HRP20172002T1 - Makrociklički inhibitori faktora xia kondenzirani sa heterociklusima - Google Patents
Makrociklički inhibitori faktora xia kondenzirani sa heterociklusima Download PDFInfo
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- HRP20172002T1 HRP20172002T1 HRP20172002TT HRP20172002T HRP20172002T1 HR P20172002 T1 HRP20172002 T1 HR P20172002T1 HR P20172002T T HRP20172002T T HR P20172002TT HR P20172002 T HRP20172002 T HR P20172002T HR P20172002 T1 HRP20172002 T1 HR P20172002T1
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- chf
- alkyl
- pharmaceutically acceptable
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Classifications
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- 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
- C07D471/12—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 three hetero rings
- C07D471/18—Bridged systems
-
- 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
-
- 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
-
- 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
- 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
- C07D487/08—Bridged systems
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (12)
1. Spoj sa Formulom (Ia):
[image]
ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
--- je opcionalna veza;
prsten A je nezavisno odabran od
[image]
R1 je nezavisno odabrano od H, F, OH, i C1-4 alkil;
R2 je nezavisno odabrano od H, F, i OH;
R3 je nezavisno odabrano od H, C1-4 alkil,
C1-4haloalkil, -(CH2)n-OR5, -(CH2)n-C(O)OR5, C3-6 cikloalkil po izboru supstituiran sa halogenom, i 5- do 6-očlani heteroaril koji sadrži ugljikove atome i 1-2 atoma dušika i po izboru supstituiran sa R1; pod uvjetom da je samo jedna R3 grupa prisutna na prstenu;
R4 je nezavisno odabrano od H, OH, F, OC1-4 alkil, C1-4 alkil, i CN;
R5 je nezavisno odabrano od H i C1-4 alkil;
R6 je nezavisno odabrano od H, F, Cl, Br, CN, OCH3, CH3, C(O)CH3, CHF2, CCH3F2, CF3, OCHF2, NHC(O)C1-4 alkil, C3-6 cikloalkil, i 5-očlani heterociklus supstituiran sa R9;
R7 je nezavisno odabrano od H i F;
R8 je nezavisno odabrano od H, F, Cl, i OCH3;
R9 je nezavisno odabrano od H, cijano, C1-4 alkil, haloalkil, i halogen; i
n, u svakom slučaju, je cijeli broj izabran od 1 i 2.
2. Spoj iz patentnog zahtjeva 1 koji ima Formulu (IIa):
[image]
ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
prsten A je nezavisno odabran od
[image]
R1 je nezavisno odabrano od H i C1-3 alkil;
R2 je nezavisno odabrano od H i F;
R3 je nezavisno odabrano od H, C1-3 alkil,
C1-3haloalkil, -(CH2)n-OR5, -(CH2)n-C(O)OR5, i C3-4 cikloalkil po izboru supstituiran sa halogenom;
R4 je nezavisno odabrano od H i F;
R5 je nezavisno odabrano od H i C1-4 alkil;
R6 je nezavisno odabrano od H, F, Cl, Br, CN, CF3, C(O)CH3, CHF2, CCH3F2, CF3, OCHF2,
[image]
R7 je nezavisno odabrano od H i F;
R8 je nezavisno odabrano od H, F, Cl, i OCH3;
R9 je nezavisno odabrano od H, CHF2, i CF3;
R9' je nezavisno odabrano od H, F, Cl, CN, CHF2, i CF3; i
n, u svakom slučaju, je cijeli broj izabran od 1 i 2.
3. Spoj iz patentnog zahtjeva 2, ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
R1 je nezavisno odabrano od H, CH3, i CH(CH3)2;
R2 je nezavisno odabrano od H i F;
R3 je nezavisno odabrano od H, CH3, CD3, CH2CH3, -CHF2, -CH2CHF2, -CH2CF3, -CH2CH2OH, CH2CH2OC(CH3)3, -CH2C(O)OH, ciklopropil po izboru supstituiran sa F, i ciklobutil;
R6 je nezavisno odabrano od H, F, Cl, Br, CN, CF3, C(O)CH3, CHF2, CCH3F2, CF3, OCHF2,
[image]
R7 je nezavisno odabrano od H i F;
R8 je nezavisno odabrano od H, F, Cl, i OCH3;
R9 je nezavisno odabrano od H, CHF2, i CF3; i
R9' je nezavisno odabrano od H, F, Cl, CN, CHF2, i CF3.
