N-[2-(4-fluorophenyl)ethyl]-2-bromoacetamide | 209398-45-8

• 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-[2-(4-fluorophenyl)ethyl]-2-bromoacetamide
• 英文别名: 2-bromo-N-[2-(4-fluorophenyl)ethyl]acetamide
• CAS: 209398-45-8
• 化学式: C₁₀H₁₁BrFNO
• 分子量: 260.106
• InChiKey: PDWGDZZDEXFEAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  伊布替尼中间体N-2 、 N-[2-(4-fluorophenyl)ethyl]-2-bromoacetamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以79%的产率得到2-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-N-(4-fluorophenethyl)acetamide
  参考文献：
  名称：

  新型吡唑并嘧啶基衍生物的设计和合成作为可逆的 BTK 抑制剂，在套细胞淋巴瘤中具有有效的抗增殖活性

  摘要：

  布鲁顿酪氨酸激酶（BTK）抑制剂的开发在B细胞恶性肿瘤和自身免疫性疾病的治疗中具有重要的价值和意义。在此，设计了一类新型的基于吡唑并嘧啶的 BTK 抑制剂，并在套细胞淋巴瘤 (MCL) 细胞系中进行了评估。我们证明，与先导化合物相比，目标化合物在提高抗增殖活性方面取得了很大进展。化合物13c、13g、13h、13l、13n和13o在 MCL 细胞系中表现出有效的抗增殖活性，具有个位数微摩尔效力。此外，化合物13l在 Z138 细胞中以剂量依赖性方式特别扰乱线粒体膜电位并增加活性氧水平。13l通过半胱天冬酶 3 介导的 Z138 细胞凋亡途径诱导细胞凋亡。总体而言，这项研究为开发抗肿瘤药物提供了有价值的先导化合物。

  DOI：

  10.1007/s00044-022-02861-7
• 作为产物：
  描述：

  溴乙酰氯 、 4-氟苯乙胺 在 三乙胺 作用下， 反应 2.0h， 生成 N-[2-(4-fluorophenyl)ethyl]-2-bromoacetamide
  参考文献：
  名称：

  Solid phase synthesis of a 1,3,5-trisubstituted pyridinium salt library

  摘要：

  DOI：

  10.1016/s0040-4039(98)00683-2

文献信息

• 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.
• Design and synthesis of novel 1-substituted 3-(6-phenoxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine analogs as selective BTK inhibitors for the treatment of mantle cell lymphoma
  作者：Fansheng Ran、Yang Liu、Shengping Yu、Kaiwen Guo、Wendi Tang、Xin Chen、Guisen Zhao

  DOI：10.1016/j.bioorg.2019.103367

  日期：2020.1

  Ibrutinib (IBN), a first-in-class BTK-inhibitor, was approved by the FDA for the treatment of mantle cell lymphoma (MCL). Although IBN shows excellent performance as an anti-lymphoma agent, it has some undesirable side effects due to its off-target activities. Our studies yielded a novel series of 3-(6-phenoxypyridin-3-yl)-4-amine-1H-pyrazolo [3,4-d]pyrimidine derivatives capable of potent inhibition of Bruton's tyrosine kinase (BTK). Notably, compound 13e explained potent BTK inhibitory activity and could completely inhibit the phosphorylation of BTK and PLC gamma 2 in Z138 cells at low micromolar concentration. Compared with IBN, compound 13e improved anti-proliferative activities 3-40 folds in MCL cell lines with IC50 values lower than 1 mu M. Low micromolar doses of 13e could induce strong cell apoptosis in Jeko-1 and Z138 cells. In addition, compound 13e showed greater BTK selectivity and higher stability in human liver microsomes than IBN and potential safety improvement for the treatment of MCL.