(8R,9S,10R,13S,14S,17R)-17-hydroxy-10,13-dimethyl-17-[2-(4-pyridin-2-ylpiperazin-1-yl)acetyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one | 111640-72-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (8R,9S,10R,13S,14S,17R)-17-hydroxy-10,13-dimethyl-17-[2-(4-pyridin-2-ylpiperazin-1-yl)acetyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 111640-72-3
• 化学式: C₃₀H₄₁N₃O₃
• 分子量: 491.674
• InChiKey: LYTYUUDBKBQJJF-WUDNVTLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2-吡啶基)哌嗪 、 21-bromo-17α-hydroxy-4-pregnene-3,20-dione 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以31%的产率得到(8R,9S,10R,13S,14S,17R)-17-hydroxy-10,13-dimethyl-17-[2-(4-pyridin-2-ylpiperazin-1-yl)acetyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
  参考文献：
  名称：

  Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma

  摘要：

  A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma.

  DOI：

  10.1021/jm00166a010

文献信息

• C20 Through C26 amino steroids
  申请人：THE UPJOHN COMPANY

  公开号：EP0263213B1

  公开（公告）日：1995-09-06
• C20 THROUGH C26 AMINO STEROIDS
  申请人：THE UPJOHN COMPANY

  公开号：EP0238545B1

  公开（公告）日：1995-11-15
• US5380841A
  申请人：——

  公开号：US5380841A

  公开（公告）日：1995-01-10
• Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma
  作者：E. Jon Jacobsen、John M. McCall、Donald E. Ayer、Fred J. VanDoornik、John R. Palmer、Kenneth L. Belonga、J. Mark Braughler、Edward D. Hall、David J. Houser

  DOI：10.1021/jm00166a010

  日期：1990.4

  A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma.