(S)-5,5-dimethyl-4-phenyl-3-(1,4-dioxaspiro[4.5]decan-8-yl)oxazolidin-2-one | 1466571-21-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-5,5-dimethyl-4-phenyl-3-(1,4-dioxaspiro[4.5]decan-8-yl)oxazolidin-2-one
• CAS: 1466571-21-0
• 化学式: C₁₉H₂₅NO₄
• 分子量: 331.412
• InChiKey: WSLCIQKEERPIDH-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  48.0
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-5,5-dimethyl-4-phenyl-3-(1,4-dioxaspiro[4.5]decan-8-yl)oxazolidin-2-one 在 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 17.33h， 生成 4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yltrifluoromethanesulfonate
  参考文献：
  名称：

  Structure-Based Design of 2-Aminopyridine Oxazolidinones as Potent and Selective Tankyrase Inhibitors

  摘要：

  Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model.

  DOI：

  10.1021/ml4003315
• 作为产物：
  描述：

  (S)-1-氨基-2-甲基-1-苯丙-2-醇 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 6.25h， 生成 (S)-5,5-dimethyl-4-phenyl-3-(1,4-dioxaspiro[4.5]decan-8-yl)oxazolidin-2-one
  参考文献：
  名称：

  Structure-Based Design of 2-Aminopyridine Oxazolidinones as Potent and Selective Tankyrase Inhibitors

  摘要：

  Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model.

  DOI：

  10.1021/ml4003315