(9H-fluoren-9-yl)methyl (R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro-[2,4'-bithiazole]-4-carboxylate | 1621325-96-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (9H-fluoren-9-yl)methyl (R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro-[2,4'-bithiazole]-4-carboxylate
• CAS: 1621325-96-9
• 化学式: C₂₈H₂₉N₃O₄S₂
• 分子量: 535.688
• InChiKey: ZWGCZLZYVKAXOE-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.78
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  89.88
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (9H-fluoren-9-yl)methyl (R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro-[2,4'-bithiazole]-4-carboxylate 在 4-二甲氨基吡啶 、 二乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Evaluation of class I HDAC isoform selectivity of largazole analogues

  摘要：

  Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, a series of analogues with modifications in the valine or the linker region were prepared and evaluated for their class I isoform selectivity. The inhibition profile showed that the C2 position of largazole has an optimal steric requirement for efficient HDAC inhibition and that substitution of the trans-alkene in the linker with an aromatic group results in complete loss of activity. This data will aid the design of class I isoform selective HDAC inhibitors.

  DOI：

  10.1016/j.bmcl.2014.07.006
• 作为产物：
  描述：

  (R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro-[2,4'-bithiazole]-4-carboxylic acid 、 9-芴甲醇 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以63%的产率得到(9H-fluoren-9-yl)methyl (R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro-[2,4'-bithiazole]-4-carboxylate
  参考文献：
  名称：

  Evaluation of class I HDAC isoform selectivity of largazole analogues

  摘要：

  Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, a series of analogues with modifications in the valine or the linker region were prepared and evaluated for their class I isoform selectivity. The inhibition profile showed that the C2 position of largazole has an optimal steric requirement for efficient HDAC inhibition and that substitution of the trans-alkene in the linker with an aromatic group results in complete loss of activity. This data will aid the design of class I isoform selective HDAC inhibitors.

  DOI：

  10.1016/j.bmcl.2014.07.006

文献信息

• Synthesis and biological evaluation of largazole zinc-binding group analogs
  作者：Bumki Kim、Ranjala Ratnayake、Hyunji Lee、Guqin Shi、Sabrina L. Zeller、Chenglong Li、Hendrik Luesch、Jiyong Hong

  DOI：10.1016/j.bmc.2017.03.071

  日期：2017.6

  largazole analogs have been prepared to define structural requirements for its HDAC inhibitory activity. However, previous structure-activity relationship studies have heavily investigated the macrocycle region of largazole, while there have been only limited efforts to probe the effect of various zinc-binding groups (ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with various

  组蛋白乙酰化是经过广泛研究的翻译后修饰，作为表观遗传调节剂起着重要作用。它受组蛋白乙酰转移酶（HATs）和组蛋白脱乙酰酶（HDACs）的控制。在多种不同的疾病中均观察到HDACs的过表达和组蛋白的乙酰化过低，这导致HDACs最近成为人们关注的药物靶标。天然产物拉尔唑是迄今为止发现的最有效的天然HDAC抑制剂之一，并且已经制备了许多拉尔唑类似物以定义对其HDAC抑制活性的结构要求。但是，先前的结构-活性关系研究已经对拉拉唑的大环区域进行了深入研究，虽然只有有限的努力来探究各种锌结合基团（ZBGs）对HDAC抑制的影响。在这里，我们制备了一系列具有各种ZBG的largazole类似物，并评估了它们对HDAC的抑制作用和细胞毒性。尽管所测试的类似物均不如拉格唑那样有效或具有选择性，但每个ZBG的Zn2 +结合亲和力均与HDAC抑制作用和细胞毒性有关。我们希望我们的发现将有助于加深对ZBGs在HD
• [EN] MACROCYCLIC COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] COMPOSÉS MACROCYCLIQUES ET MÉTHODES DE TRAITEMENT ASSOCIÉES
  申请人：UNIV FLORIDA

  公开号：WO2015200699A3

  公开（公告）日：2016-05-26