6-acetyl-2-butyl-3,4-dihydro-2H-1,4-benzoxazin-3-one | 871946-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-acetyl-2-butyl-3,4-dihydro-2H-1,4-benzoxazin-3-one
• 英文别名: 6-acetyl-2-butyl-4H-1,4-benzoxazin-3-one
• CAS: 871946-57-5
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: XLLCAXQUHQAYKE-UHFFFAOYSA-N

物化性质

• 熔点：
  109-110 °C
• 沸点：
  444.6±45.0 °C(predicted)
• 密度：
  1.114±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-acetyl-2-butyl-3,4-dihydro-2H-1,4-benzoxazin-3-one 在 sodium tetrahydroborate 、 溴 、 sodium hydride 、 溶剂黄146 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 2-Butyl-6-(1-hydroxy-2-imidazol-1-yl-ethyl)-4-methyl-4H-benzo[1,4]oxazin-3-one
  参考文献：
  名称：

  Design, Synthesis, and Microbiological Evaluation of New Candida albicans CYP51 Inhibitors

  摘要：

  In a program aimed at the design and synthesis of novel azole inhibitors of Candida albicans CYP51 (CA-CYP51), a series of azole 1,4-benzothiazines (BT) and 1,4-benzoxazines (BO) were recently synthesized. A morphological study of the enzyme active site highlighted a hydrophobic access channel, and a docking study pointed out that the C-2 position of the BT or BO nucleus was oriented toward the access channel. Here, we report the design, synthesis, and microbiological evaluation of C-2-alkyl BT and BO compounds. In both series, introduction of the alkyl chain maintained and in some cases improved the anti-Candida in vitro activity; however, there was not always a strict correlation between in vitro and in vivo activity for several compounds.

  DOI：

  10.1021/jm050685j
• 作为产物：
  描述：

  2-溴己酰氯 、 1-(3-氨基-4-羟基苯基)乙酮 在 苄基三乙基氯化铵 、 碳酸氢钠 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以40%的产率得到6-acetyl-2-butyl-3,4-dihydro-2H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  Design, Synthesis, and Microbiological Evaluation of New Candida albicans CYP51 Inhibitors

  摘要：

  In a program aimed at the design and synthesis of novel azole inhibitors of Candida albicans CYP51 (CA-CYP51), a series of azole 1,4-benzothiazines (BT) and 1,4-benzoxazines (BO) were recently synthesized. A morphological study of the enzyme active site highlighted a hydrophobic access channel, and a docking study pointed out that the C-2 position of the BT or BO nucleus was oriented toward the access channel. Here, we report the design, synthesis, and microbiological evaluation of C-2-alkyl BT and BO compounds. In both series, introduction of the alkyl chain maintained and in some cases improved the anti-Candida in vitro activity; however, there was not always a strict correlation between in vitro and in vivo activity for several compounds.

  DOI：

  10.1021/jm050685j

文献信息

• Design, Synthesis, and Microbiological Evaluation of New <i>Candida albicans </i>CYP51 Inhibitors
  作者：Fausto Schiaffella、Antonio Macchiarulo、Lara Milanese、Anna Vecchiarelli、Gabriele Costantino、Donatella Pietrella、Renata Fringuelli

  DOI：10.1021/jm050685j

  日期：2005.12.1

  In a program aimed at the design and synthesis of novel azole inhibitors of Candida albicans CYP51 (CA-CYP51), a series of azole 1,4-benzothiazines (BT) and 1,4-benzoxazines (BO) were recently synthesized. A morphological study of the enzyme active site highlighted a hydrophobic access channel, and a docking study pointed out that the C-2 position of the BT or BO nucleus was oriented toward the access channel. Here, we report the design, synthesis, and microbiological evaluation of C-2-alkyl BT and BO compounds. In both series, introduction of the alkyl chain maintained and in some cases improved the anti-Candida in vitro activity; however, there was not always a strict correlation between in vitro and in vivo activity for several compounds.