8-amino-N-phenyloctanamide | 651767-94-1

• 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: 8-amino-N-phenyloctanamide
• 英文别名: 8-Amino-N-phenyloctanamide
• CAS: 651767-94-1
• 化学式: C₁₄H₂₂N₂O
• 分子量: 234.341
• InChiKey: OKIXXSHHRYJXGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  溴乙酰溴 、 8-amino-N-phenyloctanamide 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 8-(2-Bromo-acetylamino)-octanoic acid phenylamide
  参考文献：
  名称：

  Novel histone deacetylase inhibitors: design, synthesis, enzyme inhibition, and binding mode study of SAHA-Based non-hydroxamates

  摘要：

  In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were designed and synthesized as (i) substrate (acetyl lysine) analogues (compounds 3-7), (ii) analogues bearing various functional groups expected to chelate zinc ion (compounds 8-15), and (iii) analogues bearing nucleophilic functional groups which could bind covalently to HDACs (compounds 16-18). In this series, semicarbazide 8b and bromoacetamides 18b,c were found to be potent HDAC inhibitors for non-hydroxamates. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.048
• 作为产物：
  描述：

  壬二酸 在 palladium on activated charcoal 二苯基膦叠氮化物 、 氢气 、 三乙胺 作用下， 以 甲醇 、 苯 为溶剂， 生成 8-amino-N-phenyloctanamide
  参考文献：
  名称：

  Novel histone deacetylase inhibitors: design, synthesis, enzyme inhibition, and binding mode study of SAHA-Based non-hydroxamates

  摘要：

  In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were designed and synthesized as (i) substrate (acetyl lysine) analogues (compounds 3-7), (ii) analogues bearing various functional groups expected to chelate zinc ion (compounds 8-15), and (iii) analogues bearing nucleophilic functional groups which could bind covalently to HDACs (compounds 16-18). In this series, semicarbazide 8b and bromoacetamides 18b,c were found to be potent HDAC inhibitors for non-hydroxamates. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.048

文献信息

• Rational design of metabolically stable HDAC inhibitors: An overhaul of trifluoromethyl ketones
  作者：Banerjee Riddhidev、Karaj Endri、Lamichhane Sabitri、N. Kotsull, Lauren、Kuganesan Nishanth、Isailovic Dragan、Pflum Mary Kay H、Slama James、Taylor William、Tillekeratne L. M. Viranga

  DOI：10.1016/j.ejmech.2022.114807

  日期：2022.12

  regulation of gene expression using histone deacetylase (HDAC) inhibitors is a promising strategy for developing new anticancer agents. The most common HDAC inhibitors are hydroxamates, which, though highly potent, have limitations due to their poor pharmacokinetic properties and lack of isoform selectivity. Trifluoromethylketones (TFMK) developed as alternatives to hydroxamates are rapidly metabolized to inactive

  使用组蛋白脱乙酰酶 (HDAC) 抑制剂对基因表达进行表观遗传调控是开发新型抗癌药物的一种有前景的策略。最常见的 HDAC 抑制剂是异羟肟酸盐，虽然其效力很高，但由于其药代动力学特性较差且缺乏同工型选择性而具有局限性。作为异羟肟酸替代品而开发的三氟甲基酮（TFMK）在体内迅速代谢为无活性的三氟甲醇，这阻碍了它们作为潜在候选药物的进一步发展。为了克服这一限制，我们设计了三氟丙酮酰胺（TFPA）作为 TFMK 替代品。酮羰基旁边额外的吸电子基团的存在使得酮的水合物形式更加稳定，从而防止其在体内代谢还原为醇。此外，这种结构修饰降低了 TFMK 基团作为共价弹头消除脱靶效应的潜力。抑制剂帽基团的额外结构变化使得类似物在细胞毒性测定中的IC 50值范围从高纳摩尔到低微摩尔，并且它们对癌细胞比正常细胞更具选择性。一些最活跃的类似物以低纳摩尔 IC 50值抑制 HDAC 酶，并且被发现对 HDAC8 比