(E)-N-(2-methyl-3phenylallyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide | 1375800-51-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (E)-N-(2-methyl-3phenylallyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide
• 英文别名: N-[(E)-2-methyl-3-phenylprop-2-enyl]-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide
• CAS: 1375800-51-3
• 化学式: C₂₆H₃₂N₂O₃
• 分子量: 420.552
• InChiKey: GTCPVFWDKLPXPL-LVZFUZTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二噁烷-6-羧酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (E)-N-(2-methyl-3phenylallyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide
  参考文献：
  名称：

  Synthesis, modeling and functional activity of substituted styrene-amides as small-molecule CXCR7 agonists

  摘要：

  The chemokine receptor CXCR7 is an atypical G protein-coupled receptor as it preferentially signals through the beta-arrestin pathway rather than through G proteins. CXCR7 is thought to be of importance in cancer and the development of CXCR7-targeting ligands is of huge importance to further elucidate the pharmacology and the therapeutic potential of CXCR7. In the present study, we synthesized 24 derivatives based on a compound scaffold patented by Chemocentryx and obtained CXCR7 ligands with pK(i) values ranging from 5.3 to 8.1. SAR studies were supported by computational 3D Fingerprint studies, revealing several important affinity descriptors. Two key compounds (29 and 30, VUF11207 and VUF11403) were found to be high-potency ligands that induce recruitment of beta-arrestin2 and subsequent internalization of CXCR7, making them important tool compounds in future CXCR7 research. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.041

文献信息

• Synthesis, modeling and functional activity of substituted styrene-amides as small-molecule CXCR7 agonists
  作者：Maikel Wijtmans、David Maussang、Francesco Sirci、Danny J. Scholten、Meritxell Canals、Azra Mujić-Delić、Milagros Chong、Kristell L.S. Chatalic、Hans Custers、Elwin Janssen、Chris de Graaf、Martine J. Smit、Iwan J.P. de Esch、Rob Leurs

  DOI：10.1016/j.ejmech.2012.02.041

  日期：2012.5

  The chemokine receptor CXCR7 is an atypical G protein-coupled receptor as it preferentially signals through the beta-arrestin pathway rather than through G proteins. CXCR7 is thought to be of importance in cancer and the development of CXCR7-targeting ligands is of huge importance to further elucidate the pharmacology and the therapeutic potential of CXCR7. In the present study, we synthesized 24 derivatives based on a compound scaffold patented by Chemocentryx and obtained CXCR7 ligands with pK(i) values ranging from 5.3 to 8.1. SAR studies were supported by computational 3D Fingerprint studies, revealing several important affinity descriptors. Two key compounds (29 and 30, VUF11207 and VUF11403) were found to be high-potency ligands that induce recruitment of beta-arrestin2 and subsequent internalization of CXCR7, making them important tool compounds in future CXCR7 research. (C) 2012 Elsevier Masson SAS. All rights reserved.