JP5897333B2 - ベンゾオキサゾールキナーゼ阻害剤および使用方法 - Google Patents
ベンゾオキサゾールキナーゼ阻害剤および使用方法 Download PDFInfo
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- JP5897333B2 JP5897333B2 JP2011534529A JP2011534529A JP5897333B2 JP 5897333 B2 JP5897333 B2 JP 5897333B2 JP 2011534529 A JP2011534529 A JP 2011534529A JP 2011534529 A JP2011534529 A JP 2011534529A JP 5897333 B2 JP5897333 B2 JP 5897333B2
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- alkyl
- aryl
- alkenyl
- alkynyl
- heteroaryl
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023139324A (ja) * | 2008-11-03 | 2023-10-03 | 武田薬品工業株式会社 | ベンゾオキサゾールキナーゼ阻害剤および使用方法 |
Families Citing this family (134)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1831225A2 (en) | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| KR20090017498A (ko) | 2006-04-04 | 2009-02-18 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | Pi3 키나제 길항물질 |
| WO2009046448A1 (en) | 2007-10-04 | 2009-04-09 | Intellikine, Inc. | Chemical entities and therapeutic uses thereof |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| WO2009088990A1 (en) | 2008-01-04 | 2009-07-16 | Intellikine, Inc. | Certain chemical entities, compositions and methods |
| EP2252293B1 (en) | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| US8993580B2 (en) * | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| BRPI0915231A2 (pt) * | 2008-07-08 | 2018-06-12 | Intellikine Inc | compostos inibidores de quinase e métodos de uso |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| DK2358720T3 (en) | 2008-10-16 | 2016-06-06 | Univ California | Heteroarylkinaseinhibitorer fused-ring |
| EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| US9085560B2 (en) | 2009-08-17 | 2015-07-21 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
| WO2011047384A2 (en) | 2009-10-16 | 2011-04-21 | The Regents Of The University Of California | Methods of inhibiting ire1 |
| US8604032B2 (en) | 2010-05-21 | 2013-12-10 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| WO2011149937A1 (en) | 2010-05-24 | 2011-12-01 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
| EP2616082A2 (en) * | 2010-09-17 | 2013-07-24 | Mount Sinai School Of Medicine | Methods and compositions for inhibiting autophagy for the treatment of fibrosis |
| EP2637669A4 (en) | 2010-11-10 | 2014-04-02 | Infinity Pharmaceuticals Inc | Heterocyclic compounds and their use |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| EP2655619A4 (en) * | 2010-12-23 | 2014-10-22 | Genentech Inc | COMBINATION THERAPY FROM AUTOPHAGIA AND HEMMER FOR THE TREATMENT OF NEOPLASMS |
| NZ612909A (en) | 2011-01-10 | 2015-09-25 | Infinity Pharmaceuticals Inc | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
| JP5808826B2 (ja) * | 2011-02-23 | 2015-11-10 | インテリカイン, エルエルシー | 複素環化合物およびその使用 |
| US20140357651A1 (en) | 2011-05-04 | 2014-12-04 | Yi Liu | Combination pharmaceutical compositions and uses thereof |
| WO2012154608A1 (en) * | 2011-05-06 | 2012-11-15 | Intellikine, Llc | Reactive mtor and pi3 kinase inhibitors and uses thereof |
| EP2704723A4 (en) * | 2011-05-06 | 2014-12-24 | Univ California | TREATMENT OF POLYCYSTIC DISEASES |
| TWI565709B (zh) | 2011-07-19 | 2017-01-11 | 英菲尼提製藥股份有限公司 | 雜環化合物及其用途 |
| EP2734520B1 (en) | 2011-07-19 | 2016-09-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| MX2014001662A (es) * | 2011-08-11 | 2014-08-26 | Intellikine Llc | Polimeros inhibidores de cinasas. |
| RU2014111823A (ru) | 2011-08-29 | 2015-10-10 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения и их применения |
| WO2013077921A2 (en) | 2011-09-02 | 2013-05-30 | The Regents Of The University Of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
| IN2014CN02315A (OSRAM) * | 2011-09-30 | 2015-06-19 | Dana Farber Cancer Inst Inc | |
| EP2776441A4 (en) * | 2011-11-08 | 2015-04-08 | Intellikine Llc | TREATMENT METHOD WITH MULTIPLE PHARMACEUTICAL AGENTS |
| HK1201271A1 (en) | 2011-11-11 | 2015-08-28 | Intellikine, Llc | Kinase inhibitor polymorphs |
| US20130209543A1 (en) * | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
| WO2013087647A1 (en) | 2011-12-15 | 2013-06-20 | Bayer Intellectual Property Gmbh | Substituted benzothienyl - pyrrolotriazines and uses thereof in the treatment cancer |
| UY34484A (es) | 2011-12-15 | 2013-07-31 | Bayer Ip Gmbh | Benzotienilo-pirrolotriazinas disustituidas y sus usos |
| CA2865021C (en) | 2012-02-23 | 2020-06-30 | Bayer Intellectual Property Gmbh | Substituted benzothienyl-pyrrolotriazines and uses thereof |
| CA2868302A1 (en) | 2012-03-23 | 2013-09-26 | Dennis M. Brown | Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| BR112014028881A2 (pt) | 2012-05-23 | 2017-06-27 | Hoffmann La Roche | populações de células, banco de células, métodos de obtenção de uma população de células, métodos de identificação de um fator, métodos de seleção, métodos de fornecimento de terapia, populações de hepatócitos e método de obtenção de células |
| CN103420994B (zh) * | 2012-05-24 | 2016-04-06 | 天津药物研究院 | 作为前药的达比加群酯衍生物及其制备方法和用途 |
| SI2861595T1 (sl) | 2012-06-13 | 2017-04-26 | Incyte Holdings Corporation | Substituirane triciklične spojine kot inhibitorji fgfr |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| EP2872161B1 (en) | 2012-06-26 | 2020-12-16 | Del Mar Pharmaceuticals | Dianhydrogalactitol for use in treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| CN102838627A (zh) * | 2012-09-10 | 2012-12-26 | 盛世泰科生物医药技术(苏州)有限公司 | 2-氨基苯并恶唑-5-硼酸的合成 |
| KR20150061651A (ko) | 2012-09-26 | 2015-06-04 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Ire1의 조절 |
| WO2014052550A1 (en) * | 2012-09-27 | 2014-04-03 | Thomas Jefferson University | Use of parp inhibitors to treat breast cancer |
| CA2890105C (en) | 2012-11-01 | 2023-03-21 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| KR20150079745A (ko) | 2012-11-08 | 2015-07-08 | 리젠 파마슈티컬스 소시에떼 아노님 | Pde4 억제제 및 pi3 델타 또는 이중 pi3 델타-감마 키나아제 억제제를 함유하는 약제학적 조성물 |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| US9050345B2 (en) | 2013-03-11 | 2015-06-09 | Bristol-Myers Squibb Company | Pyrrolotriazines as potassium ion channel inhibitors |
| US10130609B2 (en) | 2013-03-13 | 2018-11-20 | University Health Network | Pyrazole derivatives and their uses thereof |
| US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| US20160089371A1 (en) * | 2013-03-15 | 2016-03-31 | Intellikine, Llc | Combination of Kinase Inhibitors and Uses Thereof |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| AU2014251038A1 (en) | 2013-04-08 | 2015-11-26 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| LT2986610T (lt) | 2013-04-19 | 2018-04-10 | Incyte Holdings Corporation | Bicikliniai heterociklai, kaip fgfr inhibitoriai |
| US9682083B2 (en) * | 2013-05-14 | 2017-06-20 | Nerviano Medical Sciences S.R.L. | Pyrrolo[2,3-D]pyrimidine derivatives, process for their preparation and their use as kinase inhibitors |
| CN104250250A (zh) * | 2013-06-25 | 2014-12-31 | 苏州科捷生物医药有限公司 | 4-芳香胺基嘧啶类化合物及其抗肿瘤用途 |
