol Myers Squibb Co | Macrociclos de diamida como inhibidores del factor XIA |
| JP7033454B2 (ja) | 2015-06-30 | 2022-03-10 | カンバーランド ファーマシューティカルズ，インコーポレーテッド | Ａｅｒｄ／喘息におけるトロンボキサン受容体拮抗薬 |
| WO2017007756A1 (en) | 2015-07-06 | 2017-01-12 | Rodin Therapeutics, Inc | Hetero-halo inhibitors of histone deacetylase |
| EP3319968A1 (en) | 2015-07-06 | 2018-05-16 | Rodin Therapeutics, Inc. | Heterobicyclic n-aminophenyl-amides as inhibitors of histone deacetylase |
| 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 |
| EP3368036B1 (en) | 2015-10-29 | 2022-07-20 | Merck Sharp & Dohme LLC | Macrocyclic pyridine-n-oxide derivatives as factor xia inhibitors |
| 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 |
| CN108473495B (zh) | 2015-11-20 | 2022-04-12 | 福马治疗有限公司 | 作为泛素-特异性蛋白酶1抑制剂的嘌呤酮 |
| WO2017119508A1 (ja) * | 2016-01-07 | 2017-07-13 | 藤森工業株式会社 | 採血管、試薬及びそれらを利用した血液性状分析方法 |
| CN107540659A (zh) * | 2016-06-29 | 2018-01-05 | 四川科伦博泰生物医药股份有限公司 | 四氢异喹啉类化合物、其制备方法、药物组合物及其用途 |
| WO2018039094A1 (en) | 2016-08-22 | 2018-03-01 | Merck Sharp & Dohme Corp. | Pyridine-1-oxide derivatives and their use as factor xia inhibitors |
| HUE057849T2 (hu) | 2017-01-11 | 2022-06-28 | Alkermes Inc | Hiszton deacetiláz biciklusos gátlói |
| LT3664802T (lt) | 2017-08-07 | 2022-06-27 | Alkermes, Inc. | Bicikliniai histonų deacetilazės inhibitoriai |
| 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 |
| KR20210069079A (ko) * | 2018-09-28 | 2021-06-10 | 얀센 파마슈티카 엔.브이. | 모노아실글리세롤 리파아제 조절제 |
| MY205440A (en) * | 2018-09-28 | 2024-10-21 | Janssen Pharmaceutica Nv | Monoacylglycerol lipase modulators |
| MX2021004566A (es) * | 2018-10-22 | 2021-06-08 | C4X Discovery Ltd | Compuestos terapeuticos. |
| CN111727186B (zh) * | 2018-11-11 | 2022-11-08 | 上海海雁医药科技有限公司 | 双杂环取代的吡啶-2(1h)-酮衍生物、其制法与医药上的用途 |
| JP7697934B2 (ja) | 2019-09-30 | 2025-06-24 | ヤンセン ファーマシューティカ エヌ．ベー． | 放射線標識されたｍｇｌ ｐｅｔリガンド |
| CN114761408B (zh) * | 2019-12-19 | 2023-09-15 | 贝达药业股份有限公司 | Kras g12c抑制剂及其在医药上的应用 |
| JP2023534704A (ja) * | 2020-07-22 | 2023-08-10 | ヤンセン ファーマシューティカ エヌ．ベー． | 第ｘｉａ因子阻害剤として有用な化合物 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003041641A2 (en) * | 2001-11-09 | 2003-05-22 | Bristol-Myers Squibb Company | Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity |
| CN1441785A (zh) * | 2000-05-11 | 2003-09-10 | 布里斯托尔-迈尔斯斯奎布公司 | 可用作生长激素促分泌素的四氢异喹啉类似物 |
| WO2005014533A2 (en) * | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1525186A (fr) | 1967-03-29 | 1968-05-17 | Roussel Uclaf | Nouvelles pénicillines et procédé de préparation |
| EP0028489B1 (en) | 1979-11-05 | 1983-10-05 | Beecham Group Plc | Enzyme derivatives, and their preparation |
| US4843062A (en) | 1987-12-23 | 1989-06-27 | American Home Products Corporation | N-acyl-N-napthoylglycines as aldose reductase inhibitors |
| DE4034829A1 (de) | 1990-11-02 | 1992-05-07 | Merck Patent Gmbh | Cyclopeptide |
| JP3190431B2 (ja) | 1991-07-01 | 2001-07-23 | 三菱化学株式会社 | ケトン誘導体 |
| GB9206757D0 (en) | 1992-03-27 | 1992-05-13 | Ferring Bv | Novel peptide receptor ligands |
| US5624936A (en) | 1995-03-29 | 1997-04-29 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| WO1996034010A2 (en) | 1995-03-29 | 1996-10-31 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5869682A (en) | 1996-04-03 | 1999-02-09 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| CA2249617A1 (en) | 1996-04-03 | 1997-10-09 | S. Jane Desolms | Inhibitors of farnesyl-protein transferase |
| PE121699A1 (es) | 1997-02-18 | 1999-12-08 | Boehringer Ingelheim Pharma | Heterociclos biciclicos disustituidos como inhibidores de la trombina |
| ZA985247B (en) | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
| WO2000077027A2 (en) | 1999-06-14 | 2000-12-21 | Tularik Limited | Serine protease inhibitors |
| TWI243828B (en) | 1998-03-19 | 2005-11-21 | Vertex Pharma | Inhibitors of caspases |
| TR200003429T2 (tr) | 1998-05-26 | 2001-07-23 | Warner-Lambert Company | Hücresel çoğalma inhibitörleri olarak bisiklik pirimidinler ve bisiklik 3,4-dihidropirimidinler. |
