AU2003298571B2 - Pyrazolo[1,5-a]pyrimidines compounds as cyclin dependent kinase inhibitors - Google Patents
Pyrazolo[1,5-a]pyrimidines compounds as cyclin dependent kinase inhibitors Download PDFInfo
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- AU2003298571B2 AU2003298571B2 AU2003298571A AU2003298571A AU2003298571B2 AU 2003298571 B2 AU2003298571 B2 AU 2003298571B2 AU 2003298571 A AU2003298571 A AU 2003298571A AU 2003298571 A AU2003298571 A AU 2003298571A AU 2003298571 B2 AU2003298571 B2 AU 2003298571B2
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- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 title description 7
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 title description 3
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- 125000003118 aryl group Chemical group 0.000 claims description 60
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- 150000003839 salts Chemical class 0.000 claims description 46
- -1 4-(methylsulfonyl)phenyl Chemical group 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 34
- 239000012453 solvate Substances 0.000 claims description 34
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US40802902P | 2002-09-04 | 2002-09-04 | |
| US60/408,029 | 2002-09-04 | ||
| PCT/US2003/027491 WO2004026229A2 (en) | 2002-09-04 | 2003-09-03 | Pyrazolo[1,5-a]pyrimidines compounds as cyclin dependent kinase inhibitors |
Publications (2)
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| AU2003298571A1 AU2003298571A1 (en) | 2004-04-08 |
| AU2003298571B2 true AU2003298571B2 (en) | 2006-10-19 |
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| AU2003298571A Ceased AU2003298571B2 (en) | 2002-09-04 | 2003-09-03 | Pyrazolo[1,5-a]pyrimidines compounds as cyclin dependent kinase inhibitors |
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| EP1388541A1 (en) * | 2002-08-09 | 2004-02-11 | Centre National De La Recherche Scientifique (Cnrs) | Pyrrolopyrazines as kinase inhibitors |
| MXPA05002113A (es) | 2002-08-23 | 2005-06-03 | Sloan Kettering Inst Cancer | Sintesis de epotilonas, intermediarios para ellas, analogos y usos de los mismos. |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7601724B2 (en) * | 2002-09-04 | 2009-10-13 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| KR20050033659A (ko) * | 2002-09-04 | 2005-04-12 | 쉐링 코포레이션 | 사이클린 의존성 키나제 억제제로서의 피라졸로[1,5-ａ]피리미딘 화합물 |
| US7205308B2 (en) * | 2002-09-04 | 2007-04-17 | Schering Corporation | Trisubstituted 7-aminopyrazolopyrimidines as cyclin dependent kinase inhibitors |
| EP1599482A4 (en) * | 2003-02-28 | 2008-10-01 | Teijin Pharma Ltd | PYRAZOLO1,5-A PYRIMIDINE DERIVATIVES |
| EP1608652A1 (en) * | 2003-03-31 | 2005-12-28 | Vernalis (Cambridge) Limited | Pyrazolopyrimidine compounds and their use in medicine |
| WO2005035516A1 (ja) * | 2003-10-10 | 2005-04-21 | Ono Pharmaceutical Co., Ltd. | 新規縮合複素環化合物およびその用途 |
| US20080287405A1 (en) * | 2004-05-14 | 2008-11-20 | Thannickal Victor J | Compositions and Methods Relating to Protein Kinase Inhibitors |
| ES2368930T3 (es) | 2004-09-06 | 2011-11-23 | Bayer Pharma Aktiengesellschaft | Pirazolopirimidinas como inhibidores de proteína cinasa b (akt). |
