[[(2R,3R,4R,5R)-5-(6-氨基-2-氯-嘌呤-9-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-羟基-磷酰]氧基膦酸 | 16506-88-0

• 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
• 中文名称: [[(2R,3R,4R,5R)-5-(6-氨基-2-氯-嘌呤-9-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-羟基-磷酰]氧基膦酸
• 英文名称: 2-chloroadenosine-5'-diphosphate
• 英文别名: 2-chloroadenosine diphosphate；2-chloroadenosine-5'-O-diphosphate；PF10；2-Cl-ADP；2-Chloro-ADP；[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate
• CAS: 16506-88-0
• 化学式: C₁₀H₁₄ClN₅O₁₀P₂
• 分子量: 461.649
• InChiKey: POWNGKCXGCOKLX-UUOKFMHZSA-N

物化性质

• 沸点：
  847.4±75.0 °C(Predicted)
• 密度：
  2.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  28
• 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：
  233
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2-氯-9-(5-O-膦酰-beta-D-来苏呋喃糖基)-9H-嘌呤-6-胺 在 三正丁胺 、 N,N'-羰基二咪唑 、 tris(tributylammonium) phosphate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以39%的产率得到[[(2R,3R,4R,5R)-5-(6-氨基-2-氯-嘌呤-9-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-羟基-磷酰]氧基膦酸
  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

文献信息

• Hydrolysis of P2-Purinoceptor agonists by a purified ectonucleotidase from the bovine aorta, the ATP-diphosphohydrolase
  作者：Maryse Picher、Jean Sévigny、Pédro D'Orléans-Juste、Adrien R. Beaudoin

  DOI：10.1016/0006-2952(96)00086-x

  日期：1996.6

  Pharmacologists are becoming more and more aware of the possibility that certain ATP analogues currently used to classify the P-2-purinoceptors are dephosphorylated by ectonucleotidases. In this study, we provide evidence that in the vascular system, these purine analogues are hydrolysed by an ATP-diphosphohydrolase (ATPDase). This enzyme is known as the major plasma membrane nucleotidase of endothelial and smooth muscle cells, and is believed to dephosphorylate extracellular triphospho- and diphosphonucleosides. Assays were conducted with a purified ATPDase from smooth muscle cells of bovine aorta. At a concentration of 250 mu M, adenosine 5'-(alpha,beta-methylene) triphosphonate (alpha,beta-metATP), adenosine 5'-(beta,gamma-methylene) triphosphonate (beta,gamma-metATP), adenosine 5'-(alpha,beta-methylene) diphosphonate (alpha,beta-metADP), adenylyl 5'-(beta,gamma-imido) diphosphonate (beta,gamma-imidoATP) and adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) all resisted dephosphorylation, whereas 2-chloroadenosine triphosphate (2-chloroATP), 2-methylthioadenosine triphosphate (2-MeSATP) and 8-bromoadenosine triphosphate (8-bromoATP) were hydrolysed at 99, 63, and 20% of the rate of ATP hydrolysis, respectively. All the non-hydrolysable analogues tested, except alpha,beta-metADP, competed with ATP and ADP for the ATPDase catalytic site, reducing their hydrolysis by 35-50%. Apparent K-m values for ATP and ADP were estimated at 14.1 and 12.0 mu M, respectively, whereas apparent K-m and K-i values for the purine analogues ranged from 12 to 28 mu M These results strongly support the view that (1) the ATPDase is expected to reduce substantially the P-2-response induced by ATP, ADP, and some hydrolysable agonists; and (2) by competing with the hydrolysis of endogenously released ATP and ADP, non-hydrolysable analogues could alter the amplitude or direction of the cellular response induced by these natural substrates.
• White blood cell functional assay
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20040253650A1

  公开（公告）日：2004-12-16

  A method of rapidly assaying nucleotide receptor P2X 7 pore activity in white blood cells contained within a blood sample. A method according to the invention includes the steps of: (a) labeling the white blood cells with a white blood cell-specific label; (b) depolarizing the labeled white blood cells with an isotonic depolarizing solution; (c) contacting the labeled white blood cells with a dye and a P2X 7 agonist in an amount sufficient to activate nucleotide receptor P2X 7 pore activity; (d) contacting the labeled white blood cells with a divalent cation in an amount sufficient to deactivate nucleotide receptor P2X 7 pore activity; and (e) analyzing dye uptake in labeled white blood cells whereby nucleotide receptor P2X 7 pore activity is quantified by the amount of dye taken up in labeled white blood cells treated with P2X 7 agonist relative to labeled white blood cells in the absence of P2X 7 agonist.
• Functional Genomic Pore Assay For Mixed Cell Populations
  申请人：Denlinger Loren C.

  公开号：US20090053204A1

  公开（公告）日：2009-02-26

  A method of assaying nucleotide receptor P2X 7 pore activity in white blood cells contained within a mixed cell sample is provided comprising labeling white blood cells with a white blood cell-specific label; depolarizing the labeled white blood cells with an isotonic depolarizing solution; contacting the labeled white blood cells with dye and a P2X 7 agonist in an amount sufficient to activate P2X 7 pore activity; contacting the labeled white blood cells with a divalent cation in an amount sufficient to deactivate P2X 7 pore activity; and analyzing dye uptake whereby P2X 7 pore activity is quantified by the amount of dye taken up in labeled white blood cells treated with the P2X 7 agonist relative to labeled white blood cells in the absence of said P2X 7 agonist, said P2X 7 pore activity being corrected for sample age and by subtraction of P2X 7 pore activity contributed by nonviable white blood cells.
• US7560243B2
  申请人：——

  公开号：US7560243B2

  公开（公告）日：2009-07-14
• US7960131B2
  申请人：——

  公开号：US7960131B2

  公开（公告）日：2011-06-14