2,2',2'',2'''-(4,8-bis-dibutylamino-pyrimido[5,4-d]pyrimidine-2,6-diylbisazanediyl)-tetrakis-ethanol | 107631-01-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2,2',2'',2'''-(4,8-bis-dibutylamino-pyrimido[5,4-d]pyrimidine-2,6-diylbisazanediyl)-tetrakis-ethanol
• 英文别名: N⁴,N⁴,N⁸,N⁸-tetrabutyl-N²,N²,N⁶,N⁶-tetrakis-(2-hydroxy-ethyl)-pyrimido[5,4-d]pyrimidine-2,4,6,8-tetrayltetraamine；N⁴,N⁴,N⁸,N⁸-Tetrabutyl-N²,N²,N⁶,N⁶-tetrakis-(2-hydroxy-aethyl)-pyrimido[5,4-d]pyrimidin-2,4,6,8-tetrayltetraamin；2-({6-[Bis(2-hydroxyethyl)amino]-4,8-bis(dibutylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol；2-[[2-[bis(2-hydroxyethyl)amino]-4,8-bis(dibutylamino)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol
• CAS: 107631-01-6
• 化学式: C₃₀H₅₆N₈O₄
• 分子量: 592.826
• InChiKey: UTMGQCIXSKRSNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  42
• 可旋转键数：
  24
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,4,6,8-四氯嘧啶并[5,4-d]嘧啶 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 6.33h， 生成 2,2',2'',2'''-(4,8-bis-dibutylamino-pyrimido[5,4-d]pyrimidine-2,6-diylbisazanediyl)-tetrakis-ethanol
  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

• Synthesis, Flow Cytometric Evaluation, and Identification of Highly Potent Dipyridamole Analogues as Equilibrative Nucleoside Transporter 1 Inhibitors
  作者：Wenwei Lin、John K. Buolamwini

  DOI：10.1021/jm070311l

  日期：2007.8.1

  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.