benzyl (E)-(5S)-6,6-dimethyl-5-<(tert-butoxycarbonyl)amino>-4-oxo-2-heptenoate | 176504-91-9

• 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 (E)-(5S)-6,6-dimethyl-5-<(tert-butoxycarbonyl)amino>-4-oxo-2-heptenoate
• 英文别名: benzyl (E,5S)-6,6-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxohept-2-enoate
• CAS: 176504-91-9
• 化学式: C₂₁H₂₉NO₅
• 分子量: 375.465
• InChiKey: AKYLQZFGEYIMAF-QFQMRYFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (E)-(5S)-6,6-dimethyl-5-<(tert-butoxycarbonyl)amino>-4-oxo-2-heptenoate 在 四氢吡咯 、 四(三苯基膦)钯 、 sodium hydride 作用下， 以 二氯甲烷 、 乙腈 、 xylene 为溶剂， 反应 8.0h， 生成 (S)-2-((S)-3-tert-Butoxycarbonylamino-4,4-dimethyl-2-oxo-pentyl)-succinic acid 1-benzyl ester
  参考文献：
  名称：

  Peptidomimetic Inhibitors of Herpes Simplex Virus Ribonucleotide Reductase with Improved in Vivo Antiviral Activity

  摘要：

  We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.

  DOI：

  10.1021/jm960324r
• 作为产物：
  描述：

  (S)-2-((叔丁氧羰基)氨基)-3,3-二甲基丁酸甲酯 在 正丁基锂 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 2.58h， 生成 benzyl (E)-(5S)-6,6-dimethyl-5-<(tert-butoxycarbonyl)amino>-4-oxo-2-heptenoate
  参考文献：
  名称：

  A Practical and Diastereoselective Synthesis of Ketomethylene Dipeptide Isosteres of the Type AAΨ[COCH₂]Asp

  摘要：

  DOI：

  10.1021/jo951988w

文献信息

• A Practical and Diastereoselective Synthesis of Ketomethylene Dipeptide Isosteres of the Type AAΨ[COCH₂]Asp
  作者：Robert Déziel、Raymond Plante、Valérie Caron、Louis Grenier、Montse Llinas-Brunet、Jean-Simon Duceppe、Eric Malenfant、Neil Moss

  DOI：10.1021/jo951988w

  日期：1996.1.1
• Peptidomimetic Inhibitors of Herpes Simplex Virus Ribonucleotide Reductase with Improved <i>in Vivo</i> Antiviral Activity
  作者：Neil Moss、Pierre Beaulieu、Jean-Simon Duceppe、Jean-Marie Ferland、Michel Garneau、Jean Gauthier、Elise Ghiro、Sylvie Goulet、Ingrid Guse、Jorge Jaramillo、Montse Llinas-Brunet、Éric Malenfant、Raymond Plante、Martin Poirier、Francois Soucy、Dominik Wernic、Christiane Yoakim、Robert Déziel

  DOI：10.1021/jm960324r

  日期：1996.1.1

  We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.