N,N'-Bis-(4-methoxy-benzyl)-N,N'-dimethyl-2,6-bis-(3-triisopropylsilanyloxy-propoxy)-pyrimido[5,4-d]pyrimidine-4,8-diamine | 213840-40-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N,N'-Bis-(4-methoxy-benzyl)-N,N'-dimethyl-2,6-bis-(3-triisopropylsilanyloxy-propoxy)-pyrimido[5,4-d]pyrimidine-4,8-diamine
• CAS: 213840-40-5
• 化学式: C₄₈H₇₈N₆O₆Si₂
• 分子量: 891.355
• InChiKey: KPFRNSDBTWTUBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.63
• 重原子数：
  62.0
• 可旋转键数：
  26.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  113.42
• 氢给体数：
  0.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  N,N'-Bis-(4-methoxy-benzyl)-N,N'-dimethyl-2,6-bis-(3-triisopropylsilanyloxy-propoxy)-pyrimido[5,4-d]pyrimidine-4,8-diamine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 3-[2-(3-Hydroxypropoxy)-4,8-bis[(4-methoxyphenyl)methyl-methylamino]pyrimido[5,4-d]pyrimidin-6-yl]oxypropan-1-ol
  参考文献：
  名称：

  Resistance-Modifying Agents. 11. Pyrimido[5,4-d]pyrimidine Modulators of Antitumor Drug Activity. Synthesis and Structure−Activity Relationships for Nucleoside Transport Inhibition and Binding to α₁-Acid Glycoprotein

  摘要：

  The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, alpha(1)-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of H-3-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4'-methoxybenzylamino, 3',4'dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.

  DOI：

  10.1021/jm040772w
• 作为产物：
  描述：

  1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8-(3H,7H)-tetrone 在 sodium hydroxide 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 9.33h， 生成 N,N'-Bis-(4-methoxy-benzyl)-N,N'-dimethyl-2,6-bis-(3-triisopropylsilanyloxy-propoxy)-pyrimido[5,4-d]pyrimidine-4,8-diamine
  参考文献：
  名称：

  Resistance-Modifying Agents. 11. Pyrimido[5,4-d]pyrimidine Modulators of Antitumor Drug Activity. Synthesis and Structure−Activity Relationships for Nucleoside Transport Inhibition and Binding to α₁-Acid Glycoprotein

  摘要：

  The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, alpha(1)-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of H-3-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4'-methoxybenzylamino, 3',4'dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.

  DOI：

  10.1021/jm040772w