Bis(1,4-dioxaspiro[4.5]decan-8-yl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Bis(1,4-dioxaspiro[4.5]decan-8-yl)methanone
• 英文别名: bis(1,4-dioxaspiro[4.5]decan-8-yl)methanone
• 化学式: C₁₇H₂₆O₅
• 分子量: 310.39
• InChiKey: AFLZHWXXXZLFJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,4-dioxaspiro[4.5]dec-7-ene-8-carbaldehyde 在 正丁基锂 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， -78.0~23.0 ℃ 、101.33 kPa 条件下， 反应 33.53h， 生成 Bis(1,4-dioxaspiro[4.5]decan-8-yl)methanone
  参考文献：
  名称：

  Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

  摘要：

  We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4',4'-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.

  DOI：

  10.1021/acs.jmedchem.6b01592