N-(3-benzyloxyphenyl)-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-(3-benzyloxyphenyl)-2-bromoacetamide
• 英文别名: N-[3-(benzyloxy)phenyl]-2-bromo-N-methylacetamide；N-[3-(Benzyloxy)phenyl]-2-bromoacetamide；2-bromo-N-(3-phenylmethoxyphenyl)acetamide
• 化学式: C₁₅H₁₄BrNO₂
• 分子量: 320.186
• InChiKey: NLPHPYDKLFUNPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3-benzyloxyphenyl)-2-bromoacetamide 在 lithium aluminium tetrahydride 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~60.0 ℃ 、405.33 kPa 条件下， 反应 5.0h， 生成 3-[2-(4-phenylpiperazin-1-yl)ethylamino]phenol
  参考文献：
  名称：

  Towards the development of 5-HT7 ligands combining serotonin-like and arylpiperazine moieties

  摘要：

  Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed and synthesized a set of compounds including both a 5-hydroxyindol-3-ylethyl and a 1-arylpiperazine moieties connected by a short linker. The compounds were tested for their affinity for human 5-HT7 serotonin receptor. We further prepared a novel series of 5-HT7 ligands, where the 5-hydroxyindol-3-ylethyl moiety was bioisosterically replaced by a 3-hydroxyanilinoalkyl one. Among the newly synthesized compounds, potent ligands at the 5-HT7 receptor, behaving as antagonists in functional tests, were identified, even if they showed limited subtype selectivity. Docking studies within a model of the 5-HT7 receptor showed that the binding site can actually accommodate both moieties, with the serotonin-like one in the putative orthosteric site and the arylpiperazine one occupying an accessory pocket. The present results demonstrate that it is possible to devise and develop new 5-HT7 ligands merging two privileged structures in the same molecule.

  DOI：

  10.1016/j.ejmech.2014.04.034
• 作为产物：
  描述：

  N-(3-羟基苯基)乙酰胺 在 氯化亚砜 、 potassium tert-butylate 、 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 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 N-(3-benzyloxyphenyl)-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

• Benzoquinones as inhibitors of botulinum neurotoxin serotype A
  作者：Paul T. Bremer、Mark S. Hixon、Kim D. Janda

  DOI：10.1016/j.bmc.2014.06.004

  日期：2014.8

  Although botulinum neurotoxin serotype A (BoNT/A) is known for its use in cosmetics, it causes a potentially fatal illness, botulism, and can be used as a bioterror weapon. Many compounds have been developed that inhibit the BoNTA zinc-metalloprotease light chain (LC), however, none of these inhibitors have advanced to clinical trials. In this study, a fragment-based approach was implemented to develop

  虽然肉毒杆菌神经毒素血清型 A (BoNT/A) 因其在化妆品中的使用而闻名，但它会导致潜在的致命疾病肉毒杆菌中毒，并可用作生物恐怖武器。已经开发出许多抑制 BoNTA 锌金属蛋白酶轻链 (LC) 的化合物，但是，这些抑制剂均未进行临床试验。在这项研究中，实施了基于片段的方法来开发 BoNT/A LC 的新型共价抑制剂。首先，针对 BoNT/A LC 筛选亲电子片段，发现苯醌 (BQ) 衍生物具有活性。在动力学研究中，BQ 化合物充当不可逆抑制剂，推测可能共价修饰 BoNT/A LC 的半胱氨酸 165。尽管大多数 BQ 衍生物在体外对谷胱甘肽具有高度反应性，一些化合物（如天然产物萘他林）表现出低硫醇反应性和良好的 BoNT/A 抑制。为了增加 BQ 片段的效力，采用计算对接研究来阐明一种支架，该支架可以与 Cys165 相邻位点结合，同时将 BQ 片段定位在 Cys165 上进行共价修饰
• Synthesis and Evaluation of a Class of Compounds Inhibiting the Growth of Stromal Antigen 2 ( <i>STAG2</i> )‐Mutant Ewing Sarcoma Cells
  作者：Nenggang Zhang、Keng‐Fu Lin、Christian Yang、Scott Peruski、Debananda Pati、Scott R. Gilbertson

  DOI：10.1002/cmdc.202100653

  日期：2022.5.4

  Going STAG: Selectively inhibiting cancer cells that lack stromal antigen 2 (STAG2) is an attractive approach for cancer therapy, particularly Ewing sarcoma. Herein we report a small-molecule, StagX1, and the synthesis of derivatives of such by a new route. These compounds selectively inhibit cancer cells that lack STAG2.

  走向 STAG：选择性抑制缺乏基质抗原 2 (STAG2) 的癌细胞是一种有吸引力的癌症治疗方法，尤其是尤文肉瘤。在这里，我们报告了一种小分子 StagX1，以及通过新途径合成此类衍生物的方法。这些化合物选择性地抑制缺乏 STAG2 的癌细胞。
• 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.
• 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.
• Towards the development of 5-HT7 ligands combining serotonin-like and arylpiperazine moieties
  作者：Gilberto Spadoni、Annalida Bedini、Silvia Bartolucci、Daniele Pala、Marco Mor、Teresa Riccioni、Franco Borsini、Walter Cabri、Diana Celona、Mauro Marzi、Giorgio Tarzia、Silvia Rivara、Patrizia Minetti

  DOI：10.1016/j.ejmech.2014.04.034

  日期：2014.6

  Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed and synthesized a set of compounds including both a 5-hydroxyindol-3-ylethyl and a 1-arylpiperazine moieties connected by a short linker. The compounds were tested for their affinity for human 5-HT7 serotonin receptor. We further prepared a novel series of 5-HT7 ligands, where the 5-hydroxyindol-3-ylethyl moiety was bioisosterically replaced by a 3-hydroxyanilinoalkyl one. Among the newly synthesized compounds, potent ligands at the 5-HT7 receptor, behaving as antagonists in functional tests, were identified, even if they showed limited subtype selectivity. Docking studies within a model of the 5-HT7 receptor showed that the binding site can actually accommodate both moieties, with the serotonin-like one in the putative orthosteric site and the arylpiperazine one occupying an accessory pocket. The present results demonstrate that it is possible to devise and develop new 5-HT7 ligands merging two privileged structures in the same molecule.