4. Spoj iz patentnog zahtjeva 1 koji ima Formulu (IIIa):
[image]
ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
prsten A je nezavisno odabran od
[image]
R1 je nezavisno odabrano od H, CH3, i CH(CH3)2;
R2 je nezavisno odabrano od H i F;
R3 je nezavisno odabrano od H, CH2C(=O)OH, CH2C(=O)OCH2CH3,
[image]
R4 je nezavisno odabrano od H i F;
R6 je nezavisno odabrano od H, F, Cl, Br, CN, CF3, C(O)CH3, CHF2, CCH3F2, CF3, OCHF2,
[image]
R7 je nezavisno odabrano od H i F;
R8 je nezavisno odabrano od H, F, Cl, i OCH3;
R9 je nezavisno odabrano od H, CHF2, i CF3; i
R9' je nezavisno odabrano od H, F, Cl, CN, CHF2, i CF3.
5. Spoj iz patentnog zahtjeva 1, ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
R3 je nezavisno odabrano od H, CH3, CD3, CH2CH3, -CHF2, -CH2CHF2, -CH2CF3, -CH2CH2OH, CH2CH2OC(CH3)3, -CH2C(O)OH, CH2C(=O)OH, CH2C(=O)OCH2CH3, ciklopropil po izboru supstituiran sa F, i ciklobutil,
[image]
R6 je nezavisno odabrano od H, F, Cl, Br, CN, CF3, C(O)CH3, CHF2, CCH3F2, CF3, OCHF2,
[image]
R7 je nezavisno odabrano od H i F;
R8 je Cl;
R9 je nezavisno odabrano od H, CHF2, i CF3; i
R9' je nezavisno odabrano od H, F, Cl, CN, CHF2, i CF3;
6. Spoj koji ima Formulu (IV):
[image]
ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
prsten A je nezavisno odabran od
[image]
R1 je nezavisno odabrano od H i C1-3alkil;
R2 je nezavisno odabrano od H i F;
R3 je nezavisno odabrano od H, CD3, CHF2, i CH3;
R4 je nezavisno odabrano od H i halogen;
R7 je nezavisno odabrano od H i F;
R8 je nezavisno odabrano od H, F, Cl, i OCH3; i
R9 je nezavisno odabrano od H, F, Cl, CN, i CF3.
7. Spoj koji ima Formulu (V):
[image]
ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol, gdje:
prsten A je nezavisno odabran od
[image]
R1 je nezavisno odabrano od H i C1-3alkil;
R2 je nezavisno odabrano od H i F;
R3 je nezavisno odabrano od H, CD3, CHF2, i CH3;
R4 je nezavisno odabrano od H i halogen;
R6 je nezavisno odabrano od H, F, Cl, Br, CN, CF3, C(O)CH3, CHF2, CCH3F2, CF3, OCHF2,
[image]
R7 je nezavisno odabrano od H i F;
R8 je nezavisno odabrano od H, F, Cl, i OCH3;
R9 je nezavisno odabrano od H, CHF2, i CF3; i
R9' je nezavisno odabrano od H, F, Cl, CN, CHF2, i CF3.
8. Spoj u skladu sa patentnim zahtjevom 1, 6 ili 7 odabran sa liste koja se sastoji od
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ili stereoizomer, tautomer, njegova farmaceutski prihvatljiva sol.
9. Farmaceutska kompozicija koja sadrži jedan ili više spojeva u skladu sa bilo kojim od patentnih zahtjeva 1-8 i farmaceutski prihvatljiv nosač ili razblaživač.
10. Spoj u skladu sa bilo kojim od patentnih zahtjeva 1-8, ili stereoizomer, tautomer, ili njegova farmaceutski prihvatljiva sol ili kompozicija u skladu sa patentnim zahtjevom 9 za primjenu kao medikament.
11. Spoj u skladu sa bilo kojim od patentnih zahtjeva 1-8, ili stereoizomer, tautomer, ili njegova farmaceutski prihvatljiva sol za primjenu u liječenju i/ili profilaksi tromboembolijskog poremećaja, gdje tromboembolijski poremećaj je odabran od arterijskih kardiovaskularnih tromboembolijskih poremećaja, venskih tromboembolijskih poremećaja, i tromboembolijskih poremećaja u komorama srca ili u perifernoj cirkulaciji.
