CA2583428A1 - Bicyclic heteroaryl pde4b inhibitors - Google Patents
Bicyclic heteroaryl pde4b inhibitors Download PDFInfo
- Publication number
- CA2583428A1 CA2583428A1 CA002583428A CA2583428A CA2583428A1 CA 2583428 A1 CA2583428 A1 CA 2583428A1 CA 002583428 A CA002583428 A CA 002583428A CA 2583428 A CA2583428 A CA 2583428A CA 2583428 A1 CA2583428 A1 CA 2583428A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- compound
- pde4b
- bound
- group
- 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.)
- Abandoned
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Classifications
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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| US60740704P | 2004-09-03 | 2004-09-03 | |
| US60/607,407 | 2004-09-03 | ||
| PCT/US2005/031322 WO2006026754A2 (en) | 2004-09-03 | 2005-09-02 | Bicyclic heteroaryl pde4b inhibitors |
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| CA2583428A1 true CA2583428A1 (en) | 2006-03-09 |
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| CA002583428A Abandoned CA2583428A1 (en) | 2004-09-03 | 2005-09-02 | Bicyclic heteroaryl pde4b inhibitors |
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| JP (1) | JP2008512380A (enExample) |
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| AU (1) | AU2005279795A1 (enExample) |
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Families Citing this family (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6663602B2 (en) | 2000-06-16 | 2003-12-16 | Novo Nordisk A/S | Injection device |
| JP4698677B2 (ja) | 2004-10-21 | 2011-06-08 | ノボ・ノルデイスク・エー／エス | 巻き上げ式ペン型の薬剤送達装置のダイヤルダウン機構 |
| CA2609126A1 (en) * | 2005-05-20 | 2006-11-30 | Vertex Pharmaceuticals Incorporated | Pyrrolopyridines useful as inhibitors of protein kinase |
| US7572807B2 (en) | 2005-06-09 | 2009-08-11 | Bristol-Myers Squibb Company | Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
| US7579360B2 (en) | 2005-06-09 | 2009-08-25 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| ES2373329T3 (es) | 2005-06-24 | 2012-02-02 | Bayer Bioscience N.V. | Métodos para alterar la reactividad de paredes celulares de plantas. |
| DE102006012617A1 (de) * | 2006-03-20 | 2007-09-27 | Merck Patent Gmbh | 4-(Pyrrolopyridinyl)-pyrimidinyl-2-amin-derivate |
| JP5253387B2 (ja) | 2006-05-18 | 2013-07-31 | ノボ・ノルデイスク・エー／エス | モード固定手段を備えている注入装置 |
| US8097699B2 (en) | 2006-08-30 | 2012-01-17 | Rsr Limited | Crystal structure of thyroid stimulating hormone receptor |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| GB0702456D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | New combination |
| MX2010000617A (es) | 2007-07-17 | 2010-05-17 | Plexxikon Inc | Compuestos y metodos para modulacion de cinasa, e indicaciones de estos. |
| US8119658B2 (en) | 2007-10-01 | 2012-02-21 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| WO2009067597A1 (en) * | 2007-11-21 | 2009-05-28 | Decode Genetics Ehf | 4- (or 5-) substituted catechol derivatives |
| US9283337B2 (en) | 2007-12-20 | 2016-03-15 | Astrazeneca Ab | Dispenser and method for entraining powder in an airflow |
| US8158636B2 (en) | 2008-05-19 | 2012-04-17 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| TW201036957A (en) | 2009-02-20 | 2010-10-16 | Astrazeneca Ab | Novel salt 628 |
| US9211383B2 (en) | 2009-07-01 | 2015-12-15 | Astrazeneca Ab | Dispenser and method for entraining powder in an airflow |
