8-(tert-butyldimethylsilyloxymethyl)-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one | 1079991-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 8-(tert-butyldimethylsilyloxymethyl)-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one
• 英文别名: 8-[[Tert-butyl(dimethyl)silyl]oxymethyl]-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4-one
• CAS: 1079991-25-5
• 化学式: C₂₃H₂₉NO₅Si
• 分子量: 427.572
• InChiKey: PQYDFHBYTQYIJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.01
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(tert-butyldimethylsilyloxymethyl)-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以99%的产率得到8-(hydroxymethyl)-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Phenanthridine-Based Bcl-X_L Inhibitors

  摘要：

  Despite their structural similarities, the natural products chelerythrine (5) and sanguinarine (6) target different binding sites on the pro-survival Bcl-X-L protein. This paper details the synthesis of phenanthridine-based analogues of the natural products that were used to probe this difference in binding profiles. The inhibitory constants for these compounds were then measured in a fluorescence polarization assay against Bcl-X-L. and the tagged Bak-BH3 peptide. The results led to structure-activity relationship studies, which identified the structural motifs required for binding-site specificity as well as inhibitory activity. We also identified synthetic analogues of the natural products that display similar binding modes but with more potent IC50 values.

  DOI：

  10.1021/jm8005433
• 作为产物：
  描述：

  5-bromo-N-(4-(tert-butyldimethylsilyloxymethyl)phenyl)-N-(methoxymerthyl)benzo[d][1,3]dioxole-4-carboxamide 在 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以71%的产率得到8-(tert-butyldimethylsilyloxymethyl)-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Phenanthridine-Based Bcl-X_L Inhibitors

  摘要：

  Despite their structural similarities, the natural products chelerythrine (5) and sanguinarine (6) target different binding sites on the pro-survival Bcl-X-L protein. This paper details the synthesis of phenanthridine-based analogues of the natural products that were used to probe this difference in binding profiles. The inhibitory constants for these compounds were then measured in a fluorescence polarization assay against Bcl-X-L. and the tagged Bak-BH3 peptide. The results led to structure-activity relationship studies, which identified the structural motifs required for binding-site specificity as well as inhibitory activity. We also identified synthetic analogues of the natural products that display similar binding modes but with more potent IC50 values.

  DOI：

  10.1021/jm8005433