2-chloro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide

• 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: 2-chloro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide
• 英文别名: (+/-)-2-Chloro-N-[(1RS,2RS,4RS)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl]acetamide；2-chloro-N-[(1R,2R,4R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]acetamide
• 化学式: C₁₂H₂₀ClNO
• 分子量: 229.75
• InChiKey: PYXCVNYPFHGKLE-LNLATYFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-乙基哌嗪 、 2-chloro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以35%的产率得到2-(4-ethylpiperazin-1-yl)-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide
  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
• 作为产物：
  描述：

  白樟油 在 sodium tetrahydroborate 、 盐酸羟胺 、 sodium acetate 、 三乙胺 、 nickel dichloride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 2-chloro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide
  参考文献：
  名称：

  基于西伯利亚冷杉和（+）-樟脑的（-）-冰片酚发现一种新型的痘苗病毒抑制剂。

  摘要：

  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。

  DOI：

  10.1002/cbdv.201800153

文献信息

• 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。
• Synthesis and structural isomerism of sterically hindered isobornyl amide tethered N-heterocyclic carbene complexes
  作者：William R. Kerr、Marie A. Squire、Christopher M. Fitchett

  DOI：10.1016/j.jorganchem.2022.122519

  日期：2022.12

  Enantiomerically pure chelating NHC-isobornylamide 1 was prepared and reacted with palladium and platinum salts. This gave monodentate complexes with carbonate (Pd12CO3, 4), and chelating or monodentate complexes with acetylacetonate M1acac (M = Pd (5a), Pt (5b)) and M1(acac)2 (M = Pd (7a), Pt (7b)). This is in contrast to the reactions of the achiral NHC-cyclohexylamide derivative 2, which gave only

  制备对映体纯螯合 NHC-异冰片酰胺1并与钯盐和铂盐反应。这产生了与碳酸盐 (Pd 1 2 CO 3 , 4 ) 的单齿络合物，以及与乙酰丙酮化物 M 1 acac (M = Pd ( 5a )、Pt ( 5b )) 和 M 1 (acac) 2 (M = Pd )的螯合或单齿络合物( 7a )、铂( 7b ))。这与非手性 NHC-环己酰胺衍生物2的反应相反，后者仅产生螯合复合物 (M 2 acac (M = Pd ( 6a ), Pt ( 6b )））。1和2与 Pd(allyl)Cl的反应仅得到单齿配合物8 (Pd 1 (allyl)Cl) 和9 (Pd 2 (allyl)Cl)。使用 X 射线晶体学在固态结构上表征了几种配合物，这表明，当螯合时，手性异冰片基的显着空间体积指向金属原子。这也在单齿7a和7b的形成中得到证实，这表明酰胺键的 E/Z 异构。我们能够将主要异构体识别为 Z
• LYSENKOV, V. I., ZH. ORGAN. XIMII, 25,(1989) N, S. 1570-1571
  作者：LYSENKOV, V. I.

  DOI：——

  日期：——
• 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.