| AU2010321883A1 (en) | 2009-11-18 | 2012-05-31 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
| MX2012007429A (es) | 2009-12-23 | 2012-07-23 | Plexxikon Inc | Compuestos y metodos para la modulacion de quinasa e indicaciones de la misma. |
| KR20130004266A (ko) | 2010-02-10 | 2013-01-09 | 아스트라제네카 유케이 리미티드 | 흡입기용의 충전된 캐니스터의 제공 방법 |
| TWI510487B (zh) | 2010-04-21 | 2015-12-01 | Plexxikon Inc | 用於激酶調節的化合物和方法及其適應症 |
| JO3131B1 (ar) | 2010-04-27 | 2017-09-20 | Glaxosmithkline Llc | مركبات كيميائية |
| CN103140490A (zh) | 2010-07-15 | 2013-06-05 | 百时美施贵宝公司 | 氮杂吲唑化合物 |
| IN2013MN00222A (enExample) | 2010-07-21 | 2015-05-29 | Astrazeneca Ab | |
| RU2013104637A (ru) | 2010-07-21 | 2014-08-27 | Астразенека Аб | Ингалятор |
| EA028821B9 (ru) | 2011-02-07 | 2018-10-31 | Плексксикон, Инк. | Соединения и способы для модуляции киназ, а также показания к их применению |
| EP2487159A1 (en) | 2011-02-11 | 2012-08-15 | MSD Oss B.V. | RorgammaT inhibitors |
| BR112013029163A2 (pt) | 2011-05-17 | 2017-01-31 | Plexxikon Inc | modulação quinase e indicações dos mesmos |
| EP2731436B1 (en) * | 2011-07-15 | 2017-03-08 | VIIV Healthcare UK Limited | 2-(pyrrolo[2,3-b]pyridine-5-yl)-2-(t-butoxy)-acetic acid derivatives as hiv replication inhibitors for the treatment of aids |
| GB201115874D0 (en) | 2011-09-14 | 2011-10-26 | Astrazeneca Ab | Inhaler |
| JP6069351B2 (ja) | 2011-12-29 | 2017-02-01 | ノボ・ノルデイスク・エー／エス | ダイアルアップ／ダイアルダウン投与機構を有するねじりバネ式ねじ巻き自動注射器 |
| US9358235B2 (en) | 2012-03-19 | 2016-06-07 | Plexxikon Inc. | Kinase modulation, and indications therefor |
| WO2013155123A1 (en) * | 2012-04-10 | 2013-10-17 | Georgia State University Research Foundation, Inc. | Compositions and methods for treating otitis media and other conditions with inhibitors of cyld |
| WO2014026329A1 (en) | 2012-08-15 | 2014-02-20 | Merck Sharp & Dohme Corp. | N-alkylated indole and indazole compounds as rorgammat inhibitors and uses thereof |
| WO2014026327A1 (en) | 2012-08-15 | 2014-02-20 | Merck Sharp & Dohme Corp. | 4-heteroaryl substituted benzoic acid compounds as rorgammat inhibitors and uses thereof |
| WO2014026330A1 (en) | 2012-08-15 | 2014-02-20 | Merck Sharp & Dohme Corp. | 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF |
| AU2013312477B2 (en) | 2012-09-06 | 2018-05-31 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| TWI617552B (zh) | 2012-12-21 | 2018-03-11 | 普雷辛肯公司 | 用於激酶調節及其適應症之化合物及方法 |
| MA38333A1 (fr) | 2013-02-19 | 2017-02-28 | Pfizer | Composés d'azabenzimidazole en tant qu'inhibiteurs d'isozymes pde4 pour le traitement de troubles du snc et d'autres affections |
| TWI634111B (zh) | 2013-03-15 | 2018-09-01 | 普雷辛肯公司 | 雜環化合物及其用途 |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| RU2015149937A (ru) | 2013-05-30 | 2017-07-06 | Плексксикон Инк. | Соединения для модулирования киназы и показания к их применению |
| WO2015134536A1 (en) | 2014-03-04 | 2015-09-11 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US10131669B2 (en) | 2014-07-24 | 2018-11-20 | Pfizer Inc. | Pyrazolopyrimidine compounds |
| MD20170011A2 (ro) | 2014-08-06 | 2017-08-31 | Pfizer Inc. | Compuşi imidazopiridazinici |
| JP6832846B2 (ja) | 2014-09-15 | 2021-02-24 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | ヘテロ環化合物およびその用途 |
| US10221142B2 (en) | 2015-02-11 | 2019-03-05 | Merck Sharp & Dohme Corp. | Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof |
