| 1449745-02-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• CAS: 1449745-02-1
• 化学式: C₉H₁₆N₂*C₁₄H₂₀N₂O₇P₂S₅
• 分子量: 702.839
• InChiKey: NGGOFJGIKRRDTF-RMSBXQGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  41.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  116.61
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 、 potassium tert-butylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 7.75h， 生成 P1-(uridine-5')-methylenebisphosphonodithioate tris-ammonium salt
  参考文献：
  名称：

  Nucleoside-(5′→P) Methylenebisphosphonodithioate Analogues: Synthesis and Chemical Properties

  摘要：

  Nucleoside-(5'-> P) methylenebisphosphonodithioate analogues are bioisosteres of natural nucleotides. The potential therapeutic applications of these analogues are limited by their relative instability. With a view toward improving their chemical and metabolic stability as well as their affinity toward zinc ions, we developed a novel nucleotide scaffold, nucleoside-5'-tetrathiobisphosphonate. We synthesized P1-(uridine/adenosine-5')-methylenebisphosphonodithioate, 2 and 3, and P1,P2-di(uridine/adenosine-5')-methylenebisphosphonodithioate, 4 and 5. Using H-1 and P-31 NMR-monitored Zn2+/Mg2+ titrations, we found that 5 coordinated Zn2+. by both N7 nitrogen atoms and both dithiophosphonate moieties, whereas 3 coordinated Zn2+ by an N7 nitrogen atom and P-beta. Both 3 and 5 did not coordinate Mg2+ ions. P-31 NMR-monitored kinetic studies showed that 3 was more stable at pD 1.5 than 5, with t(1/2) of 44 versus 9 h, respectively, and at pD 11 both showed no degradation for at least 2 weeks. However, 5 was more stable than 3 under an air-oxidizing atmosphere, with t(1/2) of at least 3 days versus 14 h, respectively. Analogues 3 and 5 were highly stable to NPP1,3 and NTPDase1,2,3,8 hydrolysis (0-7%). However, they were found to be poor ectonucleotidase inhibitors. Although 3 and 5 did not prove to be effective inhibitors of zinc-containing NPP1/3, which is involved in the pathology of osteoarthritis and diabetes, they may be promising zinc chelators for the treatment of other health disorders involving an excess of zinc ions.

  DOI：

  10.1021/jo400931n
• 作为产物：
  描述：

  、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 2',3'-O-(甲氧基亚甲基)尿苷 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Nucleoside-(5′→P) Methylenebisphosphonodithioate Analogues: Synthesis and Chemical Properties

  摘要：

  Nucleoside-(5'-> P) methylenebisphosphonodithioate analogues are bioisosteres of natural nucleotides. The potential therapeutic applications of these analogues are limited by their relative instability. With a view toward improving their chemical and metabolic stability as well as their affinity toward zinc ions, we developed a novel nucleotide scaffold, nucleoside-5'-tetrathiobisphosphonate. We synthesized P1-(uridine/adenosine-5')-methylenebisphosphonodithioate, 2 and 3, and P1,P2-di(uridine/adenosine-5')-methylenebisphosphonodithioate, 4 and 5. Using H-1 and P-31 NMR-monitored Zn2+/Mg2+ titrations, we found that 5 coordinated Zn2+. by both N7 nitrogen atoms and both dithiophosphonate moieties, whereas 3 coordinated Zn2+ by an N7 nitrogen atom and P-beta. Both 3 and 5 did not coordinate Mg2+ ions. P-31 NMR-monitored kinetic studies showed that 3 was more stable at pD 1.5 than 5, with t(1/2) of 44 versus 9 h, respectively, and at pD 11 both showed no degradation for at least 2 weeks. However, 5 was more stable than 3 under an air-oxidizing atmosphere, with t(1/2) of at least 3 days versus 14 h, respectively. Analogues 3 and 5 were highly stable to NPP1,3 and NTPDase1,2,3,8 hydrolysis (0-7%). However, they were found to be poor ectonucleotidase inhibitors. Although 3 and 5 did not prove to be effective inhibitors of zinc-containing NPP1/3, which is involved in the pathology of osteoarthritis and diabetes, they may be promising zinc chelators for the treatment of other health disorders involving an excess of zinc ions.

  DOI：

  10.1021/jo400931n