(9R,10R)-9,10-dihydroxy-2,5,8,8-tetramethyl-9,10-dihydro-4H,8H-pyrano[2,3-f]chromen-4-one | 1253850-16-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (9R,10R)-9,10-dihydroxy-2,5,8,8-tetramethyl-9,10-dihydro-4H,8H-pyrano[2,3-f]chromen-4-one
• CAS: 1253850-16-6
• 化学式: C₁₆H₁₈O₅
• 分子量: 290.316
• InChiKey: LGEOGQPABOAMJD-UKRRQHHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  21.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79.9
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (9R,10R)-9,10-dihydroxy-2,5,8,8-tetramethyl-9,10-dihydro-4H,8H-pyrano[2,3-f]chromen-4-one 、 (1S)-(-)-莰烷酰氯 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以54%的产率得到[(9R,10R)-2,5,8,8-tetramethyl-4-oxo-9-[(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl]oxy-9,10-dihydropyrano[2,3-h]chromen-10-yl] (1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate
  参考文献：
  名称：

  Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure–activity relationships of novel dicamphanoyl-2′,2′-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents

  摘要：

  In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIV(NL4-3) with EC(50) and therapeutic index (TI) values ranging from 0.036 mu M to 0.14 mu M and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC(50) 0.049 and 0.054 mu M; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC(50) 0.11 and 0.19 mu M; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.065
• 作为产物：
  描述：

  2,5,8,8-tetramethyl-4H,8H-pyrano[2,3-f]chromen-4-one 在 potassium osmate(VI) dihydrate 、 (8a,9R,8′′′a,9′′′R)-9,9′-[(2,5-diphenylpyrimidine-4,6-diyl)bis(oxy)]bis(6′-methoxy-10,11-dihydrocinchonan) 、 甲基磺酰胺 、 potassium carbonate 、 potassium hexacyanoferrate(III) 作用下， 以 水 、 叔丁醇 为溶剂， 生成 (9R,10R)-9,10-dihydroxy-2,5,8,8-tetramethyl-9,10-dihydro-4H,8H-pyrano[2,3-f]chromen-4-one
  参考文献：
  名称：

  Anti-AIDS agents 89. Identification of DCX derivatives as anti-HIV and chemosensitizing dual function agents to overcome P-gp-mediated drug resistance for AIDS therapy

  摘要：

  In this study, 19 dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-dihydropyranoxanth-one (DCX) derivatives, previously discovered as novel anti-HIV agents, were evaluated for their potential to reverse multi-drug resistance (MDR) in a cancer cell line over-expressing P-glycoprotein (P-gp). Seven compounds fully reversed resistance to vincristine (VCR) at 4 mu M, a 20-fold enhancement compared to the first generation chemosensitizer, verapamil (4 mu M). The mechanism of action of DCPs and DCXs was also resolved, since the most active compounds (3, 4, and 7) significantly increased intracellular drug accumulation due, in part, to inhibiting the P-gp mediated drug efflux from cells. We conclude that DCPs (3 and 4) and DCXs (7, 11, and 17) can exhibit polypharmacologic behavior by acting as dual inhibitors of HIV replication and chemoresistance mediated by P-gp. As such, they may be useful in combination therapy to overcome P-gp-associated drug resistance for AIDS treatment. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.037