| US10160755B2 (en) | 2015-04-08 | 2018-12-25 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| SMT202000535T1 (it) | 2015-05-06 | 2020-11-10 | Plexxikon Inc | Forme solide di composto modulante chinasi |
| JP6530826B2 (ja) | 2015-05-06 | 2019-06-12 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | キナーゼを修飾する１ｈ−ピロロ［２，３−ｂ］ピリジン誘導体の合成 |
| US10829484B2 (en) | 2015-07-28 | 2020-11-10 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| CA2999253C (en) | 2015-09-21 | 2021-10-26 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| EP3368516B1 (en) | 2015-10-27 | 2020-07-15 | Merck Sharp & Dohme Corp. | SUBSTITUTED BICYCLIC PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF |
| JP2018531958A (ja) | 2015-10-27 | 2018-11-01 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | ＲＯＲγＴ阻害薬としてのヘテロアリール置換安息香酸及びその使用 |
| EP3368539B1 (en) | 2015-10-27 | 2020-12-02 | Merck Sharp & Dohme Corp. | Substituted indazole compounds as ror gamma t inhibitors and uses thereof |
| WO2017100201A1 (en) | 2015-12-07 | 2017-06-15 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP3430005B1 (en) | 2016-03-16 | 2021-12-08 | Plexxikon Inc. | Compounds and methods for kinase modulation and indications therefore |
| AU2017269335B2 (en) | 2016-05-26 | 2021-07-01 | Recurium Ip Holdings, Llc | EGFR inhibitor compounds |
| TW201815766A (zh) | 2016-09-22 | 2018-05-01 | 美商普雷辛肯公司 | 用於ｉｄｏ及ｔｄｏ調節之化合物及方法以及其適應症 |
| AU2017395023B2 (en) | 2016-12-23 | 2022-04-07 | Plexxikon Inc. | Compounds and methods for CDK8 modulation and indications therefor |
| WO2018175311A1 (en) | 2017-03-20 | 2018-09-27 | Plexxikon Inc. | Crystalline forms of 4-(1-(1,1-di(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1h- pyrrolo[3,2-b]pyridin-3-yl)benzoic acid that inhibits bromodomain |
| US10428067B2 (en) | 2017-06-07 | 2019-10-01 | Plexxikon Inc. | Compounds and methods for kinase modulation |
| JP7170030B2 (ja) | 2017-07-25 | 2022-11-11 | プレキシコン インコーポレーテッド | キナーゼを調節する化合物の製剤 |
| US10717735B2 (en) | 2017-10-13 | 2020-07-21 | Plexxikon Inc. | Solid forms of a compound for modulating kinases |
| EP3700574B1 (en) | 2017-10-27 | 2024-08-28 | Plexxikon Inc. | Formulations of a compound modulating kinases |
| CN112119072A (zh) | 2018-03-20 | 2020-12-22 | 普莱希科公司 | 用于ido和tdo调节的化合物和方法，以及其适应症 |
| WO2020210366A1 (en) | 2019-04-09 | 2020-10-15 | Plexxikon Inc. | Condensed azines for ep300 or cbp modulation and indications therefor |
| US12509444B2 (en) | 2019-12-06 | 2025-12-30 | Plexxikon Inc. | Compounds and methods for CD73 modulation and indications therefor |
| WO2021216898A1 (en) | 2020-04-23 | 2021-10-28 | Plexxikon Inc. | Compounds and methods for cd73 modulation and indications therefor |
| EP4143168A1 (en) | 2020-04-29 | 2023-03-08 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| US11628176B2 (en) | 2020-08-21 | 2023-04-18 | Opna Bio SA | Combinational drug therapies |
| CN113754796B (zh) * | 2021-10-18 | 2022-09-30 | 中国石油大学(华东) | 一种萘修饰交联的β-环糊精凝胶、制备方法及应用 |
| TW202430172A (zh) * | 2023-01-17 | 2024-08-01 | 大陸商瑞石生物醫藥有限公司 | Ｐｄｅ４抑制劑、其製備方法及其在醫藥上的應用 |
| CN116370640A (zh) * | 2023-04-26 | 2023-07-04 | 中国医学科学院基础医学研究所 | Pde4b抑制剂在制备预防和/或治疗肺动脉高压的药物中的应用 |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US587707A (en) * | 1897-08-10 | Tension device for sewing-machine binders | ||
| GB1573212A (en) | 1976-04-15 | 1980-08-20 | Technicon Instr | Immunoassay for gentamicin |
| US4568649A (en) | 1983-02-22 | 1986-02-04 | Immunex Corporation | Immediate ligand detection assay |
