methyl 2,4-bis(tert-butyldimethylsilanyloxy)-3-chloro-6-methylbenzoate | 811788-11-1

• 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: methyl 2,4-bis(tert-butyldimethylsilanyloxy)-3-chloro-6-methylbenzoate
• 英文别名: Methyl 4,6-bis[[tert-butyl(dimethyl)silyl]oxy]-3-chloro-2-methylbenzoate
• CAS: 811788-11-1
• 化学式: C₂₁H₃₇ClO₄Si₂
• 分子量: 445.146
• InChiKey: HTXLLSKWDGBAIB-UHFFFAOYSA-N

物化性质

• 沸点：
  435.4±45.0 °C(Predicted)
• 密度：
  1.011±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2,4-bis(tert-butyldimethylsilanyloxy)-3-chloro-6-methylbenzoate 在 sodium chlorite 、 sodium dihydrogenphosphate 、 臭氧 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 25.33h， 生成 methyl 4,6-bis(tert-butyldimethylsilanyloxy)-2-(2-carboxyethyl)-3-chloro-benzoate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Radicicol and Geldanamycin Chimera, Radamide

  摘要：

  A chimera composed of the natural products radicicol and geldanamycin has been prepared through an amide linkage connecting the resorcinol moiety of radicicol to the quinone ring of geldanamycin. The inhibitory activity of these compounds was determined by their ability to inhibit Hsp90's inherent ATPase activity along with degradation of the Hsp90 client protein, HER-2 in MCF-7 breast cancer cells.

  DOI：

  10.1021/ol048266o
• 作为产物：
  描述：

  2,4-二羟基-6-甲基苯甲酸甲酯 在 calcium hypochlorite 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 14.0h， 生成 methyl 2,4-bis(tert-butyldimethylsilanyloxy)-3-chloro-6-methylbenzoate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Radicicol and Geldanamycin Chimera, Radamide

  摘要：

  A chimera composed of the natural products radicicol and geldanamycin has been prepared through an amide linkage connecting the resorcinol moiety of radicicol to the quinone ring of geldanamycin. The inhibitory activity of these compounds was determined by their ability to inhibit Hsp90's inherent ATPase activity along with degradation of the Hsp90 client protein, HER-2 in MCF-7 breast cancer cells.

  DOI：

  10.1021/ol048266o

文献信息

• Design, Synthesis, and StructureActivity Relationships for Chimeric Inhibitors of Hsp90
  作者：Gang Shen、Mingwen Wang、Timothy R. Welch、Brian S. J. Blagg

  DOI：10.1021/jo061054f

  日期：2006.9.1

  Inhibition of the 90 kDa heat shock protein (Hsp90) family of molecular chaperones represents a promising new chemotherapeutic approach toward the treatment of several cancers. Previous studies have demonstrated that the natural products, radicicol and geldanamycin, are potent inhibitors of the Hsp90 N-terminal ATP binding site. The cocrystal structures of these molecules bound to Hsp90 have been determined, and through molecular modeling and superimposition of these ligands, hybrids of radicicol and geldanamycin have been designed. A series of macrocylic chimeras of radicicol and geldanamycin and the corresponding seco-agents have been prepared and evaluated for both antiproliferative activity and their ability to induce Hsp90-dependent client protein degradation.
• Synthesis and Evaluation of Radamide Analogues, A Chimera of Radicicol and Geldanamycin
  作者：M. Kyle Hadden、Brian S. J. Blagg

  DOI：10.1021/jo900278g

  日期：2009.7.3

  Previously, we reported the Hsp90 inhibitory activity of radamide, an open chain amide chimera of geldanamycin and radicicol. Attempts to further expand upon structure-activity relationships for this class of Hsp90 inhibitors led to the preparation of a series of radamide analogues focused on differing tether lengths and quinone mimics. In addition, the cup-shaped conformation adopted by the two natural products when bound to the Hsp90 N-terminal ATP binding pocket suggests that conformationally biased compounds may demonstrate improved binding and inhibition. The preparation and evaluation of radamide analogues with cisltrans alpha,beta-unsaturated amides yielded compounds that exhibit improved antiproliferative activity. In addition, several analogues demonstrated the ability to induce degradation of Hsp90-dependent oncogenic signaling proteins in vitro, a hallmark of Hsp90 N-terminal inhibition.
• Design, Synthesis, and Biological Evaluation of Conformationally Constrained <i>cis</i>-Amide Hsp90 Inhibitors
  作者：Adam S. Duerfeldt、Gary E. L. Brandt、Brian S. J. Blagg

  DOI：10.1021/ol900783m

  日期：2009.6.4

  Conformationally constrained cis-amide chimeric inhibitors of Hsp90 have been synthesized and evaluated for their Hsp90 inhibitory activity. These new compounds exhibited Hsp90 ATPase inhibition and induced Hsp90-dependent client protein degradation in a dose-dependent manner. Biological data reported herein suggests that amide bond isomerization of geldanamycin derivatives plays an important role in affinity for the heteroprotein complex present in cancer cells.
• Design, Synthesis, and Evaluation of a Radicicol and Geldanamycin Chimera, Radamide
  作者：Randell C. Clevenger、Brian S. J. Blagg

  DOI：10.1021/ol048266o

  日期：2004.11.1

  A chimera composed of the natural products radicicol and geldanamycin has been prepared through an amide linkage connecting the resorcinol moiety of radicicol to the quinone ring of geldanamycin. The inhibitory activity of these compounds was determined by their ability to inhibit Hsp90's inherent ATPase activity along with degradation of the Hsp90 client protein, HER-2 in MCF-7 breast cancer cells.