2-(6′-aminobenzo[b]thiophen-3′-yl)-6,8,8-triethyldesmosdumotin B

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-(6′-aminobenzo[b]thiophen-3′-yl)-6,8,8-triethyldesmosdumotin B
• 英文别名: 2-(6-Amino-1-benzothiophen-3-yl)-6,8,8-triethyl-5-hydroxychromene-4,7-dione；2-(6-amino-1-benzothiophen-3-yl)-6,8,8-triethyl-5-hydroxychromene-4,7-dione
• 化学式: C₂₃H₂₃NO₄S
• 分子量: 409.506
• InChiKey: SXOJQODEQIGJOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(6′-aminobenzo[b]thiophen-3′-yl)-6,8,8-triethyldesmosdumotin B 、 丙酰氯 在 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 4.0h， 以100%的产率得到2-(6′-propanamidobenzo[b]thiophen-3′-yl)-6,6,8-triethyldesmosdumotin B
  参考文献：
  名称：

  Antitubulin effects of aminobenzothiophene-substituted triethylated chromones

  摘要：

  In the course of our continuing studies on the 2-(benzo[b] thiophene-3'-yl)-6,8,8-triethyldesmosdumotin B (TEDB-TB) series, we designed and synthesized nine amino-TEDB-TB derivatives to improve pharmaceutical properties, identify structure activity relationships, and discover novel antitubulin agents. Among all newly synthesized amino-TEDB-TBs, the 5'- and 6'-amino derivatives, 6 and 7, exhibited significant antiproliferative activity against five human tumor cell lines, including an MDR subline overexpressing P-gp. The IC50 values of 0.50-1.01 mu M were 3-6 times better than those of previously reported hydroxy-TEDB-TBs. Compounds 6 and 7 inhibited tubulin polymerization, induced both depolymerization of interphase microtubules and multiple spindle formations, and caused cell arrest at prometaphase. Among all compounds, compound 7 scored best pharmaceutically with LogP 2.11 and biologically with greater antiproliferative activity and induction of cell cycle arrest at prometaphase. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2017.04.055
• 作为产物：
  描述：

  2-acetyl-4,4,6-triethyl-3-hydroxy-5-methoxycyclohexa-2,5-dien-1-one 在 硫酸 、 碘 、 三溴化硼 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 23.0h， 生成 2-(6′-aminobenzo[b]thiophen-3′-yl)-6,8,8-triethyldesmosdumotin B
  参考文献：
  名称：

  Antitubulin effects of aminobenzothiophene-substituted triethylated chromones

  摘要：

  In the course of our continuing studies on the 2-(benzo[b] thiophene-3'-yl)-6,8,8-triethyldesmosdumotin B (TEDB-TB) series, we designed and synthesized nine amino-TEDB-TB derivatives to improve pharmaceutical properties, identify structure activity relationships, and discover novel antitubulin agents. Among all newly synthesized amino-TEDB-TBs, the 5'- and 6'-amino derivatives, 6 and 7, exhibited significant antiproliferative activity against five human tumor cell lines, including an MDR subline overexpressing P-gp. The IC50 values of 0.50-1.01 mu M were 3-6 times better than those of previously reported hydroxy-TEDB-TBs. Compounds 6 and 7 inhibited tubulin polymerization, induced both depolymerization of interphase microtubules and multiple spindle formations, and caused cell arrest at prometaphase. Among all compounds, compound 7 scored best pharmaceutically with LogP 2.11 and biologically with greater antiproliferative activity and induction of cell cycle arrest at prometaphase. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2017.04.055

文献信息

• Antitubulin effects of aminobenzothiophene-substituted triethylated chromones
  作者：Yukiko Kobayashi、Yohei Saito、Masuo Goto、Kyoko Nakagawa-Goto

  DOI：10.1016/j.bmcl.2017.04.055

  日期：2017.6

  In the course of our continuing studies on the 2-(benzo[b] thiophene-3'-yl)-6,8,8-triethyldesmosdumotin B (TEDB-TB) series, we designed and synthesized nine amino-TEDB-TB derivatives to improve pharmaceutical properties, identify structure activity relationships, and discover novel antitubulin agents. Among all newly synthesized amino-TEDB-TBs, the 5'- and 6'-amino derivatives, 6 and 7, exhibited significant antiproliferative activity against five human tumor cell lines, including an MDR subline overexpressing P-gp. The IC50 values of 0.50-1.01 mu M were 3-6 times better than those of previously reported hydroxy-TEDB-TBs. Compounds 6 and 7 inhibited tubulin polymerization, induced both depolymerization of interphase microtubules and multiple spindle formations, and caused cell arrest at prometaphase. Among all compounds, compound 7 scored best pharmaceutically with LogP 2.11 and biologically with greater antiproliferative activity and induction of cell cycle arrest at prometaphase. (C) 2017 Published by Elsevier Ltd.