2,6-dichloro-N⁴,N⁸-di-n-propyl-pyrimido[5,4-d]pyrimidine-4,8-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2,6-dichloro-N⁴,N⁸-di-n-propyl-pyrimido[5,4-d]pyrimidine-4,8-diamine
• 英文别名: 2,6-Dichloro-N4,N8-di-n-propyl-pyrimido[5,4-d]pyrimidine-4,8-diamine；2,6-dichloro-4-N,8-N-dipropylpyrimido[5,4-d]pyrimidine-4,8-diamine
• 化学式: C₁₂H₁₆Cl₂N₆
• 分子量: 315.205
• InChiKey: CKUKHEJKLBPVFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-N⁴,N⁸-di-n-propyl-pyrimido[5,4-d]pyrimidine-4,8-diamine 在 盐酸 作用下， 以 乙醚 、 乙醇 、 水 、 正丁醇 为溶剂， 反应 78.5h， 生成 N²,N²,N⁶-triethyl-N⁴,N⁸-di-n-propyl-pyrimido[5,4-d]pyrimidine-2,4,6,8-tetraamine hydrochloride
  参考文献：
  名称：

  [EN] NOVEL BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME
  [FR] NOUVEAUX COMPOSÉS DE MODULATION DU CONTRÔLE DE LA RESPIRATION ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2014151462A4
• 作为产物：
  描述：

  2,4,6,8-四羟基嘧啶并[5,4-D]嘧啶 在 五氯化磷 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 26.5h， 生成 2,6-dichloro-N⁴,N⁸-di-n-propyl-pyrimido[5,4-d]pyrimidine-4,8-diamine
  参考文献：
  名称：

  [EN] NOVEL BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME
  [FR] NOUVEAUX COMPOSÉS DE MODULATION DU CONTRÔLE DE LA RESPIRATION ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2014151462A4

文献信息

• NOVEL BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME
  申请人：GALLEON PHARMACEUTICALS, INC.

  公开号：US20160046635A1

  公开（公告）日：2016-02-18

  The present invention includes pyrimido[5,4-d]pyrimidines that are useful in the prevention and/or treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of preventing and/or treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one compound of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one compound of the invention.

  本发明涉及对呼吸控制疾病或障碍的预防和/或治疗有用的嘧啶并[5,4-d]嘧啶。本发明还包括一种预防和/或治疗受访者的呼吸系统疾病或障碍的方法，包括向受访者施用本发明中至少一种化合物的治疗有效量。本发明还包括一种预防不稳定或稳定受访者呼吸节律的方法，包括向受访者施用本发明中至少一种化合物的治疗有效量。
• 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.
• US9643971B2
  申请人：——

  公开号：US9643971B2

  公开（公告）日：2017-05-09
• [EN] NOVEL BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME<br/>[FR] NOUVEAUX COMPOSÉS DE MODULATION DU CONTRÔLE DE LA RESPIRATION ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GALLEON PHARMACEUTICALS INC

  公开号：WO2014151462A4

  公开（公告）日：2014-11-13