5-(2-bromophenyl)thiophene-2-carbaldehyde

• 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: 5-(2-bromophenyl)thiophene-2-carbaldehyde
• 化学式: C₁₁H₇BrOS
• mdl: MFCD06410182
• 分子量: 267.146
• InChiKey: IQUYPNNYNSJOEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(2-bromophenyl)thiophene-2-carbaldehyde 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 N-[[5-(2-bromophenyl)thiophen-2-yl]methylidene]hydroxylamine
  参考文献：
  名称：

  Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane

  摘要：

  As the continuous rise in the incidence of antibiotic resistance, it is urgent to develop novel chemical scaffolds with antibacterial activities to control the spread of resistance to conventional antibiotics. In this study, a series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives were designed and synthesized by modifying the hit compound (N-2-isobutyl-N-4-((4-methyl-2-phenylthiazol-5-yl) methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in vitro and in vivo. Among the tested compounds, compound 14g (N4-((5-(3-bromophenyl)thiophen-2-yl)-methyl)N-2-isobutylpyrimidine-2,4-diamine) displayed the best antibacterial activities, which was not only capable of inhibiting E. coil and S. aureus growth at concentrations as low as 2 and 3 mu g/mL in vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound 14g was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure is challenging to induce bacterial resistance, which suggested that compound 14g may be a kind of promising alternatives to antibiotics against bacteria. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112141
• 作为产物：
  描述：

  5-溴噻吩-2-甲醛 、 2-溴苯基硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 乙醇 为溶剂， 反应 0.08h， 生成 5-(2-bromophenyl)thiophene-2-carbaldehyde
  参考文献：
  名称：

  Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane

  摘要：

  As the continuous rise in the incidence of antibiotic resistance, it is urgent to develop novel chemical scaffolds with antibacterial activities to control the spread of resistance to conventional antibiotics. In this study, a series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives were designed and synthesized by modifying the hit compound (N-2-isobutyl-N-4-((4-methyl-2-phenylthiazol-5-yl) methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in vitro and in vivo. Among the tested compounds, compound 14g (N4-((5-(3-bromophenyl)thiophen-2-yl)-methyl)N-2-isobutylpyrimidine-2,4-diamine) displayed the best antibacterial activities, which was not only capable of inhibiting E. coil and S. aureus growth at concentrations as low as 2 and 3 mu g/mL in vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound 14g was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure is challenging to induce bacterial resistance, which suggested that compound 14g may be a kind of promising alternatives to antibiotics against bacteria. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112141

文献信息

• <i>In vitro</i> ADME characterization of a very potent 3-acylamino-2-aminopropionic acid-derived GluN2C-NMDA receptor agonist and its ester prodrugs
  作者：Elena Bechthold、Lucie Grey、Emil Diamant、Judith Schmidt、Ruben Steigerwald、Fabao Zhao、Kasper B. Hansen、Lennart Bunch、Rasmus P. Clausen、Bernhard Wünsch

  DOI：10.1515/hsz-2022-0229

  日期：2023.3.28

  fast hydrolyzed to afford the acid UA3-10. Incubation with pig liver esterase and mouse serum led to rapid hydrolysis of the esters 12a–c. The isopropyl ester 12c showed a promising logD 7.4 value of 3.57 and the highest stability in the presence of pig liver esterase and mouse serum. These results demonstrate that ester prodrugs of UA3-10 can potentially afford improved bioavailability and CNS penetration

  GluN2C 亚基主要但不完全存在于小脑内的 NMDA 受体中。拮抗剂如 UBP1700 和正变构调节剂包括 PYD-106 和 3-酰氨基-2-氨基丙酸衍生物如 UA3-10 ((R)-2-amino-3-[5-(2-bromophenyl)thiophen-2-yl]carboxamido}propionic acid) 代表了有前途的工具化合物，用于研究含有 GluN2C 的 NMDA 受体在大脑信号转导中的作用。然而，由于其高极性，氨基酸 UA3-10 的生物利用度和 CNS 渗透预计相当低。在此，制备了 NMDA 受体甘氨酸位点激动剂 UA3-10 的三种酯前药 12a–c 并进行了药代动力学表征。酯 12a–c 显示出更高的亲脂性（更高的 log丁 7.4值）比酸 UA3-10 但与人血清白蛋白的结合几乎相同。酸 UA3-10 在与小鼠肝微粒体和 NADPH 孵育后相当稳定，但酯