12. Spoj ili stereoizomer, tautomer, ili njegova farmaceutski prihvatljiva sol za primjenu u skladu sa patentnim zahtjevom 11, gdje tromboembolijski poremećaj je odabran od nestabilne angine, akutnog koronarnog sindroma, atrijalne fibrilacije, infarkta miokarda, prolaznog ishemijskog napada, moždanog udara, ateroskleroze, periferne okluzivne arterijske bolesti, venske tromboze, duboke venske tromboze, tromboflebitisa, arterijske embolije, koronarne arterijske tromboze, cerebralne arterijske tromboze, cerebralne embolije, bubrežne embolije, plućne embolije, i tromboze koja nastaje od medicinskih implantata, uređaja, ili procedura u kojima je krv izložena umjetnoj površini koja izaziva trombozu.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461933948P | 2014-01-31 | 2014-01-31 | |
| PCT/US2015/013647 WO2015116882A1 (en) | 2014-01-31 | 2015-01-30 | Macrocyclic factor xia inhibitors condensed with heterocycles |
| EP15705427.1A EP3099688B1 (en) | 2014-01-31 | 2015-01-30 | Macrocyclic factor xia inhibitors condensed with heterocycles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20172002T1 true HRP20172002T1 (hr) | 2018-02-09 |
Family
ID=52484569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20172002TT HRP20172002T1 (hr) | 2014-01-31 | 2015-01-30 | Makrociklički inhibitori faktora xia kondenzirani sa heterociklusima |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US20170057961A1 (hr) |
| EP (1) | EP3099688B1 (hr) |
| JP (1) | JP6419836B2 (hr) |
| CN (1) | CN106459051B (hr) |
| AR (1) | AR099228A1 (hr) |
| BR (1) | BR112016016741B1 (hr) |
| CA (1) | CA2937738C (hr) |
| CY (1) | CY1120534T1 (hr) |
| DK (1) | DK3099688T3 (hr) |
| EA (1) | EA032650B1 (hr) |
| ES (1) | ES2655540T3 (hr) |
| HR (1) | HRP20172002T1 (hr) |
| HU (1) | HUE038060T2 (hr) |
| LT (1) | LT3099688T (hr) |
| MX (1) | MX2016009385A (hr) |
| NO (1) | NO2760821T3 (hr) |
| PL (1) | PL3099688T3 (hr) |
| PT (1) | PT3099688T (hr) |
| RS (1) | RS56785B1 (hr) |
| SI (1) | SI3099688T1 (hr) |
| SM (1) | SMT201800024T1 (hr) |
| TW (1) | TWI703144B (hr) |
| UY (1) | UY35972A (hr) |
| WO (1) | WO2015116882A1 (hr) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2766346T1 (sl) | 2011-10-14 | 2017-05-31 | Bristol-Myers Squibb Company | Substituirane tetrahidroizokinolinske spojine kot faktor xia inhibitorji |
| EP2978751B1 (en) | 2013-03-25 | 2018-12-05 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| NO2760821T3 (hr) | 2014-01-31 | 2018-03-10 | ||
| KR20240017118A (ko) | 2014-01-31 | 2024-02-06 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 XIa 억제제로서의 헤테로시클릭 P2' 기를 갖는 마크로사이클 |
| EP3189047B1 (en) | 2014-09-04 | 2018-12-26 | Bristol-Myers Squibb Company | Diamide macrocycles that are fxia inhibitors |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| NO2721243T3 (hr) * | 2014-10-01 | 2018-10-20 | ||
| JP6742348B2 (ja) | 2015-06-19 | 2020-08-19 | 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ジアミド大員環 |
| US10676477B2 (en) | 2015-07-29 | 2020-06-09 | Bristol-Myers Squibb Company | Factor XIa macrocycle inhibitors bearing a non-aromatic P2' group |
| 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 |
| 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 |
| MX387515B (es) * | 2015-10-29 | 2025-03-18 | Merck Sharp & Dohme Llc | Inhibidores de factor xia. |
