2-[(14)C]ethyl bromoacetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[(14)C]ethyl bromoacetate
• 英文别名: ethyl bromo(2-(14)C)acetate；ethyl bromo[2-14C]acetate；2-[(14)C]BrCH2CO2Et；ethyl 2-bromoacetate
• 化学式: C₄H₇BrO₂
• 分子量: 168.991
• InChiKey: PQJJJMRNHATNKG-YZRHJBSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  7
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-硝基咪唑 、 2-[(14)C]ethyl bromoacetate 在 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 Ethyl 2-(2-nitroimidazol-1-yl)acetate
  参考文献：
  名称：

  [14C]-依他硝唑的体内药代动力学

  摘要：

  与其他硝基芳族放射增敏剂一样，依他硝唑主要通过两个分子基团显示其生物活性：硝基基团和连接到咪唑环 1 位氮上的侧链。 为了监测这两个部分在体内的行为，标记为制备了侧链第 2 位含有一个 14C 原子的依他硝唑，并以 2 gm-2 的剂量给予四名患者：通过极谱法滴定 NO2 组或测定不同的体液和组织中依他硝唑的浓度。侧链携带的总放射性。在血液和尿液中发现了两种不同的依他硝唑浓度曲线，如通过两种方法确定的。发现以总放射性测量时的浓度高于通过极谱法测量时的浓度；这种差异在血液中 (49%) 大于在尿液中 (27%)。由于这两种方法涉及测定依他硝唑分子的不同部分，我们假设药物的降解来解释这些差异。

  DOI：

  10.1002/jlcr.2580340502
• 作为产物：
  描述：

  2-溴-乙酸-2-14C 、 乙醇 、 氯化亚砜 以74%的产率得到
  参考文献：
  名称：

  HARTMAN, J. D.;HUANG, C. C.;BUTLER, D. E., J. LABELLED COMPOUNDS AND RADIOPHARM., 1984, 21, N 4, 347-352

  摘要：

  DOI：

文献信息

• [14C] and [3H]-labelling of Ragaglitazar: A dual acting PPAR? and PPAR? agonist with hypolipidemic and anti-diabetic activity
  作者：Jesper B. Kristensen、Steen K. Johansen、Jacob S. Valsborg、Lars Martiny、Christian Foged

  DOI：10.1002/jlcr.690

  日期：2003.4

  Currently, Ragaglitazar is being developed as a drug for the treatment of hyperglycaemia and hyperlipidemia in patients with type 2 diabetes. Here, we report the labelling of Ragaglitazar with carbon-14 and tritium for in vivo and in vitro investigations. Two different carbon-14 labelled as well as two different tritium labelled tracers of Ragaglitazar were synthesised. The carbon-14 label was introduced from either ethyl bromo[2-14C]acetate (5 steps/33% overall yield) or [U-14C]phenoxazine (4 steps/48% overall yield). Tritium was incorporated either by catalytic tritiation of an alkene precursor followed by chiral HPLC separation (2 steps/17% overall yield) or by catalytic tritium–halogen exchange of an aryl bromide precursor (2 steps/68% overall yield). Copyright © 2003 John Wiley & Sons, Ltd.

  目前，Ragaglitazar正在开发作为治疗2型糖尿病患者高血糖和高脂血症的药物。我们在此报告了Ragaglitazar的碳-14和氚标记，以便进行体内和体外研究。合成了两种不同的碳-14标记以及两种不同的氚标记的Ragaglitazar示踪剂。碳-14标记是通过乙基溴[2-14C]醋酸酯（5个步骤/总产率33%）或[U-14C]苯咯唑（4个步骤/总产率48%）引入的。氚的引入则是通过对烯烃前体的催化氚化反应后再进行手性HPLC分离（2个步骤/总产率17%），或通过芳基溴化物前体的催化氚-卤素交换（2个步骤/总产率68%）进行的。版权 © 2003 John Wiley & Sons, Ltd.
• Synthesis of BMS-309403-Related Compounds, Including [14C]BMS-309403, a Radioligand for Adipocyte Fatty Acid Binding Protein
  作者：Toshihiko Okada、Makoto Hiromura、Masato Otsuka、Shuichi Enomoto、Hiroyuki Miyachi

  DOI：10.1248/cpb.60.164

  日期：——

  Adipocyte fatty acid binding protein (A-FABP; FABP4), which is predominantly expressed in macrophages and adipose tissue, regulates fatty acid storage and lipolysis, and is also an important mediator of inflammation. Here, we report a synthesis of 14C-labeled 2-[2′-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy]acetic acid (BMS309403), a potent and selective small-molecular FABP4 inhibitor, as a chemical tool for investigating the roles of FABP4 in inflammatory and metabolic disorders. The structure–activity relationship of several BMS derivatives for inhibition of FABP4 is also reported.

  脂肪细胞脂肪酸结合蛋白（A-FABP；FABP4）主要在巨噬细胞和脂肪组织中表达，调节脂肪酸储存和脂肪分解，也是炎症的重要介质。这里，我们报告了一种 14C 标记的 2-[2′-(5-乙基-3,4-二苯基-1H-吡唑-1-基)联苯-3-基氧基]乙酸（BMS309403）的合成，这是一种强效、选择性的小分子 FABP4 抑制剂，是研究 FABP4 在炎症和代谢紊乱中作用的化学工具。报告还介绍了几种 BMS 衍生物抑制 FABP4 的结构-活性关系。
• Development of a Liver-Targeted Stearoyl-CoA Desaturase (SCD) Inhibitor (MK-8245) to Establish a Therapeutic Window for the Treatment of Diabetes and Dyslipidemia
  作者：Renata M. Oballa、Liette Belair、W. Cameron Black、Kelly Bleasby、Chi Chung Chan、Carole Desroches、Xiaobing Du、Robert Gordon、Jocelyne Guay、Sebastien Guiral、Michael J. Hafey、Emelie Hamelin、Zheng Huang、Brian Kennedy、Nicolas Lachance、France Landry、Chun Sing Li、Joseph Mancini、Denis Normandin、Alessandro Pocai、David A. Powell、Yeeman K. Ramtohul、Kathryn Skorey、Dan Sørensen、Wayne Sturkenboom、Angela Styhler、Deena M. Waddleton、Hao Wang、Simon Wong、Lijing Xu、Lei Zhang

  DOI：10.1021/jm200319u

  日期：2011.7.28

  The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ believed to be responsible for the therapeutic efficacy (liver) while minimizing its exposure in the tissues associated with mechanism-based SCD depletion of essential lubricating lipids (skin and eye). These efforts led to the discovery of MK-8245 (7), a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window.
• Small-scale synthesis of mevalonolactone and its 3-ethyl-2-14C homolog
  作者：William F. Gray、Gary L. Deets、Theodore Cohen

  DOI：10.1021/jo01276a053

  日期：1968.12
• Synthesis of a Carbon-14 Ring-labeled Benzthiophene via Degradation and Recyclization of an Unlabeled Benzthiophene
  作者：Scott W. Landvatter

  DOI：10.3987/com-96-7395

  日期：——