1-adamantan-1-yl-3-(4-hydroxycyclohexyl)urea | 885009-83-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-adamantan-1-yl-3-(4-hydroxycyclohexyl)urea
• 英文别名: trans-1-(4-hydroxy-cyclohexyl)-3-tricyclo[3.3.1.13,7] decan-1-yl-urea
• CAS: 885009-83-6
• 化学式: C₁₇H₂₈N₂O₂
• 分子量: 292.422
• InChiKey: YHZXOUHNBSOYQD-QVTUNDJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  61.36
• 氢给体数：
  3.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-adamantan-1-yl-3-(4-hydroxycyclohexyl)urea 在 重铬酸吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以85%的产率得到1-adamantan-1-yl-3-(4-oxocyclohexyl)urea
  参考文献：
  名称：

  Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors

  摘要：

  A series of N,N'-disubstituted ureas having a conformationally restricted cis- or traiis-1,4-cyclohexane alpha to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 +/- 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models.

  DOI：

  10.1021/jm070270t
• 作为产物：
  描述：

  异氰酸1-金刚烷酯 、 trans-4-aminocyclohexanol hydrochloride 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以100%的产率得到1-adamantan-1-yl-3-(4-hydroxycyclohexyl)urea
  参考文献：
  名称：

  用醚基官能化的1,3-二取代脲是有效的可溶性环氧化物水解酶抑制剂，具有改善的药代动力学特性。

  摘要：

  可溶性环氧水解酶（sEH）是用于治疗高血压和炎症的治疗靶标。被醚基官能化的1,3-二取代脲是有效的sEH抑制剂。然而，它们相对较低的代谢稳定性导致不良的药代动力学性质。为了提高其生物利用度，我们研究了在醚功能上掺入各种极性基团对抑制能力，物理性质，体外代谢稳定性和药代动力学性质的影响。结构-活性关系研究表明，脲基团和醚官能团之间的疏水性连接基对于保持其效能是必要的。此外，具有极性基团的脲-醚抑制剂，例如二甘醇或吗啉，可显着改善其物理性质和代谢稳定性，而不会丧失任何抑制效力。此外，使用所得抑制剂在鼠和犬模型中获得了改善的药代动力学性质。这些发现将有助于在高血压和发炎的动物模型中使用sEH抑制剂。

  DOI：

  10.1021/jm070705c

文献信息

• Inhibitors for the soluble epoxide hydrolase
  申请人：Hammock D. Bruce

  公开号：US20060270609A1

  公开（公告）日：2006-11-30

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可用于治疗疾病的可溶性环氧酶（sEH）抑制剂，其中包含多个药效团。
• Inhibitors for the Soluble Epoxide Hydrolase
  申请人：HAMMOCK BRUCE D.

  公开号：US20110021448A1

  公开（公告）日：2011-01-27

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可用于治疗疾病的可溶性环氧酶（sEH）抑制剂，其中包含多个药效团。
• [EN] IMPROVED INHIBITORS FOR THE SOLUBLE EPOXIDE HYDROLASE<br/>[FR] INHIBITEURS AMELIORES DE L'EPOXYDE HYDROLASE SOLUBLE
  申请人：UNIV CALIFORNIA

  公开号：WO2006045119A3

  公开（公告）日：2007-02-08
• Synthesis and biological evaluation of sorafenib- and regorafenib-like sEH inhibitors
  作者：Sung Hee Hwang、Aaron T. Wecksler、Guodong Zhang、Christophe Morisseau、Long V. Nguyen、Samuel H. Fu、Bruce D. Hammock

  DOI：10.1016/j.bmcl.2013.05.011

  日期：2013.7

  To reduce the pro-angiogenic effects of sEH inhibition, a structure-activity relationship (SAR) study was performed by incorporating structural features of the anti-angiogenic multi-kinase inhibitor sorafenib into soluble epoxide hydrolase (sEH) inhibitors. The structural modifications of this series of molecules enabled the altering of selectivity towards the pro-angiogenic kinases C-RAF and vascular endothelial growth factor receptor-2 (VEGFR-2), while retaining their sEH inhibition. As a result, sEH inhibitors with greater potency against C-RAF and VEGFR-2 were obtained. Compound 4 (t-CUPM) possesses inhibition potency higher than sorafenib towards sEH but similar against C-RAF and VEGFR-2. Compound 7 (t-CUCB) selectively inhibits sEH, while inhibiting HUVEC cell proliferation, a potential anti-angiogenic property, without liver cancer cell cytotoxicity. The data presented suggest a potential rational approach to control the angiogenic responses stemming from sEH inhibition. (C) 2013 Elsevier Ltd. All rights reserved.
• US7662910B2
  申请人：——

  公开号：US7662910B2

  公开（公告）日：2010-02-16