利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

32 条记录 (耗时 0.049 秒)

    Bisfluoroalkyl-1,4-benzodiazepinone compounds
    2.
    发明授权
    Bisfluoroalkyl-1,4-benzodiazepinone compounds 有权
    双氟烷基-1,4-苯并二氮杂酮化合物

    公开(公告)号：US08629136B2

    公开(公告)日：2014-01-14

    申请号：US13426730

    申请日：2012-03-22

    申请人： Ashvinikumar V. Gavai ,  Claude A. Quesnelle ,  Soong-Hoon Kim ,  Francis Y. Lee

    发明人： Ashvinikumar V. Gavai ,  Claude A. Quesnelle ,  Soong-Hoon Kim ,  Francis Y. Lee

    IPC分类号： C07D243/24 ,  A61K31/5513 ,  A61P35/00

    CPC分类号： C07D243/24 ,  A61K31/138 ,  A61K31/337 ,  A61K31/5513 ,  A61K31/555 ,  A61K31/573 ,  A61K45/06 ,  A61K2300/00

    摘要： Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R1 is —CH2CF3 or —CH2CH2CF3; R2 is —CH2CF3, —CH2CH2CF3, or —CH2CH2CH2CF3; R3 is H or —CH3; each Ra is independently F, Cl, —CN, —OCH3, and/or —NHCH2CH2OCH3; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

    摘要翻译： 公开了式（I）的化合物或其前药; 其中：R1是-CH2CF3或-CH2CH2CF3; R2是-CH2CF3，-CH2CH2CF3或-CH2CH2CH2CF3; R3是H或-CH3; 每个R a独立地是F，Cl，-CN，-OCH 3和/或-NHCH 2 CH 2 OCH 3; 并且z为零，1或2.还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓各种治疗领域（例如癌症）中疾病或病症的发展。

    Method of treating chronic myelogenous leukemia cells
    4.
    发明授权
    Method of treating chronic myelogenous leukemia cells 有权
    治疗慢性骨髓性白血病细胞的方法

    公开(公告)号：US07799788B2

    公开(公告)日：2010-09-21

    申请号：US12364009

    申请日：2009-02-02

    申请人： Kapil N. Bhalla ,  Francis Y. Lee

    发明人： Kapil N. Bhalla ,  Francis Y. Lee

    IPC分类号： A61K31/497

    CPC分类号： A61K31/4745 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

    摘要： Here, the inventors disclose the treatment of imatinib mesylate resistant chronic myelogenous leukemia cells with a cotreatment of vorinostat (SAHA, suberoylanilide hydroxamic acid) and dasatinib, a dual Abl/Src kinase (TK) inhibitor. Combined treatment of cultured human CML and BaF3 cells with vorinostat and dasatinib induced more apoptosis than either agent alone, as well as synergistically induced loss of clonogenic survival, which was associated with greater depletion of Bcr-Abl, p-CrkL and p-STAT5 levels. Co-treatment with dasatinib and vorinostat also attenuated the levels of Bcr-AblE255K and Bcr-AblT315I and induced apoptosis of BaF3 cells with ectopic expression of the mutant forms of Bcr-Abl. Finally, co-treatment of the primary CML cells with vorinostat and dasatinib induced more loss of cell viability and depleted Bcr-Abl or Bcr-AblT315I, p-STAT5 and p-CrkL levels than either agent alone.

    摘要翻译： 在这里，发明人公开了通过联合维生素（SAHA，辛二酰苯胺异羟肟酸）和达沙替尼（双重Abl / Src激酶（TK））抑制剂的治疗来治疗甲磺酸伊马替尼耐药性慢性骨髓性白血病细胞。 培养的人CML和BaF3细胞与伏立诺他和达沙替尼的联合治疗诱导出比单独的任一种更多的凋亡，以及协同诱导的克隆形成存活的损失，其与Bcr-Abl，p-CrkL和p-STAT5水平的更大的消耗相关 。 与dasatinib和伏立诺他治的联合治疗也减弱了Bcr-AblE255K和Bcr-AblT315I的水平，并诱导了Bcr-Abl突变形式异位表达BaF3细胞凋亡。 最后，原代CML细胞与伏立诺他和达沙替尼的共同治疗比单独使用任一试剂诱导更多的细胞活力丧失和消耗Bcr-Abl或Bcr-AblT315I，p-STAT5和p-CrkL水平。

    Methods of Identifying and Treating Individuals Exhibiting Complex Karyotypes
    6.
    发明申请
    Methods of Identifying and Treating Individuals Exhibiting Complex Karyotypes 审中-公开
    识别和处理复杂核型的个体的方法

    公开(公告)号：US20090197893A1

    公开(公告)日：2009-08-06

    申请号：US12085733

    申请日：2006-11-30

    申请人： Francis Y. Lee ,  Charles L. Sawyers ,  Neil P. Shah

    发明人： Francis Y. Lee ,  Charles L. Sawyers ,  Neil P. Shah

    IPC分类号： A61K31/496 ,  C12Q1/68 ,  A61P35/00 ,  A61P35/02

    CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156

    摘要： The invention described herein relates to diagnostic and therapeutic methods and compositions useful in the management of disorders, for example cancers, involving cells that harbor complex karyotypes. The present invention also related to mutant BCR-ABL kinase proteins, and to diagnostic and therapeutic methods and compositions useful in the management of disorders, for example cancers, involving cells that express such mutant BCR-ABL kinase proteins.

