1-哌嗪羧酸,4-[2-氯-2-(4-氟苯基)乙基]-,乙基酯 | 106000-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-哌嗪羧酸,4-[2-氯-2-(4-氟苯基)乙基]-,乙基酯
• 英文名称: 1-<2-Chloro-2-(4-fluorophenyl)ethyl>-4-ethoxycarbonylpiperazine
• 英文别名: ethyl 4-[2-chloro-2-(4-fluorophenyl)ethyl]piperazine-1-carboxylate；1-ethoxycarbonyl-4-[2-chloro-2-(4-fluorophenyl)ethyl]piperazine
• CAS: 106000-09-3
• 化学式: C₁₅H₂₀ClFN₂O₂
• 分子量: 314.787
• InChiKey: ZXLJOGZSTRQXGK-UHFFFAOYSA-N

物化性质

• 沸点：
  397.7±42.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 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：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-哌嗪羧酸,4-[2-氯-2-(4-氟苯基)乙基]-,乙基酯 在 氢氧化钾 作用下， 以 乙醇 、 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 、 氯化亚砜 作用下， 以 乙醇 、 氯仿 、 苯 为溶剂， 生成 1-哌嗪羧酸,4-[2-氯-2-(4-氟苯基)乙基]-,乙基酯
  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

• Potential antitussives: Synthesis and pharmacology of a series of 1-[2-amino-2-(4-fluorophenyl)ethyl]-4-(2-benzoylpropyl)piperazines
  作者：Zdeněk Vejdělek、Miroslav Protiva

  DOI：10.1135/cccc19832977

  日期：——

  Compound V, obtained by a reaction of 2-chloro-4'-fluoroacetophenone with 1-(ethoxycarbonyl)piperazine, was reduced with sodium borohydride to the amino alcohol VIf. The hydrochloride of VIf was treated with thionyl chloride to give the hydrochloride of 1-[2-chloro-2-(4-fluorophenyl)ethyl]-4-(ethoxycarbonyl)piperazine (VIg). The crude VIg was subjected to substitution reactions with diethylamine, pyrrolidine, piperidine, morpholine and 1-methylpiperazine in benzene at 60 °C. The obtained aminocarbamates VIa-VIe were hydrolyzed with concentrated ethanolic potassium hydroxide and gave the amines VIIa-VIIe. Mannich reactions of the hydrochlorides of these compounds with paraformaldehyde and propiophenone (and 4-hydroxypropiophenone, respectively) resulted in the title compounds IIIa-IIIe, IVa,b and IVd,e. Only substances IIIa and IIId were found to have an antitussic activity in rats and guinea-pigs comparable to that of eprazinone (I). In higher doses they brought about central depression, ataxia and ptosis in mice and some of them adrenolytic and hypotensive effects in rats.

  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。
• 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。
• 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.