2-(8-amino-1,4-dioxaspiro[4.5]decan-8-yl)acetic acid | 889949-15-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(8-amino-1,4-dioxaspiro[4.5]decan-8-yl)acetic acid
• CAS: 889949-15-9
• 化学式: C₁₀H₁₇NO₄
• 分子量: 215.249
• InChiKey: JTEBCEBWWIDILZ-UHFFFAOYSA-N

物化性质

• 沸点：
  389.1±42.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  86.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(8-amino-1,4-dioxaspiro[4.5]decan-8-yl)acetic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以91%的产率得到2-(8-amino-1,4-dioxaspiro[4.5]decan-8-yl)ethanol
  参考文献：
  名称：

  Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa

  摘要：

  Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.

  DOI：

  10.1016/j.bmc.2014.07.040

文献信息

• Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa
  作者：Folkert Reck、David E. Ehmann、Thomas J. Dougherty、Joseph V. Newman、Sussie Hopkins、Gregory Stone、Nikunj Agrawal、Paul Ciaccio、John McNulty、Herbert Barthlow、Jennifer O’Donnell、Kosalaram Goteti、John Breen、Janelle Comita-Prevoir、Mark Cornebise、Mark Cronin、Charles J. Eyermann、Bolin Geng、Greg R. Carr、Lakshmipathi Pandarinathan、Xuejun Tang、Andrew Cottone、Liang Zhao、Natascha Bezdenejnih-Snyder

  DOI：10.1016/j.bmc.2014.07.040

  日期：2014.10

  Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.