1,1'-(octane-1,8-diyl)-bis[3-(adamantan-1-yl)urea] | 1607795-38-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: 1,1'-(octane-1,8-diyl)-bis[3-(adamantan-1-yl)urea]
• 英文别名: 1,1'-(Octane-1,8-diyl)bis[3-(adamantan-1-yl)urea]；1-(1-adamantyl)-3-[8-(1-adamantylcarbamoylamino)octyl]urea
• CAS: 1607795-38-9
• 化学式: C₃₀H₅₀N₄O₂
• 分子量: 498.753
• InChiKey: NPQIICPUOXXMIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  82.3
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  草酰氯 、 1,1'-(octane-1,8-diyl)-bis[3-(adamantan-1-yl)urea] 以 四氢呋喃 为溶剂， 反应 2.0h， 以82%的产率得到1,1'-(octane-1,8-diyl)bis[3-(adamantan-1-yl)imidazolidine-2,4,5-trione]
  参考文献：
  名称：

  1,3-（金刚烷-1（2）-基）-咪唑烷-2,4,5-三酮和3,3'-（金刚烷-1-基）-双（1-烷基咪唑烷-2）的合成及抑制活性，4,5-三酮）

  摘要：

  一系列1,3-（金刚烷-1（2）-基）咪唑烷-2,4,5-三酮和1,1'-（烷烃-1，n-二基）双[3-（金刚烷-1- yl）imidazolidine-2,4,5-triones]是通过环化1,3-双[adamantan-1（2）-ylureas]和1,1'-（烷基-1，n-二基）bis [3 ]合成的-（（金刚烷-1-基）脲）与草酰氯在温和条件下高产。在体外测试所有合成的化合物作为可溶性人环氧化物水解酶的抑制剂。许多化合物具有很高的抑制活性（IC 50 1.6–650 nM），这使其成为有前途的可溶性环氧化物水解酶抑制剂。

  DOI：

  10.1007/s10593-017-2174-x
• 作为产物：
  描述：

  1,8-二异氰基辛烷 、 金刚烷胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以99%的产率得到1,1'-(octane-1,8-diyl)-bis[3-(adamantan-1-yl)urea]
  参考文献：
  名称：

  Synthesis of adamantyl-containing 1,3-disubstituted diureas and thioureas, efficient targeted inhibitors of human soluble epoxide hydrolase

  摘要：

  合成了一系列含有刚性烷基的1,3-二取代二脲和硫脲，这些化合物在脲基团与刚性烷基取代基之间具有不同的间隔，且已研究其对哺乳动物和人类可溶性环氧化酶水解酶（sEH，E.C. 3.3.2.10）的抑制活性。合成的化合物在0.4–2.8 nmol L−1的浓度范围内表现出高抑制活性。抑制剂结构与其活性之间的关系已经确定。

  DOI：

  10.1007/s11172-015-1043-y

文献信息

• Synthesis and properties of diadamantyl-containing symmetric diureas as target-oriented inhibitors of human soluble epoxide hydrolase
  作者：V. V. Burmistrov、G. M. Butov、D. S. Karlov、V. A. Palyulin、N. S. Zefirov、C. Morisseau、B. D. Hammock

  DOI：10.1134/s1068162016030067

  日期：2016.7

  A series of target-oriented competitive inhibitors of human soluble epoxide hydrolase have been synthesized. The compounds retain the inhibitory properties at concentrations down to 4 nM. Based on the results of molecular modeling, it has been shown that the high inhibitory activity of this series of compounds is achieved by a unique mode of the binding to the active site of the enzyme.

  已经合成了一系列以靶标为导向的人可溶性环氧化物水解酶的竞争性抑制剂。这些化合物在低至 4 nM 的浓度下仍保持抑制特性。基于分子建模的结果，表明该系列化合物的高抑制活性是通过与酶活性位点结合的独特模式实现的。
• Imidazolidine-2,4,5- and pirimidine-2,4,6-triones – New primary pharmacophore for soluble epoxide hydrolase inhibitors with enhanced water solubility
  作者：Vladimir Burmistrov、Christophe Morisseau、Vladimir D'yachenko、Dmitry Karlov、Gennady M. Butov、Bruce D. Hammock

