N,N-dimethyl-4-[4-[(E)-2-phenylethenyl]pyrimidin-2-yl]piperazine-1-sulfonamide | 357951-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N,N-dimethyl-4-[4-[(E)-2-phenylethenyl]pyrimidin-2-yl]piperazine-1-sulfonamide
• CAS: 357951-08-7
• 化学式: C₁₈H₂₃N₅O₂S
• 分子量: 373.479
• InChiKey: NBNHANNCMZKGMN-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-4-[4-[(E)-2-phenylethenyl]pyrimidin-2-yl]piperazine-1-sulfonamide 在 sodium periodate 、 四氧化锇 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 4-(4-Formyl-pyrimidin-2-yl)-piperazine-1-sulfonic acid dimethylamide
  参考文献：
  名称：

  Sorbitol Dehydrogenase Inhibitors (SDIs):  A New Potent, Enantiomeric SDI, 4-[2-1R-Hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic Acid Dimethylamide

  摘要：

  We report here on our medicinal chemistry and pharmacology efforts to provide a potent sorbitol dehydrogenase inhibitor (SDI) as a tool to probe a recently disclosed hypothesis centered on the role of sorbitol dehydrogenase (SDH) in the second step of the polyol pathway, under conditions of high glucose flux. Starting from a weak literature lead, 2, and through newly developed structure-activity relationships, we have designed and executed an unambiguous synthesis of enantiomeric SDI, 6, which is at least 10x more potent than 2. Also, 6 potently inhibits SDH in streptozotocin-diabetic rat sciatic nerve. We have described an expedient synthesis of a key building template, 33, for future research in the SDI area that may facilitate the discovery of even more potent SDIs with longer duration of action in vivo.

  DOI：

  10.1021/jm0102001
• 作为产物：
  描述：

  N,N-二甲基-1-哌嗪磺酰胺 在 偶氮二异丁腈 、 TEA 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N,N-dimethyl-4-[4-[(E)-2-phenylethenyl]pyrimidin-2-yl]piperazine-1-sulfonamide
  参考文献：
  名称：

  Sorbitol Dehydrogenase Inhibitors (SDIs):  A New Potent, Enantiomeric SDI, 4-[2-1R-Hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic Acid Dimethylamide

  摘要：

  We report here on our medicinal chemistry and pharmacology efforts to provide a potent sorbitol dehydrogenase inhibitor (SDI) as a tool to probe a recently disclosed hypothesis centered on the role of sorbitol dehydrogenase (SDH) in the second step of the polyol pathway, under conditions of high glucose flux. Starting from a weak literature lead, 2, and through newly developed structure-activity relationships, we have designed and executed an unambiguous synthesis of enantiomeric SDI, 6, which is at least 10x more potent than 2. Also, 6 potently inhibits SDH in streptozotocin-diabetic rat sciatic nerve. We have described an expedient synthesis of a key building template, 33, for future research in the SDI area that may facilitate the discovery of even more potent SDIs with longer duration of action in vivo.

  DOI：

  10.1021/jm0102001

文献信息

• Sorbitol Dehydrogenase Inhibitors (SDIs):  A New Potent, Enantiomeric SDI, 4-[2-1<i>R</i>-Hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic Acid Dimethylamide
  作者：Banavara L. Mylari、Peter J. Oates、David A. Beebe、Nathaniel S. Brackett、James B. Coutcher、Michael S. Dina、William J. Zembrowski

  DOI：10.1021/jm0102001

  日期：2001.8.1

  We report here on our medicinal chemistry and pharmacology efforts to provide a potent sorbitol dehydrogenase inhibitor (SDI) as a tool to probe a recently disclosed hypothesis centered on the role of sorbitol dehydrogenase (SDH) in the second step of the polyol pathway, under conditions of high glucose flux. Starting from a weak literature lead, 2, and through newly developed structure-activity relationships, we have designed and executed an unambiguous synthesis of enantiomeric SDI, 6, which is at least 10x more potent than 2. Also, 6 potently inhibits SDH in streptozotocin-diabetic rat sciatic nerve. We have described an expedient synthesis of a key building template, 33, for future research in the SDI area that may facilitate the discovery of even more potent SDIs with longer duration of action in vivo.