JP2002526500A - プロテインキナーゼ阻害剤としてのピロロピリミジン - Google Patents
プロテインキナーゼ阻害剤としてのピロロピリミジンInfo
- Publication number
- JP2002526500A JP2002526500A JP2000574112A JP2000574112A JP2002526500A JP 2002526500 A JP2002526500 A JP 2002526500A JP 2000574112 A JP2000574112 A JP 2000574112A JP 2000574112 A JP2000574112 A JP 2000574112A JP 2002526500 A JP2002526500 A JP 2002526500A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- pyrrolo
- amino
- pyrimidin
- 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.)
- Pending
Links
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Classifications
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- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
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Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
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US10083398P | 1998-09-18 | 1998-09-18 | |
US10083298P | 1998-09-18 | 1998-09-18 | |
US10094698P | 1998-09-18 | 1998-09-18 | |
US10083498P | 1998-09-18 | 1998-09-18 | |
US60/100,946 | 1998-09-18 | ||
US60/100,834 | 1998-09-18 | ||
US60/100,832 | 1998-09-18 | ||
US60/100,833 | 1998-09-18 | ||
PCT/US1999/021560 WO2000017203A1 (en) | 1998-09-18 | 1999-09-17 | Pyrrolopyrimidines as protein kinase inhibitors |
Publications (1)
Publication Number | Publication Date |
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JP2002526500A true JP2002526500A (ja) | 2002-08-20 |
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ID=27493158
Family Applications (1)
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JP2000574112A Pending JP2002526500A (ja) | 1998-09-18 | 1999-09-17 | プロテインキナーゼ阻害剤としてのピロロピリミジン |
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Country | Link |
---|---|
EP (1) | EP1114053A1 (id) |
JP (1) | JP2002526500A (id) |
KR (1) | KR20010085824A (id) |
CN (1) | CN1335849A (id) |
AU (1) | AU753555C (id) |
BG (1) | BG105346A (id) |
BR (1) | BR9913887A (id) |
CA (1) | CA2344249A1 (id) |
CZ (1) | CZ2001960A3 (id) |
HK (1) | HK1039326A1 (id) |
HU (1) | HUP0200403A3 (id) |
ID (1) | ID29028A (id) |
IL (1) | IL141866A0 (id) |
NO (1) | NO20011356L (id) |
NZ (1) | NZ510588A (id) |
PL (1) | PL346700A1 (id) |
SK (1) | SK3842001A3 (id) |
TR (1) | TR200101186T2 (id) |
WO (1) | WO2000017203A1 (id) |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003519676A (ja) * | 2000-01-13 | 2003-06-24 | トゥラリック インコーポレイテッド | 抗菌剤 |
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JP2015509107A (ja) * | 2012-01-31 | 2015-03-26 | ナンジン アルゲン ファルマ カンパニー リミテッドNanjing Allgen Pharma Co. Ltd. | ブルトンチロシンキナーゼ阻害薬としての環状分子 |
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JPWO2015068767A1 (ja) * | 2013-11-08 | 2017-03-09 | 小野薬品工業株式会社 | ピロロピリミジン誘導体 |
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Families Citing this family (82)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
ES2274634T3 (es) | 1998-08-29 | 2007-05-16 | Astrazeneca Ab | Compuestos de pirimidina. |
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EE05351B1 (et) | 1999-12-10 | 2010-10-15 | Pfizer Products Inc. | Prrolo[2,3-d]primidiinhendid |
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GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
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WO2001072751A1 (en) * | 2000-03-29 | 2001-10-04 | Knoll Gesellschaft Mit Beschraenkter Haftung | Pyrrolopyrimidines as tyrosine kinase inhibitors |
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US7081454B2 (en) | 2001-03-28 | 2006-07-25 | Bristol-Myers Squibb Co. | Tyrosine kinase inhibitors |
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GB0311274D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
AR045037A1 (es) | 2003-07-10 | 2005-10-12 | Aventis Pharma Sa | Tetrahidro-1h-pirazolo [3,4-c] piridinas sustituidas, composiciones que las contienen y su utilizacion. |
