16,17a-dioxo-17-aza-D-homo-5-androsten-3β-ol | 158661-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 16,17a-dioxo-17-aza-D-homo-5-androsten-3β-ol
• 英文别名: (4aS,4bR,8S,10aR,10bS,12aS)-8-hydroxy-10a,12a-dimethyl-4a,4b,5,7,8,9,10,10b,11,12-decahydro-4H-naphtho[2,1-f]isoquinoline-1,3-dione
• CAS: 158661-62-2
• 化学式: C₁₉H₂₇NO₃
• 分子量: 317.428
• InChiKey: IECROBYLYFHSPC-NRNRTASOSA-N

物化性质

• 沸点：
  508.7±50.0 °C(predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  16,17a-dioxo-17-aza-D-homo-5-androsten-3β-ol 在 sodium tetrahydroborate 、 戊醇 、 sodium 、 aluminum isopropoxide 作用下， 以 1,4-二氧六环 、 甲醇 、 环己酮 、 甲苯 为溶剂， 反应 8.02h， 生成 17-methyl-3β-pyrrolidino-17-aza-D-homo-5-androstene
  参考文献：
  名称：

  Synthesis and biological activity of 17-azasteroidal neuromuscular-blocking agents

  摘要：

  The new analogues, containing nitrogen at the 17-position instead of the 17a-position, of chandonium iodide 2 have been prepared and evaluated for potential neuromuscular-blocking activity in in vitro studies using chick-biventer cervicis preparations. There is a slight increase in the interonium distance between the 2 quaternary heads of 13(DPJ-240). All the bisquatemary compounds 13 (DPJ-240), 14 (DPJ-252), 15 (DPJ-262), 16 (DPJ-260) and 17 (DPJ-261) showed potent neuromuscular-blocking activity but slightly less than chandonium iodide 2. Monoquaternary ammonium derivatives 12 (DPJ-246), 21 (DPJ-245), 23 (DPJ-246) and 24 (DPJ-243) of 17-azasteroids were also synthesized and pharmacologically tested. They exhibited weak neuromuscular-blocking activity as compared to the bisquatemary compounds and chandonium iodide 2.

  DOI：

  10.1016/0223-5234(94)90056-6
• 作为产物：
  描述：

  去氢表雄酮 在 氢氧化钾 、 potassium tert-butylate 、 溶剂黄146 、 亚硝酸异戊酯 作用下， 以 甲醇 为溶剂， 反应 18.5h， 生成 16,17a-dioxo-17-aza-D-homo-5-androsten-3β-ol
  参考文献：
  名称：

  Synthesis and biological activity of 17-azasteroidal neuromuscular-blocking agents

  摘要：

  The new analogues, containing nitrogen at the 17-position instead of the 17a-position, of chandonium iodide 2 have been prepared and evaluated for potential neuromuscular-blocking activity in in vitro studies using chick-biventer cervicis preparations. There is a slight increase in the interonium distance between the 2 quaternary heads of 13(DPJ-240). All the bisquatemary compounds 13 (DPJ-240), 14 (DPJ-252), 15 (DPJ-262), 16 (DPJ-260) and 17 (DPJ-261) showed potent neuromuscular-blocking activity but slightly less than chandonium iodide 2. Monoquaternary ammonium derivatives 12 (DPJ-246), 21 (DPJ-245), 23 (DPJ-246) and 24 (DPJ-243) of 17-azasteroids were also synthesized and pharmacologically tested. They exhibited weak neuromuscular-blocking activity as compared to the bisquatemary compounds and chandonium iodide 2.

  DOI：

  10.1016/0223-5234(94)90056-6

文献信息

• Synthesis and Preliminary Screening of Novel A- and D-Ring Modified Steroids as Aromatase Inhibitors
  作者：Mange Ram Yadav、Prafulla M. Sabale、Rajani Giridhar、Dharmendra Baria、Christina Zimmer、Rolf W. Hartmann

  DOI：10.2174/157018011797655322

  日期：2011.12.1

  Estrogens are responsible for the growth of hormone-dependant breast cancer. Regulation of estrogen biosynthesis is considered as a potential therapeutic strategy for the control of breast cancer. The enzyme aromatase catalyzes conversion of androgens into estrogens in the last step of estrogen biosynthesis. Inhibition of aromatase is adopted as an efficient approach for the prevention and treatment of breast cancer. Many steroidal and nonsteroidal aromatase inhibitors have been developed and are used clinically for breast cancer therapy. In this report, it has been tried to incorporate some structural features (six membered lactam ring) of nonsteroidal aromatase inhibitors like aminoglutethimide and rogletimide into the A-/D-ring of the steroid nucleus with certain additional features responsible for binding to the enzyme aromatase. Some ring-A [17β-hydroxy-4-(4-substitutedphenyl)-4-aza-5-androsten-3-one] and ring-D modified steroidal compounds [4-substituted-17a-aza-D-homo-4-androstene-3,17-dione, 4-substituted-17-aza-Dhomo- 4-androstene-3,16,17a-trione, 4-substituted-17a-methyl-17a-aza-D-homo-4-androsten-3-one] were synthesized and screened for binding to the aromatase enzyme. None of the synthesized compounds showed promising aromatase inhibiting activity leading to the conclusion that structurally the original androstane ring skeleton should not be tampered with, for obtaining good aromatase inhibiting activity.

  雌激素是激素依赖性乳腺癌生长的主要原因。雌激素生物合成的调控已被认为是对乳腺癌进行控制的潜在治疗策略。芳香化酶是一种酶，它促进了雄激素转化为雌激素，这是雌激素生物合成的最后一步。因此，抑制芳香化酶成为预防和治疗乳腺癌的有效方法。现已开发出许多甾体和非甾体类芳香化酶抑制剂，并用于临床乳腺癌治疗。在本报告中，我们试图将一些非甾体类芳香化酶抑制剂（如氨基导眠能和洛格尔替酯）的结构特征（六元内酰胺环）引入甾体母核的A环和D环中，并加入一些能够与芳香化酶结合的结构特征。我们合成了一些A环[17β-羟基-4-(4-取代苯基)-4-氮杂-5-雄甾烯-3-酮]和D环修饰的甾体类化合物[4-取代-17α-氮杂-D-高-4-雄甾烯-3,17-二酮、4-取代-17-氮杂-D-高-4-雄甾烯-3,16,17α-三酮、4-取代-17α-甲基-17α-氮杂-D-高-4-雄甾烯-3-酮]，并测试了它们与芳香化酶的结合能力。然而，合成的化合物均未显示出良好的芳香化酶抑制活性，这表明在结构上，原初的雄甾烷环骨架不应被改动，以获得良好的芳香化酶抑制活性。
• Synthesis and biological activity of steroidal imide
  作者：AK Verma、DP Jindal

  DOI：10.1016/0223-5234(96)88243-2

  日期：1995.1