3,4-bis(benzyloxy)-6-[(E)-2-[4-(trifluoromethyl)phenyl]-ethenyl]pyridazine | 1425512-05-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4-bis(benzyloxy)-6-[(E)-2-[4-(trifluoromethyl)phenyl]-ethenyl]pyridazine
• 英文别名: 3,4-bis(benzyloxy)-6-[(E)-2-[4-(trifluoromethyl)phenyl]thenyl]pyridazine；(E)-3,4-bis(benzyloxy)-6-(4-(trifluoromethyl)styryl)pyridazine；3,4-bis(phenylmethoxy)-6-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]pyridazine
• CAS: 1425512-05-5
• 化学式: C₂₇H₂₁F₃N₂O₂
• 分子量: 462.471
• InChiKey: DENXAWKOHQIDGO-DTQAZKPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3,4-bis(benzyloxy)-6-[(E)-2-[4-(trifluoromethyl)phenyl]-ethenyl]pyridazine 在 palladium 10% on activated carbon 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 4-hydroxy-6-{2-[4-(trifluoromethyl)phenyl]ethyl}pyridazin-3(2H)-one
  参考文献：
  名称：

  4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors

  摘要：

  D-Amino acid oxidase (DAAO) catalyzes the oxidation of D-amino acids including D-serine, a coagonist of the N-methyl-D-aspartate receptor. We identified a series of 4-hydroxypyridazin-3(2H)-one derivatives as novel DAAO inhibitors with high potency and substantial cell permeability using fragment-based drug design. Comparisons of complex structures deposited in the Protein Data Bank as well as those determined with in-house fragment hits revealed that a hydrophobic subpocket was formed perpendicular to the flavin ring by flipping Tyr224 in a ligand-dependent manner. We investigated the ability of the initial fragment hit, 3-hydroxy-pyridine-2(1H)-one, to fill this subpocket with the aid of complex structure information. 3-ydroxy-5-(2-phenylethyl)pyridine-2(1H)-one exhibited the predicted binding mode and demonstrated high inhibitory activity for human DAAO in enzyme- and cell-based assays. We further designed and synthesized 4-hydroxypyridazin-3(2H)-one derivatives, which are equivalent to the 3-hydroxy-pyridine-2(1H)-one series but lack cell toxicity. 6-[2-(3,5-Difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one was found to be effective against MK-801-induced cognitive deficit in the Y-maze.

  DOI：

  10.1021/jm400095b
• 作为产物：
  描述：

  3-[(E)-4-(Trifluoromethyl)styryl][1,4]benzodioxino[2,3-c]pyridazine 生成 3,4-bis(benzyloxy)-6-[(E)-2-[4-(trifluoromethyl)phenyl]-ethenyl]pyridazine
  参考文献：
  名称：

  J. Med. Chem. 2013, 56, 3582-3592

  摘要：

  DOI：

文献信息

• [EN] PYRIDAZINONE COMPOUNDS AND THEIR USE AS DAAO INHIBITORS<br/>[FR] COMPOSÉS DE PYRIDAZINONE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA DAAO
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013027000A1

  公开（公告）日：2013-02-28

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 and R2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式（I）的化合物及其药用盐，其中R1和R2如规范中定义，其制备方法，含有它们的药物组合物以及它们在治疗中的用途。
• NOVEL COMPOUNDS
  申请人：FARNABY William

  公开号：US20130052281A1

  公开（公告）日：2013-02-28

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式（I）的化合物及其药用盐，其中R1和R2如规范中定义，以及它们的制备方法、含有它们的药物组合物以及它们在治疗中的用途。
• PYRIDAZINONE COMPOUNDS AND THEIR USE AS DAAO INHIBITORS
  申请人：Farnaby William

  公开号：US20150030704A1

  公开（公告）日：2015-01-29

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式(I)的化合物及其药学上可接受的盐，其中R1和R2如规范所定义，其制备过程，含有它们的制药组合物以及它们在治疗方面的用途。
• Pyridazinone compounds and their use as DAAO inhibitors
  申请人：Farnaby William

  公开号：US09290456B2

  公开（公告）日：2016-03-22

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 and R2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式（I）的化合物及其药学上可接受的盐，其中R1和R2如规范所定义，其制备过程，含有它们的制药组合物以及它们在治疗中的使用。
• Dihydroxy aromatic heterocyclic compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US10202399B2

  公开（公告）日：2019-02-12

  Provided is a compound having a D-amino acid oxidase (DAAO) inhibitory action, and useful as, for example, a prophylaxis and/or therapeutic agent for schizophrenia or neuropathic pain. The present inventors have studied a compound that inhibits DAAO, and confirm that a dihydroxy aromatic heterocyclic compound has a DAAO inhibitory action, and completed the present invention. That is, the dihydroxy aromatic heterocyclic compound of the present invention has a good DAAO inhibitory action, and can be used as a prophylaxis and/or therapeutic agent for, for example, schizophrenia or neuropathic pain.

  本发明提供了一种具有 D-氨基酸氧化酶（DAAO）抑制作用的化合物，可用作精神分裂症或神经病理性疼痛的预防和/或治疗剂等。本发明人对一种抑制 DAAO 的化合物进行了研究，确认一种二羟基芳香杂环化合物具有 DAAO 抑制作用，并完成了本发明。也就是说，本发明的二羟基芳香杂环化合物具有良好的 DAAO 抑制作用，可用作精神分裂症或神经病理性疼痛等的预防和/或治疗剂。