4-甲氧基-1H-吲哚-2-硼酸频那醇酯 | 1072811-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 4-甲氧基-1H-吲哚-2-硼酸频那醇酯
• 英文名称: 4-methoxyindole-2-boronic acid pinacol ester
• 英文别名: 4-methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole
• CAS: 1072811-21-2
• 化学式: C₁₅H₂₀BNO₃
• 分子量: 273.14
• InChiKey: IRATVBPKOAAZGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  43.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  4-甲氧基-1H-吲哚-2-硼酸频那醇酯 在 sodium carbonate 、 caesium carbonate 、 三(邻甲基苯基)磷 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 5-(1-ethyl-4-methoxy-1H-indol-2-yl)picolinic acid trifluoroacetate
  参考文献：
  名称：

  Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain

  摘要：

  一系列新型取代吡啶甲酸在β-外位点表现出对肉毒杆菌A型神经毒素轻链的低微摩尔抑制作用。

  DOI：

  10.1039/c6cc06749b
• 作为产物：
  描述：

  7-氯吲哚-2-硼酸频那醇酯 、 4-甲氧基吲哚 生成 4-甲氧基-1H-吲哚-2-硼酸频那醇酯
  参考文献：
  名称：

  Fused bicyclic mTOR inhibitors

  摘要：

  化合物I式（或其药学上可接受的盐）是mTOR抑制剂，可用于治疗癌症。

  公开号：

  US08796455B2

文献信息

• Overcoming Mutagenicity and Ion Channel Activity: Optimization of Selective Spleen Tyrosine Kinase Inhibitors
  作者：J. Michael Ellis、Michael D. Altman、Alan Bass、John W. Butcher、Alan J. Byford、Anthony Donofrio、Sheila Galloway、Andrew M. Haidle、James Jewell、Nancy Kelly、Erica K. Leccese、Sandra Lee、Matthew Maddess、J. Richard Miller、Lily Y. Moy、Ekundayo Osimboni、Ryan D. Otte、M. Vijay Reddy、Kerrie Spencer、Binyuan Sun、Stella H. Vincent、Gwendolyn J. Ward、Grace H. C. Woo、Chiming Yang、Hani Houshyar、Alan B. Northrup

  DOI：10.1021/jm5018169

  日期：2015.2.26

  bacterial mutagenicity in the Ames test using TA97a Salmonella strain, and subsequent study demonstrated that this mutagenicity was pervasive throughout the series. Identification of intercalation as a likely mechanism for the mutagenicity-enabled modification of the core scaffold. Implementation of a DNA binding assay as a prescreen and models in DNA allowed resolution of the mutagenicity risk, affording

  描述了开发一系列具有良好药物样特性的高促动素选择性脾酪氨酸激酶（Syk）抑制剂。通过X射线晶体学分析，以及对选定化学空间内核心的系统调查（以配体结合效率为重点），发现了早期的铅。通过调节包括log D，PSA和p K a在内的物理化学性质来指导初始化学型中固有的hERG离子通道活性的减弱。PSA被证明对预期的化合物设计最有效。使用TA97a沙门氏菌的Ames试验进一步分析了先进化合物的细菌致突变性菌株，随后的研究表明，这种诱变性在整个系列中普遍存在。插入的鉴定是核心支架诱变启用修饰的可能机制。将DNA结合测定作为DNA的预筛选和模型，可以解决诱变风险，为分子提供了有利的效价，选择性，药代动力学和脱靶特性。
• Carboxamide Spleen Tyrosine Kinase (Syk) Inhibitors: Leveraging Ground State Interactions To Accelerate Optimization
  作者：J. Michael Ellis、Michael D. Altman、Brandon Cash、Andrew M. Haidle、Rachel L. Kubiak、Matthew L. Maddess、Youwei Yan、Alan B. Northrup

  DOI：10.1021/acsmedchemlett.6b00353

  日期：2016.12.8

  Optimization of a series of highly potent and kinome selective carbon-linked carboxamide spleen tyrosine kinase (Syk) inhibitors with favorable drug-like properties is described. A pervasive Ames liability in an analogous nitrogen-linked carboxamide series was obviated by replacement with a carbon-linked moiety. Initial efforts lacked on-target potency, likely due to strain induced between the hinge

  描述了一系列具有良好的类药物特性的高效，高能动性选择性碳连接羧酰胺脾酪氨酸激酶（Syk）抑制剂的优化方法。通过用碳连接的部分取代，避免了类似的氮连接的羧酰胺系列中普遍的艾姆斯（Ames）责任。最初的努力缺乏对目标的效力，这可能是由于铰链结合酰胺和溶剂前沿杂环之间诱导的应变所致。考虑到基态和键态能级可以快速实现改进的溶剂前沿取代基，从而提供亚纳摩尔的Syk效力和高的kinome选择性。通过使用TA97a沙门氏菌菌株的Ames试验评估，这些分子也没有致突变性风险。
• 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有非小细胞肺癌、胰腺癌、结肠癌或乳腺癌肿瘤或转移瘤的患者的方法，包括同时或顺序给患者施用治疗有效量的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作用的药物，其中该药物为mTOR抑制剂，可以加入其他抗癌药物或放疗等额外的药物或治疗方法。本发明还提供了一种治疗患者肿瘤或转移瘤的方法，包括同时或顺序给患者施用治疗有效量的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作用的药物，其中该药物为一种mTOR抑制剂，可结合并直接抑制mTORC1和mTORC2激酶。本发明还提供了一种制药组合物，包括一种EGFR激酶抑制剂和一种可结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂，以及药学上可接受的载体。本发明中可用于实施方法的EGFR激酶抑制剂的首选示例是化合物依洛替尼盐酸盐（也称为TARCEVA®）。
• Combination anti-cancer therapy
  申请人：Bhagwat Shripad

  公开号：US20090274698A1

  公开（公告）日：2009-11-05

  The present invention 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 anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, or ionizing radiation. The present invention also provides a pharmaceutical composition comprising an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. 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 the anti-cancer agent melphalan or 5-FU, and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases.

  本发明提供了一种治疗患者肿瘤或肿瘤转移的方法，包括同时或顺序给患者施用抗癌药物或提高肿瘤细胞pAkt水平的治疗剂量和结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。这样的抗癌药物或治疗剂包括多柔比星、顺铂或电离辐射。本发明还提供了一种药物组合，包括抗癌药物或提高肿瘤细胞pAkt水平的治疗剂量和结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂，以及药学上可接受的载体。本发明还提供了一种治疗患者肿瘤或肿瘤转移的方法，包括同时或顺序给患者施用治疗剂量的抗癌药物美法仑或5-FU和结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。
• FUSED BICYCLIC mTOR INHIBITORS
  申请人：Chen Xin

  公开号：US20100099679A1

  公开（公告）日：2010-04-22

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

  公式（I）所代表的化合物或其药学上可接受的盐，是mTOR的抑制剂，可用于癌症的治疗。