JP2017504642A5 - - Google Patents
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- JP2017504642A5 JP2017504642A5 JP2016549279A JP2016549279A JP2017504642A5 JP 2017504642 A5 JP2017504642 A5 JP 2017504642A5 JP 2016549279 A JP2016549279 A JP 2016549279A JP 2016549279 A JP2016549279 A JP 2016549279A JP 2017504642 A5 JP2017504642 A5 JP 2017504642A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- independently selected
- substituted
- cycloalkyl
- heterocyclyl
- 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.)
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- 125000000217 alkyl group Chemical group 0.000 claims 190
- 125000000623 heterocyclic group Chemical group 0.000 claims 122
- 229910052739 hydrogen Inorganic materials 0.000 claims 75
- 229910052799 carbon Inorganic materials 0.000 claims 53
- 229910052731 fluorine Inorganic materials 0.000 claims 51
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 48
- 229910052736 halogen Inorganic materials 0.000 claims 43
- 150000002367 halogens Chemical class 0.000 claims 43
- 125000003118 aryl group Chemical group 0.000 claims 37
- 229910052801 chlorine Inorganic materials 0.000 claims 33
- 125000004452 carbocyclyl group Chemical group 0.000 claims 31
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 30
- 229910052760 oxygen Inorganic materials 0.000 claims 26
- 229910052757 nitrogen Inorganic materials 0.000 claims 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 21
- 125000003545 alkoxy group Chemical group 0.000 claims 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims 19
- 125000001188 haloalkyl group Chemical group 0.000 claims 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 19
- 229910052794 bromium Inorganic materials 0.000 claims 17
- -1 —S (═O) 2 NH 2 Chemical group 0.000 claims 15
- 150000003839 salts Chemical class 0.000 claims 13
- 150000001875 compounds Chemical class 0.000 claims 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 7
- 125000004432 carbon atom Chemical group C* 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 208000035475 disorder Diseases 0.000 claims 7
- 230000009424 thromboembolic effect Effects 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 125000005842 heteroatom Chemical group 0.000 claims 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 4
- 125000002947 alkylene group Chemical group 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 229910052805 deuterium Inorganic materials 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 125000003342 alkenyl group Chemical group 0.000 claims 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims 3
- 125000006809 haloalkylaminocarbonyl group Chemical group 0.000 claims 3
- 229910052740 iodine Inorganic materials 0.000 claims 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 2
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 125000004450 alkenylene group Chemical group 0.000 claims 2
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims 2
- 125000001769 aryl amino group Chemical group 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000005221 halo alkyl carbonyl amino group Chemical group 0.000 claims 2
- 125000005241 heteroarylamino group Chemical group 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 230000000069 prophylactic effect Effects 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 1
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 1
- 206010008088 Cerebral artery embolism Diseases 0.000 claims 1
- 206010008092 Cerebral artery thrombosis Diseases 0.000 claims 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims 1
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 1
- 206010014513 Embolism arterial Diseases 0.000 claims 1
- 208000032382 Ischaemic stroke Diseases 0.000 claims 1
- 208000010378 Pulmonary Embolism Diseases 0.000 claims 1
- 206010063544 Renal embolism Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
- 125000004104 aryloxy group Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 210000005242 cardiac chamber Anatomy 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 1
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 201000010849 intracranial embolism Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 230000003836 peripheral circulation Effects 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 201000005060 thrombophlebitis Diseases 0.000 claims 1
- 230000001052 transient effect Effects 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461933942P | 2014-01-31 | 2014-01-31 | |
| US61/933,942 | 2014-01-31 | ||
| US201462058293P | 2014-10-01 | 2014-10-01 | |
| US62/058,293 | 2014-10-01 | ||
| PCT/US2015/013654 WO2015116886A1 (en) | 2014-01-31 | 2015-01-30 | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019060181A Division JP6854067B2 (ja) | 2014-01-31 | 2019-03-27 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017504642A JP2017504642A (ja) | 2017-02-09 |
| JP2017504642A5 true JP2017504642A5 (enExample) | 2018-06-07 |
| JP6505727B2 JP6505727B2 (ja) | 2019-04-24 |
Family
ID=52484570
