3β-hydroxy-17β-acetamido-androst-5-en-7-one | 1037262-18-2

• 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: 3β-hydroxy-17β-acetamido-androst-5-en-7-one
• 英文别名: 3β-hydroxy-17β-acetamide-androst-5-en-7-one
• CAS: 1037262-18-2
• 化学式: C₂₁H₃₁NO₃
• 分子量: 345.482
• InChiKey: COAFYIFEEDQEHZ-BULBTXNYSA-N

物化性质

• 熔点：
  270-271 °C(Solvent: Methanol)
• 沸点：
  563.2±49.0 °C(predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  25.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  66.4
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-17β-acetamido-androst-5-en-7-one 、 在 4-二甲氨基吡啶 作用下， 以 甲苯 为溶剂， 反应 1.5h， 以70%的产率得到17β-acetamide-androst-5-en-7-one-3β-yl 2-[4-N,N-bis(2-chloroethyl)amino-phenyl]butanoate
  参考文献：
  名称：

  芳香氮芥子碱2- [4-N，N-双（2-氯乙基）氨基-苯基]丁酸（2-PHE-BU）的甾族酸酯：合成和体内生物学评估。

  摘要：

  根据计算机内预测的结果并努力扩展我们的构效关系研究，芳族氮芥2- [4-N，N-双（2-氯乙基）氨基-苯基]丁酸（合成了2-PHE-BU），并与各种甾醇共轭。评价所得的甾族酯在荷P388白血病小鼠中的体内毒性和抗白血病活性。与游离的2-PHE-BU相比，新的衍生物显示出显着降低的毒性并略微提高了抗白血病活性。但是，无论是用于计算机模拟的模板甾体酯还是先前合成的芳族氮芥菜甾醇酯，它们都没有被证明是优越的。

  DOI：

  10.1097/cad.0b013e328357f687
• 作为产物：
  描述：

  3β-acetoxy-17β-acetamido-androst-5-en-7-one 在 甲醇 、 sodium carbonate 作用下， 反应 20.0h， 以98%的产率得到3β-hydroxy-17β-acetamido-androst-5-en-7-one
  参考文献：
  名称：

  Rational design, synthesis, and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters

  摘要：

  The synthesis and the in vivo evaluation against leukemias P388 and L1210 of six new alkylating steroidal esters are described. The esteric derivatives incorporating the 17 beta-acetamido-B-lactamic steroidal skeleton exhibited increased antileukemic activity and lower toxicity, compared to the 17 beta-acetamido-7-keto analogs. Among the 17 beta-acetamido-B-lactamic steroidal esters, the most potent compound afforded four out of six cures in leukemia P388 and was measured to be almost non-toxic, producing significant low levels of toxicity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.015

文献信息

• A new approach for evaluating in vivo anti-leukemic activity using the SCE assay
  作者：Venetia Karayianni、Eleftheria Mioglou、Zafiroula Iakovidou、Dionysios Mourelatos、Manolis Fousteris、Anna Koutsourea、Evaggelia Arsenou、Sotiris Nikolaropoulos

  DOI：10.1016/s1383-5718(02)00286-3

  日期：2003.2

  Three newly synthesised steroidal esteric derivatives of nitrogen mustard (compounds 1-3) were comparatively studied on a molar basis regarding their ability to induce sister chromatid exchanges (SCEs) in normal human lymphocytes in vitro and therapeutic effects on leukemia P388 bearing mice. Compounds 1 and 3 are modified steroidal esters of p-methyl-m-N,N-bis(2-chloroethyl)amino benzoic acid, and compound 2 is a modified steroidal ester of chlorambucil. All compounds induced statistically significant increases in SCEs and decreases in proliferation rate indices (PRIs) of cultured human lymphocytes and significantly increased the life span of P388 bearing mice. In this study, the doses applied for therapeutic purposes upon leukemia P388 bearing mice in vivo were derived from cytogenetic observations in normal human lymphocytes in vitro. A substantially better therapeutic effect was obtained compared to the effect achieved after the use of quite higher doses related with LD10 values. We have demonstrated that the order of anti-tumour effectiveness of the treatment schedules of the three newly synthesised compounds tested (at doses derived from cytogenetic observations) coincides with the order of the cytogenetic effects they induce. The SCE assay appears to have an application in the clinical prediction of tumour sensitivity to potential chemotherapeutics. (C) 2002 Elsevier Science B.V. All rights reserved.