| US4626513A (en) | 1983-11-10 | 1986-12-02 | Massachusetts General Hospital | Method and apparatus for ligand detection |
| DE3483099D1 (de) | 1984-03-15 | 1990-10-04 | Immunex Corp | Test zur sofortigen feststellung von liganden, testsatz und seine herstellung. |
| US5688655A (en) | 1988-02-10 | 1997-11-18 | Ict Pharmaceuticals, Inc. | Method of screening for protein inhibitors and activators |
| US5700637A (en) | 1988-05-03 | 1997-12-23 | Isis Innovation Limited | Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays |
| US6054270A (en) | 1988-05-03 | 2000-04-25 | Oxford Gene Technology Limited | Analying polynucleotide sequences |
| US5658775A (en) | 1988-05-17 | 1997-08-19 | Sloan-Kettering Institute For Cancer Research | Double copy retroviral vector |
| US4861891A (en) | 1988-08-31 | 1989-08-29 | Pfizer Inc. | Antidepressant N-substituted nicotinamide compounds |
| JP3082204B2 (ja) | 1988-09-01 | 2000-08-28 | ホワイトヘッド・インスティチュート・フォー・バイオメディカル・リサーチ | 両栄養性および環境栄養性宿主域を持つ組換え体レトロウイルス |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5527681A (en) | 1989-06-07 | 1996-06-18 | Affymax Technologies N.V. | Immobilized molecular synthesis of systematically substituted compounds |
| US5800992A (en) | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5744101A (en) | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
| AU7906691A (en) | 1990-05-23 | 1991-12-10 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | Adeno-associated virus (aav)-based eucaryotic vectors |
| CA2113990A1 (en) | 1991-07-26 | 1993-02-18 | Frederick L. Moolten | Cancer therapy utilizing malignant cells |
| US5632957A (en) | 1993-11-01 | 1997-05-27 | Nanogen | Molecular biological diagnostic systems including electrodes |
| JPH05236997A (ja) | 1992-02-28 | 1993-09-17 | Hitachi Ltd | ポリヌクレオチド捕捉用チップ |
| US5840485A (en) | 1993-05-27 | 1998-11-24 | Selectide Corporation | Topologically segregated, encoded solid phase libraries |
| ES2289194T3 (es) | 1993-05-27 | 2008-02-01 | Aventis Pharmaceuticals Inc. | Bibliotecas en fase solida codificadas, segregadas topologicamente. |
| US5631236A (en) | 1993-08-26 | 1997-05-20 | Baylor College Of Medicine | Gene therapy for solid tumors, using a DNA sequence encoding HSV-Tk or VZV-Tk |
| US5426039A (en) | 1993-09-08 | 1995-06-20 | Bio-Rad Laboratories, Inc. | Direct molecular cloning of primer extended DNA containing an alkane diol |
| US6045996A (en) | 1993-10-26 | 2000-04-04 | Affymetrix, Inc. | Hybridization assays on oligonucleotide arrays |
| US6468742B2 (en) | 1993-11-01 | 2002-10-22 | Nanogen, Inc. | Methods for determination of single nucleic acid polymorphisms using bioelectronic microchip |
| US5965452A (en) | 1996-07-09 | 1999-10-12 | Nanogen, Inc. | Multiplexed active biologic array |
| JP2928079B2 (ja) | 1994-02-14 | 1999-07-28 | 永信薬品工業股▲ふん▼有限公司 | １−（置換ベンジル）−３−（置換アリール）縮合ピラゾール類、その製造法及びその用途 |
| US5807522A (en) | 1994-06-17 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for fabricating microarrays of biological samples |
| US5763198A (en) | 1994-07-22 | 1998-06-09 | Sugen, Inc. | Screening assays for compounds |
| US5556752A (en) | 1994-10-24 | 1996-09-17 | Affymetrix, Inc. | Surface-bound, unimolecular, double-stranded DNA |
| US5830645A (en) | 1994-12-09 | 1998-11-03 | The Regents Of The University Of California | Comparative fluorescence hybridization to nucleic acid arrays |
