尿素-14C | 594-05-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 中文名称: 尿素-14C
• 英文名称: [¹⁴C]urea
• 英文别名: Urea, C-14；diamino(114C)methanone
• CAS: 594-05-8
• 化学式: CH₄N₂O
• 分子量: 62.0446
• InChiKey: XSQUKJJJFZCRTK-NJFSPNSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  4
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  2
• 氢受体数：
  1

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：本记录中的信息指的是尿素C 14作为诊断剂的使用。关于在母乳喂养期间使用尿素C 14的信息尚不可用。然而，将尿素C 14直接给予儿科患者被认为是安全的。国际指南指出，在给予尿素C 14后不需要中断母乳喂养。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Information in this record refers to the use of urea C 14 as a diagnostic agent. No information is available on the use of urea C 14 during breastfeeding. However, administration of urea C 14 directly to pediatric patients is considered to be safe. International guidelines state that breastfeeding need not be interrupted after administration of urea C 14. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 危险品标志：
  Xn,R
• 安全说明：
  S22,S26,S36
• 危险类别码：
  R40,R36/37/38
• 危险品运输编号：
  UN 2910 7

反应信息

• 作为反应物：
  描述：

  尿素-14C 在 一水合肼 作用下， 以 乙醇 、 异戊醇 为溶剂， 反应 12.0h， 生成 [14C]semicarbazide hydrochloride
  参考文献：
  名称：

  Synthesis of [3-14C]- and [5-14C]-labelled 5-nitro-1,2,4-triazol-3-one (NTO) and study of its chemical decomposition

  摘要：

  The chemical decomposition of NTO 1 and its corresponding amine ATO 2 was investigated. To make easier the identification of the decomposition products, we synthesized C-14-labelled NTO and ATO. Our results confirmed the high stability of the NTO triazolone ring. Its scission can be achieved partially by sulfuric acid under intensive heat and pressure. The triazolone ring of ATO was cleaved in alkaline solution. Carbon dioxide is evolved leaving a polar compound assumed to be aminoguanidine. The deamination of ATO was achieved by nitrosation. In dilute HCl (0.15N), 2 equivalents of NO2- lead to the triazolone: Lb, through a radical de-diazotation of the diazo intermediate. With 3 to 10 equivalents of NO2-, the nitrosation leads exclusively to the azide 6.

  DOI：

  10.1002/(sici)1099-1344(199912)42:12<1203::aid-jlcr276>3.0.co;2-f
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 盐酸 作用下， 生成 尿素-14C
  参考文献：
  名称：

  Zbarsky; Fischer, Canadian Journal of Research, Section B: Chemical Sciences, 1949, vol. 27, p. 84

  摘要：

  DOI：

文献信息

• Synthesis of radioactive and stable isotope labeled tirilazad mesylate
  作者：W. T. Stolle、J. A. Easter、E. H. Chew、J. P. McGrath、J. R. Palmer、R. S. P. Hsi

  DOI：10.1002/jlcr.2580341208

  日期：1994.12

  Tirilazad mesylate, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate, is a potent lipid peroxidation inhibitor capable of suppressing progression of tissue damage caused by trauma or ischemia. Several isotopically labeled versions of the compound have been synthesized for conducting in vitro and in vivo metabolic transformations of this experimental drug. These include labeling with carbon-14 at the 16α-methyl group of the steroid portion of the molecule, or at the C-2 position of the pyrimidine ring; also with deuterium at the steroid 16α-methyl group, and/or with carbon-13 at C-2, C-4, and C-6, and with nitrogen-15 at N-1 and N-3 of the pyrimidine ring.

  Tirilazad美克酸盐，21-[4-(2,6-二（1-吡咯烷基）-4-嘧啶基）-1-哌嗪基]-16α-甲基-孕-1,4,9(11)-三烯-3,20-二酮单甲烷磺酸盐，是一种有效的脂质过氧化抑制剂，能够抑制由创伤或缺血引起的组织损伤进展。已经合成了几种同位素标记的该化合物用于进行该实验药物的体外和体内代谢转化。这些标记包括在分子类固醇部分的16α-甲基基团处用碳-14标记，或在嘧啶环的C-2位置；也包括在类固醇的16α-甲基基团处用氘标记，以及在C-2、C-4和C-6处用碳-13标记，和在嘧啶环的N-1与N-3处用氮-15标记。
• Synthesis of highly pure¹⁴C-labelled<i>DL</i>-allantoin and¹³C NMR analysis of labelling integrity
  作者：Simon G. Patching

