{4-[(2β,3α,5α,20R)-3,20-dihydroxypregnan-2-yl]piperazin-1-yl}[(2S)-1-{[(4S)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]carbonyl}pyrrolidin-2-yl]methanone | 1414928-31-6

• 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: {4-[(2β,3α,5α,20R)-3,20-dihydroxypregnan-2-yl]piperazin-1-yl}[(2S)-1-{[(4S)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]carbonyl}pyrrolidin-2-yl]methanone
• 英文别名: [4-[(2S,3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-17-[(1R)-1-hydroxyethyl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-2-yl]piperazin-1-yl]-[(2S)-1-[(4S)-4-prop-1-en-2-ylcyclohexene-1-carbonyl]pyrrolidin-2-yl]methanone
• CAS: 1414928-31-6
• 化学式: C₄₀H₆₃N₃O₄
• 分子量: 649.958
• InChiKey: YLPJGXTZCRZAHE-LKLVZKKMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  47
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (5α,20R)-pregn-2-en-20-ol 在 哌嗪 、 咪唑 、 水 、 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 25.0h， 生成 {4-[(2β,3α,5α,20R)-3,20-dihydroxypregnan-2-yl]piperazin-1-yl}[(2S)-1-{[(4S)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]carbonyl}pyrrolidin-2-yl]methanone
  参考文献：
  名称：

  Solid-phase chemical synthesis and in vitro biological evaluation of novel 2β-piperazino-(20R)-5α-pregnane-3α,20-diol N-derivatives as anti-leukemic agents

  摘要：

  The steroid nucleus is an interesting scaffold for the development of new therapeutic agents. Within the goal of identifying anticancer agents, new pregnane derivatives were prepared by using a sequence of liquid and solid-phase reactions. After we dehydrated epi-allopregnanolone in on step with diethylaminosulfur trifluoride and generated a 2,3 alpha-epoxide, the regio- and stereo-selective aminolysis of this epoxide enabled us to obtain a 2 beta-piperazino-pregnane, whose secondary amine was protected as N-Fmoc-derivative. Using the difference in reactivity between OHs 3 and 20, we linked the pregnane nucleus-selectively on the polystyrene diethylbutylsilane resin via the OH in position 20. We next achieved in parallel the coupling of an amino acid (1st level of diversity) and the coupling of a carboxylic acid (2nd level of diversity) to generate two libraries of pregnane derivatives. The compounds inhibited the HL-60 leukemia cell growth and the most potent were three compounds (PO, LPC-37 and LPC-48) with a L-proline as first level of diversity and a cyclohexyl-carbonyl, a naphthalene-2-carbonyl or a 3-acetylbenzoyl as second level of diversity. LPC-48 efficiently inhibited HL-60 cell proliferation with IC50 value of 1.9 mu M and exhibited a low toxicity on normal peripheral blood lymphocytes (IC50=31 mu M). These results encouraged us to further evaluate the biological activity of these new aminosteroids by investigating their preliminary mechanism of action. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.07.012