(E)-3-(4-(2-(1-cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxamido)acetamido)phenyl)acrylic acid compound with 2,2,2-trifluoroacetic acid (1:1) | 1254322-59-2

• 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: (E)-3-(4-(2-(1-cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxamido)acetamido)phenyl)acrylic acid compound with 2,2,2-trifluoroacetic acid (1:1)
• CAS: 1254322-59-2
• 化学式: C₂HF₃O₂*C₂₉H₂₈N₄O₅
• 分子量: 626.589
• InChiKey: MFRNDHZQVQMTNF-FNXZNAJJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  45.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 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：

  、 三氟乙酸 、 1-环己基-2-(3-呋喃)-1H-苯并咪唑-5-羧酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 以4%的产率得到(E)-3-(4-(2-(1-cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxamido)acetamido)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