[3H]-2-Chloro-2'-deoxy-adenosine monophosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: [3H]-2-Chloro-2'-deoxy-adenosine monophosphate
• 英文别名: 2-chloro-2'-deoxyadenosine 5'-monophosphate；2-chloro-2'-deoxyadenosine-5'-monophosphate；2-chloro-deoxy-AMP；2CdAMP；PF3；2-chlorodeoxyadenosine monophosphate；2-Chloro-2'-deoxyadenosine monophosphate；[(2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate
• 化学式: C₁₀H₁₃ClN₅O₆P
• 分子量: 365.67
• InChiKey: BXJWGKMZENUHLS-KVQBGUIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [3H]-2-Chloro-2'-deoxy-adenosine monophosphate 在 三正丁胺 、 N,N'-羰基二咪唑 、 三丁基焦磷酸铵 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以47%的产率得到2-chloro-2'-deoxyadenosine-5'-trisphosphate
  参考文献：
  名称：

  2-ClATP exerts anti-tumoural actions not mediated by P2 receptors in neuronal and glial cell lines

  摘要：

  We investigated the effects of the ATP analogue and P2 receptor agonist 2-ClATP on growth and survival of different neuronal (PC12, PC12nnr5 and SH-SY5Y) and glial (U87 and U373) cell lines, by the use of direct count of intact nuclei, fluorescence microscopy, fluorescence-activated cell sorter analysis (FACS) and high pressure liquid chromatography (HPLC). 2-ClATP lowered the number of cultured PC12nnr5, SH-SY5Y, U87 and U373 cells to almost 5%, and of PC12 cells to about 35% after 3-4 days of treatment. EC50 was in the 5-25 muM range, with 2-ClATP behaving as a cytotoxic or cytostatic agent. Analysis of the biological mechanisms demonstrated that pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (P2 receptor antagonist and nucleotidases inhibitor), but not Caffeine or CGS-15493 (PI receptor antagonists) effectively prevented 2-ClATP-induced toxicity. 2-ClATP metabolic products (2-ClADP, 2-ClAMP, 2-Cladenosine) and new synthesis derivatives (2-CldAMP, 2-Cldadenosine-3',5'-bisphosphate and 2-CldATP) exerted similar cytotoxic actions. Inhibition of both serum nucleotidases and purine nucleoside transporters strongly reduced 2-ClATP-induced cell death, which was conversely increased by the nucleotide hydrolyzing enzyme apyrase. The adenosine kinase inhibitor 5-iodotubericidin totally prevented 2-ClATP or 2-Cladenosine-induced toxicity.In summary, our findings indicate that 2-ClATP exerts either cell cycle arrest or cell death, acting neither on P2 nor on P1 receptors, but being extracellularly metabolized into 2-Cladenosine, intracellularly transported and re-phosphorylated. (C) 2003 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2003.09.015
• 作为产物：
  描述：

  克拉屈滨 在 recombinant human deoxycytidine kinase (EC 2.7.1.74) 、 5’-三磷酸腺苷 作用下， 以 various solvent(s) 为溶剂， 生成 [3H]-2-Chloro-2'-deoxy-adenosine monophosphate
  参考文献：
  名称：

  Differences in kinetic properties of pure recombinant human and mouse deoxycytidine kinase

  摘要：

  Human and mouse deoxycytidine kinase (dCK) (EC 2.7.1.74) were cloned and expressed in Escherichia coli. Michaelis-Menten kinetics were determined for the purified enzymes with 2'-deoxycytidine (dCyd), 2'-deoxyadenosine (dAdo), 2-chloro-2'-deoxyadenosine (CdA), 2',3'-dideoxycytidine (ddCyd) and 9-beta-D-arabinofuranosylguanine (araG) as substrates and ATP and UTP as phosphate donors. Both human and mouse dCK showed highest affinity to dCyd with K-m values of 0.05-0.2 mu M. The anti-leukaemic compound CdA was the superior substrate of the nucleoside analogues tested. Both enzymes were able to efficiently utilize ATP and UTP as phosphate donors. However, the use of UTP instead of ATP as phosphate donor decreased K-m values for all substrates investigated. The kinetic properties of mouse and human dCK differed in that the human enzyme showed higher affinity for the substrates dAdo, CdA, ddCyd and araG. The human enzyme also showed higher affinity for ATP and UTP. The ability to phosphorylate dCyd was, however, similar for both human and mouse dCK. At physiological concentration of the feedback inhibitor dCTP, mouse dCK showed lower activity than human dCK for all substrates investigated.

