(3R,5S,7R,10S,11S,13R)-11-((ethoxycarbonyl)amino)-17-((R)-5-methoxy-5-oxopentan-2-yl)-10,13-dimethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diyl diacetate

• 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,7R,10S,11S,13R)-11-((ethoxycarbonyl)amino)-17-((R)-5-methoxy-5-oxopentan-2-yl)-10,13-dimethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diyl diacetate
• 英文别名: (3R,5S,7R,8S,9S,10S,11S,13R,14S,17R)-11-(ethoxycarbonylamino)-17-[(R)-5-methoxy-5-oxopentan-2-yl]-10,13-dimethyl-12-oxo-hexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diyl diacetate；methyl (4R)-4-[(3R,5S,7R,8S,9S,10S,11S,13R,14S,17R)-3,7-diacetyloxy-11-(ethoxycarbonylamino)-10,13-dimethyl-12-oxo-1,2,3,4,5,6,7,8,9,11,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• 化学式: C₃₂H₄₉NO₉
• 分子量: 591.742
• InChiKey: AJDBZNBFWMRPBR-QPQVPFOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  胆酸甲酯 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 Jones reagent 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 溴 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 、 苯 为溶剂， -20.0~60.0 ℃ 、275.8 kPa 条件下， 反应 165.08h， 生成 (3R,5S,7R,10S,11S,13R)-11-((ethoxycarbonyl)amino)-17-((R)-5-methoxy-5-oxopentan-2-yl)-10,13-dimethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diyl diacetate
  参考文献：
  名称：

  [EN] 11 -SUBSTITUTED BILE ACID DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND USE OF THESE COMPOUNDS AS MEDICAMENTS
  [FR] DÉRIVÉS D'ACIDES BILIAIRES 11-SUBSTITUÉS, LEUR PROCÉDÉ DE PRÉPARATION ET UTILISATION DE CES COMPOSÉS À TITRE DE MÉDICAMENTS

  摘要：

  本发明公开了一种在C-11处具有取代氮功能的新型胆酸衍生物，以及其合成方法。这些C-11取代的胆酸衍生物表现出抗癌和抗结核活性。

  公开号：

  WO2015087340A1

文献信息

• Design and synthesis of 11α-substituted bile acid derivatives as potential anti-tuberculosis agents
  作者：Vandana S. Pore、Jaisingh M. Divse、Chaitanya R. Charolkar、Laxman U. Nawale、Vijay M. Khedkar、Dhiman Sarkar

  DOI：10.1016/j.bmcl.2015.08.006

  日期：2015.10

  We have synthesized a series of novel 11 alpha-triazoyl bile acid derivatives. In addition, we also have synthesized N-alkyl and N-acyl derivatives of C-11 amino bile acid esters. All the compounds were evaluated for the inhibitory activity against Mycobacterium tuberculosis H37Ra (MTB) at 30 mu g/mL level. Four lead compounds (2b, 3, 7 and 8) were further confirmed from their dose dependent effect against MTB. These compounds were found to be active against Dormant and active stage MTB under both in vitro as well as within THP1 host macrophages. The most promising compound 2b showed strong antitubercular activities against MTB under in vitro and ex vivo (IC90 value of similar to 3 mu g/mL) conditions and almost insignificant cytotoxicity up to 100 mu g/mL against THP-1, A549 and PANC-1 human cancer cell lines. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity. Molecular docking studies of these compounds into the active site of DprE1 enzyme revealed a similar binding mode to native ligands in the crystal structure thereby helping to establish a structural basis of inhibition of MTB. The synthesized compounds were analyzed for ADME properties and showed potential to develop good oral drug candidates. Our results clearly indicate the identification of some novel, selective and specific inhibitors against MTB that can be explored further for potential antitubercular drug. (C) 2015 Elsevier Ltd. All rights reserved.