4-(8-((3,4-dimethoxyphenyl)amino)imidazo[1,2-a]pyrazin-6-yl)-2-methylbenzamide | 1181328-52-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(8-((3,4-dimethoxyphenyl)amino)imidazo[1,2-a]pyrazin-6-yl)-2-methylbenzamide
• 英文别名: 4-[8-(3,4-Dimethoxyanilino)imidazo[1,2-a]pyrazin-6-yl]-2-methylbenzamide
• CAS: 1181328-52-8
• 化学式: C₂₂H₂₁N₅O₃
• 分子量: 403.44
• InChiKey: NCWGWLLQUVYIOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6,8-二溴咪唑并[1,2-a]吡嗪 在 四(三苯基膦)钯 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 异丙醇 为溶剂， 反应 22.25h， 生成 4-(8-((3,4-dimethoxyphenyl)amino)imidazo[1,2-a]pyrazin-6-yl)-2-methylbenzamide
  参考文献：
  名称：

  GS-9973，脾酪氨酸激酶的选择性和口服有效抑制剂的发现

  摘要：

  脾酪氨酸激酶（Syk）在自身免疫，炎症和肿瘤疾病适应症中是有吸引力的药物靶标。最先进的Syk抑制剂，R406，1（或它的前药形式fostamatinib，2），已在多个治疗适应症中显示出功效，但其临床进展已经由已被归因，至少部分剂量限制性不利影响的阻碍，到的脱靶活性1。预期选择性更高的Syk抑制剂将提供更大的治疗窗口。在本文中，我们报告了一系列新型咪唑并[1,2- a ]吡嗪Syk抑制剂的发现和优化。这项工作在GS-9973，鉴定高潮68是一种高度选择性和口服有效的Syk抑制剂，目前正在针对自身免疫和肿瘤学适应症进行临床评估。

  DOI：

  10.1021/jm500228a

文献信息

• CERTAIN SUBSTITUTED AMIDES, METHOD OF MAKING, AND METHOD OF USE THEREOF
  申请人：Mitchell Scott A.

  公开号：US20090221612A1

  公开（公告）日：2009-09-03

  Certain chemical entities chosen from compounds represented by Formula I and pharmaceutically acceptable salts and mixtures thereof, are provided herein. Pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include cancer (e.g., B-cell lymphoma and leukemia), autoimmune diseases, inflammatory diseases, acute inflammatory reactions, and allergic disorders. Methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

  本文提供了从公式I所代表的化合物中选择的某些化学实体及其药学上可接受的盐和混合物。药物组合物包括至少一种化学实体和一个或多个药学上可接受的载体。揭示了治疗对Syk活性抑制有反应的某些疾病和障碍的患者的方法，包括向这些患者施用至少一种化学实体的数量，以减少疾病或障碍的症状或体征。这些疾病包括癌症（例如B细胞淋巴瘤和白血病）、自身免疫性疾病、炎症性疾病、急性炎症反应和过敏性疾病。治疗方法包括单独使用至少一种化学实体或与一种或多种其他治疗剂联合使用至少一种化学实体。还提供了一种确定样品中Syk激酶存在或不存在的方法。
• 6-ARYL-IMIDAZ0[L, 2-A]PYRAZINE DERIVATIVES, METHOD OF MAKING, AND METHOD OF USE THEREOF
  申请人：CGI Pharmaceuticals, Inc.

  公开号：EP2252617A1

  公开（公告）日：2010-11-24
• US8697699B2
  申请人：——

  公开号：US8697699B2

  公开（公告）日：2014-04-15
• [EN] 6-ARYL-IMIDAZ0[L, 2-A] PYRAZINE DERIVATIVES, METHOD OF MAKING, AND METHOD OF USE THEREOF<br/>[FR] DÉRIVÉS DE 6-ARYLIMIDAZO[L,2-A]PYRAZINE, LEUR PROCÉDÉ DE FABRICATION ET LEUR PROCÉDÉ D'UTILISATION
  申请人：CGI PHARMACEUTICALS INC

  公开号：WO2009102468A1

  公开（公告）日：2009-08-20

  Certain chemical entities chosen from compounds represented by Formula I and pharmaceutically acceptable salts and mixtures thereof, are provided herein. Pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include cancer (e.g., B -cell lymphoma and leukemia), autoimmune diseases, inflammatory diseases, acute inflammatory reactions, and allergic disorders. Methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for determining the presence or absence of Syk kinase in a sample. Formula I
• Discovery of GS-9973, a Selective and Orally Efficacious Inhibitor of Spleen Tyrosine Kinase
  作者：Kevin S. Currie、Jeffrey E. Kropf、Tony Lee、Peter Blomgren、Jianjun Xu、Zhongdong Zhao、Steve Gallion、J. Andrew Whitney、Deborah Maclin、Eric B. Lansdon、Patricia Maciejewski、Ann Marie Rossi、Hong Rong、Jennifer Macaluso、James Barbosa、Julie A. Di Paolo、Scott A. Mitchell

  DOI：10.1021/jm500228a

  日期：2014.5.8

  expected that a more selective Syk inhibitor would provide a greater therapeutic window. Herein we report the discovery and optimization of a novel series of imidazo[1,2-a]pyrazine Syk inhibitors. This work culminated in the identification of GS-9973, 68, a highly selective and orally efficacious Syk inhibitor which is currently undergoing clinical evaluation for autoimmune and oncology indications.

  脾酪氨酸激酶（Syk）在自身免疫，炎症和肿瘤疾病适应症中是有吸引力的药物靶标。最先进的Syk抑制剂，R406，1（或它的前药形式fostamatinib，2），已在多个治疗适应症中显示出功效，但其临床进展已经由已被归因，至少部分剂量限制性不利影响的阻碍，到的脱靶活性1。预期选择性更高的Syk抑制剂将提供更大的治疗窗口。在本文中，我们报告了一系列新型咪唑并[1,2- a ]吡嗪Syk抑制剂的发现和优化。这项工作在GS-9973，鉴定高潮68是一种高度选择性和口服有效的Syk抑制剂，目前正在针对自身免疫和肿瘤学适应症进行临床评估。