2-(4-(2-氨基乙基)苯基硫代)-2-甲基丙酸叔丁酯 | 247923-33-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(4-(2-氨基乙基)苯基硫代)-2-甲基丙酸叔丁酯
• 英文名称: 1,1-dimethylethyl 2-[[4-(2-aminoethyl)phenyl]thio]-2-methyl-propanoate
• 英文别名: 2-[4-(aminoethyl)pheylsulfanyl]-2-methylpropionic acid tert-butyl ester；tert-butyl 2-[4-(2-aminoethyl)-phenylsulfanyl]-2-methylpropanoate；tert-butyl 2-(4-(2-aminoethyl)phenylthio)-2-methylpropanoate；t-Butyl 2-(4-(2-aminoethyl)phenylthio)-2-methylpropionate；tert-butyl 2-[4-(2-amino-ethyl)-phenylsulfanyl]-2-methyl-propionate；tert-butyl 2-[4-(2-aminoethyl)phenylthio]-2-methylpropionate；tert-butyl 2-[4-(2-aminoethyl)phenyl]sulfanyl-2-methylpropanoate
• CAS: 247923-33-7
• 化学式: C₁₆H₂₅NO₂S
• 分子量: 295.446
• InChiKey: RBWSVDKKZKPEHT-UHFFFAOYSA-N

物化性质

• 熔点：
  155-160 °C
• 沸点：
  393.0±32.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-(2-氨基乙基)苯基硫代)-2-甲基丙酸叔丁酯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 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-巯基苯甲醇 在 硼烷四氢呋喃络合物 、 六氯乙烷 、 三苯基膦 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 10.0h， 生成 2-(4-(2-氨基乙基)苯基硫代)-2-甲基丙酸叔丁酯
  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

文献信息

• Propionic acid derivatives
  申请人：——

  公开号：US20030032671A1

  公开（公告）日：2003-02-13

  The present application relates to novel potent PPAR-alpha-activating compounds for treating, for example, coronary heart disease, and to their preparation.

  本申请涉及用于治疗冠心病等疾病的新型有效的PPAR-alpha激活化合物及其制备。
• A Facile One-Pot Preparation of Alkyl Aminoaryl Sulfides for the Synthesis of GW7647 as an Agonist of Peroxisome Proliferator-Activated Receptor α
  作者：Jungyeob Ham、Sung Jin Cho、Jaeyoung Ko、Jungwook Chin、Heonjoong Kang

  DOI：10.1021/jo060361i

  日期：2006.7.1

  We have developed two simple and high yielding one-pot syntheses of alkyl aminoaryl sulfides containing a series of four-steps: in situ protection of the free amine by reaction with a Grignard reagent, halogen−lithium exchange, sulfur insertion, and a substitution reaction with various electrophiles. Through this protocol, we have successfully synthesized tert-butyl-2-[4-(2-aminoethyl)phenylsulfan

  我们开发了两个简单且高产率的一锅合成烷基氨基芳基硫醚，包含一系列四个步骤：通过与格氏试剂的反应原位保护游离胺，卤素-锂交换，硫插入和取代反应与各种亲电试剂。通过该方案，我们以92％的收率成功合成了叔丁基-2- [4-（2-（2-氨基乙基）苯基硫烷基] -2-甲基丙酸酯，这是合成GW7647和GW9578（脲基TiBAs）的关键中间体。此外，我们能够将GW7647的总产量提高到66％，是先前报道的产量的3倍。
• Process for Preparing the Intermediate Compounds for Pparalpha Ligands
  申请人：Kang Heonjoong

  公开号：US20080269516A1

  公开（公告）日：2008-10-30

  The present invention provides a process for preparing the compounds of formula (II) according to a single reaction, which is an important intermediate compound for synthesizing GW7647 (III) and GW9578 (IV) activating Peroxisome Proliferator Activated Receptor (HPPAR α).

  本发明提供了一种制备式化合物的方法（II），该方法根据单一反应进行，这是合成GW7647（III）和GW9578（IV）激活过氧化物酶体增殖激活受体（HPPAR α）的重要中间化合物。
• Novel and Efficient Synthesis of <i>tert</i>-Butyl-2-(4-(2-aminoethyl)phenylthio)-2-methylpropanoate, a Key Intermediate in the Synthesis of Ureido Thioisobutyric Acid
  作者：Jigar Desai、Anil Argade、Sanjay Gite、Kiran Shah、Laxmikant Pavase、Pravin Thombare、Pankaj Patel

  DOI：10.1080/00397911003644399

  日期：2011.2.7

  [image omitted] A convenient and cost-effective synthesis of pharmacologically important tert-butyl-2-(4-2-aminoethyl)phenylthio)-2-methylpropanoate from commercially available 2-2-phenyl-1-ethanol is described.
• A Ureido-Thioisobutyric Acid (GW9578) Is a Subtype-Selective PPARα Agonist with Potent Lipid-Lowering Activity
  作者：Peter J. Brown、Deborah A. Winegar、Kelli D. Plunket、Linda B. Moore、Michael C. Lewis、Joan G. Wilson、Scott S. Sundseth、Cecilia S. Koble、Zhengdong Wu、James M. Chapman、Jürgen M. Lehmann、Steven A. Kliewer、Timothy M. Willson

  DOI：10.1021/jm9903601

  日期：1999.9.1