3-alpha-Aminocholestane | 2206-20-4

• 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: 3-alpha-Aminocholestane
• 英文别名: (3R,5S,10S,13R,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine
• CAS: 2206-20-4；2206-21-5；62532-40-5；62560-52-5；115792-55-7；115792-56-8
• 化学式: C₂₇H₄₉N
• 分子量: 387.693
• InChiKey: RJNGJYWAIUJHOJ-SHFMBRIGSA-N

物化性质

• 熔点：
  104.5-105.5℃ (methanol )
• 沸点：
  160 °C(Press: 0.1 Torr)
• 密度：
  0.930±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿：30mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

制备方法与用途

生物活性

3α-Aminocholestane 是含有选择性 SH2 结构域的肌醇-5'-磷酸酶 1 (SHIP1) 的抑制剂，其 IC50 值约为 2.5 μM。

靶点

IC50: 2.5 μM (SHIP1)

体外研究

OPM2 cell viability is effectively reduced by 3α-Aminocholestane (3AC) treatment. RPMI8226 and U266 cells show significantly less sensitivity to 3α-Aminocholestane treatment when compare with OPM2 cells, although viability is decreased significantly at concentrations of ≥12.5 μM. Treatment with 3α-Aminocholestane for 36 h severely reduces the percentage of cells in the S phase, which is accompanied by an increase of cells in the G2/M phase. In contrast, in the less proliferative RPMI8226 and U266 cells, cell cycle progression is blocked in the G0/G1 phase upon 3α-Aminocholestane treatment, in conjunction with a reduced percentage of cells undergoing the S phase.

体内研究

It is found that 3α-Aminocholestane (3AC) results in reduced multiple myeloma (MM) growth in vivo , as determined by quantitation of free human Igλ light chain in the plasma after OPM2 challenge. In addition, reduced numbers of circulating OPM2 cells, as determined by human HLA-ABC staining, is observed in peripheral blood from 3α-Aminocholestane-treated mice compare with vehicle controls. Most importantly, 3α-Aminocholestane treatment results in significantly enhanced survival of mice after tumor challenge. In 3α-Aminocholestane-treated mice that resist treatment, it is found that MM tumors exhibit an upregulation of SHIP2, reminiscent of in vitro treatment of OPM2 cells and suggesting that SHIP1 inhibition may select for tumor cells with increased SHIP2 expression.

反应信息

• 作为反应物：
  描述：

  3-alpha-Aminocholestane 在 甲醇 作用下， 以 氯仿 为溶剂， 反应 44.0h， 生成 3-[(3R,5S,10S,13R,17R)-17-((R)-1,5-Dimethyl-hexyl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-3-ylamino]-propionic acid
  参考文献：
  名称：

  A Synthesis ofN-Substituted β-Alanines: Michael Addition of Amines to Trimethylsilyl Acrylate

  摘要：

  对甲基硅烯丙烯酸酯 (1) 进行的迈克尔加成反应中，原级和次级胺 (2) 分别得到良好产率的 β-(烷基氨基) 和 β-(二烷基氨基) -丙酸 (4)。

  DOI：

  10.1055/s-1989-27440
• 作为产物：
  描述：

  (3R,5S,10S,13R,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-N-[(1S)-1-phenylethyl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine 以57%的产率得到
  参考文献：
  名称：

  KNUPP, G.;FRAHM, A. W., ARCH. PHARM., 1985, 318, N 6, 535-542

  摘要：

  DOI：