2-(3,4-dichlorophenyl)-4-hydroxyphthalazin-1(2H)-one

• 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: 2-(3,4-dichlorophenyl)-4-hydroxyphthalazin-1(2H)-one
• 英文别名: Phthalazine-1,4(2H,3H)-dione, 2-(3,4-dichlorohenyl)-；3-(3,4-dichlorophenyl)-2H-phthalazine-1,4-dione
• 化学式: C₁₄H₈Cl₂N₂O₂
• 分子量: 307.136
• InChiKey: YVKYHTVGVNMDFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 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：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(3,4-dichlorophenyl)-4-hydroxyphthalazin-1(2H)-one 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 生成 2-(3,4-dichlorophenyl)-4-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)propoxy)phthalazin-1(2H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of new 6-hydroxypyridazinone benzisoxazoles: Potential multi-receptor-targeting atypical antipsychotics

  摘要：

  In recent years, multi-targeting directed ligands have attracted great interest as possible new atypical antipsychotics. Combinations of dopamine and serotonin receptor ligands within single molecules might afford new therapeutic opportunities. Herein, we describe the synthesis of a novel series of 6-hydroxypyridazinone benzisoxazoles and their binding behaviors to different receptors in terms of atypical antipsychotic behaviors. The most potent compound (46) exhibited excellent affinities for certain receptors (D-2, K-i = 0.5 +/- 0.07 nM; 5-HT1A, K-i = 5.9 +/- 0.8 nM; 5-HT2A, K-i = 0.3 +/- 0.01 nM; 5-HT6, K-i = 0.5 +/- 0.04 nM) and combined with low affinities for the H-1, 5-HT2C, and adrenergic alpha(1) receptors. In contrast to risperidone, compound 46 exhibited a high cataleptic threshold; this may be useful in the development of a novel class of drugs treating schizophrenia. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.09.008
• 作为产物：
  描述：

  苯酐 、 3,4-二氯苯肼盐酸盐 在 盐酸 作用下， 以 水 为溶剂， 反应 9.0h， 以78.2%的产率得到2-(3,4-dichlorophenyl)-4-hydroxyphthalazin-1(2H)-one
  参考文献：
  名称：

  新型的合成和生物学评价σ 1个受体配体用于治疗神经性疼痛：6- Hydroxypyridazinones

  摘要：

  通过使用6- hydroxypyridazinone框架，一个新的系列有效的σ的1具有药理antineuropathic疼痛活性相关的受体的配体合成并在本文中被描述。在体外受体结合研究显示高σ 1个受体亲和力（ķ我σ 1 = 1.4纳米）和优良的选择性超过不仅σ 2受体（1366倍），但也其他CNS目标（肾上腺素，μ阿片，sertonerigic受体等-）表示2-（3,4-二氯苯基）-6-（3-（哌啶-1-基）丙氧基）哒嗪-3（2 H）-1 （化合物54）。化合物54在小鼠福尔马林模型和大鼠慢性压迫性神经损伤疼痛（CCI）模型中显示出剂量依赖性的抗痛觉过敏特性。此外，化合物的功能活性54使用苯妥英进行了评价，表明化合物为σ 1受体拮抗剂。此外，在抗痛觉过敏剂量的轮状试验中未发现运动障碍，在运动活动试验中未见镇静副作用。最后但并非最不重要的一点是，还指出了良好的安全性和良好的药代动力学特性。

  DOI：

  10.1021/acs.jmedchem.5b01416

文献信息

• Synthesis and Biological Evaluation of Novel σ₁ Receptor Ligands for Treating Neuropathic Pain: 6-Hydroxypyridazinones
  作者：Xudong Cao、Yin Chen、Yifang Zhang、Yu Lan、Juecheng Zhang、Xiangqing Xu、Yinli Qiu、Song Zhao、Xin Liu、Bi-Feng Liu、Guisen Zhang

