2,3-dichloro-4-triisopropylsilanyloxy-benzoyl chloride | 515846-31-8

• 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: 2,3-dichloro-4-triisopropylsilanyloxy-benzoyl chloride
• 英文别名: 2,3-Dichloro-4-[[tris(1-methylethyl)silyl]oxy]benzoyl chloride；2,3-dichloro-4-tri(propan-2-yl)silyloxybenzoyl chloride
• CAS: 515846-31-8
• 化学式: C₁₆H₂₃Cl₃O₂Si
• 分子量: 381.802
• InChiKey: VDGRDBAPMDDECA-UHFFFAOYSA-N

物化性质

• 沸点：
  397.7±42.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.93
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,3-dichloro-4-triisopropylsilanyloxy-benzoyl chloride 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 (R)-4-[2,3-dichloro-4-(5-{1-[2-(2-guanidino-4-methyl-pentanoylamino)acetyl]-piperidin-4-yl}-1-methyl-1H-pyrazol-3-yl)-phenoxymethyl]-benzoic acid methyl ester trifluoroacetate
  参考文献：
  名称：

  Discovery of a Potent Small Molecule IL-2 Inhibitor through Fragment Assembly

  摘要：

  Using a site-directed fragment discovery method called tethering, we have identified a 60 nM small molecule antagonist of a cytokine/receptor interaction (IL-2/IL2Ralpha) with cell-based activity. Starting with a low micromolar hit, we employed a combination of tethering, structural biology, and computational analysis to design a focused set of 20 compounds. Eight of these compounds were at least 5-fold more active than the original hit. One of these compounds showed a 50-fold enhancement and represents the highest affinity inhibitor reported against this protein-protein target class. This method of coupling selected fragments with a low micromolar hit shows great potential for generating high-affinity lead compounds.

  DOI：

  10.1021/ja034247i
• 作为产物：
  描述：

  2,3-dichloro-4-triisopropylsilanyloxy-benzoic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 2,3-dichloro-4-triisopropylsilanyloxy-benzoyl chloride
  参考文献：
  名称：

  [EN] TARGETED BIFUNCTIONAL DEGRADERS
  [FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS

  摘要：

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。

  公开号：

  WO2021072269A1

文献信息

• [EN] BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS<br/>[FR] PETITES MOLÉCULES BIFONCTIONNELLES POUR CIBLER LA DÉGRADATION SÉLECTIVE DE PROTÉINES CIRCULANTES
  申请人：UNIV YALE

  公开号：WO2019199634A4

  公开（公告）日：2019-12-05
• Integrating Fragment Assembly and Biophysical Methods in the Chemical Advancement of Small-Molecule Antagonists of IL-2:  An Approach for Inhibiting Protein−Protein Interactions
  作者：Brian C. Raimundo、Johan D. Oslob、Andrew C. Braisted、Jennifer Hyde、Robert S. McDowell、Mike Randal、Nathan D. Waal、Jennifer Wilkinson、Chul H. Yu、Michelle R. Arkin

  DOI：10.1021/jm049967u

  日期：2004.6.1

  Fragment assembly has shown promise for discovering small-molecule antagonists for difficult targets, including protein-protein interactions. Here, we describe a process for identifying a 60 nM inhibitor of the interleukin-2 (IL-2)/IL-2 receptor (IL-2Ralpha) interaction. By use of fragment-based approaches, a compound with millimolar affinity was evolved to a hit series with low micromolar activity, and these compounds were optimized into a lead series with nanomolar affinity. Fragment assembly was useful not only for hit identification, but also for lead optimization. Throughout the discovery process, biophysical methods and structural biology demonstrated that compounds bound reversibly to IL-2 at the IL-2 receptor binding site.
• Identification of nonpeptidic small-molecule inhibitors of interleukin-2
  作者：Nathan D. Waal、Wenjin Yang、Johan D. Oslob、Michelle R. Arkin、Jennifer Hyde、Wanli Lu、Robert S. McDowell、Chul H. Yu、Brian C. Raimundo

  DOI：10.1016/j.bmcl.2004.12.045

  日期：2005.2

  The identification, design, and synthesis of a series of novel sulfamide- and urea-based small-molecule antagonists of the protein-protein interaction IL-2/IL-2Ralpha are described. Installation of a furan carboxylic acid fragment onto a low-micromolar sulfamide resulted in a 23-fold improvement in activity, providing a sub-micromolar, nonpeptidic IL-2 inhibitor (IC50 = 0.60 muM). (C) 2005 Elsevier Ltd. All rights reserved.