2-(4-cyclopropyl-6,6-dimethyl-2-oxomorpholin-3-yl)-N-(4-isopropylphenyl)acetamide | 1312607-77-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(4-cyclopropyl-6,6-dimethyl-2-oxomorpholin-3-yl)-N-(4-isopropylphenyl)acetamide
• 英文别名: 2-(4-cyclopropyl-6,6-dimethyl-2-oxomorpholin-3-yl)-N-(4-propan-2-ylphenyl)acetamide
• CAS: 1312607-77-4
• 化学式: C₂₀H₂₈N₂O₃
• 分子量: 344.454
• InChiKey: YZJCQUXDWSZELS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-(benzyl(2-hydroxy-2-methylpropyl)amino)acetate 在 palladium 10% on activated carbon 、 氢气 、 sodium cyanoborohydride 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸甲酯 、 乙基苯 、 甲苯 为溶剂， 反应 32.5h， 生成 2-(4-cyclopropyl-6,6-dimethyl-2-oxomorpholin-3-yl)-N-(4-isopropylphenyl)acetamide
  参考文献：
  名称：

  2-(2-Oxo-morpholin-3-yl)-acetamide Derivatives as Broad-Spectrum Antifungal Agents

  摘要：

  From a fungicidal screen, we identified 2-(2-oxo-morpholin-3-yl)-acetamide derivatives as fungicidal agents against Candida species, additionally characterized by antifungal activity against Aspergillus species. However, development of this series was hampered by low plasmatic stability. Introduction of a gem-dimethyl on the 6-position of the morpholin-2-one core led to considerable improvement in plasmatic stability while maintaining in vitro antifungal activity. Further optimization of the series resulted in the discovery of N-(biphenyl-3-ylmethyl)-2-(4-ethyl-6,6-dimethyl-2-oxomorpholin-3-yl)acetamide (87), which, in addition to fungicidal activity against Candida species, shows promising and broad antifungal in vitro activity against various fungi species, such as molds and dermatophytes. In vivo efficacy was also demonstrated in a murine model of systemic Candida albicans infection with a significant fungal load reduction in kidneys.

  DOI：

  10.1021/jm501814x

文献信息

• [EN] ANTIFUNGAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIFONGIQUES
  申请人：UNIV LEUVEN KATH

  公开号：WO2011072345A1

  公开（公告）日：2011-06-23

  The present invention relates to a series of novel compounds which have been shown to possess antifungal activity. The invention therefore relates to the new compounds, methods for their preparation, pharmaceutical compositions comprising them and to the compounds for use as a medicament, more in particular antifungal medicament.

  本发明涉及一系列已被证明具有抗真菌活性的新化合物。因此，该发明涉及新化合物、其制备方法、包含它们的药物组合物以及用作药物，尤其是抗真菌药物的化合物。
• ANTIFUNGAL COMPOUNDS
  申请人：Bardiot Dorothée

  公开号：US20120252801A1

  公开（公告）日：2012-10-04

  The present invention relates to a series of novel compounds which have been shown to possess antifungal activity. The invention therefore relates to the new compounds, methods for their preparation, pharmaceutical compositions comprising them and to the compounds for use as a medicament, more in particular antifungal medicament.

  本发明涉及一系列已被证明具有抗真菌活性的新化合物。因此，该发明涉及新化合物、其制备方法、包含它们的药物组合物以及用作药物，尤其是抗真菌药物的化合物。
• 2-(2-Oxo-morpholin-3-yl)-acetamide Derivatives as Broad-Spectrum Antifungal Agents
  作者：Dorothée Bardiot、Karin Thevissen、Katrijn De Brucker、Annelies Peeters、Paul Cos、Carlos P. Taborda、Michael McNaughton、Louis Maes、Patrick Chaltin、Bruno P. A. Cammue、Arnaud Marchand

  DOI：10.1021/jm501814x

  日期：2015.2.12

  From a fungicidal screen, we identified 2-(2-oxo-morpholin-3-yl)-acetamide derivatives as fungicidal agents against Candida species, additionally characterized by antifungal activity against Aspergillus species. However, development of this series was hampered by low plasmatic stability. Introduction of a gem-dimethyl on the 6-position of the morpholin-2-one core led to considerable improvement in plasmatic stability while maintaining in vitro antifungal activity. Further optimization of the series resulted in the discovery of N-(biphenyl-3-ylmethyl)-2-(4-ethyl-6,6-dimethyl-2-oxomorpholin-3-yl)acetamide (87), which, in addition to fungicidal activity against Candida species, shows promising and broad antifungal in vitro activity against various fungi species, such as molds and dermatophytes. In vivo efficacy was also demonstrated in a murine model of systemic Candida albicans infection with a significant fungal load reduction in kidneys.