ethyl (5R)-5-[(3aR,4S,7aS)-7a-methyl-4-triethylsilyloxy-3,3a,4,5,6,7-hexahydroinden-1-yl]-2,2-difluoro-3-hydroxyhexanoate | 212123-96-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: ethyl (5R)-5-[(3aR,4S,7aS)-7a-methyl-4-triethylsilyloxy-3,3a,4,5,6,7-hexahydroinden-1-yl]-2,2-difluoro-3-hydroxyhexanoate
• CAS: 212123-96-1
• 化学式: C₂₄H₄₂F₂O₄Si
• 分子量: 460.677
• InChiKey: DPUNHCLILJEJFT-ORUUTUCSSA-N

物化性质

• 沸点：
  498.1±45.0 °C(predicted)
• 密度：
  1.06±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl (5R)-5-[(3aR,4S,7aS)-7a-methyl-4-triethylsilyloxy-3,3a,4,5,6,7-hexahydroinden-1-yl]-2,2-difluoro-3-hydroxyhexanoate 在 吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 23.0h， 生成 ethyl (5R)-5-[(3aR,4S,7aS)-7a-methyl-4-triethylsilyloxy-3,3a,4,5,6,7-hexahydroinden-1-yl]-2,2-difluorohexanoate
  参考文献：
  名称：

  Noncalcemic, Antiproliferative, Transcriptionally Active, 24-Fluorinated Hybrid Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃. Synthesis and Preliminary Biological Evaluation

  摘要：

  Four new hybrid analogues of 1 alpha,25-dihydroxyvitamin D-3 (1) have been synthesized in a convergent manner by joining A-ring and C,D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side chain, was designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analogue with 1 beta,3 alpha-substituent stereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically desirable combination of in vitro high antiproliferative activity in two different cell lines and high transcriptional activity with also low calcemic activity in vivo.

  DOI：

  10.1021/jm980031t
• 作为产物：
  描述：

  (R)-3-((3aR,4S,7aS)-7a-Methyl-4-triethylsilanyloxy-3a,4,5,6,7,7a-hexahydro-3H-inden-1-yl)-butyronitrile 在 二异丁基氢化铝 、 锌 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 ethyl (5R)-5-[(3aR,4S,7aS)-7a-methyl-4-triethylsilyloxy-3,3a,4,5,6,7-hexahydroinden-1-yl]-2,2-difluoro-3-hydroxyhexanoate
  参考文献：
  名称：

  Noncalcemic, Antiproliferative, Transcriptionally Active, 24-Fluorinated Hybrid Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃. Synthesis and Preliminary Biological Evaluation

  摘要：

  Four new hybrid analogues of 1 alpha,25-dihydroxyvitamin D-3 (1) have been synthesized in a convergent manner by joining A-ring and C,D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side chain, was designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analogue with 1 beta,3 alpha-substituent stereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically desirable combination of in vitro high antiproliferative activity in two different cell lines and high transcriptional activity with also low calcemic activity in vivo.

  DOI：

  10.1021/jm980031t

文献信息

• Noncalcemic, Antiproliferative, Transcriptionally Active, 24-Fluorinated Hybrid Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃. Synthesis and Preliminary Biological Evaluation
  作者：Gary H. Posner、Jae Kyoo Lee、Qiang Wang、Sara Peleg、Martin Burke、Henry Brem、Patrick Dolan、Thomas W. Kensler

  DOI：10.1021/jm980031t

  日期：1998.7.1

  Four new hybrid analogues of 1 alpha,25-dihydroxyvitamin D-3 (1) have been synthesized in a convergent manner by joining A-ring and C,D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side chain, was designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analogue with 1 beta,3 alpha-substituent stereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically desirable combination of in vitro high antiproliferative activity in two different cell lines and high transcriptional activity with also low calcemic activity in vivo.