Family Applications (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016549277A Active JP6464176B2 (ja) | 2014-01-31 | 2015-01-30 | 芳香族ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2016549279A Active JP6505727B2 (ja) | 2014-01-31 | 2015-01-30 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2019000516A Active JP6630004B2 (ja) | 2014-01-31 | 2019-01-07 | 芳香族ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2019060181A Active JP6854067B2 (ja) | 2014-01-31 | 2019-03-27 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2021039989A Active JP7325464B2 (ja) | 2014-01-31 | 2021-03-12 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2023125512A Pending JP2023133468A (ja) | 2014-01-31 | 2023-08-01 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2025166031A Pending JP2025185049A (ja) | 2014-01-31 | 2025-10-02 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016549277A Active JP6464176B2 (ja) | 2014-01-31 | 2015-01-30 | 芳香族ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019000516A Active JP6630004B2 (ja) | 2014-01-31 | 2019-01-07 | 芳香族ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2019060181A Active JP6854067B2 (ja) | 2014-01-31 | 2019-03-27 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2021039989A Active JP7325464B2 (ja) | 2014-01-31 | 2021-03-12 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2023125512A Pending JP2023133468A (ja) | 2014-01-31 | 2023-08-01 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
| JP2025166031A Pending JP2025185049A (ja) | 2014-01-31 | 2025-10-02 | ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環 |
Country Status (32)
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201116559D0 (en) | 2011-09-26 | 2011-11-09 | Univ Leuven Kath | Novel viral replication inhibitors |
| EP2766346B1 (en) | 2011-10-14 | 2017-03-29 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| JP6479763B2 (ja) | 2013-03-25 | 2019-03-06 | 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アゾール含有のテトラヒドロイソキノリン |
| NO2760821T3 (enExample) | 2014-01-31 | 2018-03-10 | ||
| PE20210470A1 (es) * | 2014-01-31 | 2021-03-08 | Bristol Myers Squibb Co | Macrociclos con grupos p2' heterociclicos como inhibidores del factor xia |
| EP2913330A1 (en) * | 2014-02-27 | 2015-09-02 | Laboratoire Biodim | Condensed derivatives of imidazole useful as pharmaceuticals |
| CN107074821B (zh) | 2014-09-04 | 2020-05-22 | 百时美施贵宝公司 | 为fxia抑制剂的二酰胺大环化合物 |
| NO2721243T3 (enExample) * | 2014-10-01 | 2018-10-20 | ||
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| CA2963203A1 (en) | 2014-10-01 | 2016-04-07 | Merck Patent Gmbh | Boronic acid derivatives |
| JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| 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 |
| JO3703B1 (ar) | 2015-07-09 | 2021-01-31 | Bayer Pharma AG | مشتقات أوكسوبيريدين مستبدلة |
| KR102086934B1 (ko) * | 2015-07-29 | 2020-03-09 | 브리스톨-마이어스 스큅 컴퍼니 | 알킬 또는 시클로알킬 P2' 모이어티를 갖는 인자 XIa 마크로시클릭 억제제 |
| CN114805365B (zh) | 2015-07-29 | 2024-07-23 | 百时美施贵宝公司 | 携带非芳族p2′基团的因子xia新大环 |
| JOP20160198B1 (ar) | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JO3633B1 (ar) | 2015-09-16 | 2020-08-27 | Katholieke Univ Leuven Ku Leuven Research & Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| CA2998902C (en) * | 2015-10-29 | 2024-03-26 | Merck Sharp & Dohme Corp. | Macrocyclic compounds 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 |
| WO2017151746A1 (en) | 2016-03-02 | 2017-09-08 | Bristol-Myers Squibb Company | Diamide macrocycles having factor xia inhibiting activity |
| ES2882488T3 (es) | 2016-03-31 | 2021-12-02 | Janssen Pharmaceuticals Inc | Derivados de indol sustituidos como inhibidores de la replicación vírica del dengue |
| ES2923771T3 (es) | 2016-03-31 | 2022-09-30 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengue |
| ES3010298T3 (en) | 2016-04-01 | 2025-04-02 | Janssen Pharmaceuticals Inc | Substituted indole compound derivatives as dengue viral replication inhibitors |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| AR109304A1 (es) | 2016-08-10 | 2018-11-21 | Sumitomo Chemical Co | Compuesto de oxadiazol y su uso |
| US10143681B2 (en) | 2016-08-22 | 2018-12-04 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
| 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 |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| ES2929667T3 (es) | 2017-05-22 | 2022-11-30 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicación vírica de dengue |
| DK3630724T3 (da) | 2017-05-22 | 2021-07-26 | Janssen Pharmaceuticals Inc | Substituerede indolinderivater som inhibitorer af virusreplikation af denguevirus |
| WO2019011166A1 (zh) * | 2017-07-14 | 2019-01-17 | 四川科伦博泰生物医药股份有限公司 | 大环酰胺化合物及其药物组合物和用途 |
| TWI880924B (zh) * | 2019-04-11 | 2025-04-21 | 美商必治妥美雅史谷比公司 | 製備(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)-酮之新穎合成選項 |
| JP2022526656A (ja) * | 2019-04-11 | 2022-05-25 | ブリストル－マイヤーズ スクイブ カンパニー | 治療血漿濃度に達するために増強された非晶質固体および溶解製剤の性能 |
| CN113677682B (zh) * | 2019-04-16 | 2023-05-30 | 华润生物医药有限公司 | 作为XIa因子抑制剂的大环衍生物 |
| 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 |
| TWI749881B (zh) * | 2019-11-21 | 2021-12-11 | 大陸商深圳信立泰藥業股份有限公司 | 二氧代哌類衍生物、其製備方法及其在醫藥上的應用 |
| MX2022012523A (es) * | 2020-04-10 | 2022-11-07 | Bristol Myers Squibb Co | Formas cristalinas de (9r,13s)-13-{4-[5-cloro-2-(4-cloro-1h-1,2,3- triazol-1-il)fenil]-6-oxo-1,6-dihidropirimidin-1-il}-3-(difluorom etil)-9-metil-3,4,7,15-tetraazatriciclo[12.3.1.0 2,6]octadeca-1(18),2(6),4,14,16-pentaen-8-ona. |
| 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 |
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| WO2025224678A1 (en) | 2024-04-25 | 2025-10-30 | Assia Chemical Industries Ltd. | Solid state forms of milvexian and process for preparation thereof |
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