首页> 外国专利> CERTAIN HETEROCYCLIC SUBSTITUTED IMIDAZO1,2-APYRAZIN-8-YLAMINES AND METHODS OF INHIBITION OF BRUTON’S TYROSINE KINASE BY SUCH COMPOUNDS

CERTAIN HETEROCYCLIC SUBSTITUTED IMIDAZO1,2-APYRAZIN-8-YLAMINES AND METHODS OF INHIBITION OF BRUTON’S TYROSINE KINASE BY SUCH COMPOUNDS

机译:某些杂环取代的咪唑并[1,2-A]吡嗪-8-酰胺类化合物及通过此类化合物抑制巴豆酪氨酸激酶的方法

摘要

Compounds of formula (I) and all pharmaceutically acceptable forms thereof, are described herein. The variables R1, R2, R3, Z2, and Q, shown in Formula I are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I, 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 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 as a single active agent or administering a compound of Formula I 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 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.
机译:本文描述了式(I)的化合物及其所有药学上可接受的形式。式I中所示的变量R1,R2,R3,Z2和Q在本文中定义。本文提供了包含一种或多种式I的化合物或这种化合物的可药用形式以及一种或多种可药用的载体,赋形剂或稀释剂的药物组合物。还提供了治疗患有对酪氨酸激酶活性抑制有反应的某些疾病的患者的方法。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。此类方法包括向此类患者施用有效减轻疾病迹象或症状的量的式I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性反应。因此,治疗方法包括给予足够量的本文提供的化合物或盐以减轻症状或减慢这些疾病的进展。其他实施方案包括治疗其他动物的方法,所述其他动物包括家畜和家养伴侣动物,其患有对激酶活性的抑制有响应的疾病。治疗方法包括给予式I化合物作为单一活性剂或与一种或多种其他治疗剂组合给予式I化合物。一种确定样品中Btk存在的方法,包括在允许检测Btk活性的条件下,使样品与式I化合物或其形式接触,检测样品中Btk活性的水平,然后确定存在或不存在。样本中没有Btk。

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