methyl N-[(1R)-2-[(2S)-2-[5-[3,5-difluoro-4-[4-[2-[(3R)-4-[(2R)-2-(methoxycarbonylamino)-2-phenyl-acetyl]morpholin-3-yl]-1H-imidazol-5-yl]-1-piperidyl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl]carbamate | 1228668-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl N-[(1R)-2-[(2S)-2-[5-[3,5-difluoro-4-[4-[2-[(3R)-4-[(2R)-2-(methoxycarbonylamino)-2-phenyl-acetyl]morpholin-3-yl]-1H-imidazol-5-yl]-1-piperidyl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl]carbamate
• 英文别名: methyl N-[(1R)-2-[(2S)-2-[5-[3,5-difluoro-4-[4-[2-[(3R)-4-[(2R)-2-(methoxycarbonylamino)-2-phenylacetyl]morpholin-3-yl]-1H-imidazol-5-yl]piperidin-1-yl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate
• CAS: 1228668-54-9
• 化学式: C₄₅H₄₉F₂N₉O₇
• 分子量: 865.937
• InChiKey: FGZHNJDGXPZYIL-CDBYGCFJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  63
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  187
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (3S)-3,4-吗啉二羧酸 4-叔丁酯 在 盐酸 、 Pd(OH)2/C 、 ammonium acetate 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 、 O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate 作用下， 以 1,4-二氧六环 、 乙醇 、 邻二甲苯 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 methyl N-[(1R)-2-[(2S)-2-[5-[3,5-difluoro-4-[4-[2-[(3R)-4-[(2R)-2-(methoxycarbonylamino)-2-phenyl-acetyl]morpholin-3-yl]-1H-imidazol-5-yl]-1-piperidyl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl]carbamate
  参考文献：
  名称：

  Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors

  摘要：

  This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.057

文献信息

• INHIBITORS OF HCV NS5A
  申请人：Li Leping

  公开号：US20110237579A1

  公开（公告）日：2011-09-29

  The invention relates to non-macrocyclic, non-peptidic, substituted heterocyclic compounds useful for inhibiting hepatitis C virus (“HCV”) replication, particularly functions of the non-structural 5A (“NS5A”) protein of HCV

  本发明涉及一种非大环、非肽、取代杂环化合物，用于抑制丙型肝炎病毒（“HCV”）复制，特别是HCV的非结构蛋白5A（“NS5A”）蛋白的功能。
• Inhibitors of HCV NS5A
  申请人：Presidio Pharmaceuticals, Inc.

  公开号：EP2774927A1

  公开（公告）日：2014-09-10

  The invention relates to non-macrocyclic, non-peptidic, substituted heterocyclic compounds useful for inhibiting hepatitis C virus ("HCV" replication, particularly functions of the non-structural 5A ("NS5A") protein of HCV.

  本发明涉及可用于抑制丙型肝炎病毒（"HCV"）复制，特别是抑制 HCV 非结构 5A（"NS5A"）蛋白功能的非大环、非肽、取代杂环化合物。
• US9120779B2
  申请人：——

  公开号：US9120779B2

  公开（公告）日：2015-09-01
• [EN] INHIBITORS OF HCV NS5A<br/>[FR] INHIBITEURS DU VIRUS DE L'HÉPATITE C DE TYPE NS5A
  申请人：PRESIDIO PHARMACEUTICALS INC

  公开号：WO2010065681A1

  公开（公告）日：2010-06-10

  The invention relates to non-macrocyclic, non-peptidic, substituted heterocyclic compounds useful for inhibiting hepatitis C virus ("HCV") replication, particularly functions of the non-structural 5A ("NS5A") protein of HCV
• Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors
  作者：Min Zhong、Eric Peng、Ningwu Huang、Qi Huang、Anja Huq、Meiyen Lau、Richard Colonno、Leping Li

  DOI：10.1016/j.bmcl.2014.10.057

  日期：2014.12

  This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration. (C) 2014 Elsevier Ltd. All rights reserved.