N¹-(benzyloxy)-N⁸-phenyloctanediamide

• 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: N¹-(benzyloxy)-N⁸-phenyloctanediamide
• 英文别名: N-phenyl-N'-phenylmethoxyoctanediamide
• 化学式: C₂₁H₂₆N₂O₃
• 分子量: 354.449
• InChiKey: KQODFZXYJOSWAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹-(benzyloxy)-N⁸-phenyloctanediamide 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 以88 %的产率得到伏立诺他
  参考文献：
  名称：

  阳光或 UVA 光介导的羧酸合成异羟肟酸

  摘要：

  报道了阳光或 UVA 光介导的从羧酸和受保护的羟胺合成异羟肟酸的方法，其关键步骤是电荷转移复合物的形成。DI-HRMS 的机理研究为各种中间体的形成提供了实验证据。合成了两种异羟肟酸药物（伏立诺他和布非昔美）。

  DOI：

  10.1002/ejoc.202300046
• 作为产物：
  描述：

  苯胺 在 4-二甲氨基吡啶 、 三氯溴甲烷 作用下， 以 乙腈 为溶剂， 反应 8.0h， 生成 N¹-(benzyloxy)-N⁸-phenyloctanediamide
  参考文献：
  名称：

  阳光或 UVA 光介导的羧酸合成异羟肟酸

  摘要：

  报道了阳光或 UVA 光介导的从羧酸和受保护的羟胺合成异羟肟酸的方法，其关键步骤是电荷转移复合物的形成。DI-HRMS 的机理研究为各种中间体的形成提供了实验证据。合成了两种异羟肟酸药物（伏立诺他和布非昔美）。

  DOI：

  10.1002/ejoc.202300046

文献信息

• [EN] BIOORTHOGONAL COMPOUNDS COMPRISING A PROPARGYL GROUP FOR TREATING CANCER<br/>[FR] COMPOSÉS BIOORTHOGONAUX COMPRENANT UN GROUPE PROPARGYLE POUR LE TRAITEMENT DU CANCER
  申请人：UNIV COURT UNIV OF EDINBURGH

  公开号：WO2017199028A1

  公开（公告）日：2017-11-23

  A method of preparing an active agent or a salt thereof from a prodrug first compound (1) comprising a propargyl group connected to an oxygen that is directly or indirectly connected to the active agent is provided, wherein the bond between the propargyl group and the oxygen is cleaved by reacting the first compound with palladium or gold, thereby releasing the active agent. Prodrug compositions suitable for use in the method are also provided.

  提供一种从前体第一化合物（1）中制备活性剂或其盐的方法，该化合物包括与直接或间接连接到活性剂的氧原子相连接的丙炔基，其中通过将第一化合物与钯或金反应来断裂丙炔基和氧之间的键，从而释放活性剂。还提供了适用于该方法的前体药物组合物。
• Efficient Palladium-Triggered Release of Vorinostat from a Bioorthogonal Precursor
  作者：Belén Rubio-Ruiz、Jason T. Weiss、Asier Unciti-Broceta

  DOI：10.1021/acs.jmedchem.6b01426

  日期：2016.11.10

  Bioorthogonal uncaging strategies have recently emerged as an experimental therapeutic approach to control drug release. Herein we report a novel masking strategy that enables to modulate the metal chelating properties of hydroxamic acid groups by bioorthogonal chemistry using Pd-functionalized resins. This novel approach allowed to devise an inactive precursor of the histone deacetylase inhibitor

  生物正交解笼策略最近已经出现，作为一种控制药物释放的实验性治疗方法。本文中，我们报告了一种新颖的掩蔽策略，该策略能够通过使用Pd官能化树脂的生物正交化学来调节异羟肟酸基团的金属螯合性能。这种新颖的方法可以设计出组蛋白脱乙酰基酶抑制剂伏立诺他的无活性前体，它在神经胶质瘤和肺癌的细胞培养模型中被异质Pd催化有效地解开了。
• <i>O</i>-Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity
  作者：Victoriano Corpas-López、Mavys Tabraue-Chávez、Yudibeth Sixto-López、Sonia Panadero-Fajardo、Fernando Alves de Lima Franco、José F. Domínguez-Seglar、Francisco Morillas-Márquez、Francisco Franco-Montalbán、Mónica Díaz-Gavilán、José Correa-Basurto、Julián López-Viota、Margarita López-Viota、José Pérez del Palacio、Mercedes de la Cruz、Nuria de Pedro、Joaquina Martín-Sánchez、José A. Gómez-Vidal

  DOI：10.1021/acs.jmedchem.9b02016

  日期：2020.6.11

  Leishmania (L.) infantum causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that O-alkyl hydroxamate derivatives displayed potent and selective in vitro activity against the amastigote stage of L. infantum while no activity was observed against promastigotes. Compound 5 showed potent in vivo activity against L. infantum. Moreover, the combination of compound 5 supported on gold nanoparticles and meglumine antimoniate was also effective in vivo and improved the activity of these compounds compared to that of the individual treatment. Docking studies showed that compound 5 did not reach highly conserved pocket C and established interactions with the semiconserved residues V44, A45, R242, and E243 in pocket A of LiSIR2rp1. The surface space determined by these four amino acids is not conserved in human sirtuins. Compound 5 represents a new class of selective ligands with antileishmanial activity.
• Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release
  作者：Kevin B. Daniel、Eric D. Sullivan、Yao Chen、Joshua C. Chan、Patricia A. Jennings、Carol A. Fierke、Seth M. Cohen

  DOI：10.1021/acs.jmedchem.5b00539

  日期：2015.6.11

  Histone deacetylase inhibitors (HDACi) target abnormal epigenetic states associated with a variety of pathologies, including cancer. Here, the development of a prodrug of the canonical broad-spectrum HDACi suberoylanilide hydroxamic acid (SAHA) is described. Although hydroxamic acids are utilized universally in the development of metalloenzyme inhibitors, they are considered to be poor pharmacophores with reduced activity in vivo. We developed a prodrug of SAHA by appending a promoiety, sensitive to thiols, to the hydroxamic acid warhead (termed SAHA-TAP). After incubation of SAHA-TAP with an HDAC, the thiol of a conserved HDAC cysteine residue becomes covalently tagged with the promoiety, initiating a cascade reaction that leads to the release of SAHA. Mass spectrometry and enzyme kinetics experiments validate that the cysteine residue is covalently appended with the TAP promoiety. SAHA-TAP demonstrates cytotoxicity activity against various cancer cell lines. This strategy represents an original prodrug design with a dual mode of action for HDAC inhibition.
• BIOORTHOGONAL COMPOUNDS COMPRISING A PROPARGYL GROUP FOR TREATING CANCER
  申请人：THE UNIVERSITY COURT OF THE UNIVERSITY OF EDINBURGH

  公开号：US20200289554A1

  公开（公告）日：2020-09-17

  A method of preparing an active agent or a salt thereof from a pro-drug first compound (1) comprising a propargyl group connected to an oxygen that is directly or indirectly connected to the active agent is provided, wherein the bond between the propargyl group and the oxygen is cleaved by reacting the first compound with palladium or gold, thereby releasing the active agent. Prodrug compositions suitable for use in the method are also provided.