3-Chloro-4,6-bis(methoxymethoxy)-2-(2-oxooct-7-enyl)benzoic acid | 1222967-72-7

• 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: 3-Chloro-4,6-bis(methoxymethoxy)-2-(2-oxooct-7-enyl)benzoic acid
• CAS: 1222967-72-7
• 化学式: C₁₉H₂₅ClO₇
• 分子量: 400.856
• InChiKey: ADPILBRABOZKCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-Chloro-4,6-bis(methoxymethoxy)-2-(2-oxooct-7-enyl)benzoic acid 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 43.0h， 生成 (E)-16-chloro-17,19-bis(methoxymethoxy)-3-methyl-4,5,6,7,10,11,12,13-octahydrobenzo[c][1]oxacycloheptadecine-1,14(3H,15H)-dione
  参考文献：
  名称：

  Identification of Natural Compound Radicicol as a Potent FTO Inhibitor

  摘要：

  The fat mass and obesity-associated protein (FTO), as an m(6)A demethylase, is involved in many human diseases. Virtual screening and similarity search in combination with bioactivity assay lead to the identification of the natural compound radicicol as a potent FTO inhibitor, which exhibits a dose-dependent inhibition of FTO demethylation activity with an IC50 value of 16.04 mu M. Further ITC experiments show that the binding between radicicol and FTO was mainly entropy-driven. Crystal structure analysis reveals that radicicol adopts an L-shaped conformation in the FTO binding site and occupies the same position as N-CDPCB, a previously identified small molecular inhibitor of FTO. Unexpectedly, however, the 1,3-diol group conserved in radicicol and N-CDPCB assumes strikingly different orientations for interaction with FTO. The identification of radicicol as an FTO inhibitor and revelation of its recognition mechanism not only opens the possibility of developing new therapeutic strategies for treatment of leukemia but also provide clues for elucidation of the acting mechanisms of radicicol, which is a possible clinical candidate worth in-depth study.

  DOI：

  10.1021/acs.molpharmaceut.8b00522
• 作为产物：
  描述：

  ethyl 2-(5-chloro-6,8-bis(methoxymethoxy)-1-oxo-1H-isochromen-3-yl)hept-6-enoate 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 18.0h， 生成 3-Chloro-4,6-bis(methoxymethoxy)-2-(2-oxooct-7-enyl)benzoic acid
  参考文献：
  名称：

  靶向Hsp90伴侣：Hsp90的新型间苯二酸大内酯抑制剂的合成

  摘要：

  已经通过化学合成制备了一系列的苯并马甲内酯，并被评估为热休克蛋白90（Hsp90）的抑制剂，HSP90是新型癌症治疗剂的新兴靶标。描述了天然产物radicicol的这些间苯二酸大内酯类似物的新合成，其中关键步骤是酰化和开裂高邻苯二甲酸酐以生成异香豆素，然后进行开环易位以形成大环。该方法已扩展到一系列新的结合了1,2,3-三唑环的内酯。

  DOI：

  10.1002/chem.200902766

文献信息

• An Improved Synthesis of Resorcylic Acid Macrolactone Inhibitors of Hsp90
  作者：Christopher Moody、James Day、Alexander Blake

  DOI：10.1055/s-0029-1217329

  日期：——

  A synthesis of resorcylic acid macrolactone analogues of the natural product radicicol is described in which the key steps are the acylation and ring opening of a homophthalic anhydride to give an isocoumarin, followed by a ring-closing metathesis to form the macrocycle.

  本文介绍了天然产物根赤壳菌素类化合物中，一种含有间苯二甲酸酐衍生物的合成方法，关键步骤包括酰化反应和环打开以生成异香豆素，随后通过环闭合的交叉复分解反应形成大环结构。
• Targeting the Hsp90 Chaperone: Synthesis of Novel Resorcylic Acid Macrolactone Inhibitors of Hsp90
  作者：James E. H. Day、Swee Y. Sharp、Martin G. Rowlands、Wynne Aherne、Paul Workman、Christopher J. Moody

  DOI：10.1002/chem.200902766

  日期：——

  A series of benzo‐macrolactones has been prepared by chemical synthesis, and evaluated as inhibitors of heat shock protein 90 (Hsp90), an emerging attractive target for novel cancer therapeutic agents. A new synthesis of these resorcylic acid macrolactone analogues of the natural product radicicol is described in which the key steps are the acylation and ring opening of a homophthalic anhydride to

  已经通过化学合成制备了一系列的苯并马甲内酯，并被评估为热休克蛋白90（Hsp90）的抑制剂，HSP90是新型癌症治疗剂的新兴靶标。描述了天然产物radicicol的这些间苯二酸大内酯类似物的新合成，其中关键步骤是酰化和开裂高邻苯二甲酸酐以生成异香豆素，然后进行开环易位以形成大环。该方法已扩展到一系列新的结合了1,2,3-三唑环的内酯。
• Identification of Natural Compound Radicicol as a Potent FTO Inhibitor
  作者：Ruiyong Wang、Zhifu Han、Bingjie Liu、Bin Zhou、Ning Wang、Qingwei Jiang、Yan Qiao、Chuanjun Song、Jijie Chai、Junbiao Chang

  DOI：10.1021/acs.molpharmaceut.8b00522

  日期：2018.9.4

  The fat mass and obesity-associated protein (FTO), as an m(6)A demethylase, is involved in many human diseases. Virtual screening and similarity search in combination with bioactivity assay lead to the identification of the natural compound radicicol as a potent FTO inhibitor, which exhibits a dose-dependent inhibition of FTO demethylation activity with an IC50 value of 16.04 mu M. Further ITC experiments show that the binding between radicicol and FTO was mainly entropy-driven. Crystal structure analysis reveals that radicicol adopts an L-shaped conformation in the FTO binding site and occupies the same position as N-CDPCB, a previously identified small molecular inhibitor of FTO. Unexpectedly, however, the 1,3-diol group conserved in radicicol and N-CDPCB assumes strikingly different orientations for interaction with FTO. The identification of radicicol as an FTO inhibitor and revelation of its recognition mechanism not only opens the possibility of developing new therapeutic strategies for treatment of leukemia but also provide clues for elucidation of the acting mechanisms of radicicol, which is a possible clinical candidate worth in-depth study.