[4-(6-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone | 886854-84-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: [4-(6-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone
• 英文别名: (4-((6-bromoimidazo [1, 2-a] pyrazin-8-yl)amino)phenyl)(morpholino)methanone；[4-[(6-bromoimidazo[1,2-a]pyrazin-8-yl)amino]phenyl]-morpholin-4-ylmethanone
• CAS: 886854-84-8
• 化学式: C₁₇H₁₆BrN₅O₂
• 分子量: 402.25
• InChiKey: JAASGQCWDWDBRY-UHFFFAOYSA-N

物化性质

• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(6-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone 在 四(三苯基膦)钯 lithium aluminium tetrahydride 、 sodium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 异丁酰胺 为溶剂， 反应 34.58h， 生成 6-tert-butyl-N-{2-methyl-3-[8-(4-morpholin-4-ylmethyl-phenylamino)-imidazo[1,2-a]pyrazin-6-yl]-phenyl}-nicotinamide
  参考文献：
  名称：

  WO2008/33858

  摘要：

  公开号：
• 作为产物：
  描述：

  吗啉(4-硝基苯基)甲酮 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 [4-(6-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone
  参考文献：
  名称：

  [EN] N-SUBSTITUTED HETEROCYCLIC DERIVATIVES AS KINASE INHIBITORS
  [FR] DÉRIVÉS HÉTÉROCYCLIQUES N-SUBSTITUÉS À TITRE D'INHIBITEURS DE KINASES

  摘要：

  本发明提供了式（I）的N-取代新异环衍生物作为蛋白激酶抑制剂，其中R1、R2和'n'的含义与规范中给出的含义相同，并且其药学上可接受的盐在治疗和预防疾病或紊乱方面具有用处，特别是它们在抑制激酶酶有优势的疾病或紊乱中的用途，更特别是BTK酶。本发明还提供了合成和给予激酶抑制剂化合物的方法。本发明还提供了包含至少一种激酶抑制剂化合物的药物配方，以及药学上可接受的载体、稀释剂或赋形剂。

  公开号：

  WO2014125410A1

文献信息

• Inhibitors of bruton's tyrosine kinase
  申请人：Kondru Rama K.

  公开号：US20100016302A1

  公开（公告）日：2010-01-21

  This application discloses 6-Phenyl-imidazo[1,2-a]pyrazine derivatives according to generic Formulae I-V: wherein, variables Q, R, Y 1 , Y 2 , Y 3 , Y 4 , n, and m are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions comprising compounds of Formulae I-V and at least one carrier, diluent or excipient.

  该应用程序根据通用公式I-V 揭示了6-苯基咪唑并[1,2-a]吡嗪衍生物： 其中，变量Q、R、Y1、Y2、Y3、Y4、n 和m 如本文所述定义，这些衍生物抑制Btk。本文所披露的化合物可用于调节Btk 的活性并治疗与过度Btk 活性相关的疾病。这些化合物进一步可用于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了包含公式I-V 化合物和至少一种载体、稀释剂或赋形剂的组合物。
• [EN] IMIDAZO[1,2-A]PYRAZIN-8-YLAMINES AND METHOD OF INHIBITION OF BRUTON'S TYROSINE KINASE BY SUCH COMPOUNDS<br/>[FR] IMIDAZO[1,2-A]PYRAZIN-8-YLAMINES ET METHODES D'INHIBITION DE LA TYROSINE KINASE DE BRUTON PAR DE TELS COMPOSES
  申请人：CELLULAR GENOMICS INC

  公开号：WO2005014599A1

  公开（公告）日：2005-02-17

  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.