| AU2014293013A1 (en) | 2013-07-26 | 2016-03-17 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
| SG10201902074UA (en) | 2013-10-04 | 2019-04-29 | Infinity Pharmaceuticals Inc | Heterocyclic compounds and uses thereof |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CA2929181A1 (en) | 2013-11-13 | 2015-05-21 | Novartis Ag | Mtor inhibitors for enhancing the immune response |
| US20170304288A1 (en) * | 2013-11-20 | 2017-10-26 | Texas Southern University | Formulations of Methionine Aminopeptidase Inhibitors for Treating Infectious Diseases |
| EP4026909A1 (en) | 2013-12-19 | 2022-07-13 | Novartis AG | Human mesothelin chimeric antigen receptors and uses thereof |
| EP3087101B1 (en) | 2013-12-20 | 2024-06-05 | Novartis AG | Regulatable chimeric antigen receptor |
| EP3593812A3 (en) | 2014-03-15 | 2020-05-27 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
| CN113616656B (zh) | 2014-03-19 | 2023-02-17 | 无限药品股份有限公司 | 用于治疗PI3K-γ介导的障碍的杂环化合物 |
| WO2015148623A1 (en) | 2014-03-26 | 2015-10-01 | Millennium Pharmaceuticals, Inc. | Treatment of fibrotic respiratory disorders |
| WO2015148615A1 (en) | 2014-03-26 | 2015-10-01 | Millennium Pharmaceuticals, Inc. | Treatment of bronchiolitis obliterans syndrome |
| WO2015148626A1 (en) * | 2014-03-26 | 2015-10-01 | Millennium Pharmaceuticals, Inc. | Treatment of fibrotic disorders |
| SI3888674T1 (sl) | 2014-04-07 | 2024-08-30 | Novartis Ag | Zdravljenje raka z uporabo antigenskega himernega receptorja proti-CD19 |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2016011394A1 (en) * | 2014-07-18 | 2016-01-21 | The General Hospital Corporation | Imaging agents for neural flux |
| US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
| JP6831777B2 (ja) | 2014-07-21 | 2021-02-17 | ノバルティス アーゲー | Cd33キメラ抗原受容体を使用する癌の処置 |
| EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
| WO2016019300A1 (en) | 2014-07-31 | 2016-02-04 | Novartis Ag | Subset-optimized chimeric antigen receptor-containing t-cells |
| AU2015301460B2 (en) | 2014-08-14 | 2021-04-08 | Novartis Ag | Treatment of cancer using GFR alpha-4 chimeric antigen receptor |
| WO2016028896A1 (en) | 2014-08-19 | 2016-02-25 | Novartis Ag | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment |
| CN107073066B (zh) | 2014-09-11 | 2021-09-17 | 加利福尼亚大学董事会 | mTORC1抑制剂 |
| US10577417B2 (en) | 2014-09-17 | 2020-03-03 | Novartis Ag | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2016057705A1 (en) | 2014-10-08 | 2016-04-14 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
| US10118890B2 (en) | 2014-10-10 | 2018-11-06 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
| ES2749679T3 (es) | 2014-10-22 | 2020-03-23 | Bristol Myers Squibb Co | Compuestos de pirrolotriazina amina sustituidos como inhibidores de PI3k |
| US10214537B2 (en) | 2014-10-22 | 2019-02-26 | Bristol-Myers Squibb Company | Bicyclic heteroaryl amine compounds |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| WO2016106351A1 (en) * | 2014-12-23 | 2016-06-30 | Millennium Pharmaceuticals, Inc. | Combination of raf inhibitors and mtor inhibitors |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| SG10201913036RA (en) | 2015-02-20 | 2020-02-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US20180140602A1 (en) | 2015-04-07 | 2018-05-24 | Novartis Ag | Combination of chimeric antigen receptor therapy and amino pyrimidine derivatives |
| CN108473957B (zh) | 2015-04-17 | 2024-07-16 | 诺华股份有限公司 | 改善嵌合抗原受体表达细胞的功效和扩增的方法 |
| EP3286211A1 (en) | 2015-04-23 | 2018-02-28 | Novartis AG | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
| AU2016322552B2 (en) | 2015-09-14 | 2021-03-25 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| JP7034084B2 (ja) | 2016-03-28 | 2022-03-11 | インサイト・コーポレイション | Tam阻害剤としてのピロロトリアジン化合物 |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN107513068A (zh) * | 2016-06-16 | 2017-12-26 | 中国科学院上海药物研究所 | 一种具有fgfr抑制活性的新型化合物及其制备和应用 |
| WO2017223422A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| EP3487878A4 (en) | 2016-07-20 | 2020-03-25 | University of Utah Research Foundation | CAR-T CD229 LYMPHOCYTES AND METHODS OF USE |
| WO2018049127A1 (en) * | 2016-09-08 | 2018-03-15 | Sabila Biosciences Llc | 1,2-dithiolane compounds useful in neuroprotection, autoimmune and cancer diseases and conditions |
| CN110225927B (zh) | 2016-10-07 | 2024-01-12 | 诺华股份有限公司 | 用于治疗癌症的嵌合抗原受体 |
| WO2018144791A1 (en) * | 2017-02-03 | 2018-08-09 | Millennium Pharmaceuticals, Inc. | Combination of vps34 inhibitors and mtor inhibitors |
| GB201705971D0 (en) * | 2017-04-13 | 2017-05-31 | Cancer Res Tech Ltd | Inhibitor compounds |
| EP3615055A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| US20200148682A1 (en) * | 2017-06-06 | 2020-05-14 | Cornell University | Akt isozyme-specific covalent inhibitors derived from redox-signaling lipids |
| WO2019210153A1 (en) | 2018-04-27 | 2019-10-31 | Novartis Ag | Car t cell therapies with enhanced efficacy |
| KR102859103B1 (ko) | 2018-05-01 | 2025-09-12 | 레볼루션 메디슨즈, 인크. | mTOR 억제제로서의 C26-연결된 라파마이신 유사체 |
| WO2019213282A1 (en) | 2018-05-01 | 2019-11-07 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
| PE20212112A1 (es) | 2018-05-01 | 2021-11-04 | Revolution Medicines Inc | Analogos de rapamicina ligados a c40, c28 y c-32 como inhibidores de mtor |
| PL3788047T3 (pl) | 2018-05-04 | 2025-04-14 | Incyte Corporation | Stałe postacie inhibitora fgfr i sposoby ich otrzymywania |
| KR20210018264A (ko) | 2018-05-04 | 2021-02-17 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| CA3102279A1 (en) | 2018-06-01 | 2019-12-05 | Cornell University | Combination therapy for pi3k-associated disease or disorder |
| US12194023B2 (en) | 2018-11-29 | 2025-01-14 | The Research Foundation For The State University Of New York | Compositions and methods for modular control of bioorthogonal ligation |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| EP3980010A4 (en) | 2019-06-04 | 2023-06-07 | Arcus Biosciences, Inc. | 2,3,5-TRISUBSTITUTED PYRAZOLO[1,5-A]PYRIMIDINE COMPOUNDS |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CR20220169A (es) | 2019-10-14 | 2022-10-27 | Incyte Corp | Heterociclos bicíclicos como inhibidores de fgfr |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| US20210205322A1 (en) * | 2020-01-08 | 2021-07-08 | Albert Einstein College Of Medicine | Rictor-targeted therapy in the management of brain metastases |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EP4146828A4 (en) * | 2020-05-07 | 2024-07-17 | Lutronic Vision Inc. | Stimulation of the healing process on the retinal pigment epithelium after r:gen with rtf technology |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含fgfr抑制劑及nectin-4靶向劑之組合療法 |
| EP4352060A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US11939331B2 (en) | 2021-06-09 | 2024-03-26 | Incyte Corporation | Tricyclic heterocycles as FGFR inhibitors |
| CA3256390A1 (en) | 2022-05-25 | 2023-11-30 | Revolution Medicines, Inc. | CANCER TREATMENT METHODS USING AN MTOR INHIBITOR |