| WO2017151746A1 (en) | 2016-03-02 | 2017-09-08 | Bristol-Myers Squibb Company | Diamide macrocycles having factor xia inhibiting activity |
| EP3500556B1 (en) | 2016-08-22 | 2023-08-02 | Merck Sharp & Dohme LLC | Pyridine-1-oxide derivatives and their use as factor xia inhibitors |
| KR20190084310A (ko) | 2016-11-23 | 2019-07-16 | 바이엘 크롭사이언스 악티엔게젤샤프트 | 살충제로서의 2-[3-(알킬술포닐)-2H-인다졸-2-일]-3H-이미다조[4,5-b]피리딘 유도체 및 유사한 화합물 |
| UY37556A (es) | 2017-01-10 | 2018-07-31 | Bayer Ag | Derivados heterocíclicos como pesticidas |
| AU2018208422B2 (en) | 2017-01-10 | 2021-11-11 | Bayer Aktiengesellschaft | Heterocyclene derivatives as pest control agents |
| CN110062757B (zh) * | 2017-01-18 | 2022-03-04 | 广东东阳光药业有限公司 | 凝血因子XIa抑制剂及其用途 |
| CN110922412A (zh) * | 2018-09-20 | 2020-03-27 | 复旦大学 | 具有抗精神病作用药物化合物的不对称合成方法 |
| US12018027B2 (en) | 2019-04-16 | 2024-06-25 | China Resources Biopharmaceutical Company Limited | Macrocyclic derivatives acting as XIa factor inhibitor |
| JP2022540833A (ja) * | 2019-07-08 | 2022-09-20 | ゲイリー シャープ イノベーションズ インコーポレイテッド | 高コントラストを有する、偏光系のコンパクトなコリメータ |
| JP7286001B2 (ja) * | 2019-07-23 | 2023-06-02 | メッドシャイン ディスカバリー インコーポレイテッド | 第ＸＩａ因子阻害剤としての大環状誘導体 |
| TW202229280A (zh) * | 2020-10-12 | 2022-08-01 | 美商必治妥美雅史谷比公司 | （６ｒ，１０ｓ）－１０－｛４－［５－氯－２－（４－氯－１ｈ－１，２，３－三唑－１－基）苯基］－６－側氧基－１（６ｈ）－嘧啶基｝－１－（二氟甲基）－６－甲基－１，４，７，８，９，１０－六氫－１１，１５－（亞甲橋基）吡唑并［４，３－ｂ］［１，７］二氮雜環十四炔－５（６ｈ）－酮之製備方法 |
| TWI877478B (zh) * | 2021-04-21 | 2025-03-21 | 大陸商上海美悦生物科技發展有限公司 | FXIa抑制劑及其藥物組合物、製備方法和用途 |
| AU2024309220A1 (en) * | 2023-06-30 | 2026-01-29 | Shenzhen Salubris Pharmaceuticals Co., Ltd | Polysubstituted macrocyclic compound, and preparation method therefor and use thereof |
Family Cites Families (107)
| 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 |
| 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 |
| WO1996034010A2 (en) | 1995-03-29 | 1996-10-31 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5624936A (en) | 1995-03-29 | 1997-04-29 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| AU717298B2 (en) | 1996-04-03 | 2000-03-23 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5869682A (en) | 1996-04-03 | 1999-02-09 | Merck & Co., Inc. | 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 |
| TW557297B (en) | 1997-09-26 | 2003-10-11 | Abbott Lab | Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same |
| CA2324226C (en) | 1998-03-19 | 2012-06-05 | Vertex Pharmaceuticals Incorporated | Inhibitors of caspases |
| EE200000706A (et) | 1998-05-26 | 2002-06-17 | Warner-Lambert Company | Bitsüklilised pürimidiinid ja bitsüklilised 3,4-dihüdropürimidiinid kui rakkude proliferatsiooni inhibiitorid |
| 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) |
| KR20010101355A (ko) | 1999-01-02 | 2001-11-14 | 로버트 흐라이탁, 미쉘 베스트 | 신규한 말론산 유도체, 이의 제조 방법, 이의 용도 및이를 함유하는 약제학적 조성물(인자 ｘａ 활성 억제) |
| IL145771A0 (en) | 1999-04-09 | 2002-07-25 | Basf Ag | Low-molecular inhibitors of complement proteases |
| 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 |
| JP2004507456A (ja) | 2000-05-11 | 2004-03-11 | ブリストル−マイヤーズ スクイブ カンパニー | 成長ホルモン分泌促進薬として有用なテトラヒドロイソキノリン類縁体 |
| 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 |
| WO2003011222A2 (en) | 2001-07-27 | 2003-02-13 | Merck & Co., Inc. | Thrombin inhibitors |
| US6951840B2 (en) | 2001-08-31 | 2005-10-04 | Eli Lilly And Company | Lipoglycopeptide antibiotics |
