NO20023713L - 2-benzotiazolyl-urea-derivater samt anvendelse derav som proteinkinaseinhibitorer - Google Patents
2-benzotiazolyl-urea-derivater samt anvendelse derav som proteinkinaseinhibitorer Download PDFInfo
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- NO20023713L NO20023713L NO20023713A NO20023713A NO20023713L NO 20023713 L NO20023713 L NO 20023713L NO 20023713 A NO20023713 A NO 20023713A NO 20023713 A NO20023713 A NO 20023713A NO 20023713 L NO20023713 L NO 20023713L
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- alkyl
- isotopes
- compound
- prodrugs
- phenyl
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US18084100P | 2000-02-07 | 2000-02-07 | |
PCT/US2001/003803 WO2001057008A1 (fr) | 2000-02-07 | 2001-02-06 | Derives de 2-benzothiazolyle uree et leur utilisation en tant qu'inhibiteurs de proteine kinase |
Publications (2)
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NO20023713D0 NO20023713D0 (no) | 2002-08-06 |
NO20023713L true NO20023713L (no) | 2002-10-04 |
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Application Number | Title | Priority Date | Filing Date |
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NO20023713A NO20023713L (no) | 2000-02-07 | 2002-08-06 | 2-benzotiazolyl-urea-derivater samt anvendelse derav som proteinkinaseinhibitorer |
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US (1) | US7091227B2 (fr) |
EP (1) | EP1254123A1 (fr) |
JP (1) | JP2003521543A (fr) |
KR (1) | KR20020084116A (fr) |
CN (1) | CN1422262A (fr) |
AR (1) | AR030189A1 (fr) |
AU (1) | AU2001236698A1 (fr) |
BG (1) | BG107062A (fr) |
BR (1) | BR0108085A (fr) |
CA (1) | CA2398754A1 (fr) |
HU (1) | HUP0300359A2 (fr) |
IL (1) | IL151045A0 (fr) |
MX (1) | MXPA02007632A (fr) |
NO (1) | NO20023713L (fr) |
PL (1) | PL357099A1 (fr) |
SK (1) | SK12712002A3 (fr) |
WO (1) | WO2001057008A1 (fr) |
ZA (1) | ZA200206235B (fr) |
Families Citing this family (123)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
EP1158985B1 (fr) | 1999-01-13 | 2011-12-28 | Bayer HealthCare LLC | DIPHENYLE UREES A SUBSTITUTION OMEGA-CARBOXY ARYLE EN TANT QU'INHIBITEURS DE LA KINASE p38 |
AU2001280229B2 (en) * | 2000-08-21 | 2006-12-07 | Pacific Corporation | Novel thiourea derivatives and the pharmaceutical compositions containing the same |
US6492521B2 (en) * | 2000-11-03 | 2002-12-10 | Cytec Technology Corp. | Hindered amine light stabilizers based on multi-functional carbonyl compounds and methods of making same |
US6727247B2 (en) | 2001-12-10 | 2004-04-27 | Hoffman-La Roche Inc. | Substituted benzothiazole amide derivatives |
WO2003068229A1 (fr) | 2002-02-11 | 2003-08-21 | Bayer Pharmaceuticals Corporation | N-oxydes de pyridine, de quinoline, et d'isoquinoline en tant qu'inhibiteurs de kinase |
ES2425739T3 (es) | 2002-02-11 | 2013-10-17 | Bayer Healthcare Llc | Sorafenib-tosilato para el tratamiento de enfermedades caracterizadas por angiogénesis anormal |
