(E)-1-methyl-3-(2-pyridinylmethyl)-5-(2-pyridinylmethylidene)-4-piperidone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (E)-1-methyl-3-(2-pyridinylmethyl)-5-(2-pyridinylmethylidene)-4-piperidone
• 英文别名: (5E)-1-methyl-3-(pyridin-2-ylmethyl)-5-(pyridin-2-ylmethylidene)piperidin-4-one
• 化学式: C₁₈H₁₉N₃O
• 分子量: 293.368
• InChiKey: XNBNPTNODRUPCB-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-1-methyl-3-(2-pyridinylmethyl)-5-(2-pyridinylmethylidene)-4-piperidone 在 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以57%的产率得到(E)-1-methyl-3-(2-pyridinylmethyl)-5-(2-pyridinylmethylidene)-4-hydroxypiperidine
  参考文献：
  名称：

  Liver S9 Fraction-Derived Metabolites of Curcumin Analogue UBS109

  摘要：

  To address the shortcomings of the natural product curcumin, many groups have created analogues that share similar structural features while displaying superior properties, particularly in anticancer drug discovery. Relatively unexplored have been the mechanisms by which such compounds are metabolized. A comprehensive in vitro study of a curcumin analogue (UBS109) in liver S9 fractions from five different species is presented. Further, we examine the cell-based bioactivity of the major metabolites. In spite of the fact that UBS109 reduces tumor growth in mice, it is quickly metabolized in vitro and 94% protein bound in mouse plasma. The primary monounsaturated metabolite is only modestly bioactive against MDA-MB-231 breast cancer cells. These observations suggest that while the alpha,beta-unsaturated ketone common to curcumin analogues is important for bioactivity, protein binding and tissue distribution may serve to protect UBS109 from full metabolism in vivo while allowing it to exert a pharmacological effect by means of slow drug release.

  DOI：

  10.1021/ml4002453
• 作为产物：
  描述：

  (E)-1-methyl-3,5-bis(2-pyridinylmethylidene)-4-piperidone 在 glucose 6-phosphate 、 potassium chloride 、 氧气 、 还原型辅酶II(NADPH)四钠盐 、 6-[[[5-(2,4-二氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-3,4,5-三羟基四氢吡喃-2-羧酸 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 生成 (E)-1-methyl-3-(2-pyridinylmethyl)-5-(2-pyridinylmethylidene)-4-piperidone
  参考文献：
  名称：

  Liver S9 Fraction-Derived Metabolites of Curcumin Analogue UBS109

  摘要：

  To address the shortcomings of the natural product curcumin, many groups have created analogues that share similar structural features while displaying superior properties, particularly in anticancer drug discovery. Relatively unexplored have been the mechanisms by which such compounds are metabolized. A comprehensive in vitro study of a curcumin analogue (UBS109) in liver S9 fractions from five different species is presented. Further, we examine the cell-based bioactivity of the major metabolites. In spite of the fact that UBS109 reduces tumor growth in mice, it is quickly metabolized in vitro and 94% protein bound in mouse plasma. The primary monounsaturated metabolite is only modestly bioactive against MDA-MB-231 breast cancer cells. These observations suggest that while the alpha,beta-unsaturated ketone common to curcumin analogues is important for bioactivity, protein binding and tissue distribution may serve to protect UBS109 from full metabolism in vivo while allowing it to exert a pharmacological effect by means of slow drug release.

  DOI：

  10.1021/ml4002453