N'-Hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinecarboximidamide | 468067-75-6

• 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: N'-Hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinecarboximidamide
• 英文别名: N'-hydroxy-2,4-dioxo-1H-pyrimidine-5-carboximidamide
• CAS: 468067-75-6
• 化学式: C₅H₆N₄O₃
• 分子量: 170.128
• InChiKey: HYODOBTXWOICRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N'-Hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinecarboximidamide 、 (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 1-O-[(Z)-[amino-(2,4-dioxo-1H-pyrimidin-5-yl)methylidene]amino] 4-O-tert-butyl (2R)-2-(3-cyclohexylpropyl)butanedioate
  参考文献：
  名称：

  Potent and Selective Nonpeptidic Inhibitors of Procollagen C-Proteinase

  摘要：

  6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (K-i 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (> 10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 +/- 2% at 10 mu M and was very effective at penetrating human skin in vitro with a TED flux of 1.5 mu g/cm(2)/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent.

  DOI：

  10.1021/jm061010z
• 作为产物：
  描述：

  5-氰基尿嘧啶 在 盐酸羟胺 、 三乙胺 作用下， 以 甲醇 为溶剂， 生成 N'-Hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinecarboximidamide
  参考文献：
  名称：

  3-heterocyclylpropanohydroxamic acid PCP inhibitors

  摘要：

  式(I)的化合物及其盐、溶剂合物、水合物和前药是有用的PCP抑制剂，制备这些化合物的方法，包含这些化合物的组合物，以及使用这些化合物治疗PCP介导的疾病或病症的方法。

  公开号：

  US20030069291A1