  DOI：10.1021/acs.jmedchem.5b01416

  日期：2016.4.14

  framework, a new series of potent σ1 receptor ligands associated with pharmacological antineuropathic pain activity was synthesized and is described in this article. In vitro receptor binding studies revealed high σ1 receptor affinity (Ki σ1 = 1.4 nM) and excellent selectivity over not only σ2 receptor (1366-fold) but also other CNS targets (adrenergic, μ-opioid, sertonerigic receptors, etc.) for 2-(3,4-d

  通过使用6- hydroxypyridazinone框架，一个新的系列有效的σ的1具有药理antineuropathic疼痛活性相关的受体的配体合成并在本文中被描述。在体外受体结合研究显示高σ 1个受体亲和力（ķ我σ 1 = 1.4纳米）和优良的选择性超过不仅σ 2受体（1366倍），但也其他CNS目标（肾上腺素，μ阿片，sertonerigic受体等-）表示2-（3,4-二氯苯基）-6-（3-（哌啶-1-基）丙氧基）哒嗪-3（2 H）-1 （化合物54）。化合物54在小鼠福尔马林模型和大鼠慢性压迫性神经损伤疼痛（CCI）模型中显示出剂量依赖性的抗痛觉过敏特性。此外，化合物的功能活性54使用苯妥英进行了评价，表明化合物为σ 1受体拮抗剂。此外，在抗痛觉过敏剂量的轮状试验中未发现运动障碍，在运动活动试验中未见镇静副作用。最后但并非最不重要的一点是，还指出了良好的安全性和良好的药代动力学特性。
• Synthesis and biological evaluation of new 6-hydroxypyridazinone benzisoxazoles: Potential multi-receptor-targeting atypical antipsychotics
  作者：Xudong Cao、Yin Chen、Yifang Zhang、Yinli Qiu、Minquan Yu、Xiangqing Xu、Xin Liu、Bi-Feng Liu、Guisen Zhang

  DOI：10.1016/j.ejmech.2016.09.008

  日期：2016.11

  In recent years, multi-targeting directed ligands have attracted great interest as possible new atypical antipsychotics. Combinations of dopamine and serotonin receptor ligands within single molecules might afford new therapeutic opportunities. Herein, we describe the synthesis of a novel series of 6-hydroxypyridazinone benzisoxazoles and their binding behaviors to different receptors in terms of atypical antipsychotic behaviors. The most potent compound (46) exhibited excellent affinities for certain receptors (D-2, K-i = 0.5 +/- 0.07 nM; 5-HT1A, K-i = 5.9 +/- 0.8 nM; 5-HT2A, K-i = 0.3 +/- 0.01 nM; 5-HT6, K-i = 0.5 +/- 0.04 nM) and combined with low affinities for the H-1, 5-HT2C, and adrenergic alpha(1) receptors. In contrast to risperidone, compound 46 exhibited a high cataleptic threshold; this may be useful in the development of a novel class of drugs treating schizophrenia. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Ru(II)-Catalyzed C–H Activation and Annulation Reaction via Carbon–Carbon Triple Bond Cleavage
  作者：Rashmi Prakash、Bidisha R. Bora、Romesh C. Boruah、Sanjib Gogoi

  DOI：10.1021/acs.orglett.8b00643

  日期：2018.4.20

  An unprecedented Ru(II)-catalyzed C–H activation and annulation reaction, which proceeds via C–C triple bond cleavage, is reported. This reaction of 2-phenyldihydrophthalazinediones with alkynes, which works most efficiently in the presence of bidented ligand 1,3-bis(diphenylphosphino)propane, affords good yields of substituted quinazolines.

  据报道，空前的Ru（II）催化的CH活化和环化反应是通过CC的三键裂解而进行的。2-苯基二氢酞嗪二酮与炔烃的这种反应在双键配体1,3-双（二苯基膦基）丙烷的存在下最有效地进行，产生了高产率的取代喹唑啉。