US7312215B2 (en) | 2003-07-29 | 2007-12-25 | Bristol-Myers Squibb Company | Benzimidazole C-2 heterocycles as kinase inhibitors |
US7338957B2 (en) * | 2003-08-28 | 2008-03-04 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
EP1687309A1 (en) * | 2003-11-17 | 2006-08-09 | Pfizer Products Inc. | Pyrrolopyrimidine compounds useful in treatment of cancer |
TW200528101A (en) | 2004-02-03 | 2005-09-01 | Astrazeneca Ab | Chemical compounds |
UA89493C2 (uk) | 2004-04-02 | 2010-02-10 | Оси Фармасьютикалз, Инк. | 6,6-біциклічні кільцеві заміщені гетеробіциклічні інгібітори протеїнкіназ |
EP1773836B1 (en) | 2004-05-27 | 2012-09-05 | Pfizer Products Inc. | Pyrrolopyrimidine derivatives useful in cancer treatment |
TW200613306A (en) | 2004-07-20 | 2006-05-01 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
RU2007138264A (ru) * | 2005-03-17 | 2009-09-10 | Новартис АГ (CH) | N-[3-(1-АМИНО-5,6,7,8-ТЕТРАГИДРО-2,4,4b-ТРИАЗАФЛУОРЕН-9-ИЛ)ФЕНИЛ]БЕНЗАМИДЫ В КАЧЕСТВЕ ИНГИБИТОРОВ ТИРОЗИН/ТРЕОНИНКИНАЗ, ПРЕЖДЕ ВСЕГО КИНАЗ В-RAF |
CA2623125A1 (en) | 2005-09-20 | 2007-03-29 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
EP1934213A1 (en) | 2005-09-30 | 2008-06-25 | Astra Zeneca AB | Imidazo [1,2-a] pyridine having anti-cell-proliferation activity |
AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
CN101490046A (zh) | 2006-05-09 | 2009-07-22 | 辉瑞产品公司 | 环烷基氨基酸衍生物及其药物组合物 |
US8217177B2 (en) * | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
CN101808994B (zh) | 2007-07-17 | 2013-05-15 | 普莱希科公司 | 用于激酶调节的化合物和方法以及其适应症 |
ES2467109T3 (es) | 2008-08-20 | 2014-06-11 | Zoetis Llc | Compuestos de pirrolo[2,3-d]pirimidina |
MX2011004824A (es) | 2008-11-07 | 2012-01-12 | Triact Therapeutics Inc | Uso de derivados de butano catecólico en terapia contra el cáncer. |
JP2012518657A (ja) | 2009-02-25 | 2012-08-16 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 併用抗癌治療 |
US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
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WO2010099363A1 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
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US20130005733A1 (en) | 2010-03-09 | 2013-01-03 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
WO2012120469A1 (en) * | 2011-03-08 | 2012-09-13 | Novartis Ag | Fluorophenyl bicyclic heteroaryl compounds |
JP2014519813A (ja) | 2011-04-25 | 2014-08-21 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 癌薬剤発見、診断、および治療におけるemt遺伝子シグネチャーの使用 |
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US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス,インク. | 癌治療 |
WO2015035410A1 (en) | 2013-09-09 | 2015-03-12 | Triact Therapeutic, Inc. | Cancer therapy |
MA38961A1 (fr) | 2013-09-30 | 2018-05-31 | Pharmacyclics Llc | Composés 3-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine substitués inhibiteurs de la tyrosine kinase de bruton utilisés pour traiter par exemple les maladies auto-immunes, respiratoires et inflammatoires, cancer, mastocytose et osteoporose |
CA2833701A1 (en) * | 2013-11-19 | 2015-05-19 | Pharmascience Inc. | Protein kinase inhibitors |
CA2834528A1 (en) * | 2013-11-26 | 2015-05-26 | Pharmascience Inc. | Protein kinase inhibitors |
AP2016009297A0 (en) * | 2014-02-03 | 2016-06-30 | Cadila Healthcare Ltd | Novel heterocyclic compounds |
US20170231986A1 (en) | 2014-08-11 | 2017-08-17 | Acerta Pharma B.V. | Therapeutic Combinations of a BTK Inhibitor, a PI3K Inhibitor, a JAK-2 Inhibitor, and/or a BCL-2 Inhibitor |
US10112924B2 (en) | 2015-12-02 | 2018-10-30 | Astraea Therapeutics, Inc. | Piperdinyl nociceptin receptor compounds |
KR20180094940A (ko) * | 2015-12-02 | 2018-08-24 | 아스트레아 테라퓨틱스 엘엘씨 | 피페리디닐 노시셉틴 수용체 화합물 |
WO2021038540A1 (en) | 2019-08-31 | 2021-03-04 | Sun Pharma Advanced Research Company Limited | Cycloalkylidene carboxylic acids and derivatives as btk inhibitors |
