8-bromo-N-phenyloctanamide | 792933-06-3

• 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-bromo-N-phenyloctanamide
• CAS: 792933-06-3
• 化学式: C₁₄H₂₀BrNO
• 分子量: 298.223
• InChiKey: UDNMLGBGUNNKIV-UHFFFAOYSA-N

物化性质

• 沸点：
  438.4±28.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 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：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  8-bromo-N-phenyloctanamide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 8-mercapto-N-phenyloctanamide
  参考文献：
  名称：

  人组蛋白脱乙酰基酶的新型抑制剂：基于SAHA的非异羟肟酸酯的设计，合成，酶抑制和癌细胞生长抑制。

  摘要：

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。

  DOI：

  10.1021/jm049207j
• 作为产物：
  描述：

  壬二酸 在 氯化亚砜 、 水 、 对甲苯磺酸 、 silver nitrate 、 三乙胺 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 17.83h， 生成 8-bromo-N-phenyloctanamide
  参考文献：
  名称：

  Synthesis, antiproliferation, and docking studies of N-phenyl-lipoamide and 8-mercapto-N-phenyloctanamide derivatives: effects of C6 position thiol moiety

  摘要：

  Some N-phenyl lipoamide and 8-mercapto-N-phenyloctanamide derivatives were synthesized and their in vitro antiproliferative activity was evaluated. The experimental results indicated that 8-mercapto-N-phenyloctanamides might be good histone deacetylase inhibitors rather than N-phenyl lipoamides, who had thiol moiety at C6 position. To verify the antiproliferation data on structural basis, in silico docking studies of the representative compounds into the crystal structure of histone deacetylase-like protein using AutoDock 4.0 program were performed. Furthermore, sulfur acetylated 8-mercapto-N-phenyloctanamide improved its in vitro antiproliferative activity, probably due to the increasing of its cell membrane permeability. While the identification of enzymatic target of N-phenyl lipoamides with dithiolane is still ongoing.

  DOI：

  10.1007/s00044-011-9879-7

文献信息

• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET PROCÉDÉS
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2013066836A1

  公开（公告）日：2013-05-10

  The present invention relates to compounds that inhibit histone deacetylase (HDAC) enzymes, the preparation of these compounds or salts of said compound, the use of these compounds in the treatment of neurodegenerative diseases or conditions ameliorated by inhibition of HDAC activity and pharmaceutical compositions that are comprised of these compounds.

  本发明涉及抑制组蛋白去乙酰化酶（HDAC）酶的化合物，这些化合物或该化合物的盐的制备，这些化合物在治疗神经退行性疾病或通过抑制HDAC活性改善的病症中的使用，以及由这些化合物组成的药物组合物。
• Synthesis and anticancer evaluation of α-lipoic acid derivatives
  作者：Shi-Jie Zhang、Qiu-Fu Ge、Dian-Wu Guo、Wei-Xiao Hu、Hua-Zhang Liu

  DOI：10.1016/j.bmcl.2010.03.112

  日期：2010.5

  α-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 μg/mL. Compound 17m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which

  合成了α-硫辛酸衍生物，并评估了其对NCI-460，HO-8910，KB，BEL-7402和PC-3细胞系的体外抗癌活性。结果，对于大多数化合物而言，它们表现出剂量依赖性的抑制特性，并且几种化合物在100μg/ mL的剂量下具有良好的抑制作用。进一步选择化合物17m用于针对ICR小鼠中的S180异种移植物的体内评估，该化合物通过200mg / kg体重的胃内给药具有24.7％的肿瘤重量抑制。此外，LD 50在小鼠17米通过IG超过1000毫克/公斤体重。
• 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
• Thiol-based SAHA analogues as potent histone deacetylase inhibitors
  作者：Takayoshi Suzuki、Akiyasu Kouketsu、Azusa Matsuura、Arihiro Kohara、Shin-ichi Ninomiya、Kohfuku Kohda、Naoki Miyata

  DOI：10.1016/j.bmcl.2004.03.063

  日期：2004.6

  In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a series of thiol-based compounds modeled after suberoylanilide hydroxamic acid (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated. Compound 6, in which the hydroxamic acid of SAHA was replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. (C) 2004 Elsevier Ltd. All rights reserved.
• Novel Inhibitors of Human Histone Deacetylases:  Design, Synthesis, Enzyme Inhibition, and Cancer Cell Growth Inhibition of SAHA-Based Non-hydroxamates
  作者：Takayoshi Suzuki、Yuki Nagano、Akiyasu Kouketsu、Azusa Matsuura、Sakiko Maruyama、Mineko Kurotaki、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1021/jm049207j

  日期：2005.2.1

  To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。