5,8-bis(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one | 1079991-32-4

• 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: 5,8-bis(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one
• 英文别名: 5,8-Bis(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4-one
• CAS: 1079991-32-4
• 化学式: C₁₈H₁₇NO₅
• 分子量: 327.337
• InChiKey: IZVRATZQKWCYIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 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：

  5,8-bis(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one 在 二异丁基氢化铝 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 盐酸 作用下， 以 四氢呋喃 、 甲苯 、 水 为溶剂， 反应 2.25h， 以100%的产率得到8-(methoxymethyl)-5-methyl-[1,3]dioxolo[4,5-i]phenanthridinium chloride
  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：

  8-(hydroxymethyl)-5-(methoxymethyl)-[1,3]dioxolo[4,5-i]phenanthridin-4(5H)-one 、 硫酸二甲酯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 6.33h， 以96%的产率得到5,8-bis(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

文献信息

• Structure−Activity Relationship Studies of Phenanthridine-Based Bcl-X_L Inhibitors
  作者：Paul H. Bernardo、Kah-Fei Wan、Thirunavukkarasu Sivaraman、Jin Xu、Felicity K. Moore、Alvin W. Hung、Henry Y. K. Mok、Victor C. Yu、Christina L. L. Chai

  DOI：10.1021/jm8005433

  日期：2008.11.13

  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.