3β-hydroxy-22-aza-cholestan-5-ene

• 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-22-aza-cholestan-5-ene
• 英文别名: (3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-17-[1-(3-methylbutylamino)ethyl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
• 化学式: C₂₆H₄₅NO
• 分子量: 387.649
• InChiKey: PCLDERUMTJBTMY-BKHUXWMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  异戊胺 、 孕烯醇酮醋酸酯 在 对甲苯磺酸 、 sodium tetrahydroborate 作用下， 以 甲苯 、 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 3β-hydroxy-22-aza-cholestan-5-ene
  参考文献：
  名称：

  Structure–activity relationship of Aza-steroids as PI-PLC inhibitors

  摘要：

  A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and 3 beta -hydroxy-22,25-diazacholestane (8b) were among the most active of these inhibitors, with IC50 values of 7.4 and 7.5 muM, respectively. The 20 alpha epimer, 8a2 (IC50 = 0.64 muM), whose stereochemistry at C-20 coincides with that of cholesterol, was found 50 times more potent than the 20 beta epimer, 8a1 (IC50 = 32.2 muM). In diaza-estrone derivatives, the 3-methoxy group on the aromatic A-ring of 23 exhibited moderate PI-PLC inhibitory activity (IC50 = 19.7 muM), while compound with a free hydroxyl group (21) was inactive. However, in diaza-pregnane derivatives, epimers with a 3-hydroxyl group (8a, IC50 = 7.4 muM) exhibited more potent PI-PLC inhibitory activity than their counterparts with 3-methoxyl group on the non-aromatic A-ring (26, IC50 = 17.4 muM). We have illustrated in our previous publication that 3-hydroxyl-6-aza steroids are potent PI-PLC inhibitors.(3) However, simultaneous presence of the 6-aza and 22,25-diaza moieties in one molecule as in 13, led to loss of activity. Epimeric mixture 8a showed selective growth inhibition effects in the NCI in vitro tumor cell screen with a mean GI(50) value (MG-MID) of 5.75 muM for 54 tumors. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(00)00302-3

文献信息

• Structure–activity relationship of Aza-steroids as PI-PLC inhibitors
  作者：W Xie

  DOI：10.1016/s0968-0896(00)00302-3

  日期：2001.5

  A number of aza-steroids were synthesized as potent phosphatidylinositol phospholipase C (PI-PLC) inhibitors. The epimeric mixtures 22,25-diazacholesterol (8a) and 3 beta -hydroxy-22,25-diazacholestane (8b) were among the most active of these inhibitors, with IC50 values of 7.4 and 7.5 muM, respectively. The 20 alpha epimer, 8a2 (IC50 = 0.64 muM), whose stereochemistry at C-20 coincides with that of cholesterol, was found 50 times more potent than the 20 beta epimer, 8a1 (IC50 = 32.2 muM). In diaza-estrone derivatives, the 3-methoxy group on the aromatic A-ring of 23 exhibited moderate PI-PLC inhibitory activity (IC50 = 19.7 muM), while compound with a free hydroxyl group (21) was inactive. However, in diaza-pregnane derivatives, epimers with a 3-hydroxyl group (8a, IC50 = 7.4 muM) exhibited more potent PI-PLC inhibitory activity than their counterparts with 3-methoxyl group on the non-aromatic A-ring (26, IC50 = 17.4 muM). We have illustrated in our previous publication that 3-hydroxyl-6-aza steroids are potent PI-PLC inhibitors.(3) However, simultaneous presence of the 6-aza and 22,25-diaza moieties in one molecule as in 13, led to loss of activity. Epimeric mixture 8a showed selective growth inhibition effects in the NCI in vitro tumor cell screen with a mean GI(50) value (MG-MID) of 5.75 muM for 54 tumors. (C) 2001 Published by Elsevier Science Ltd.