Family Cites Families (364)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB812366A (en) | 1955-08-18 | 1959-04-22 | Wellcome Found | Improvements in and relating to derivatives of pyrimidine and the preparation thereof |
| GB937725A (en) | 1960-05-11 | 1963-09-25 | Ciba Ltd | Pyrazolo[3:4-d]pyrimidines |
| DE2004713A1 (de) | 1970-02-03 | 1971-08-12 | Boehnnger Mannheim GmbH, 6800 Mann heim Waldhof | Nitrofuryl triazolo pyrimidine und Verfahren zu ihrer Herstellung |
| US3657744A (en) | 1970-05-08 | 1972-04-25 | Univ Minnesota | Method for fixing prosthetic implants in a living body |
| IT1153216B (it) | 1981-10-16 | 1987-01-14 | Schering Ag | Procedimento per la preparazione di composti cianoeterociclici |
| DE3406533A1 (de) | 1984-02-23 | 1985-08-29 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verwendung von adenosin-derivaten als antiallergica und arzneimittel, die diese enthalten |
| US5310731A (en) | 1984-06-28 | 1994-05-10 | Whitby Research, Inc. | N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardiac vasodilators and antihypertensive agents |
| JPS61109797A (ja) | 1984-11-01 | 1986-05-28 | Yuki Gosei Yakuhin Kogyo Kk | 標識化ヌクレオチドおよび標識化ポリヌクレオチド |
| US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US5040548A (en) | 1989-06-01 | 1991-08-20 | Yock Paul G | Angioplasty mehtod |
| US5350395A (en) | 1986-04-15 | 1994-09-27 | Yock Paul G | Angioplasty apparatus facilitating rapid exchanges |
| US5061273A (en) | 1989-06-01 | 1991-10-29 | Yock Paul G | Angioplasty apparatus facilitating rapid exchanges |
| US4748982A (en) | 1987-01-06 | 1988-06-07 | Advanced Cardiovascular Systems, Inc. | Reinforced balloon dilatation catheter with slitted exchange sleeve and method |
| US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
| WO1990003370A1 (en) | 1988-09-28 | 1990-04-05 | Microprobe Corporation | DERIVATIVES OF PYRAZOLO[3,4-d]PYRIMIDINE |
| CA1322628C (en) | 1988-10-04 | 1993-10-05 | Richard A. Schatz | Expandable intraluminal graft |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| US5428125A (en) | 1989-07-17 | 1995-06-27 | The Dow Chemical Company | Mesogenic polycyanates and thermosets thereof |
| US5442039A (en) | 1989-07-17 | 1995-08-15 | The Dow Chemical Company | Mesogenic polycyanates and thermosets thereof |
| US5674278A (en) | 1989-08-24 | 1997-10-07 | Arterial Vascular Engineering, Inc. | Endovascular support device |
| US5292331A (en) | 1989-08-24 | 1994-03-08 | Applied Vascular Engineering, Inc. | Endovascular support device |
| US6344053B1 (en) | 1993-12-22 | 2002-02-05 | Medtronic Ave, Inc. | Endovascular support device and method |
| US5763597A (en) | 1989-09-15 | 1998-06-09 | Metabasis Therapeutics, Inc. | Orally active adenosine kinase inhibitors |
| US5795977A (en) | 1989-09-15 | 1998-08-18 | Metabasis Therapeutics, Inc. | Water soluble adenosine kinase inhibitors |
| US5674998A (en) | 1989-09-15 | 1997-10-07 | Gensia Inc. | C-4' modified adenosine kinase inhibitors |
| US5763596A (en) | 1989-09-15 | 1998-06-09 | Metabasis Therapeutics, Inc. | C-4' modified adenosine kinase inhibitors |
| US5646128A (en) | 1989-09-15 | 1997-07-08 | Gensia, Inc. | Methods for treating adenosine kinase related conditions |
| US5506347A (en) | 1993-02-03 | 1996-04-09 | Gensia, Inc. | Lyxofuranosyl analogues of adenosine |
| US5721356A (en) | 1989-09-15 | 1998-02-24 | Gensia, Inc. | Orally active adenosine kinase inhibitors |
| GB9009542D0 (en) | 1990-04-27 | 1990-06-20 | Beecham Group Plc | Novel compounds |
| GB9113137D0 (en) | 1990-07-13 | 1991-08-07 | Ici Plc | Thioxo heterocycles |
| US5563257A (en) | 1990-08-20 | 1996-10-08 | Boehringer Mannheim Gmbh | Phospholipid derivatives of nucleosides |
| DE4026265A1 (de) * | 1990-08-20 | 1992-02-27 | Boehringer Mannheim Gmbh | Neue phospholipid-derivate von nucleosiden, deren herstellung sowie deren verwendung als antivirale arzneimittel |
| WO1992005177A1 (en) | 1990-09-25 | 1992-04-02 | Rhone-Poulenc Rorer International (Holdings) Inc. | Compounds having antihypertensive and anti-ischemic properties |
| US5561134A (en) | 1990-09-25 | 1996-10-01 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
| US5652366A (en) | 1990-09-25 | 1997-07-29 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | DI (1R)-(-)camphosulfonic acid) salt, preparation thereof and use thereof |
| GB9103839D0 (en) | 1991-02-23 | 1991-04-10 | Smithkline Beecham Plc | Pharmaceuticals |
| IL104369A0 (en) | 1992-01-13 | 1993-05-13 | Smithkline Beecham Corp | Novel compounds and compositions |
| US5916891A (en) * | 1992-01-13 | 1999-06-29 | Smithkline Beecham Corporation | Pyrimidinyl imidazoles |
| DE4204032A1 (de) | 1992-02-12 | 1993-08-19 | Boehringer Mannheim Gmbh | Neue liponucleotide, deren herstellunmg sowie deren verwendung als antivirale arzneimittel |
| DE4204031A1 (de) | 1992-02-12 | 1993-08-19 | Boehringer Mannheim Gmbh | Neue lipidphosphonsaeure-nucleosid-konjugate sowie deren verwendung als antivirale arzneimittel |
| WO1993018035A1 (en) | 1992-03-04 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
| GB9208135D0 (en) | 1992-04-13 | 1992-05-27 | Ludwig Inst Cancer Res | Polypeptides having kinase activity,their preparation and use |
| DE69333955D1 (de) | 1992-04-24 | 2006-02-02 | Stanford Res Inst Int | Targeting homologer sequenzen in eukaryotenzellen |
| CA2117476C (en) | 1992-06-19 | 2000-02-22 | R. Andrew Wood | Infrared camera with thermoelectric temperature stabilization |
| US6057305A (en) | 1992-08-05 | 2000-05-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiretroviral enantiomeric nucleotide analogs |
| TW444018B (en) | 1992-12-17 | 2001-07-01 | Pfizer | Pyrazolopyrimidines |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| 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 |
| AU6672794A (en) | 1993-11-05 | 1995-05-23 | Biochem Pharma Inc. | Antineoplastic heteronaphthoquinones |
| IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| US5654307A (en) | 1994-01-25 | 1997-08-05 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
| US6632789B1 (en) * | 1994-04-29 | 2003-10-14 | The United States Of America As Represented By The Secretary Of The Navy | Methods for modulating T cell responses by manipulating intracellular signal transduction |
| DE4418690A1 (de) | 1994-05-28 | 1996-01-11 | Boehringer Mannheim Gmbh | Neue Lipidester von Nucleosid-Monophosphaten und deren Verwendung als immunsuppressive Arzneimittel |
| US6323201B1 (en) | 1994-12-29 | 2001-11-27 | The Regents Of The University Of California | Compounds for inhibition of ceramide-mediated signal transduction |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| ES2150113T3 (es) | 1995-04-03 | 2000-11-16 | Novartis Ag | Derivados de pirazol y procedimientos para la preparacion de los mismos. |
| US6312894B1 (en) | 1995-04-03 | 2001-11-06 | Epoch Pharmaceuticals, Inc. | Hybridization and mismatch discrimination using oligonucleotides conjugated to minor groove binders |
| DK0821671T3 (da) | 1995-04-20 | 2001-04-23 | Pfizer | Arylsulfonylhydroxamsyrederivater som MMP- og TNF-inhibitorer |
