(R,E)-3-(4-(2-(1-cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxamido)propanamido)phenyl)acrylic acid compound with 2,2,2-trifluoroacetic acid (1:1) | 1254322-65-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R,E)-3-(4-(2-(1-cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxamido)propanamido)phenyl)acrylic acid compound with 2,2,2-trifluoroacetic acid (1:1)
• CAS: 1254322-65-0
• 化学式: C₂HF₃O₂*C₃₁H₃₂N₄O₅
• 分子量: 654.643
• InChiKey: LFMHADAPJXLFIL-GYVLLFFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.68
• 重原子数：
  47.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  163.76
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2-{[1-(1-cyclohexyl-2-furan-3-yl-1H-benzoimidazol-5-yl)-methanoyl]-amino}-2-methyl-propionic acid 、 (E)-ethyl 3-(4-aminophenyl)acrylate 、 三氟乙酸 在 4-二甲氨基吡啶 、 bromo-tris-dimethylamino-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 以57%的产率得到(R,E)-3-(4-(2-(1-cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxamido)propanamido)phenyl)acrylic acid compound with 2,2,2-trifluoroacetic acid (1:1)
  参考文献：
  名称：

  Importance of Ligand Bioactive Conformation in the Discovery of Potent Indole-Diamide Inhibitors of the Hepatitis C Virus NS5B

  摘要：

  Significant advances have led to receptor induced-fit and conformational selection models for describing bimolecular recognition, but a more comprehensive view must evolve to also include ligand shape and conformational changes. Here, we describe an example where a ligand's "structural hinge" influences potency by inducing an "L-shape" bioactive conformation, and due to its solvent exposure in the complex, reasonable conformation-activity-relationships can be qualitatively attributed. From a ligand design perspective, this feature was exploited by successful linker hopping to an alternate "structural hinge" that led to a new and promising chemical series which matched the ligand bioactive conformation and the pocket bioactive space. Using a combination of X-ray crystallography, NMR and modeling with support from binding-site resistance mutant studies and photoaffinity labeling experiments, we were able to derive inhibitor-polymerase complexes for various chemical series.

  DOI：

  10.1021/ja101358s