JP2014532070A5 - - Google Patents
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- JP2014532070A5 JP2014532070A5 JP2014535924A JP2014535924A JP2014532070A5 JP 2014532070 A5 JP2014532070 A5 JP 2014532070A5 JP 2014535924 A JP2014535924 A JP 2014535924A JP 2014535924 A JP2014535924 A JP 2014535924A JP 2014532070 A5 JP2014532070 A5 JP 2014532070A5
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- Prior art keywords
- alkyl
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- conh
- alkylene
- case
- 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 201
- 229910052739 hydrogen Inorganic materials 0.000 claims 42
- 125000002947 alkylene group Chemical group 0.000 claims 29
- 125000000623 heterocyclic group Chemical group 0.000 claims 24
- 125000005843 halogen group Chemical group 0.000 claims 22
- 229910052799 carbon Inorganic materials 0.000 claims 21
- 125000003545 alkoxy group Chemical group 0.000 claims 16
- 229910052760 oxygen Inorganic materials 0.000 claims 15
- 229910052717 sulfur Inorganic materials 0.000 claims 15
- 229910052731 fluorine Inorganic materials 0.000 claims 14
- 150000003839 salts Chemical class 0.000 claims 14
- 125000005842 heteroatom Chemical group 0.000 claims 12
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 11
- 125000004432 carbon atom Chemical group C* 0.000 claims 10
- 150000001875 compounds Chemical class 0.000 claims 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 8
- 229910052757 nitrogen Inorganic materials 0.000 claims 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 150000001721 carbon Chemical group 0.000 claims 5
- 229910052801 chlorine Inorganic materials 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 208000035475 disorder Diseases 0.000 claims 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 5
- 150000003536 tetrazoles Chemical group 0.000 claims 5
- 230000009424 thromboembolic effect Effects 0.000 claims 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
- 239000005711 Benzoic acid Substances 0.000 claims 4
- -1 NR 6 Inorganic materials 0.000 claims 4
- 235000010233 benzoic acid Nutrition 0.000 claims 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 4
- 239000012453 solvate Substances 0.000 claims 4
- 125000003003 spiro group Chemical group 0.000 claims 4
- 150000003852 triazoles Chemical group 0.000 claims 4
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims 2
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims 2
- 208000010125 myocardial infarction Diseases 0.000 claims 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- OOTZQCRNOWJDAW-FMIVXFBMSA-N 1-[2-[(E)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-1-[(4-fluorophenyl)carbamoyl]-3,4-dihydro-1H-isoquinolin-5-yl]-5-methylpyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)C2C(=O)NC1=CC=C(F)C=C1 OOTZQCRNOWJDAW-FMIVXFBMSA-N 0.000 claims 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 200000000007 Arterial disease 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
- 208000010378 Pulmonary Embolism Diseases 0.000 claims 1
- 206010063544 Renal embolism Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 125000005275 alkylenearyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 230000002612 cardiopulmonary effect Effects 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000001631 haemodialysis Methods 0.000 claims 1
- 230000000322 hemodialysis Effects 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 201000010849 intracranial embolism Diseases 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- WPQYFEJHDXLPFN-RMKNXTFCSA-N n-(4-carbamoylphenyl)-2-[(e)-3-[5-chloro-4-fluoro-2-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-piperazin-1-yl-3,4-dihydro-1h-isoquinoline-1-carboxamide Chemical compound C1=CC(C(=O)N)=CC=C1NC(=O)C1C(C=CC=C2N3CCNCC3)=C2CCN1C(=O)\C=C\C1=CC(Cl)=C(F)C=C1N1N=NN=C1 WPQYFEJHDXLPFN-RMKNXTFCSA-N 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 230000000306 recurrent effect Effects 0.000 claims 1
- LYDRKKWPKKEMNZ-UHFFFAOYSA-N tert-butyl benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1 LYDRKKWPKKEMNZ-UHFFFAOYSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 201000005060 thrombophlebitis Diseases 0.000 claims 1
- 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
- 230000002861 ventricular Effects 0.000 claims 1
- 0 CC(C)c1cc(**)cc(C)c1* Chemical compound CC(C)c1cc(**)cc(C)c1* 0.000 description 9
- FGQBGDBLZZPFCM-UHFFFAOYSA-N CN(CCOC1)C1=O Chemical compound CN(CCOC1)C1=O FGQBGDBLZZPFCM-UHFFFAOYSA-N 0.000 description 1
- SJRJJKPEHAURKC-UHFFFAOYSA-N CN1CCOCC1 Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
- KDTVWEHAAISPNW-UHFFFAOYSA-N CN1CCSCC1 Chemical compound CN1CCSCC1 KDTVWEHAAISPNW-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547292P | 2011-10-14 | 2011-10-14 | |
| US61/547,292 | 2011-10-14 | ||
| PCT/US2012/059969 WO2013056060A1 (en) | 2011-10-14 | 2012-10-12 | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014532070A JP2014532070A (ja) | 2014-12-04 |
| JP2014532070A5 true JP2014532070A5 (enExample) | 2015-12-03 |
