(E)-3-(1-(1-(benzo[d]oxazol-2-yl)ethyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide | 1370748-79-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: (E)-3-(1-(1-(benzo[d]oxazol-2-yl)ethyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide
• 英文别名: (E)-3-[1-[1-(1,3-benzoxazol-2-yl)ethyl]triazol-4-yl]-N-hydroxyprop-2-enamide
• CAS: 1370748-79-0
• 化学式: C₁₄H₁₃N₅O₃
• 分子量: 299.289
• InChiKey: ZEZCJMLXWZCSJD-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl 1-(2-hydroxyphenylcarbamoyl)ethylcarbamate 在 copper(ll) sulfate pentahydrate 、 triethylphosphite copper(I) iodide complex 、 三异丙基硅烷 、 triflic azide 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 27.0h， 生成 (E)-3-(1-(1-(benzo[d]oxazol-2-yl)ethyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide
  参考文献：
  名称：

  Discovery and Extensive in Vitro Evaluations of NK-HDAC-1: A Chiral Histone Deacetylase Inhibitor as a Promising Lead

  摘要：

  Herein, further SAR studies of lead compound NSC746457 (Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X. W.; Chen, M.; Fang, L. Y.; Sun; D. X.; Wang. P. G. J. Med. Chem. 2008, SI, 7417-7427) were performed, including the replacement of the trans-styryl moiety with a 2-substituted benzo-hetero aromatic ring and the introduction of a substituent onto the central methylene carbon. A promising chiral lead, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide (12, NK-HDAC-1), was discovered and showed about 1 order of magnitude more potency than SAHA in both enzymatic and cellular assays. For the in vitro safety tests, NK-HDAC-1 was far less toxic to nontransformed cells than tumor cells and showed no significant inhibition activity against CYP-3A4. The pharmaceutical properties (LogD, solubility, liver micrsomal stability (t1/2), plasma stability (t1/2), and apparent permeability) strongly suggested that NK-HDAC-1 might be superior to SAHA in bioavailability and in vivo half-life.

  DOI：

  10.1021/jm201496g