| FR2876582B1 (fr) * | 2004-10-15 | 2007-01-05 | Centre Nat Rech Scient Cnrse | Utilisation de derives de pyrrolo-pyrazines pour la fabrication de medicaments pour le traitement de la mucoviscidose et de maladies liees a un defaut d'adressage des proteines dans les cellules |
| DE602005014891D1 (de) * | 2004-12-21 | 2009-07-23 | Schering Corp | PYRAZOLOÄ1,5-AÜPYRIMIDINE ALS ANTAGONISTEN DES ADENOSIN-A2a-REZEPTORS |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| US7700773B2 (en) | 2005-09-09 | 2010-04-20 | Schering Corporation | 4-cyano, 4-amino, and 4-aminomethyl derivatives of pyrazolo[1,5-a]pyridines, pyrazolo[1,5-c]pyrimidines and 2H-indazole compounds and 5-cyano, 5-amino, and 5-aminomethyl derivatives of imidazo[1,2-a]pyridines, and imidazo[1,5-a]pyrazines as cyclin dependent kinase inhibitors |
| EP1940389A2 (en) | 2005-10-21 | 2008-07-09 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| WO2007053596A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007118844A1 (de) * | 2006-04-13 | 2007-10-25 | Basf Se | Substituierte pyrazolopyrimidine, verfahren zu ihrer herstellung und ihre verwendung zur bekämpfung von schadpilzen sowie sie enthaltende mittel |
| CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| EP2027127A1 (en) * | 2006-05-22 | 2009-02-25 | Shering Corporation | Pyrazolo [1, 5-a]pyrimidines as cdk inhibitors |
| US8008307B2 (en) | 2006-08-08 | 2011-08-30 | Millennium Pharmaceuticals, Inc. | Heteroaryl compounds useful as inhibitors of E1 activating enzymes |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| CA2670285A1 (en) * | 2006-12-05 | 2008-06-12 | Arena Pharmaceuticals, Inc. | Processes for preparing (r)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine and intermediates thereof |
| MX2010011069A (es) * | 2008-04-07 | 2010-11-12 | Irm Llc | Compuestos y composiciones como inhibidores de cinasa. |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| US8993535B2 (en) | 2009-09-04 | 2015-03-31 | Merck Sharp & Dohme Corp. | Modulators of cell cycle checkpoints and their use in combination with checkpoint kinase inhibitors |
| RU2607453C2 (ru) * | 2009-12-04 | 2017-01-10 | Сенхва Байосайенсиз, Инк. | Пиразолопиримидины и родственные гетероциклы как ск2 ингибиторы |
| WO2011090738A2 (en) | 2009-12-29 | 2011-07-28 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
| WO2012149157A2 (en) * | 2011-04-26 | 2012-11-01 | Bioenergenix | Heterocyclic compounds for the inhibition of pask |
| EP2723746A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| US9382239B2 (en) | 2011-11-17 | 2016-07-05 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-Jun-N-terminal kinase (JNK) |
| WO2013123169A1 (en) | 2012-02-17 | 2013-08-22 | Millennium Pharmaceuticals, Inc. | Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme |
| CN102633803A (zh) * | 2012-05-03 | 2012-08-15 | 盛世泰科生物医药技术(苏州)有限公司 | 一种5,7-二氯吡唑并[1,5-a]嘧啶的合成方法 |
| USRE48175E1 (en) | 2012-10-19 | 2020-08-25 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
