ethyl (3-benzyloxy-17-oxoestra-1,3,5(10)-trien-16α-yl)acetate | 345294-87-3

• 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: ethyl (3-benzyloxy-17-oxoestra-1,3,5(10)-trien-16α-yl)acetate
• 英文别名: ethyl 2-[(8R,9S,13S,14S,16S)-13-methyl-17-oxo-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-16-yl]acetate
• CAS: 345294-87-3
• 化学式: C₂₉H₃₄O₄
• 分子量: 446.587
• InChiKey: WEHIYQNPNGPDBB-BBFXAVQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (3-benzyloxy-17-oxoestra-1,3,5(10)-trien-16α-yl)acetate 在 氯化亚砜 、 lithium tri-t-butoxyaluminum hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 11.75h， 生成 methyl (3-benzyloxy-17β-hydroxyestra-1,3,5(10)-trien-16α-yl)acetate
  参考文献：
  名称：

  Estradiol-16α-carboxylic Acid Esters as Locally Active Estrogens

  摘要：

  We attempted to design analogues of estradiol to act as locally active estrogens without significant systemic action. We synthesized a series of 16a-carboxylic acid substituted steroids and their esters and tested their action in several assays of estrogenic action, including estrogen receptor (ER) binding, estrogenic potency in Ishikawa cells (human endometrial carcinoma), rat uterine weight (systemic action), and mouse vaginal reductases (local action). All of the estradiol substituted carboxylic acids (formic, acetic and propionic acids) were devoid of estrogenic action. To the contrary, many of the esters had marked estrogenic potency in the receptor and the Ishikawa assays. The esters of the 16 alpha -formic acid series had the highest ER affinity with little difference between the straight-chain alcohol esters (from methyl to n-butyl). However, estrogenic action in the Ishikawa assay decreased precipitously with esters longer than the ethyl ester. This decrease correlated well with the increased rate of esterase hydrolysis of longer esters as determined in incubations with rat hepatic microsomes. The most promising candidates, the methyl, ethyl, and fluoroethyl esters of the formate series, were tested for systemic and local action in the in vivo models. All three, especially the fluoroethyl ester, showed divergence between systemic and local estrogenic action. These metabolically labile estrogens will be extremely useful for the therapeutic treatment of the vaginal dyspareunia of menopause in women for whom systemic estrogens are contraindicated.

  DOI：

  10.1021/jm000523h
• 作为产物：
  描述：

  3-O-苄基雌酮 、 溴乙酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 7.5h， 以35%的产率得到ethyl (3-benzyloxy-17-oxoestra-1,3,5(10)-trien-16α-yl)acetate
  参考文献：
  名称：

  Estradiol-16α-carboxylic Acid Esters as Locally Active Estrogens

  摘要：

  We attempted to design analogues of estradiol to act as locally active estrogens without significant systemic action. We synthesized a series of 16a-carboxylic acid substituted steroids and their esters and tested their action in several assays of estrogenic action, including estrogen receptor (ER) binding, estrogenic potency in Ishikawa cells (human endometrial carcinoma), rat uterine weight (systemic action), and mouse vaginal reductases (local action). All of the estradiol substituted carboxylic acids (formic, acetic and propionic acids) were devoid of estrogenic action. To the contrary, many of the esters had marked estrogenic potency in the receptor and the Ishikawa assays. The esters of the 16 alpha -formic acid series had the highest ER affinity with little difference between the straight-chain alcohol esters (from methyl to n-butyl). However, estrogenic action in the Ishikawa assay decreased precipitously with esters longer than the ethyl ester. This decrease correlated well with the increased rate of esterase hydrolysis of longer esters as determined in incubations with rat hepatic microsomes. The most promising candidates, the methyl, ethyl, and fluoroethyl esters of the formate series, were tested for systemic and local action in the in vivo models. All three, especially the fluoroethyl ester, showed divergence between systemic and local estrogenic action. These metabolically labile estrogens will be extremely useful for the therapeutic treatment of the vaginal dyspareunia of menopause in women for whom systemic estrogens are contraindicated.

  DOI：

  10.1021/jm000523h

文献信息

• [EN] 17BETA-HYDROXYSTEROID DEHYDROGENASE INHIBITORS<br/>[FR] COMPOSE
  申请人：STERIX LTD

  公开号：WO2004085457A3

  公开（公告）日：2005-02-03
• Estradiol-16α-carboxylic Acid Esters as Locally Active Estrogens
  作者：David C. Labaree、Toni Y. Reynolds、Richard B. Hochberg

  DOI：10.1021/jm000523h

  日期：2001.5.1

  We attempted to design analogues of estradiol to act as locally active estrogens without significant systemic action. We synthesized a series of 16a-carboxylic acid substituted steroids and their esters and tested their action in several assays of estrogenic action, including estrogen receptor (ER) binding, estrogenic potency in Ishikawa cells (human endometrial carcinoma), rat uterine weight (systemic action), and mouse vaginal reductases (local action). All of the estradiol substituted carboxylic acids (formic, acetic and propionic acids) were devoid of estrogenic action. To the contrary, many of the esters had marked estrogenic potency in the receptor and the Ishikawa assays. The esters of the 16 alpha -formic acid series had the highest ER affinity with little difference between the straight-chain alcohol esters (from methyl to n-butyl). However, estrogenic action in the Ishikawa assay decreased precipitously with esters longer than the ethyl ester. This decrease correlated well with the increased rate of esterase hydrolysis of longer esters as determined in incubations with rat hepatic microsomes. The most promising candidates, the methyl, ethyl, and fluoroethyl esters of the formate series, were tested for systemic and local action in the in vivo models. All three, especially the fluoroethyl ester, showed divergence between systemic and local estrogenic action. These metabolically labile estrogens will be extremely useful for the therapeutic treatment of the vaginal dyspareunia of menopause in women for whom systemic estrogens are contraindicated.