8-isopentyl-7-hydroxy-chroman-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 3,4-二氢香豆素
• 英文名称: 8-isopentyl-7-hydroxy-chroman-2-one
• 英文别名: 8-isopentyl-7-hydroxychroman-2-one；7-Hydroxy-8-(3-methylbutyl)-3,4-dihydrochromen-2-one
• 化学式: C₁₄H₁₈O₃
• 分子量: 234.295
• InChiKey: VUMTXCSRVWFHTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-isopentyl-7-hydroxy-chroman-2-one 在 甲醇 、 18-冠醚-6 、 氯甲酸乙酯 、 四丁基碘化铵 、 potassium carbonate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 8.0h， 生成 N-hydroxy-7-(3-hydroxy-4-(2-hydroxycarbamoylethyl)-2-isopentyl-phenoxy)heptanamide
  参考文献：
  名称：

  Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors

  摘要：

  Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.002
• 作为产物：
  描述：

  蛇床子提取物 在 palladium on activated charcoal 氢气 、 三溴化硼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 8-isopentyl-7-hydroxy-chroman-2-one
  参考文献：
  名称：

  Identification and structure-activity relationship studies of osthol, a cytotoxic principle from Cnidium monnieri

  摘要：

  Osthol (1) was isolated from the fruit of Cnidium monnieri as a cytotoxic principle. Its structure-activity relationship study reveals that the 3,4-olefinic bond is essential for its cytotoxic activity, and the prenyl (C-5) unit attached at the 8 position enhances the cytotoxicity. Analogues 7 and 8 that have a longer alkoxy unit at the 7 position showed ten times higher cytotoxicity than 1. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00315-0

文献信息

• Synthesis of<i>N</i>-Hydroxycinnamides Capped with a Naturally Occurring Moiety as Inhibitors of Histone Deacetylase
  作者：Wei-Jan Huang、Ching-Chow Chen、Shi-Wei Chao、Shoei-Sheng Lee、Fen-Lin Hsu、Yeh-Lin Lu、Ming-Fang Hung、Chung-I Chang

  DOI：10.1002/cmdc.200900494

  日期：2010.4.6

  Histone deacetylase (HDAC) inhibitors are regarded as promising therapeutics for the treatment of cancer. All reported HDAC inhibitors contain three pharmacophoric features: a zinc‐chelating group, a hydrophobic linker, and a hydrophobic cap for surface recognition. In this study we investigated the effectiveness of osthole, a hydrophobic Chinese herbal compound, as the surface recognition cap in hydroxamate‐based

  组蛋白脱乙酰基酶（HDAC）抑制剂被认为是治疗癌症的有前途的疗法。所有已报道的HDAC抑制剂均具有三个药效学特征：锌螯合基团，疏水性连接基团和用于表面识别的疏水性帽。在这项研究中，我们研究了疏水性中草药化合物osthole作为HDAC抑制剂的异羟肟酸酯类化合物表面识别帽的有效性。合成了9种基于osthole的新型N-羟基肉桂酸酯，并筛选了其酶抑制活性。化合物9  d，9  e，9  g表现出抑制活性（IC 50 = 24.5，20.0，19.6 n M）对抗HeLa细胞中的核HDACs的作用，其可与亚磺酰苯胺异羟肟酸（SAHA; IC 50 = 24.5 n M）相比，后者是临床上用于治疗皮肤T细胞淋巴瘤（CTCL）的有效抑制剂。尽管化合物9  d和9  e对HDAC1和HDAC6表现出类似SAHA的活性，但化合物9  g对HDAC1的选择性更高。化合物9  d表现出最佳的细胞效应，这是比
• Identification and structure-activity relationship studies of osthol, a cytotoxic principle from Cnidium monnieri
  作者：Yukio Hitotsuyanagi、Hiroshi Kojima、Hiroshi Ikuta、Koichi Takeya、Hideji Itokawa

  DOI：10.1016/0960-894x(96)00315-0

  日期：1996.8

  Osthol (1) was isolated from the fruit of Cnidium monnieri as a cytotoxic principle. Its structure-activity relationship study reveals that the 3,4-olefinic bond is essential for its cytotoxic activity, and the prenyl (C-5) unit attached at the 8 position enhances the cytotoxicity. Analogues 7 and 8 that have a longer alkoxy unit at the 7 position showed ten times higher cytotoxicity than 1. Copyright (C) 1996 Elsevier Science Ltd
• Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors
  作者：Wei-Jan Huang、Ching-Chow Chen、Shi-Wei Chao、Chia-Chun Yu、Chen-Yui Yang、Jih-Hwa Guh、Yun-Chieh Lin、Chiao-I. Kuo、Ping Yang、Chung-I. Chang

  DOI：10.1016/j.ejmech.2011.06.002

  日期：2011.9

  Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines. (C) 2011 Elsevier Masson SAS. All rights reserved.