17α-O-[2’(R)]tetrahydropyranyloxypregn-4-ene-3,20-dione | 1312467-41-6

• 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: 17α-O-[2’(R)]tetrahydropyranyloxypregn-4-ene-3,20-dione
• 英文别名: 17α-O-[2'(R)]tetrahydropyranyl-5β-pregn-4-ene-3,20-dione；(8R,9S,10R,13S,14S,17R)-17-acetyl-10,13-dimethyl-17-[(2R)-oxan-2-yl]oxy-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 1312467-41-6
• 化学式: C₂₆H₃₈O₄
• 分子量: 414.585
• InChiKey: VITNBFPRGNLXMN-CMDGYKDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 、 17Alpha-羟基黄体酮 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 168.0h， 以19%的产率得到17α-O-[2’(R)]tetrahydropyranyloxypregn-4-ene-3,20-dione
  参考文献：
  名称：

  [EN] NEW STEROID INHIBITORS OF PGP FOR USE FOR INHIBITING MULTIDRUG RESISTANCE
  [FR] NOUVEAUX INHIBITEURS STÉROÏDIENS DE PGP POUR EMPLOI DANS L'INHIBITION DE LA RÉSISTANCE PLÉIOTROPE

  摘要：

  本发明涉及一种化合物，其化学式为(I)，用于逆转或抑制多药耐药。

  公开号：

  WO2011073419A1

文献信息

• Synthesis of New Steroidal Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance and Biological Evaluation on K562/R7 Erythroleukemia Cells
  作者：Marc Rolland de Ravel、Ghina Alameh、Maxime Melikian、Zahia Mahiout、Agnès Emptoz-Bonneton、Eva-Laure Matera、Thierry Lomberget、Roland Barret、Luc Rocheblave、Nadia Walchshofer、Sonia Beltran、Lucienne El Jawad、Elisabeth Mappus、Catherine Grenot、Michel Pugeat、Charles Dumontet、Marc Le Borgne、Claude Yves Cuilleron

  DOI：10.1021/jm501676v

  日期：2015.2.26

  A simple route for improving the potency of progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification or etherification of hydroxylated 5 alpha/beta-pregnane-3,20-dione or 5 beta-cholan-3-one precursors. X-ray crystallography of representative 7 alpha-, 11 alpha-, and 17 alpha-(2'R/S)-O-tetrahydropyranyl ether diastereoisomers revealed different combinations of axial-equatorial configurations of the anomeric oxygen. Substantial stimulation of accumulation and chemosensitization was observed on K562/R7 erythroleukemia cells resistant to doxorubicin, especially using 7 alpha,11 alpha-O-disubstituted derivatives of 5 alpha/beta-pregnane-3,20-dione, among which the 5 beta-H-7 alpha-benzoyloxy-11 alpha-(2'R)-O-tetrahydropyranyl ether 22a revealed promising properties (accumulation index 2.9, IC50 0.5 mu M versus 1.2 and 10.6 mu M for progesterone), slightly overcoming those of verapamil and cyclosporin A. Several 7 alpha,12 alpha-O-disubstituted derivatives of 5 beta-cholan-3-one proved even more active, especially the 7 alpha-O-methoxymethyl-12 alpha-benzoate 56 (accumulation index 3.8, IC50 0.2 mu M). The panel of modulating effects from different O-substitutions at a same position suggests a structural influence of the substituent completing a simple protection against stimulating effects of hydroxyl groups on P-gp-mediated transport.