N-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-hydroxyacetamide | 6743-05-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-hydroxyacetamide
• 英文别名: N-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-2-hydroxy-acetamide；1,3-Dimethyl-4-amino-5-hydroxyacetylaminouracil；6-Amino-1,3-dimethyl-5-hydroxyacetamidouracil；N-(4-amino-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)-2-hydroxyacetamide
• CAS: 6743-05-1
• 化学式: C₈H₁₂N₄O₄
• 分子量: 228.208
• InChiKey: HKYAZICYQDDWMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  羟基乙酸 、 5,6-二氨基-1,3-二甲基脲嘧啶 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 、 N-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-hydroxyacetamide
  参考文献：
  名称：

  [EN] SMALL MOLECULE ALDEHYDE DEHYDROGENASE INHIBITORS AND METHODS OF USE THEREOF
  [FR] PETITES MOLÉCULES INHIBITEURS DES ALDÉHYDE-DÉSHYDROGÉNASES ET LEURS MÉTHODES D'UTILISATION

  摘要：

  本发明涉及公式(I)的化合物、盐和溶剂化物。公式(I)的某些化合物是醛脱氢酶(ALDH)的强效和选择性抑制剂，ALDH是一类在解毒各种细胞毒性的异生物质和生物源性醛方面发挥关键作用的酶。因此，公式(I)的化合物可用于治疗需要ALDH抑制的疾病，包括癌症、炎症性疾病和肥胖。本发明还包括用于抑制醛脱氢酶(ALDH)的组合物和方法。

  公开号：

  WO2016086008A1

文献信息

• Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1)
  作者：Shyh-Ming Yang、Adam Yasgar、Bettina Miller、Madhu Lal-Nag、Kyle Brimacombe、Xin Hu、Hongmao Sun、Amy Wang、Xin Xu、Kimloan Nguyen、Udo Oppermann、Marc Ferrer、Vasilis Vasiliou、Anton Simeonov、Ajit Jadhav、David J. Maloney

  DOI：10.1021/acs.jmedchem.5b00577

  日期：2015.8.13

  Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess important physiological and toxicological functions in areas such as CNS, metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression and catalytic activity are vital biomarkers in a number of malignancies and cancer stem cells, highlighting the need for the identification and development of small molecule ALDH inhibitors. A new series of theophylline-based analogs as potent ALDH1A1 inhibitors is described. The optimization of hits identified from a quantitative high throughput screening (qHTS) campaign led to analogs with improved potency and early ADME properties. This chemotype exhibits highly selective inhibition against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isozymes as well as other dehydrogenases such as HPGD and HSD17 beta 4. Moreover, the pharrnacokinetic evaluation of selected analog 64 (NCT-501) is also highlighted.
• [EN] SMALL MOLECULE ALDEHYDE DEHYDROGENASE INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] PETITES MOLÉCULES INHIBITEURS DES ALDÉHYDE-DÉSHYDROGÉNASES ET LEURS MÉTHODES D'UTILISATION
  申请人：US HEALTH

  公开号：WO2016086008A1

  公开（公告）日：2016-06-02

  Described herein are compounds, salts and solvates of the formula (I). Certain compounds of formula (I) are potent and selective inhibitors of aldehyde dehydrogenases (ALDH), a family of enzymes that play a critical role in detoxification of various cytotoxic xenogenic and biogenic aldehydes. As such, compounds of formula (I) are useful for treating disorders in which ALDH inhibition is needed, including cancer, inflammatory disorders, and obesity. The disclosure also includes compositions, and methods for inhibiting aldehyde dehydrogenases (ALDH).

  本发明涉及公式(I)的化合物、盐和溶剂化物。公式(I)的某些化合物是醛脱氢酶(ALDH)的强效和选择性抑制剂，ALDH是一类在解毒各种细胞毒性的异生物质和生物源性醛方面发挥关键作用的酶。因此，公式(I)的化合物可用于治疗需要ALDH抑制的疾病，包括癌症、炎症性疾病和肥胖。本发明还包括用于抑制醛脱氢酶(ALDH)的组合物和方法。