| US5977061A (en) | 1995-04-21 | 1999-11-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | N6 - substituted nucleotide analagues and their use |
| US5593997A (en) | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| US6403599B1 (en) | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
| PT831911E (pt) * | 1995-06-07 | 2002-09-30 | Searle & Co | Terapeutica de combinacao de espironolactona e antagonista da angiotensina ii para o tratamento de insuficiencia cardiaca congestiva |
| US5665721A (en) | 1995-06-07 | 1997-09-09 | Abbott Laboratories | Heterocyclic substituted cyclopentane compounds |
| WO1996040256A1 (en) * | 1995-06-07 | 1996-12-19 | G.D. Searle & Co. | Method to treat cardiofibrosis with a combination of an angiotensin ii antagonist and spironolactone |
| ATE209047T1 (de) | 1995-06-07 | 2001-12-15 | Searle & Co | Epoxysteroide aldosteronantagonist und angiotensin ii rezeptor antagonist kombinationstherapie zur behandlung von congestivem herzversagen |
| US5763885A (en) | 1995-12-19 | 1998-06-09 | Loral Infrared & Imaging Systems, Inc. | Method and apparatus for thermal gradient stabilization of microbolometer focal plane arrays |
| GB9521987D0 (en) | 1995-10-26 | 1996-01-03 | Ludwig Inst Cancer Res | Phosphoinositide 3-kinase modulators |
| DE69624081T2 (de) | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| US5747235A (en) * | 1996-01-26 | 1998-05-05 | Eastman Kodak Company | Silver halide light sensitive emulsion layer having enhanced photographic sensitivity |
| CH690773A5 (de) | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| DE19603576A1 (de) | 1996-02-01 | 1997-08-07 | Bayer Ag | Acylierte 4-Amino und 4-Hydrazinopyrimidine |
| US5914488A (en) | 1996-03-05 | 1999-06-22 | Mitsubishi Denki Kabushiki Kaisha | Infrared detector |
| GB9611460D0 (en) | 1996-06-01 | 1996-08-07 | Ludwig Inst Cancer Res | Novel lipid kinase |
| BR9711805A (pt) | 1996-06-20 | 2002-01-15 | Regents The Univesity Of Texas | Compostos e métodos para providenciar preparações farmacologicamente ativas e uso dos mesmos |
| YU1899A (sh) | 1996-07-18 | 2000-03-21 | Pfizer Inc. | Inhibitori matričnih metaloproteaza na bazi fosfinata |
| EA199900139A1 (ru) | 1996-08-23 | 1999-08-26 | Пфайзер, Инк. | Производные арилсульфониламиногидроксамовой кислоты |
| WO1998014450A1 (en) | 1996-10-02 | 1998-04-09 | Novartis Ag | Pyrimidine derivatives and processes for the preparation thereof |
| US5919808A (en) | 1996-10-23 | 1999-07-06 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US6251901B1 (en) | 1996-10-23 | 2001-06-26 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US5990169A (en) | 1996-10-23 | 1999-11-23 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US5965573A (en) | 1996-10-23 | 1999-10-12 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US6153631A (en) | 1996-10-23 | 2000-11-28 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US5922753A (en) | 1996-10-23 | 1999-07-13 | Zymogenetics, Inc. | Methods for treating bone deficit conditions with benzothiazole |
| US5994358A (en) | 1996-10-23 | 1999-11-30 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US5948776A (en) | 1996-10-23 | 1999-09-07 | Zymogenetic, Inc. | Compositions and methods for treating bone deficit conditions |
| US6342514B1 (en) * | 1996-10-23 | 2002-01-29 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| US5858753A (en) | 1996-11-25 | 1999-01-12 | Icos Corporation | Lipid kinase |
| JP4094066B2 (ja) | 1996-12-06 | 2008-06-04 | 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 | インターロイキン−1β変換酵素のインヒビター |
| US6093737A (en) | 1996-12-30 | 2000-07-25 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| AU5131998A (en) | 1997-01-06 | 1998-08-03 | Pfizer Inc. | Cyclic sulfone derivatives |
| US6303636B1 (en) | 1997-02-03 | 2001-10-16 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| AU5493598A (en) | 1997-02-07 | 1998-08-26 | Pfizer Inc. | N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases |
| US6390821B1 (en) * | 1997-02-07 | 2002-05-21 | Princeton University | Engineered protein kinases which can utilize modified nucleotide triphosphate substrates |
| CN1247531A (zh) | 1997-02-11 | 2000-03-15 | 辉瑞大药厂 | 芳基磺酰基异羟肟酸衍生物 |
| EP0970084B1 (en) | 1997-03-19 | 2003-06-04 | Basf Aktiengesellschaft | Pyrrolo 2,3d]pyrimidines and their use as tyrosine kinase inhibitors |
| US7863444B2 (en) | 1997-03-19 | 2011-01-04 | Abbott Laboratories | 4-aminopyrrolopyrimidines as kinase inhibitors |
| AU6780398A (en) * | 1997-03-28 | 1998-10-22 | Du Pont Merck Pharmaceutical Company, The | Heterocyclic integrin inhibitor prodrugs |
| AU7449598A (en) | 1997-05-23 | 1998-12-11 | Nippon Shinyaku Co. Ltd. | Medicinal composition for prevention or treatment of hepatopathy |
| GB9711650D0 (en) | 1997-06-05 | 1997-07-30 | Pfizer Ltd | Compounds useful in therapy |
| US6207679B1 (en) | 1997-06-19 | 2001-03-27 | Sepracor, Inc. | Antimicrobial agents uses and compositions related thereto |
| US6340759B1 (en) | 1997-10-02 | 2002-01-22 | Eisai Co., Ltd. | Fused pyridine derivatives |
| US6649631B1 (en) | 1997-10-23 | 2003-11-18 | The Board Of Regents Of The University Of Texas System | Compositions and methods for treating bone deficit conditions |
| WO1999024432A1 (fr) | 1997-11-12 | 1999-05-20 | Mitsubishi Chemical Corporation | Derives de purine et medicament les renfermant en tant qu'ingredient actif |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| US6191170B1 (en) | 1998-01-13 | 2001-02-20 | Tularik Inc. | Benzenesulfonamides and benzamides as therapeutic agents |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| US6127121A (en) | 1998-04-03 | 2000-10-03 | Epoch Pharmaceuticals, Inc. | Oligonucleotides containing pyrazolo[3,4-D]pyrimidines for hybridization and mismatch discrimination |
| US7715989B2 (en) | 1998-04-03 | 2010-05-11 | Elitech Holding B.V. | Systems and methods for predicting oligonucleotide melting temperature (TmS) |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| US6251689B1 (en) | 1998-05-14 | 2001-06-26 | Telik, Inc. | Methods for the solid phase synthesis of combinatorial libraries of benzimidazoles benzoxazoles benzothiazoles and derivatives thereof |
| PL204628B1 (pl) | 1998-06-02 | 2010-01-29 | Osi Pharmaceuticals | Pochodna pirolo[2,3d]pirymidyny, jej zastosowanie i sposoby wytwarzania tej pochodnej i preparaty farmaceutyczne |
| JP2000072773A (ja) | 1998-08-28 | 2000-03-07 | Zeria Pharmaceut Co Ltd | プリン誘導体 |
| US6713474B2 (en) | 1998-09-18 | 2004-03-30 | Abbott Gmbh & Co. Kg | Pyrrolopyrimidines as therapeutic agents |
| DE69928414T2 (de) | 1998-09-18 | 2006-08-03 | Abbott Gmbh & Co. Kg | 4-aminopyrrolopyrimidine als kinaseinhibitoren |
| HUP0105063A2 (hu) | 1998-11-16 | 2002-04-29 | Basf Ag | 3-[Benz(ox/ti)azol-7-il]-1H-pirimidin-2,4-dionok |
| US6319660B1 (en) | 1998-12-28 | 2001-11-20 | Eastman Kodak Company | Color photographic element containing speed improving compound |
| CA2369895C (en) | 1999-01-11 | 2010-12-21 | Princeton University | High affinity inhibitors for target validation and uses thereof |
