1-t-butoxycarbonyl-4-(2-(methanesulfonyloxymethyl)phenyl)-piperazine | 209160-88-3

• 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: 1-t-butoxycarbonyl-4-(2-(methanesulfonyloxymethyl)phenyl)-piperazine
• 英文别名: tert-butyl 4-[2-(methylsulfonyloxymethyl)phenyl]piperazine-1-carboxylate
• CAS: 209160-88-3
• 化学式: C₁₇H₂₆N₂O₅S
• 分子量: 370.47
• InChiKey: KFBGMTULOPXEFT-UHFFFAOYSA-N

物化性质

• 沸点：
  537.759±50.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.234±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  84.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-t-butoxycarbonyl-4-(2-(methanesulfonyloxymethyl)phenyl)-piperazine 在 sodium hydroxide 作用下， 以 乙腈 为溶剂， 生成 4-(2-[1,2,4]Triazol-4-ylmethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Aryl piperazine melanocortin MC4 receptor agonists

  摘要：

  Incorporation of substituted phenyl piperazine privileged structures into a known MC4 specific dipeptoid consensus sequence resulted in a series of potent (EC50 = 24 nM) and selective MC4-R agonists. We report the SAR of this series of compounds using in vitro cAMP functional assays in cells transfected with the MC4 or other melancortin receptors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00796-0
• 作为产物：
  描述：

  1-(2-苯甲腈)哌嗪 在 4-二甲氨基吡啶 、 氢氧化钾 、 硼烷 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成 1-t-butoxycarbonyl-4-(2-(methanesulfonyloxymethyl)phenyl)-piperazine
  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

文献信息

• Discovery and pharmacological characterization of aryl piperazine and piperidine ethers as dual acting norepinephrine reuptake inhibitors and 5-HT1A partial agonists
  作者：David L. Gray、Wenjian Xu、Brian M. Campbell、Amy B. Dounay、Nancy Barta、Susan Boroski、Lynne Denny、Lori Evans、Nancy Stratman、Al Probert

  DOI：10.1016/j.bmcl.2009.10.014

  日期：2009.12

  including attention deficit hyperactivity disorder (ADHD) and depression. Targeted screening of NRI-active compounds for binding to the 5-HT1A receptor provided a series of thiomorpholinone hits with this dual activity profile. Several iterations of design, synthesis, and testing led to substituted piperidine diphenyl ethers which are potent NRIs with 5-HT1A partial agonist properties. In addition,

  这都是去甲肾上腺素再摄取抑制剂（NRI）和5-HT的化合物阿部分激动剂可具有治疗神经精神障碍包括注意力缺陷多动障碍（ADHD）和抑郁症的潜力。针对与5-HT 1A受体结合的NRI活性化合物的靶向筛选，提供了一系列具有这种双重活性特征的硫吗啉代酮。设计，合成和测试导致取代的哌啶二苯醚作为强力的NRI与5-HT1的若干次迭代一个部分激动剂性质。此外，这些分子的优化提供了对多巴胺（DAT）和5-羟色胺（SERT）再摄取转运蛋白具有NRI选择性的化合物。单胺和5-HT 1A 还介绍了从已开发的哌啶二苯醚系列中选择的化合物的体外功能活性。
• Substituted aryl piperazines as neurokinin antagonists
  申请人：Merck & Co., Inc.

  公开号：US05607936A1

  公开（公告）日：1997-03-04

  Disclosed are substituted aryl piperazines of Formula I ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis. In particular compounds of Formula I are shown to be neurokinin antagonists.

  本文披露了Formula I的取代芳基哌嗪化合物，是一种在治疗炎症性疾病、疼痛或偏头痛、哮喘和呕吐方面有用的快速激肽受体拮抗剂。特别是Formula I的化合物被证明是神经激肽拮抗剂。
• SUBSTITUTED ARYL PIPERAZINES AS NEUROKININ ANTAGONISTS
  申请人：Merck & Co., Inc.

  公开号：EP0783498A1

  公开（公告）日：1997-07-16
• EP0783498A4
  申请人：——

  公开号：EP0783498A4

  公开（公告）日：1998-04-15
• US5607936A
  申请人：——

  公开号：US5607936A

  公开（公告）日：1997-03-04