  DOI：10.1002/jlcr.1614

  日期：2009.7

  A number of synthetic approaches are assessed to prepare allantoin labelled with 14C given certain requirements and technical limitations. A method that fulfils these criteria is described to achieve the synthesis of highly pure 14C-labelled allantoin with the label introduced to the ureido carbonyl group in the final step by reaction of 5-chlorohydantoin with [14C]urea. The chosen method favours high purity at the expense of radiochemical yield, which is achieved at a level of 8%. The integrity of the label is then investigated by performing an NMR analysis of 13C-labelled allantoin synthesized by the same method. The 13C NMR spectrum confirms partial scrambling of the label to the C-2 position by equilibration of the product via a putative bicyclic intermediate, which had been suggested by other workers. The 14C-labelled allantoin synthesized by this method is therefore assigned as DL-[H2N14CO/14C-2]allantoin. This study also includes the first full characterization of a side product, 5-hydroxy-5-methoxyhydantoin, obtained by the reaction of a 5-hydroxyhydantoin intermediate with the methanol solvent. Copyright © 2009 John Wiley & Sons, Ltd.

  鉴于某些要求和技术限制，对制备 14C 标记尿囊素的一些合成方法进行了评估。本文介绍了一种符合这些标准的方法，通过 5-氯海因与[14C]脲的反应，在最后一步将标记引入脲基羰基，从而合成高纯度的 14C 标记尿囊素。所选方法有利于提高纯度，但牺牲了放射化学产率，使产率达到 8%。然后，通过对以相同方法合成的 13C 标记尿囊素进行核磁共振分析，研究标记的完整性。13C NMR 光谱证实，标签部分扰乱了 C-2 位置，通过一个假定的双环中间体对产物进行平衡，其他研究人员也曾提出过这一观点。因此，用这种方法合成的 14C 标记尿囊素被命名为 DL-[H2N14CO/14C-2]尿囊素。本研究还首次全面鉴定了一种副产品--5-羟基-5-甲氧基尿囊素，它是由 5-羟基尿囊素中间体与甲醇溶剂反应得到的。Copyright © 2009 John Wiley & Sons, Ltd. All Rights Reserved.
• Synthesis of [H‐3]‐ and [C‐14]‐labeled elagolix
  作者：Eric D. Soli、Bruce W. Surber、Aimee D. Reed

  DOI：10.1002/jlcr.3908

  日期：2021.6.15

  Gonadotropin-releasing hormone (GnRH) receptor antagonists are an important class of compounds designed to block the pituitary gland from synthesizing follicle-stimulating hormone and luteinizing hormone for the treatment of sex hormone dependent disorders. Elagolix (ABT-620) is currently approved for the treatment of pain associated with endometriosis and as a combination with estradiol and norethindrone acetate is approved for management of heavy menstrual bleeding due to uterine fibroids. In order to support the development of elagolix, we prepared [3H]elagolix for preclinical metabolism studies and [14C]elagolix for environmental risk assessment studies.

  促性腺激素释放激素（GnRH）受体拮抗剂是一类重要的化合物，旨在阻止垂体合成卵泡刺激素和黄体生成素，以治疗性激素依赖性疾病。Elagolix（ABT-620）目前被批准用于治疗子宫内膜异位症引起的疼痛，与雌二醇和醋酸炔诺酮的复方制剂被批准用于治疗子宫肌瘤引起的大量月经出血。为了支持艾拉戈利的开发，我们制备了用于临床前代谢研究的[3H]艾拉戈利和用于环境风险评估研究的[14C]艾拉戈利。
• A novel synthesis of [2-14C]2,5-dichloropyrimidine
  作者：Scott B. Tran、Brad D. Maxwell、Hong Wu、Samuel J. Bonacorsi

  DOI：10.1002/jlcr.1940

  日期：2011.11

  [2-14 C]2,5-dichloropyrimidine is a useful reagent for labeling biologically active compounds for use in hepatocyte transport studies, protein covalent binding, and metabolic profiling. This paper describes a novel five-step synthesis of [2-14 C]2,5-dichloropyrimidine from readily available [14C]urea by way of a boronic acid intermediate. A total of 4.34 mCi of [2-14 C]2,5-dichloropyrimidine was obtained with a specific activity of 226.0 μCi/mg (33.7 mCi/mmol). The radiochemical purity was 95.8%, and the overall radiochemical yield was 22% based on 20 mCi of [14C]urea starting material. Copyright © 2011 John Wiley & Sons, Ltd.