| US5837815A (en) | 1994-12-15 | 1998-11-17 | Sugen, Inc. | PYK2 related polypeptide products |
| US5959098A (en) | 1996-04-17 | 1999-09-28 | Affymetrix, Inc. | Substrate preparation process |
| US6117681A (en) | 1995-03-29 | 2000-09-12 | Bavarian Nordic Research Inst. A/S | Pseudotyped retroviral particles |
| US6110456A (en) | 1995-06-07 | 2000-08-29 | Yale University | Oral delivery or adeno-associated viral vectors |
| US5856174A (en) | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
| US5866411A (en) | 1995-09-08 | 1999-02-02 | Pedersen; Finn Skou | Retroviral vector, a replication system for said vector and avian or mammalian cells transfected with said vector |
| US5747276A (en) | 1995-09-15 | 1998-05-05 | The Scripps Research Institute | Screening methods for the identification of novel antibiotics |
| WO1997016533A1 (en) | 1995-10-31 | 1997-05-09 | The Regents Of The University Of California | Mammalian artificial chromosomes and methods of using same |
| US6022963A (en) | 1995-12-15 | 2000-02-08 | Affymetrix, Inc. | Synthesis of oligonucleotide arrays using photocleavable protecting groups |
| US6013440A (en) | 1996-03-11 | 2000-01-11 | Affymetrix, Inc. | Nucleic acid affinity columns |
| US6025155A (en) | 1996-04-10 | 2000-02-15 | Chromos Molecular Systems, Inc. | Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes |
| US6057100A (en) | 1996-06-07 | 2000-05-02 | Eos Biotechnology, Inc. | Oligonucleotide arrays |
| US5922557A (en) | 1997-01-09 | 1999-07-13 | Merck & Co., Inc. | System for stably expressing a high-affinity camp phosphodiesterase and use thereof |
| US6294330B1 (en) | 1997-01-31 | 2001-09-25 | Odyssey Pharmaceuticals Inc. | Protein fragment complementation assays for the detection of biological or drug interactions |
| JP2001514506A (ja) | 1997-03-07 | 2001-09-11 | トロピックス・インコーポレーテッド | プロテアーゼ阻害剤分析 |
| TR200001847T2 (tr) | 1997-04-04 | 2002-06-21 | Pfizer Products Inc. | Nikotinamid Türevleri |
| CA2238283C (en) | 1997-05-30 | 2002-08-20 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of neoplastic lesions, pharmaceutical compositions from such compounds and uses of such compounds and compositions for treating neoplastic lesions |
| US6096718A (en) | 1997-06-05 | 2000-08-01 | Gene Targeting Corp. | Tissue specific adenovirus vectors for breast cancer treatment |
| US6826296B2 (en) | 1997-07-25 | 2004-11-30 | Affymetrix, Inc. | Method and system for providing a probe array chip design database |
| WO1999009217A1 (en) | 1997-08-15 | 1999-02-25 | Hyseq, Inc. | Methods and compositions for detection or quantification of nucleic acid species |
| CN100367024C (zh) | 1997-09-11 | 2008-02-06 | 生物风险公司 | 制备高密度阵列的方法 |
| US6178384B1 (en) | 1997-09-29 | 2001-01-23 | The Trustees Of Columbia University In The City Of New York | Method and apparatus for selecting a molecule based on conformational free energy |
| US6465178B2 (en) | 1997-09-30 | 2002-10-15 | Surmodics, Inc. | Target molecule attachment to surfaces |
| MA24682A1 (fr) | 1997-10-23 | 1999-07-01 | Smithkline Beecham Corp | Formes polymorphes nouvelles de cipamfylline, procede pour leur preparation et compositions les contenant |
| YU22400A (sh) | 1997-10-27 | 2003-08-29 | Agouron Pharmaceuticals Inc. | Supstituisana 4-amino-tiazol-2-i jedinjenja kao cdks inhibitori |
| US6537749B2 (en) | 1998-04-03 | 2003-03-25 | Phylos, Inc. | Addressable protein arrays |
