AU1235 | 1338780-86-1

• 物质功能分类: 化学试剂 - 有机试剂 - 脲
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: AU1235
• 英文别名: 1-(1-Adamantyl)-3-(2,3,4-trifluorophenyl)urea
• CAS: 1338780-86-1
• 化学式: C₁₇H₁₉F₃N₂O
• 分子量: 324.346
• InChiKey: PYDHHHKUANVSJV-UHFFFAOYSA-N

物化性质

• 沸点：
  377.7±42.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：6 mg/ml（18.50 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

AU1235 是一种金刚烷基尿素，有效抑制结核分枝杆菌（Mycobacterium tuberculosis）蛋白 MmpL3。

靶点

Target	Value
MmpL3	()

体外研究

AU1235 对耐多药（MDR）的结核分枝杆菌株同样有效，这些菌株对异烟肼、利福平和吡嗪酰胺具有抗性，并且还表现出对链霉素、氟喹诺酮类药物及乙胺丁醇的抗性。此外，AU1235 还能抑制非结核分枝杆菌（如非结核分枝杆菌麦地那氏分枝杆菌和非结核分枝杆菌假汉逊分枝杆菌），但其最低抑菌浓度（MIC）为 3.2 至 6.4 μg/ml，明显高于对结核分枝杆菌和牛型分枝杆菌巴松坡亚种 BCG 的抑制效果。

反应信息

• 作为产物：
  描述：

  2,3,4-三氟苯基异氰酸酯 、 盐酸金刚烷胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到AU1235
  参考文献：
  名称：

  Exploring the size of the lipophilic unit of the soluble epoxide hydrolase inhibitors

  摘要：

  Soluble epoxide hydrolase (sEH) inhibitors are potential drugs for several diseases. Adamantyl ureas are excellent sEH inhibitors but have limited metabolic stability. Herein, we report the effect of replacing the adamantane group by alternative polycyclic hydrocarbons on sEH inhibition, solubility, permeability and metabolic stability. Compounds bearing smaller or larger polycyclic hydrocarbons than adamantane yielded all good inhibition potency of the human sEH (0.4 <= IC50 <= 21.7 nM), indicating that sEH is able to accommodate inhibitors of very different size. Human liver microsomal stability of diamantane containing inhibitors is lower than that of their corresponding adamantane counterparts.

  DOI：

  10.1016/j.bmc.2019.115078

文献信息

• [EN] ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS<br/>[FR] ANALOGUES D'ADAMANTYLURÉES UTILISÉS EN TANT QU'INHIBITEURS D'HYDROLASE ÉPOXYDE SOLUBLE
  申请人：UNIV BARCELONA

  公开号：WO2017017048A1

  公开（公告）日：2017-02-02

  N-(2-oxaadamantan-1-yl)ureas of formula I, where R3 is H, C1-C3 alkyl, cyclohexyl or phenyl; R is -[CH2]n -Y; n is 0-15; in -[CH2]n - 0-n/3 of the methylene groups are optionally replaced by non adjacent oxygen atoms; and Y is a 3- or 4-substituted phenyl, a 3- or 4-substituted cyclohexyl, a N-substituted piperidin-4-yl, a N-substituted piperidin-3-yl, a di- or tri-fluorosubstituted phenyl, 4-chloro-3-trifluoromethylphenyl, 3-chloro-4-trifluoromethylphenyl, 4-fluoro-3-trifluoromethylphenyl, or 3-fluoro-4-trifluoromethylphenyl; have epoxide hydrolase (sEH) inhibitory activities similar to those of their N-(adamantan-1-yl)urea analogs. Thus, compounds I are useful as API for the treatment of sEH mediated diseases. Besides, in general, compounds (I) have higher water solubilities and lower melting points, what make them more promising from the point of view of pharmacokinetics and formulation.

  式I的N-(2-氧杂孔莫烷-1-基)脲，其中R3为H、C1-C3烷基、环己基或苯基；R为-[CH2]n-Y；n为0-15；在-[CH2]n-中，0-n/3的亚甲基基团可选择性地被非相邻的氧原子取代；Y为3-或4-取代苯基、3-或4-取代环己基、N-取代哌啶-4-基、N-取代哌啶-3-基、二氟或三氟取代苯基、4-氯-3-三氟甲基苯基、3-氯-4-三氟甲基苯基、4-氟-3-三氟甲基苯基或3-氟-4-三氟甲基苯基；具有环氧化酶（sEH）抑制活性，类似于其N-(孔莫烷-1-基)脲类似物。因此，化合物I可用作治疗sEH介导疾病的API。此外，一般而言，化合物（I）具有较高的水溶性和较低的熔点，这使它们在药代动力学和配方方面更具有前景。
• ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
  申请人：Universitat de Barcelona

  公开号：EP3328854A1

  公开（公告）日：2018-06-06
• Exploring the size of the lipophilic unit of the soluble epoxide hydrolase inhibitors
  作者：Sandra Codony、Elena Valverde、Rosana Leiva、José Brea、M. Isabel Loza、Christophe Morisseau、Bruce D. Hammock、Santiago Vázquez

  DOI：10.1016/j.bmc.2019.115078

  日期：2019.10

  Soluble epoxide hydrolase (sEH) inhibitors are potential drugs for several diseases. Adamantyl ureas are excellent sEH inhibitors but have limited metabolic stability. Herein, we report the effect of replacing the adamantane group by alternative polycyclic hydrocarbons on sEH inhibition, solubility, permeability and metabolic stability. Compounds bearing smaller or larger polycyclic hydrocarbons than adamantane yielded all good inhibition potency of the human sEH (0.4 <= IC50 <= 21.7 nM), indicating that sEH is able to accommodate inhibitors of very different size. Human liver microsomal stability of diamantane containing inhibitors is lower than that of their corresponding adamantane counterparts.