公开(公告)号：US20050176753A1

公开(公告)日：2005-08-11

申请号：US10512927

申请日：2003-04-28

申请人： Mark Bilodeau ,  Mark Fraley ,  Zhicai Wu

发明人： Mark Bilodeau ,  Mark Fraley ,  Zhicai Wu

IPC分类号： A61K31/09 ,  A61K31/4196 ,  A61K31/437 ,  A61K31/444 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/551 ,  A61K31/575 ,  A61K31/737 ,  A61K38/00 ,  A61K38/21 ,  A61P17/00 ,  A61P19/00 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  C07D471/04

CPC分类号： C07D471/04

摘要： The present invention relates to imidazopyridine compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

摘要翻译： 本发明涉及抑制，调节和/或调节酪氨酸激酶信号转导的咪唑并吡啶化合物，含有这些化合物的组合物，及其用于治疗酪氨酸激酶依赖性疾病和病症如血管生成，癌症，肿瘤生长， 动脉粥样硬化，年龄相关性黄斑变性，糖尿病性视网膜病变，炎症性疾病等。

公开(公告)号：US20050096344A1

公开(公告)日：2005-05-05

申请号：US10900662

申请日：2004-07-28

申请人： Mark Fraley ,  Kenneth Arrington ,  Mark Bilodeau ,  George Hartman ,  William Hoffman ,  Yuntae Kim ,  Randall Hungate

发明人： Mark Fraley ,  Kenneth Arrington ,  Mark Bilodeau ,  George Hartman ,  William Hoffman ,  Yuntae Kim ,  Randall Hungate

IPC分类号： A61K31/495 ,  A61K45/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/02 ,  A61K31/4745 ,  C07D491/02 ,  C07D498/02

CPC分类号： C07D401/14 ,  A61K31/495 ,  A61K45/06 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  A61K2300/00

摘要： The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

公开(公告)号：US20060134767A1

公开(公告)日：2006-06-22

申请号：US10520492

申请日：2003-07-03

申请人： Carolyn Buser-Doepner ,  Paul Coleman ,  Christopher Cox ,  Mark Fraley ,  Robert Garbaccio ,  George Hartman ,  David Heimbrook ,  Lawrence Kuo ,  Hans Huber ,  Vinod Sardana ,  Maricel Torrent ,  Youwei Yan

发明人： Carolyn Buser-Doepner ,  Paul Coleman ,  Christopher Cox ,  Mark Fraley ,  Robert Garbaccio ,  George Hartman ,  David Heimbrook ,  Lawrence Kuo ,  Hans Huber ,  Vinod Sardana ,  Maricel Torrent ,  Youwei Yan

IPC分类号： C12N9/12 ,  G06F19/00

CPC分类号： C07K14/47 ,  C07K2299/00 ,  C12N9/14 ,  G01N33/6803 ,  G01N2500/04 ,  G16B15/00 ,  G16B20/00

摘要： The present invention is directed to the identification, characterization and three-dimensional structure of a novel ligand binding site of KSP. Binding of ligands to the novel binding site result in a conformational change in the three-dimensional structure of the protein and a modulation of the activity of KSP. This conformational change in turn results in the formation of a novel binding pocket in the KSP protein, which comprises the novel binding site of the instant invention.

摘要翻译： 本发明涉及KSP新型配体结合位点的鉴定，表征和三维结构。 配体与新结合位点的结合导致蛋白质三维结构的构象变化和KSP活性的调节。 这种构象变化又导致在KSP蛋白质中形成新的结合口袋，其包含本发明的新结合位点。

公开(公告)号：US20050171122A1

公开(公告)日：2005-08-04

申请号：US10497414

申请日：2002-12-02

申请人： Mark Fraley ,  George Hartman ,  William Hoffman

发明人： Mark Fraley ,  George Hartman ,  William Hoffman

IPC分类号： A61K31/519 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/00 ,  A61P1/04 ,  A61P9/00 ,  A61P13/08 ,  A61P13/10 ,  A61P15/00 ,  A61P17/02 ,  A61P17/06 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P37/02 ,  A61P37/06 ,  A61P43/00 ,  C07D487/02 ,  C07D498/02 ,  C07D513/04 ,  C07D519/00

CPC分类号： C07D513/04

摘要： The present invention relates to azolopyrimidinone compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

公开(公告)号：US20100292241A1

公开(公告)日：2010-11-18

申请号：US12863636

申请日：2009-01-14

申请人： Edward Brnardic ,  Mark Fraley ,  Mark Layton ,  Robert Garbaccio

发明人： Edward Brnardic ,  Mark Fraley ,  Mark Layton ,  Robert Garbaccio

IPC分类号： A61K31/4985 ,  A61K31/5025 ,  A61K31/519 ,  A61K31/517 ,  A61K31/4365 ,  A61K31/437 ,  A61K31/4725 ,  A61K31/4709 ,  A61K31/4439 ,  A61K31/428 ,  A61K31/425 ,  A61K31/421 ,  C07D487/04 ,  C07D471/04 ,  C07D495/04 ,  C07D215/38 ,  C07D413/14 ,  C07D413/10 ,  C07D263/04 ,  A61P25/18

