cis-4-(4-fluoro-phenoxy)-cyclohexylamine | 916489-73-1

• 英文名称: cis-4-(4-fluoro-phenoxy)-cyclohexylamine
• 英文别名: cis-4-(4-fluorophenoxy)cyclohexylamine
• CAS: 916489-73-1
• 化学式: C₁₂H₁₆FNO
• 分子量: 209.264
• InChiKey: PQOUJGMSVPGFRX-KLPPZKSPSA-N

物化性质

• 沸点：
  309.5±32.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.47
• 重原子数：
  15.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.25
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  cis-4-(4-fluoro-phenoxy)-cyclohexylamine 在 lithium hydroxide 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Solid-phase combinatorial approach for the optimization of soluble epoxide hydrolase inhibitors

  摘要：

  A 192-member library of N,N'-disubstituted urea inhibitors was synthesized by a solid-phase method. The ureas were tested for their inhibitory activities against recombinant human soluble epoxide hydrolase. Simple carbocyclic or paralmeta-substituted phenyl groups showed inhibition potencies that were equal to or greater than adamantane-based sEH inhibitors, while the presence of bulky or ionizable groups close to the urea group dramatically decreased their activities. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.078
• 作为产物：
  描述：

  trans-4-aminocyclohexanol hydrochloride 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 一水合肼 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 24.5h， 生成 cis-4-(4-fluoro-phenoxy)-cyclohexylamine
  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

文献信息

• Explorations of Substituted Urea Functionality for the Discovery of New Activators of the Heme-Regulated Inhibitor Kinase
  作者：Ting Chen、Khuloud Takrouri、Sung Hee-Hwang、Sandeep Rana、Revital Yefidoff-Freedman、Jose Halperin、Amarnath Natarajan、Christophe Morisseau、Bruce Hammock、Michael Chorev、Bertal H. Aktas

  DOI：10.1021/jm400793v

  日期：2013.12.12

  chemotypes that activate HRI, we screened a ∼1900 member N,N′-disubstituted urea library in the surrogate eIF2α phosphorylation assay, identifying N-aryl,N′-cyclohexylphenoxyurea as a promising scaffold. We validated hit compounds as a bona fide HRI activators in secondary assays and explored the contributions of substitutions on the N-aryl and N′-cyclohexylphenoxy groups to their activity by studying

  血红素调节抑制剂激酶 (HRI) 是一种真核翻译起始因子 2 α (eIF2α) 激酶，在细胞增殖、分化和对细胞质应激的适应中起着关键作用。HRI 还是血红蛋白疾病（如 β-地中海贫血）的关键调节剂。我们之前将N , N '-二芳基脲鉴定为 HRI 的有效激活剂，适用于研究这一重要激酶的生物学。以展开激活HRI化学型的剧目，我们筛选一个~1900构件Ñ，Ñ '二取代的脲在替代eIF2α的磷酸化测定，鉴定库Ñ -芳基，Ñ'-环己基苯氧基脲作为一种有前途的支架。我们在二次测定中验证了命中化合物作为真正的 HRI 激活剂，并通过研究互补类似物的重点文库探索了N-芳基和N'-环己基苯氧基上的取代对其活性的贡献。我们在替代 eIF2α 磷酸化和细胞增殖测定中测试了这些N-芳基、N'-环己基苯氧基脲，证明了显着改善的生物活性和特异性。我们认为这些化合物代表了开发有效和特定 HRI 激活剂的主要候选物。
• [EN] SUBSTITUTED UREA EIF2α KINASE ACTIVATORS<br/>[FR] ACTIVATEURS SUBSTITUÉS DE L'URÉE-KINASE EIF2&Agr;
  申请人：BRIGHAM & WOMENS HOSPITAL

  公开号：WO2015038778A1

  公开（公告）日：2015-03-19

  This disclosure relates to substituted urea eIF2α kinase activators including methods of making and using the same. For example, such activators can include cycloalkyl aryl ureas, which activate at least one eIF2α kinase. These compounds may be useful for treatment of diseases such as, for example, cancer, hemolytic anemia not caused by infectious agents, Wolcott-Rallison syndrome, neurodegenerative disease, tuberous sclerosis complex, fragile-X syndrome, autism spectrum disorder, and ribosomal defect disease.

  本公开涉及替代脲eIF2α激酶激活剂，包括其制备和使用方法。例如，这些激活剂可以包括环烷基芳基脲，其激活至少一种eIF2α激酶。这些化合物可能对治疗疾病有用，例如癌症、非感染性溶血性贫血、沃尔科特-拉里森综合征、神经退行性疾病、结节性硬化症、脆性X综合征、自闭症谱系障碍和核糖体缺陷疾病。
• 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