4-thio-5'-uridylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl)anhydride | 1280117-31-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-thio-5'-uridylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl)anhydride
• 英文别名: 4-Thio-5''-uridylic Acid(1,1-Chloro-1-phosphonomethyl-1-phosphonyl)anhydride；[dichloro-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2-oxo-4-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methyl]phosphonic acid
• CAS: 1280117-31-8
• 化学式: C₁₀H₁₅Cl₂N₂O₁₃P₃S
• 分子量: 567.128
• InChiKey: LUWOVOPRCPGURH-XVFCMESISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  265
• 氢给体数：
  7
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2',3',5'-三乙酰尿苷 在 劳森试剂 、 三正丁胺 、 氨 、 水 、 三乙基碳酸氢铵缓冲液 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 以 甲醇 、 磷酸三乙酯 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 42.08h， 生成 4-thio-5'-uridylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl)anhydride
  参考文献：
  名称：

  Structural Modifications of UMP, UDP, and UTP Leading to Subtype-Selective Agonists for P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y(2), P2Y(4), and P2Y(6) receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y(2) receptor, 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 mu M at P2Y(2) and > 70-fold selectivity versus P2Y(4) and P2Y(6) receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y(4) agonist (EC50 4.98 mu M > 20-fold selective vs P2Y(2) and P2Y(6)). In contrast, :replacement of the 2-keto function in UDP by NH yielded a potent P2Y(2) agonist (12g, iso-CDP, EC50 = 0.604 mu M, > 100-fold selective). In an attempt to obtain metabolically stable UTP analogues, beta,gamma-dichloro- and beta,gamma-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y(2), and in some cases also by P2Y(6), than by P2Y(4) receptors. 4-Thio-beta,gamma-difluoromethylene-UTP (14g) was a potent P2Y(2) agonist with an EC50 value of 0.134 mu M and > 50-fold selectivity. N3-Phenacyl-beta,gamma-dichloromethylene-UTP (14b) proved to be a potent P2Y(6) receptor agonist (EC50 0.142 mu M) with high selectivity versus P2Y(4) (50-fold) and moderate selectivity versus P2Y(2) receptors (6-fold).

  DOI：

  10.1021/jm1016297

文献信息

• Structural Modifications of UMP, UDP, and UTP Leading to Subtype-Selective Agonists for P2Y₂, P2Y₄, and P2Y₆ Receptors
  作者：Ali El-Tayeb、Aidong Qi、Robert A. Nicholas、Christa E. Müller

  DOI：10.1021/jm1016297

  日期：2011.4.28

  A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y(2), P2Y(4), and P2Y(6) receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y(2) receptor, 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 mu M at P2Y(2) and > 70-fold selectivity versus P2Y(4) and P2Y(6) receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y(4) agonist (EC50 4.98 mu M > 20-fold selective vs P2Y(2) and P2Y(6)). In contrast, :replacement of the 2-keto function in UDP by NH yielded a potent P2Y(2) agonist (12g, iso-CDP, EC50 = 0.604 mu M, > 100-fold selective). In an attempt to obtain metabolically stable UTP analogues, beta,gamma-dichloro- and beta,gamma-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y(2), and in some cases also by P2Y(6), than by P2Y(4) receptors. 4-Thio-beta,gamma-difluoromethylene-UTP (14g) was a potent P2Y(2) agonist with an EC50 value of 0.134 mu M and > 50-fold selectivity. N3-Phenacyl-beta,gamma-dichloromethylene-UTP (14b) proved to be a potent P2Y(6) receptor agonist (EC50 0.142 mu M) with high selectivity versus P2Y(4) (50-fold) and moderate selectivity versus P2Y(2) receptors (6-fold).