2β-(piperazin-1-yl)-5α-androstane-3α,17β-diol | 941672-70-4

• 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: 2β-(piperazin-1-yl)-5α-androstane-3α,17β-diol
• 英文别名: (2β,3α,5α,17β)-2-(piperazin-1-yl)androstane-3,17-diol；(2I(2),3I+/-,5I+/-,17I(2))-2-(1-Piperazinyl)androstane-3,17-diol；(2S,3S,5S,8R,9S,10S,13S,14S,17S)-10,13-dimethyl-2-piperazin-1-yl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol
• CAS: 941672-70-4
• 化学式: C₂₃H₄₀N₂O₂
• 分子量: 376.583
• InChiKey: MBEPODKLEFVXLV-NQBGTIOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  壬酸 、 2β-(piperazin-1-yl)-5α-androstane-3α,17β-diol 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2β-(4-nonanoylpiperazin-1-yl)-5α-androstane-3α,17β-diol
  参考文献：
  名称：

  Chemical synthesis of 2β-amino-5α-androstane-3α,17β-diol N-derivatives and their antiproliferative effect on HL-60 human leukemia cells

  摘要：

  Even though few steroids are used for the treatment of leukemia, 2 beta-(4-methylpiperazinyl)-5 alpha-androstane-3 alpha,17 beta-diol (1) was recently reported for its ability to inhibit the proliferation of human leukemia HL-60 cells. With an efficient procedure that we had developed for the aminolysis of hindered steroidal epoxides, we synthesized a series of 2 beta-amino-5 alpha-androstane-3 alpha,17 beta-diol N-derivatives structurally similar to 1. Hence, the opening of 2,3 alpha-epoxy-5 alpha-androstan-17 beta-diol with primary and secondary amines allowed the synthesis of aminosteroids with diverse length, rami. cation, and functionalization of the 2 beta-side chain. Sixty-four steroid derivatives were tested for their capacity to inhibit the proliferation of HL-60 cells; thus obtaining first structure - activity relationship results. Ten aminosteroids with long alkyl chains (7 - 16 carbons) or bulky groups (diphenyl or adamantyl) have shown antiproliferative activity over 78% at 10 mu M and superior to that of the lead compound. The 3,3-diphenylpropylamino, 4-nonylpiperazinyl and octylamino derivatives of 5 alpha-androstane-3 alpha,17 beta-diol inhibited the HL-60 cell growth with IC(50) of 3.1, 4.2 and 6.4 mu M, respectively. They were also found to induce the HL-60 cell differentiation. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.031
• 作为产物：
  描述：

  哌嗪 、 2-羧基阿拉伯糖醇1-磷酸酯 以 水 为溶剂， 反应 24.0h， 以69%的产率得到2β-(piperazin-1-yl)-5α-androstane-3α,17β-diol
  参考文献：
  名称：

  [EN] 2-(N-SUBSTITUTED PIPERAZINYL) STEROID DERIVATIVES
  [FR] DÉRIVÉS DE STÉROÏDES DE TYPE 2-(PIPÉRAZINYLE N-SUBSTITUÉ)

  摘要：

  本文描述了化学式I的新型化学试剂。更具体地，本文披露了对多种癌细胞系表现出细胞毒性的2-(N-取代哌嗪基)孕酮和2-(N-取代哌嗪基)雄烷衍生物。 (I)

  公开号：

  WO2010060215A1

文献信息

• 2-(N-Substituted Piperazinyl) Steroid Derivatives
  申请人：Poirier Donald

  公开号：US20110312926A1

  公开（公告）日：2011-12-22

  Novel chemical agents are described herein. More specifically, 2-(N-substituted piperazinyl) pregnane and 2-(N-substituted piperazinyl) androstane derivatives exhibiting cytotoxicity on a variety of cancer cell lines are disclosed herein.

  本文描述了新型化学药剂。更具体地，本文揭示了对多种癌细胞系表现出细胞毒性的2-(N-取代哌嗪基)孕酮和2-(N-取代哌嗪基)雄烷衍生物。
• Chemical synthesis, cytotoxicity, selectivity and bioavailability of 5α-androstane-3α,17β-diol derivatives
  作者：Diana Ayan、René Maltais、Audrey Hospital、Donald Poirier

  DOI：10.1016/j.bmc.2014.09.026

  日期：2014.11

  Aminosteroid derivatives represent a new family of compounds with promising antiproliferative activity over different cancer cell lines. Among all the aminosteroid derivatives synthesised in our laboratory, we have identified E-37P as one of the more potent when tested in vitro. Unfortunately, the pharmacokinetic properties of E-37P decrease its effectiveness when tested in vivo. To improve the bioavailability and increase the efficiency of aminosteroid E-37P, two series of analog compounds were synthesised by classic chemical synthesis, they were then characterized, and the concentration that inhibits 50% of cell proliferation (IC50) was determined on different cell lines. RM-133, a 5 alpha-androstane-3 alpha, 17 beta-diol derivative with a quinoline nucleus at the end of the piperazine-proline side-chain at position 2 beta and an ethinyl at position 17 alpha, showed very good antiproliferative activity among the five cancer cell lines studied (IC50 = 0.1, 0.1, 0.1, 2.0 and 1.1 mu M for HL-60, MCF-7, T-47D, LNCaP and WEHI-3, respectively). Moreover, the plasmatic concentration of RM-133 at 3 h, when injected subcutaneously in rats, was 2.3-fold higher than that of E-37P (151 vs 64.8 ng/mL). Furthermore, RM-133 weakly inhibited the two representative liver enzymes, CYP3A4 and CYP2D6, indicating a very low risk of drug-drug interactions. The cytotoxicity of RM-133 against normal cells was tested on peripheral blood lymphocytes (PBL) obtained from different donors and previously activated with phytohemagglutinin-L. PBL responded differently to treatment with RM-133, we observed a stimulation of cell proliferation and/or cytotoxicity in a dose-dependent manner. Based on these results, additional studies are currently underway to evaluate the selectivity of our lead compound against normal cell lines in a more detailed fashion. (C) 2014 Elsevier Ltd. All rights reserved.
• US8653054B2
  申请人：——

  公开号：US8653054B2

  公开（公告）日：2014-02-18