| WO2014066743A1 (en) | 2012-10-25 | 2014-05-01 | Bioenergenix | Heterocyclic compounds for the inhibition of pask |
| US10392389B2 (en) | 2012-10-25 | 2019-08-27 | Bioenergenix Llc | Heterocyclic compounds for the inhibition of PASK |
| TWI618706B (zh) | 2012-12-07 | 2018-03-21 | 維泰克斯製藥公司 | 用作ａｔｒ激酶抑制劑之化合物 |
| KR20150130491A (ko) | 2013-03-13 | 2015-11-23 | 제넨테크, 인크. | 피라졸로 화합물 및 그것의 용도 |
| EP2970288A1 (en) | 2013-03-15 | 2016-01-20 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| JP2016512815A (ja) | 2013-03-15 | 2016-05-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体 |
| JP2016512239A (ja) | 2013-03-15 | 2016-04-25 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な化合物 |
| BR112015032902A8 (pt) | 2013-07-02 | 2019-12-24 | Millennium Pharm Inc | compostos de heteroarila, seus usos e composições farmacêuticas |
| WO2015058126A1 (en) | 2013-10-18 | 2015-04-23 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of prolferative diseases |
| WO2015058140A1 (en) | 2013-10-18 | 2015-04-23 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
| EP3077397B1 (en) | 2013-12-06 | 2019-09-18 | Vertex Pharmaceuticals Inc. | 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamide compound useful as atr kinase inhibitor, its preparation, different solid forms and radiolabelled derivatives thereof |
| EP3087069B1 (en) | 2013-12-23 | 2019-01-30 | Norgine B.V. | Compounds useful as ccr9 modulators |
| JP6509238B2 (ja) * | 2014-01-22 | 2019-05-08 | キュロヴィル・アクチボラグ | 治療に有用なピラゾロ［１，５−ａ］ピリミジン−７−アミン誘導体 |
| PT3152212T (pt) | 2014-06-05 | 2020-03-13 | Vertex Pharma | Derivados radiomarcados de um composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]-pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor de atr quinase, preparação do dito composto e diferentes formas sólidas do mesmo |
| NZ727399A (en) | 2014-06-17 | 2022-07-29 | Vertex Pharma | Method for treating cancer using a combination of chk1 and atr inhibitors |
| US9683003B2 (en) | 2014-07-01 | 2017-06-20 | Millennium Pharmaceuticals, Inc. | Heteroaryl compounds useful as inhibitors of SUMO activating enzyme |
| CN105294683B (zh) * | 2014-07-26 | 2018-01-23 | 广东东阳光药业有限公司 | Cdk类小分子抑制剂的化合物及其用途 |
| CA2972239A1 (en) | 2014-12-23 | 2016-06-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| EP3273966B1 (en) * | 2015-03-27 | 2023-05-03 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| AU2016276963C1 (en) | 2015-06-12 | 2021-08-05 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| EP4019515A1 (en) | 2015-09-09 | 2022-06-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| EP3355926A4 (en) | 2015-09-30 | 2019-08-21 | Vertex Pharmaceuticals Inc. | METHOD FOR THE TREATMENT OF CANCER WITH A COMBINATION OF DNA DAMAGING AGENTS AND ATR INHIBITORS |
| MX2018006250A (es) | 2015-11-18 | 2018-09-05 | Genzyme Corp | Biomarcador de enfermedad poliquistica renal y usos del mismo. |
| TWI703149B (zh) * | 2017-11-16 | 2020-09-01 | 美商美國禮來大藥廠 | 用於抑制cdk7之化合物 |
| EP3849981B1 (en) | 2018-09-10 | 2023-02-01 | Eli Lilly and Company | Pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives useful in the treatment of psoriasis and systemic lupus erythematosus |