| EP1427415B1 (en) | 2001-09-21 | 2009-08-12 | Brystol-Myers Squibb Company | Lactam-containing compounds and derivatives thereof as factor xa inhibitors |
| WO2003041641A2 (en) | 2001-11-09 | 2003-05-22 | Bristol-Myers Squibb Company | Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity |
| WO2003106438A1 (en) | 2002-06-18 | 2003-12-24 | The Scripps Research Institute | Synthesis of diazonamide "a" core |
| 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 |
| WO2005014533A2 (en) | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
| US7417063B2 (en) | 2004-04-13 | 2008-08-26 | Bristol-Myers Squibb Company | Bicyclic 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 |
| US7429604B2 (en) | 2004-06-15 | 2008-09-30 | Bristol Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| BRPI0513310A (pt) | 2004-07-12 | 2008-05-06 | Idun Pharmaceuticals Inc | análogos de tetrapeptìdeo |
| JP5236293B2 (ja) | 2005-01-13 | 2013-07-17 | ブリストル−マイヤーズ スクイブ カンパニー | Ｘｉａ因子阻害剤としての置換ビアリール化合物 |
| 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 |
| WO2007047608A2 (en) | 2005-10-14 | 2007-04-26 | Epix Pharmaceuticals, Inc. | Fibrin targeted therapeutics |
| BRPI0618523A2 (pt) | 2005-11-11 | 2011-09-06 | Hoffmann La Roche | compostos de aminas cìclicas fundidas carbocìclicas, composições farmacêuticas e usos dos mesmos |
| AU2006325746A1 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| US8466295B2 (en) | 2005-12-14 | 2013-06-18 | Bristol-Myers Squibb Company | Thiophene derivatives as factor XIa inhibitors |
| EP1981854B1 (en) | 2005-12-14 | 2011-06-01 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| PE20071132A1 (es) | 2005-12-23 | 2007-12-14 | Bristol Myers Squibb Co | Compuestos macrociclicos como inhibidores del factor viia |
| EP2102189B1 (en) | 2006-12-15 | 2015-07-29 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| PE20081775A1 (es) | 2006-12-20 | 2008-12-18 | Bristol Myers Squibb Co | Compuestos macrociclicos como inhibidores del factor viia |
| EP2152664B1 (en) | 2007-06-13 | 2014-09-03 | Bristol-Myers Squibb Company | Dipeptide analogs as coagulation factor inhibitors |
| EP2265601B1 (en) | 2008-03-13 | 2012-02-01 | Bristol-Myers Squibb Company | Pyridazine derivatives as factor xia inhibitors |
| WO2010151317A1 (en) | 2009-06-22 | 2010-12-29 | 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 |
| CA2789622C (en) * | 2010-02-11 | 2018-04-03 | Bristol-Myers Squibb Company | Macrocycles as factor xia inhibitors |
| EP2729150B1 (en) | 2011-07-08 | 2016-09-14 | 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 |
| SI2766346T1 (sl) | 2011-10-14 | 2017-05-31 | Bristol-Myers Squibb Company | Substituirane tetrahidroizokinolinske spojine kot faktor xia inhibitorji |
| WO2013056034A1 (en) | 2011-10-14 | 2013-04-18 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2899183B1 (en) | 2011-10-14 | 2018-09-19 | Bristol-Myers Squibb Company | Substituted Tetrahydroisoquinoline Compounds as Factor Xia Inhibitors |
| DK2794597T3 (en) | 2011-12-21 | 2018-01-15 | Ono Pharmaceutical Co | PYRIDINON AND PYRIMIDINON DERIVATIVES AS FACTOR XIA INHIBITORS |
| GB2497806A (en) | 2011-12-21 | 2013-06-26 | Ono Pharmaceutical Co | Pyridinone and pyrimidinone derivatives as factor XIa inhibitors |
