N-(3,4-dimethoxyphenyl)-6-(1H-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine | 1229206-47-6

• 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: N-(3,4-dimethoxyphenyl)-6-(1H-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine
• CAS: 1229206-47-6
• 化学式: C₂₁H₁₈N₆O₂
• 分子量: 386.413
• InChiKey: YRFUVUYUKBPPHG-UHFFFAOYSA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  89.4
• 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 22.33h， 生成 N-(3,4-dimethoxyphenyl)-6-(1H-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine
  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

• [EN] IMIDAZOPYRAZINE SYK INHIBITORS<br/>[FR] INHIBITEURS D'IMIDAZOPYRAZINE SYK
  申请人：CGI PHARMACEUTICALS INC

  公开号：WO2010068257A1

  公开（公告）日：2010-06-17

  Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. 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 provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

  本文提供了某些咪唑吡嗪化合物及其制药组合物。提供了治疗对Syk活性抑制响应的某些疾病和疾病的患者的方法，包括向这些患者施用至少一种有效减少疾病或疾病症状的化学实体的剂量。还提供了一种确定样本中Syk激酶存在或不存在的方法。
• IMIDAZOPYRAZINE SYK INHIBITORS
  申请人：Mitchell Scott A.

  公开号：US20100222323A1

  公开（公告）日：2010-09-02

  Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. 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 provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

  本文提供了某些咪唑吡嗪及其制药组合物。提供了治疗对Syk活性抑制有反应的某些疾病和疾病的患者的方法，包括向这些患者施用至少一种化学物质的有效量，以减少疾病或疾病的症状。还提供了一种确定样品中Syk激酶存在或不存在的方法。
• IMIDAZOPYRIZINE SYK INHIBITORS
  申请人：GILEAD CONNECTICUT, INC.

  公开号：US20130237521A1

  公开（公告）日：2013-09-12

  Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. 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 provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

  本文提供了某些咪唑吡嗪和其药物组成物。提供了治疗对Syk活性抑制有反应的某些疾病和疾病的患者的方法，包括向这些患者施用至少一种化学物质的量，以减少疾病或疾病的症状或迹象。还提供了用于确定样品中Syk激酶的存在或缺失的方法。
• THERAPIES FOR TREATING CANCER
  申请人：GILEAD CALISTOGA LLC

  公开号：US20140051696A1

  公开（公告）日：2014-02-20

  Provided herein are methods that relate to a novel therapeutic strategy for treatment of cancer, including hematological malignancies such as leukemia, lymphoma, and multiple myeloma. In particular, the method includes administration of a PI3Kδ inhibitor and a Syk inhibitor.
• SYK INHIBITORS
  申请人：Gilead Sciences, Inc.

  公开号：US20180071303A1

  公开（公告）日：2018-03-15

  The application provides methods reducing the side effects of chemotherapy and radiotherapy, including, hematopoietic toxicity, anemia, myelosuppression, pancytopenia, thrombocytopenia, neutropenia, lymphopenia, leukopenia, stomatitis and alopecia. The application provides a method for increasing the number of, neutrophil counts and platelet counts in a patient in need thereof, comprising administering an effective of an inhibitor of spleen tyrosine kinase (SYKi). The present application provides methods for treating myelosuppresive disorders by the administration of a SYKi. In certain embodiments, the myelosuppression is induced by the administration of one or more myelosuppressive agents, for example, anti-cancer drugs. The present application provides methods for treating AML/ALL in a patient with 11q23/MLL abnormalities comprising the step of administering an effective amount of a SYKi to said patient.