  本文描述了化合物的化学式（I-a）及其所有药用可接受形式。在化学式I-a中显示的变量R1、R2、R3、Z1、Q和A在此处被定义。本文提供了含有一个或多个化学式（I-a）化合物或该化合物的药用可接受形式以及一个或多个药用可接受载体、辅料或稀释剂的药物组合物。还提供了治疗对酪氨酸激酶活性抑制敏感的患者的方法。在某些实施例中，这些疾病对Btk活性和/或B细胞增殖的抑制敏感。这些方法包括向这些患者投予有效减轻疾病症状的化学式（I-a）化合物的量。这些疾病包括癌症、自身免疫和/或炎症性疾病或急性炎症反应。因此，治疗方法包括向患者投予足够量的本文所述的化合物或盐，以减轻这些疾病的症状或减缓其进展。其他实施例包括治疗其他动物，包括牲畜和驯养的伴侣动物，患有对激酶活性抑制敏感的疾病的方法。治疗方法包括将化学式（I-a）的化合物作为单一活性剂或将化学式（I-a）的化合物与一个或多个其他治疗剂结合使用。一种确定样品中Btk存在的方法，包括将样品与化学式（I-a）的化合物或其形式接触，在允许检测Btk活性的条件下，检测样品中Btk活性的水平，并从中确定样品中Btk的存在或不存在。
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130150360A1

  公开（公告）日：2013-06-13

  This application discloses compounds according to generic Formula I: wherein the variables are defined as described herein, and which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation, such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.

  本申请披露了根据通用式I定义的化合物：其中变量如本文所述，并且抑制Btk。本文披露的化合物对调节Btk的活性并治疗与Btk活性过高相关的疾病有用。这些化合物还有助于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了含有通用式I化合物和至少一种载体、稀释剂或赋形剂的组合物。
• Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton's tyrosine kinase by such compounds
  申请人：Currie S. Kevin

  公开号：US20050090499A1

  公开（公告）日：2005-04-28

  Compounds of Formula I-a and all pharmaceutically-acceptable forms thereof, are described herein. The variables R 1 , R 2 , R 3 , Z 1 , 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.

  本文介绍了I-a公式化合物及其所有药学上可接受的形式。公式I-a中所示的变量R1、R2、R3、Z1、Q和A在本文中有定义。本文提供了含有一种或多种I-a公式化合物或其药学上可接受的形式以及一种或多种药学上可接受的载体、赋形剂或稀释剂的制药组合物。本文还提供了治疗对酪氨酸激酶活性抑制具有反应性的某些疾病的方法。在某些实施例中，这些疾病对Btk活性和/或B细胞增殖的抑制具有反应性。这些方法包括向这些患者施用足够量的I-a公式化合物，以减少疾病的症状或症状。这些疾病包括癌症、自身免疫和/或炎症性疾病或急性炎症反应。因此，治疗方法包括向患者施用足够量的本文所提供的化合物或盐，以减轻这些疾病的症状或减缓其进展。其他实施例包括治疗其他动物，包括牲畜和驯养的伴侣动物，这些动物患有对激酶活性抑制具有反应性的疾病。治疗方法包括将I-a公式化合物作为单一活性剂或与一种或多种其他治疗剂联合使用。一种用于确定样品中Btk存在的方法，包括将样品与I-a公式化合物或其形式接触，在允许检测Btk活性的条件下，检测样品中Btk活性的水平，然后确定样品中Btk的存在或不存在。
• Certain imidazo[1,2-a]pyrazin-8-ylamines, method of making, and method of use thereof
  申请人：Currie S. Kevin

  公开号：US20060178367A1

  公开（公告）日：2006-08-10

  Chemical entities chosen from compounds of Formula 1 and pharmaceutically acceptable salts, solvates, crystal forms, chelates, non-covalent complexes, prodrugs, and mixtures thereof, are described herein. Pharmaceutical compositions comprising at least one chemical entity of Formula 1, together with at least one pharmaceutically acceptable vehicle chosen from carriers adjuvants, and excipients, are described. Methods of treating patients suffering from certain diseases responsive to inhibition of Btk activity and/or B-cell proliferation are described. Methods for determining the presence of Btk in a sample are described.

  本文描述了从1号式化合物中选择的化学实体及其药学上可接受的盐、溶剂化物、晶体形式、螯合物、非共价复合物、前药和混合物。本文还描述了包含1号式化学实体至少一种和至少一种药学上可接受的载体、辅料和赋形剂的制药组合物。本文还描述了治疗对Btk活性和/或B细胞增殖抑制有反应的某些疾病患者的方法。本文还描述了检测样品中Btk存在的方法。