methyl 4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(5-(5-cyanopyridin-2-ylamino)-5-oxopent-3-ynyl)benzoate | 1164274-47-8

• 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: methyl 4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(5-(5-cyanopyridin-2-ylamino)-5-oxopent-3-ynyl)benzoate
• 英文别名: Methyl 4,6-bis[[tert-butyl(dimethyl)silyl]oxy]-3-chloro-2-[5-[(5-cyanopyridin-2-yl)amino]-5-oxopent-3-ynyl]benzoate
• CAS: 1164274-47-8
• 化学式: C₃₁H₄₂ClN₃O₅Si₂
• 分子量: 628.316
• InChiKey: JCGVQYNPMCZKMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(5-(5-cyanopyridin-2-ylamino)-5-oxopent-3-ynyl)benzoate 在 Lindlar's catalyst 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以48%的产率得到methyl (Z)-4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(5-(5-cyanopyridin-2-ylamino)-5-oxopent-3-enyl)benzoate
  参考文献：
  名称：

  Synthesis and Evaluation of Radamide Analogues, A Chimera of Radicicol and Geldanamycin

  摘要：

  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.

  DOI：

  10.1021/jo900278g
• 作为产物：
  描述：

  2-氨基-5-氰基吡啶 、 methyl 4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(5-methoxy-5-oxopent-3-ynyl)benzoate 在 三甲基铝 、 potassium carbonate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 1.0h， 以85%的产率得到methyl 4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(5-(5-cyanopyridin-2-ylamino)-5-oxopent-3-ynyl)benzoate
  参考文献：
  名称：

  Synthesis and Evaluation of Radamide Analogues, A Chimera of Radicicol and Geldanamycin

  摘要：

  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.

  DOI：

  10.1021/jo900278g

文献信息

• 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.