RU2340605C2 (ru) | 2002-06-27 | 2008-12-10 | Ново Нордиск А/С | Арилкарбонильные производные в качестве терапевтических средств |
KR101116627B1 (ko) | 2002-06-27 | 2012-10-09 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
JP2006502133A (ja) * | 2002-08-10 | 2006-01-19 | アステックス、セラピューティックス、リミテッド | サイクリン依存キナーゼ(cdk)インヒビターとしての3−(カルボニル)1h−インダゾール化合物 |
US7056925B2 (en) | 2002-08-13 | 2006-06-06 | Abbott Laboratories | Urea kinase inhibitors |
US20040034038A1 (en) * | 2002-08-13 | 2004-02-19 | Goaquan Li | Urea kinase inhibitors |
EP2426122A1 (fr) * | 2002-10-24 | 2012-03-07 | Merck Patent GmbH | Dérivés d'urée de méthylène comme inhibteurs de RAF kinase |
JP4690889B2 (ja) | 2002-10-24 | 2011-06-01 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | メチレン尿素誘導体 |
US7582635B2 (en) | 2002-12-24 | 2009-09-01 | Purdue Pharma, L.P. | Therapeutic agents useful for treating pain |
AU2003303678A1 (en) * | 2003-01-03 | 2004-08-10 | Genzyme Corporation | Urea derivatives and their use as anti-inflammatory agents |
US7390670B2 (en) * | 2003-02-20 | 2008-06-24 | Lumigen, Inc. | Signalling compounds and methods for detecting hydrogen peroxide |
UY28213A1 (es) | 2003-02-28 | 2004-09-30 | Bayer Pharmaceuticals Corp | Nuevos derivados de cianopiridina útiles en el tratamiento de cáncer y otros trastornos. |
MXPA05009103A (es) * | 2003-02-28 | 2006-04-18 | Bayer Pharmaceuticals Corp | Derivados de 2-oxo-1,3,5-perhidrotriazapina utiles en el tratamiento de trastornos hiper-proliferativos, por angiogenesis, e inflamatorios. |
ATE440835T1 (de) * | 2003-03-06 | 2009-09-15 | Glaxo Group Ltd | Heterozyklische harnstoff-derivate für die behandlung von schmerzen. |
US7514562B2 (en) * | 2003-03-07 | 2009-04-07 | Glaxo Group Limited | Urea derivatives and their use as vanilloid receptor antagonists in the treatment of pain |
GB0305426D0 (en) * | 2003-03-08 | 2003-04-16 | Glaxo Group Ltd | Novel compounds |
PL1636585T3 (pl) | 2003-05-20 | 2008-10-31 | Bayer Healthcare Llc | Diarylowe pochodne mocznika inhibowane kinazą |
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. |
KR101139557B1 (ko) | 2003-07-23 | 2012-04-30 | 바이엘 파마슈티칼스 코포레이션 | 질환 및 상태의 치료 및 예방을 위한 플루오로 치환오메가-카르복시아릴 디페닐 우레아 |
ES2466818T3 (es) | 2003-09-26 | 2014-06-11 | Exelixis, Inc. | Moduladores c-Met y métodos de uso |
EP1680431A1 (fr) * | 2003-10-17 | 2006-07-19 | Rigel Pharmaceuticals, Inc. | Compositions de benzothiazole et de thiazole'5,5-b!pyridine et leur utilisation comme inhibiteurs de l'ubiquitine ligase |
JP2007512255A (ja) | 2003-11-13 | 2007-05-17 | アンビット バイオサイエンシス コーポレーション | キナーゼ調節因子としての尿素誘導体 |
MXPA06007667A (es) | 2004-01-06 | 2006-09-01 | Novo Nordisk As | Heteroaril-ureas y su uso como activadores de glucocinasa. |
EP1711495A2 (fr) * | 2004-01-23 | 2006-10-18 | Amgen Inc. | Quinolines, chinazolines, pyridines et pyrimidines et leur utilsation dans le traitement d'inflammation, angiogenèse et le cancer |
