Benzoicacid,3-chloro-4,6-bis(ethoxymethoxy)-2-methyl-,2-(trimethylsilyl)ethylester | 1007313-80-5

• 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: Benzoicacid,3-chloro-4,6-bis(ethoxymethoxy)-2-methyl-,2-(trimethylsilyl)ethylester
• 英文别名: 2-trimethylsilylethyl 3-chloro-4,6-bis(ethoxymethoxy)-2-methylbenzoate
• CAS: 1007313-80-5
• 化学式: C₁₉H₃₁ClO₆Si
• 分子量: 418.99
• InChiKey: BQILHYGUTOLDRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  hepta-2,6-dienoic acid methoxy-methylamide 、 Benzoicacid,3-chloro-4,6-bis(ethoxymethoxy)-2-methyl-,2-(trimethylsilyl)ethylester 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以50%的产率得到
  参考文献：
  名称：

  针对 HSP90 的 Pochonin 文库的不同合成和已鉴定抑制剂的体内功效。

  摘要：

  The heat shock protein 90 (HSP90) has emerged as one of the most exciting therapeutic target in recent years.[1, 2] Despite the seemingly ubiquitous function of this constitutively expressed chaperone, its role in stabilizing conformationally labile proteins has implications in pathologies ranging from oncology to neurodegenerative diseases. Most of HSP90’s endogenous clients[3] are key regulators of cell signaling which are destabilized and degraded in the absence of HSP90’s chaperoning activity. The dependence of transformed cells on HSP90 is further heightened by the fact that many oncogenic mutations, while increasing the activity of pro-growth signaling pathways, are less stable than their wild type counterpart and have an increased dependence on HSP90’s chaperoning activity.[4] A clinically relevant example is the heightened dependence of drug resistant Bcr-Abl mutants on HSP90’s activity and the fact that HSP90 inhibitors in combination with Abl inhibitors remain effective against such mutants.[5, 6] Accordingly, HSP90 inhibition provides a broad and effective target for anticancer treatment. Furthermore, HSP90 inhibitors can act synergistically with a cytotoxic agent.[7] HSP90 is also implicated in regulating the fate of a number of conformationally unstable proteins which underlie the development of neurodegenerative diseases.[8] It has been shown that HSP90 inhibitors can reduce protein aggregates in cellular and animal models of Huntington disease,[9] spinal and bulbar muscular atrophy,[10] Parkinson disease,[11] and other Tau protein-related neurodegenerative diseases.[12]

  DOI：

  10.1002/anie.200800233
• 作为产物：
  描述：

  苔色酸 、 2-(三甲硅基)乙醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以80%的产率得到Benzoicacid,3-chloro-4,6-bis(ethoxymethoxy)-2-methyl-,2-(trimethylsilyl)ethylester
  参考文献：
  名称：

  WO2008/21213

  摘要：

  公开号：

文献信息

• [EN] SYNTHESIS OF RESORCYLIC ACID LACTONES USEFUL AS THERAPEUTIC AGENTS<br/>[FR] SYNTHÈSE DE LACTONES D'ACIDE RÉSORCYLIQUE UTILES EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：UNIV STRASBOURG

  公开号：WO2009091921A1

  公开（公告）日：2009-07-23

  Disclosed are macrocyclic compounds of formulae I, I', II, II', III, III', IV, and V, which are analogs of the pochonin resorcylic acid lactones, pharmaceutical compositions comprising the compounds, and methods and uses comprising the compounds for the treatment of diseases mediated by kinases and Heat Shock Protein 90 HSP90.

  公开的是式I、I'、II、II'、III、III'、IV和V的大环化合物，它们是pochonin resorcylic acid lactones的类似物，包括这些化合物的药物组合物，以及包括这些化合物用于治疗由激酶和热休克蛋白90 HSP90介导的疾病的方法和用途。
• Synthesis of pochoxime prodrugs as potent HSP90 inhibitors
  作者：Cuihua Wang、Sofia Barluenga、Girish K. Koripelly、Jean-Gonzague Fontaine、Ruihong Chen、Jin-Chen Yu、Xiaodong Shen、John C. Chabala、James V. Heck、Allan Rubenstein、Nicolas Winssinger

  DOI：10.1016/j.bmcl.2009.04.030

  日期：2009.7

  Pochoximes are potent inhibitors of heat shock protein 90 (HSP90) based on the radicicol pharmacophores. Herein we present a pharmacokinetics and pharmacodynamics evaluation of this compound series as well as a phosphate prodrug strategy to facilitate formulation and improve oral bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] MACROCYCLIC PRODRUG COMPOUNDS USEFUL AS THERAPEUTICS<br/>[FR] COMPOSÉS DE PROMÉDICAMENTS MACROCYCLIQUES UTILISÉS COMME AGENTS THÉRAPEUTIQUES
  申请人：NEXGENIX PHARMACEUTICALS

  公开号：WO2009105755A3

  公开（公告）日：2009-11-12
• WO2008/21213
  申请人：——

  公开号：——

  公开（公告）日：——
• Divergent Synthesis of a Pochonin Library Targeting HSP90 and In Vivo Efficacy of an Identified Inhibitor
  作者：Sofia Barluenga、Cuihua Wang、Jean-Gonzague Fontaine、Kaïss Aouadi、Kristin Beebe、Shinji Tsutsumi、Len Neckers、Nicolas Winssinger

  DOI：10.1002/anie.200800233

  日期：2008.5.26

  The heat shock protein 90 (HSP90) has emerged as one of the most exciting therapeutic target in recent years.[1, 2] Despite the seemingly ubiquitous function of this constitutively expressed chaperone, its role in stabilizing conformationally labile proteins has implications in pathologies ranging from oncology to neurodegenerative diseases. Most of HSP90’s endogenous clients[3] are key regulators of cell signaling which are destabilized and degraded in the absence of HSP90’s chaperoning activity. The dependence of transformed cells on HSP90 is further heightened by the fact that many oncogenic mutations, while increasing the activity of pro-growth signaling pathways, are less stable than their wild type counterpart and have an increased dependence on HSP90’s chaperoning activity.[4] A clinically relevant example is the heightened dependence of drug resistant Bcr-Abl mutants on HSP90’s activity and the fact that HSP90 inhibitors in combination with Abl inhibitors remain effective against such mutants.[5, 6] Accordingly, HSP90 inhibition provides a broad and effective target for anticancer treatment. Furthermore, HSP90 inhibitors can act synergistically with a cytotoxic agent.[7] HSP90 is also implicated in regulating the fate of a number of conformationally unstable proteins which underlie the development of neurodegenerative diseases.[8] It has been shown that HSP90 inhibitors can reduce protein aggregates in cellular and animal models of Huntington disease,[9] spinal and bulbar muscular atrophy,[10] Parkinson disease,[11] and other Tau protein-related neurodegenerative diseases.[12]