methyl (4R)-4-[(2-hydroxypentadecanoyl)amino]-6-methylheptanoate | 724784-51-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (4R)-4-[(2-hydroxypentadecanoyl)amino]-6-methylheptanoate
• 英文别名: methyl (4R)-4-(2-hydroxypentadecanoylamino)-6-methylheptanoate
• CAS: 724784-51-4
• 化学式: C₂₄H₄₇NO₄
• 分子量: 413.641
• InChiKey: WFGRBOSQWWAWPW-ZMFCMNQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  29
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (4R)-4-[(2-hydroxypentadecanoyl)amino]-6-methylheptanoate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Novel 2-Oxoamides in Vitro, in Cells, and in Vivo

  摘要：

  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.

  DOI：

  10.1021/jm030485c
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 methyl (4R)-4-[(2-hydroxypentadecanoyl)amino]-6-methylheptanoate
  参考文献：
  名称：

  Inhibition of Group IVA Cytosolic Phospholipase A₂ by Novel 2-Oxoamides in Vitro, in Cells, and in Vivo

  摘要：

  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.

  DOI：

  10.1021/jm030485c

文献信息

• 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.