ethyl 4-[2-(4-fluorophenyl)-2-(4-isopropylpiperazin-1-yl)ethyl]piperazine-1-carboxylate | 552885-52-6

• 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-(4-isopropylpiperazin-1-yl)ethyl]piperazine-1-carboxylate
• 英文别名: 1-ethoxycarbonyl-4-[2-(4-fluorophenyl)-2-(4-isopropylpiperazino)ethyl]piperazine；ethyl 4-[2-(4-fluorophenyl)-2-(4-propan-2-ylpiperazin-1-yl)ethyl]piperazine-1-carboxylate
• CAS: 552885-52-6
• 化学式: C₂₂H₃₅FN₄O₂
• 分子量: 406.544
• InChiKey: CGNKJIDDKCDFTA-UHFFFAOYSA-N

物化性质

• 沸点：
  477.1±45.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  39.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-[2-(4-fluorophenyl)-2-(4-isopropylpiperazin-1-yl)ethyl]piperazine-1-carboxylate 在 氢氧化钾 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Structure–activity relationships of novel piperazines as antagonists for the melanocortin-4 receptor

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.12.039
• 作为产物：
  描述：

  2-氯代-4'-氟苯乙酮 在 sodium tetrahydroborate 、 氯化亚砜 、 N-乙基异丙基胺 作用下， 以 乙醇 、 氯仿 、 苯 为溶剂， 生成 ethyl 4-[2-(4-fluorophenyl)-2-(4-isopropylpiperazin-1-yl)ethyl]piperazine-1-carboxylate
  参考文献：
  名称：

  二苯甲基类似物的合成及其对黑皮质素4受体和5-羟色胺转运蛋白的亲和力。

  摘要：

  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。

  DOI：

  10.1248/cpb.55.1044

文献信息

• Piperazine derivative
  申请人：Nakazato Atsuro

  公开号：US20060084657A1

  公开（公告）日：2006-04-20

  A piperazine derivative represented by the formula (1): wherein n is an integer of 1 to 8; R 1 represents hydrogen or C 1-10 alkyl; A represents CH or nitrogen; Ar 1 represents phenyl or substituted phenyl; and Y represents a group represented by the formula Y 1 -Y 2 -Ar 2 or Y 3 -Y 4 (Ar 5 )-Ar 6 or a pharmaceutically acceptable salt of the derivative. The novel piperazine derivative has MC4 receptor antagonistic activity.

  一种由式（1）表示的哌嗪衍生物： 其中n为1至8的整数；R1表示氢或C1-10烷基；A表示CH或氮；Ar1表示苯基或取代苯基；Y表示由式Y1-Y2-Ar2或Y3-Y4（Ar5）-Ar6表示的基团，或该衍生物的药学上可接受的盐。该新型哌嗪衍生物具有MC4受体拮抗活性。
• PIPERAZINE DERIVATIVE
  申请人：Taisho Pharmaceutical Co. Ltd.

  公开号：EP1468990A1

  公开（公告）日：2004-10-20

  A piperazine derivative represented by the formula (1):    wherein n is an integer of 1 to 8; R1 represents hydrogen or C1-10 alkyl; A represents CH or nitrogen; Ar1 represents phenyl or substituted phenyl; and Y represents a group represented by the formula Y1-Y2-Ar2 or Y3-Y4(Ar5)-Ar6 or a pharmaceutically acceptable salt of the derivative. The novel piperazine derivative has MC4 receptor antagonistic activity.

  一种由式（1）代表的哌嗪衍生物： 其中 n 为 1 至 8 的整数；R1 代表氢或 C1-10 烷基；A 代表 CH 或氮；Ar1 代表苯基或取代苯基；Y 代表由式 Y1-Y2-Ar2 或 Y3-Y4(Ar5)-Ar6 所代表的基团或该衍生物的药学上可接受的盐。新型哌嗪衍生物具有 MC4 受体拮抗活性。
• EP1468990
  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.
• 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。