FR2868421B1 (fr) * | 2004-04-01 | 2008-08-01 | Aventis Pharma Sa | Nouveaux benzothiazoles et leur utilisation comme medicaments |
US7550499B2 (en) * | 2004-05-12 | 2009-06-23 | Bristol-Myers Squibb Company | Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
AU2005263592A1 (en) * | 2004-07-20 | 2006-01-26 | Siena Biotech S.P.A | Modulators of alpha7 nicotinic acetylcholine receptors and therapeutic uses thereof |
KR20070064660A (ko) | 2004-10-07 | 2007-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | Pi3 키나제 |
KR20070062998A (ko) * | 2004-10-13 | 2007-06-18 | 메르크 파텐트 게엠베하 | 키나제 억제제로서의 복소환 치환된 비스아릴우레아 유도체 |
MX2007007226A (es) * | 2004-12-17 | 2007-08-21 | Lilly Co Eli | Antagonistas receptores novedosos de hormona concentradora de melanina (mch). |
JP2008526728A (ja) * | 2004-12-30 | 2008-07-24 | ケマジス・リミテッド | ナトリウムトリアセトキシボロヒドリドを用いた還元による、プラミペキソール及びその光学異性体混合物の新規製造方法 |
WO2006071035A1 (fr) * | 2004-12-31 | 2006-07-06 | Lg Life Sciences, Ltd. | Nouveaux derives de ([1,3]thiazolo[5,4-b]pyridin-2-yl)-2-carboxamide |
EP1954696B1 (fr) * | 2005-01-19 | 2011-02-23 | Bristol-Myers Squibb Company | Dérivés 2-phénoxy-n-(1,3,4-thiadizol-2-yl)pyridin-3-amine et composés similaires en tant que inhibiteurs du récepteur p2y1 pour le traitement de maladies thromboemboliques |
TW200640443A (en) * | 2005-02-23 | 2006-12-01 | Alcon Inc | Methods for treating ocular angiogenesis, retinal edema, retinal ischemia, and diabetic retinopathy using selective RTK inhibitors |
GB0508471D0 (en) * | 2005-04-26 | 2005-06-01 | Celltech R&D Ltd | Therapeutic agents |
EP1896466B1 (fr) * | 2005-06-27 | 2011-04-13 | Bristol-Myers Squibb Company | Antagonistes heterocycliques a liaison n du recepteur p2y1, utiles pour traiter des etats pathologiques thrombotiques |
ES2352796T3 (es) | 2005-06-27 | 2011-02-23 | Bristol-Myers Squibb Company | Antagonistas cíclicos unidos a c del receptor p2y1 útiles en el tratamiento de afecciones trombóticas. |
WO2007002584A1 (fr) | 2005-06-27 | 2007-01-04 | Bristol-Myers Squibb Company | Mimetiques lineaires de l’uree antagonistes du recepteur p2y1, utilises dans le traitement des troubles thrombotiques |
US7714002B2 (en) * | 2005-06-27 | 2010-05-11 | Bristol-Myers Squibb Company | Carbocycle and heterocycle antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
CA2617788A1 (fr) * | 2005-08-04 | 2007-02-15 | Apogee Biotechnology Corporation | Inhibiteurs de la sphingosine kinase et leurs methodes d'utilisation |
FR2891273B1 (fr) * | 2005-09-27 | 2007-11-23 | Aventis Pharma Sa | NOUVEAUX DERIVES BENZIMIDAZOLES ET BENZOTHIAZOLES, LEUR PREPARATION ET LEUR UTILISATION PHARMACEUTIQUE NOTAMMENT COMME INHIBITEURS DE CMet |
PE20070978A1 (es) * | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
GB0606429D0 (en) * | 2006-03-30 | 2006-05-10 | Novartis Ag | Organic compounds |