| CZ27399A3 (cs) * | 1999-01-26 | 2000-08-16 | Ústav Experimentální Botaniky Av Čr | Substituované dusíkaté heterocyklické deriváty, způsob jejich přípravy, tyto deriváty pro použití jako léčiva, farmaceutická kompozice a kombinovaný farmaceutický přípravek tyto deriváty obsahující a použití těchto derivátů pro výrobu léčiv |
| EP1040831A3 (en) | 1999-04-02 | 2003-05-02 | Pfizer Products Inc. | Use of corticotropin releasing factor (CRF) antagonists to prevent sudden death |
| SE515856C2 (sv) | 1999-05-19 | 2001-10-22 | Ericsson Telefon Ab L M | Bärare för elektronikkomponenter |
| HK1046402A1 (zh) | 1999-06-03 | 2003-01-10 | Basf Aktiengesellschaft | Benzothiazinone和benzoxazinone化合物 |
| US6387894B1 (en) * | 1999-06-11 | 2002-05-14 | Pfizer Inc. | Use of CRF antagonists and renin-angiotensin system inhibitors |
| 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 |
| TWI262914B (en) * | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| GB9919588D0 (en) | 1999-08-18 | 1999-10-20 | Hoechst Schering Agrevo Gmbh | Fungicidal compounds |
| WO2001016114A2 (en) | 1999-08-27 | 2001-03-08 | Chemocentryx, Inc. | Heterocyclic compounds and methods for modulating cxcr3 function |
| CA2385736C (en) * | 1999-09-16 | 2011-11-15 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| NZ517758A (en) | 1999-09-17 | 2004-06-25 | Abbott Gmbh & Co | Pyrazolopyrimidines useful as therapeutic agents |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| US6506769B2 (en) | 1999-10-06 | 2003-01-14 | Boehringer Ingelheim Pharmaceuticals, Inc. | Heterocyclic compounds useful as inhibitors of tyrosine kinases |
| JP5036112B2 (ja) | 1999-10-06 | 2012-09-26 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | チロシンキナーゼのインヒビターとして有益な複素環化合物 |
| US6472153B1 (en) | 1999-10-26 | 2002-10-29 | Epoch Biosciences, Inc. | Hybridization-triggered fluorescent detection of nucleic acids |
| US6660845B1 (en) | 1999-11-23 | 2003-12-09 | Epoch Biosciences, Inc. | Non-aggregating, non-quenching oligomers comprising nucleotide analogues; methods of synthesis and use thereof |
| GB0002032D0 (en) | 2000-01-28 | 2000-03-22 | Zeneca Ltd | Chemical compounds |
| US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| US6613798B1 (en) | 2000-03-30 | 2003-09-02 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
| US7115653B2 (en) | 2000-03-30 | 2006-10-03 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| KR100785363B1 (ko) | 2000-04-25 | 2007-12-18 | 이코스 코포레이션 | 인간 포스파티딜-이노시톨 3-키나제 델타의 억제제 |
| CA2410514A1 (en) | 2000-05-30 | 2001-12-06 | Advanced Research & Technology Institute | Compositions and methods for identifying agents which modulate pten function and pi-3 kinase pathways |
| MXPA02012271A (es) | 2000-06-27 | 2004-09-06 | Genelabs Tech Inc | Nuevos compuestos que poseen actividad antibacteriana, antifungal o antitumor. |
| US6534691B2 (en) | 2000-07-18 | 2003-03-18 | E. I. Du Pont De Nemours And Company | Manufacturing process for α-olefins |
| AU2002213467A1 (en) * | 2000-10-11 | 2002-04-22 | Chemocentryx, Inc. | Modulation of ccr4 function |
| AU1312502A (en) | 2000-10-11 | 2002-04-22 | Pe Corp Ny | Fluorescent nucleobase conjugates having anionic linkers |
| JP2002131859A (ja) | 2000-10-19 | 2002-05-09 | Konica Corp | 撮影用赤外感光性ハロゲン化銀写真感光材料及び赤外感光性ハロゲン化銀乳剤 |
| US6890747B2 (en) * | 2000-10-23 | 2005-05-10 | Warner-Lambert Company | Phosphoinositide 3-kinases |
| CZ20031910A3 (cs) | 2000-12-11 | 2003-12-17 | Tularik Inc. | Sloučenina s antagonistickými účinky na CXCR3 a farmaceutický postředek |
| US7157487B2 (en) | 2000-12-28 | 2007-01-02 | Daiichi Pharmaceutical Co., Ltd. | Vla-4 inhibitors |
| SK286630B6 (sk) | 2001-01-22 | 2009-02-05 | Merck & Co., Inc. | Nukleozidové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
| US7105499B2 (en) | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| MXPA03008560A (es) | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
| US7250569B2 (en) | 2001-04-26 | 2007-07-31 | New York University School Of Medicine | Method for dissolving nanostructural materials |
| ES2282410T3 (es) | 2001-05-08 | 2007-10-16 | Kudos Pharmaceuticals Limited | Derivados de isoquinolinona como inhibidores de parp. |
| WO2002094264A1 (en) | 2001-05-23 | 2002-11-28 | Tularik Inc. | Ccr4 antagonists |
| CA2450628A1 (en) | 2001-06-13 | 2002-12-19 | Genesoft Pharmaceuticals, Inc. | Benzothiophene compounds having antiinfective activity |
| US20030236198A1 (en) | 2001-06-13 | 2003-12-25 | Genesoft, Inc. | Antipathogenic benzamide compounds |
| JP2005505507A (ja) * | 2001-06-13 | 2005-02-24 | ジーンソフト ファーマシューティカルズ インコーポレイテッド | 抗感染活性を有するイソキノリン化合物 |
| EP1463742A4 (en) | 2001-06-21 | 2006-05-10 | Ariad Pharma Inc | NEW PYRAZOLO AND PYRROLO PYRIMIDINES AND THEIR USES |
| GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| ES2274986T3 (es) * | 2001-08-01 | 2007-06-01 | MERCK & CO., INC. | Derivados de benzimidazo 4,5-f/isoquinolinona. |
| AU2002327422A1 (en) | 2001-08-03 | 2003-03-18 | Abbott Laboratories | Method of identifying inhibitors of lck |
| CN101513402B (zh) | 2001-08-10 | 2012-03-21 | 盐野义制药株式会社 | 抗病毒药 |
| JP2003073357A (ja) | 2001-09-03 | 2003-03-12 | Mitsubishi Pharma Corp | アミド化合物を含有するRhoキナーゼ阻害剤 |
| AU2002368274A1 (en) | 2001-09-13 | 2004-06-03 | Genesoft, Inc. | Methods of treating infection by drug resistant bacteria |
| AUPR769501A0 (en) | 2001-09-14 | 2001-10-11 | Biomolecular Research Institute Limited | Cytokine receptor 1 |
| US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TWI330183B (OSRAM) * | 2001-10-22 | 2010-09-11 | Eisai R&D Man Co Ltd | |
| WO2003037860A2 (en) | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| US7319858B2 (en) | 2001-11-16 | 2008-01-15 | Cingular Wireless Ii, Llc | System and method for querying message information |
| AU2002350217A1 (en) | 2001-12-04 | 2003-06-17 | Bristol-Myers Squibb Company | Glycinamides as factor xa inhibitors |
| JP4085237B2 (ja) | 2001-12-21 | 2008-05-14 | 日本電気株式会社 | 携帯電話の利用契約システムと通信方法 |
| ES2421511T3 (es) | 2001-12-21 | 2013-09-03 | X Ceptor Therapeutics Inc | Moduladores de LXR |
| WO2003057212A1 (en) | 2001-12-26 | 2003-07-17 | Genelabs Technologies, Inc. | Polyamide derivatives possessing antibacterial, antifungal or antitumor activity |
| US7414036B2 (en) | 2002-01-25 | 2008-08-19 | Muscagen Limited | Compounds useful as A3 adenosine receptor agonists |
| US20030225098A1 (en) | 2002-03-21 | 2003-12-04 | Hirst Gavin C. | Kinase inhibitors |
| AU2003225933A1 (en) | 2002-03-22 | 2003-10-13 | Cellular Genomics, Inc. | AN IMPROVED FORMULATION OF CERTAIN PYRAZOLO(3,4-d) PYRIMIDINES AS KINASE MODULATORS |
| US8247424B2 (en) | 2002-03-26 | 2012-08-21 | Zentopharm Gmbh | Fredericamycin derivatives |
| US7166293B2 (en) | 2002-03-29 | 2007-01-23 | Carlsbad Technology, Inc. | Angiogenesis inhibitors |
| DE10217046A1 (de) | 2002-04-17 | 2003-11-06 | Bioleads Gmbh | Fredericamycin-Derivate |
| AU2003223012A1 (en) | 2002-04-26 | 2003-11-10 | Pfizer Products Inc. | Pyrimidine-2, 4, 6-trione metallo-proteinase inhibitors |
