tert-butyl N-[(2S,3R)-4-[(2S,4R)-2-(tert-butylcarbamoyl)-4-(2,6-dimethylpyrimidin-4-yl)sulfanylpiperidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate | 154611-90-2

• 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: tert-butyl N-[(2S,3R)-4-[(2S,4R)-2-(tert-butylcarbamoyl)-4-(2,6-dimethylpyrimidin-4-yl)sulfanylpiperidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 154611-90-2
• 化学式: C₃₁H₄₇N₅O₄S
• 分子量: 585.811
• InChiKey: BLAIWIHPTBZISE-KEVKATSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S,3R)-4-[(2S,4R)-2-(tert-butylcarbamoyl)-4-(2,6-dimethylpyrimidin-4-yl)sulfanylpiperidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.83h， 生成 (2S,4R)-1-{(2R,3S)-3-[2-(2,6-Dimethyl-phenoxy)-acetylamino]-2-hydroxy-4-phenyl-butyl}-4-(2,6-dimethyl-pyrimidin-4-ylsulfanyl)-piperidine-2-carboxylic acid tert-butylamide
  参考文献：
  名称：

  2‘,6‘-Dimethylphenoxyacetyl:  A New Achiral High Affinity P₃-P₂ Ligand for Peptidomimetic-Based HIV Protease Inhibitors

  摘要：

  Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P-3-P-2 quinaldic-valine portion of 1 was replaced by 2',6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P-3-P-2 position of hydroxyethylamine-based HIV protease inhibitors.

  DOI：

  10.1021/jm990336n
• 作为产物：
  描述：

  2-氨基-4-氯-6-甲基嘧啶 在 盐酸 、 sodium hydride 、 lithium chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.33h， 生成 tert-butyl N-[(2S,3R)-4-[(2S,4R)-2-(tert-butylcarbamoyl)-4-(2,6-dimethylpyrimidin-4-yl)sulfanylpiperidin-1-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate
  参考文献：
  名称：

  2‘,6‘-Dimethylphenoxyacetyl:  A New Achiral High Affinity P₃-P₂ Ligand for Peptidomimetic-Based HIV Protease Inhibitors

  摘要：

  Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P-3-P-2 quinaldic-valine portion of 1 was replaced by 2',6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P-3-P-2 position of hydroxyethylamine-based HIV protease inhibitors.

  DOI：

  10.1021/jm990336n

文献信息

• 2‘,6‘-Dimethylphenoxyacetyl:  A New Achiral High Affinity P₃-P₂ Ligand for Peptidomimetic-Based HIV Protease Inhibitors
  作者：Pierre L. Beaulieu、Paul C. Anderson、Dale R. Cameron、Gilbert Croteau、Vida Gorys、Chantal Grand-Maître、Daniel Lamarre、Francine Liard、William Paris、Louis Plamondon、François Soucy、Diane Thibeault、Dominik Wernic、Christiane Yoakim、Susan Pav、Liang Tong

  DOI：10.1021/jm990336n

  日期：2000.3.1

  Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P-3-P-2 quinaldic-valine portion of 1 was replaced by 2',6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P-3-P-2 position of hydroxyethylamine-based HIV protease inhibitors.