1-adamantan-1-yl-3-(3-hydroxyphenyl)urea

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-adamantan-1-yl-3-(3-hydroxyphenyl)urea
• 英文别名: 1-Adamantan-1-yl-3-(3-hydroxy-phenyl)-urea；1-(1-adamantyl)-3-(3-hydroxyphenyl)urea
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: FBTNUWJYRWKVCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-adamantan-1-yl-3-(3-hydroxyphenyl)urea 、 2-(2-乙氧基乙氧基)乙基溴 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以90%的产率得到1-Adamantan-1-yl-3-{3-[2-(2-ethoxyethoxy)ethoxy]phenyl}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
• 作为产物：
  描述：

  异氰酸1-金刚烷酯 、 3-氨基苯酚 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到1-adamantan-1-yl-3-(3-hydroxyphenyl)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

• The use of substituted carbocyclic compounds as rotamases inhibitors
  申请人：Jerini AG

  公开号：EP1402888A1

  公开（公告）日：2004-03-31

  The present invention is related to the use of a compound as an inhibitor to a rotamase, whereby the compound has the structure:         A-X-Y     (I) wherein A is cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; X is a spacer and is selected from X1 or X2, wherein X1 is selected from the group comprising -[(CRaRb)n-NRc-CO-NRd-(CRaRb)m]t-, -[(CRaRb)n-NRc-CS-NRd-(CRaRb)m]t-, -[(CRaRb)n-NRc-C(N-CN)-NRd-(CRaRb)m]t-, -[(CRaRb)n-NRc-C(N-Re)-NRd-(CRaRb)m]t-, -[(CRaRb)n-CO-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-CO-O-(CRaRb)m]t-, -[(CRaRb)n-O-CO-NRc-(CRaRb)m]t-, -[(CRaRb)n-O-(CRaRb)m]t-, -[(CRaRb)n-SRc-(CRaRb)m]t-; wherein X2 is selected from the group comprising - [(CRaRb)n-CO-(CRaRb)m]t-, -[(CRaRb)n-CS-(CRaRb)m]t-, -[(CRaRb)n-NRc-CO-(CRaRb)m]t-, -[(CRaRb)n-CO-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-CS-(CRaRb)m]t-, -[(CRaRb)n-CS-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-SO2-(CRaRb)m]t-, -[(CRaRb)n-SO2-NRc-(CRaRb)m]t-, -[(CRaRb)n-SO-(CRaRb)m]t-, -[(CRaRb)n-SO2-(CRaRb)m]t-, -[(CRaRb)n]t-; wherein n and m are independently selected from each other and are any integer between 0 and 10 provided that if n is 0, m is different from 0, and if m is 0, n is different from 0; wherein t is independently selected from n and/or m and is any integer between 0 and 10; wherein Ra, Rb, Rc, Rd and Re are independently from each other selected from the group comprising H, alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl; and wherein Y is selected from the group comprising alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heterocyclyl, substituted heterocyclyl, mono-unsaturated heterocyclyl, poly-unsaturated heterocyclyl, mono-substituted poly-unsaturated heterocyclyl, poly-substituted poly-unsaturated heterocyclyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl, wherein Y is different from a peptide.

