1-(2-chloro-5-nitrobenzyl)-1H-imidazole | 1097788-41-4

• 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: 1-(2-chloro-5-nitrobenzyl)-1H-imidazole
• 英文别名: 1-[(2-Chloro-5-nitrophenyl)methyl]imidazole
• CAS: 1097788-41-4
• 化学式: C₁₀H₈ClN₃O₂
• 分子量: 237.645
• InChiKey: BOJRFMLDDOSXDT-UHFFFAOYSA-N

物化性质

• 沸点：
  438.1±30.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-5-nitrobenzyl)-1H-imidazole 在 盐酸 、 5%-palladium/activated carbon 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 以92%的产率得到1-(5-amino-2-chlorobenzyl)-1H-imidazol-3-ium hydrochloride
  参考文献：
  名称：

  咪唑衍生物对金属-β-内酰胺酶IMP-1的合成及抑制活性的研究。

  摘要：

  由于过度使用或滥用β-内酰胺类抗生素，细菌中的突变会导致抗生素耐药性。细菌可以对抗生素产生耐药性的一种策略是分泌金属β-内酰胺酶，该酶可以打开β-内酰胺抗生素的内酰胺环并使它们失活。这个问题对人类健康构成威胁，克服这种情况的一种策略是将β-内酰胺类抗生素与抑制剂并用。迄今为止，尚无关于金属β-内酰胺酶（MBL）的临床可用抑制剂的报道，而丝氨酸β-内酰胺酶的临床抑制剂对MBL毫无用处。因此，找到一种有效的MBL抑制剂非常重要。在这项研究中，主要合成了咪唑衍生物，并测定了它们的抑制活性。后来，计算机结合模型用于预测配体进入酶活性位点的构型和构象。用IC演示了两个分子针对MBL（IMP-1）的39 µM中的50和46 µM中的50。

  DOI：

  10.1016/j.bioorg.2019.103277
• 作为产物：
  描述：

  咪唑 、 2-氯-5-硝基苯甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 1-(2-chloro-5-nitrobenzyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis, Antimalarial Activity, and Preclinical Pharmacology of a Novel Series of 4′-Fluoro and 4′-Chloro Analogues of Amodiaquine. Identification of a Suitable “Back-Up” Compound for N-tert-Butyl Isoquine

  摘要：

  On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline arnodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites,, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.

  DOI：

  10.1021/jm8012757

文献信息

• Synthesis, Antimalarial Activity, and Preclinical Pharmacology of a Novel Series of 4′-Fluoro and 4′-Chloro Analogues of Amodiaquine. Identification of a Suitable “Back-Up” Compound for <i>N-tert</i>-Butyl Isoquine
  作者：Paul M. O’Neill、Alison E. Shone、Deborah Stanford、Gemma Nixon、Eghbaleh Asadollahy、B. Kevin Park、James L. Maggs、Phil Roberts、Paul A. Stocks、Giancarlo Biagini、Patrick G. Bray、Jill Davies、Neil Berry、Charlotte Hall、Karen Rimmer、Peter A. Winstanley、Stephen Hindley、Ramesh B. Bambal、Charles B. Davis、Martin Bates、Stephanie L. Gresham、Richard A. Brigandi、Federico M. Gomez-de-las-Heras、Domingo V. Gargallo、Silvia Parapini、Livia Vivas、Hollie Lander、Donatella Taramelli、Stephen A. Ward

  DOI：10.1021/jm8012757

  日期：2009.4.9

  On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline arnodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites,, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.
• Synthesis and investigation of inhibitory activities of imidazole derivatives against the metallo-β-lactamase IMP-1
  作者：Omid Khalili Arjomandi、Mahboubeh Kavoosi、Hadi Adibi

  DOI：10.1016/j.bioorg.2019.103277

  日期：2019.11

  of β-lactam antibiotics with an inhibitor. So far, no clinically available inhibitors of metallo β-lactamases (MBLs) reported and the clinically inhibitors of serine β-lactamase are useless for MBLs. Accordingly, finding a potent inhibitor of the MBLs being very important. In this study, imidazole derivatives primarily were synthesized and their inhibitory activity were measured. Later in silico binding

  由于过度使用或滥用β-内酰胺类抗生素，细菌中的突变会导致抗生素耐药性。细菌可以对抗生素产生耐药性的一种策略是分泌金属β-内酰胺酶，该酶可以打开β-内酰胺抗生素的内酰胺环并使它们失活。这个问题对人类健康构成威胁，克服这种情况的一种策略是将β-内酰胺类抗生素与抑制剂并用。迄今为止，尚无关于金属β-内酰胺酶（MBL）的临床可用抑制剂的报道，而丝氨酸β-内酰胺酶的临床抑制剂对MBL毫无用处。因此，找到一种有效的MBL抑制剂非常重要。在这项研究中，主要合成了咪唑衍生物，并测定了它们的抑制活性。后来，计算机结合模型用于预测配体进入酶活性位点的构型和构象。用IC演示了两个分子针对MBL（IMP-1）的39 µM中的50和46 µM中的50。