| WO2004039774A2 (en) | 2002-05-23 | 2004-05-13 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
| WO2003106426A1 (en) | 2002-06-14 | 2003-12-24 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| US7265111B2 (en) | 2002-06-27 | 2007-09-04 | Sanofi-Aventis Deutschland Gmbh | Adenosine analogues and their use as pharmaceutical agents |
| EP1531815B1 (en) | 2002-06-27 | 2014-09-24 | Novo Nordisk A/S | Glucokinase activators |
| RU2340605C2 (ru) | 2002-06-27 | 2008-12-10 | Ново Нордиск А/С | Арилкарбонильные производные в качестве терапевтических средств |
| DE10230917A1 (de) | 2002-07-09 | 2004-02-05 | Bioleads Gmbh | Fredericamycin-Derivate |
| WO2004006906A2 (en) | 2002-07-15 | 2004-01-22 | Combinatorx, Incorporated | Methods for the treatment of neoplasms |
| JP2006503008A (ja) | 2002-08-13 | 2006-01-26 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | マトリクスメタロプロテイナーゼ阻害物質としての4−ヒドロキシキノリン誘導体 |
| NZ538420A (en) | 2002-08-16 | 2007-06-29 | Kinacia Pty Ltd | Inhibition of phosphoinositide 3-kinase beta |
| US20040048853A1 (en) | 2002-08-21 | 2004-03-11 | Gustave Bergnes | Compounds, compositions, and methods |
| US20030139427A1 (en) | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
| JP4487774B2 (ja) | 2002-09-30 | 2010-06-23 | 萬有製薬株式会社 | 2−アミノベンズイミダゾール誘導体 |
| JP2004161716A (ja) | 2002-11-15 | 2004-06-10 | Takeda Chem Ind Ltd | Jnk阻害剤 |
| UA80171C2 (en) | 2002-12-19 | 2007-08-27 | Pfizer Prod Inc | Pyrrolopyrimidine derivatives |
| AU2003301020A1 (en) | 2002-12-20 | 2004-07-22 | Sankyo Company, Limited | Isoquinolinone derivatives and their use as therapeutic agents |
| US7365094B2 (en) * | 2002-12-23 | 2008-04-29 | 4Sc Ag | Compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents |
| WO2004056746A1 (en) | 2002-12-23 | 2004-07-08 | 4Sc Ag | Cycloalkene dicarboxylic acid compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents |
| US7247736B2 (en) | 2002-12-23 | 2007-07-24 | 4Sc Ag | Method of identifying inhibitors of DHODH |
| KR20050106081A (ko) | 2003-03-06 | 2005-11-08 | 디에스엠 아이피 어셋츠 비.브이. | α-아미노 카보닐 화합물의 제조방법 |
| US7550590B2 (en) | 2003-03-25 | 2009-06-23 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| GB0306907D0 (en) | 2003-03-26 | 2003-04-30 | Angiogene Pharm Ltd | Boireductively-activated prodrugs |
| WO2004089297A2 (en) | 2003-04-02 | 2004-10-21 | Suntory Pharmaceutical Research Laboratories, Llc | Compounds and methods for treatment of thrombosis |
| EP1646615B1 (en) | 2003-06-06 | 2009-08-26 | Vertex Pharmaceuticals Incorporated | Pyrimidine derivatives as modulators of atp-binding cassette transporters |
| US7429596B2 (en) | 2003-06-20 | 2008-09-30 | The Regents Of The University Of California | 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof |
| WO2005002585A1 (en) | 2003-07-02 | 2005-01-13 | Warner-Lambert Company Llc | Combination of an allosteric inhibitor of matrix metalloproteinase-13 and a ligand to an alpha-2-delta receptor |
| AU2004260689B8 (en) | 2003-07-29 | 2008-05-15 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| GB0317951D0 (en) | 2003-07-31 | 2003-09-03 | Trigen Ltd | Compounds |
| WO2005014532A1 (en) | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions and methods of use |
| US7208601B2 (en) | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| WO2005016349A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Methods of inhibiting leukocyte accumulation |
| US20050043239A1 (en) * | 2003-08-14 | 2005-02-24 | Jason Douangpanya | Methods of inhibiting immune responses stimulated by an endogenous factor |
| MXPA06001758A (es) | 2003-08-15 | 2006-08-11 | Irm Llc | Anilino purinas sustituidas en la posicion 6 utiles como inhibidores de rtk. |
| US7390820B2 (en) | 2003-08-25 | 2008-06-24 | Amgen Inc. | Substituted quinolinone derivatives and methods of use |
| WO2005044181A2 (en) | 2003-09-09 | 2005-05-19 | Temple University-Of The Commonwealth System Of Higher Education | Protection of tissues and cells from cytotoxic effects of ionizing radiation by abl inhibitors |
| US7138401B2 (en) | 2003-09-18 | 2006-11-21 | Conforma Therapeutics Corporation | 2-aminopurine analogs having HSP90-inhibiting activity |
| GB0322409D0 (en) | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| MXPA06003996A (es) | 2003-10-08 | 2006-07-05 | Irm Llc | Compuestos y composiciones como inhibidores de la proteina cinasa. |
| TWI344364B (en) | 2003-11-10 | 2011-07-01 | Synta Pharmaceuticals Corp | Fused heterocyclic compounds |
| JP2007511596A (ja) | 2003-11-17 | 2007-05-10 | ファイザー・プロダクツ・インク | 癌の治療において有用なピロロピリミジン化合物 |
| AR046845A1 (es) | 2003-11-21 | 2005-12-28 | Novartis Ag | Derivados de 1h-imidazo[4,5-c]quinolina para tratamiento de enfermedades dependientes de las proteino-quinasas |
| WO2005061460A1 (en) | 2003-12-08 | 2005-07-07 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| CA2548951A1 (en) | 2003-12-22 | 2005-07-14 | Gilead Sciences, Inc. | Kinase inhibitor phosphonate conjugates |
| WO2005063766A2 (en) | 2003-12-23 | 2005-07-14 | Novartis Ag | Bicyclic heterocyclic p-38 kinase inhibitors |
| US20050239809A1 (en) | 2004-01-08 | 2005-10-27 | Watts Stephanie W | Methods for treating and preventing hypertension and hypertension-related disorders |
| CA2553724A1 (en) | 2004-02-03 | 2005-08-18 | Abbott Laboratories | Aminobenzoxazoles as therapeutic agents |
| AU2005212092B2 (en) | 2004-02-13 | 2011-01-20 | Msd K.K. | Fused-ring 4-oxopyrimidine derivative |
| US20050187418A1 (en) | 2004-02-19 | 2005-08-25 | Small Brooke L. | Olefin oligomerization |
| CN1980929A (zh) | 2004-02-24 | 2007-06-13 | 比奥阿克松医疗技术股份有限公司 | 4-取代哌啶衍生物 |
| EP1720878A1 (en) | 2004-02-27 | 2006-11-15 | F.Hoffmann-La Roche Ag | Heteroaryl-fused pyrazolo derivatives |
| JP2007523938A (ja) | 2004-02-27 | 2007-08-23 | エフ.ホフマン−ラ ロシュ アーゲー | ピラゾールの縮合誘導体 |
| EP2168968B1 (en) | 2004-04-02 | 2017-08-23 | OSI Pharmaceuticals, LLC | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| US20070293489A1 (en) | 2004-04-02 | 2007-12-20 | Jerry Adams | Substituted Pyrazolopyrimidines |
| ZA200609259B (en) | 2004-04-30 | 2008-07-30 | Takeda Pharmaceutical | Heterocyclic amide compound and use thereof as an mmp-13 inhibitor |
| DE102004022897A1 (de) | 2004-05-10 | 2005-12-08 | Bayer Cropscience Ag | Azinyl-imidazoazine |
| CA2730540A1 (en) | 2004-05-13 | 2005-12-01 | Vanderbilt University | Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis |
| ES2873875T3 (es) | 2004-05-13 | 2021-11-04 | Icos Corp | Quinazolinonas como inhibidores de fosfatidilinositol 3-quinasa delta humano |
| WO2005117889A1 (en) | 2004-05-25 | 2005-12-15 | Icos Corporation | Methods for treating and/or preventing aberrant proliferation of hematopoietic |
| EP1750715A1 (en) | 2004-06-04 | 2007-02-14 | Icos Corporation | Methods for treating mast cell disorders |
| GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| WO2006038865A1 (en) | 2004-10-01 | 2006-04-13 | Betagenon Ab | Nucleotide derivatives for the treatment of type 2 diabetes and other disorders |
