5-bromo-2,3-bis(methoxymethoxy)pyridine | 1417710-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-bromo-2,3-bis(methoxymethoxy)pyridine
• 英文别名: 5-Bromo-2,3-bis(methoxymethoxy)pyridine
• CAS: 1417710-68-9
• 化学式: C₉H₁₂BrNO₄
• 分子量: 278.103
• InChiKey: SBLYHXHQCJSLKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-bromo-2,3-bis(methoxymethoxy)pyridine 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 21.0h， 生成 5-[(3-fluorobenzyl)sulfanyl]-3-hydroxypyridin-2(1H)-one
  参考文献：
  名称：

  5- OR 6-SUBSTITUTED 3-HYDROXY-2(1H)-PYRIDINONES AS D-AMINO ACID OXIDASE (DAAO) INHIBITORS IN THERAPY OF DISEASES SUCH AS SCHIZOPHRENIA, COGNITIVE DISORDER AND PAID

  摘要：

  本发明提供了化合物的公式（I）及其在药学上可接受的盐，其中R1是氢或氟，A和B中的一个是R2，另一个是一个基团—X—Y—R3。R3代表一个碳环或杂环。其他变量如规范中所定义。还声明了它们的制备方法、含有它们的药物组合物以及通过调节D-氨基酸氧化酶酶（DAAO）在治疗精神分裂症、认知障碍和疼痛等疾病方面的用途。

  公开号：

  US20140243353A1
• 作为产物：
  描述：

  5-溴-2,3-二羟基吡啶 、 氯甲基甲基醚 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以51%的产率得到5-bromo-2,3-bis(methoxymethoxy)pyridine
  参考文献：
  名称：

  [EN] 5- OR 6 - SUBSTITUTED 3 - HYDROXY - 2 ( 1H) - PYRIDINONES AS D-AMINO ACID OXIDASE (DAAO) INHIBITORS IN THERAPY OF DISEASES SUCH AS SCHIZOPHRENIA, COGNITIVE DISORDER AND PAIN
  [FR] 3-HYDROXY-2(1H)-PYRIDINONES 5- OU 6- SUBSTITUÉES UTILISÉES EN TANT QU'INHIBITEURS DE D-ACIDE AMINÉ OXYDASE (DAAO) EN THÉRAPIE DE MALADIES TELLES QUE LA SCHIZOPHRÉNIE, UN TROUBLE COGNITIF ET LA DOULEUR

  摘要：

  本发明提供了式(I)的化合物及其药用盐，其中R1为氢或氟，A和B中的一个为R2，另一个为-X-Y-R3基团。R3代表一个碳环或杂环。进一步的变量如规范中所定义。还声明了它们的制备方法，包含它们的药物组合物以及通过调节D-氨基酸氧化酶（DAAO）在治疗精神分裂症、认知障碍和疼痛等疾病中的用途。

  公开号：

  WO2013004996A1

文献信息

• [EN] 5- OR 6 - SUBSTITUTED 3 - HYDROXY - 2 ( 1H) - PYRIDINONES AS D-AMINO ACID OXIDASE (DAAO) INHIBITORS IN THERAPY OF DISEASES SUCH AS SCHIZOPHRENIA, COGNITIVE DISORDER AND PAIN<br/>[FR] 3-HYDROXY-2(1H)-PYRIDINONES 5- OU 6- SUBSTITUÉES UTILISÉES EN TANT QU'INHIBITEURS DE D-ACIDE AMINÉ OXYDASE (DAAO) EN THÉRAPIE DE MALADIES TELLES QUE LA SCHIZOPHRÉNIE, UN TROUBLE COGNITIF ET LA DOULEUR
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013004996A1

  公开（公告）日：2013-01-10

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 is hydrogen or fluorine, one of A and B is R2, the other is a group -X-Y-R3. R3 represents a carbocyclic or heterocyclic ring. Further variables are as defined in the specification. Also claimed are- processes for their preparation, pharmaceutical compositions containing them and their use in therapy of diseases such as schizophrenia, cognitive disorders and pain by modulating the D-amino acid oxidase enzyme (DAAO).

  本发明提供了式(I)的化合物及其药用盐，其中R1为氢或氟，A和B中的一个为R2，另一个为-X-Y-R3基团。R3代表一个碳环或杂环。进一步的变量如规范中所定义。还声明了它们的制备方法，包含它们的药物组合物以及通过调节D-氨基酸氧化酶（DAAO）在治疗精神分裂症、认知障碍和疼痛等疾病中的用途。
• 5- or 6-substituted 3-hydroxy-2 (1 H)-pyridinones as D-amino acid oxidase (DAAO) inhibitors in therapy of diseases such as schizophrenia, cognitive disorder and pain
  申请人：Farnaby William

  公开号：US09180122B2

  公开（公告）日：2015-11-10

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 is hydrogen or fluorine, one of A and B is R2, the other is a group —X—Y—R3. R3 represents a carbocyclic or heterocyclic ring. Further variables are as defined in the specification. Also claimed are—processes for their preparation, pharmaceutical compositions containing them and their use in therapy of diseases such as schizophrenia, cognitive disorders and pain by modulating the D-amino acid oxidase enzyme (DAAO).

  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是氢或氟，A和B中的一个是R2，另一个是—X—Y—R3基团。R3代表碳环或杂环。进一步的变量如规范中所定义。还要求它们的制备过程，包含它们的制药组合物以及通过调节D-氨基酸氧化酶（DAAO）酶来治疗精神分裂症、认知障碍和疼痛等疾病的用途。
• 4-Hydroxypyridazin-3(2<i>H</i>)-one Derivatives as Novel <scp>d</scp>-Amino Acid Oxidase Inhibitors
  作者：Takeshi Hondo、Masaichi Warizaya、Tatsuya Niimi、Ichiji Namatame、Tomohiko Yamaguchi、Keita Nakanishi、Toshihiro Hamajima、Katsuya Harada、Hitoshi Sakashita、Yuzo Matsumoto、Masaya Orita、Makoto Takeuchi

  DOI：10.1021/jm400095b

  日期：2013.5.9

  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.
• 5- OR 6 - SUBSTITUTED 3 - HYDROXY - 2 ( 1H) - PYRIDINONES AS D-AMINO ACID OXIDASE (DAAO) INHIBITORS IN THERAPY OF DISEASES SUCH AS SCHIZOPHRENIA, COGNITIVE DISORDER AND PAIN
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2729449B1

  公开（公告）日：2017-10-18
• US9180122B2
  申请人：——

  公开号：US9180122B2

  公开（公告）日：2015-11-10