(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 3-(4-ethylpiperazin-1-yl)propanoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 3-(4-ethylpiperazin-1-yl)propanoate
• 英文别名: [(1S,2R,4S)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl] 3-(4-ethylpiperazin-1-yl)propanoate
• 化学式: C₁₉H₃₄N₂O₂
• 分子量: 322.491
• InChiKey: BSKWMRLURFYVGO-FRQCXROJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  冰片 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 3-(4-ethylpiperazin-1-yl)propanoate
  参考文献：
  名称：

  Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process

  摘要：

  In this study, we screened a large library of (+)-camphor and (-)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC₅₀ values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus. Compound 3b (As-358) exhibited the good antiviral potency (IC₅₀ = 3.7 μM, SI = 118) against Marburg virus, while the hydrochloride salt of this compound 3b·HCl had a strong inhibitory effect against Ebola virus (IC₅₀ = 9.1 μM, SI = 31) and good in vivo safety (LD₅₀ > 1000 mg/kg). The results of molecular docking and in vitro mutagenesis analyses suggest that the synthesized compounds bind to the active binding site of EBOV glycoprotein similar to the known inhibitor toremifene.

  DOI：

  10.1016/j.ejmech.2020.112726

文献信息

• Synthesis and in vitro study of novel borneol derivatives as potent inhibitors of the influenza A virus
  作者：A. S. Sokolova、O. I. Yarovaya、M. D. Semenova、A. A. Shtro、I. R. Orshanskaya、V. V. Zarubaev、N. F. Salakhutdinov

  DOI：10.1039/c6md00657d

  日期：——

  Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (−)-borneol and (−)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the influenza virus A/Puerto Rico/8/34 (H1N1). Compounds 7, 16 and 26 containing a morpholine fragment exhibited the highest

  在本文中，我们介绍了设计和合成一系列新型（-）-冰片和（-）-异冰片的杂环衍生物，作为A型流感病毒的有效抑制剂。测试了所有化合物对MDCK细胞的毒性以及对流感病毒A / Puerto Rico / 8/34（H1N1）的病毒抑制活性。化合物7，16和26含有一个吗啉片段表现出最高效率剂抑制流感病毒A（H1N1）为82，45和65，相应的选择性的指标的复制。导数9（SI = 23）和18含有1-甲基哌嗪基序的（SI = 25）显示中等的抗病毒活性。对这一系列新的冰片衍生物的结构活性分析表明，抗病毒活性需要1,7,7-三甲基双环[2.2.1]庚烷骨架。
• Discovery of a New Class of Inhibitors of Vaccinia Virus Based on (−)-Borneol from <i>Abies sibirica</i> and (+)-Camphor
  作者：Anastasiya S. Sokolova、Olga I. Yarovaya、Nikolay I. Bormotov、Larisa N. Shishkina、Nariman F. Salakhutdinov

  DOI：10.1002/cbdv.201800153

  日期：2018.9

  A series of the bornyl ester/amide derivatives with N-containing heterocycles were designed and synthesized as vaccinia virus (VV) inhibitors. Bioassay results showed that among the designed compounds, derivatives 6, 13, 14, 34, 36 and 37 showed the best inhibitory activity against VV with the IC50 values of 12.9, 17.9, 3.4, 2.5, 12.5 and 7.5 μm, respectively, and good cytotoxicity. The primary structure-activity

  设计并合成了一系列带有含N杂环的冰片酯/酰胺衍生物，作为痘苗病毒（VV）抑制剂。生物测定结果表明，在设计的化合物中，衍生物6、13、14、34、36和37对VV的抑制作用最佳，IC50值分别为12.9、17.9、3.4、2.5、12.5和7.5μm，效果良好。细胞毒性。初步的结构-活性关系（SAR）研究表明，饱和的N-杂环（例如吗啉或4-甲基哌啶）与1,7,7-三甲基双环[2.2.1]庚烷骨架的组合有利于抗病毒活性。
• Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors
  作者：Anastasiya S. Sokolova、Olga I. Yarovaya、Lana V. Kuzminykh、Anna A. Shtro、Artem M. Klabukov、Anastasia V. Galochkina、Yulia V. Nikolaeva、Galina D. Petukhova、Sophia S. Borisevich、Edward M. Khamitov、Nariman F. Salakhutdinov

  DOI：10.3390/ph15111390

  日期：——

  Respiratory syncytial virus (RSV) causes acute respiratory infections, thus, posing a serious threat to the health of infants, children, and elderly people. In this study, we have discovered a series of potent RSV entry inhibitors with the (-)-borneol scaffold. The active compounds 3b, 5a, 5c, 7b, 9c, 10b, 10c, and 14b were found to exhibit activity against RSV A strain A2 in НЕр-2 cells. The most

  呼吸道合胞病毒（RSV）引起急性呼吸道感染，严重威胁婴儿、儿童和老年人的健康。在这项研究中，我们发现了一系列具有 (-)-冰片支架的有效 RSV 进入抑制剂。发现活性化合物3b、5a、5c、7b、9c、10b、10c和14b在 НЕр-2 细胞中表现出抗 RSV A 菌株 A2 的活性。最活跃的物质，3b（IC 50 = 8.9 μM，SI = 111）和5a（IC 50= 5.0 μM，SI = 83），比已知的抗病毒剂利巴韦林（IC 50 = 80.0 μM，SI = 50）表现出更强的效力。添加时间分析和温度变化研究表明，化合物3b、5a和6b可能通过与介导膜融合的病毒 F 蛋白相互作用来抑制 RSV 进入，而它们既不与 G 蛋白结合也不抑制 RSV 与靶标的结合细胞。应用分子建模和分子动力学程序，提出了化合物3b和5a的结合模式。总之，这项研究的结果表明 (-)-冰片酯是开发新的抗
• Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process
  作者：Anastasiya S. Sokolova、Olga I. Yarovaya、Anastasiya V. Zybkina、Ekaterina D. Mordvinova、Nadezhda S. Shcherbakova、Anna V. Zaykovskaya、Dmitriy S. Baev、Tatyana G. Tolstikova、Dmitriy N. Shcherbakov、Oleg V. Pyankov、Rinat A. Maksyutov、Nariman F. Salakhutdinov

  DOI：10.1016/j.ejmech.2020.112726

  日期：2020.12

  In this study, we screened a large library of (+)-camphor and (-)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC₅₀ values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus. Compound 3b (As-358) exhibited the good antiviral potency (IC₅₀ = 3.7 μM, SI = 118) against Marburg virus, while the hydrochloride salt of this compound 3b·HCl had a strong inhibitory effect against Ebola virus (IC₅₀ = 9.1 μM, SI = 31) and good in vivo safety (LD₅₀ > 1000 mg/kg). The results of molecular docking and in vitro mutagenesis analyses suggest that the synthesized compounds bind to the active binding site of EBOV glycoprotein similar to the known inhibitor toremifene.