N-{2-[2-(dimethylamino)ethoxy]phenyl}piperazine | 444606-74-0

• 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: N-{2-[2-(dimethylamino)ethoxy]phenyl}piperazine
• 英文别名: dimethyl-[2-(2-piperazin-1-yl-phenoxy)-ethyl]-amine；Dimethyl({2-[2-(piperazin-1-yl)phenoxy]ethyl})amine；N,N-dimethyl-2-(2-piperazin-1-ylphenoxy)ethanamine
• CAS: 444606-74-0
• 化学式: C₁₄H₂₃N₃O
• mdl: MFCD16498462
• 分子量: 249.356
• InChiKey: MZUBUHQECMSCCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  27.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-{2-[2-(dimethylamino)ethoxy]phenyl}piperazine 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel Arylpiperazines as Potent and Selective Agonists of the Melanocortin Subtype-4 Receptor

  摘要：

  The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-D-Tic-D-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (K-i = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (K-i = 6600 nM). Sulfonamide 39 (K-i = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (K-i = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (K-i = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.

  DOI：

  10.1021/jm0304109
• 作为产物：
  描述：

  二甲氨基氯乙烷盐酸 、 1-(2-羟基苯基)-哌嗪-4-羧酸叔丁酯 在 18-冠醚-6 、 potassium carbonate 、 potassium iodide 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 生成 N-{2-[2-(dimethylamino)ethoxy]phenyl}piperazine
  参考文献：
  名称：

  Piperazine- and piperidine-derivatives as melanocortin receptor agonists

  摘要：

  本发明涉及公式I的黑素皮质素受体激动剂，可用于治疗肥胖症、糖尿病以及男性和/或女性性功能障碍。

  公开号：

  US20040082590A1

文献信息

• PIPERAZINE- AND PIPERIDINE-DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1370558A1

  公开（公告）日：2003-12-17
• US7186715B2
  申请人：——

  公开号：US7186715B2

  公开（公告）日：2007-03-06
• [EN] PIPERAZINE- AND PIPERIDINE-DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS<br/>[FR] DERIVES DE PIPERAZINE ET DE PIPERIDINE EN TANT QU'AGONISTES DU RECEPTEUR DE LA MELANOCORTINE
  申请人：LILLY CO ELI

  公开号：WO2002059117A1

  公开（公告）日：2002-08-01

  The present invention relates to melanocortin receptor agonists of formula I,which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction.
• Piperazine- and piperidine-derivatives as melanocortin receptor agonists
  申请人：——

  公开号：US20040082590A1

  公开（公告）日：2004-04-29

  The present invention relates to melanocortin receptor agonists of formula I, which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction. 1

  本发明涉及公式I的黑素皮质素受体激动剂，可用于治疗肥胖症、糖尿病以及男性和/或女性性功能障碍。
• Synthesis and Structure−Activity Relationships of Novel Arylpiperazines as Potent and Selective Agonists of the Melanocortin Subtype-4 Receptor
  作者：Timothy I. Richardson、Paul L. Ornstein、Karin Briner、Matthew J. Fisher、Ryan T. Backer、C. Kelly Biggers、Michael P. Clay、Paul J. Emmerson、Larry W. Hertel、Hansen M. Hsiung、Saba Husain、Steven D. Kahl、Jonathan A. Lee、Terry D. Lindstrom、Michael J. Martinelli、John P. Mayer、Jeffery T. Mullaney、Thomas P. O'Brien、Joseph M. Pawlak、Kevin D. Revell、Jikesh Shah、John M. Zgombick、R. Jason Herr、Alex Melekhov、Peter B. Sampson、Chi-Hsin R. King

  DOI：10.1021/jm0304109

  日期：2004.1.1

  The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-D-Tic-D-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (K-i = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (K-i = 6600 nM). Sulfonamide 39 (K-i = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (K-i = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (K-i = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.