CPC分类号： C07D495/04 ,  C07D263/22 ,  C07D263/24 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D471/04 ,  C07D487/04

摘要： The present invention is directed to 3,5-disubstituted-1,3-oxazolidin-2-one derivatives which are potentiators of metabotropic glutamate receptors, including the mGluR2 receptor, and which are useful in the treatment or prevention of neuro-ological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

摘要翻译： 本发明涉及作为代谢型谷氨酸受体的增强剂（包括mGluR2受体）的3,5-二取代-1,3-恶唑烷-2-酮衍生物，其可用于治疗或预防神经和精神病学 与谷氨酸功能障碍相关的疾病和涉及代谢型谷氨酸受体的疾病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及代谢型谷氨酸受体的疾病中的用途。

公开(公告)号：US20080004259A1

公开(公告)日：2008-01-03

申请号：US11795189

申请日：2006-02-03

申请人： Kenneth Arrington ,  Mark Fraley ,  Robert Garbaccio ,  Shaei Huang ,  Craig Lindsley ,  Justin Steen ,  Feng Yang

发明人： Kenneth Arrington ,  Mark Fraley ,  Robert Garbaccio ,  Shaei Huang ,  Craig Lindsley ,  Justin Steen ,  Feng Yang

IPC分类号： A61K31/416 ,  A61K31/41 ,  A61K31/4192 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/551 ,  A61P35/00 ,  C07D211/12 ,  C07D231/56 ,  C07D243/08 ,  C07D249/04 ,  C07D257/04 ,  C07D403/14 ,  C07D413/14

CPC分类号： C07D403/04 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/10

摘要： The instant invention provides for compounds which comprise substituted indolyl indazoles that inhibit CHK1 activity. The instant compounds provide a novel mechanism of action with unexpected advantageous properties; such unexpected advantageous properties may include increased cellular potency/solubility, greater selectivity, enhanced pharmacokinetic properties, lack of off target activity and so on. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound to a patient in need of treatment of cancer.

摘要翻译： 本发明提供了包含抑制CHK1活性的取代的吲哚吲嗪的化合物。 本发明化合物提供具有意想不到的有利性质的新颖作用机理; 这种意想不到的有利性质可以包括增加的细胞效能/溶解度，更大的选择性，增强的药代动力学性质，缺乏目标活性等。 本发明还提供了包含这种抑制化合物的组合物和通过将该化合物给予需要治疗癌症的患者来抑制CHK1活性的方法。

公开(公告)号：US20070129356A1

公开(公告)日：2007-06-07

申请号：US10582826

申请日：2004-12-15

申请人： Kenneth Arrington ,  Mark Fraley ,  George Hartman

发明人： Kenneth Arrington ,  Mark Fraley ,  George Hartman

IPC分类号： A61K31/541 ,  A61K31/5377 ,  A61K31/513 ,  C07D239/36

CPC分类号： C07D239/36

摘要： The present invention relates to 2-phenylpyrimidinone compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

摘要翻译： 本发明涉及可用于治疗细胞增殖性疾病，用于治疗与KSP驱动蛋白活性相关的病症和用于抑制KSP驱动蛋白的2-苯基嘧啶酮化合物。 本发明还涉及包含这些化合物的组合物，以及使用它们治疗哺乳动物癌症的方法。

公开(公告)号：US20060063942A1

公开(公告)日：2006-03-23

申请号：US10517576

申请日：2003-06-12

申请人： Kenneth Arrington ,  Mark Fraley

发明人： Kenneth Arrington ,  Mark Fraley

IPC分类号： C07D403/02 ,  C07D207/00

CPC分类号： C07D207/27 ,  C07D207/20

摘要： The present invention relates to dihydropyrazole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

公开(公告)号：US20050032817A1

公开(公告)日：2005-02-10

申请号：US10497382

申请日：2002-12-02

申请人： Mark Fraley ,  George Hartman

发明人： Mark Fraley ,  George Hartman

IPC分类号： A61K31/138 ,  A61K31/4465 ,  A61K31/4535 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K31/5517 ,  A61K39/395 ,  A61K45/00 ,  A61P35/00 ,  C07D491/04 ,  C07D491/048 ,  C07D519/00 ,  C07D491/02

CPC分类号： C07D491/04

摘要： The present invention relates to furanopyrimidinone compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

摘要翻译： 本发明涉及可用于治疗细胞增殖性疾病，治疗与KSP驱动蛋白活性相关的疾病和用于抑制KSP驱动蛋白的呋喃并嘧啶酮化合物。 本发明还涉及包含这些化合物的组合物，以及使用它们治疗哺乳动物癌症的方法。

公开(公告)号：US20080032980A1

公开(公告)日：2008-02-07

申请号：US11630302

申请日：2005-06-27

申请人： Mark Fraley ,  George Hartman

发明人： Mark Fraley ,  George Hartman

IPC分类号： A61K31/496 ,  A61K31/4155 ,  A61K31/5377 ,  C07D401/06 ,  C07D413/06 ,  C07D403/06 ,  A61P35/00 ,  A61K31/454

CPC分类号： C07D231/06 ,  C07D487/08

摘要： The present invention relates to dihydropyrazole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.