((S)-2-Benzothiazol-2-yl-2-hydroxy-1-methyl-ethyl)-carbamic acid tert-butyl ester | 198955-58-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: ((S)-2-Benzothiazol-2-yl-2-hydroxy-1-methyl-ethyl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-(1,3-benzothiazol-2-yl)-1-hydroxypropan-2-yl]carbamate
• CAS: 198955-58-7
• 化学式: C₁₅H₂₀N₂O₃S
• 分子量: 308.401
• InChiKey: NPVXVWVBZSCUII-QHGLUPRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  99.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ((S)-2-Benzothiazol-2-yl-2-hydroxy-1-methyl-ethyl)-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (S)-2-Amino-1-benzothiazol-2-yl-propan-1-ol
  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：

  tert-butyl {(S)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl}carbamate 在 lithium aluminium tetrahydride 、 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 3.7h， 生成 ((S)-2-Benzothiazol-2-yl-2-hydroxy-1-methyl-ethyl)-carbamic acid tert-butyl ester
  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 (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
• Peptidomimetic Inhibitors of the Human Cytomegalovirus Protease
  作者：William Ogilvie、Murray Bailey、Marc-André Poupart、Abraham、Amit Bhavsar、Pierre Bonneau、Josée Bordeleau、Yves Bousquet、Catherine Chabot、Jean-Simon Duceppe、Gulrez Fazal、Sylvie Goulet、Chantal Grand-Maître、Ingrid Guse、Ted Halmos、Pierre Lavallée、Michael Leach、Eric Malenfant、Jeff O'Meara、Raymond Plante、Céline Plouffe、Martin Poirier、François Soucy、Christiane Yoakim、Robert Déziel

  DOI：10.1021/jm970104t

  日期：1997.12.1

  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.