JOP20220087A1 (ar) * | 2019-10-11 | 2023-01-30 | Incyte Corp | أمينات ثنائية الحلقة كمثبطات لـ cdk2 |
CN112961159B (zh) * | 2020-03-05 | 2022-07-01 | 四川大学华西医院 | 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途 |
CN112961158B (zh) * | 2020-03-05 | 2022-07-01 | 四川大学华西医院 | 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途 |
US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
CN117402161A (zh) * | 2022-07-06 | 2024-01-16 | 上海科恩泰生物医药科技有限公司 | 一种具有fgfr抑制作用的亚砜亚胺类化合物、包含其的药物组合物及其用途 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3036390A1 (de) * | 1980-09-26 | 1982-05-13 | Troponwerke GmbH & Co KG, 5000 Köln | Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen |
CA2100863A1 (en) * | 1991-01-23 | 1992-07-24 | David A. Bullough | Adenosine kinase inhibitors |
IL108523A0 (en) * | 1993-02-03 | 1994-05-30 | Gensia Inc | Pharmaceutical compositions containing adenosine kinase inhibitors for preventing or treating conditions involving inflammatory responses and pain |
CA2200210A1 (en) * | 1994-09-29 | 1996-04-04 | Novartis Ag | Pyrrolo[2,3-d]pyrimidines and their use |
US6143749A (en) * | 1995-06-07 | 2000-11-07 | Abbott Laboratories | Heterocyclic substituted cyclopentane compounds |
US5665721A (en) * | 1995-06-07 | 1997-09-09 | Abbott Laboratories | Heterocyclic substituted cyclopentane compounds |
CH690773A5 (de) * | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
WO1997032879A1 (de) * | 1996-03-06 | 1997-09-12 | Novartis Ag | 7-ALKYL-PYRROLO[2,3-d]PYRIMIDINE |
CA2249739A1 (en) * | 1996-03-15 | 1997-09-25 | Novartis Ag | Novel n-7-heterocyclyl pyrrolo[2,3-d]pyridines and their use |
AU748884B2 (en) * | 1997-03-19 | 2002-06-13 | Abbott Gmbh & Co. Kg | Pyrrolo(2,3d)pyrimidines and their use as tyrosine kinase inhibitors |
-
1999
- 1999-09-17 EP EP99969415A patent/EP1114053A1/en not_active Withdrawn
- 1999-09-17 HU HU0200403A patent/HUP0200403A3/hu unknown
- 1999-09-17 IL IL14186699A patent/IL141866A0/xx unknown
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- 1999-09-17 CA CA002344249A patent/CA2344249A1/en not_active Abandoned
- 1999-09-17 ID IDW20010652A patent/ID29028A/id unknown
- 1999-09-17 CN CN99813217A patent/CN1335849A/zh active Pending
- 1999-09-17 AU AU60484/99A patent/AU753555C/en not_active Ceased
- 1999-09-17 BR BR9913887-5A patent/BR9913887A/pt not_active IP Right Cessation
- 1999-09-17 WO PCT/US1999/021560 patent/WO2000017203A1/en not_active Application Discontinuation
- 1999-09-17 SK SK384-2001A patent/SK3842001A3/sk unknown
- 1999-09-17 PL PL99346700A patent/PL346700A1/xx unknown
- 1999-09-17 CZ CZ2001960A patent/CZ2001960A3/cs unknown
- 1999-09-17 JP JP2000574112A patent/JP2002526500A/ja active Pending
- 1999-09-17 NZ NZ510588A patent/NZ510588A/en unknown
-
2001
- 2001-03-15 BG BG105346A patent/BG105346A/xx unknown
- 2001-03-16 NO NO20011356A patent/NO20011356L/no not_active Application Discontinuation
-
2002
- 2002-01-11 HK HK02100227.3A patent/HK1039326A1/zh unknown
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Also Published As
Publication number | Publication date |
---|---|
AU753555B2 (en) | 2002-10-24 |
CZ2001960A3 (cs) | 2001-10-17 |
HK1039326A1 (zh) | 2002-04-19 |
AU753555C (en) | 2003-07-03 |
SK3842001A3 (en) | 2002-04-04 |
AU6048499A (en) | 2000-04-10 |
BR9913887A (pt) | 2001-10-23 |
CA2344249A1 (en) | 2000-03-30 |
NZ510588A (en) | 2003-08-29 |
TR200101186T2 (tr) | 2001-10-22 |
EP1114053A1 (en) | 2001-07-11 |
BG105346A (en) | 2001-12-29 |
IL141866A0 (en) | 2002-03-10 |
NO20011356D0 (no) | 2001-03-16 |
NO20011356L (no) | 2001-05-16 |
ID29028A (id) | 2001-07-26 |
KR20010085824A (ko) | 2001-09-07 |
HUP0200403A3 (en) | 2004-07-28 |
PL346700A1 (en) | 2002-02-25 |
WO2000017203A1 (en) | 2000-03-30 |
CN1335849A (zh) | 2002-02-13 |
HUP0200403A2 (en) | 2002-06-29 |
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