methyl N-[(1S)-1-[(2S,4S)-2-[5-[5-[2-[(2S,4S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-4-methyl-pyrrolidin-2-yl]-1,3-benzoxazol-5-yl]thieno[3,2-b]thiophen-2-yl]-1,3-benzoxazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate | 1335208-75-7

• 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: methyl N-[(1S)-1-[(2S,4S)-2-[5-[5-[2-[(2S,4S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-4-methyl-pyrrolidin-2-yl]-1,3-benzoxazol-5-yl]thieno[3,2-b]thiophen-2-yl]-1,3-benzoxazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate
• 英文别名: methyl N-[(2S)-1-[(2S,4S)-2-[5-[5-[2-[(2S,4S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-4-methylpyrrolidin-2-yl]-1,3-benzoxazol-5-yl]thieno[3,2-b]thiophen-2-yl]-1,3-benzoxazol-2-yl]-4-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1335208-75-7
• 化学式: C₄₄H₅₀N₆O₈S₂
• 分子量: 855.048
• InChiKey: WFSLUJIRMISDOK-YPARNQAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  60
• 可旋转键数：
  12
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  226
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,5-双(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)噻吩并[3,2-b]噻吩 在 palladium diacetate 、 碳酸氢钠 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 2-甲基四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 methyl N-[(1S)-1-[(2S,4S)-2-[5-[5-[2-[(2S,4S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-4-methyl-pyrrolidin-2-yl]-1,3-benzoxazol-5-yl]thieno[3,2-b]thiophen-2-yl]-1,3-benzoxazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate
  参考文献：
  名称：

  Synthesis and evaluation of NS5A inhibitors containing diverse heteroaromatic cores

  摘要：

  Inhibitors of the HCV NS5A nonstructural protein are showing promising clinical potential in the treatment of hepatitis C when used in combination with other direct-acting antiviral agents. Current NS5A clinical candidates such as daclatasvir, ledipasvir, and ombitasvir share a common pharmacophore that features a pair of (S)-methoxycarbonylvaline capped pyrrolidines linked to various cores by amides, imidazoles and/or benzimidazoles. In this Letter, we describe the evaluation of NS5A inhibitors which contain alternative heteroaromatic replacements for these amide mimetics. The SAR knowledge gleaned in the optimization of scaffolds containing benzoxazoles was parlayed toward the identification of potent NS5A inhibitors containing other heteroaromatic replacements such as indoles and imidazopyridines. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.042