3-(3-Dimethylamino-prop-1-ynyl)-indazole-1-carboxylic acid tert-butyl ester | 459133-75-6

• 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: 3-(3-Dimethylamino-prop-1-ynyl)-indazole-1-carboxylic acid tert-butyl ester
• 英文别名: 1,1-Dimethylethyl 3-[3-(dimethylamino)-1-propyn-1-yl]-1H-indazole-1-carboxylate；tert-butyl 3-[3-(dimethylamino)prop-1-ynyl]indazole-1-carboxylate
• CAS: 459133-75-6
• 化学式: C₁₇H₂₁N₃O₂
• 分子量: 299.373
• InChiKey: SQQJTMNFYQHPFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-Dimethylamino-prop-1-ynyl)-indazole-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以90%的产率得到3-(1H-indazol-3-yl)-N,N-dimethylprop-2-yn-1-amine
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of 3-Ethynyl-1H-indazoles as Inhibitors of the Phosphatidylinositol 3-Kinase Signaling Pathway

  摘要：

  A new series of 3-ethynyl-1H-indazoles has been synthesized and evaluated in both biochemical and cell-based assays as potential kinase inhibitors. Interestingly, a selected group of compounds identified from this series exhibited low micromolar inhibition against critical components of the PI3K pathway, targeting PI3K, PDK1, and mTOR kinases. A combination of computational modeling and structure-activity relationship studies reveals a possible novel mode for PI3K inhibition, resulting in a PI3K alpha isoform-specific compound. Hence, by targeting the most oncogenic mutant isoform of PI3K, the compound displays antiproliferative activity both in monolayer human cancer cell cultures and in three-dimensional tumor models. Because of its favorable physicochemical, in vitro ADME and drug-like properties, we propose that this novel ATP mimetic scaffold could prove useful in deriving novel selecting and multikinase inhibitors for clinical use.

  DOI：

  10.1021/jm100825h
• 作为产物：
  描述：

  3-碘吲唑 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 TEA 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 3-(3-Dimethylamino-prop-1-ynyl)-indazole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Sonogashira cross-coupling reaction of 3-iodoindazoles with various terminal alkynes: a mild and flexible strategy to design 2-aza tryptamines

  摘要：

  This paper describes a Sonogashira-type cross-coupling reaction of 3-iodoindazoles various terminal alkynes as a general route to 3-alkynylindazoles. The Coupling reaction is illustrated by the preparation of ne indazolylpropiolic or propargylic derivatives. Scope and limitation of the method are outlined. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)00393-3

文献信息

• Sonogashira cross-coupling reaction of 3-iodoindazoles with various terminal alkynes: a mild and flexible strategy to design 2-aza tryptamines
  作者：Anca Arnautu、Valérie Collot、Javier Calvo Ros、Carole Alayrac、Bernhard Witulski、Sylvain Rault

  DOI：10.1016/s0040-4039(02)00393-3

  日期：2002.4

  This paper describes a Sonogashira-type cross-coupling reaction of 3-iodoindazoles various terminal alkynes as a general route to 3-alkynylindazoles. The Coupling reaction is illustrated by the preparation of ne indazolylpropiolic or propargylic derivatives. Scope and limitation of the method are outlined. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Design, Synthesis, and Structure−Activity Relationships of 3-Ethynyl-1<i>H</i>-indazoles as Inhibitors of the Phosphatidylinositol 3-Kinase Signaling Pathway
  作者：Elisa Barile、Surya K. De、Coby B. Carlson、Vida Chen、Christine Knutzen、Megan Riel-Mehan、Li Yang、Russell Dahl、Gary Chiang、Maurizio Pellecchia

  DOI：10.1021/jm100825h

  日期：2010.12.9

  A new series of 3-ethynyl-1H-indazoles has been synthesized and evaluated in both biochemical and cell-based assays as potential kinase inhibitors. Interestingly, a selected group of compounds identified from this series exhibited low micromolar inhibition against critical components of the PI3K pathway, targeting PI3K, PDK1, and mTOR kinases. A combination of computational modeling and structure-activity relationship studies reveals a possible novel mode for PI3K inhibition, resulting in a PI3K alpha isoform-specific compound. Hence, by targeting the most oncogenic mutant isoform of PI3K, the compound displays antiproliferative activity both in monolayer human cancer cell cultures and in three-dimensional tumor models. Because of its favorable physicochemical, in vitro ADME and drug-like properties, we propose that this novel ATP mimetic scaffold could prove useful in deriving novel selecting and multikinase inhibitors for clinical use.