4-(2,6-dimethylmorpholino)-1(2H)-phthalazinone | 78755-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-(2,6-dimethylmorpholino)-1(2H)-phthalazinone
• 英文别名: 4-(2,6-dimethylmorpholin-4-yl)-2H-phthalazin-1-one
• CAS: 78755-21-2
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: HTWLCOZPOOIXRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  53.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  iodoferrocene 、 4-(2,6-dimethylmorpholino)-1(2H)-phthalazinone 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 作用下， 以 三乙胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以23%的产率得到4-(2,6-dimethylmorpholino)-2-ferrocenylphthalazin-1(2H)-one
  参考文献：
  名称：

  N -ferrocenylpyridazinones and new organic analogues: Synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation

  摘要：

  Employing an optimized Pd-catalyzed cross-coupling reaction promoted by CuI, novel N-ferrocenylpyridazinones along with N-phenyl- and N-(2-pyridyl) analogues were synthesized from readily available heterocyclic precursors, iodoferrocene, iodobenzene and 2-bromopyridine. With exception of the ferrocenylation of 6-ferrocenylpyridazin-3(2H)-one yielding both N- and O-substituted products, the studied reactions exclusively afforded N-aryl lactams. The novel compounds exhibited cytotoxicity towards HEPG2 and HT-29 human malignant cells under in vitro conditions. The measured IC50 values supplemented with the results of cyclic voltammetry and DFT calculations suggest that the cytotoxic activity of the N- and O-ferrocenyl-substituted derivatives and the decreased effect of the N-phenyl analogues seem to be at least partly associated with the potential to generate reactive oxygen species (ROS). This interpretation, allowing the prediction of characteristic substituent-dependent SAR, was supported by the results of related studies on the practically inactive N-(2-pyridyl)pyridazinones assumed to be present in protonated chelate forms with highly a decreased propensity to undergo ionization. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2017.09.015
• 作为产物：
  描述：

  4-氯-1(2H)-酞嗪酮 、 2,6-二甲基吗啉 以72%的产率得到
  参考文献：
  名称：

  KOERMENDY K.; RUFF F., ACTA CHIM. ACAD. SCI. HUNG., 1981, 106, NO 2, 155-166

  摘要：

  DOI：

文献信息

• POTASSIUM CHANNEL MODULATORS
  申请人：Brown Brian S.

  公开号：US20120289500A1

  公开（公告）日：2012-11-15

  Disclosed herein are KCNQ potassium channels modulators of formula (I) wherein ring G 1 , R 1 , and R 2 are as defined in the specification. Compositions comprising such compounds; and methods for treating conditions and disorders using such compounds and compositions are also described.

  本文披露了式（I）的KCNQ钾通道调节剂，其中环G、R1和R2如规范中所定义。还描述了包含这些化合物的组合物；以及使用这些化合物和组合物治疗疾病和疾病的方法。
• Koermendy, K.; Ruff, F., Acta Chimica Academiae Scientiarum Hungaricae, 1981, vol. 106, # 2, p. 155 - 166
  作者：Koermendy, K.、Ruff, F.

  DOI：——

  日期：——
• US8859549B2
  申请人：——

  公开号：US8859549B2

  公开（公告）日：2014-10-14
• [EN] CONDENSED 2 - CARBAMOYLPYRIDAZINONES AS POTASSIUM CHANNEL MODULATORS<br/>[FR] 2-CARBAMOYLPYRIDAZINONES CONDENSÉES EN TANT QUE MODULATEURS DES CANAUX POTASSIQUES
  申请人：ABBOTT LAB

  公开号：WO2012158399A1

  公开（公告）日：2012-11-22

  Disclosed herein are KCNQ potassium channels modulators of formula (I) wherein ring G1, R1, and R2 are as defined in the specification. Compositions comprising such compounds; and methods for treating conditions and disorders using such compounds and compositions are also described.
• N -ferrocenylpyridazinones and new organic analogues: Synthesis, cyclic voltammetry, DFT analysis and in vitro antiproliferative activity associated with ROS-generation
  作者：Tamás Jernei、Szilvia Bősze、Rita Szabó、Ferenc Hudecz、Katalin Majrik、Antal Csámpai

  DOI：10.1016/j.tet.2017.09.015

  日期：2017.10

  Employing an optimized Pd-catalyzed cross-coupling reaction promoted by CuI, novel N-ferrocenylpyridazinones along with N-phenyl- and N-(2-pyridyl) analogues were synthesized from readily available heterocyclic precursors, iodoferrocene, iodobenzene and 2-bromopyridine. With exception of the ferrocenylation of 6-ferrocenylpyridazin-3(2H)-one yielding both N- and O-substituted products, the studied reactions exclusively afforded N-aryl lactams. The novel compounds exhibited cytotoxicity towards HEPG2 and HT-29 human malignant cells under in vitro conditions. The measured IC50 values supplemented with the results of cyclic voltammetry and DFT calculations suggest that the cytotoxic activity of the N- and O-ferrocenyl-substituted derivatives and the decreased effect of the N-phenyl analogues seem to be at least partly associated with the potential to generate reactive oxygen species (ROS). This interpretation, allowing the prediction of characteristic substituent-dependent SAR, was supported by the results of related studies on the practically inactive N-(2-pyridyl)pyridazinones assumed to be present in protonated chelate forms with highly a decreased propensity to undergo ionization. (C) 2017 Elsevier Ltd. All rights reserved.