(2β,3α,5α)-3-hydroxy-2-(4-{[(2S)-1-(quinolin-2-ylcarbonyl)pyrrolidin-2-yl]carbonyl}piperazin-1-yl)androstan-17-one | 1228036-75-6

• 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: (2β,3α,5α)-3-hydroxy-2-(4-{[(2S)-1-(quinolin-2-ylcarbonyl)pyrrolidin-2-yl]carbonyl}piperazin-1-yl)androstan-17-one
• 英文别名: (2S,3S,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-2-[4-[(2S)-1-(quinoline-2-carbonyl)pyrrolidine-2-carbonyl]piperazin-1-yl]-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
• CAS: 1228036-75-6
• 化学式: C₃₈H₅₀N₄O₄
• 分子量: 626.839
• InChiKey: XPCQPZXYBZFMOG-OBLTXFSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  46
• 可旋转键数：
  3
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  94
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2β,3α,5α)-3-hydroxy-2-(4-{[(2S)-1-(quinolin-2-ylcarbonyl)pyrrolidin-2-yl]carbonyl}piperazin-1-yl)androstan-17-one 在 copper(I) bromide 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以44%的产率得到
  参考文献：
  名称：

  一种氨基甾体化合物及其制备方法和应用

  摘要：

  本申请提供了一种氨基甾体化合物及其制备方法和应用，所述氨基甾体化合物包括如式I或式II所示的化学式中的至少一种， 其中，R1、R2、R3、R4、R5独立地选自H、含卤素基团、C1～C10的烷基、C2～C10的烯基、C2～C10的炔基、C3～C10的环烷基、C6～C10芳基或C5～C10杂芳基；并且R1、R2中至少一个为含卤素基团；R3、R4、R5中至少一个为含卤素基团。

  公开号：

  CN114702544A
• 作为产物：
  描述：

  2α,3α-epoxy-5α-androstan-17-one 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (2β,3α,5α)-3-hydroxy-2-(4-{[(2S)-1-(quinolin-2-ylcarbonyl)pyrrolidin-2-yl]carbonyl}piperazin-1-yl)androstan-17-one
  参考文献：
  名称：

  Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133

  摘要：

  The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2014.01.008

文献信息

• 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.