(E)-5-[(hydroxylamino)methyl]-3-[5-methyl-3-(2-methylpropyl)hexylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one | 388622-21-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-5-[(hydroxylamino)methyl]-3-[5-methyl-3-(2-methylpropyl)hexylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one
• 英文别名: (3E)-5-[(hydroxyamino)methyl]-3-[5-methyl-3-(2-methylpropyl)hexylidene]-5-(phenylmethoxymethyl)oxolan-2-one
• CAS: 388622-21-7
• 化学式: C₂₄H₃₇NO₄
• 分子量: 403.562
• InChiKey: KWGDIRVVVZGSOQ-SSDVNMTOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-5-[(hydroxylamino)methyl]-3-[5-methyl-3-(2-methylpropyl)hexylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one 在 三氯化硼 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 生成 (E)-N-hydroxy-N-({2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxo-(2-2,3-dihydrofuryl)}methyl)-2,2-dimethylpropanamide
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 19. Synthesis and Protein Kinase C Binding Affinity of Diacylglycerol Lactones Bearing an N-Hydroxylamide Side Chain

  摘要：

  The structures of N-hydroxylamides 1a and 1b, previously reported by Lee et al. in J. Med. Chem. 2001, 44, 4309-4312 as strong protein kinase C (PK-C) ligands, were incorrect and correspond instead to esters 2a and 2b, respectively. Here, we report the synthesis and complete characterization of 1a and 1b together with the associated biological activity in terms of PK-C binding affinity.

  DOI：

  10.1021/jm030082c
• 作为产物：
  描述：

  5-[(4-methoxyphenoxy)methyl]-5-[(phenylmethoxy)methyl]-3,4,5-trihydrofuran-2-one 在 草酰氯 、 ammonium cerium(IV) nitrate 、 sodium cyanoborohydride 、 溶剂黄146 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 6.92h， 生成 (E)-5-[(hydroxylamino)methyl]-3-[5-methyl-3-(2-methylpropyl)hexylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 19. Synthesis and Protein Kinase C Binding Affinity of Diacylglycerol Lactones Bearing an N-Hydroxylamide Side Chain

  摘要：

  The structures of N-hydroxylamides 1a and 1b, previously reported by Lee et al. in J. Med. Chem. 2001, 44, 4309-4312 as strong protein kinase C (PK-C) ligands, were incorrect and correspond instead to esters 2a and 2b, respectively. Here, we report the synthesis and complete characterization of 1a and 1b together with the associated biological activity in terms of PK-C binding affinity.

  DOI：

  10.1021/jm030082c

文献信息

• Conformationally Constrained Analogues of Diacylglycerol. 18. The Incorporation of a Hydroxamate Moiety into Diacylglycerol-Lactones Reduces Lipophilicity and Helps Discriminate between <i>sn-1</i> and <i>sn-2</i> Binding Modes to Protein Kinase C (PK-C). Implications for Isozyme Specificity
  作者：Jeewoo Lee、Kee-Chung Han、Ji-Hye Kang、Larry L. Pearce、Nancy E. Lewin、Shunqi Yan、Samira Benzaria、Marc C. Nicklaus、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm0103965

  日期：2001.12.1

  approach to reduce the log P in a series of diacylglycerol (DAG)-lactones known for their high binding affinity for protein kinase C (PK-C) is presented. Branched alkyl groups with reduced lipophilicity were selected and combined with the replacement of the ester or lactone oxygens by NH or NOH groups. Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue

  提出了一种减少一系列二酰基甘油（DAG）-内酯中的log P的方法，这些内酯对蛋白激酶C（PK-C）具有高结合亲和力。选择具有降低的亲脂性的支链烷基，并结合用NH或NOH基团取代酯或内酯氧。具有等排N-羟基酰胺基臂的化合物6a代表迄今为止已知的最有效和最不亲脂的DAG类似物。
• Conformationally Constrained Analogues of Diacylglycerol. 19. Synthesis and Protein Kinase C Binding Affinity of Diacylglycerol Lactones Bearing an <i>N</i>-Hydroxylamide Side Chain
  作者：Yongseok Choi、Ji-Hye Kang、Nancy E. Lewin、Peter M. Blumberg、Jeewoo Lee、Victor E. Marquez

  DOI：10.1021/jm030082c

  日期：2003.6.1

  The structures of N-hydroxylamides 1a and 1b, previously reported by Lee et al. in J. Med. Chem. 2001, 44, 4309-4312 as strong protein kinase C (PK-C) ligands, were incorrect and correspond instead to esters 2a and 2b, respectively. Here, we report the synthesis and complete characterization of 1a and 1b together with the associated biological activity in terms of PK-C binding affinity.