6-amino-2-[(4-fluorobenzyl)sulfanyl]pyrimidin-4(3H)-one | 401579-89-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-amino-2-[(4-fluorobenzyl)sulfanyl]pyrimidin-4(3H)-one
• 英文别名: 4-amino-2-[(4-fluorophenyl)methylsulfanyl]-1H-pyrimidin-6-one
• CAS: 401579-89-3
• 化学式: C₁₁H₁₀FN₃OS
• mdl: MFCD03536212
• 分子量: 251.284
• InChiKey: FFWQYIZYGIMBBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  92.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氨基-2-硫脲嘧啶 、 4-氟溴苄 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 17.0h， 生成 6-amino-2-[(4-fluorobenzyl)sulfanyl]pyrimidin-4(3H)-one
  参考文献：
  名称：

  Discovery and optimization of aminopyrimidinones as potent and state-dependent Nav1.7 antagonists

  摘要：

  Clinical genetic data have shown that the product of the SCN9A gene, voltage-gated sodium ion channel Nav1.7, is a key control point for pain perception and a possible target for a next generation of analgesics. Sodium channels, however, historically have been difficult drug targets, and many of the existing structure-activity relationships (SAR) have been defined on pharmacologically modified channels with indirect reporter assays. Herein we describe the discovery, optimization, and SAR of potent aminopyrimidinone Nav1.7 antagonists using electrophysiology-based assays that measure the ligand-receptor interaction directly. Within this series, rapid functionalization at the polysubstituted aminopyrimidinone head group enabled exploration of SAR and of pharmacokinetic properties. Lead optimized N-Me-aminopyrimidinone 9 exhibited improved Nav1.7 potency, minimal off-target hERG liability, and improved rat PK properties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.111

文献信息

• Discovery and optimization of aminopyrimidinones as potent and state-dependent Nav1.7 antagonists
  作者：Hanh Nho Nguyen、Howie Bregman、John L. Buchanan、Bingfan Du、Elma Feric、Liyue Huang、Xingwen Li、Joseph Ligutti、Dong Liu、Annika B. Malmberg、David J. Matson、Jeff S. McDermott、Vinod F. Patel、Ben Wilenkin、Anruo Zou、Stefan I. McDonough、Erin F. DiMauro

  DOI：10.1016/j.bmcl.2011.11.111

  日期：2012.1

  Clinical genetic data have shown that the product of the SCN9A gene, voltage-gated sodium ion channel Nav1.7, is a key control point for pain perception and a possible target for a next generation of analgesics. Sodium channels, however, historically have been difficult drug targets, and many of the existing structure-activity relationships (SAR) have been defined on pharmacologically modified channels with indirect reporter assays. Herein we describe the discovery, optimization, and SAR of potent aminopyrimidinone Nav1.7 antagonists using electrophysiology-based assays that measure the ligand-receptor interaction directly. Within this series, rapid functionalization at the polysubstituted aminopyrimidinone head group enabled exploration of SAR and of pharmacokinetic properties. Lead optimized N-Me-aminopyrimidinone 9 exhibited improved Nav1.7 potency, minimal off-target hERG liability, and improved rat PK properties. (C) 2011 Elsevier Ltd. All rights reserved.