(Z)-5-[(4R,4aS,6aR,7R,9aS,9bS)-4,6a-dimethyl-7-[(2R)-6-methylheptan-2-yl]-2-oxo-4a,5,6,7,8,9,9a,9b-octahydro-1H-cyclopenta[f]isochromen-4-yl]pent-2-enenitrile | 253343-12-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (Z)-5-[(4R,4aS,6aR,7R,9aS,9bS)-4,6a-dimethyl-7-[(2R)-6-methylheptan-2-yl]-2-oxo-4a,5,6,7,8,9,9a,9b-octahydro-1H-cyclopenta[f]isochromen-4-yl]pent-2-enenitrile
• CAS: 253343-12-3
• 化学式: C₂₇H₄₃NO₂
• 分子量: 413.644
• InChiKey: PIKMPFHAGPWQAM-QPCQJECTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-5-[(4R,4aS,6aR,7R,9aS,9bS)-4,6a-dimethyl-7-[(2R)-6-methylheptan-2-yl]-2-oxo-4a,5,6,7,8,9,9a,9b-octahydro-1H-cyclopenta[f]isochromen-4-yl]pent-2-enenitrile 在 10percent Pd/C 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 5-[(4R,4aS,6aR,7R,9aS,9bS)-4,6a-dimethyl-7-[(2R)-6-methylheptan-2-yl]-2-oxo-4a,5,6,7,8,9,9a,9b-octahydro-1H-cyclopenta[f]isochromen-4-yl]pentanoic acid
  参考文献：
  名称：

  Syntheses and Biological Activities of a Novel Group of Steroidal Derived Inhibitors for Human CDC25A Protein Phosphatase

  摘要：

  Silica gel supported pyrolysis of an azido-homo-oxa steroid led to rearrangement, presumably by a mechanism similar to that of solution phase Schmidt fragmentation, to produce a group of novel inhibitors for the oncogenic cell cycle regulator Cdc25A phosphatase. Cyano-containing acid 17, one of the best inhibitors in this group, inhibited the activity of Cdc25A protein phosphatase reversibly and noncompetitively with an IC50 value of 2.2 muM Structure-activity relationships revealed that a phosphate surrogate such as a carboxyl or a xanthate group is required for inhibitory activity, and a hydrophobic alkyl chain, such as the cholesteryl side chain, contributes greatly to the potency. Without the cyano group, acid 26 and xanthate 27 were found to be more selective over Cdc25A (IC50 = 5.1 muM and 1.1 muM, respectively) than toward CD45 (IC50 > 100 muM, in each case), a receptor protein tyrosine phosphatase. Several of these inhibitors showed antiproliferative activities in the NCI 60-human tumor cell line screen. These steroidal derived Cdc25 inhibitors provide unique leads for the development of dual-specificity protein phosphatase inhibitors.

  DOI：

  10.1021/jm0004401
• 作为产物：
  描述：

  3β-acetoxy-6-oxa-7a-homocholest-4-en-7-one 在 sodium azide 、 silica gel 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 (Z)-5-[(4R,4aS,6aR,7R,9aS,9bS)-4,6a-dimethyl-7-[(2R)-6-methylheptan-2-yl]-2-oxo-4a,5,6,7,8,9,9a,9b-octahydro-1H-cyclopenta[f]isochromen-4-yl]pent-2-enenitrile
  参考文献：
  名称：

  Novel CDC25A Phosphatase Inhibitors from Pyrolysis of 3-α-Azido-B-homo-6-oxa-4-cholesten-7-one on Silica Gel

  摘要：

  DOI：

  10.1021/jm980500r

文献信息

• Novel CDC25A Phosphatase Inhibitors from Pyrolysis of 3-α-Azido-B-homo-6-oxa-4-cholesten-7-one on Silica Gel
  作者：Hairuo Peng、Leon H. Zalkow、Robert T. Abraham、Garth Powis

  DOI：10.1021/jm980500r

  日期：1998.11.1
• Syntheses and Biological Activities of a Novel Group of Steroidal Derived Inhibitors for Human CDC25A Protein Phosphatase
  作者：Hairuo Peng、Wenge Xie、Diane M. Otterness、John P. Cogswell、Randy T. McConnell、H. Luke Carter、Garth Powis、Robert T. Abraham、Leon H. Zalkow

  DOI：10.1021/jm0004401

  日期：2001.3.1

  Silica gel supported pyrolysis of an azido-homo-oxa steroid led to rearrangement, presumably by a mechanism similar to that of solution phase Schmidt fragmentation, to produce a group of novel inhibitors for the oncogenic cell cycle regulator Cdc25A phosphatase. Cyano-containing acid 17, one of the best inhibitors in this group, inhibited the activity of Cdc25A protein phosphatase reversibly and noncompetitively with an IC50 value of 2.2 muM Structure-activity relationships revealed that a phosphate surrogate such as a carboxyl or a xanthate group is required for inhibitory activity, and a hydrophobic alkyl chain, such as the cholesteryl side chain, contributes greatly to the potency. Without the cyano group, acid 26 and xanthate 27 were found to be more selective over Cdc25A (IC50 = 5.1 muM and 1.1 muM, respectively) than toward CD45 (IC50 > 100 muM, in each case), a receptor protein tyrosine phosphatase. Several of these inhibitors showed antiproliferative activities in the NCI 60-human tumor cell line screen. These steroidal derived Cdc25 inhibitors provide unique leads for the development of dual-specificity protein phosphatase inhibitors.