N-(4-benzoylphenyl)-2-bromoacetamide

• 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: N-(4-benzoylphenyl)-2-bromoacetamide
• 化学式: C₁₅H₁₂BrNO₂
• 分子量: 318.17
• InChiKey: APERNMZNTWPFGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-benzoylphenyl)-2-bromoacetamide 、 4,6-二甲基-2-巯基嘧啶 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-benzoylphenyl)-2-((4,6-dimethylpyrimidin-2-yl)thio)acetamide
  参考文献：
  名称：

  Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)- N -phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors

  摘要：

  Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl) thio)-N-phenylacetamide derivatives as SIRT2 inhibitors. SAR analyses with new synthesized derivatives revealed a number of new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an IC50 value of 42 nM. The selectivity analyses found that 28e has a very good selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a potent ability to inhibit human breast cancer cell line MCF-7 and increase the acetylation of alpha-tubulin in a dose-dependent manner. This study will aid further efforts to develop highly potent and selective SIRT2 inhibitors for the treatment of cancer and other related diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.010
• 作为产物：
  描述：

  4-氨基二苯甲酮 、 溴乙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 生成 N-(4-benzoylphenyl)-2-bromoacetamide
  参考文献：
  名称：

  Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)- N -phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors

  摘要：

  Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl) thio)-N-phenylacetamide derivatives as SIRT2 inhibitors. SAR analyses with new synthesized derivatives revealed a number of new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an IC50 value of 42 nM. The selectivity analyses found that 28e has a very good selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a potent ability to inhibit human breast cancer cell line MCF-7 and increase the acetylation of alpha-tubulin in a dose-dependent manner. This study will aid further efforts to develop highly potent and selective SIRT2 inhibitors for the treatment of cancer and other related diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.010

文献信息

• Ligand-based design and synthesis of novel sodium channel blockers from a combined phenytoin–lidocaine pharmacophore
  作者：Yuesheng Wang、Paulianda J. Jones、Timothy W. Batts、Victoria Landry、Manoj K. Patel、Milton L. Brown

  DOI：10.1016/j.bmc.2008.10.031

  日期：2009.10

  maps described a binding site predominately hydrophobic in nature. This model was then used to design and predict a series of novel sodium channel blockers that utilized overlapping structural features of phenytoin, hydroxy amides, and the local anesthetic lidocaine. Synthesis and evaluation of these compounds for their ability to inhibit [(3)H]-batrachotoxin revealed that these compounds have potent sodium

  电压门控钠通道仍然是开发新型阻滞剂的丰富领域。在这项研究中，我们使用比较分子场分析 (CoMFA)，一种基于配体的设计策略，生成基于局部麻醉剂、乙内酰脲和 α-羟基苯酰胺的 3D 模型，以阐明其在神经元钠通道中的结合位点的 SAR。通过偏最小二乘法 (PLS) 分析体外钠通道结合活性（表示为 pIC(50)）和 CoMFA 描述符列的相关性生成最终非交叉验证模型，训练集 q(2)=0.926。CoMFA 立体和静电图描述了本质上主要是疏水性的结合位点。然后使用该模型来设计和预测一系列新型钠通道阻滞剂，这些阻滞剂利用苯妥英、羟基酰胺、和局部麻醉剂利多卡因。合成和评价这些化合物抑制 [(3) H]-batrachotoxin 的能力表明这些化合物具有有效的钠通道阻滞作用。此外，CoMFA 模型能够准确预测这些化合物与神经元钠通道的结合。化合物 37 的合成和随后的钠通道评估（预测 IC(50)=7
• WATER-SOLUBLE DEGRADABLE PHOTO-CROSSLINKER
  申请人：Swan Dale G.

  公开号：US20110144373A1

  公开（公告）日：2011-06-16

  Described herein is a degradable linking agent that includes a core molecule with one or more charged groups; and one or more photoreactive groups covalently attached to the core molecule by one or more degradable linkers.

  本文描述了一种可降解的连接剂，包括一个具有一个或多个带电基团的核心分子；以及通过一个或多个可降解的连接链连接到核心分子的一个或多个光敏反应基团。
• Structure−Activity Relationships in the Binding of Chemically Derivatized CD4 to gp120 from Human Immunodeficiency Virus
  作者：Hui Xie、Danny Ng、Sergey N. Savinov、Barna Dey、Peter D. Kwong、Richard Wyatt、Amos B. Smith、Wayne A. Hendrickson

  DOI：10.1021/jm070564e

  日期：2007.10.1

  The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp 120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp 120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp 120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
• 10.1002/ddr.22224
  作者：Kaya, Selen Gozde、Eren, Gokcen、Massarotti, Alberto、Bakar-Ates, Filiz、Ozkan, Erva、Gozelle, Mahmut、Ozkan, Yesim

  DOI：10.1002/ddr.22224

  日期：——

  AbstractThe mammalian cytoplasmic protein SIRT2, a class III histone deacetylase family member, possesses NAD+‐dependent lysine deacetylase/deacylase activity. Dysregulation of SIRT2 has been implicated in the pathogenesis of several diseases, including neurological and metabolic disorders and cancer; thus, SIRT2 emerges as a potential therapeutic target. Herein, we identified a series of diaryl acetamides (ST61‐ST90) by the structural optimization of our hit STH2, followed by enhanced SIRT2 inhibitory potency and selectivity. Among them, ST72, ST85, and ST88 selectively inhibited SIRT2 with IC50 values of 9.97, 5.74, and 8.92 μM, respectively. Finally, the entire study was accompanied by in silico prediction of binding modes of docked compounds and the stability of SIRT2‐ligand complexes. We hope our findings will provide substantial information for designing selective inhibitors of SIRT2.
• Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)- N -phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors
  作者：Lingling Yang、Xiaobo Ma、Chen Yuan、Yanying He、Ling Li、Sha Fang、Wei Xia、Tao He、Shan Qian、Zhihong Xu、Guobo Li、Zhouyu Wang

  DOI：10.1016/j.ejmech.2017.04.010

  日期：2017.7

  Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl) thio)-N-phenylacetamide derivatives as SIRT2 inhibitors. SAR analyses with new synthesized derivatives revealed a number of new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an IC50 value of 42 nM. The selectivity analyses found that 28e has a very good selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a potent ability to inhibit human breast cancer cell line MCF-7 and increase the acetylation of alpha-tubulin in a dose-dependent manner. This study will aid further efforts to develop highly potent and selective SIRT2 inhibitors for the treatment of cancer and other related diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.