(8S,9S,13S,14S)-7,8,9,11,12,13,14,15-octahydro-2-adamantyl-3-hydroxy-13-methyl-6H-cyclopenta[a]phenanthrene-16-carboxylic acid

• 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: (8S,9S,13S,14S)-7,8,9,11,12,13,14,15-octahydro-2-adamantyl-3-hydroxy-13-methyl-6H-cyclopenta[a]phenanthrene-16-carboxylic acid
• 英文别名: MG 2778；(8S,9S,13S,14S)-2-(1-adamantyl)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthrene-16-carboxylic acid
• 化学式: C₂₉H₃₆O₃
• 分子量: 432.603
• InChiKey: BMPHHXLSHLLKNZ-SQKRYUCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-甲氧基雌酮 在 甲醇 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 sodium hydroxide 、 sodium thiomethoxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 正己烷 、 二氯甲烷 、 苯 为溶剂， 反应 103.0h， 生成 (8S,9S,13S,14S)-7,8,9,11,12,13,14,15-octahydro-2-adamantyl-3-hydroxy-13-methyl-6H-cyclopenta[a]phenanthrene-16-carboxylic acid
  参考文献：
  名称：

  Targeting RORs nuclear receptors by novel synthetic steroidal inverse agonists for autoimmune disorders

  摘要：

  Designing novel inverse agonists of NR ROR gamma t still represents a challenge for the pharmaceutical community to develop therapeutics for treating immune diseases. By exploring the structure of NRs natural ligands, the representative arotenoid ligands and RORs specific ligands share some chemical homologies which can be exploited to design a novel molecular structure characterized by a polycyclic core bearing a polar head and a hydrophobic tail. Compound MG 2778 (8), a cyclopenta[a]phenantrene derivative, was identified as lead compound which was chemically modified at position 2 in order to obtain a small library for preliminary SARs. Cell viability and estrogenic activity of compounds 7, 8, 19a, 30, 31 and 32 were evaluated to attest selectivity. The selected 7, 8, 19a and 31 compounds were assayed in a Gal4 UAS-Luc co-transfection system in order to determine their ability to modulate ROR gamma t activity in a cellular environment. They were evaluated as inverse agonists taken ursolic acid as reference compound. The potency of compounds was lower than that of ursolic acid, but their efficacy was similar. Compound 19a was the most active, significantly reducing ROR gamma t activity at low micromolar concentrations. (c) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.02.018