  DOI：

  10.1016/0006-2952(95)00129-n

文献信息

• Facile Small Scale Synthesis of Nucleoside 5′-Phosphate Mixtures
  作者：Robert S. Jansen、Hilde Rosing、Jan HM Schellens、Jos H. Beijnen

  DOI：10.1080/15257770903451546

  日期：2010.1

  phosphorylate small amounts of nucleosides (0.05 μmol) into mixtures of their 5′-mono-, di-, and triphosphates in a one-pot reaction. The nucleosides were first converted into their dichlorophosphates using a large excess (15–18 equivalents) of phosphorous oxychloride in trimethylphosphate. The large excess resulted in good dichlorophosphate yields (46–76%) for the four nucleosides tested. Upon the addition

  我们提出了一种简便的方法，可以在一锅反应中将少量的核苷（0.05μmol）磷酸化为5'-单-，二-和三磷酸的混合物。首先使用磷酸三甲酯中大量过量的氯氧化磷（15-18当量）将核苷转化为其二氯磷酸酯。大量过量导致所测试的四种核苷的二氯磷酸酯收率良好（46–76％）。在将磷酸三丁铵与另外的三丁胺（均20当量）一起加入后，将二氯磷酸酯转化为含有等量的单磷酸酯，二磷酸酯和三磷酸酯的混合物。所提出的方法已成功地应用于合成稳定同位素标记的核苷酸的混合物，该混合物可用作定量质谱分析中的内标。
• Novel deoxyadenosine phosphate compounds and methods of making and using the same
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0190726A2

  公开（公告）日：1986-08-13

  Nucleotide compounds are provided, namely 2-chloro-2'-deoxyadenosine 5'-phosphate compounds (I) especially as the monosodium and disodium salt, as well as a method for their production, pharmaceutical compositions comprising the compounds, and methods of treatment using the compounds in dosage form. The compounds of the invention have pharmacological properties and are useful antimicrobial agents, antiviral agents, and antileukemic agents.

  本发明提供了核苷酸化合物，即 2-氯-2'-脱氧腺苷-5'-磷酸化合物 (I)，尤其是单钠盐和二钠盐，还提供了其生产方法、包含该化合物的药物组合物以及使用该化合物进行治疗的方法。 本发明的化合物具有药理特性，是有用的抗菌剂、抗病毒剂和抗白血病剂。
• Novel deoxyadenosine compounds and methods of making and using the same
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0351795A2

  公开（公告）日：1990-01-24

  3′-Acyl-2-chloro-2′-deoxy-5′-adenylic acids (I) as well as a method for their production, pharmaceuti­cal compositions comprising the compounds, and methods of treatment using the compound in dosage forms. The compounds of the invention have pharmacological properties and are useful antimicrobial agents and antitumor agents.

  3′-酰基-2-氯-2′-脱氧-5′-腺苷酸(Ⅰ)及其生产方法、含有本发明化合物的药物组合物和使用本发明化合物剂型的治疗方法。本发明的化合物具有药理特性，是有用的抗菌剂和抗肿瘤剂。
• Oral administration of nucleoside monophosphates
  申请人：Merck Serono S.A.

  公开号：EP2428201A1

  公开（公告）日：2012-03-14

  The invention relates to the oral pharmaceutical compositions comprising the nucleosides in form of their monophosphates.

  本发明涉及包含单磷酸形式核苷的口服药物组合物。
• NUCLEOTIDE ANALOGUES FOR TOPICAL TREATMENT OF PROLIFERATIVE DISEASE OF THE SKIN
  申请人：HOSTETLER, Karl Y.

  公开号：EP0831855A1

  公开（公告）日：1998-04-01