    摘要翻译： 本文描述的发明涉及可用于治疗病症（例如涉及携带复杂核型的细胞的癌症）的诊断和治疗方法和组合物。 本发明还涉及突变体BCR-ABL激酶蛋白，以及可用于治疗病症（例如涉及表达这种突变型BCR-ABL激酶蛋白的细胞）的癌症的诊断和治疗方法和组合物。

    Methods of using EPHA2 for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells
    7.
    发明授权
    Methods of using EPHA2 for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells 有权
    使用EPHA2预测与乳腺细胞相互作用和/或调节蛋白酪氨酸激酶和/或蛋白酪氨酸激酶途径的化合物的活性的方法

    公开(公告)号：US07504211B2

    公开(公告)日：2009-03-17

    申请号：US10648593

    申请日：2003-08-26

    申请人： Fei Huang ,  Xia Han ,  Karen A. Reeves ,  Lukas C. Amler ,  Craig R. Fairchild ,  Francis Y. Lee ,  Peter Shaw

    发明人： Fei Huang ,  Xia Han ,  Karen A. Reeves ,  Lukas C. Amler ,  Craig R. Fairchild ,  Francis Y. Lee ,  Peter Shaw

    IPC分类号： C12Q1/00 ,  C12Q1/68

    CPC分类号： C07K14/47 ,  A61K38/00 ,  C12Q1/6837 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/158

    摘要： The present invention describes polynucleotides that have been discovered to correlate to the relative sensitivity or resistance of cells, e.g., breast cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit, protein tyrosine kinases, such as, for example, members of the Src family of tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other protein tyrosine kinases, including, Bcr-abl, Jak, PDGFR, c-kit and Eph receptors. These polynucleotides have been shown to have utility in predicting the resistance and sensitivity of breast cell lines to the compounds. Such polynucleotides comprise polynucleotide predictor or marker sets useful in methods of predicting drug response, and as prognostic or diagnostic indicators in disease management, particularly in those disease areas, e.g., breast cancer, in which signaling through one or more of the aforementioned Src tyrosine and protein tyrosine kinases is involved with the disease process.

    摘要翻译： 本发明描述了已被发现与将细胞例如乳腺细胞系的相对敏感性或抗性相关的多核苷酸与用蛋白酪氨酸激酶相互作用并调节，例如抑制蛋白酪氨酸激酶的化合物的治疗， 酪氨酸激酶Src家族成员，如Src，Fgr，Fyn，Yes，Blk，Hck，Lck和Lyn，以及其他蛋白酪氨酸激酶，包括Bcr-abl，Jak，PDGFR，c-kit和Eph 受体。 已经显示这些多核苷酸可用于预测乳腺细胞系对化合物的抗性和敏感性。 这样的多核苷酸包括可用于预测药物反应的方法的多核苷酸预测物或标志物组，以及疾病管理中的预后或诊断指标，特别是在那些疾病领域，例如乳腺癌中，其中通过一种或多种上述Src酪氨酸和 蛋白酪氨酸激酶参与疾病过程。

    Aziridinyl-epothilone compounds
    9.
    发明授权
    Aziridinyl-epothilone compounds 有权
    氮丙啶基 - 埃坡霉素化合物

    公开(公告)号：US07872145B2

    公开(公告)日：2011-01-18

    申请号：US11753785

    申请日：2007-05-25

    申请人： Gregory D. Vite ,  Francis Y. Lee ,  Christopher P. Leamon ,  Iontcho R. Vlahov

    发明人： Gregory D. Vite ,  Francis Y. Lee ,  Christopher P. Leamon ,  Iontcho R. Vlahov

    IPC分类号： C07D277/22 ,  C07D203/26

    CPC分类号： C07D491/04 ,  A61K47/551 ,  A61K47/65

    摘要： The present invention is directed to aziridinyl epothilone compounds as further described herein, and/or pharmaceutically-acceptable salts and/or solvates thereof having the following Formula: wherein K is —O—, —S—, or —NR7—; A is —(CR8R9)—(CH2)m—Z—wherein Z is —(CHR10)—, —C(═O)—, —C(═O)—C(═O)—, —OC(═O)—, —N(R11)C(═O)—, —SO2—, or —N(R11)SO2—; B1 is hydroxyl or cyano and R1 is hydrogen or B1 and R1 are taken together to form a double bond; R2, R3, and R5 are, independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; or R2 and R3 may be taken together with the carbon to which they are attached to form an optionally substituted cycloalkyl; R4 is hydrogen, alkyl, alkenyl, substituted alkyl, substituted alkenyl, aryl, or substituted aryl; R6 is hydrogen, alkyl or substituted alkyl; R7, R8, R9, R10, R11 and R12 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, or substituted heteroaryl; and R13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.

    摘要翻译： 本发明涉及如本文进一步描述的氮杂环丙烷基埃坡霉素化合物和/或其药学上可接受的盐和/或溶剂合物，其具有下式：其中K是-O - ， - S-或-NR 7 - ; A是 - （CR 8 R 9） - （CH 2）m-Z-，其中Z是 - （CHR 10） - ， - C（= O） - ， - C（= O）-C（= O） - ， - OC ） - ， - N（R 11）C（= O） - ， - SO 2 - 或-N（R 11）SO 2 - ; B1是羟基或氰基，R1是氢或B1和R1一起形成双键; R2，R3和R5独立地是氢，烷基，取代的烷基，芳基或取代的芳基; 或者R 2和R 3可以与它们所连接的碳一起形成任选取代的环烷基; R4是氢，烷基，烯基，取代的烷基，取代的烯基，芳基或取代的芳基; R6是氢，烷基或取代的烷基; R7，R8，R9，R10，R11和R12独立地是氢，烷基，取代的烷基，环烷基，取代的环烷基，芳基，取代的芳基，杂环烷基，取代的杂环烷基，杂芳基或取代的杂芳基; 并且R 13是芳基，取代的芳基，杂芳基或取代的杂芳基。