6α-n-pentylandrost-4-ene-3,17-dione | 59251-70-6

• 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: 6α-n-pentylandrost-4-ene-3,17-dione
• 英文别名: 6alpha-Pentyl-4-androstene-3,17-dione；(6S,8R,9S,10R,13S,14S)-10,13-dimethyl-6-pentyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 59251-70-6
• 化学式: C₂₄H₃₆O₂
• 分子量: 356.549
• InChiKey: VIEGBWJBDLNCHK-QEDSVCCZSA-N

物化性质

• 沸点：
  486.5±45.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6α-n-pentylandrost-4-ene-3,17-dione 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 生成 methyl 3-[(3S,3aS,5aS,6R,8S,9aS,9bS)-3-hydroxy-3a,6-dimethyl-7-oxo-8-pentyl-1,2,3,4,5,5a,8,9,9a,9b-decahydrocyclopenta[a]naphthalen-6-yl]propanoate
  参考文献：
  名称：

  Secoandrostansäurenal对映体前列腺素类似物-II：6-戊基-4-nor-3,5-seco-androstan-3-säuren

  摘要：

  描述了对映体四氢-PGA 1类似物48的合成。另外homoacid 50，其pentanor类似物39及其差向异构体51，所述6-脱氧化合物13和16以及内酯类14，53，56和68制备为密切相关的化合物48。简单的雄烷烷衍生物用作合成的起始材料。关键中间体是4、32和63。

  DOI：

  10.1016/0040-4020(75)80159-1
• 作为产物：
  描述：

  3β,17β-diacetoxy-5,6α-epoxy-5α-androstane 在 chromium(VI) oxide 、 甲醇 、 sodium hydroxide 、 硫酸 作用下， 生成 6α-n-pentylandrost-4-ene-3,17-dione
  参考文献：
  名称：

  Secoandrostansäurenal对映体前列腺素类似物-II：6-戊基-4-nor-3,5-seco-androstan-3-säuren

  摘要：

  描述了对映体四氢-PGA 1类似物48的合成。另外homoacid 50，其pentanor类似物39及其差向异构体51，所述6-脱氧化合物13和16以及内酯类14，53，56和68制备为密切相关的化合物48。简单的雄烷烷衍生物用作合成的起始材料。关键中间体是4、32和63。

  DOI：

  10.1016/0040-4020(75)80159-1

文献信息

• Time-Dependent Inactivation of Aromatase by 6-Alkylandrosta-1,4-diene-3,17-diones. Effects of Length and Configuration of the 6-Alkyl Group
  作者：Mitsuteru Numazawa、Mariko Oshibe、Satoshi Yamaguchi、Mii Tachibana

  DOI：10.1021/jm950720u

  日期：1996.1.1

  structure-activity relationship of varying the 6-n-alkyl substituents (C-1--C-7) to the time-dependent inactivation activity. All of the inhibitors synthesized were powerful to good competitive inhibitors of aromatase, with apparent Ki's ranging from 4.7 to 54 nM. The 6beta-ethyl (4b) and 6beta-n-pentyl (4e) compounds were the most potent among them (Ki = 4.7 and 5.0 nM for 4b and 4e, respectively).

  合成了一系列6α-和6β-烷基雄甾烯-1,4-二烯-3,17-二酮（3和4），并作为人类胎盘微粒体中芳香化酶的时间依赖性灭活剂进行了评估，以了解其结构活性关系。将6-正烷基取代基（C-1--C-7）改变为随时间变化的灭活活性。合成的所有抑制剂均是芳香酶的良好竞争抑制剂，其表观Ki范围为4.7至54 nM。6beta-乙基（4b）和6beta-n-戊基（4e）化合物是其中最有效的化合物（4b和4e的Ki分别为4.7和5.0 nM）。在一系列的6-α-烷基甾族化合物中，在6-位具有C-1--C-4的抑制剂3a-d以及6个α-正庚基（3g）化合物没有。相反，在6β-烷基甾族化合物系列中，只有甲基类似物4a会以时间依赖性方式使芳香化酶失活，而在C-6beta处具有两个以上碳原子的其他烷基类固醇则没有。底物雄烯二酮可防止失活，并且在每种情况下均未观察到L-半胱氨酸对失活的显着影响。这些结果以及使用P
• Numazawa, Mitsuteru; Oshibe, Mariko, Steroids, 1995, vol. 60, # 8, p. 576 - 581
  作者：Numazawa, Mitsuteru、Oshibe, Mariko

  DOI：——

  日期：——
• 6-Alkylandrosta-4,6-diene-3,17-diones and their 1,4,6-triene analogs as aromatase inhibitors
  作者：Mitsuteru Numazawa、Mariko Oshibe、Satoshi Yamaguchi

  DOI：10.1016/s0039-128x(97)86814-6

  日期：1997.8

  Two series of 6-alkylandrosta-4,6-diene-3,17-diones (5) and their 1,4,6-triene analogs 6 were synthesized as aromatase inhibitors to gain insight into the structure-activity relationship between varying the 6-n-alkyl substituents (C-1-C-7) and inhibitory activity. All of the steroids synthesized were extremely powerful competitive inhibitors of aromatase in human placental microsomes, with apparent K-i values for the 6-alkyl-4,6-diene steroids 5 ranging from 17 to 36 nM and with those for the 1,4,6-triene steroids 6 ranging from 2.5 to 58 nM. The 6-ethyl-1,4,6-triene compound 6b (K-i = 2.5 nM) was the most potent inhibitor among them. The 6-alkyl-1,4,6-triene steroids 6, except for the 6-methyl analog 6a, had higher affinity for aromatase than the natural substrate androstenedione (K-m = 24 nM), and their inhibitory activities were more potent than the corresponding 4,6-diene steroids 5. In a series of the 4,6-diene steroids 5, compounds 5c-f with the n-alkyl chain substituents (C-3 to C-6) also had slightly higher affinity than androstenedione for aromatase. All of the 1,4,6-triene steroids 6 inactivated aromatase in a time-dependent manner, with k(inact) values ranging from 0.021 to 0.074 min(-1); in contrast, the 4,6-diene analogs 5 did not. The inactivation was prevented by androstenedione, and no significant effect of L-cysteine on the inactivation was observed in each case. These results indicate that the length of the n-alkyl substituent at C-6 of androsta-1,4,6-triene-3,17-dione (6h), rather than its 4,6-diene analog 5h, plays a critical role in tight binding to the active site of aromatase. No significant correlation was observed between affinity for the enzyme and the inactivation ability of the 6-alkyl-1,4,6-trienes. (C) 1997 by Elsevier Science Inc.