(17-Hydroxy-3-oxo-4-androsten-6β-yl)malonsaeure-dimethylester | 59452-35-6

• 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: (17-Hydroxy-3-oxo-4-androsten-6β-yl)malonsaeure-dimethylester
• 英文别名: dimethyl 2-[(6S,8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-6-yl]propanedioate
• CAS: 59452-35-6
• 化学式: C₂₄H₃₄O₆
• 分子量: 418.53
• InChiKey: KFHLMRJGGOGDBE-VBXJQWQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (17-Hydroxy-3-oxo-4-androsten-6β-yl)malonsaeure-dimethylester 在 lithium hydroxide 、 lithium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 ((6S,8R,9S,10R,13S,14S,17S)-17-Hydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl)-acetic acid
  参考文献：
  名称：

  Design and synthesis of a new fluorescent probe for cytochrome P450 3A4 (CYP 3A4)

  摘要：

  Inhibition of CYP 3A4 catalytic activity is a principal mechanism for in vivo drug-drug interactions, sometimes leading to severe toxic effects. Rapid in vitro testing for CYP 3A4 high affinity/high inhibition potential has become part of the standard investigations for new drug candidates. Unfortunately, the complexity of the kinetics associated with CYP 3A4 catalyzed reactions (multiple substrates binding, non Michaelis-Menten kinetics) make these tests either inaccurate or tedious. We have designed and synthesized a new fluorescent probe, a testosterone substituted at the 6beta- position with a fluorescent deazaflavine moiety which is able to inhibit to the same extent the hydroxylation of compounds known to bind to different sites in the CYP 3A4 active site. Furthermore, the binding of this compound and its displacement from the active site can be followed by fluorescence measurements, which allows a rapid evaluation of the CYP 3A4 affinity of any new drug candidate. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.027
• 作为产物：
  描述：

  睾酮 、 丙二酸二甲酯 在 sodium chloride 、 palladium dichloride 、 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 56.0h， 生成 (17-Hydroxy-3-oxo-4-androsten-6β-yl)malonsaeure-dimethylester
  参考文献：
  名称：

  Design and synthesis of a new fluorescent probe for cytochrome P450 3A4 (CYP 3A4)

  摘要：

  Inhibition of CYP 3A4 catalytic activity is a principal mechanism for in vivo drug-drug interactions, sometimes leading to severe toxic effects. Rapid in vitro testing for CYP 3A4 high affinity/high inhibition potential has become part of the standard investigations for new drug candidates. Unfortunately, the complexity of the kinetics associated with CYP 3A4 catalyzed reactions (multiple substrates binding, non Michaelis-Menten kinetics) make these tests either inaccurate or tedious. We have designed and synthesized a new fluorescent probe, a testosterone substituted at the 6beta- position with a fluorescent deazaflavine moiety which is able to inhibit to the same extent the hydroxylation of compounds known to bind to different sites in the CYP 3A4 active site. Furthermore, the binding of this compound and its displacement from the active site can be followed by fluorescence measurements, which allows a rapid evaluation of the CYP 3A4 affinity of any new drug candidate. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.027

文献信息

• Handschuh, Dieter; Voelter, Wolfgang, Liebigs Annalen der Chemie, 1989, p. 1007 - 1016
  作者：Handschuh, Dieter、Voelter, Wolfgang

  DOI：——

  日期：——