N-[4-hydroxy-2-[4-[(1S,3R,5R,9R,13R)-9-(hydroxymethyl)-16,16-dimethyl-7,11-dioxo-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecan-3-yl]butyl]phenyl]acetamide | 1431705-76-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: N-[4-hydroxy-2-[4-[(1S,3R,5R,9R,13R)-9-(hydroxymethyl)-16,16-dimethyl-7,11-dioxo-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecan-3-yl]butyl]phenyl]acetamide
• CAS: 1431705-76-8
• 化学式: C₂₉H₄₁NO₉
• 分子量: 547.646
• InChiKey: CEKRSAHOOABOIH-SRNYKQFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (1S,3R,5R,9R,13R)-16,16-dimethyl-9-(phenylmethoxymethyl)-3-[4-(3-phenylmethoxyphenyl)butyl]-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione 在 sodium tetrahydroborate 、 18-冠醚-6 、 nickel(II) chloride hexahydrate 、 palladium on activated charcoal 、 氢气 、 四丁基硝酸铵 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 N-[4-hydroxy-2-[4-[(1S,3R,5R,9R,13R)-9-(hydroxymethyl)-16,16-dimethyl-7,11-dioxo-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecan-3-yl]butyl]phenyl]acetamide
  参考文献：
  名称：

  Structure–activity studies on the side chain of a simplified analog of aplysiatoxin (aplog-1) with anti-proliferative activity

  摘要：

  We have recently developed a simplified analog of aplysiatoxin (aplog-1) as an activator of protein kinase C (PKC) with anti-proliferative activity like bryostain 1. To identify sites in aplog-1 that could be readily modified to optimize therapeutic performance and to develop a molecular probe for examining the analog's mode of action, substituent effects on the phenol ring were systematically examined. Whereas hydrophilic acetamido derivatives were less active than aplog-1 in inhibiting cancer cell growth and binding to PKCS, introduction of hydrophobic bromine and iodine atoms enhanced both biological activities. The anti-proliferative activity was found to correlate closely with molecular hydrophobicity, and maximal activity was observed at a log P value of 4.0-4.5. On the other hand, an induction test with Epstein-Barr virus early antigen demonstrated that these derivatives have less tumor-promoting activity in vitro than aplog-1 regardless of the hydrophobicity of their substituents. These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.013

文献信息

• Structure–activity studies on the side chain of a simplified analog of aplysiatoxin (aplog-1) with anti-proliferative activity
  作者：Hiroaki Kamachi、Keisuke Tanaka、Ryo C. Yanagita、Akira Murakami、Kazuma Murakami、Harukuni Tokuda、Nobutaka Suzuki、Yu Nakagawa、Kazuhiro Irie

  DOI：10.1016/j.bmc.2013.03.013

  日期：2013.5

  We have recently developed a simplified analog of aplysiatoxin (aplog-1) as an activator of protein kinase C (PKC) with anti-proliferative activity like bryostain 1. To identify sites in aplog-1 that could be readily modified to optimize therapeutic performance and to develop a molecular probe for examining the analog's mode of action, substituent effects on the phenol ring were systematically examined. Whereas hydrophilic acetamido derivatives were less active than aplog-1 in inhibiting cancer cell growth and binding to PKCS, introduction of hydrophobic bromine and iodine atoms enhanced both biological activities. The anti-proliferative activity was found to correlate closely with molecular hydrophobicity, and maximal activity was observed at a log P value of 4.0-4.5. On the other hand, an induction test with Epstein-Barr virus early antigen demonstrated that these derivatives have less tumor-promoting activity in vitro than aplog-1 regardless of the hydrophobicity of their substituents. These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1. (C) 2013 Elsevier Ltd. All rights reserved.