(3aR,7aS)-1-[(2R)-6-ethyl-5,5-difluoro-6-trimethylsilyloxyoctan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one | 212124-24-8

• 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)-6-ethyl-5,5-difluoro-6-trimethylsilyloxyoctan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one
• CAS: 212124-24-8
• 化学式: C₂₃H₄₀F₂O₂Si
• 分子量: 414.652
• InChiKey: NGSNEKSBOFBIEI-SLYNCCJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.15
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 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)-6-ethyl-5,5-difluoro-6-trimethylsilyloxyoctan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 6.17h， 生成
  参考文献：
  名称：

  Low-Calcemic, Highly Antiproliferative, 1-Difluoromethyl Hybrid Analogs of the Natural Hormone 1α,25-Dihydroxyvitamin D₃:  Design, Synthesis, and Preliminary Biological Evaluation

  摘要：

  Replacing the 1 alpha-OH group of the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (calcitriol) by a 1 alpha-CHF2 group and incorporating a potentiating side chain produced two new hybrid analogs 6 and 7. Both of these two hybrid analogs are as transcriptionally active as calcitriol and are strongly antiproliferative in vitro but are low-calcemic in vivo.

  DOI：

  10.1021/jm0609925
• 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 、 3 A molecular sieve 、 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 40.0h， 生成 (3aR,7aS)-1-[(2R)-6-ethyl-5,5-difluoro-6-trimethylsilyloxyoctan-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.
• Low-Calcemic, Highly Antiproliferative, 1-Difluoromethyl Hybrid Analogs of the Natural Hormone 1α,25-Dihydroxyvitamin D₃:  Design, Synthesis, and Preliminary Biological Evaluation
  作者：Sara Peleg、Kimberly S. Petersen、Byung Chul Suh、Patrick Dolan、Elin S. Agoston、Thomas W. Kensler、Gary H. Posner

  DOI：10.1021/jm0609925

  日期：2006.12.1

  Replacing the 1 alpha-OH group of the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (calcitriol) by a 1 alpha-CHF2 group and incorporating a potentiating side chain produced two new hybrid analogs 6 and 7. Both of these two hybrid analogs are as transcriptionally active as calcitriol and are strongly antiproliferative in vitro but are low-calcemic in vivo.