3-[(4bS,6aS,6bR,10S,11aR,11bR)-9-octyl-2-hydroxy-6a-methyl-8-oxo-4b,5,6,6a,6b,8,9,10,11a,11b,12,13-dodecahydronaphtho[2',1':4,5]indeno[2,1-e][1,3]oxazin-10-yl]benzamide

• 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-[(4bS,6aS,6bR,10S,11aR,11bR)-9-octyl-2-hydroxy-6a-methyl-8-oxo-4b,5,6,6a,6b,8,9,10,11a,11b,12,13-dodecahydronaphtho[2',1':4,5]indeno[2,1-e][1,3]oxazin-10-yl]benzamide
• 英文别名: 3-[(1R,2R,5S,9R,10S,13S)-17-hydroxy-10-methyl-6-octyl-7-oxo-8-oxa-6-azapentacyclo[11.8.0.02,10.04,9.014,19]henicosa-3,14(19),15,17-tetraen-5-yl]benzamide
• 化学式: C₃₅H₄₄N₂O₄
• 分子量: 556.745
• InChiKey: SXPITTNVHXHWFF-KOXALAKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-O-methoxymethylestrone 在 盐酸 、 sodium tetrahydroborate 、 水 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 potassium hydroxide 、 palladium dichloride 、 三氯氧磷 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 15.5h， 生成 3-[(4bS,6aS,6bR,10S,11aR,11bR)-9-octyl-2-hydroxy-6a-methyl-8-oxo-4b,5,6,6a,6b,8,9,10,11a,11b,12,13-dodecahydronaphtho[2',1':4,5]indeno[2,1-e][1,3]oxazin-10-yl]benzamide
  参考文献：
  名称：

  Identification of fused 16β,17β-oxazinone-estradiol derivatives as a new family of non-estrogenic 17β-hydroxysteroid dehydrogenase type 1 inhibitors

  摘要：

  A new family of cyclic carbamate-estradiol derivatives has been designed to remove the intrinsic estrogenic activity of a parent acyclic compound reported as a potent inhibitor of 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1). The synthesis of two series of fused 16 beta,17 beta-oxazinone-estradiol derivatives, saturated compounds 7a-d and unsaturated compounds 10a-d, led to the identification of 10b, a 17 beta-HSD1 inhibitor (IC50 = 1.4 mu M) without estrogenic activity in estrogen-sensitive T-47D cells. Interestingly, this compound was found selective over 17 beta-HSD2 and 17 beta-HSD12. A computational analysis of inhibitors into 17 beta-HSD1 by molecular docking also revealed interesting structure activity relationships that could be helpful in the design of new generation of 16 beta,17 beta-oxazinone-estradiol analogs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.059

文献信息

• Identification of fused 16β,17β-oxazinone-estradiol derivatives as a new family of non-estrogenic 17β-hydroxysteroid dehydrogenase type 1 inhibitors
  作者：René Maltais、Alexandre Trottier、Audrey Delhomme、Xavier Barbeau、Patrick Lagüe、Donald Poirier

  DOI：10.1016/j.ejmech.2015.01.059

  日期：2015.3

  A new family of cyclic carbamate-estradiol derivatives has been designed to remove the intrinsic estrogenic activity of a parent acyclic compound reported as a potent inhibitor of 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1). The synthesis of two series of fused 16 beta,17 beta-oxazinone-estradiol derivatives, saturated compounds 7a-d and unsaturated compounds 10a-d, led to the identification of 10b, a 17 beta-HSD1 inhibitor (IC50 = 1.4 mu M) without estrogenic activity in estrogen-sensitive T-47D cells. Interestingly, this compound was found selective over 17 beta-HSD2 and 17 beta-HSD12. A computational analysis of inhibitors into 17 beta-HSD1 by molecular docking also revealed interesting structure activity relationships that could be helpful in the design of new generation of 16 beta,17 beta-oxazinone-estradiol analogs. (C) 2015 Elsevier Masson SAS. All rights reserved.