(E)-3-(4-(((adamantan-1-ylmethyl)(13C)(methyl)amino)methyl)phenyl)-N-hydroxyacrylamide | 1629052-59-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4-(((adamantan-1-ylmethyl)(13C)(methyl)amino)methyl)phenyl)-N-hydroxyacrylamide
• 英文别名: (E)-3-(4-((((3r,5r,7r)-adamantan-1-ylmethyl)(methyl)amino)methyl)phenyl)-N-hydroxyacrylamide；[11C]martinostat；Martinostat C-11；(E)-3-[4-[[1-adamantylmethyl((111C)methyl)amino]methyl]phenyl]-N-hydroxyprop-2-enamide
• CAS: 1629052-59-0
• 化学式: C₂₂H₃₀N₂O₂
• 分子量: 353.481
• InChiKey: WNIDBXBLQFPAJA-WKEKCCTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  [11C]methyl iodide 、 (E)-3-(4-((((3r,5r,7r)-adamantan-1-ylmethyl)amino)methyl)-phenyl)-N-hydroxyacrylamide 以 二甲基亚砜 为溶剂， 反应 0.07h， 生成 (E)-3-(4-(((adamantan-1-ylmethyl)(13C)(methyl)amino)methyl)phenyl)-N-hydroxyacrylamide
  参考文献：
  名称：

  [EN] IMAGING HISTONE DEACETYLASES WITH A RADIOTRACER USING POSITRON EMISSION TOMOGRAPHY
  [FR] IMAGERIE D'HISTONE DÉSACÉTYLASES AU MOYEN D'UN RADIOTRACEUR À L'AIDE DE LA TOMOGRAPHIE PAR ÉMISSION DE POSITRONS

  摘要：

  本文揭示了用于正电子发射断层扫描的组蛋白去乙酰化酶成像试剂，以及利用这些组蛋白去乙酰化酶成像试剂的相关成像方法。组蛋白去乙酰化酶成像试剂可以是具有以下结构的化合物（I）：其中R1是包括正电子发射体的基团；R2代表氢，或取代或未取代的烷基，或取代或未取代的芳基，或取代或未取代的杂环芳基；n是选自0或1的整数。在化合物（I）的一个版本中，R1是包括一个脱氢环辛基团的基团。

  公开号：

  WO2015058106A1

文献信息

• [EN] IMAGING HISTONE DEACETYLASES WITH A RADIOTRACER USING POSITRON EMISSION TOMOGRAPHY<br/>[FR] IMAGERIE D'HISTONE DÉSACÉTYLASES AU MOYEN D'UN RADIOTRACEUR À L'AIDE DE LA TOMOGRAPHIE PAR ÉMISSION DE POSITRONS
  申请人：GEN HOSPITAL CORP

  公开号：WO2015058106A1

  公开（公告）日：2015-04-23

  Disclosed herein are histone deacetylase imaging agents for positron emission tomography and related imaging methods using the histone deacetylase imaging agents. The histone deacetylase imaging agents may be a compound of formula (I): wherein R1 is a moiety including a positron emitter; R2 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and n is an integer selected from 0 or 1. In one version of the compound of formula (I), R1 is a moiety including an adamantyl group.

  本文揭示了用于正电子发射断层扫描的组蛋白去乙酰化酶成像试剂，以及利用这些组蛋白去乙酰化酶成像试剂的相关成像方法。组蛋白去乙酰化酶成像试剂可以是具有以下结构的化合物（I）：其中R1是包括正电子发射体的基团；R2代表氢，或取代或未取代的烷基，或取代或未取代的芳基，或取代或未取代的杂环芳基；n是选自0或1的整数。在化合物（I）的一个版本中，R1是包括一个脱氢环辛基团的基团。
• High‐yielding, automated radiosynthesis of [ ¹¹ C]martinostat using [ ¹¹ C]methyl triflate
  作者：Robert Hopewell、Dean Jolly、Qian Ying Li、Karen Ross、I‐Huang Tsai、Monica Lacatus‐Samoila、Jean‐Paul Soucy、Eliane Kobayashi、Pedro Rosa‐Neto、Gassan Massarweh

