dimethyl 2,6-diisopropyl-4-hydroxy-3,5-pyridine-dicarboxylate | 470717-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: dimethyl 2,6-diisopropyl-4-hydroxy-3,5-pyridine-dicarboxylate
• 英文别名: diMethyl 2,6-diisopropyl-4-hydroxy-3,5-pyridine-dicarboxylate；dimethyl 4-oxo-2,6-di(propan-2-yl)-1H-pyridine-3,5-dicarboxylate
• CAS: 470717-49-8
• 化学式: C₁₅H₂₁NO₅
• 分子量: 295.335
• InChiKey: LOXLDVUKEKOTFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 2,6-diisopropyl-4-hydroxy-3,5-pyridine-dicarboxylate 在 lithium aluminium tetrahydride 、 potassium carbonate 、 红铝 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 0.5h， 生成 1-[4-(2-Benzyloxy-4-fluoro-phenyl)-2,6-diisopropyl-5-vinyl-pyridin-3-yl]-ethanol
  参考文献：
  名称：

  Integration of optimized substituent patterns to produce highly potent 4-aryl-pyridine glucagon receptor antagonists

  摘要：

  Optimized substituent patterns in 4-arul-puridine glucagon receptor antagonists were merged to produce highly potent derivatives containing both a 3-[(1R)-hydroxyethyl] and a 2'-hydroxy group. Due to restricted rotation of the phenyl-pyridine bond, these analogues exist as four isomers. A diastereoselective methylcopper reaction as developed to facilitate the synthesis, and single isomers ere isolated with activities in the range IC50 = 10 25 nM. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00736-9
• 作为产物：
  描述：

  dimethyl 2,6-diisopropyl-4-oxo-2H-pyran-3,5-dicarboxylate 在 氨 作用下， 以 甲醇 为溶剂， 以92%的产率得到dimethyl 2,6-diisopropyl-4-hydroxy-3,5-pyridine-dicarboxylate
  参考文献：
  名称：

  Optimization of the 4-aryl group of 4-aryl-pyridine glucagon antagonists: development of an efficient, alternative synthesis

  摘要：

  A narrow structure-activity relationship was established for the 4-aryl group in 4-aryl-pyridine glucagon antagonists, with only small substituents being well-tolerated, and only at the 3'- and 4'-positions. However, substitution with a 2'-hydroxy group gave a ca. 3-fold increase in activity (e.g., 4'-fluoro-2'-hydroxy analogue 33, IC50 = 190 nM). For efficient preparation of 2'-substituted phenylpyridines, a novel synthesis via pyrones and 4-methoxy-pyridines was developed. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00143-9

文献信息

• Integration of optimized substituent patterns to produce highly potent 4-aryl-pyridine glucagon receptor antagonists
  作者：Gaetan H. Ladouceur、James H. Cook、Donald L. Hertzog、J.Howard Jones、Thomas Hundertmark、Mary Korpusik、Timothy G. Lease、James N. Livingston、Margit L. MacDougall、Martin H. Osterhout、Kathleen Phelan、Romulo H. Romero、William R. Schoen、Chunning Shao、Roger A. Smith

  DOI：10.1016/s0960-894x(02)00736-9

  日期：2002.12

  Optimized substituent patterns in 4-arul-puridine glucagon receptor antagonists were merged to produce highly potent derivatives containing both a 3-[(1R)-hydroxyethyl] and a 2'-hydroxy group. Due to restricted rotation of the phenyl-pyridine bond, these analogues exist as four isomers. A diastereoselective methylcopper reaction as developed to facilitate the synthesis, and single isomers ere isolated with activities in the range IC50 = 10 25 nM. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Optimization of the 4-aryl group of 4-aryl-pyridine glucagon antagonists: development of an efficient, alternative synthesis
  作者：Roger A. Smith、Donald L. Hertzog、Martin H. Osterhout、Gaetan H. Ladouceur、Mary Korpusik、Mark A. Bobko、J.Howard Jones、Kathleen Phelan、Romulo H. Romero、Thomas Hundertmark、Margit L. MacDougall、James N. Livingston、William R. Schoen

  DOI：10.1016/s0960-894x(02)00143-9

  日期：2002.5

  A narrow structure-activity relationship was established for the 4-aryl group in 4-aryl-pyridine glucagon antagonists, with only small substituents being well-tolerated, and only at the 3'- and 4'-positions. However, substitution with a 2'-hydroxy group gave a ca. 3-fold increase in activity (e.g., 4'-fluoro-2'-hydroxy analogue 33, IC50 = 190 nM). For efficient preparation of 2'-substituted phenylpyridines, a novel synthesis via pyrones and 4-methoxy-pyridines was developed. (C) 2002 Elsevier Science Ltd. All rights reserved.