顺式-3-(8-氨基-1-溴咪唑并[1,5-a]吡嗪-3-基)-1-甲基环丁醇 | 936901-75-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1,5-a]吡嗪
• 中文名称: 顺式-3-(8-氨基-1-溴咪唑并[1,5-a]吡嗪-3-基)-1-甲基环丁醇
• 英文名称: 3-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol
• 英文别名: cis-3-(8-amino-1-bromo-imidazo[1,5-a]pyrazin-3-yl)-1-methyl-cyclobutanol；cis-3-(8-Amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol；3-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutan-1-ol
• CAS: 936901-75-6
• 化学式: C₁₁H₁₃BrN₄O
• 分子量: 297.154
• InChiKey: ADYHPYNMZMANBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  76.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-苯基-7-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)喹啉 、 顺式-3-(8-氨基-1-溴咪唑并[1,5-a]吡嗪-3-基)-1-甲基环丁醇 在 2-苯基-7-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)喹啉 作用下， 以65的产率得到linsitinib
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF THE COMPOUND OSI - 906
  [FR] PROCÉDÉ DE PRÉPARATION DU COMPOSÉ OSI-906

  摘要：

  制备酪氨酸激酶抑制剂OSI-906的过程包括在特定条件下将化合物（2）与化合物（6）偶联。

  公开号：

  WO2012016095A1
• 作为产物：
  描述：

  3-(8-BROMO-1-CHLOROH-PYRROLO[1,2-A]PYRAZIN-6-YL)CYCLOBUTANONE无结构图 在 ammonium hydroxide 作用下， 以 四氢呋喃 、 水 、 异丙醇 为溶剂， 反应 18.0h， 生成 顺式-3-(8-氨基-1-溴咪唑并[1,5-a]吡嗪-3-基)-1-甲基环丁醇
  参考文献：
  名称：

  Discovery of Novel Insulin-Like Growth Factor-1 Receptor Inhibitors with Unique Time-Dependent Binding Kinetics

  摘要：

  This letter describes a series of small molecule inhibitors of IGF-1R with unique time-dependent binding kinetics and slow off-rates. Structure activity and structure kinetic relationships were elucidated and guided further optimizations within the series, culminating in compound 2. With an IGF-1R dissociative half-life (t(1/2)) of >100 h, compound 2 demonstrated, significant and extended pp effects in conjunction with tumor growth inhibition to xenograft models at a remarkably low and intermittent dose, which correlated with the observed in vitro slow off-rate properties.

  DOI：

  10.1021/ml400160a

文献信息

• Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors
  申请人：Buck A. Elizabeth

  公开号：US20070280928A1

  公开（公告）日：2007-12-06

  The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

  本发明提供了一种治疗患者体内NSCL、胰腺、结肠或乳腺癌肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是mTOR抑制剂，可以附加其他药物或治疗，如其他抗癌药物或放射治疗。本发明还提供了一种治疗患者体内肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是一种能够结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。本发明还提供了一种制药组合物，包括一种能够结合并直接抑制mTORC1和mTORC2激酶的EGFR激酶抑制剂和mTOR抑制剂，以及一种药用载体。本发明中可用于实施该方法的EGFR激酶抑制剂的首选示例是化合物厄洛替尼盐酸盐（也称为TARCEVA®）。
• Fused bicyclic mTOR inhibitors
  申请人：Chen Xin

  公开号：US20070112005A1

  公开（公告）日：2007-05-17

  Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

  由化学式(I)代表的化合物或其药用可接受的盐，是mTOR的抑制剂，可用于癌症的治疗。
• SUBSTITUTED IMIDAZOPYR- AND IMIDAZOTRI-AZINES
  申请人：Crew Andrew P.

  公开号：US20090286768A1

  公开（公告）日：2009-11-19

  Fused pyridine-based bicyclic compounds having the structure of Formula I, as defined herein, pharmaceutically acceptable salts thereof, preparation, compositions, and disease treatment therewith. This abstract does not define or limit the invention.

  基于融合吡啶的双环化合物具有如下所定义的结构，其药学上可接受的盐，制备方法，组合物及其用于疾病治疗。本摘要不定义或限制该发明。
• [EN] DEUTERATED TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYROSINE KINASE DEUTÉRÉS
  申请人：OSI PHARM INC

  公开号：WO2011060112A1

  公开（公告）日：2011-05-19

  Compounds of Formula I, as shown below and defined herein: enriched in deuterium, and pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers mediated at least in part by IGF-1 R and/or IR.

  以下公式I的化合物，其定义如下：富含氘的化合物，以及其药学上可接受的盐，合成，中间体，配方和治疗相关疾病的方法，包括至少部分通过IGF-1 R和/或IR介导的癌症。
• Fused Bicyclic mTor Inhibitors
  申请人：Chen Xin

  公开号：US20090163468A1

  公开（公告）日：2009-06-25

  Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

  化合物式(I)或其药学上可接受的盐，是mTOR的抑制剂，可用于治疗癌症。