  本发明涉及将某种化合物作为旋转酶的抑制剂使用，其中该化合物具有以下结构：        A-X-Y     (I)其中A为环烷基、取代环烷基、杂环烷基、取代杂环烷基、芳基、取代芳基、杂芳基或取代杂芳基；X为间隔物，可从X1或X2中选择，其中X1可从以下组中选择：-[(CRaRb)n-NRc-CO-NRd-(CRaRb)m]t-，-[(CRaRb)n-NRc-CS-NRd-(CRaRb)m]t-，-[(CRaRb)n-NRc-C(N-CN)-NRd-(CRaRb)m]t-，-[(CRaRb)n-NRc-C(N-Re)-NRd-(CRaRb)m]t-，-[(CRaRb)n-CO-NRc-(CRaRb)m]t-，-[(CRaRb)n-NRc-(CRaRb)m]t-，-[(CRaRb)n-NRc-CO-O-(CRaRb)m]t-，-[(CRaRb)n-O-CO-NRc-(CRaRb)m]t-，-[(CRaRb)n-O-(CRaRb)m]t-，-[(CRaRb)n-SRc-(CRaRb)m]t-；其中X2可从以下组中选择：-[(CRaRb)n-CO-(CRaRb)m]t-，-[(CRaRb)n-CS-(CRaRb)m]t-，-[(CRaRb)n-NRc-CO-(CRaRb)m]t-，-[(CRaRb)n-CO-NRc-(CRaRb)m]t-，-[(CRaRb)n-NRc-CS-(CRaRb)m]t-，-[(CRaRb)n-CS-NRc-(CRaRb)m]t-，-[(CRaRb)n-NRc-SO2-(CRaRb)m]t-，-[(CRaRb)n-SO2-NRc-(CRaRb)m]t-，-[(CRaRb)n-SO-(CRaRb)m]t-，-[(CRaRb)n-SO2-(CRaRb)m]t-，-[(CRaRb)n]t-；其中n和m相互独立选择，为0到10之间的任意整数，条件是如果n为0，则m与0不同，如果m为0，则n与0不同；其中t从n和/或m中独立选择，为0到10之间的任意整数；其中Ra、Rb、Rc、Rd和Re相互独立选择，可从H、烷基、环烷基、芳基、杂芳基和杂环烷基中选择；Y可从烷基、取代烷基、环烷基、取代环烷基、环烯基、取代环烯基、杂环烷基、取代杂环烷基、单不饱和杂环烷基、多不饱和杂环烷基、单取代多不饱和杂环烷基、多取代多不饱和杂环烷基、芳基、取代芳基、杂芳基和取代杂芳基中选择，其中Y与肽不同。
• New compounds for the inhibition of undesired cell proliferation and use thereof
  申请人：Jerini AG

  公开号：EP1402887A1

  公开（公告）日：2004-03-31

  The present invention is related to the use of a compound for the manufacture of a medicament for the treatment of a disease, whereby the disease involves an abnormal cell proliferation, an undesired cell proliferation, an abnormal mitosis and/or an undesired mitosis. whereby the compound has the structure:         A-X-Y     (I) wherein A is cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; X is a spacer and is selected from X1 or X2, wherein X1 is selected from the group comprising -[(CRaRb)n-NRc-CO-NRd-(CRaRb)m]t-, [(CRaRb)n-NRc-CS-NRd-(CRaRb)m]t-, -[(CRaRb)n-NRc-C(N-CN)-NRd-(CRaRb)m]t-, -[(CRaRb)n-NRc-C(N-Re)-NRd-(CRaRb)m]t-, -[(CRaRb)n-CO-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-CO-O-(CRaRb)m]t-, -[(CRaRb)n-O-CO-NRc-(CRaRb)m]t-, -[(CRaRb)n-O-(CRaRb)m]t-, -[(CRaRb)n-SRc-(CRaRb)m]t-; wherein X2 is selected from the group comprising -[(CRaRb)n-CO-(CRaRb)m]t-, -[(CRaRb)n-CS-(CRaRb)m]t-, -[(CRaRb)n-NRc-CO-(CRaRb)m]t-, -[(CRaRb)n-CO-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-CS-(CRaRb)m]t-, -[(CRaRb)n-CS-NRc-(CRaRb)m]t-, -[(CRaRb)n-NRc-SO2-(CRaRb)m]t-, -[(CRaRb)n-SO2-NRc-(CRaRb)m]t-, -[(CRaRb)n-SO-(CRaRb)m]t-, -[(CRaRb)n-SO2-(CRaRb)m]t-, -[(CRaRb)n]t-; wherein n and m are independently selected from each other and are any integer between 0 and 10 provided that if n is 0, m is different from 0, and if m is 0, n is different from 0; wherein t is independently selected from n and/or m and is any integer between 0 and 10; wherein Ra, Rb, Rc, Rd and Re are independently from each other selected from the group comprising H, alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl; and wherein Y is selected from the group comprising alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heterocyclyl, substituted heterocyclyl, mono-unsaturated heterocyclyl, poly-unsaturated heterocyclyl, mono-substituted poly-unsaturated heterocyclyl, poly-substituted poly-unsaturated heterocyclyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl, wherein Y is different from a peptide.

