(3aR,7aS)-1-[(2R)-5,5-difluoro-6-methyl-6-trimethylsilyloxyheptan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one | 212124-18-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (3aR,7aS)-1-[(2R)-5,5-difluoro-6-methyl-6-trimethylsilyloxyheptan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one
• CAS: 212124-18-0
• 化学式: C₂₁H₃₆F₂O₂Si
• 分子量: 386.598
• InChiKey: WKXPCGSSHAXTDL-OXFYSEKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.37
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3aR,7aS)-1-[(2R)-5,5-difluoro-6-methyl-6-trimethylsilyloxyheptan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one 在 四丁基氟化铵 、 苯基锂 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 生成 JK-1624-F2-2
  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 吡啶 、 重铬酸吡啶 、 偶氮二异丁腈 、 Celite 、 四丁基氟化铵 、 三正丁基氢锡 、 二异丁基氢化铝 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 59.5h， 生成 (3aR,7aS)-1-[(2R)-5,5-difluoro-6-methyl-6-trimethylsilyloxyheptan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one
  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.