  DOI：10.1002/jlcr.3968

  日期：2022.5.30

  Histone deacetylases (HDACs) mediate epigenetic mechanisms implicated in a broad range of central nervous system dysfunction, including neurodegenerative diseases and neuropsychiatric disorders. [11C]Martinostat allows in vivo quantification of class I/IIb HDACs and may be useful for the quantification of drug–occupancy relationship, facilitating drug development for disease modifying therapies. The present study reports a radiosynthesis of [11C]martinostat using [11C]methyl triflate in ethanol, as opposed to the originally described synthesis using [11C]methyl iodide and DMSO. [11C]Methyl triflate is trapped in a solution of 2 mg of precursor 1 dissolved in anhydrous ethanol (400 μl), reacted at ambient temperature for 5 min and purified by high-performance liquid chromatography; 1.5–1.8 GBq (41–48 mCi; n = 3) of formulated [11C]martinostat was obtained from solid-phase extraction using a hydrophilic–lipophilic cartridge in a radiochemical yield of 11.4% ± 1.1% (nondecay corrected to trapped [11C]MeI), with a molar activity of 369 ± 53 GBq/μmol (9.97 ± 1.3 Ci/μmol) at the end of synthesis (40 min) and validated for human use. This methodology was used at our production site to produce [11C]martinostat in sufficient quantities of activity to scan humans, including losses incurred from decay during pre-release quality control testing.

  组蛋白去乙酰化酶（HDACs）介导的表观遗传机制与多种中枢神经系统功能障碍有关，包括神经退行性疾病和神经精神疾病。[11C]马汀诺司他（Martinostat）可以对 I/IIb 类 HDAC 进行体内定量，并可用于药物占位关系的定量，从而促进改变疾病疗法的药物开发。本研究报告了在乙醇中使用[11C]三氟甲基酯对[11C]马丁诺司特的放射合成，而不是最初描述的使用[11C]碘甲烷和二甲基亚砜的合成。[11C]三氟甲基甲烷被截留在 2 毫克前体 1 溶于无水乙醇（400 微升）的溶液中，在环境温度下反应 5 分钟，然后用高效液相色谱法纯化；1.5-1.8 GBq (41-48 mCi; n = 3)的配制[11C]马汀诺司特，使用亲水亲脂滤芯进行固相萃取，放射化学收率为 11.4% ± 1.1%（未衰减校正为截留[11C]MeI），合成结束时（40 分钟）摩尔活性为 369 ± 53 GBq/μmol (9.97 ± 1.3 Ci/μmol)，并通过人体使用验证。我们的生产基地采用这种方法生产出的[11C]马替诺司他具有足够的活性，可以对人体进行扫描，包括在释放前质量控制测试过程中因衰变造成的损失。
• HISTONE DEACETYLASE INHIBITORS
  申请人：The General Hospital Corporation

  公开号：US20170349540A1

  公开（公告）日：2017-12-07

  Provided herein are brain penetrant histone deacetylase (HDAC) inhibitors useful for treating diseases or disorders associated with HDAC. An exemplary HDAC inhibitor provided herein exhibits a brain-to-plasma ratio of 20:1. Pharmaceutical compositions comprising HDAC inhibitors and methods for treating diseases associated with HDAC are also provided.
• In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs
  作者：Changning Wang、Frederick A. Schroeder、Hsiao-Ying Wey、Ronald Borra、Florence F. Wagner、Surya Reis、Sung Won Kim、Edward B. Holson、Stephen J. Haggarty、Jacob M. Hooker

  DOI：10.1021/jm500872p

  日期：2014.10.9

  Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting in the context of cardiovascular disease and central nervous system dysfunciton Development of a molecular agent for non-invasive imaing to elucidate the distribution and functional role of HDACs in humans will accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and validation of an HDAC imaging agent, [C-11]6. Our imaging results demonstrate that this probe has high specificity, good selectivity, and appropriate kinetics and distribution for imaging HDACs in the brian, heart, kidney, pancreas. and spleen. Our findings support the translational potential for [C-11]6 for human epigenetic imaging.