| WO2013111107A1 (en) | 2012-01-27 | 2013-08-01 | Novartis Ag | Aminopyridine derivatives as plasma kallikrein inhibitors |
| WO2013111108A1 (en) | 2012-01-27 | 2013-08-01 | 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 |
| BR112014027952B1 (pt) | 2012-05-10 | 2022-06-21 | Bayer Pharma Aktiengesellschaft | Anticorpos monoclonais humanos capazes de se ligarem ao fator de coagulação xi, seu uso, composição farmacêutica e medicamento os compreendendo, ácido nucleico que o codifica, bem como vetor |
| GB201209138D0 (en) | 2012-05-24 | 2012-07-04 | Ono Pharmaceutical Co | Compounds |
| EP2876105A4 (en) | 2012-07-19 | 2016-01-13 | Sumitomo Dainippon Pharma Co Ltd | 1- (CYCLOALKYL-CARBONYL) PROLIN DERIVATIVE |
| LT2882734T (lt) * | 2012-08-03 | 2016-12-12 | Bristol-Myers Squibb Company | Dihidropiridonai, kaip xia faktoriaus slopikliai |
| PT2880026T (pt) * | 2012-08-03 | 2017-05-03 | Bristol Myers Squibb Co | Dihidropiridona p1 como inibidores de fator xia |
| US9315519B2 (en) | 2012-10-12 | 2016-04-19 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor XIa inhibitors |
| EP2906551B1 (en) | 2012-10-12 | 2018-02-28 | Bristol-Myers Squibb Company | Crystalline forms of a factor xia inhibitor |
| WO2014059214A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2934538B1 (en) | 2012-12-19 | 2021-03-31 | Merck Sharp & Dohme Corp. | Factor ixa inhibitors |
| GB201300304D0 (en) | 2013-01-08 | 2013-02-20 | Kalvista Pharmaceuticals Ltd | Benzylamine derivatives |
| GB2510407A (en) | 2013-02-04 | 2014-08-06 | Kalvista Pharmaceuticals Ltd | Aqueous suspensions of kallikrein inhibitors for parenteral administration |
| EP2978751B1 (en) | 2013-03-25 | 2018-12-05 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| TWI633089B (zh) | 2013-03-28 | 2018-08-21 | 拜耳製藥股份有限公司 | 經取代的酮基吡啶衍生物 |
| US9475809B2 (en) | 2013-07-23 | 2016-10-25 | Bayer Pharma Aktiengesellschaft | Substituted oxopyridine derivatives and use thereof as factor xia/plasma |
| EP3049407A1 (de) | 2013-09-26 | 2016-08-03 | Bayer Pharma Aktiengesellschaft | Substituierte phenylalanin-derivate als faktor xia modulatoren |
| EP3049410A1 (de) | 2013-09-26 | 2016-08-03 | Bayer Pharma Aktiengesellschaft | Substituierte phenylalanin-derivate als faktor xia modulatoren |
| WO2015044172A1 (de) | 2013-09-26 | 2015-04-02 | Bayer Pharma Aktiengesellschaft | Substituierte phenylalanin-derivate |
| TW201605828A (zh) | 2013-09-26 | 2016-02-16 | 拜耳製藥股份有限公司 | 經取代苯丙胺酸衍生物（三） |
| WO2015044167A1 (de) | 2013-09-26 | 2015-04-02 | Bayer Pharma Aktiengesellschaft | Substituierte phenylalanin-derivate als faktor xia modulatoren |
| AP2016009095A0 (en) | 2013-09-26 | 2016-03-31 | Bayer Pharma AG | Substituted phenylalanine derivatives |
| WO2015044169A1 (de) | 2013-09-26 | 2015-04-02 | Bayer Pharma Aktiengesellschaft | Substituierte phenylalanin-derivate |
| WO2015044170A1 (de) | 2013-09-26 | 2015-04-02 | Bayer Pharma Aktiengesellschaft | Substituierte phenylalanin-derivate und ihre verwendung zur behandlung von thrombotischen / thromboembolischen erkrankungen |
| EP3049435A4 (en) | 2013-09-27 | 2017-03-29 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| EP3054944B1 (en) | 2013-10-07 | 2019-12-04 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| JP6337750B2 (ja) | 2013-11-22 | 2018-06-06 | 小野薬品工業株式会社 | 化合物 |
