Acetic acid (3S,3aS,9aS,9bS)-3a-ethyl-7-oxo-1,2,3,3a,4,7,8,9,9a,9b-decahydro-6-oxa-cyclopenta[a]naphthalen-3-yl ester | 4222-93-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Acetic acid (3S,3aS,9aS,9bS)-3a-ethyl-7-oxo-1,2,3,3a,4,7,8,9,9a,9b-decahydro-6-oxa-cyclopenta[a]naphthalen-3-yl ester
• CAS: 4222-93-9
• 化学式: C₁₆H₂₂O₄
• 分子量: 278.348
• InChiKey: NVNHQZYAESZFFE-DUPGQFARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Acetic acid (3S,3aS,9aS,9bS)-3a-ethyl-7-oxo-1,2,3,3a,4,7,8,9,9a,9b-decahydro-6-oxa-cyclopenta[a]naphthalen-3-yl ester 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 乙酸酐 、 lithium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 lithium bromide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.75h， 生成 (3S,3aS,9aS,9bS)-3a-Ethyl-3-hydroxy-6-methyl-1,2,3,3a,8,9,9a,9b-octahydro-cyclopenta[a]naphthalen-7-one
  参考文献：
  名称：

  Antiandrogenic activity of a series of des-A-steroid derivatives

  摘要：

  In the search for new antiandrogens, a number of des-A-steroids were prepared by condensation of Grignard reagents with lactone 3. From the resulting key intermediates 5, various structural modifications were performed such as the introduction of an additional unsaturation to afford dienones 8 and aromatic derivatives 10 or the introduction of an alkyl substituent mostly in position 10 (11-13) but also in some cases in position 16 (22). In addition, 13-ethyl analogues were also prepared from lactone 4. The relative binding affinities (RBAs) for the androgen receptor of these compounds were determined under various conditions. Some compounds exhibit a capacity to interact with the receptor comparable to that of testosterone. One of the most potent compounds is 17beta-hydroxy-des-A-androsta-9,11-dien-5-one (8b), RBA value 73% of that of testosterone. More interestingly, several compounds were found to have an antiandrogenic profile in vitro and in vivo. One of the most effective compounds is 10-ethyl-17beta-hydroxy-des-A-estra-9-en-5-one (5c), which exhibits a strong local antiandrogenic activity in hamsters, without any significant systemic antiandrogenic effects. The corresponding 17beta-acetyl derivative (RU 38882) has been selected for extended pharmacological studies.

  DOI：

  10.1021/jm00150a009