4-(4-fluoro-phenyl)-2H-phthalazin-1-one | 1766-63-8

• 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: 4-(4-fluoro-phenyl)-2H-phthalazin-1-one
• 英文别名: 4-(4-fluorophenyl)phthalazin-1(2H)-one；4-(4-fluorophenyl)-1-phthalazinone；4-(4-fluoro-phenyl)-2H-phthalazin-1-one；4-<4-Fluor-phenyl>-phthalazinon-(1(2H))；4-(4-fluorophenyl)-2H-phthalazin-1-one
• CAS: 1766-63-8
• 化学式: C₁₄H₉FN₂O
• mdl: MFCD00829940
• 分子量: 240.237
• InChiKey: ZMXMVYKPVMNLOJ-UHFFFAOYSA-N

物化性质

• 熔点：
  267.0-268.5 °C
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-fluoro-phenyl)-2H-phthalazin-1-one 在 三氯氧磷 作用下， 反应 1.5h， 以93%的产率得到1-氯-4-(4-氟苯基)酞嗪
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 1-aminophthalazinium salts as GABAA receptor antagonists

  摘要：

  The synthesis and in vitro GABA(A) activity as GABA(A) antagonists of some 1-aminophthalazinium salts and imidazophthalazines are reported. Structure-activity relationships and a molecular, modelling study allowed us to define the features which determine receptor affinity within this class of compounds.

  DOI：

  10.1016/0223-5234(94)90205-4
• 作为产物：
  描述：

  2-(4-氟苯酰基)苯甲酸 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以86%的产率得到4-(4-fluoro-phenyl)-2H-phthalazin-1-one
  参考文献：
  名称：

  Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-Imidazolyl)alkyl]-1(2H)-phthalazinones

  摘要：

  A number of 4-substituted 2-[omega-(1-imidazolyl)allryl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane Az synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.

  DOI：

  10.1021/jm00077a008

文献信息

• Palladium-Catalyzed Acylation Reactions: A One-Pot Diversified Synthesis of Phthalazines, Phthalazinones and Benzoxazinones
  作者：Basuli Suchand、Gedu Satyanarayana

  DOI：10.1002/ejoc.201800159

  日期：2018.5.24

  proceeds through [Pd]‐catalyzed acylation and nucleophilic cyclocondensation with dinucleophilic reagents. This process was based on direct coupling with simple bench‐top aldehydes without the assistance of directing group and without activating the carbonyl group. The process is highly advantageous because it employs simple nitrogen‐based nucleophiles, and non‐toxic and readily accessible aldehydes as the

  提出了一种用于酞嗪、酞嗪酮和苯并恶嗪酮多样化合成的连续单锅策略。该策略通过 [Pd] 催化的酰化和与双亲核试剂的亲核环缩合反应进行。该过程基于与简单的台式醛直接偶联，没有导向基团的帮助，也没有活化羰基。该方法非常有利，因为它使用简单的氮基亲核试剂和无毒且易于获得的醛作为羰基来源。最重要的是，该策略被应用于 PDE-4 抑制剂的一锅合成。
• 酞嗪酮类化合物、其制备方法、药物组合物及用途
  申请人：中国科学院上海药物研究所

  公开号：CN109384727B

  公开（公告）日：2023-07-28

  一种式I所示的酞嗪酮类化合物或其异构体或其药学上可接受的盐、酯、前药或溶剂合物，其制备方法，药物组合物及其在制备登革热病毒抑制剂中的用途。所述酞嗪酮类化合物结构如式I所示。该类化合物或其药物组合物具有抗登革病毒活性以及较好的选择性，可用于预防和/或治疗登革热病毒感染。
• Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors
  作者：Dong Lu、Jianan Liu、Yunzhe Zhang、Feifei Liu、Limin Zeng、Runze Peng、Li Yang、Huazhou Ying、Wei Tang、Wuhong Chen、Jianping Zuo、Xiankun Tong、Tao Liu、Youhong Hu

  DOI：10.1016/j.ejmech.2018.01.008

  日期：2018.2

  Using a dengue replicon cell line-based screening, we identified 3-(dimethylamino)propyl(3-((4-(4-fluorophenyl)-1-oxophthalazin-2(1H)-yl)methyl)phenyl)carbamate (10a) as a potent DENV-2 inhibitor, with an IC50 value of 0.64 μM. A series of novel phthalazinone derivatives based on hit 10a were synthesized and evaluated for their in vitro anti-DENV activity and cytotoxicity. The subsequent SAR study

  使用基于登革热复制子细胞系的筛选，我们确定了3-（二甲基氨基）丙基（3-（（（4-（4-氟苯基）-1-氧酞嗪-2（1H）-基）甲基）苯基）氨基甲酸酯（10a）作为有效的DENV-2抑制剂，IC 50值为0.64μM。合成了一系列基于命中10a的新型酞嗪酮衍生物，并对其体外抗-DENV活性和细胞毒性进行了评估。随后的SAR研究和优化导致发现最有前途的化合物14l，该化合物显示出强大的抗-DENV-2活性，对DENV-2 RNA复制的IC 50值低，为0.13μM，选择性高（SI = 89.2）。可接受的药代动力学资料。
• Rhodium(III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2<i>H</i> )-one Scaffolds via C-H Bond Activation
  作者：Xuxin Du、Hongcen Hou、Yongli Zhao、Shouri Sheng、Junmin Chen

  DOI：10.1002/ejoc.201901731

  日期：2020.3.8

  Rhodium(III)‐catalyzed selective C–H bond mono‐/bialkynylation of 4‐aryl phthalazin‐1(2H)‐one was developed. The silver salt AgSbF6 are demonstrated to play a vital role in promoting the bialkynylation reactions. Additionally, 6‐aryl pyridazin‐3(2H)‐one scaffold is amenable to the selective monoalkynylation and sequential bialkynylation, respectively. The present alkynylation strategy is simple, efficient

  开发了铑（III）催化的4-芳基酞嗪-1（2 H）-one的选择性C H键单/双炔基化。银盐AgSbF 6被证明在促进双炔基化反应中起着至关重要的作用。此外，6-芳基哒嗪-3（2 H）-one支架分别适用于选择性单炔基化和顺序双炔基化。当前的炔基化策略简单，有效，并且在空气气氛下具有高的官能团耐受性和广泛的底物范围。
• 4-Arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1)
  作者：Chae Jo Lim、Soo Hee Kim、Byung Ho Lee、Kwang-Seok Oh、Kyu Yang Yi

  DOI：10.1016/j.bmcl.2011.10.111

  日期：2012.1

  A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a highly potent MCH-R1 inhibitor with an IC50 = 1 nM. However, further investigations showed that this substance has unacceptable pharmacokinetic properties including a high clearance and volume of distribution. (C) 2011 Elsevier Ltd. All rights reserved.