1-(2-chloro-5-nitro-benzyl)-4-isopropyl piperazine | 1138471-32-5

• 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-nitro-benzyl)-4-isopropyl piperazine
• 英文别名: 1-(2-chloro-5-nitrobenzyl)-4-isopropyl-piperazine；1-[(2-Chloro-5-nitrophenyl)methyl]-4-propan-2-ylpiperazine
• CAS: 1138471-32-5
• 化学式: C₁₄H₂₀ClN₃O₂
• 分子量: 297.785
• InChiKey: IBKYGWNFZOKKKX-UHFFFAOYSA-N

物化性质

• 沸点：
  401.1±40.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-5-nitro-benzyl)-4-isopropyl piperazine 在 盐酸 、 tin 、 水 作用下， 反应 1.5h， 以80%的产率得到4-chloro-3-(4-isopropyl-piperazin-1-ylmethyl)-phenylamine
  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
• 作为产物：
  描述：

  1-异丙基哌嗪 、 2-溴甲基-1-氯-4-硝基苯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以29%的产率得到1-(2-chloro-5-nitro-benzyl)-4-isopropyl piperazine
  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

• US7531553B2
  申请人：——

  公开号：US7531553B2

  公开（公告）日：2009-05-12
• 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.