PF4

• 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: PF4
• 英文别名: diammonium (2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-[(hydrogen phosphonatooxy)methyl]oxolan-3-yl hydrogen phosphate；[(2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-2-(phosphonooxymethyl)oxolan-3-yl] dihydrogen phosphate
• 化学式: C₁₀H₁₄ClN₅O₉P₂
• 分子量: 445.65
• InChiKey: FCTUCHUTNSXNIZ-KVQBGUIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  212
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  克拉屈滨 在 磷酸三甲酯 、 Proton Sponge 、 三氯氧磷 作用下， 反应 1.0h， 生成 PF4
  参考文献：
  名称：

  脱氧腺苷二磷酸衍生物作为 P2Y1 受体的有效拮抗剂。

  摘要：

  腺苷3',5'-和2',5'-二磷酸先前被证明可作为P2Y1受体的竞争性拮抗剂(Boyer等人Mol.Pharmacol.1996, 50, 1323-1329)。已合成了 2'- 和 3'-脱氧腺苷二磷酸类似物，在腺嘌呤环的 2- 和 6- 位、核糖部分和磷酸基团上含有各种结构修饰，目的是开发更有效和选择性的 P2Y1对手。进行了腺苷核苷前体的一步磷酸化反应。通过测量其刺激火鸡红细胞膜中磷脂酶 C（激动剂作用）和抑制 10 nM 2-MeSATP 引起的磷脂酶 C 刺激（拮抗剂作用）的能力，确定每种类似物对 P2Y1 受体的活性。 2'-和3'-脱氧修饰均具有良好的耐受性。 N6-甲基修饰既增强​​了 2'-脱氧腺苷 3',5'-二磷酸的拮抗效力 (IC50 330 nM) 17 倍，又消除了先导化合物观察到的残留激动剂特性。 N6-乙基修饰提供了作为拮抗剂的中等效力，而N6-丙基完全消除了激动剂和拮抗剂特性。

  DOI：

  10.1021/jm970433l

文献信息

• 2-ClATP exerts anti-tumoural actions not mediated by P2 receptors in neuronal and glial cell lines
  作者：Nadia D’Ambrosi、Stefano Costanzi、Daniela F Angelini、Rosaria Volpini、Giuseppe Sancesario、Gloria Cristalli、Cinzia Volonté

  DOI：10.1016/j.bcp.2003.09.015

  日期：2004.2

  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.
• Deoxyadenosine Bisphosphate Derivatives as Potent Antagonists at P2Y₁ Receptors
  作者：Emidio Camaioni、José L. Boyer、Arvind Mohanram、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm970433l

  日期：1998.1.1

  adenosine nucleoside precursors were carried out. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-MeSATP (antagonist effect). Both 2'- and 3'-deoxy modifications were well tolerated. The N6-methyl modification both enhanced

  腺苷3',5'-和2',5'-二磷酸先前被证明可作为P2Y1受体的竞争性拮抗剂(Boyer等人Mol.Pharmacol.1996, 50, 1323-1329)。已合成了 2'- 和 3'-脱氧腺苷二磷酸类似物，在腺嘌呤环的 2- 和 6- 位、核糖部分和磷酸基团上含有各种结构修饰，目的是开发更有效和选择性的 P2Y1对手。进行了腺苷核苷前体的一步磷酸化反应。通过测量其刺激火鸡红细胞膜中磷脂酶 C（激动剂作用）和抑制 10 nM 2-MeSATP 引起的磷脂酶 C 刺激（拮抗剂作用）的能力，确定每种类似物对 P2Y1 受体的活性。 2'-和3'-脱氧修饰均具有良好的耐受性。 N6-甲基修饰既增强​​了 2'-脱氧腺苷 3',5'-二磷酸的拮抗效力 (IC50 330 nM) 17 倍，又消除了先导化合物观察到的残留激动剂特性。 N6-乙基修饰提供了作为拮抗剂的中等效力，而N6-丙基完全消除了激动剂和拮抗剂特性。