N2,N2,N6,N6-tetrakis(2-methoxyethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N2,N2,N6,N6-tetrakis(2-methoxyethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine
• 英文别名: 2-N,2-N,6-N,6-N-tetrakis(2-methoxyethyl)-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazine-2,6-diamine；2-N,2-N,6-N,6-N-tetrakis(2-methoxyethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine
• 化学式: C₂₈H₄₈N₈O₄
• 分子量: 560.74
• InChiKey: GDAALJDXRYUSDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  双嘧达莫 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以84%的产率得到N2,N2,N6,N6-tetrakis(2-methoxyethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine
  参考文献：
  名称：

  Dipyridamole Inhibits Lipogenic Gene Expression by Retaining SCAP-SREBP in the Endoplasmic Reticulum

  摘要：

  DOI：

  10.1016/j.chembiol.2020.10.003

文献信息

• Active agent delivery systems and methods for protecting and administering active agents
  申请人：Shire LLC

  公开号：EP2080511A2

  公开（公告）日：2009-07-22

  A composition comprising a polypeptide and an active agent covalently attached to the polypeptide. Also provided is a method for delivery of an active agent to a patient comprising administering to the patient a composition comprising a polypeptide and an active agent covalently attached to the polypeptide. Also provided is a method for protecting an active agent from degradation comprising covalently attaching the active agent to a polypeptide. Also provided is a method for controlling release of an active agent from a composition comprising covalently attaching the active agent to the polypeptide.

  一种由多肽和与多肽共价连接的活性剂组成的组合物。还提供了一种向患者施用活性剂的方法，包括向患者施用一种组合物，该组合物包括多肽和与多肽共价连接的活性剂。还提供了一种保护活性剂不降解的方法，包括将活性剂共价连接到多肽上。还提供了一种控制活性剂从组合物中释放的方法，包括将活性剂共价连接到多肽上。
• Active agent delivery sytems and methods for protecting and administering active agents
  申请人：Shire LLC

  公开号：EP2266590A2

  公开（公告）日：2010-12-29

  The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

  本发明涉及活性剂给药系统，更具体地说，涉及由与活性剂共价连接的氨基酸（作为单个氨基酸或肽）组成的组合物以及给药共轭活性剂组合物的方法。
• Delivery system and methods for protecting and administering dextroamphetamine
  申请人：Shire LLC

  公开号：EP2316469A1

  公开（公告）日：2011-05-04

  The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

  本发明涉及活性剂给药系统，更具体地说，涉及由与活性剂共价连接的氨基酸（作为单个氨基酸或肽）组成的组合物以及给药共轭活性剂组合物的方法。
• Resistance-Modifying Agents. 11. Pyrimido[5,4-<i>d</i>]pyrimidine Modulators of Antitumor Drug Activity. Synthesis and Structure−Activity Relationships for Nucleoside Transport Inhibition and Binding to α₁-Acid Glycoprotein
  作者：Nicola J. Curtin、Hannah C. Barlow、Karen J. Bowman、A. Hilary Calvert、Richard Davison、Bernard T. Golding、Bing Huang、Peter J. Loughlin、David R. Newell、Peter G. Smith、Roger J. Griffin

  DOI：10.1021/jm040772w

  日期：2004.9.1

  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.
• 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.