| US6307049B1 (en) | 1998-09-30 | 2001-10-23 | The Procter & Gamble Co. | Heterocyclic 2-substituted ketoamides |
| EP1016663A1 (en) | 1999-01-02 | 2000-07-05 | Aventis Pharma Deutschland GmbH | Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor Xa activity) |
| TR200101903T2 (tr) | 1999-01-02 | 2001-11-21 | Aventis Pharma Deutschland Gmbh | Yeni malonik asit türevleri, bunların preparasyon işlemleri. |
| JP4489976B2 (ja) | 1999-04-09 | 2010-06-23 | ビーエーエスエフ ソシエタス・ヨーロピア | 補体プロテアーゼの低分子インヒビター |
| DE19962924A1 (de) | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| EP1125925A1 (en) | 2000-02-15 | 2001-08-22 | Applied Research Systems ARS Holding N.V. | Amine derivatives for the treatment of apoptosis |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| AR035216A1 (es) | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| WO2003016248A2 (en) | 2001-08-17 | 2003-02-27 | Bristol-Myers Squibb Company Patent Department | Bicyclic hydroxamates as inhibitors of matrix metalloproteinases and/or tnf-$g(a) converting enzyme (tace) |
| CN104744461A (zh) | 2001-09-21 | 2015-07-01 | 百时美施贵宝公司 | 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂 |
| GB0206033D0 (en) | 2002-03-14 | 2002-04-24 | Pfizer Ltd | Compounds useful in therapy |
| US20040180855A1 (en) | 2003-02-19 | 2004-09-16 | Schumacher William A. | Methods of treating thrombosis with reduced risk of increased bleeding times |
| US7138412B2 (en) | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
| US7129264B2 (en) | 2003-04-16 | 2006-10-31 | Bristol-Myers Squibb Company | Biarylmethyl indolines and indoles as antithromboembolic agents |
| US7417063B2 (en) | 2004-04-13 | 2008-08-26 | Bristol-Myers Squibb Company | Bicyclic heterocycles useful as serine protease inhibitors |
| US7429604B2 (en) | 2004-06-15 | 2008-09-30 | Bristol Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
| CA2573644A1 (en) | 2004-07-12 | 2006-02-16 | Idun Pharmaceuticals, Inc. | Tetrapeptide analogs |
| EP1841504B1 (en) | 2005-01-13 | 2014-11-19 | Bristol-Myers Squibb Company | Substituted biaryl compounds as factor xia inhibitors |
| US20060183771A1 (en) | 2005-02-17 | 2006-08-17 | Seiffert Dietmar A | Novel combination of selective factor VIIa and/or factor XIa inhibitors and selective plasma kallikrein inhibitors |
| AU2006259075B2 (en) | 2005-06-17 | 2012-02-09 | Basf Se | Process of producing bleach boosters |
| JP4955009B2 (ja) | 2005-11-11 | 2012-06-20 | エフ．ホフマン−ラ ロシュ アーゲー | 凝固因子Ｘａの阻害剤としての炭素環式縮合環アミン |
| WO2007070816A2 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Thiophene derivatives as factor xia inhibitors |
| EP1966141A1 (en) | 2005-12-14 | 2008-09-10 | Brystol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| NZ568595A (en) | 2005-12-14 | 2010-04-30 | Bristol Myers Squibb Co | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor Xla inhibitors |
| SG174095A1 (en) | 2006-08-23 | 2011-09-29 | Valeant Pharmaceuticals Int | Derivatives of 4-(n-azacycloalkyl) anilides as potassium channel modulators |
| EP2102189B1 (en) | 2006-12-15 | 2015-07-29 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| CN101784516B (zh) * | 2007-06-13 | 2014-07-02 | 百时美施贵宝公司 | 作为凝血因子抑制剂的二肽类似物 |
| BRPI0813230A2 (pt) | 2007-06-28 | 2014-12-23 | Novartis Ag | Moduladores de calicreína 7 |
| US8324199B2 (en) | 2008-03-13 | 2012-12-04 | Bristol-Myers Squibb Company | Pyridazine derivatives as factor xia inhibitors |
| US8624040B2 (en) | 2009-06-22 | 2014-01-07 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
| US8513433B2 (en) | 2009-07-02 | 2013-08-20 | Angion Biomedica Corp. | Small molecule inhibitors of PARP activity |
| WO2011017296A1 (en) | 2009-08-04 | 2011-02-10 | Schering Corporation | 4, 5, 6-trisubstituted pyrimidine derivatives as factor ixa inhibitors |
| NZ602266A (en) | 2010-02-11 | 2014-05-30 | Bristol Myers Squibb Co | Macrocycles as factor xia inhibitors |
| US9161924B2 (en) | 2011-07-08 | 2015-10-20 | Merck Sharp & Dohme Corp. | Factor IXa 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 |