| HK1226390A1 (zh) | 2014-01-14 | 2017-09-29 | 大日本住友制药株式会社 | 缩合5-恶唑烷酮衍生物 |
| NO2760821T3 (hr) | 2014-01-31 | 2018-03-10 | ||
| KR20240017118A (ko) | 2014-01-31 | 2024-02-06 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 XIa 억제제로서의 헤테로시클릭 P2' 기를 갖는 마크로사이클 |
| US9499532B2 (en) | 2014-02-07 | 2016-11-22 | eXIthera Pharmaceuticals Inc. | Therapeutic compounds and compositions |
| WO2015123093A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| EP3104701B1 (en) | 2014-02-11 | 2019-01-30 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| EP3104702B1 (en) | 2014-02-11 | 2022-08-10 | Merck Sharp & Dohme LLC | Factor xia inhibitors |
| CN105829298B (zh) | 2014-02-14 | 2019-02-01 | 四川海思科制药有限公司 | 一种吡啶酮或嘧啶酮衍生物、及其制备方法和应用 |
| LT3113772T (lt) | 2014-03-07 | 2020-12-28 | Biocryst Pharmaceuticals, Inc. | Trifluormetilo pakeistieji pirazolai kaip žmogaus plazmos kalikreino inhibitoriai |
| WO2015160634A1 (en) | 2014-04-16 | 2015-10-22 | Merck Sharp & Dohme Corp. | Factor ixa inhibitors |
| WO2015160636A1 (en) | 2014-04-16 | 2015-10-22 | Merck Sharp & Dohme Corp. | Factor ixa inhibitors |
| KR20150136294A (ko) | 2014-05-27 | 2015-12-07 | 주식회사 레고켐 바이오사이언스 | 인자 ＸＩａ 억제 활성을 가지는 신규한 화합물 |
| RU2016150410A (ru) | 2014-05-28 | 2018-06-28 | Мерк Шарп И Доум Корп. | Ингибиторы фактора xia |
| WO2016046157A1 (de) | 2014-09-24 | 2016-03-31 | Bayer Pharma Aktiengesellschaft | Faktor xia hemmende pyridobenzazepin- und pyridobenzazocin-derivate |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| NO2721243T3 (hr) | 2014-10-01 | 2018-10-20 | ||
| MX385021B (es) | 2014-12-10 | 2025-03-14 | Ono Pharmaceutical Co | Derivado de dihidroindolizinona. |
| JP6742348B2 (ja) | 2015-06-19 | 2020-08-19 | 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ジアミド大員環 |
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2012
- 2012-08-31 NO NO12780535A patent/NO2760821T3/no unknown
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2015
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- 2015-01-30 CN CN201580017759.3A patent/CN106459051B/zh active Active
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| PT3099688T (pt) | 2018-01-15 |
| MX2016009385A (es) | 2016-09-16 |
| US10273236B2 (en) | 2019-04-30 |
| JP2017504640A (ja) | 2017-02-09 |
| CN106459051A (zh) | 2017-02-22 |
| EA201691561A1 (ru) | 2017-01-30 |
| TW201615640A (zh) | 2016-05-01 |
| CY1120534T1 (el) | 2019-07-10 |
| CA2937738C (en) | 2023-01-17 |
| JP6419836B2 (ja) | 2018-11-07 |
| SI3099688T1 (sl) | 2017-12-29 |
| BR112016016741B1 (pt) | 2023-01-17 |
| US20180222907A1 (en) | 2018-08-09 |
| PL3099688T3 (pl) | 2018-03-30 |
| HUE038060T2 (hu) | 2018-09-28 |
| SMT201800024T1 (it) | 2018-03-08 |
| LT3099688T (lt) | 2017-12-27 |
| EA032650B1 (ru) | 2019-06-28 |
| US20170057961A1 (en) | 2017-03-02 |
| CN106459051B (zh) | 2018-10-16 |
| BR112016016741A2 (hr) | 2017-08-08 |
| EP3099688B1 (en) | 2017-10-18 |
| NO2760821T3 (hr) | 2018-03-10 |
| DK3099688T3 (en) | 2018-01-15 |
| RS56785B1 (sr) | 2018-04-30 |
| UY35972A (es) | 2015-07-31 |
| EP3099688A1 (en) | 2016-12-07 |
| AR099228A1 (es) | 2016-07-06 |
| CA2937738A1 (en) | 2015-08-06 |
| WO2015116882A1 (en) | 2015-08-06 |
| ES2655540T3 (es) | 2018-02-20 |
| TWI703144B (zh) | 2020-09-01 |
| US20170342071A1 (en) | 2017-11-30 |
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