1-(adamant-1-ylmethyl)-3-[(3-methylisoxazol-5-yl)methyl]urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(adamant-1-ylmethyl)-3-[(3-methylisoxazol-5-yl)methyl]urea
• 英文别名: 1-(1-adamantylmethyl)-3-[(3-methyl-1,2-oxazol-5-yl)methyl]urea
• 化学式: C₁₇H₂₅N₃O₂
• 分子量: 303.404
• InChiKey: APGILQCNCDVVOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-甲基异恶唑-5-甲胺 、 1-(isocyanatomethyl)adamantane 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以85%的产率得到1-(adamant-1-ylmethyl)-3-[(3-methylisoxazol-5-yl)methyl]urea
  参考文献：
  名称：

  1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors

  摘要：

  Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed. Overall, the presence of methyl on the nodal positions of adamantane yields higher water solubility than previously reported urea-based sEH inhibitors while maintaining high inhibition potency. However, it did not improve microsomal stability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.066

文献信息

• Synthesis and Study of 1,3- and 1,3,3-Substituted Ureas Containing Isoxazole and Adamantane Fragments
  作者：G. M. Butov、V. V. Burmistrov、I. L. Dalinger、I. A. Vatsadze、T. K. Shkineva、D. V. Danilov

  DOI：10.1007/s10593-015-1643-3

  日期：2015.3

  A series of 1,3-disubstituted and 1,3,3-trisubstituted isoxazolyl- and adamantyl-functionalized ureas was synthesized. The resulting compounds are potent inhibitors of soluble epoxide hydrolase. The compounds were obtained in high yields under mild conditions. Water solubility of the synthesized ureas was found to exceed significantly that of known analogs.
• 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors
  作者：Vladimir Burmistrov、Christophe Morisseau、Dmitry Danilov、Todd R. Harris、Igor Dalinger、Irina Vatsadze、Tatiana Shkineva、Gennady M. Butov、Bruce D. Hammock

  DOI：10.1016/j.bmcl.2015.10.066

  日期：2015.12

  Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed. Overall, the presence of methyl on the nodal positions of adamantane yields higher water solubility than previously reported urea-based sEH inhibitors while maintaining high inhibition potency. However, it did not improve microsomal stability. (C) 2015 Elsevier Ltd. All rights reserved.