| AU2005301957B2 (en) | 2004-11-03 | 2012-02-23 | Department Of Health And Human Services | Novobiocin analogues as anticancer agents |
| US8212012B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| US7622451B2 (en) | 2004-11-03 | 2009-11-24 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| US8212011B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues |
| GB0425035D0 (en) | 2004-11-12 | 2004-12-15 | Novartis Ag | Organic compounds |
| EP1831225A2 (en) | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| US8946444B2 (en) | 2004-11-23 | 2015-02-03 | Ptc Therapeutics, Inc. | Tetrahydrocarbazoles as active agents for inhibiting VEGF production by translational control |
| TW200637843A (en) | 2005-01-10 | 2006-11-01 | Bristol Myers Squibb Co | Phenylglycinamide derivatives useful as anticoagulants |
| US20060156485A1 (en) | 2005-01-14 | 2006-07-20 | The Procter & Gamble Company | Keratin dyeing compounds, keratin dyeing compositions containing them, and use thereof |
| PE20061119A1 (es) * | 2005-01-19 | 2006-11-27 | Aventis Pharma Sa | PIRAZOLO PIRIDINAS SUSTITUIDAS COMO INHIBIDORES DE CINASAS FAK, KDR Y Tie |
| GB0501999D0 (en) | 2005-02-01 | 2005-03-09 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| US20080287469A1 (en) | 2005-02-17 | 2008-11-20 | Diacovo Thomas G | Phosphoinositide 3-Kinase Inhibitors for Inhibiting Leukocyte Accumulation |
| US7579348B2 (en) | 2005-02-25 | 2009-08-25 | Pgxhealth, Llc | Derivatives of 8-substituted xanthines |
| US20090124654A1 (en) | 2005-03-01 | 2009-05-14 | Mjalli Adnan M M | Aryl and Heteroaryl Compounds, Compositions, Methods of Use |
| CN101184395A (zh) | 2005-04-06 | 2008-05-21 | Irm责任有限公司 | 包含二芳基胺的化合物和组合物及其作为类固醇激素核受体调节剂的用途 |
| KR100781704B1 (ko) | 2005-04-20 | 2007-12-03 | 에스케이케미칼주식회사 | 피리딘 유도체와 이의 제조방법, 및 이를 포함하는약제조성물 |
| GT200600167A (es) | 2005-04-22 | 2007-03-14 | Derivados de dihidrobenzofurano y usos de los mismos | |
| EP1879657A2 (en) | 2005-04-25 | 2008-01-23 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of compounds to enhance processivity of telomerase |
| EA017278B9 (ru) | 2005-06-22 | 2013-01-30 | Кемосентрикс, Инк. | Соединения азаиндазола и способы применения |
| DE602006015658D1 (de) * | 2005-06-27 | 2010-09-02 | Amgen Inc | Entzündungshemmende arylnitrilverbindungen |
| US20100168102A9 (en) | 2005-07-11 | 2010-07-01 | Devgen Nv | Amide Derivatives as Kinase Inhibitors |
| BRPI0615522A2 (pt) | 2005-07-11 | 2012-04-10 | Devgen Nv | derivados da amida como inibidores da quinase |
| GB0516723D0 (en) | 2005-08-15 | 2005-09-21 | Novartis Ag | Organic compounds |
| WO2007025090A2 (en) | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Heterobicyclic and - tricyclic inhibitors of mapk/erk kinase |
| JP2009506006A (ja) | 2005-08-25 | 2009-02-12 | エフ.ホフマン−ラ ロシュ アーゲー | p38MAPキナーゼ阻害剤およびその使用方法 |
| EP1919914A2 (en) | 2005-08-25 | 2008-05-14 | F.Hoffmann-La Roche Ag | P38 map kinase inhibitors and methods for using the same |
| WO2007025534A1 (de) | 2005-09-01 | 2007-03-08 | Bioagency Ag | Fredericamycin-derivate |
| TW200800887A (en) | 2005-09-29 | 2008-01-01 | Wyeth Corp | Phenylaminopropanol derivatives and methods of their use |
| AU2006316605B2 (en) | 2005-11-17 | 2012-04-26 | Osi Pharmaceuticals, Inc. | Fused bicyclic mTOR inhibitors |
| JP2009516742A (ja) * | 2005-11-22 | 2009-04-23 | メルク エンド カムパニー インコーポレーテッド | インドールオレキシン受容体アンタゴニスト |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| US20080299113A1 (en) | 2005-12-19 | 2008-12-04 | Arnold Lee D | Combined treatment with and composition of 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitor and anti-cancer agents |
| TW201307354A (zh) | 2005-12-29 | 2013-02-16 | Abbott Lab | 蛋白質激酶抑制劑 |
| US7659274B2 (en) | 2006-01-25 | 2010-02-09 | Osi Pharmaceuticals, Inc. | Unsaturated mTOR inhibitors |
| US20080058521A1 (en) | 2006-01-26 | 2008-03-06 | Wyeth | Processes for the preparation of compounds |
| WO2007103308A2 (en) | 2006-03-07 | 2007-09-13 | Array Biopharma Inc. | Heterobicyclic pyrazole compounds and methods of use |
| US7651687B2 (en) | 2006-03-13 | 2010-01-26 | Osi Pharmaceuticals, Inc. | Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors |
| ES2987558T3 (es) | 2006-03-24 | 2024-11-15 | Bioverativ Therapeutics Inc | PC5 como enzima de procesamiento de propéptido de factor IX |
| JP2009531443A (ja) | 2006-03-29 | 2009-09-03 | フォールドアールエックス ファーマシューティカルズ インコーポレーティッド | α−シヌクレイン毒性の抑制 |
| KR20090017498A (ko) | 2006-04-04 | 2009-02-18 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | Pi3 키나제 길항물질 |
| WO2007121453A2 (en) | 2006-04-17 | 2007-10-25 | The Regents Of The University Of California | 2-hydroxy-1-oxo 1,2 dihydro isoquinoline chelating agents |
| GB0607948D0 (en) * | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
| US7673786B2 (en) | 2006-04-21 | 2010-03-09 | Shell Oil Company | Welding shield for coupling heaters |
| PE20080361A1 (es) | 2006-04-21 | 2008-06-03 | Novartis Ag | Compuestos derivados de purina como activadores del receptor de adenosina a2a |
| GB0607950D0 (en) | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
| JP2009536161A (ja) | 2006-04-25 | 2009-10-08 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| EP2037931A2 (en) | 2006-04-25 | 2009-03-25 | Astex Therapeutics Limited | Pharmaceutical combinations of pk inhibitors and other active agents |
| DE102006020327A1 (de) | 2006-04-27 | 2007-12-27 | Bayer Healthcare Ag | Heterocyclisch substituierte, anellierte Pyrazol-Derivate und ihre Verwendung |
| EP2029593A1 (en) | 2006-05-22 | 2009-03-04 | AstraZeneca AB | Indole derivatives |
| GB0610242D0 (en) | 2006-05-23 | 2006-07-05 | Novartis Ag | Organic compounds |
| US20080003254A1 (en) * | 2006-05-23 | 2008-01-03 | Abbott Laboratories | Systems and methods for delivering a rapamycin analog that do not inhibit human coronary artery endothelial cell migration |
| GB0610317D0 (en) | 2006-05-24 | 2006-07-05 | Medical Res Council | Antiparasitic compounds and compositions |
| ES2344760T3 (es) * | 2006-07-20 | 2010-09-06 | Amgen Inc. | Compuestos de piridona sustituidos y metodo de uso. |
| EP2049502B1 (en) | 2006-07-28 | 2012-01-04 | Novartis AG | 2,4-substituted quinazolines as lipid kinase inhibitors |
| WO2008021389A2 (en) * | 2006-08-16 | 2008-02-21 | Exelixis, Inc. | Using pi3k and mek modulators in treatments of cancer |
| CA2661307C (en) * | 2006-08-22 | 2016-07-19 | Technion Research And Development Foundation Ltd. | Heterocyclic derivatives binding to the peripheral-type benzodiazepine receptor (pbr) |
| JP2010501593A (ja) * | 2006-08-24 | 2010-01-21 | セレネックス, インコーポレイテッド | イソキノリン、キナゾリンおよびフタラジン誘導体 |
| WO2008025755A1 (de) | 2006-09-01 | 2008-03-06 | Basf Se | Verwendung von n-haltigen heterozyklen in dermokosmetika |
| ES2528316T3 (es) | 2006-09-01 | 2015-02-06 | Senhwa Biosciences, Inc. | Moduladores de la serina-treonina proteína quinasa y de PARP |
| EP1903044A1 (en) | 2006-09-14 | 2008-03-26 | Novartis AG | Adenosine Derivatives as A2A Receptor Agonists |
