1-(isocyanatomethyl)adamantane | 69887-12-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(isocyanatomethyl)adamantane
• 英文别名: (adamantan-1-yl)methyl isocyanate；(1-adamantyl)methyl isocyanate；1-Adamantylmethyl isocyanate
• CAS: 69887-12-3
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: WFGBYEKUXXAETP-UHFFFAOYSA-N

物化性质

• 沸点：
  274.1±9.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  29.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,6-己二胺 、 1-(isocyanatomethyl)adamantane 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以99%的产率得到1,1'-(hexane-1,6-diyl)bis(3-(adamantan-1-ylmethyl)urea)
  参考文献：
  名称：

  Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2014.03.016
• 作为产物：
  描述：

  1-金刚烷乙酸 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 5.0h， 生成 1-(isocyanatomethyl)adamantane
  参考文献：
  名称：

  萘-，蒽-和pyr基-金刚烷双脲衍生物聚集体的光物理研究

  摘要：

  Adamantaneurea衍生物1 - 13的合成和它们的光物理性质的影响。化合物1 - 13是由刚性的金刚烷部分的，1或2个脲基团和发色团的不同，以及金刚烷和脲之间和/或尿素和发色团之间的亚甲基间隔基。在CH 3 CN和DMSO中测量了荧光量子产率和单线激发态寿命。发现在金刚烷和尿素之间具有亚甲基间隔基的分子在CH 3 CN中聚集，而在DMSO中未观察到聚集。9-氨基蒽衍生物10的聚集趋势最高在两种溶剂中聚集的pyr衍生物13。由于脲之间的分子间氢键和芳族发色团的π，π堆积，可能发生聚集。芘13可能引起的准分子激光和分子间的聚集。

  DOI：

  10.1016/j.jphotochem.2011.12.005

文献信息

• Structure-Activity Relationships of C1 and C6 Side Chains of Zaragozic Acid A Derivatives
  作者：Mitree M. Ponpipom、Narindar N. Girotra、Robert L. Bugianesi、Cathleen D. Roberts、Gregory D. Berger、Robert M. Burk、Robert W. Marquis、William H. Parsons、Kenneth F. Bartizal

  DOI：10.1021/jm00049a022

  日期：1994.11

  esters. In the preparation of C6 ethers, C4 and C4,6 bisethers were also isolated; their relative activity is: C6 > C4 > C4,6. These C6 long-chain derivatives are subnanomolar squalene synthase inhibitors; they are, however, only weakly active in inhibiting hepatic cholesterol synthesis in mice. The C6 short-chain derivatives are much less active in vitro, but they all have improved oral activity in

  系统地修改了一种有效的角鲨烯合酶抑制剂za​​ragozic A的C6酰基侧链，以改善其生物学活性。将C6侧链简化为辛酸酯具有有害作用。增加线性链长度可提高体外活性，直至十四烷酸酯为止。ω-苯氧基比ω-苯基更好的活性增强剂。制备了许多C6氨基甲酸酯，醚和碳酸酯，发现它们具有与C6酯相似的活性。在制备C6醚时，还分离出C4和C4,6双醚。它们的相对活性为：C6> C4> C4,6。这些C6长链衍生物是亚纳摩尔角鲨烯合酶抑制剂。然而，它们仅在抑制小鼠肝胆固醇合成中具有弱活性。C6短链衍生物在体外的活性低得多，但它们在小鼠中的口服活性均得到改善。正丁酰基类似物的C1烷基侧链（ED50为4.5 mg / kg）的修饰不能进一步提高po活性。这些C6长链衍生物中的许多也是体外有效的抗真菌剂。
• 5-Fluorouracil derivatives, and their pharmaceutical compositions
  申请人：Fujisawa Pharmaceutical Company, Ltd.

  公开号：US04349552A1

  公开（公告）日：1982-09-14

  A compound of the formula: ##STR1## wherein R is a bridged alicyclic group selected from the group consisting of norbornyl, norbornenyl, bicyclo[2,2,2]-heptyl and adamantyl optionally substituted by at least one substituent selected from the group consisting of lower alkyl, carboxy, lower alkoxycarbonyl, alkylidenedioxy, N,N-di(lower)alkylcarbamoyl, amino, loweralkoxycarbonylamino and halogen. The present compound is useful in the therapeutic treatment of cancer in human beings and animals.

  一种化合物的化学式为：##STR1##其中R是从诺伯尼尔、诺伯烯基、双环[2,2,2]-庚基和金刚烷基中选择的桥环脂环基，可选择地被来自较低烷基、羧基、较低烷氧羰基、烷基二氧基、N,N-双(较低)烷基氨基甲酰、氨基、较低烷氧羰胺基和卤素的至少一种取代基取代。该化合物可用于治疗人类和动物的癌症。
• Bioisosteric substitution of adamantane with bicyclic lipophilic groups improves water solubility of human soluble epoxide hydrolase inhibitors
  作者：Vladimir Burmistrov、Christophe Morisseau、Dmitry Karlov、Dmitry Pitushkin、Andrey Vernigora、Elena Rasskazova、Gennady M. Butov、Bruce D. Hammock

  DOI：10.1016/j.bmcl.2020.127430

  日期：2020.9

  A series of inhibitors of the soluble epoxide hydrolase (sEH) containing lipophilic groups of natural origin (camphanyl, norcamphanyl, furan-2-yl) were developed. Inhibitory potency ranging from 0.4 nM to 2.16 μM were obtained. While having the same level of inhibitory activity bicyclic ureas are up to 10-fold more soluble than the corresponding ureas containing adamantyl or 4-trifluoromethoxyphenyl

  开发了一系列可溶性环氧化物水解酶 (sEH) 抑制剂，这些酶含有天然来源的亲脂基团（莰基、去甲莰基、呋喃-2-基）。获得了范围从 0.4 nM 到 2.16 μM 的抑制效力。虽然具有相同水平的抑制活性，但双环脲的溶解度比含有金刚烷基或 4-三氟甲氧基苯基取代基的相应脲高 10 倍。这使它们更易于配制、生物利用度更高，因此更有希望作为治疗性 sEH 抑制剂。源自l -樟脑的化合物2b 的内/外型比源自d -樟脑的相应类似物有效 14 倍(IC 50 = 3.7 nM vs. 50.6 nM）表明对映体偏好。
• Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: VII. Synthesis and Properties 1-[(Adamantan-1-yl)methyl]-3-(fluoro, chlorophenyl) Ureas
  作者：D. V. Danilov、V. S. D’yachenko、Y. P. Kuznetsov、V. V. Burmistrov、G. M. Butov

  DOI：10.1134/s1070428021020020

  日期：2021.2

  Abstract A series of 1,3-disubstituted ureas containing a lipophilic adamantane moiety tethered to the ureido group by a methylene bridge were synthesized by the reaction of 1-(isocyanatomethyl)adamantane with monohalo- and dihaloanilines in yields of up to 92%. The synthesized ureas are target oriented inhibitors of human soluble epoxide hydrolase (sEH).

  摘要 通过1-（异氰酸根合甲基）金刚烷与单卤代和二卤代苯胺的反应，合成了一系列包含通过亚甲基桥连接到脲基的亲脂性金刚烷部分的1，3-二取代脲，产率高达92％。合成的脲是人类可溶性环氧化物水解酶（sEH）的靶向抑制剂。
• 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。