公开(公告)号：US20050090499A1

公开(公告)日：2005-04-28

申请号：US10861791

申请日：2004-06-04

申请人： Kevin Currie ,  Robert DeSimone ,  Scott Mitchell ,  Douglas Pippin ,  James Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

发明人： Kevin Currie ,  Robert DeSimone ,  Scott Mitchell ,  Douglas Pippin ,  James Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

IPC分类号： A61K31/498 ,  A61P37/02 ,  C07D487/04 ,  C07D519/00

CPC分类号： C07D487/04

摘要： Compounds of Formula I-a and all pharmaceutically-acceptable forms thereof, are described herein. The variables R1, R2, R3, Z1, Q, and A shown in Formula I-a are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I-a, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I-a effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I-a as a single active agent or administering a compound of Formula I-a in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I-a under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

摘要翻译： 本文描述式I-a化合物及其所有药学上可接受的形式。 式Ia中所示的变量R 1，R 2，R 3，Z 1，Q和A 在本文中定义。 本文提供了含有一种或多种式I-a化合物或这些化合物的药学上可接受的形式的药物组合物和一种或多种药学上可接受的载体，赋形剂或稀释剂。 还给出了治疗患有某些对抑制酪氨酸激酶活性有响应的疾病的患者的方法。 在某些实施方案中，疾病对Btk活性和/或B细胞增殖的抑制有反应。 这样的方法包括向这样的患者施用一定量的有效减少疾病体征或症状的式I-a化合物。 这些疾病包括癌症，自身免疫和/或炎性疾病或急性炎症反应。 因此，治疗方法包括施用足够量的本文提供的化合物或盐以减少症状或减缓这些疾病的进展。 其他实施方案包括治疗其它动物，包括患有对抑制激酶活性有响应的疾病的家畜和驯养的伴侣动物的方法。 治疗方法包括施用式I-a化合物作为单一活性剂或给予式I-a的化合物与一种或多种其它治疗剂的组合。 一种用于确定样品中Btk的存在的方法，包括在允许检测Btk活性，检测样品中Btk活性水平的条件下使样品与式Ia化合物或其形式接触的方法， 样品中没有Btk。

公开(公告)号：US20060183746A1

公开(公告)日：2006-08-17

申请号：US11292300

申请日：2005-12-02

申请人： Kevin Currie ,  Robert Desimone ,  Scott Mitchell ,  Douglas Pippin ,  James Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

发明人： Kevin Currie ,  Robert Desimone ,  Scott Mitchell ,  Douglas Pippin ,  James Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

IPC分类号： A61K31/498 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D519/00

摘要： Certain compounds, such as at least one chemical entity choen from compounds of Formula 1 and pharmaceutically acceptable salts, solvates, crystal forms, chelates, non-covalent complexes, prodrugs, and mixtures thereof, may in certain embodiments be used to treat patients suffering from one or more diseases responsive to inhibition of tyrosine kinase activity. The diseases may, for instance, be responsive to inhibition of Btk activity and/or B-cell proliferation. Example diseases include cancer, an autoimmune and/or inflammatory disease, and an acute inflammatory reaction.

摘要翻译： 在某些实施方案中，某些化合物，例如从式1的化合物和其药学上可接受的盐，溶剂合物，结晶形式，螯合物，非共价复合物，前药及其混合物中选择的至少一种化学实体可用于治疗患有 响应抑制酪氨酸激酶活性的一种或多种疾病。 疾病可以例如对Btk活性和/或B细胞增殖的抑制作出反应。 示例性疾病包括癌症，自身免疫和/或炎性疾病和急性炎症反应。

公开(公告)号：US20110177011A1

公开(公告)日：2011-07-21

申请号：US12018573

申请日：2008-01-23

申请人： Kevin S. Currie ,  Robert W. DeSimone ,  Scott A. Mitchell ,  Douglas A. Pippin ,  James W. Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

