(2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester | 757247-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxy-ethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidine-1-carboxylate
• CAS: 757247-80-6
• 化学式: C₁₇H₃₂F₃NO₄Si
• 分子量: 399.526
• InChiKey: CCNBBWSXXUDYKB-AGIUHOORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester 在 potassium tert-butylate 、 N,N-二异丙基乙胺 、 对甲苯磺酰氯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-[(1R,7R,7aR)-7-[tert-butyl(dimethyl)silyl]oxy-3-oxo-1-(trifluoromethyl)-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
  参考文献：
  名称：

  Discovery of Potent and Muscle Selective Androgen Receptor Modulators through Scaffold Modifications

  摘要：

  A novel series of imidazolin-2-ones were designed and synthesized as highly potent, orally active and muscle selective androgen receptor modulators (SARMs), with most of the compounds exhibiting low nM in vitro potency in androgen receptor (AR) binding and functional assays. Once daily oral treatment with the lead compound 11a (AR K-i = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in rats demonstrated that the lead compound 11a had oral bioavailability of 65% and a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the SARMs in this series are expected to provide beneficial anabolic effects on muscle with minimal androgenic effects on prostate tissue.

  DOI：

  10.1021/jm070312d
• 作为产物：
  描述：

  (2S,3R)-N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine 在 四丙基高钌酸铵 N-甲基吗啉氧化物 、 cesium fluoride 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 33.0h， 生成 (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(2,2,2-trifluoro-1-hydroxyethyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of Potent and Muscle Selective Androgen Receptor Modulators through Scaffold Modifications

  摘要：

  A novel series of imidazolin-2-ones were designed and synthesized as highly potent, orally active and muscle selective androgen receptor modulators (SARMs), with most of the compounds exhibiting low nM in vitro potency in androgen receptor (AR) binding and functional assays. Once daily oral treatment with the lead compound 11a (AR K-i = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in rats demonstrated that the lead compound 11a had oral bioavailability of 65% and a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the SARMs in this series are expected to provide beneficial anabolic effects on muscle with minimal androgenic effects on prostate tissue.

  DOI：

  10.1021/jm070312d