tert-butyl 2-(4-hydroxymethylphenylthio)-2-methylpropanoate | 1402394-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 2-(4-hydroxymethylphenylthio)-2-methylpropanoate
• 英文别名: Tert-butyl 2-[4-(hydroxymethyl)phenyl]sulfanyl-2-methylpropanoate；tert-butyl 2-[4-(hydroxymethyl)phenyl]sulfanyl-2-methylpropanoate
• CAS: 1402394-02-8
• 化学式: C₁₅H₂₂O₃S
• 分子量: 282.404
• InChiKey: WIZWSJCSNMXBKF-UHFFFAOYSA-N

物化性质

• 沸点：
  388.6±32.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(4-hydroxymethylphenylthio)-2-methylpropanoate 在 硼烷四氢呋喃络合物 、 六氯乙烷 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 生成 tert-butyl 2-(4-(2-(1-(4-cyclohexylbutyl)-3-(4-hydroxyphenyl)ureido)ethyl)phenylthio)-2-methylpropanoate
  参考文献：
  名称：

  Synthesis, radiolabeling and initial in vivo evaluation of [11C]KSM-01 for imaging PPAR-α receptors

  摘要：

  Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a ligand-activated nuclear receptor transcription factor that regulates the fatty acid beta-oxidation. An in vitro assay identified the p-methoxy phenyl ureido thiobutyric acid derivative KSM-01 (IC50 = 0.28 +/- 0.09 nM) having a higher affinity to activate PPAR-alpha than the PPAR-alpha agonist GW7647 (IC50 = 0.46 +/- 0.19 nM). In this study, we report the synthesis and initial in vivo evaluation of [C-11] KSM-01. The radiosynthesis was carried out by first alkylating the corresponding p-phenol precursor with [C-11]MeI in DMF using NaOH, followed by deprotection of the t-butyl ester group by TFA, yielding [C-11]KSM-01. SUV analysis of dynamic micro PET/CT imaging data showed that [C-11]KSM-01 accumulation was similar to 2.0-fold greater in cardiac-specific PPAR-alpha overexpressing transgenic mice compared to wild-type littermates. The post-PET biodistribution studies were consistent with these results and demonstrated 2.5-fold greater radiotracer uptake in the heart of transgenic mice compared to the wild-type littermates. These results demonstrate the potential utility of PPAR-alpha agonists as PET radiopharmaceuticals. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.010
• 作为产物：
  描述：

  4-巯基苯甲酸 在 lithium aluminium tetrahydride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 19.5h， 生成 tert-butyl 2-(4-hydroxymethylphenylthio)-2-methylpropanoate
  参考文献：
  名称：

  Synthesis, radiolabeling and initial in vivo evaluation of [11C]KSM-01 for imaging PPAR-α receptors

  摘要：

  Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a ligand-activated nuclear receptor transcription factor that regulates the fatty acid beta-oxidation. An in vitro assay identified the p-methoxy phenyl ureido thiobutyric acid derivative KSM-01 (IC50 = 0.28 +/- 0.09 nM) having a higher affinity to activate PPAR-alpha than the PPAR-alpha agonist GW7647 (IC50 = 0.46 +/- 0.19 nM). In this study, we report the synthesis and initial in vivo evaluation of [C-11] KSM-01. The radiosynthesis was carried out by first alkylating the corresponding p-phenol precursor with [C-11]MeI in DMF using NaOH, followed by deprotection of the t-butyl ester group by TFA, yielding [C-11]KSM-01. SUV analysis of dynamic micro PET/CT imaging data showed that [C-11]KSM-01 accumulation was similar to 2.0-fold greater in cardiac-specific PPAR-alpha overexpressing transgenic mice compared to wild-type littermates. The post-PET biodistribution studies were consistent with these results and demonstrated 2.5-fold greater radiotracer uptake in the heart of transgenic mice compared to the wild-type littermates. These results demonstrate the potential utility of PPAR-alpha agonists as PET radiopharmaceuticals. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.010