6-{[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methoxy}-2-butyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one | 1161221-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 6-{[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methoxy}-2-butyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one
• CAS: 1161221-25-5
• 化学式: C₂₄H₂₆BrCl₂NO₅
• 分子量: 559.284
• InChiKey: QFYWMKVXFXBWHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.95
• 重原子数：
  33.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  57.23
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  咪唑 、 6-{[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methoxy}-2-butyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one 在 potassium carbonate 作用下， 以 2,4-滴二甲胺盐 为溶剂， 反应 6.0h， 以36%的产率得到cis-2-butyl-6-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  Bulky 1,4-benzoxazine derivatives with antifungal activity

  摘要：

  For many years the development of new azole antifungals has been quite empirically based. More recently, the publication of the crystal structure of CYP51 of Mycobacterium tuberculosis (MT-CYP51) provided new opportunities to rationalize the knowledge about antifungal action of this class of compounds. Recent studies reported that a 'channel 2 opened' conformation of the enzyme could better explain the interaction with ketoconazole (KTZ)-like drugs. Conformational changes were made on our model of Candida albicans CYP51 (CA-CYP51) previously reported and docking experiments were performed. The results allowed new KTZ analogues to be designed, by predicting that the 1,4-benzoxazine moiety could replace the KTZ aryl-piperazinyl chain. The synthesis of derivatives 12 and 13 was planned.The in vitro antifungal activity was evaluated against different Candida species and low and high capsulated strains of Cryptococcus neoformans. Since the in vitro activity do not necessarily correlate with the in vivo antifungal activity the newly synthesized compounds were also tested in a murine model of systemic C. albicans infection. The therapeutic effect was evaluated in terms of animal survival and of fungal growth in the kidneys, the target organ in systemic candidiasis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.051
• 作为产物：
  描述：

  [2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methyl methanesulfonate 、 2-butyl-6-hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one 在 sodium hydride 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 5.0h， 以48%的产率得到6-{[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methoxy}-2-butyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  Bulky 1,4-benzoxazine derivatives with antifungal activity

  摘要：

  For many years the development of new azole antifungals has been quite empirically based. More recently, the publication of the crystal structure of CYP51 of Mycobacterium tuberculosis (MT-CYP51) provided new opportunities to rationalize the knowledge about antifungal action of this class of compounds. Recent studies reported that a 'channel 2 opened' conformation of the enzyme could better explain the interaction with ketoconazole (KTZ)-like drugs. Conformational changes were made on our model of Candida albicans CYP51 (CA-CYP51) previously reported and docking experiments were performed. The results allowed new KTZ analogues to be designed, by predicting that the 1,4-benzoxazine moiety could replace the KTZ aryl-piperazinyl chain. The synthesis of derivatives 12 and 13 was planned.The in vitro antifungal activity was evaluated against different Candida species and low and high capsulated strains of Cryptococcus neoformans. Since the in vitro activity do not necessarily correlate with the in vivo antifungal activity the newly synthesized compounds were also tested in a murine model of systemic C. albicans infection. The therapeutic effect was evaluated in terms of animal survival and of fungal growth in the kidneys, the target organ in systemic candidiasis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.051