发明人： Kevin S. Currie ,  Robert W. DeSimone ,  Scott A. Mitchell ,  Douglas A. Pippin ,  James W. Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

IPC分类号： A61K31/551 ,  A61K31/4985 ,  A61K31/5355 ,  A61K9/12 ,  A61P29/00 ,  A61P35/00

CPC分类号： C07D487/04

摘要： Compounds of Formula I-a and all pharmaceutically-acceptable forms thereof, are described herein.The variables R1, R2, R3, Z1, Q, and A shown in Formula I-a are defined herein.Pharmaceutical compositions containing one or more compounds of Formula I-a, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein.Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I-a effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases.Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity.Methods of treatment include administering a compound of Formula I-a as a single active agent or administering a compound of Formula I-a in combination with one or more other therapeutic agent.A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I-a under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

摘要翻译： 本文描述式I-a化合物及其所有药学上可接受的形式。 式I-a中所示的变量R1，R2，R3，Z1，Q和A在本文中定义。 本文提供了含有一种或多种式I-a化合物或这些化合物的药学上可接受的形式的药物组合物和一种或多种药学上可接受的载体，赋形剂或稀释剂。 还给出了治疗患有某些对抑制酪氨酸激酶活性有响应的疾病的患者的方法。 在某些实施方案中，疾病对Btk活性和/或B细胞增殖的抑制有反应。 这样的方法包括向这样的患者施用一定量的有效减少疾病体征或症状的式I-a化合物。 这些疾病包括癌症，自身免疫和/或炎性疾病或急性炎症反应。 因此，治疗方法包括施用足够量的本文提供的化合物或盐以减少症状或减缓这些疾病的进展。 其他实施方案包括治疗其它动物，包括患有对抑制激酶活性有响应的疾病的家畜和驯养的伴侣动物的方法。 治疗方法包括施用式I-a化合物作为单一活性剂或给予式I-a的化合物与一种或多种其它治疗剂的组合。 一种用于确定样品中Btk的存在的方法，包括在允许检测Btk活性，检测样品中Btk活性水平的条件下使样品与式Ia化合物或其形式接触的方法， 样品中没有Btk。

公开(公告)号：US07405295B2

公开(公告)日：2008-07-29

申请号：US10861791

申请日：2004-06-04

申请人： Kevin S. Currie ,  Robert W. DeSimone ,  Scott A. Mitchell ,  Douglas A. Pippin ,  James W. Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

发明人： Kevin S. Currie ,  Robert W. DeSimone ,  Scott A. Mitchell ,  Douglas A. Pippin ,  James W. Darrow ,  Xiaobing Qian ,  Mark Velleca ,  Dapeng Qian

IPC分类号： C07D417/00 ,  C07D413/00 ,  C07D471/00 ,  C07D487/00 ,  C07D491/00 ,  C07D497/00

CPC分类号： C07D487/04

摘要： Compounds of Formula I-a and all pharmaceutically-acceptable forms thereof, are described herein. The variables R1, R2, R3, Z1, Q, and A shown in Formula I-a are defined herein.Pharmaceutical compositions containing one or more compounds of Formula I-a, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein.Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I-a effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases.

摘要翻译： 本文描述式I-a化合物及其所有药学上可接受的形式。 式Ia中所示的变量R 1，R 2，R 3，Z 1，Q和A 在本文中定义。 本文提供了含有一种或多种式I-a化合物或这些化合物的药学上可接受的形式的药物组合物和一种或多种药学上可接受的载体，赋形剂或稀释剂。 还给出了治疗患有某些对抑制酪氨酸激酶活性有响应的疾病的患者的方法。 在某些实施方案中，疾病对Btk活性和/或B细胞增殖的抑制有反应。 这样的方法包括向这样的患者施用一定量的有效减少疾病体征或症状的式I-a化合物。 这些疾病包括癌症，自身免疫和/或炎性疾病或急性炎症反应。 因此，治疗方法包括施用足够量的本文提供的化合物或盐以减少症状或减缓这些疾病的进展。