3-(4-(benzyloxy)phenyl)-N-hydroxy-4,5-dihydroisoxazole-5-carboxamide | 167098-81-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-(benzyloxy)phenyl)-N-hydroxy-4,5-dihydroisoxazole-5-carboxamide
• 英文别名: 3-[4-(benzyloxy)phenyl]-N-hydroxy-4,5-dihydroisoxazole-5-carboxamide；Ca-in-5g；N-hydroxy-3-(4-phenylmethoxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxamide
• CAS: 167098-81-9
• 化学式: C₁₇H₁₆N₂O₄
• 分子量: 312.325
• InChiKey: NXVZYEJQVDIBNN-UHFFFAOYSA-N

物化性质

• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  80.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-benzyloxybenzaldehyde oxime 在 三氯异氰尿酸 、 盐酸羟胺 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 3-(4-(benzyloxy)phenyl)-N-hydroxy-4,5-dihydroisoxazole-5-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Hydroxamic Acid Derivatives as Promising Agents for the Management of Chagas Disease

  摘要：

  Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5 ''. -dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g)was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to <1 mu M). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.

  DOI：

  10.1021/jm400902y

文献信息

• Manganese-Promoted Oxidative Cyclization of Unsaturated Oximes Using Molecular Oxygen in Air under Ambient Conditions
  作者：Daisuke Yamamoto、Takuto Oguro、Yuuki Tashiro、Masayuki Soga、Kazuhito Miyashita、Yoshiaki Aso、Kazuishi Makino

  DOI：10.1002/ejoc.201600998

  日期：2016.11

  A highly efficient manganese-promoted oxidative cyclization of unsaturated oximes to afford the corresponding 4,5-dihydroisoxazoline alcohols was developed. A very low loading (generally 0.1–0.2 mol-%) of Mn(acac)3 (acac = acetylacetonate) promoted the oxidative cyclization through the direct incorporation of molecular oxygen present in air (open flask) at room temperature.

  开发了一种高效的锰促进的不饱和肟氧化环化，以提供相应的 4,5-二氢异恶唑啉醇。Mn(acac)3（acac = 乙酰丙酮化物）的负载非常低（通常为 0.1–0.2 mol-%）通过在室温下直接掺入空气（开口烧瓶）中存在的分子氧来促进氧化环化。
• Design, Synthesis, and Evaluation of Hydroxamic Acid Derivatives as Promising Agents for the Management of Chagas Disease
  作者：Giseli Capaci Rodrigues、Daniel Ferreira Feijó、Marcelo Torres Bozza、Peiwen Pan、Daniela Vullo、Seppo Parkkila、Claudiu T. Supuran、Clemente Capasso、Alcino Palermo Aguiar、Alane Beatriz Vermelho

  DOI：10.1021/jm400902y

  日期：2014.1.23

  Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5 ''. -dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g)was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to <1 mu M). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.