benzyl 4-[(4S)-4-isopropyl-2-oxo-1,3-oxazolan-3-yl]-2,2-dimethyl-4-oxobutanoate | 198955-69-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl 4-[(4S)-4-isopropyl-2-oxo-1,3-oxazolan-3-yl]-2,2-dimethyl-4-oxobutanoate
• 英文别名: benzyl 2,2-dimethyl-4-oxo-4-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]butanoate
• CAS: 198955-69-0
• 化学式: C₁₉H₂₅NO₅
• 分子量: 347.411
• InChiKey: BQGLONSCWCOQDZ-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 4-[(4S)-4-isopropyl-2-oxo-1,3-oxazolan-3-yl]-2,2-dimethyl-4-oxobutanoate 在 2,4,6-三异丙基苯磺酰叠氮化物 、 双(三甲基硅烷基)氨基钾 作用下， 生成 benzyl (3S)-3-azido-2,2-dimethyl-4-oxo-4-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]butanoate
  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：

  (S)-4-异丙基-2-唑烷酮 在 正丁基锂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 17.5h， 生成 benzyl 4-[(4S)-4-isopropyl-2-oxo-1,3-oxazolan-3-yl]-2,2-dimethyl-4-oxobutanoate
  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

文献信息

• Peptidomimetic inhibitors of the human cytomegalovirus protease
  申请人：Boehringer Ingelheim Ltd.

  公开号：US06291640B1

  公开（公告）日：2001-09-18

  A compound of formula (I) is disclosed: wherein X, z, W, Y, R1 through R5, m and n are as define herein. These compounds are peptidomimetic inhibitors of human cytomegalovirus (HCMV) protease and are useful for the treatment of human cytomegalovirus infection.

  公开了一种化合物的化学式(I)：其中X、z、W、Y、R1到R5、m和n的定义如下。这些化合物是人类巨细胞病毒（HCMV）蛋白酶的肽类模拟抑制剂，可用于治疗人类巨细胞病毒感染。
• PEPTIDOMIMETIC INHIBITORS OF THE HUMAN CYTOMEGALOVIRUS PROTEASE
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP0948523B1

  公开（公告）日：2004-03-17
• US6291640B1
  申请人：——

  公开号：US6291640B1

  公开（公告）日：2001-09-18