| 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 |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| US9732085B2 (en) | 2011-12-21 | 2017-08-15 | Ono Pharmaceutical Co., Ltd. | Pyridinone and pyrimidinone derivatives as factor Xia |
| EP2807156A1 (en) | 2012-01-27 | 2014-12-03 | Novartis AG | Aminopyridine derivatives as plasma kallikrein inhibitors |
| US20140378474A1 (en) | 2012-01-27 | 2014-12-25 | Novartis Ag | 5-membered heteroarylcarboxamide derivatives as plasma kallikrein inhibitors |
| JP2015083542A (ja) | 2012-02-08 | 2015-04-30 | 大日本住友製薬株式会社 | ３位置換プロリン誘導体 |
| EP2847228B1 (en) | 2012-05-10 | 2018-07-25 | Bayer Pharma Aktiengesellschaft | Antibodies capable of binding to the coagulation factor xi and/or its activated form factor xia and uses thereof |
| 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 |
-
2012
- 2012-10-12 WO PCT/US2012/059859 patent/WO2013055984A1/en not_active Ceased
- 2012-10-12 EP EP12778912.1A patent/EP2766345B1/en not_active Not-in-force
- 2012-10-12 ES ES12778912.1T patent/ES2572908T3/es active Active
- 2012-10-12 US US14/350,417 patent/US9108951B2/en active Active
- 2012-10-12 IN IN2806CHN2014 patent/IN2014CN02806A/en unknown
- 2012-10-12 JP JP2014535894A patent/JP6033317B2/ja not_active Expired - Fee Related
- 2012-10-12 EP EP14195397.6A patent/EP2899183B1/en not_active Not-in-force
- 2012-10-12 CN CN201280061670.3A patent/CN103987697B/zh not_active Expired - Fee Related
- 2012-10-12 ES ES14195397T patent/ES2699226T3/es active Active
-
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- 2015-07-15 US US14/799,681 patent/US9394276B2/en active Active
-
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- 2016-06-15 US US15/183,051 patent/US9725435B2/en active Active
-
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- 2017-07-07 US US15/643,891 patent/US10000466B2/en active Active
-
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- 2018-05-17 US US15/982,038 patent/US10906886B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1441785A (zh) * | 2000-05-11 | 2003-09-10 | 布里斯托尔-迈尔斯斯奎布公司 | 可用作生长激素促分泌素的四氢异喹啉类似物 |
| WO2003041641A2 (en) * | 2001-11-09 | 2003-05-22 | Bristol-Myers Squibb Company | Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity |
| WO2005014533A2 (en) * | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
Non-Patent Citations (4)
| Title |
|---|
| Highly Efficient Oxidation of Amines to Imines by Singlet Oxygen and Its Application in Ugi-Type Reactions;Gaoxi Jiang，等;《ORGANIC LETTERS》;20091015;第11卷(第20期);表4 * |
| IBX-Mediated Oxidative Ugi-Type Multicomponent Reactions: Application to the N and Cl Functionalization of Tetrahydroisoquinoline;Tifelle Ngouansavanh，等;《Angew. Chem. Int. Ed.》;20070723;第46卷(第30期);图1 * |
| Quantitative Structure–Activity Relationship Modeling of Growth Hormone Secretagogues Agonist Activity of some Tetrahydroisoquinoline 1-Carboxamides;Julio Caballero，等;《Chem Biol Drug Des》;20070101;第69卷(第1期);表1 * |
| Tetrahydroisoquinoline 1-carboxamides as growth hormone secretagogues;James J. Li，等;《Bioorganic & Medicinal Chemistry Letters》;20050401;第15卷(第7期);表1 * |
Also Published As
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| US9108951B2 (en) | 2015-08-18 |
| US20140275061A1 (en) | 2014-09-18 |
| US20160289209A1 (en) | 2016-10-06 |
| US9394276B2 (en) | 2016-07-19 |
| US9725435B2 (en) | 2017-08-08 |
| ES2572908T3 (es) | 2016-06-03 |
| US20150315200A1 (en) | 2015-11-05 |
| JP2014528479A (ja) | 2014-10-27 |
| EP2766345B1 (en) | 2016-03-16 |
| CN103987697A (zh) | 2014-08-13 |
| WO2013055984A1 (en) | 2013-04-18 |
| JP6033317B2 (ja) | 2016-11-30 |
| US10000466B2 (en) | 2018-06-19 |
| EP2899183A1 (en) | 2015-07-29 |
| US20180265494A1 (en) | 2018-09-20 |
| IN2014CN02806A (https=) | 2015-07-03 |
| EP2766345A1 (en) | 2014-08-20 |
| US20170305880A1 (en) | 2017-10-26 |
| ES2699226T3 (es) | 2019-02-08 |
| EP2899183B1 (en) | 2018-09-19 |
| US10906886B2 (en) | 2021-02-02 |
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