(2S)-2-[[(2S)-2-(3,3-dimethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-N-[(2R)-3-hydroxy-1-oxo-1-(phenylmethoxyamino)propan-2-yl]-N',N'-dimethylbutanediamide | 198955-67-8

• 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: (2S)-2-[[(2S)-2-(3,3-dimethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-N-[(2R)-3-hydroxy-1-oxo-1-(phenylmethoxyamino)propan-2-yl]-N',N'-dimethylbutanediamide
• CAS: 198955-67-8
• 化学式: C₂₈H₄₅N₅O₇
• 分子量: 563.695
• InChiKey: PJTVKZJCGRBDFJ-MIZPHKNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[(2S)-2-(3,3-dimethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-N-[(2R)-3-hydroxy-1-oxo-1-(phenylmethoxyamino)propan-2-yl]-N',N'-dimethylbutanediamide 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以53%的产率得到(2S)-N-[(3S)-1-benzyloxy-2-oxo-azetidin-3-yl]-2-[[(2S)-2-(3,3-dimethylbutanoylamino)-3,3-dimethyl-butanoyl]amino]-N',N'-dimethyl-butanediamide
  参考文献：
  名称：

  Peptidomimetic Inhibitors of the Human Cytomegalovirus Protease

  摘要：

  The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) :protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency cf 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P-1 were well tolerated by this enzyme, a fact consistent with previous observations. The S-2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P-3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and a-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P-1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.

  DOI：

  10.1021/jm970104t
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 palladium dihydroxide N-甲基吗啉 、 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 70.0h， 生成 (2S)-2-[[(2S)-2-(3,3-dimethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-N-[(2R)-3-hydroxy-1-oxo-1-(phenylmethoxyamino)propan-2-yl]-N',N'-dimethylbutanediamide
  参考文献：
  名称：

  Peptidomimetic Inhibitors of the Human Cytomegalovirus Protease

  摘要：

  The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) :protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency cf 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P-1 were well tolerated by this enzyme, a fact consistent with previous observations. The S-2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P-3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and a-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P-1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.

  DOI：

  10.1021/jm970104t