  本发明涉及一种化合物用于制造治疗疾病的药物，其中该疾病涉及异常细胞增殖、不良细胞增殖、异常有丝分裂和/或不良有丝分裂，其中该化合物具有以下结构：A-X-Y（I），其中A为环烷基、取代环烷基、杂环烷基、取代杂环烷基、芳香族、取代芳香族、杂芳香族或取代杂芳香族；X为间隔物，选择自X1或X2，其中X1选择自包括-[(CRaRb)n-NRc-CO-NRd-(CRaRb)m]t-、[(CRaRb)n-NRc-CS-NRd-(CRaRb)m]t-、-[(CRaRb)n-NRc-C(N-CN)-NRd-(CRaRb)m]t-、-[(CRaRb)n-NRc-C(N-Re)-NRd-(CRaRb)m]t-、-[(CRaRb)n-CO-NRc-(CRaRb)m]t-、-[(CRaRb)n-NRc-(CRaRb)m]t-、-[(CRaRb)n-NRc-CO-O-(CRaRb)m]t-、-[(CRaRb)n-O-CO-NRc-(CRaRb)m]t-、-[(CRaRb)n-O-(CRaRb)m]t-、-[(CRaRb)n-SRc-(CRaRb)m]t-；其中X2选择自包括-[(CRaRb)n-CO-(CRaRb)m]t-、-[(CRaRb)n-CS-(CRaRb)m]t-、-[(CRaRb)n-NRc-CO-(CRaRb)m]t-、-[(CRaRb)n-CO-NRc-(CRaRb)m]t-、-[(CRaRb)n-NRc-CS-(CRaRb)m]t-、-[(CRaRb)n-CS-NRc-(CRaRb)m]t-、-[(CRaRb)n-NRc-SO2-(CRaRb)m]t-、-[(CRaRb)n-SO2-NRc-(CRaRb)m]t-、-[(CRaRb)n-SO-(CRaRb)m]t-、-[(CRaRb)n-SO2-(CRaRb)m]t-、-[(CRaRb)n]t-；其中n和m彼此独立选择且为0和10之间的任意整数，条件是如果n为0，则m不等于0，如果m为0，则n不等于0；其中t独立选择自n和/或m，为0和10之间的任意整数；其中Ra、Rb、Rc、Rd和Re独立于彼此选择自包括H、烷基、环烷基、芳香族、杂芳香族和杂环烷基；Y选择自包括烷基、取代烷基、环烷基、取代环烷基、环烷烯基、取代环烷烯基、杂环烷基、取代杂环烷基、单不饱和杂环烷基、多不饱和杂环烷基、单取代多不饱和杂环烷基、多取代多不饱和杂环烷基、芳香族、取代芳香族、杂芳香族和取代杂芳香族，其中Y与肽不同。
• 1,3-Disubstituted Ureas Functionalized with Ether Groups are Potent Inhibitors of the Soluble Epoxide Hydrolase with Improved Pharmacokinetic Properties
  作者：In-Hae Kim、Hsing-Ju Tsai、Kosuke Nishi、Takeo Kasagami、Christophe Morisseau、Bruce D. Hammock

  DOI：10.1021/jm070705c

  日期：2007.10.1

  Soluble epoxide hydrolase (sEH) is a therapeutic target for treating hypertension and inflammation. 1,3-Disubstituted ureas functionalized with an ether group are potent sEH inhibitors. However, their relatively low metabolic stability leads to poor pharmacokinetic properties. To improve their bioavailability, we investigated the effect of incorporating various polar groups on the ether function on

  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。
• Salicylate–urea-based soluble epoxide hydrolase inhibitors with high metabolic and chemical stabilities
  作者：Takeo Kasagami、In-Hae Kim、Hsing-Ju Tsai、Kosuke Nishi、Bruce D. Hammock、Christophe Morisseau

  DOI：10.1016/j.bmcl.2009.01.069

  日期：2009.3

  We investigated N-adamantyl-N'-phenyl urea derivatives as simple sEH inhibitors. Salicylate ester derivatives have high inhibitory activities against human sEH, while the free benzoic acids are less active. The methyl salicylate derivative is a potent sEH inhibitor, which also has high metabolic and chemical stabilities; suggesting that such inhibitors are potential lead molecule for bioactive compounds acting in vivo. (C) 2009 Elsevier Ltd. All rights reserved.