US7517995B2 (en) | 2006-04-06 | 2009-04-14 | Boehringer Ingelheim International Gmbh | Thiazolyl-dihydro-cyclopentapyrazole |
JP2009532425A (ja) * | 2006-04-06 | 2009-09-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | チアゾリルジヒドロインダゾール |
US7691868B2 (en) * | 2006-04-06 | 2010-04-06 | Boehringer Ingelheim International Gmbh | Thiazolyl-dihydro-quinazoline |
US20070259855A1 (en) * | 2006-04-06 | 2007-11-08 | Udo Maier | Thiazolyl-dihydro-indazole |
EP2007774B1 (fr) | 2006-04-06 | 2012-07-25 | Boehringer Ingelheim International GmbH | Derives de thiazolyldihydroindazol utilises en tant qu'inhibiteurs de proteine kinase |
US20070238746A1 (en) * | 2006-04-06 | 2007-10-11 | Trixi Brandl | Thiazolyl-dihydro-chinazoline |
US20070238718A1 (en) * | 2006-04-06 | 2007-10-11 | Matthias Grauert | Thiazolyl-dihydro-indazole |
JP5334844B2 (ja) * | 2006-06-14 | 2013-11-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規化合物 |
GB0612428D0 (en) | 2006-06-22 | 2006-08-02 | Prolysis Ltd | Antibacterial agents |
US8481544B2 (en) | 2006-06-22 | 2013-07-09 | Biota Europe Limited | Antibacterial compositions |
ATE405554T1 (de) * | 2006-06-26 | 2008-09-15 | Helm Ag | Verfahren zur herstellung von pramipexole |
EP2045253A4 (fr) * | 2006-06-29 | 2013-01-23 | Nissan Chemical Ind Ltd | DÉRIVÉ D'ACIDE alpha-AMINÉ ET PRODUIT PHARMACEUTIQUE QUI LE COMPREND EN TANT QUE MATIÈRE ACTIVE |
US7960569B2 (en) * | 2006-10-17 | 2011-06-14 | Bristol-Myers Squibb Company | Indole antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
CL2008000119A1 (es) * | 2007-01-16 | 2008-05-16 | Wyeth Corp | Compuestos derivados de pirazol, antagonistas del receptor nicotinico de acetilcolina; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como demencia senil, alzheimer y esquizofrenia. |
ES2571533T3 (es) | 2007-04-27 | 2016-05-25 | Purdue Pharma Lp | Antagonistas de TRPV1 y usos de los mismos |
WO2008133973A1 (fr) | 2007-04-27 | 2008-11-06 | Purdue Pharma L.P. | Agents thérapeutiques utiles pour traiter la douleur |
WO2008150015A1 (fr) | 2007-06-05 | 2008-12-11 | Takeda Pharmaceutical Company Limited | Composés hétérobicycliques comme inhibiteurs de kinase |
CN101801966A (zh) * | 2007-07-18 | 2010-08-11 | 诺瓦提斯公司 | 双环杂芳基化合物和它们作为激酶抑制剂的用途 |
WO2009017822A2 (fr) * | 2007-08-02 | 2009-02-05 | Amgen Inc. | Modulateur de la pi3 kinase et leurs procédés d'utilisation |
WO2009025358A1 (fr) | 2007-08-23 | 2009-02-26 | Takeda Pharmaceutical Company Limited | Composé hétérocyclique et son utilisation |
FR2922550B1 (fr) | 2007-10-19 | 2009-11-27 | Sanofi Aventis | Nouveaux derives de 6-aryl/heteroalkyloxy benzothiazole et benzimidazole, application comme medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de cmet |
GB0724342D0 (en) * | 2007-12-13 | 2008-01-30 | Prolysis Ltd | Anitbacterial compositions |
PE20091268A1 (es) * | 2007-12-19 | 2009-09-19 | Amgen Inc | Derivados heterociclicos como inhibidores de pi3 quinasa |