| MX2021004769A (es) * | 2018-10-30 | 2021-08-24 | Kronos Bio Inc | Compuestos, composiciones, y metodos para modular la actividad cdk9. |
| AR117177A1 (es) | 2018-12-10 | 2021-07-14 | Lilly Co Eli | DERIVADOS DE 7-(METILAMINO)PIRAZOLO[1,5-A]PIRIMIDIN-3-CARBOXAMIDA COMO INHIBIDORES DE IL-23 E INFa |
| AR121251A1 (es) | 2020-02-12 | 2022-05-04 | Lilly Co Eli | Compuestos de 7-(metilamino)pirazolo[1,5-a]pirimidina-3-carboxamida |
| CN116396298A (zh) * | 2023-06-06 | 2023-07-07 | 四川维亚本苑生物科技有限公司 | CDK Ligand-1的中间体XII及CDK Ligand-1的制备方法 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US626096A (en) * | 1899-05-30 | Dust-pan | ||
| JPS4116288Y1 (US07544672-20090609-C00212.png) | 1964-11-07 | 1966-07-28 | ||
| JPS6157587A (ja) | 1984-08-29 | 1986-03-24 | Shionogi & Co Ltd | 縮合複素環誘導体および抗潰瘍剤 |
| JP2585462B2 (ja) * | 1989-10-25 | 1997-02-26 | 株式会社大塚製薬工場 | ピラゾロ［１，５―ａ］ピリミジン誘導体 |
| JP2811020B2 (ja) | 1990-04-17 | 1998-10-15 | 日本特殊陶業株式会社 | セラミックスと鋼の接合体及びその製造方法 |
| ATE174917T1 (de) * | 1991-04-22 | 1999-01-15 | Otsuka Pharma Co Ltd | Pyrazolo(1,5-a>pyrimidinderivate und sie enthaltende antiinflammatorische mittel |
| EP0628559B1 (en) | 1993-06-10 | 2002-04-03 | Beiersdorf-Lilly GmbH | Pyrimidine compounds and their use as pharmaceuticals |
| US5571813A (en) * | 1993-06-10 | 1996-11-05 | Beiersdorf-Lilly Gmbh | Fused pyrimidine compounds and their use as pharmaceuticals |
| WO1995035298A1 (fr) * | 1994-06-21 | 1995-12-28 | Otsuka Pharmaceutical Factory, Inc. | DERIVE DE PYRAZOLO[1,5-a]PYRIMIDINE |
| US5919815A (en) * | 1996-05-22 | 1999-07-06 | Neuromedica, Inc. | Taxane compounds and compositions |
| US6191131B1 (en) | 1997-07-23 | 2001-02-20 | Dupont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| US6262096B1 (en) * | 1997-11-12 | 2001-07-17 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
| US6040321A (en) * | 1997-11-12 | 2000-03-21 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
| US6413974B1 (en) * | 1998-02-26 | 2002-07-02 | Aventis Pharmaceuticals Inc. | 6,9,-disubstituted 2-[trans-(4-aminocyclohexyl) amino] purines |
| US6190131B1 (en) * | 1999-08-31 | 2001-02-20 | General Electric Co. | Non-integral balanced coverplate and coverplate centering slot for a turbine |
| FR2805160B1 (fr) | 2000-02-23 | 2002-04-05 | Oreal | Compositions pour la teinture d'oxydation des fibres keratiniques comprenant un n(2-hydroxybenzene)-carbramate ou un n-(2-hydroxybenzene)-uree et une pyrazolopyrimidine, et procedes de teinture |
| US7067520B2 (en) | 2000-11-17 | 2006-06-27 | Ishihara Sangyo Kaisha, Ltd. | Preventive or therapeutic medicines for diabetes containing fused-heterocyclic compounds or their salts |
| FR2817469B1 (fr) | 2000-12-04 | 2003-04-18 | Oreal | Composition de coloration, procede d'obtention et utilisation pour la coloration de fibres keratiniques |
| JP2004516297A (ja) | 2000-12-20 | 2004-06-03 | ソシエテ・ド・コンセイユ・ド・ルシエルシエ・エ・ダアツプリカーション・シヤンテイフイツク・（エス．セー．エール．アー．エス） | サイクリン依存性キナーゼ（ｃｄｋ）及びグリコーゲンシンターゼキナーゼ−３（ｇｓｋ−３）の阻害剤 |
| US20040102455A1 (en) * | 2001-01-30 | 2004-05-27 | Burns Christopher John | Method of inhibiting kinases |