| EP1900729A1 (en) | 2006-09-15 | 2008-03-19 | Novartis AG | Benzoxazoles and oxazolopyridines being useful as Janus kinases inhibitors |
| EP2077267A4 (en) | 2006-10-18 | 2010-04-07 | Takeda Pharmaceutical | CONDENSED HETEROCYCLIC COMPOUND |
| US7772180B2 (en) | 2006-11-09 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2441768A1 (en) | 2006-11-13 | 2012-04-18 | Eli Lilly & Co. | Thienopyrimidinones for treatment of inflammatory disorders and cancers |
| WO2008063625A2 (en) | 2006-11-20 | 2008-05-29 | Adolor Corporation | Pyridine compounds and methods of their use |
| CN101611007A (zh) | 2006-12-20 | 2009-12-23 | 先灵公司 | 新颖的jnk抑制剂 |
| KR20090101278A (ko) | 2006-12-22 | 2009-09-24 | 인더스트리얼 리서치 리미티드 | 누클레오시다제 및 포스포릴라제 억제제의 아제티딘 유사체 |
| WO2008083070A1 (en) | 2006-12-29 | 2008-07-10 | Neurogen Corporation | Crf1 receptor ligands comprising fused bicyclic heteroaryl moieties |
| MX2009007944A (es) | 2007-01-26 | 2009-08-07 | Irm Llc | Compuestos y composiciones de purina como inhibidores de quinasa para el tratamiento de enfermedades relacionadas con plasmodium. |
| US8586619B2 (en) | 2007-03-12 | 2013-11-19 | Vm Therapeutics Llc | Agents of calcium ion channel modulators |
| PL2139882T3 (pl) | 2007-03-23 | 2014-05-30 | Amgen Inc | 3-podstawione pochodne chinoliny lub chinoksaliny i ich zastosowanie jako inhibitorów 3-kinazy fosfatydyloinozytolu (pi3k) |
| CA2680783C (en) | 2007-03-23 | 2012-04-24 | Amgen Inc. | Heterocyclic compounds and their uses |
| DK2137186T3 (en) | 2007-03-23 | 2016-04-18 | Amgen Inc | Heterocyclic compounds and their uses |
| WO2008156513A2 (en) | 2007-03-29 | 2008-12-24 | University Of Connecticut | Methods to protect skeletal muscle against injury |
| CN101636397B (zh) | 2007-04-13 | 2012-06-13 | 中国人民解放军军事医学科学院毒物药物研究所 | 脲类化合物、其制备方法及其医药用途 |
| MX2009010536A (es) | 2007-04-13 | 2009-10-22 | Sanofi Aventis | Una sintesis de n-aminoindoles catalizada por un metal de transicion. |
| JP2010163361A (ja) | 2007-04-27 | 2010-07-29 | Dainippon Sumitomo Pharma Co Ltd | キノリン誘導体 |
| US7960353B2 (en) * | 2007-05-10 | 2011-06-14 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| TW200902016A (en) | 2007-05-22 | 2009-01-16 | Taigen Biotechnology Co Ltd | Kinesin inhibitors |
| US7928111B2 (en) | 2007-06-08 | 2011-04-19 | Senomyx, Inc. | Compounds including substituted thienopyrimidinone derivatives as ligands for modulating chemosensory receptors |
| US9603848B2 (en) | 2007-06-08 | 2017-03-28 | Senomyx, Inc. | Modulation of chemosensory receptors and ligands associated therewith |
| EP2173747B1 (en) | 2007-06-26 | 2011-12-21 | Sanofi | A regioselective metal catalyzed synthesis of annelated benzimidazoles and azabenzimidazoles |
| EP2170274A1 (en) | 2007-07-02 | 2010-04-07 | Technion Research and Development Foundation, Ltd. | Compositions, articles and methods comprising tspo ligands for preventing or reducing tobacco-associated damage |
| RU2345996C1 (ru) | 2007-07-17 | 2009-02-10 | Андрей Александрович Иващенко | Аннелированные азагетероциклические амиды, включающие пиримидиновый фрагмент, способ их получения и применения |
| EP2190466A4 (en) * | 2007-08-10 | 2011-12-21 | Burnham Inst Medical Research | Tissue-specific alkaline phosphatase (TNAP) activators and their use |
| MX2010001784A (es) | 2007-08-13 | 2010-03-15 | Metabasis Therapeutics Inc | Activadores novedosos de la glucocinasa. |
| PA8793301A1 (es) | 2007-08-14 | 2009-04-23 | Bayer Schering Pharma Ag | Imidazoles bicíclicos fusionados |
| WO2009044707A1 (ja) | 2007-10-03 | 2009-04-09 | Riken | ニトロトリアゾール誘導体、およびそれを用いる化合物の製造方法 |
| WO2009046448A1 (en) | 2007-10-04 | 2009-04-09 | Intellikine, Inc. | Chemical entities and therapeutic uses thereof |
| EP2217234A2 (en) | 2007-10-15 | 2010-08-18 | AstraZeneca AB | Combinations of mek inhibitors with mtor inhibitors |
| JP2009104221A (ja) * | 2007-10-19 | 2009-05-14 | Fujitsu Ltd | 情報システム |
| US20110218210A1 (en) | 2007-11-02 | 2011-09-08 | Taiga Biotechnologies | Compounds for treating abnormal cellular proliferation |
| EP2220089A4 (en) | 2007-11-13 | 2011-10-26 | Icos Corp | HEMMER OF HUMAN PHOSPHATIDYL-INOSITOL 3-KINASE-DELTA |
| US20090163481A1 (en) | 2007-12-13 | 2009-06-25 | Murphy Brian J | Ppar-delta ligands and methods of their use |
| US7960397B2 (en) | 2007-12-28 | 2011-06-14 | Institute Of Experimental Botany, Academy Of Sciences Of The Czech Republic | 6,9-disubstituted purine derivatives and their use as cosmetics and cosmetic compositions |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| WO2009088990A1 (en) * | 2008-01-04 | 2009-07-16 | Intellikine, Inc. | Certain chemical entities, compositions and methods |
| US20090181920A1 (en) | 2008-01-09 | 2009-07-16 | Pgxhealth, Llc | Intrathecal treatment of neuropathic pain with a2ar agonists |
| WO2009100406A2 (en) | 2008-02-07 | 2009-08-13 | Synta Pharmaceuticals Corp. | Topical formulations for the treatment of psoriasis |
| WO2009100326A1 (en) | 2008-02-07 | 2009-08-13 | Cv Therapeutics, Inc. | Abca-1 elevating compounds and the use thereof |
| TWI444384B (zh) | 2008-02-20 | 2014-07-11 | Gilead Sciences Inc | 核苷酸類似物及其在治療惡性腫瘤上的用途 |
| US8993580B2 (en) | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| EP2252293B1 (en) | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| CA2716856C (en) | 2008-03-20 | 2013-02-19 | Amgen Inc. | Aurora kinase modulators and method of use |
| US20090312406A1 (en) | 2008-06-12 | 2009-12-17 | Hsing-Pang Hsieh | Coumarin compounds and their use for treating viral infection |
| BRPI0915231A2 (pt) * | 2008-07-08 | 2018-06-12 | Intellikine Inc | compostos inibidores de quinase e métodos de uso |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| AU2009270983A1 (en) | 2008-07-16 | 2010-01-21 | Schering Corporation | Bicyclic heterocycle derivatives and their use as GPCR modulators |
| US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
| CN102177152A (zh) | 2008-08-11 | 2011-09-07 | 哈佛大学校长及研究员协会 | 用于抑制tRNA合成酶的卤夫酮(halofuginone)类似物和其用途 |
| WO2010039534A2 (en) | 2008-09-23 | 2010-04-08 | Georgetown University | Viral and fungal inhibitors |
| CA2738429C (en) * | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| ES2627677T3 (es) * | 2008-10-31 | 2017-07-31 | Novartis Ag | Combinación de un inhibidor de fosfatidilinositol-3-cinasa (PI3K) y un inhibidor de mTOR |
| US8476282B2 (en) * | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
| CA2749884C (en) | 2009-01-28 | 2018-01-23 | Cara Therapeutics, Inc. | Bicyclic pyrazolo-heterocycles |
| EP2400985A2 (en) | 2009-02-25 | 2012-01-04 | OSI Pharmaceuticals, LLC | Combination of an either an anti-igf-1r antibody or an igf binding protein and a small molecule igf-1r kinase inhibitor |
| WO2010118367A2 (en) | 2009-04-10 | 2010-10-14 | Progenics Pharmaceuticals, Inc. | Antiviral pyrimidines |
| EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| CN101602768B (zh) | 2009-07-17 | 2012-05-30 | 河南省农科院农副产品加工研究所 | 一种芝麻素和芝麻林素的提纯方法 |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
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