4-(2-amino-6-(4-chlorophenyl)pyrimidin-4-yl)-2-methoxyphenol | 215257-66-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(2-amino-6-(4-chlorophenyl)pyrimidin-4-yl)-2-methoxyphenol
• 英文别名: 4-[2-Amino-6-(4-chlorophenyl)pyrimidin-4-yl]-2-methoxyphenol；4-[2-amino-6-(4-chlorophenyl)pyrimidin-4-yl]-2-methoxyphenol
• CAS: 215257-66-2
• 化学式: C₁₇H₁₄ClN₃O₂
• 分子量: 327.77
• InChiKey: IKQLORBLJYVOQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  81.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  对氯苯乙酮 在 氯化亚砜 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-(2-amino-6-(4-chlorophenyl)pyrimidin-4-yl)-2-methoxyphenol
  参考文献：
  名称：

  Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia

  摘要：

  We previously reported Chalcone-4 (1) that binds the chemokine CXCL12, not its cognate receptors CXCR4 or CXCR7, and neutralizes its biological activity. However, this neutraligand suffers from limitations such as poor chemical stability, solubility, and oral activity. Herein, we report on the discovery of pyrimidinone 57 (LIT-927), a novel neutraligand of CXCL12 which displays a higher solubility than 1 and is no longer a Michael acceptor. While both 1 and 57 reduce eosinophil recruitment in a murine model of allergic airway hypereosinophilia, 57 is the only one to display inhibitory activity following oral administration. Thereby, we here describe 57 as the first orally active CXCL12 neutraligand with anti-inflammatory properties. Combined with a high binding selectivity for CXCL12 over other chemokines, 57 represents a powerful pharmacological tool to investigate CXCL12 physiology in vivo and to explore the activity of chemokine neutralization in inflammatory and related diseases.

  DOI：

  10.1021/acs.jmedchem.8b00657

文献信息

• Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia
  作者：Pierre Regenass、Dayana Abboud、François Daubeuf、Christine Lehalle、Patrick Gizzi、Stéphanie Riché、Muriel Hachet-Haas、François Rohmer、Vincent Gasparik、Damien Boeglin、Jacques Haiech、Tim Knehans、Didier Rognan、Denis Heissler、Claire Marsol、Pascal Villa、Jean-Luc Galzi、Marcel Hibert、Nelly Frossard、Dominique Bonnet

  DOI：10.1021/acs.jmedchem.8b00657

  日期：2018.9.13

  We previously reported Chalcone-4 (1) that binds the chemokine CXCL12, not its cognate receptors CXCR4 or CXCR7, and neutralizes its biological activity. However, this neutraligand suffers from limitations such as poor chemical stability, solubility, and oral activity. Herein, we report on the discovery of pyrimidinone 57 (LIT-927), a novel neutraligand of CXCL12 which displays a higher solubility than 1 and is no longer a Michael acceptor. While both 1 and 57 reduce eosinophil recruitment in a murine model of allergic airway hypereosinophilia, 57 is the only one to display inhibitory activity following oral administration. Thereby, we here describe 57 as the first orally active CXCL12 neutraligand with anti-inflammatory properties. Combined with a high binding selectivity for CXCL12 over other chemokines, 57 represents a powerful pharmacological tool to investigate CXCL12 physiology in vivo and to explore the activity of chemokine neutralization in inflammatory and related diseases.