  DOI：10.1016/j.bmcl.2019.126908

  日期：2020.2

  A series of inhibitors of the soluble epoxide hydrolase (sEH) containing imidazolidine-2,4,5-trione or pirimidine-2,4,6-trione has been synthesized. Inhibition potency of the described compounds ranges from 8.4 μM to 0.4 nM. The tested compounds possess higher water solubility than their preceding ureas. Molecular docking indicates new bond between the triones and the active site of sEH that in part

  合成了一系列含有咪唑烷-2,4,5-三酮或嘧啶-2,4,6-三酮的可溶性环氧化物水解酶（sEH）抑制剂。所述化合物的抑制能力为8.4μM至0.4nM。被测化合物比其先前的脲具有更高的水溶性。分子对接表明三酮与sEH的活性位点之间存在新的键，部分解释了所观察到的新药效基团的效力。尽管效力不如相应的脲，但本文报道的脲基团的修饰产生具有较高水溶性的化合物，因此使配制更容易。
• Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors
  作者：Vladimir Burmistrov、Christophe Morisseau、Kin Sing Stephen Lee、Diyala S. Shihadih、Todd R. Harris、Gennady M. Butov、Bruce D. Hammock

  DOI：10.1016/j.bmcl.2014.03.016

  日期：2014.5

  A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 mu M to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl) urea] (3b) was found to be a potent slow tight binding inhibitor (IC50 = 0.5 nM) with a strong binding to sEH (K-i = 3.1 nM) and a moderately long residence time on the enzyme (k(off) = 1.05 x 10(-3) s(-1); t(1/2) = 11 min). (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis of adamantyl-containing 1,3-disubstituted diureas and thioureas, efficient targeted inhibitors of human soluble epoxide hydrolase
  作者：G. M. Butov、V. V. Burmistrov、D. V. Danilov、D. A. Pitushkin、C. Morisseau、B. D. Hammock

  DOI：10.1007/s11172-015-1043-y

  日期：2015.7

  A series of adamantyl-containing 1,3-disubstituted diureas and thioureas containing different spacers between the ureylene group and the adamantyl substituent has been synthesized, their inhibitory activity against mammalian and human soluble epoxide hydrolase (sEH, E.C. 3.3.2.10) has been examined. The compounds synthesized were found to exhibit high inhibitory activity on the 0.4–2.8 nmol L−1 level. The dependence between the inhibitor structure and its activity was established

  合成了一系列含有刚性烷基的1,3-二取代二脲和硫脲，这些化合物在脲基团与刚性烷基取代基之间具有不同的间隔，且已研究其对哺乳动物和人类可溶性环氧化酶水解酶（sEH，E.C. 3.3.2.10）的抑制活性。合成的化合物在0.4–2.8 nmol L−1的浓度范围内表现出高抑制活性。抑制剂结构与其活性之间的关系已经确定。
• Synthesis and inhibitory activity of 1,3-(adamantan-1(2)-yl)- imidazolidine-2,4,5-triones and 3,3'-(adamantan-1-yl)- bis(1-alkylimidazolidine-2,4,5-triones)
  作者：Vladimir S. D’yachenko、Vladimir V. Burmistrov、Kosuke Nishi、In-Hae Kim、Gennady M. Butov

  DOI：10.1007/s10593-017-2174-x

  日期：2017.10

  A series of 1,3-(adamantan-1(2)-yl)imidazolidine-2,4,5-triones and 1,1'-(alkane-1,n-diyl)bis[3-(adamantan-1-yl)imidazolidine-2,4,5-triones] was synthesized via cyclization of 1,3-bis[adamantan-1(2)-ylureas] and 1,1'-(alkyl-1,n-diyl)bis[3-(adamantan-1-yl)ureas] with oxalyl chloride under mild conditions with high yields. All synthesized compounds were tested in vitro as inhibitors of soluble human epoxide

  一系列1,3-（金刚烷-1（2）-基）咪唑烷-2,4,5-三酮和1,1'-（烷烃-1，n-二基）双[3-（金刚烷-1- yl）imidazolidine-2,4,5-triones]是通过环化1,3-双[adamantan-1（2）-ylureas]和1,1'-（烷基-1，n-二基）bis [3 ]合成的-（（金刚烷-1-基）脲）与草酰氯在温和条件下高产。在体外测试所有合成的化合物作为可溶性人环氧化物水解酶的抑制剂。许多化合物具有很高的抑制活性（IC 50 1.6–650 nM），这使其成为有前途的可溶性环氧化物水解酶抑制剂。