12-hydroxy-dodec-7-ynoic acid | 126696-05-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 12-hydroxy-dodec-7-ynoic acid
• 英文别名: 12-Hydroxydodec-7-ynoic acid
• CAS: 126696-05-7
• 化学式: C₁₂H₂₀O₃
• 分子量: 212.289
• InChiKey: KRJLFPSGGZFBLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  12-hydroxy-dodec-7-ynoic acid 在 吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 苯 为溶剂， 反应 21.5h， 生成 15-hydroxy-4-oxo-10-pentadecynoic acid lactone
  参考文献：
  名称：

  Intramolecular acyl radical-alkene addition reactions: macrocyclization reactions

  摘要：

  DOI：

  10.1021/ja00166a044
• 作为产物：
  描述：

  5-己炔-1-醇 、 6-溴己酸 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 12-hydroxy-dodec-7-ynoic acid
  参考文献：
  名称：

  Design and synthesis of hydroxy-alkynoic acids and their methyl esters as novel activators of BK channels

  摘要：

  Physiological and pharmacological agents that activate large conductance, voltage-, and calcium- gated potassium (BK) channels located in the smooth muscle are effective vasodilators. Thus, activators of smooth muscle BK channels may be potential therapeutic tools to treat cardiovascular disease associated with vasoconstriction and/or impaired dilation, such as cerebrovascular spasm and constriction. We previously showed that lithocholic acid (LC) and other cholane derivatives activated smooth muscle BK channels and, thus, caused endothelium-independent cerebral artery dilation. However, clinical use of these cholane derivatives could be limited by the actions of these steroids, such as elevation of intracellular calcium and induction of apoptosis. Using LC as template, we designed and synthesized a series of hydroxy-alkynoic acids and corresponding methyl esters, as putative, nonsteroid BK channel activators. Indeed, the newly synthesized compounds effectively and reversibly activated rat cerebrovascular myocyte BK channel at concentrations similar to those found effective with LC. Among all the novel compounds tested, C-10 hydroxy-alkynoic acid methyl ester appears to be the most effective activator of vascular myocyte BK channels. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.080

文献信息

• Intramolecular acyl radical-alkene addition reactions: macrocyclization reactions
  作者：Dale L. Boger、Robert J. Mathvink

  DOI：10.1021/ja00166a044

  日期：1990.5
• Design and synthesis of hydroxy-alkynoic acids and their methyl esters as novel activators of BK channels
  作者：Shivaputra Patil、Anna N. Bukiya、Wei Li、Alejandro M. Dopico、Duane Miller

  DOI：10.1016/j.bmcl.2008.03.080

  日期：2008.6

  Physiological and pharmacological agents that activate large conductance, voltage-, and calcium- gated potassium (BK) channels located in the smooth muscle are effective vasodilators. Thus, activators of smooth muscle BK channels may be potential therapeutic tools to treat cardiovascular disease associated with vasoconstriction and/or impaired dilation, such as cerebrovascular spasm and constriction. We previously showed that lithocholic acid (LC) and other cholane derivatives activated smooth muscle BK channels and, thus, caused endothelium-independent cerebral artery dilation. However, clinical use of these cholane derivatives could be limited by the actions of these steroids, such as elevation of intracellular calcium and induction of apoptosis. Using LC as template, we designed and synthesized a series of hydroxy-alkynoic acids and corresponding methyl esters, as putative, nonsteroid BK channel activators. Indeed, the newly synthesized compounds effectively and reversibly activated rat cerebrovascular myocyte BK channel at concentrations similar to those found effective with LC. Among all the novel compounds tested, C-10 hydroxy-alkynoic acid methyl ester appears to be the most effective activator of vascular myocyte BK channels. (c) 2008 Elsevier Ltd. All rights reserved.