  [2-14C]2,5-二氯嘧啶是一种有用的试剂，可用于标记生物活性化合物，用于肝细胞转运研究、蛋白质共价结合和代谢分析。本文描述了一种通过硼酸中间体从容易获得的[14C]尿素合成[2-14C]2,5-二氯嘧啶的新颖五步法。共获得4.34mCi的[2-14C]2,5-二氯嘧啶，比活度为226.0μCi/mg（33.7mCi/mmol）。放射化学纯度为95.8％，基于20mCi的[ 14 C]尿素原料，总放射化学产率为22％。版权所有 © 2011 约翰·威利父子有限公司
• Synthesis and stability of a carbon-14-labeled 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor
  作者：Richard C. Burrell、Samuel J. Bonacorsi、J. Kent Rinehart、Saleem Ahmad、Khehyong Ngu、Balu Balasubramanian

  DOI：10.1002/jlcr.1810

  日期：——

  Inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) is an effective method of lowering plasma low-density lipoprotein cholesterol levels. Hemi-calcium (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate (1) is a cholesterol-lowering statin drug that effectively inhibits HMGR. An important step in the development of this compound was the synthesis of a carbon-14-labeled analog for use in preclinical absorption, distribution, metabolism and excretion studies. The synthesis of a carbon-14-labeled analog of the cholesterol-lowering statin drug 1 is described. The carbon-14-labeled compound [14C]-1 was prepared in 11 steps from [14C]-labeled urea. The overall radiochemical yield for the synthesis was 22% and the radiochemical purity of [14C]-1 was 99.9% immediately after synthesis. It was found that [14C]-1 with a specific activity of 43.2 µCi/mg decomposed at a rate of about 1.9%/month when stored at −78°C under argon. Three samples of [14C]-1 were prepared to study the chemical stability of the molecule. One sample had a specific activity of 3.8 µCi/mg and the other two contained radical inhibitors, L-ascorbic acid (1% by weight, specific activity of 10.5 µCi/mg) or BHT (1% by weight, specific activity of 9.8 µCi/mg). For these samples the decomposition rates were decreased to 0.5%/month, 0.2%/month and 0.1%/month, respectively. Copyright © 2010 John Wiley & Sons, Ltd.

  抑制3-羟基-3-甲基戊二酰辅酶-A还原酶（HMGR）是降低血浆低密度脂蛋白胆固醇水平的有效方法。半钙(3R,5S,E)-7-(4-(4-氟苯基)-6-异丙基-2-(甲基(1-甲基-1H-1,2,4-三唑-5-基)氨基) )pyrimidin-5-yl)-3,5-diHydroxyhept-6-enoate (1) 是一种降胆固醇他汀类药物，可有效抑制 HMGR。该化合物开发的一个重要步骤是合成碳 14 标记的类似物，用于临床前吸收、分布、代谢和排泄研究。 描述了降胆固醇他汀类药物 1 的碳 14 标记类似物的合成。碳14标记的化合物[14C]-1是由[14C]标记的尿素经过11个步骤制备而成。合成的总放射化学收率为22％，合成后[ 14 C]-1的放射化学纯度为99.9％。结果发现，比活度为43.2μCi/mg的[14C]-1在氩气下-78℃保存时，以大约1.9%/月的速率分解。制备了三个[14C]-1 样品来研究该分子的化学稳定性。一个样品的比活性为 3.8μCi/mg，另外两个样品含有自由基抑制剂 L-抗坏血酸（按重量计 1%，比活性为 10.5μCi/mg）或 BHT（按重量计 1%，比活性为 9.8μCi/mg） /毫克）。对于这些样品，分解率分别降至 0.5%/月、0.2%/月和 0.1%/月。版权所有 © 2010 约翰威利父子有限公司