| US6048695A (en) | 1998-05-04 | 2000-04-11 | Baylor College Of Medicine | Chemically modified nucleic acids and methods for coupling nucleic acids to solid support |
| US6288234B1 (en) | 1998-06-08 | 2001-09-11 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
| US6113913A (en) | 1998-06-26 | 2000-09-05 | Genvec, Inc. | Recombinant adenovirus |
| US6277628B1 (en) | 1998-10-02 | 2001-08-21 | Incyte Genomics, Inc. | Linear microarrays |
| US20020009764A1 (en) | 1999-10-08 | 2002-01-24 | W. Joseph Thompson | Methods for identifying compounds for inhibition of neoplastic lesions, and pharmaceutical compositions containing such compounds |
| US6277489B1 (en) | 1998-12-04 | 2001-08-21 | The Regents Of The University Of California | Support for high performance affinity chromatography and other uses |
| US6221653B1 (en) | 1999-04-27 | 2001-04-24 | Agilent Technologies, Inc. | Method of performing array-based hybridization assays using thermal inkjet deposition of sample fluids |
| PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| US6653151B2 (en) | 1999-07-30 | 2003-11-25 | Large Scale Proteomics Corporation | Dry deposition of materials for microarrays using matrix displacement |
| EP1106603A3 (en) | 1999-12-06 | 2003-11-19 | Fuji Photo Film Co., Ltd. | DNA chip and reactive solid carrier |
| US6387942B2 (en) * | 2000-06-19 | 2002-05-14 | Yung Shin Pharmaceutical Ind. Co. Ltd | Method of treating disorders related to protease-activated receptors-induced cell activation |
| US20020165237A1 (en) | 2000-08-11 | 2002-11-07 | Fryburg David Albert | Treatment of the insulin resistance syndrome |
| TWI262920B (en) | 2000-10-27 | 2006-10-01 | Elbion Ag | New 7-azaindoles, their use as inhibitors of phosphodiesterase 4, and a method for synthesizing them |
| AU2002215047A1 (en) * | 2000-11-21 | 2002-06-03 | Smithkline Beecham Plc | Isoquinoline derivatives useful in the treatment of cns disorders |
| US6774134B2 (en) * | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| CZ20031903A3 (cs) | 2001-01-31 | 2004-07-14 | Pfizer Products Inc. | Amidové deriváty thiazolyl-, oxazolyl-, pyrrolyl- a imidazolyl karboxylových kyselin užitečné jako inhibitory isozymů PDE4 |
| GB0111186D0 (en) * | 2001-05-08 | 2001-06-27 | Smithkline Beecham Plc | Novel compounds |
| FR2828693B1 (fr) | 2001-08-14 | 2004-06-18 | Exonhit Therapeutics Sa | Nouvelle cible moleculaire de la neurotoxicite |
| GB0319037D0 (en) | 2003-08-13 | 2003-09-17 | Glaxo Group Ltd | 7-Azaindole Derivatives |
-
2005
- 2005-09-02 JP JP2007530399A patent/JP2008512380A/ja active Pending
- 2005-09-02 CN CNA200580036980XA patent/CN101048407A/zh active Pending
- 2005-09-02 CA CA002583428A patent/CA2583428A1/en not_active Abandoned
- 2005-09-02 AU AU2005279795A patent/AU2005279795A1/en not_active Abandoned
- 2005-09-02 US US11/219,635 patent/US7605168B2/en active Active
- 2005-09-02 EP EP05816059A patent/EP1786813A2/en not_active Withdrawn
- 2005-09-02 WO PCT/US2005/031322 patent/WO2006026754A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP1786813A2 (en) | 2007-05-23 |
| US20060100218A1 (en) | 2006-05-11 |
| AU2005279795A1 (en) | 2006-03-09 |
| WO2006026754A3 (en) | 2007-01-11 |
| WO2006026754B1 (en) | 2007-02-22 |
| WO2006026754A2 (en) | 2006-03-09 |
| WO2006026754A9 (en) | 2006-04-20 |
| JP2008512380A (ja) | 2008-04-24 |
| CN101048407A (zh) | 2007-10-03 |
| US7605168B2 (en) | 2009-10-20 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |