2,6-dichloro-4,8-bis-(4-methyl-piperazin-1-yl)-pyrimido[5,4-d]pyrimidine | 7030-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2,6-dichloro-4,8-bis-(4-methyl-piperazin-1-yl)-pyrimido[5,4-d]pyrimidine
• 英文别名: 2,6-Dichloro-4,8-bis(4-methylpiperazin-1-yl)pyrimido[5,4-d]pyrimidine
• CAS: 7030-11-7
• 化学式: C₁₆H₂₂Cl₂N₈
• 分子量: 397.31
• InChiKey: FQCPXECBUIQFSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.23
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  64.52
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-4,8-bis-(4-methyl-piperazin-1-yl)-pyrimido[5,4-d]pyrimidine 、 二乙醇胺 以 二甲基亚砜 为溶剂， 反应 6.0h， 以273 mg的产率得到2-({6-[Bis(2-hydroxyethyl)amino]-4,8-bis(4-methylpiperazin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol
  参考文献：
  名称：

  Synthesis, Flow Cytometric Evaluation, and Identification of Highly Potent Dipyridamole Analogues as Equilibrative Nucleoside Transporter 1 Inhibitors

  摘要：

  Dipyridamole (Persantine) is a clinically used vasodilator with equilibrative nucleoside transporters I and 2 (ENT1 and ENT2) inhibitory activity albeit less potent than the prototype ENT1 inhibitor nitrobenzylmercaptopurine riboside (NBMPR). Dipyridamole is a good candidate for further exploration because it is a non-nucleoside and has a proven record of safe use in humans. A series of dipyridamole analogues were synthesized with systematic modification and evaluated as ENT1 inhibitors by flow cytometry. Compounds with much higher potency were identified, the best being 2,6-bis(diethanolamino)-4,8-diheptamethylene-iminopyrimido[5,4-d]pyrimidine (13) with a K-i of 0.49 nM compared to a Ki of 308 nM for dipyridamole. Compound 13 is similar in potency to the prototype potent ENT1 inhibitor NBMPR (0.43 nM). For the first time, a dipyridamole analogue has been identified that is equipotent with NBMPR. The SAR indicated that diethanolamine substituted analogues were more active than monoethanolamine compounds. Also, free hydroxyl groups are not essential for activity.

  DOI：

  10.1021/jm070311l
• 作为产物：
  描述：

  N-甲基哌嗪 、 2,4,6,8-四氯嘧啶并[5,4-d]嘧啶 以 四氢呋喃 为溶剂， 反应 0.33h， 生成 2,6-dichloro-4,8-bis-(4-methyl-piperazin-1-yl)-pyrimido[5,4-d]pyrimidine
  参考文献：
  名称：

  Synthesis, Flow Cytometric Evaluation, and Identification of Highly Potent Dipyridamole Analogues as Equilibrative Nucleoside Transporter 1 Inhibitors

  摘要：

  Dipyridamole (Persantine) is a clinically used vasodilator with equilibrative nucleoside transporters I and 2 (ENT1 and ENT2) inhibitory activity albeit less potent than the prototype ENT1 inhibitor nitrobenzylmercaptopurine riboside (NBMPR). Dipyridamole is a good candidate for further exploration because it is a non-nucleoside and has a proven record of safe use in humans. A series of dipyridamole analogues were synthesized with systematic modification and evaluated as ENT1 inhibitors by flow cytometry. Compounds with much higher potency were identified, the best being 2,6-bis(diethanolamino)-4,8-diheptamethylene-iminopyrimido[5,4-d]pyrimidine (13) with a K-i of 0.49 nM compared to a Ki of 308 nM for dipyridamole. Compound 13 is similar in potency to the prototype potent ENT1 inhibitor NBMPR (0.43 nM). For the first time, a dipyridamole analogue has been identified that is equipotent with NBMPR. The SAR indicated that diethanolamine substituted analogues were more active than monoethanolamine compounds. Also, free hydroxyl groups are not essential for activity.

  DOI：

  10.1021/jm070311l

文献信息

• Some Congeners and Analogs of Dipyridamole
  作者：Daniel Kaminsky、Wilson B. Lutz、Sam Lazarus

  DOI：10.1021/jm00322a041

  日期：1966.7