4-hydroxy-6-[2-(3-methoxyphenyl)ethyl]pyridazin-3(2H)-one | 1431637-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-hydroxy-6-[2-(3-methoxyphenyl)ethyl]pyridazin-3(2H)-one
• 英文别名: 4-hydroxy-6-(3-methoxyphenethyl)pyridazin-3(2H)-one；DAO-1903；6-[2-(3-Methoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione；6-[2-(3-methoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione
• CAS: 1431637-88-5
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: RPPHASUEWQGCLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (E)-(3-methoxystyryl)boronic acid 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 9.5h， 生成 4-hydroxy-6-[2-(3-methoxyphenyl)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

文献信息

• DIHYDROXY AROMATIC HETEROCYCLIC COMPOUND
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20140336165A1

  公开（公告）日：2014-11-13

  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.

  提供的是一种具有D-氨基酸氧化酶（DAAO）抑制作用的化合物，可用作例如精神分裂症或神经病性疼痛的预防和/或治疗剂。本发明人员研究了一种能够抑制DAAO的化合物，并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。换言之，本发明的二羟基芳香杂环化合物具有良好的DAAO抑制作用，并可用作例如精神分裂症或神经病性疼痛的预防和/或治疗剂。
• 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。
• Synthesis and preliminary evaluation of 4-hydroxy-6-(3-[11C]methoxyphenethyl)pyridazin-3(2H)-one, a 11C-labeled -amino acid oxidase (DAAO) inhibitor for PET imaging
  作者：Xiaoyun Deng、Yiding Zhang、Zhen Chen、Katsushi Kumata、Richard Van、Jian Rong、Tuo Shao、Akiko Hatori、Wakana Mori、Qingzhen Yu、Kuan Hu、Masayuki Fujinaga、Hsiao-Ying Wey、Yihan Shao、Lee Josephson、Giulia Murtas、Loredano Pollegioni、Ming-Rong Zhang、Steven Liang

  DOI：10.1016/j.bmcl.2020.127326

  日期：2020.8

  Selective DAAO inhibitors have demonstrated promising therapeutic effects in clinical studies, including clinically alleviating symptoms of schizophrenic patients and ameliorating cognitive function in Alzheimer's patients with early phase. Herein we report the synthesis and preliminary evaluation of a C-11-labeled positron emission tomography ligand based on a DAAO inhibitor, DAO-1903 (8). C-11-Isotopologue of 8 was prepared in high radiochemical yield with high radiochemical purity (> 99%) and high molar activity (> 37 GBq/umol). In vitro autoradiography studies indicated that the ligand possessed high in vitro specific binding to DAAO, while in vivo dynamic PET studies demonstrated that [C-11]8 failed to cross the blood-brain barrier possibly due to moderate brain efflux mechanism. Further chemical scaffold optimization is necessary to overcome limited brain permeability and improve specific binding.
• US9212147B2
  申请人：——

  公开号：US9212147B2

  公开（公告）日：2015-12-15
• US9562020B2
  申请人：——

  公开号：US9562020B2

  公开（公告）日：2017-02-07