| EP1505068A4 (en) | 2002-04-23 | 2008-03-19 | Shionogi & Co | PYRAZOLO (1,5-a) PYRIMIDINE DERIVATIVE AND INHIBITOR OF NAD (P) H OXIDASE CONTAINING SAID DERIVATIVE |
| DE10223917A1 (de) | 2002-05-29 | 2003-12-11 | Bayer Cropscience Ag | Pyrazolopyrimidine |
| TW200413377A (en) | 2002-09-04 | 2004-08-01 | Schering Corp | Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| KR20050033659A (ko) * | 2002-09-04 | 2005-04-12 | 쉐링 코포레이션 | 사이클린 의존성 키나제 억제제로서의 피라졸로[1,5-ａ]피리미딘 화합물 |
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2003
- 2003-09-03 KR KR1020057003527A patent/KR20050033659A/ko not_active Application Discontinuation
- 2003-09-03 TW TW092124336A patent/TWI329645B/zh active
- 2003-09-03 US US10/653,776 patent/US7067661B2/en not_active Expired - Lifetime
- 2003-09-03 DE DE60313872T patent/DE60313872T2/de not_active Expired - Lifetime
- 2003-09-03 WO PCT/US2003/027491 patent/WO2004026229A2/en active IP Right Grant
- 2003-09-03 CA CA2497544A patent/CA2497544C/en not_active Expired - Fee Related
- 2003-09-03 MY MYPI20071385A patent/MY145332A/en unknown
- 2003-09-03 AU AU2003298571A patent/AU2003298571B2/en not_active Ceased
- 2003-09-03 ES ES03796321T patent/ES2283868T3/es not_active Expired - Lifetime
- 2003-09-03 MY MYPI20033315A patent/MY137843A/en unknown
- 2003-09-03 JP JP2004537708A patent/JP4790265B2/ja not_active Expired - Fee Related
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- 2003-09-03 AT AT03796321T patent/ATE362474T1/de not_active IP Right Cessation
- 2003-09-03 CN CN038247011A patent/CN1701073B/zh not_active Expired - Fee Related
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- 2003-09-03 AR ARP030103188A patent/AR041133A1/es unknown
- 2003-09-04 PE PE2003000900A patent/PE20041000A1/es not_active Application Discontinuation
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- 2005-03-03 ZA ZA200501846A patent/ZA200501846B/en unknown
- 2005-06-07 HK HK05104747A patent/HK1071572A1/xx not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| TWI329645B (en) | 2010-09-01 |
| JP4790265B2 (ja) | 2011-10-12 |
| KR20050033659A (ko) | 2005-04-12 |
| MY145332A (en) | 2012-01-31 |
| HK1071572A1 (en) | 2005-07-22 |
| ES2283868T3 (es) | 2007-11-01 |
| CA2497544A1 (en) | 2004-04-01 |
| US20060178371A1 (en) | 2006-08-10 |
| ATE362474T1 (de) | 2007-06-15 |
| DE60313872T2 (de) | 2008-01-17 |
| US20040106624A1 (en) | 2004-06-03 |
| CN1701073B (zh) | 2011-06-22 |
| AR041133A1 (es) | 2005-05-04 |
| ZA200501846B (en) | 2005-09-12 |
| EP1534712A2 (en) | 2005-06-01 |
| CN1701073A (zh) | 2005-11-23 |
| EP1534712B1 (en) | 2007-05-16 |
| JP2010180235A (ja) | 2010-08-19 |
| WO2004026229A3 (en) | 2004-06-17 |
| US7067661B2 (en) | 2006-06-27 |
| MY137843A (en) | 2009-03-31 |
| NZ539161A (en) | 2006-05-26 |
| TW200413376A (en) | 2004-08-01 |
| CA2497544C (en) | 2010-11-02 |
| DE60313872D1 (de) | 2007-06-28 |
| PE20041000A1 (es) | 2004-12-29 |
| AU2003298571A1 (en) | 2004-04-08 |
| US7514442B2 (en) | 2009-04-07 |
| MXPA05002572A (es) | 2005-09-08 |
| WO2004026229A2 (en) | 2004-04-01 |
| JP2006502184A (ja) | 2006-01-19 |
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