(7Z,10Z,13Z,15E)-17(S)-hydroxydocosa-7,10,13,15-tetraenoic acid | 105835-39-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (7Z,10Z,13Z,15E)-17(S)-hydroxydocosa-7,10,13,15-tetraenoic acid
• 英文别名: 17(S)-HDoTE；(7Z,10Z,13Z,15E,17S)-17-hydroxydocosa-7,10,13,15-tetraenoic acid
• CAS: 105835-39-0
• 化学式: C₂₂H₃₆O₃
• 分子量: 348.526
• InChiKey: JALSVOZEVSMDLQ-IZCUWNJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  25
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (7Z,10Z,13Z,15E)-17(S)-hydroxydocosa-7,10,13,15-tetraenoic acid 以90%的产率得到
  参考文献：
  名称：

  HAVIV F.; RATAJCZYK J. D.; DENET R. W.; MARTIN Y. C.; DYER R. D.; CARTER +, J. MED. CHEM., 30,(1987) N 2, 254-263

  摘要：

  DOI：
• 作为产物：
  描述：

  廿二碳四烯酸 在 硫酸氢铵 、 sodium tetrahydroborate 作用下， 生成 (7Z,10Z,13Z,15E)-17(S)-hydroxydocosa-7,10,13,15-tetraenoic acid
  参考文献：
  名称：

  Structural requirements for the inhibition of 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid analogs

  摘要：

  The structural requirements for inhibition of RBL-1 (rat basophilic leukemia) 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15-HETE, 1) were studied by systematic chemical modifications of the molecule at the hydroxyl and carboxyl groups, the double bonds, and the carboxylate and omega side chains. The most potent inhibitors were analogues that contained a 5,8-cis,cis-diene system and acted as alternate substrates for the enzyme. However, several analogues in which the 5,8-diene had been reduced were also found to inhibit the enzyme. Inhibition of 5-lipoxygenase by 15-hydroxyeicosa-11,13-dienoic acid (15-HEDE) analogues was optimal in compounds that generally contained a free carboxyl group, a carboxylate side chain of nine carbons, an omega side chain of five or six carbons, a cis,trans- or trans,cis-11,13-diene or 11,13-diyne system, and a 15-hydroxyl group. Conversion of 15-HEDE to its 16-membered lactone reduced but did not eliminate 5-lipoxygenase inhibitory activity. In contrast, a 3- to 10-fold enhancement of activity occurred when 5,15-diHETE (58) or 5-HETE (56) were cyclized to their respective delta-lactones. Molecular modeling of 15-HEDE analogues, modified in the C11-C15 region, showed that inactive analogues protrude into regions in space not occupied by active analogues. These structural studies indicate that multiple regions are important for 5-lipoxygenase inhibition by both 15-HETE and 15-HEDE analogues and that no single region plays a predominant role in inhibition.

  DOI：

  10.1021/jm00385a005

文献信息

• HAVIV F.; RATAJCZYK J. D.; DENET R. W.; MARTIN Y. C.; DYER R. D.; CARTER +, J. MED. CHEM., 30,(1987) N 2, 254-263
  作者：HAVIV F.、 RATAJCZYK J. D.、 DENET R. W.、 MARTIN Y. C.、 DYER R. D.、 CARTER +

  DOI：——

  日期：——
• Structural requirements for the inhibition of 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid analogs
  作者：Fortuna Haviv、James D. Ratajczyk、Robert W. DeNet、Yvonne C. Martin、Richard D. Dyer、George W. Carter

  DOI：10.1021/jm00385a005

  日期：1987.2

  The structural requirements for inhibition of RBL-1 (rat basophilic leukemia) 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15-HETE, 1) were studied by systematic chemical modifications of the molecule at the hydroxyl and carboxyl groups, the double bonds, and the carboxylate and omega side chains. The most potent inhibitors were analogues that contained a 5,8-cis,cis-diene system and acted as alternate substrates for the enzyme. However, several analogues in which the 5,8-diene had been reduced were also found to inhibit the enzyme. Inhibition of 5-lipoxygenase by 15-hydroxyeicosa-11,13-dienoic acid (15-HEDE) analogues was optimal in compounds that generally contained a free carboxyl group, a carboxylate side chain of nine carbons, an omega side chain of five or six carbons, a cis,trans- or trans,cis-11,13-diene or 11,13-diyne system, and a 15-hydroxyl group. Conversion of 15-HEDE to its 16-membered lactone reduced but did not eliminate 5-lipoxygenase inhibitory activity. In contrast, a 3- to 10-fold enhancement of activity occurred when 5,15-diHETE (58) or 5-HETE (56) were cyclized to their respective delta-lactones. Molecular modeling of 15-HEDE analogues, modified in the C11-C15 region, showed that inactive analogues protrude into regions in space not occupied by active analogues. These structural studies indicate that multiple regions are important for 5-lipoxygenase inhibition by both 15-HETE and 15-HEDE analogues and that no single region plays a predominant role in inhibition.