WO2009111644A2 (fr) * | 2008-03-05 | 2009-09-11 | The Regents Of The University Of Michigan | Compositions et procédés pour diagnostiquer et traiter le cancer du pancréas |
WO2009133127A1 (fr) * | 2008-04-30 | 2009-11-05 | Merck Serono S.A. | Composés bicycliques fusionnés et utilisations de ceux-ci comme inhibiteurs de p13k |
US20110142839A1 (en) * | 2008-05-30 | 2011-06-16 | Vegenics Limited | Treatment of pulmonary edema |
JP2011525535A (ja) * | 2008-06-24 | 2011-09-22 | 武田薬品工業株式会社 | PI3K/mTOR阻害剤 |
FR2933981A1 (fr) * | 2008-07-18 | 2010-01-22 | Sanofi Aventis | NOUVEAUX DERIVES IMIDAZO°1,2-a!PYRIDINE, LEUR PROCEDE DE PREPARATION, LEUR APPLICATION A TITRE DE MEDICAMENTS, COMPOSITIONS PHARMACEUTIQUES ET NOUVELLE UTILISATION NOTAMMENT COMME INHIBITEURS DE MET |
FR2933980B1 (fr) * | 2008-07-18 | 2011-07-29 | Sanofi Aventis | Nouveaux derives triazolo°4,3-a!pyridine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de met |
FR2933982A1 (fr) * | 2008-07-18 | 2010-01-22 | Sanofi Aventis | Nouveaux derives imidazo°1,2-a!pyrimidine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de met |
PE20110572A1 (es) * | 2008-07-18 | 2011-08-25 | Sanofi Aventis | DERIVADOS DE IMIDAZO[1,2-a]PIRIDINA COMO INHIBIDORES DE MET |
FR2945806B1 (fr) * | 2009-05-19 | 2013-04-05 | Sanofi Aventis | Nouveaux derives imidazo[1,2-a]pyridine,procede de preparation,medicaments,compositions pharmaceutiques et utilisation notamment comme inhibiteurs de met |
US8703962B2 (en) * | 2008-10-24 | 2014-04-22 | Purdue Pharma L.P. | Monocyclic compounds and their use as TRPV1 ligands |
US8759362B2 (en) * | 2008-10-24 | 2014-06-24 | Purdue Pharma L.P. | Bicycloheteroaryl compounds and their use as TRPV1 ligands |
US8697874B2 (en) | 2008-12-01 | 2014-04-15 | Takeda Pharmaceutical Company Limited | Heterocyclic compound and use thereof |
JO3101B1 (ar) | 2008-12-02 | 2017-09-20 | Takeda Pharmaceuticals Co | مشتقات بنزوثيازول كعوامل مضادة للسرطان |
BRPI0918337A2 (pt) * | 2008-12-19 | 2017-05-30 | Abbott Lab | composto, composição farmacêutica, método de tratamento, método para tratar uma doença ou condição causada, exacerbada ou resultante de um excesso de plaquetas ou ativação indesejada de plaquetas em um paciente, método para reduzir a contagem de plaquetas circulantes em um paciente e uso |
NZ594594A (en) | 2009-01-16 | 2013-11-29 | Exelixis Inc | Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl]oxy} phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer |
UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
CN102985420B (zh) * | 2010-06-01 | 2017-07-04 | 安吉翁生物医药有限公司 | 细胞色素p450抑制剂及其用途 |
JP5876423B2 (ja) | 2010-06-22 | 2016-03-02 | 塩野義製薬株式会社 | Trpv1阻害活性を有する化合物とその使用 |
US9273043B2 (en) | 2011-06-22 | 2016-03-01 | Purdue Pharma L.P. | TRPV1 antagonists including dihydroxy substituent and uses thereof |
US9394293B2 (en) | 2011-08-10 | 2016-07-19 | Purdue Pharma L.P. | TRPV1 antagonists including dihydroxy substituent and uses thereof |
