4-(4-chloropyrimidin-2-yl)-N,N-dimethylpiperazine-1-sulfonamide | 357951-07-6

• 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: 4-(4-chloropyrimidin-2-yl)-N,N-dimethylpiperazine-1-sulfonamide
• CAS: 357951-07-6
• 化学式: C₁₀H₁₆ClN₅O₂S
• 分子量: 305.788
• InChiKey: YDMNGQNLMKRUCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  4-(4-chloropyrimidin-2-yl)-N,N-dimethylpiperazine-1-sulfonamide 在 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 偶氮二异丁腈 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 生成 4-(4-Hydroxymethyl-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：

  2,4-二氯嘧啶 、 N,N-二甲基-1-哌嗪磺酰胺 在 TEA 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(4-chloropyrimidin-2-yl)-N,N-dimethylpiperazine-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.