benzyl (2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxoheptanoate | 180511-98-2

• 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 (2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxoheptanoate
• CAS: 180511-98-2
• 化学式: C₂₇H₄₁NO₆
• 分子量: 475.626
• InChiKey: FDEQZDASMMBIHF-SIKLNZKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  98.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl (2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxoheptanoate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 (2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxoheptanoic acid
  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：

  allyl 4,4-dimethyl-3-oxopentanoate 在 四氢吡咯 、 四(三苯基膦)钯 、 sodium hydride 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.0h， 生成 benzyl (2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxoheptanoate
  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

文献信息

• 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.