6-Amino-3-methyl-1,2-dihydro-2-thioxo-4(3H)-pyrimidinone | 66433-83-8

• 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: 6-Amino-3-methyl-1,2-dihydro-2-thioxo-4(3H)-pyrimidinone
• 英文别名: 6-amino-3-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one；6-amino-3-methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one；6-Amino-3-methyl-thiouracil；6-amino-3-methyl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 66433-83-8
• 化学式: C₅H₇N₃OS
• 分子量: 157.196
• InChiKey: NHYOHEMJBBLUQL-UHFFFAOYSA-N

物化性质

• 熔点：
  255 °C
• 沸点：
  251.4±43.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  90.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-叔丁基苄溴 、 6-Amino-3-methyl-1,2-dihydro-2-thioxo-4(3H)-pyrimidinone 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以60%的产率得到6-amino-2-(4-tert-butylbenzylthio)-3-methylpyrimidin-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
• 作为产物：
  描述：

  6-氨基-2-甲基硫代-3-甲基尿嘧啶 、 sodium hydrogensulfide 以83%的产率得到
  参考文献：
  名称：

  SOUTHON I. W.; PFLEIDERER W., CHEM. BER., 1978, 111, NO 3, 971-981

  摘要：

  DOI：

文献信息

• Sulay, Piroshka B.; Ivanov, Ivo C., Liebigs Annalen der Chemie, 1987, p. 1101 - 1106
  作者：Sulay, Piroshka B.、Ivanov, Ivo C.

  DOI：——

  日期：——
• SULAY, PIROSHKA B.;IVANOV, IVO C., LIEBIGS ANN. CHEM.,(1987) N 12, 1101-1105
  作者：SULAY, PIROSHKA B.、IVANOV, IVO C.

  DOI：——

  日期：——
• 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.
• SOUTHON I. W.; PFLEIDERER W., CHEM. BER., 1978, 111, NO 3, 971-981
  作者：SOUTHON I. W.、 PFLEIDERER W.

  DOI：——

  日期：——