methyl 3-chloro-4,6-dihydroxy-2-(4-(4-methoxy-2,5-bis(methoxymethoxy)phenylamino)-4-oxobutyl)benzoate | 1164273-80-6

• 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 3-chloro-4,6-dihydroxy-2-(4-(4-methoxy-2,5-bis(methoxymethoxy)phenylamino)-4-oxobutyl)benzoate
• 英文别名: Methyl 3-chloro-4,6-dihydroxy-2-[4-[4-methoxy-2,5-bis(methoxymethoxy)anilino]-4-oxobutyl]benzoate
• CAS: 1164273-80-6
• 化学式: C₂₃H₂₈ClNO₁₀
• 分子量: 513.929
• InChiKey: PCPCUSZMCBYKDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 3-chloro-4,6-dihydroxy-2-(4-(4-methoxy-2,5-bis(methoxymethoxy)phenylamino)-4-oxobutyl)benzoate 在 三甲基氯硅烷 、 sodium iodide 、 air 、 palladium diacetate 作用下， 以 二氯甲烷 、 乙腈 、 乙酸乙酯 为溶剂， 反应 6.5h， 生成 methyl 3-chloro-4,6-dihydroxy-2-(4-(4-methoxy-3,6-dioxocyclohexa-1,4-dienylamino)-4-oxobutyl)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：

  methyl 4,6-bis(tert-butyldimethylsilyloxy)-3-chloro-2-(4-(4-methoxy-2,5-bis(methoxymethoxy)phenylamino)-4-oxobutyl)benzoate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以82%的产率得到methyl 3-chloro-4,6-dihydroxy-2-(4-(4-methoxy-2,5-bis(methoxymethoxy)phenylamino)-4-oxobutyl)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