benzyl (E,4R)-4-[(tert-butoxycarbonyl)amino]oct-2-enoate

• 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,4R)-4-[(tert-butoxycarbonyl)amino]oct-2-enoate
• 英文别名: benzyl (E,4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]oct-2-enoate
• 化学式: C₂₀H₂₉NO₄
• 分子量: 347.455
• InChiKey: BQFYZKDFBGPNJE-TUQDCPSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (E,4R)-4-[(tert-butoxycarbonyl)amino]oct-2-enoate 在 palladium on activated charcoal 盐酸 、 重铬酸吡啶 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 生成 (4R)-4-(2-oxododecanoylamino)octanoic acid
  参考文献：
  名称：

  Novel 2-Oxoamide Inhibitors of Human Group IVA Phospholipase A₂

  摘要：

  A novel class of potent human cytosolic phospholipase A(2) (GIVA PLA(2)) inhibitors was developed. These inhibitors were designed to contain the 2-oxoamide functionality and a free carboxyl group. Among the compounds tested, a long-chain 2-oxoamide containing L-gamma-norleucine was the most potent inhibitor, causing a 50% decrease in GIVA PLA2 activity at 0.009 mole fraction.

  DOI：

  10.1021/jm025538p
• 作为产物：
  描述：

  (S)-(+)-N-Boc-1-己醇 在 4-acetylamino-2,2,6,6-tetramethylpiperidine-N-oxyl 、 sodium hypochlorite 、 sodium bromide 作用下， 以 四氢呋喃 、 乙酸乙酯 、 甲苯 为溶剂， 生成 benzyl (E,4R)-4-[(tert-butoxycarbonyl)amino]oct-2-enoate
  参考文献：
  名称：

  Novel 2-Oxoamide Inhibitors of Human Group IVA Phospholipase A₂

  摘要：

  A novel class of potent human cytosolic phospholipase A(2) (GIVA PLA(2)) inhibitors was developed. These inhibitors were designed to contain the 2-oxoamide functionality and a free carboxyl group. Among the compounds tested, a long-chain 2-oxoamide containing L-gamma-norleucine was the most potent inhibitor, causing a 50% decrease in GIVA PLA2 activity at 0.009 mole fraction.

  DOI：

  10.1021/jm025538p

文献信息

• Novel 2-Oxoamide Inhibitors of Human Group IVA Phospholipase A₂
  作者：George Kokotos、Stavroula Kotsovolou、David A. Six、Violetta Constantinou-Kokotou、Christopher C. Beltzner、Edward A. Dennis

  DOI：10.1021/jm025538p

  日期：2002.7.1

  A novel class of potent human cytosolic phospholipase A(2) (GIVA PLA(2)) inhibitors was developed. These inhibitors were designed to contain the 2-oxoamide functionality and a free carboxyl group. Among the compounds tested, a long-chain 2-oxoamide containing L-gamma-norleucine was the most potent inhibitor, causing a 50% decrease in GIVA PLA2 activity at 0.009 mole fraction.
• Inhibition of Group IVA Cytosolic Phospholipase A₂ by Novel 2-Oxoamides in Vitro, in Cells, and in Vivo
  作者：George Kokotos、David A. Six、Vassilios Loukas、Timothy Smith、Violetta Constantinou-Kokotou、Dimitra Hadjipavlou-Litina、Stavroula Kotsovolou、Antonia Chiou、Christopher C. Beltzner、Edward A. Dennis

  DOI：10.1021/jm030485c

  日期：2004.7.1

  The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E-2 in cells, and demonstrate potent in vivo antiinflammatory and analgesic activity.