3,3-ethylenebis(sulfanediyl)-19-hydroxyandrost-4-en-17-one | 15343-72-3

• 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: 3,3-ethylenebis(sulfanediyl)-19-hydroxyandrost-4-en-17-one
• 英文别名: 19-hydroxyandrost-4-ene-3,17-dione 3-ethylene thioketal；(8'R,9'S,10'S,13'S,14'S)-10'-(hydroxymethyl)-13'-methylspiro[1,3-dithiolane-2,3'-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene]-17'-one
• CAS: 15343-72-3
• 化学式: C₂₁H₃₀O₂S₂
• 分子量: 378.6
• InChiKey: XQBOGTKXLFMMNB-VDWQKOAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  87.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-ethylenebis(sulfanediyl)-19-hydroxyandrost-4-en-17-one 在 咪唑 、 盐酸 、 重铬酸吡啶 、 氨 、 sodium 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 52.0h， 生成 17,17-(ethylenedioxy)androst-4-en-19-al
  参考文献：
  名称：

  Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors

  摘要：

  Androst-4-en-17-one derivatives [19-acetoxide 4, 16-bromides 14 and 15, 19,19-difluoride 18, and (19R,S)-19-acetylenic alcohol 25] and androst-4-en-17-beta-ol derivatives 3, 5, 10, 12, and 19 were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. All the 17-oxo steroids, except compound 25 and 17,19-diol 3 of this series, were effective competitive inhibitors with apparent K(i)'s ranging from 170 to 455 nM. 19,19-Difluoro steroid 18 and 19-acetylenic alcohol 25, a weak competitive inhibitor (K(i) = 7.75-mu-M), caused a time-dependent, pseudo-first-order inactivation of aromatase activity with k(inact)'s of 0.0213 and 0.1053 min-1 for compounds 18 and 25, respectively. NADPH and oxygen were required for the time-dependent inactivation, and the substrate, androst-4-ene-3,17-dione, prevented it, but a nucleophile, L-cysteine, did not in each case. The results strongly suggest that aromatase would attack the 19-carbon of steroids 18 and 25.

  DOI：

  10.1021/jm00112a028
• 作为产物：
  描述：

  19-羟基雄甾-4-烯-3,17-二酮 、 1,2-乙二硫醇 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 以2%的产率得到
  参考文献：
  名称：

  3-脱氧雄激素的合成及化学模型反应研究：证据支持人类胎盘芳香化酶催化2、3-烯醇化假说

  摘要：

  许多迄今未描述的Δ 2 -和Δ 3 -3脱氧5α雄激素衍生物（17β，19-二醇12和13，19-羟基-17-酮16和17，19氧代-17-酮18和19）以高收率合成。锂-氨还原的19-（四氢吡喃-2-基氧基）雄甾-4-烯-3- -3,17-二酮7接着夏皮罗反应允许易于施工两个Δ的2 -和Δ 3 -3脱氧5α类固醇系统。已知的Δ的改进的合成4 -3- deoxyandrogen衍生物（28，30，31）以高产量完成。19位羟基的掩蔽，以产生Δ是必要4以良好的收率-3- deoxyandrogen系统，在对比的是帐户化合物的早期合成的28和30通过Numazawa。在芳香动作第三氧化处理的化学模型进行反应与Δ 2 - ，Δ 3 - ，Δ 4 -和Δ 2,4 -3-脱氧-19-氧代- 17-酮甾族化合物（18，19，31和5分别）。结果示出了用于两个Δ需要2 -和Δ 4，以便产生Δ-unsat

  DOI：

  10.1039/p19940002237

文献信息

• Synthesis and photochemistry of 17-hydroxy-A-homo-19-nor-17.alpha.-pregn-5(10)-en-20-yn-4-one
  作者：John R. Williams、George M. Sarkisian

  DOI：10.1021/jo01313a015

  日期：1980.12
• NUMAZAWA, MITSUTERU;MUTSUMI, AYAKO;HOSHI, KUMIKO;OSHIBE, MARIKO;ISHIKAWA,+, J. MED. CHEM., 34,(1991) N, C. 2496-2504
  作者：NUMAZAWA, MITSUTERU、MUTSUMI, AYAKO、HOSHI, KUMIKO、OSHIBE, MARIKO、ISHIKAWA,+

  DOI：——

  日期：——
• US4150127A
  申请人：——

  公开号：US4150127A

  公开（公告）日：1979-04-17
• Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors
  作者：Mitsuteru Numazawa、Ayako Mutsumi、Kumiko Hoshi、Mariko Oshibe、Etsushi Ishikawa、Hiroki Kigawa

  DOI：10.1021/jm00112a028

  日期：1991.8

  Androst-4-en-17-one derivatives [19-acetoxide 4, 16-bromides 14 and 15, 19,19-difluoride 18, and (19R,S)-19-acetylenic alcohol 25] and androst-4-en-17-beta-ol derivatives 3, 5, 10, 12, and 19 were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. All the 17-oxo steroids, except compound 25 and 17,19-diol 3 of this series, were effective competitive inhibitors with apparent K(i)'s ranging from 170 to 455 nM. 19,19-Difluoro steroid 18 and 19-acetylenic alcohol 25, a weak competitive inhibitor (K(i) = 7.75-mu-M), caused a time-dependent, pseudo-first-order inactivation of aromatase activity with k(inact)'s of 0.0213 and 0.1053 min-1 for compounds 18 and 25, respectively. NADPH and oxygen were required for the time-dependent inactivation, and the substrate, androst-4-ene-3,17-dione, prevented it, but a nucleophile, L-cysteine, did not in each case. The results strongly suggest that aromatase would attack the 19-carbon of steroids 18 and 25.
• Synthesis of and chemical model reaction studies with 3-deoxyandrogens: evidence supporting a 2, 3-enolization hypothesis in human placental aromatase catalysis
  作者：Soonsin S. Oh、Cecil H. Robinson

  DOI：10.1039/p19940002237

  日期：——

  A number of hitherto undescribed Δ2- and Δ3-3-deoxy-5α-androgen derivatives (17β,19-diols 12 and 13, 19-hydroxy-17-ketones 16 and 17, 19-oxo-17-ketones 18 and 19) were synthesized in good yield. The lithium-ammonia reduction of 19-(tetrahydropyran-2-yloxy)androst-4-ene-3, 17-dione 7 followed by Shapiro reaction allowed easy construction of both Δ2- and Δ3-3-deoxy-5α-steroid systems. An improved synthesis

  许多迄今未描述的Δ 2 -和Δ 3 -3脱氧5α雄激素衍生物（17β，19-二醇12和13，19-羟基-17-酮16和17，19氧代-17-酮18和19）以高收率合成。锂-氨还原的19-（四氢吡喃-2-基氧基）雄甾-4-烯-3- -3,17-二酮7接着夏皮罗反应允许易于施工两个Δ的2 -和Δ 3 -3脱氧5α类固醇系统。已知的Δ的改进的合成4 -3- deoxyandrogen衍生物（28，30，31）以高产量完成。19位羟基的掩蔽，以产生Δ是必要4以良好的收率-3- deoxyandrogen系统，在对比的是帐户化合物的早期合成的28和30通过Numazawa。在芳香动作第三氧化处理的化学模型进行反应与Δ 2 - ，Δ 3 - ，Δ 4 -和Δ 2,4 -3-脱氧-19-氧代- 17-酮甾族化合物（18，19，31和5分别）。结果示出了用于两个Δ需要2 -和Δ 4，以便产生Δ-unsat