methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate | 871365-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate
• 英文别名: 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole-3-carboxylic methyl ester；Methyl 1-(2-trimethylsilylethoxymethyl)indazole-3-carboxylate；methyl 1-(2-trimethylsilylethoxymethyl)indazole-3-carboxylate
• CAS: 871365-85-4
• 化学式: C₁₅H₂₂N₂O₃Si
• 分子量: 306.437
• InChiKey: RUHLQEAFZGVHNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate 在 水 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 N-(1-(3-氰基苄基)-1H-吡唑-4-基)-1H-吲唑-3-甲酰胺
  参考文献：
  名称：

  Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors

  摘要：

  There is evidence that small molecule inhibitors of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signaling cascade, could represent a novel asthma therapeutic class. Moreover, given the expected chronic dosing regimen of any asthma treatment, highly selective as well as potent inhibitors would be strongly preferred in any potential therapeutic. Here we report hit-to-lead optimization of a series of indazoles that demonstrate sub-nanomolar inhibitory potency against ITK with strong cellular activity and good kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of the complexes. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.023
• 作为产物：
  描述：

  2-(三甲基硅烷基)乙氧甲基氯 、 1H-吲唑-3-羧酸甲酯 在 sodium hydride 作用下， 以 四氢呋喃 、 silicone oil 为溶剂， 反应 2.5h， 生成 methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate
  参考文献：
  名称：

  [EN] INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF
  [FR] DÉRIVÉ D'INDAZOLE ET PYRROLOPYRIDINE ET UTILISATION PHARMACEUTIQUE DE CELUI-CI

  摘要：

  本发明涉及一种新型吲唑基或吡咯吡啶基衍生物，由下面的式（1）表示，该衍生物对5-羟色胺-4受体具有激动作用或部分激动作用，并且包括含有该衍生物的药物组合物。式（1）[其中每个取代基如权利要求1所定义]

  公开号：

  WO2012169649A1

文献信息

• [EN] INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF<br/>[FR] DÉRIVÉ D'INDAZOLE ET PYRROLOPYRIDINE ET UTILISATION PHARMACEUTIQUE DE CELUI-CI
  申请人：DAINIPPON SUMITOMO PHARMA CO

  公开号：WO2012169649A1

  公开（公告）日：2012-12-13

  The present invention relates to a novel indazole- or pyrrolopyridine-derivative, represented by the formula (1) below, that has an agonistic action or a partial agonistic action against serotonin-4 receptor, and a pharmaceutical composition comprising the same. Formula (1) [wherein each substituent is as defined in claim 1]

  本发明涉及一种新型吲唑基或吡咯吡啶基衍生物，由下面的式（1）表示，该衍生物对5-羟色胺-4受体具有激动作用或部分激动作用，并且包括含有该衍生物的药物组合物。式（1）[其中每个取代基如权利要求1所定义]
• Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors
  作者：Richard M. Pastor、Jason D. Burch、Steven Magnuson、Daniel F. Ortwine、Yuan Chen、Kelly De La Torre、Xiao Ding、Charles Eigenbrot、Adam Johnson、Marya Liimatta、Yichin Liu、Steven Shia、Xiaolu Wang、Lawren C. Wu、Zhonghua Pei

  DOI：10.1016/j.bmcl.2014.04.023

  日期：2014.6

  There is evidence that small molecule inhibitors of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signaling cascade, could represent a novel asthma therapeutic class. Moreover, given the expected chronic dosing regimen of any asthma treatment, highly selective as well as potent inhibitors would be strongly preferred in any potential therapeutic. Here we report hit-to-lead optimization of a series of indazoles that demonstrate sub-nanomolar inhibitory potency against ITK with strong cellular activity and good kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of the complexes. (C) 2014 Elsevier Ltd. All rights reserved.