| JP6033319B2 JP6033319B2 (ja) | 2016-11-30 |
Family
ID=47080863
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014535924A Active JP6033319B2 (ja) | 2011-10-14 | 2012-10-12 | 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 |
Country Status (34)
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101843542B1 (ko) | 2010-02-11 | 2018-03-30 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 ＸＩａ 억제제로서의 마크로사이클 |
| 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 |
| JP6033317B2 (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 |
| UY34393A (es) * | 2011-10-14 | 2013-04-30 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor xia |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014014050A1 (ja) | 2012-07-19 | 2014-01-23 | 大日本住友製薬株式会社 | １－（シクロアルキルカルボニル）プロリン誘導体 |
| EA025392B1 (ru) | 2012-08-03 | 2016-12-30 | Бристол-Маерс Сквибб Компани | Дигидропиридон р1 в качестве ингибиторов фактора xia |
| BR112015002081A2 (pt) | 2012-08-03 | 2017-07-04 | Bristol Myers Squibb Co | di-hidropiridona p1 como inibidores de fator xia |
| WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EA032092B1 (ru) * | 2012-10-12 | 2019-04-30 | Бристол-Майерс Сквибб Компани | Кристаллические формы ингибитора фактора xia |
| US9403774B2 (en) * | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2978751B1 (en) | 2013-03-25 | 2018-12-05 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| HUE053351T2 (hu) * | 2013-06-05 | 2021-06-28 | Shanghai Lumosa Therapeutics Co Ltd | Trombolízis, trombózis elleni és gyökbefogó hármas aktivitással rendelkezõ új vegyületek, és azok szintézise, nanoszerkezete és alkalmazása |
| UY35971A (es) | 2014-01-31 | 2015-07-31 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Macrociclos con grupos p2? aromáticos como inhibidores del factor xia |
| NO2760821T3 (enExample) | 2014-01-31 | 2018-03-10 | ||
| ES2945905T3 (es) | 2014-02-07 | 2023-07-10 | Exithera Pharmaceuticals Inc | Compuestos y composiciones terapéuticos |
| EP3104702B1 (en) | 2014-02-11 | 2022-08-10 | Merck Sharp & Dohme LLC | Factor xia inhibitors |
| EP3104703B1 (en) | 2014-02-11 | 2020-11-18 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| WO2015160636A1 (en) * | 2014-04-16 | 2015-10-22 | Merck Sharp & Dohme Corp. | Factor ixa inhibitors |
| WO2015160634A1 (en) * | 2014-04-16 | 2015-10-22 | Merck Sharp & Dohme Corp. | Factor ixa inhibitors |
| EP3134408B1 (en) * | 2014-04-22 | 2020-08-12 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| EP3180317B1 (en) | 2014-07-28 | 2021-04-14 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| 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 |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| CN108026083B (zh) | 2015-06-19 | 2021-08-27 | 百时美施贵宝公司 | 作为因子xia抑制剂的二酰胺大环 |
| 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 |
| EP3868753B1 (en) | 2015-07-29 | 2022-12-21 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing a non-aromatic p2' group |
| MA43128A (fr) | 2015-10-29 | 2018-09-05 | Merck Sharp & Dohme | Inhibiteurs du facteur xia |
| 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 |
| 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 |
| US10143681B2 (en) | 2016-08-22 | 2018-12-04 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
| US10633375B2 (en) | 2016-08-31 | 2020-04-28 | Jinagsu Hengrui Medicine Co., Ltd | Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof |
| 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 |
| WO2019144811A1 (zh) * | 2018-01-26 | 2019-08-01 | 四川科伦博泰生物医药股份有限公司 | 四氢异喹啉类衍生物及其制备方法和用途 |
| JP7397797B2 (ja) | 2018-02-07 | 2023-12-13 | エクセセーラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物および組成物 |
| US11541049B2 (en) | 2018-03-28 | 2023-01-03 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Tetrahydroisoquinoline derivatives, preparation process and use thereof |
| WO2019218899A1 (zh) * | 2018-05-17 | 2019-11-21 | 四川科伦博泰生物医药股份有限公司 | 含聚乙二醇醚的四氢异喹啉酰胺化合物及其药物用途 |
| JP2021529201A (ja) | 2018-07-02 | 2021-10-28 | 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司Ｊｉａｎｇｓｕ Ｈｅｎｇｒｕｉ Ｍｅｄｉｃｉｎｅ Ｃｏ．， Ｌｔｄ． | オキシピリジンアミド誘導体の結晶形およびその調製方法 |
| WO2020092594A1 (en) * | 2018-10-30 | 2020-05-07 | Exithera Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| BR112021008345A2 (pt) * | 2018-10-30 | 2021-08-03 | Exithera Pharmaceuticals, Inc. | compostos e composições terapêuticas |
| EP4036087A4 (en) | 2019-09-27 | 2023-09-20 | Shenzhen Salubris Pharmaceuticals Co. Ltd | Fxia inhibitors and preparation method therefor and pharmaceutical use thereof |
| CN115066417B (zh) * | 2019-12-31 | 2025-05-02 | 上海京新生物医药有限公司 | 凝血因子XIa抑制剂 |
| US20230312560A1 (en) * | 2020-07-22 | 2023-10-05 | Janssen Pharmaceutica Nv | Compounds useful as factor xia inhibitors |
| AU2024259057A1 (en) * | 2023-04-19 | 2025-12-04 | Bristol-Myers Squibb Company | Use of milvexian in the treatment and prevention of thrombotic conditions in patients with cardiovascular or cerebrovascular disease |
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