O⁶-benzylpurine riboside-5′-O-[(phosphonomethyl)phosphonic acid] | 1802226-87-4

• 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: O⁶-benzylpurine riboside-5′-O-[(phosphonomethyl)phosphonic acid]
• 英文别名: Inosine, 6-O-(phenylmethyl)-, 5a(2)-[hydrogen P-(phosphonomethyl)phosphonate]；[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-phenylmethoxypurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid
• CAS: 1802226-87-4
• 化学式: C₁₈H₂₂N₄O₁₀P₂
• 分子量: 516.341
• InChiKey: JJCXNUPPWIXTFK-SCFUHWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.36
• 重原子数：
  34.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  206.58
• 氢给体数：
  5.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  肌苷 在 吡啶 、 磷酸三甲酯 、 4-二甲氨基吡啶 、 氨 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 28.09h， 生成 O⁶-benzylpurine riboside-5′-O-[(phosphonomethyl)phosphonic acid]
  参考文献：
  名称：

  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

  摘要：

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

  DOI：

  10.1021/acs.jmedchem.5b00802