WO2013049407A2 (fr) * | 2011-09-30 | 2013-04-04 | Kineta, Inc | Composés anti-viraux |
CN103987711B (zh) | 2011-10-14 | 2016-08-24 | 艾伯维公司 | 作为用于治疗癌症和免疫性和自身免疫性疾病的凋亡诱导剂的8-氨基甲酰基-2-(2,3-二取代吡啶-6-基)-1,2,3,4-四氢异喹啉衍生物 |
US8940737B2 (en) | 2011-10-14 | 2015-01-27 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
MX368081B (es) * | 2011-10-14 | 2019-09-19 | Ambit Biosciences Corp | Compuestos heterociclicos y uso de los mismos como moduladores del receptor de tirosina cinasas tipo iii. |
US9725427B2 (en) | 2012-03-16 | 2017-08-08 | Biohaven Pharmaceutical Holding Company Limited | Prodrugs of riluzole and their method of use |
MA37975B2 (fr) * | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
US9073946B2 (en) * | 2013-01-15 | 2015-07-07 | Kineta, Inc. | Anti-viral compounds |
ES2489297B1 (es) * | 2013-01-22 | 2015-06-10 | Consejo Superior De Investigaciones Científicas (Csic) | Benzotiazoles sustituidos y sus aplicaciones terapeuticas para el tratamiento de enfermedades humanas |
GB201401886D0 (en) * | 2014-02-04 | 2014-03-19 | Lytix Biopharma As | Neurodegenerative therapies |
CN105175408B (zh) * | 2014-06-04 | 2018-07-17 | 中国人民解放军第二军医大学 | 苯并噻唑类化合物及其作为药物的用途 |
CN104402875A (zh) * | 2014-12-25 | 2015-03-11 | 西安山川医药科技有限公司 | N-(2-氨基乙基)-n′-(6-取代-2-苯并噻唑基)脲及其盐类化合物的合成方法和用途 |
CN106810536A (zh) | 2015-11-30 | 2017-06-09 | 甘李药业股份有限公司 | 一种蛋白激酶抑制剂及其制备方法和医药用途 |
CN107641118B (zh) * | 2016-07-22 | 2020-11-06 | 爱科诺生物医药股份有限公司 | 具有细胞坏死抑制活性的化合物及其组合物和应用 |
KR101838615B1 (ko) | 2016-09-30 | 2018-03-15 | 숙명여자대학교산학협력단 | 신규한 벤조옥사졸 또는 벤조티아졸 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 |
CN106632403B (zh) * | 2017-01-23 | 2018-09-11 | 牡丹江医学院 | 一种手术用止痛消炎药及其制备方法 |
WO2018224455A1 (fr) | 2017-06-07 | 2018-12-13 | Basf Se | Dérivés de cyclopropyle substitués |
EP3692023B1 (fr) | 2017-10-02 | 2023-05-17 | 1st Biotherapeutics, Inc. | Composés benzothiazol et méthodes d'utilisation de ceux-ci pour traiter des troubles neurodégénératifs |
JP7414282B2 (ja) * | 2017-12-07 | 2024-01-16 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | Nsdファミリー阻害物質及びそれによる治療の方法 |
WO2019217509A1 (fr) * | 2018-05-10 | 2019-11-14 | Hb Therapeutics Inc. | Compositions et méthodes pour le traitement du cancer |
AU2019287437A1 (en) | 2018-06-12 | 2020-09-10 | Vtv Therapeutics Llc | Therapeutic uses of glucokinase activators in combination with insulin or insulin analogs |
CN108690013A (zh) * | 2018-07-02 | 2018-10-23 | 秦继伟 | 苯并[d]噻唑衍生物及其作为EGFR抑制剂在癌症治疗中的应用 |
CN108912115A (zh) * | 2018-07-02 | 2018-11-30 | 秦继伟 | 一种用于治疗肺癌的egfr酪氨酸激酶抑制剂 |
CN108570044A (zh) * | 2018-07-02 | 2018-09-25 | 秦继伟 | 一种酰胺类化合物及其合成方法和治疗癌症的用途 |
CN108997309A (zh) * | 2018-07-17 | 2018-12-14 | 中国科学技术大学苏州研究院 | 一种吡唑-4-芳基衍生物的制备方法 |
CN113271941A (zh) * | 2018-10-17 | 2021-08-17 | 法国国家科学研究中心 | 用于治疗和/或预防癌症的脲衍生物 |
