(2R,3R,4R,5S)-5-Amino-3,4-dihydroxy-2-isobutyl-7-methyl-octanoic acid {(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide | 134485-18-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2R,3R,4R,5S)-5-Amino-3,4-dihydroxy-2-isobutyl-7-methyl-octanoic acid {(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide
• CAS: 134485-18-0
• 化学式: C₂₅H₄₄N₄O₄
• 分子量: 464.649
• InChiKey: RPVCSVMHITZVAX-QYVMVQNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  33.0
• 可旋转键数：
  14.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  137.57
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5S)-5-Amino-3,4-dihydroxy-2-isobutyl-7-methyl-octanoic acid {(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 14.25h， 生成 (2R,3R,4R,5S)-3,4-二羟基-7-甲基-N-{(2S,3S)-3-甲基-1-羰基-1-[(吡啶-2-基甲基)氨基]戊烷-2-基}-2-(2-甲基丙基)-5-({N-[(萘-1-氧基)乙酰基]-L-组氨酰}氨基)辛酰胺
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005
• 作为产物：
  描述：

  {(S)-1-[(4R,5R)-2,2-Dimethyl-5-((R)-3-methyl-1-{(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-butyl)-[1,3]dioxolan-4-yl]-3-methyl-butyl}-carbamic acid tert-butyl ester 在 ethandithiol 、 乙酰氯 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 (2R,3R,4R,5S)-5-Amino-3,4-dihydroxy-2-isobutyl-7-methyl-octanoic acid {(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005