2-(para-chlorobenzylthio)-6-aminouracil

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(para-chlorobenzylthio)-6-aminouracil
• 英文别名: 6-Amino-2-(4-chloro-benzylsulfanyl)-pyrimidin-4-ol；4-amino-2-[(4-chlorophenyl)methylsulfanyl]-1H-pyrimidin-6-one
• 化学式: C₁₁H₁₀ClN₃OS
• mdl: MFCD03536210
• 分子量: 267.739
• InChiKey: NBYQRHXJDNHGJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 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：
  4

反应信息

• 作为产物：
  描述：

  6-氨基-2-硫脲嘧啶 、 4-氯苄溴 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 17.0h， 生成 2-(para-chlorobenzylthio)-6-aminouracil
  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

• Identification of novel, exosite-binding matrix metalloproteinase-13 inhibitor scaffolds
  作者：Joshua Roth、Dmitriy Minond、Etzer Darout、Qin Liu、Janelle Lauer、Peter Hodder、Gregg B. Fields、William R. Roush

  DOI：10.1016/j.bmcl.2011.09.077

  日期：2011.12

  Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhibitor 4, discovered through high-throughput screening, were synthesized to investigate

  基质金属蛋白酶 13 (MMP-13) 被认为是负责骨关节炎 (OA) 期间软骨中胶原蛋白降解的蛋白酶。在 Zn 结合位点抑制金属蛋白酶的化合物通常在 MMP 家族成员中缺乏特异性。通过高通量筛选发现的低微摩尔先导 MMP-13 抑制剂4 的类似物被合成以研究该抑制剂系列中的结构-活性关系。4 的系统修饰导致 MMP-13 抑制剂20和24的发现，它们比4对其他 MMP 的选择性更强。化合物20作为 MMP-13 抑制剂的效力也大约是原始 HTS 衍生的先导化合物4 的五倍。
• New isomeric 2-<i>ortho-(meta- and para-</i>) chloro-(bromo and nitro-)benzylthio-6-aminouracils
  作者：Elżbieta Wyrzykiewicz、Anna Szponar

  DOI：10.1002/jhet.5570380627

  日期：2001.11

  meta and para substituted derivatives of 2-benzylthio-6-aminouracils have been prepared. Electron Impact (EI) induced mass spectral fragmentation of these compounds was investigated. Fragmentation pathways are proposed on the basis of accurate mass and metastable transition measurements. The correlation between the intensities of the M+- and the selected fragment ions of these compounds is discussed

  已经制备了十种新的2-苄硫基-6-氨基尿嘧啶的邻，间和对位取代的衍生物。电子冲击（EI）诱导了这些化合物的质谱裂解。在精确的质量和亚稳态跃迁测量的基础上提出了断裂途径。讨论了M + -的强度与这些化合物的选定碎片离子之间的相关性。获得的数据为确定异构体奠定了基础。这些化合物的1 H和13 C NMR光谱使用异核（HETCOR）光谱结合明确地分配了化学位移。从这些光谱得到的数据可用于区分异构体。