(3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-3-(((4-(trifluoromethyl)benzyl)amino)methyl)hexadecahydro-17H-cyclopenta[a]phenanthren-17-one | 1326702-92-4

• 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: (3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-3-(((4-(trifluoromethyl)benzyl)amino)methyl)hexadecahydro-17H-cyclopenta[a]phenanthren-17-one
• CAS: 1326702-92-4
• 化学式: C₂₈H₃₈F₃NO₂
• 分子量: 477.61
• InChiKey: GDGUCUAZAZFFSJ-KGURPWLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.14
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  49.33
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  三光气 、 (3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-3-(((4-(trifluoromethyl)benzyl)amino)methyl)hexadecahydro-17H-cyclopenta[a]phenanthren-17-one 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以43%的产率得到(3R,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-3'-[4-(trifluoromethyl)benzyl]tetradecahydro-2'H-spiro[cyclopenta[a]phenanthrene-3,5'-[1,3]oxazolidine]-2',17(2H)-dione
  参考文献：
  名称：

  Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3

  摘要：

  17Beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) is a steroidogenic enzyme that catalyzes the transformation of 4-androstene-3,17-dione (Delta(4)-dione) into androgen testosterone (T). To provide effective inhibitors of androgen biosynthesis, we synthesized two different series (amines and carbamates) of 3 beta-substituted-androsterone derivatives and we tested their inhibitory activity on 17 beta-HSD3. From the results of our structure-activity relationship study, we identified a series of compounds producing a strong inhibition of 17 beta-HSD3 overexpressed in HEK-293 cells (homogenized cells). The most active compound when tested in intact HEK-293 transfected cells, namely (3 alpha,5 alpha)-3-{[trans-2,5-dimethyl-4-{[2-(trifluoromethyl)phenyl] sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17-one (15b), shows an IC50 value of 6 nM, this compound is thus eight times more active than our reference compound D-5-2 (IC50 = 51 nM). This new improved inhibitor did not stimulate the proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic profile. Compound 15b is thus a good candidate for further in vivo studies on rodents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.003
• 作为产物：
  描述：

  spiro-3(R)-oxirane-5α-androstan-17-one 、 4-(三氟甲基)苄胺 以 乙醇 为溶剂， 生成 (3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-3-(((4-(trifluoromethyl)benzyl)amino)methyl)hexadecahydro-17H-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3

  摘要：

  17Beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) is a steroidogenic enzyme that catalyzes the transformation of 4-androstene-3,17-dione (Delta(4)-dione) into androgen testosterone (T). To provide effective inhibitors of androgen biosynthesis, we synthesized two different series (amines and carbamates) of 3 beta-substituted-androsterone derivatives and we tested their inhibitory activity on 17 beta-HSD3. From the results of our structure-activity relationship study, we identified a series of compounds producing a strong inhibition of 17 beta-HSD3 overexpressed in HEK-293 cells (homogenized cells). The most active compound when tested in intact HEK-293 transfected cells, namely (3 alpha,5 alpha)-3-{[trans-2,5-dimethyl-4-{[2-(trifluoromethyl)phenyl] sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17-one (15b), shows an IC50 value of 6 nM, this compound is thus eight times more active than our reference compound D-5-2 (IC50 = 51 nM). This new improved inhibitor did not stimulate the proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic profile. Compound 15b is thus a good candidate for further in vivo studies on rodents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.003