CA3131059A1 (fr) | 2019-02-22 | 2020-08-27 | 1ST Biotherapeutics, Inc. | Composes d'imidazopyridinyle et leur utilisation pour le traitement de troubles neurodegeneratifs |
KR20210122192A (ko) * | 2020-03-30 | 2021-10-08 | 주식회사 이노큐어테라퓨틱스 | 벤조티아졸 유도체 화합물 |
KR20230043024A (ko) | 2020-07-24 | 2023-03-30 | 젠자임 코포레이션 | 벤글루스타트를 포함하는 제약 조성물 |
CA3191617A1 (fr) * | 2020-09-18 | 2022-03-24 | Sumitomo Pharma Co., Ltd. | Derive d'amine |
WO2022059778A1 (fr) * | 2020-09-18 | 2022-03-24 | カルナバイオサイエンス株式会社 | Dérivé d'urée cyclique |
WO2023008472A1 (fr) * | 2021-07-28 | 2023-02-02 | カルナバイオサイエンス株式会社 | Nouveau dérivé de benzothiazole |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3810988A (en) * | 1968-11-01 | 1974-05-14 | Ciba Geigy Ag | Control of phytopathogenic fungi with n-benzothiazae-2-yl n-{40 {11 propylure |
CH505543A (de) * | 1968-11-01 | 1971-04-15 | Ciba Geigy Ag | Schädlingsbekämpfungsmittel |
JPS53124265A (en) * | 1977-04-06 | 1978-10-30 | Nippon Tokushu Noyaku Seizo Kk | Urea or thiourea type compounds, their preparation and insecticides contaning the same as active agent |
JPS57175189A (en) * | 1981-04-21 | 1982-10-28 | Kyowa Hakko Kogyo Co Ltd | Benzothiazole derivative and its preparation |
US4966849A (en) | 1985-09-20 | 1990-10-30 | President And Fellows Of Harvard College | CDNA and genes for human angiogenin (angiogenesis factor) and methods of expression |
JPS62187842A (ja) * | 1985-10-25 | 1987-08-17 | Konishiroku Photo Ind Co Ltd | ハロゲン化銀写真感光材料 |
US5217999A (en) | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
DK0526488T3 (da) | 1990-04-02 | 1995-04-24 | Pfizer | Benzylphosphonsyre-tyrosinkinaseinhibitorer |
US5302606A (en) | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
WO1992020642A1 (fr) | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Composes aryle et heteroaryle bis monocycliques et/ou bicycliques qui inhibent la tyrosine kinase d'un recepteur du egf et/ou du pdgf |
WO1992021660A1 (fr) | 1991-05-29 | 1992-12-10 | Pfizer, Inc. | Composes tricycliques polyhydroxyliques inhibiteurs de la tyrosine-kinase |
GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
EP0654024A1 (fr) | 1992-08-06 | 1995-05-24 | Warner-Lambert Company | 2-thioindoles (selenoindoles) et disulfures associes (seleniures) inhibant les tyrosine kinases et presentant des proprietes antitumorales |
US5330992A (en) | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
DE69233739D1 (de) | 1992-10-28 | 2008-08-07 | Genentech Inc | Verwendung von Antagonisten des Zellwachstumsfaktors VEGF |
GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
EP0888310B1 (fr) | 1996-03-15 | 2005-09-07 | AstraZeneca AB | Derives de cinnoline et leur emploi comme medicaments |
UA54427C2 (uk) | 1996-05-01 | 2003-03-17 | Елі Ліллі Енд Компані | Спосіб лікування очних захворювань, які пов'язані з фактором васкулярного ендотеліального росту |
BR9710706A (pt) | 1996-05-01 | 1999-08-17 | Lilly Co Eli | Tratamento terap-utico para doen-as relacionadas a vegf |
GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
TW513418B (en) | 1996-07-31 | 2002-12-11 | Otsuka Pharma Co Ltd | Thiazole derivatives, their production and use |
DK2107109T3 (da) | 1996-08-23 | 2012-09-24 | Vegenics Pty Ltd | Rekombinant vaskulær endotelcelle-vækstfaktor D (VEGF-D) |
US6093742A (en) * | 1997-06-27 | 2000-07-25 | Vertex Pharmaceuticals, Inc. | Inhibitors of p38 |
JPH11130761A (ja) * | 1997-10-24 | 1999-05-18 | Otsuka Pharmaceut Co Ltd | ベンゾチアゾール誘導体 |
IL135176A0 (en) * | 1997-11-10 | 2001-05-20 | Bristol Myers Squibb Co | Benzothiazole derivatives and pharmaceutical compositions containing the same |
JPH11222431A (ja) * | 1998-01-30 | 1999-08-17 | Otsuka Pharmaceut Co Ltd | 医薬組成物 |
AU6314900A (en) | 1999-07-26 | 2001-02-13 | Banyu Pharmaceutical Co., Ltd. | Biarylurea derivatives |
-
2001
- 2001-02-06 PL PL01357099A patent/PL357099A1/xx not_active Application Discontinuation
- 2001-02-06 EP EP01908878A patent/EP1254123A1/fr not_active Withdrawn
- 2001-02-06 CN CN01807734A patent/CN1422262A/zh active Pending
- 2001-02-06 HU HU0300359A patent/HUP0300359A2/hu unknown
- 2001-02-06 JP JP2001556858A patent/JP2003521543A/ja not_active Withdrawn
- 2001-02-06 IL IL15104501A patent/IL151045A0/xx unknown
- 2001-02-06 WO PCT/US2001/003803 patent/WO2001057008A1/fr not_active Application Discontinuation
- 2001-02-06 KR KR1020027010188A patent/KR20020084116A/ko not_active Application Discontinuation
- 2001-02-06 AU AU2001236698A patent/AU2001236698A1/en not_active Abandoned
- 2001-02-06 SK SK1271-2002A patent/SK12712002A3/sk unknown
- 2001-02-06 US US09/777,554 patent/US7091227B2/en not_active Expired - Lifetime
- 2001-02-06 BR BR0108085-7A patent/BR0108085A/pt not_active Application Discontinuation
- 2001-02-06 MX MXPA02007632A patent/MXPA02007632A/es unknown
- 2001-02-06 CA CA002398754A patent/CA2398754A1/fr not_active Abandoned
- 2001-02-07 AR ARP010100543A patent/AR030189A1/es unknown
-
2002
- 2002-08-05 ZA ZA200206235A patent/ZA200206235B/en unknown
- 2002-08-06 NO NO20023713A patent/NO20023713L/no not_active Application Discontinuation
- 2002-09-04 BG BG107062A patent/BG107062A/bg unknown
Also Published As
Publication number | Publication date |
---|---|
US7091227B2 (en) | 2006-08-15 |
NO20023713D0 (no) | 2002-08-06 |
CN1422262A (zh) | 2003-06-04 |
KR20020084116A (ko) | 2002-11-04 |
HUP0300359A2 (hu) | 2003-06-28 |
JP2003521543A (ja) | 2003-07-15 |
US20030153568A1 (en) | 2003-08-14 |
BR0108085A (pt) | 2003-03-18 |
BG107062A (bg) | 2003-04-30 |
MXPA02007632A (es) | 2004-08-23 |
AU2001236698A1 (en) | 2001-08-14 |
CA2398754A1 (fr) | 2001-08-09 |
EP1254123A1 (fr) | 2002-11-06 |
ZA200206235B (en) | 2004-02-13 |
SK12712002A3 (sk) | 2003-02-04 |
IL151045A0 (en) | 2003-04-10 |
PL357099A1 (en) | 2004-07-12 |
AR030189A1 (es) | 2003-08-13 |
WO2001057008A1 (fr) | 2001-08-09 |
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