ethyl 4-[2-(4-fluorophenyl)-2-hydroxyethyl]piperazine-1-carboxylate | 89011-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 4-[2-(4-fluorophenyl)-2-hydroxyethyl]piperazine-1-carboxylate
• 英文别名: 2-(4-Ethoxycarbonylpiperazino)-1-(4-fluorophenyl)ethanol；1-ethoxycarbonyl-4-[2-(4-fluorophenyl)-2-hydroxyethyl]piperazine
• CAS: 89011-46-1
• 化学式: C₁₅H₂₁FN₂O₃
• 分子量: 296.342
• InChiKey: JBSIHYLBESSRGJ-UHFFFAOYSA-N

物化性质

• 熔点：
  56-58 °C(Solv: cyclohexane (110-82-7))
• 沸点：
  420.0±45.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-[2-(4-fluorophenyl)-2-hydroxyethyl]piperazine-1-carboxylate 在 氢氧化钾 、 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 生成 1-Ethyl-4-[1-(4-fluorophenyl)-2-piperazin-1-ylethyl]piperazine
  参考文献：
  名称：

  Structure−Activity Relationship of (1-Aryl-2-piperazinylethyl)piperazines:  Antagonists for the AGRP/Melanocortin Receptor Binding

  摘要：

  Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin action.(1) In the hypothalamus, melanocortin peptide agonists act as satiety-inducing factors that mediate their action through the melanocortin-4 receptor (MC4R) whereas AGRP is an opposing orexigenic agent. Novel inhibitors of the AGRP/MC4 binding based on (piperazinylethyl)piperazines were prepared, and their structure-activity relationship was established.

  DOI：

  10.1021/jm0255522
• 作为产物：
  描述：

  2-氯代-4'-氟苯乙酮 在 sodium tetrahydroborate 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 1.0h， 生成 ethyl 4-[2-(4-fluorophenyl)-2-hydroxyethyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Potential antitussives: Synthesis and pharmacology of a series of 1-[2-amino-2-(4-fluorophenyl)ethyl]-4-(2-benzoylpropyl)piperazines

  摘要：

  通过将2-氯-4'-氟乙酰苯酮与1-(乙氧羰基)哌嗪反应得到化合物V，然后用硼氢化钠还原为氨基醇VIf。将VIf的盐酸盐与亚硫酰氯处理得到1-[2-氯-2-(4-氟苯基)乙基]-4-(乙氧羰基)哌嗪的盐酸盐（VIg）。粗制的VIg在苯中与二乙胺、吡咯烷、哌啶、吗啉和1-甲基哌嗪进行取代反应，产生氨基氨基甲酸酯VIa-VIe。用浓缩的乙醇钾氢氧化物水解VIa-VIe，得到胺类物质VIIa-VIIe。这些化合物的盐酸盐与多聚甲醛和丙酮苯酮（和对羟基丙酮苯酮，分别）进行Mannich反应，得到标题化合物IIIa-IIIe、IVa,b和IVd,e。只有IIIa和IIId这两种物质在大鼠和豚鼠中显示出与依普拉津酮（I）相当的止咳活性。在较高剂量下，它们会导致小鼠出现中枢抑制、共济失调和上睑下垂，部分物质在大鼠中还表现出肾上腺素拮抗和降压作用。

  DOI：

  10.1135/cccc19832977

文献信息

• Synthesis of Diphenylmethyl Analogues and Their Affinity for the Melanocortin-4 Receptor and the Serotonin Transporter
  作者：Dai Nozawa、Taketoshi Okubo、Takaaki Ishii、Shigeyuki Chaki、Shigeru Okuyama、Atsuro Nakazato

  DOI：10.1248/cpb.55.1044

  日期：——

  had a relatively high affinity for the MC4 receptor. When diphenylmethyl analogues were further examined, compounds 12c and 18 were also found to exhibit a high affinity for the MC4 receptor (IC(50)=46.7 nM and 33.2 nM, respectively). Furthermore, compound 12c was also found to show a high affinity for the serotonin transporter (IC(50)=10.7 nM). Here, we describe the synthesis and biological evaluation

  在检查黑皮质素4受体（MC4受体）的拮抗剂时，我们发现含有二苯甲基部分的化合物12b对MC4受体具有相对较高的亲和力。当进一步检查二苯甲基类似物时，还发现化合物12c和18对MC4受体表现出高亲和力（分别为IC（50）= 46.7 nM和33.2 nM）。此外，还发现化合物12c对5-羟色胺转运蛋白显示出高亲和力（IC（50）= 10.7 nM）。在这里，我们描述了各种二苯基甲基类似物的合成和生物学评估，以及它们对MC4受体和血清素转运蛋白的作用。
• WO2006/133098
  申请人：——

  公开号：——

  公开（公告）日：——
• Structure–activity relationships of novel piperazines as antagonists for the melanocortin-4 receptor
  作者：Dai Nozawa、Taketoshi Okubo、Takaaki Ishii、Hiroyuki Kakinuma、Shigeyuki Chaki、Shigeru Okuyama、Atsuro Nakazato

  DOI：10.1016/j.bmc.2006.12.039

  日期：2007.3

  During the investigation of antagonists for the MC4 receptor, we found that 10ab having a naphthyl group showed almost the same binding affinity for the MC4 receptor as that of the lead compound I with a benzoyl group. We also developed a new type of compounds.. namely, bis-piperazines, and found that the bis-piperazines 10 exhibited a high affinity for the MC4 receptor. In particular, (-)-10bg exhibited the highest affinity for the MC4 receptor with an IC50 value of 8.13 nM. In this paper, we present the design, synthesis, and structure-activity relationships of the novel bis-piperazines as MC4 receptor antagonists. (c) 2007 Elsevier Ltd. All rights reserved.
• EP1468990
  申请人：——

  公开号：——

  公开（公告）日：——
• VEJDELEK, Z.;PROTIVA, M., COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 10, 2977-2988
  作者：VEJDELEK, Z.、PROTIVA, M.

  DOI：——

  日期：——