2-(3,3-dimethylbutyl)-6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione | 1562524-40-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-(3,3-dimethylbutyl)-6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione
• 英文别名: 2-(3,3-Dimethylbutyl)-6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione；2-(3,3-dimethylbutyl)-1,2,4-triazinane-3,5,6-trione
• CAS: 1562524-40-6
• 化学式: C₉H₁₅N₃O₃
• 分子量: 213.236
• InChiKey: DXXZTSQGZURJJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-(benzyloxy)-2-(3,3-dimethylbutyl)-1,2,4-triazine-3,5(2H,4H)-dione 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、20.68 kPa 条件下， 反应 1.0h， 生成 2-(3,3-dimethylbutyl)-6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione
  参考文献：
  名称：

  6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel d-Amino Acid Oxidase Inhibitors

  摘要：

  A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives were synthesized as inhibitors of D-amino acid oxidase (DAAO). Many compounds in this series were found to be potent DAAO inhibitors, with IC50 values in the double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione pharmacophore appears metabolically resistant to O-glucuronidation unlike other structurally related DAAO inhibitors. Among them, 6-hydroxy-2-(naphthalen-1-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione 11h was found to be selective over a number of targets and orally available in mice. Furthermore, oral coadministration of D-serine with 11h enhanced the plasma levels of D-serine in mice compared to the oral administration of D-serine alone, demonstrating its ability to serve as a pharmacoenhancer of D-serine.

  DOI：

  10.1021/acs.jmedchem.5b00482

文献信息

• [EN] INHIBITORS OF D-AMINO ACID OXIDASE<br/>[FR] INHIBITEURS D'ACIDE AMINÉ D OXYDASE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2014025993A1

  公开（公告）日：2014-02-13

  D-amino acid oxidase (DAAO) inhibitors and methods of their use, either alone or in combination with D-serine or D-alanine, to facilitate allosteric activation of NMDA receptor-mediated neurotransmission and methods of their use as therapeutic agents for treating a subject afflicted with one or more cognitive-disorders, such as schizophrenia, including subjects suffering from negative symptoms and cognitive impairments, post-traumatic stress disorder (PTSD), or pain, are disclosed.

  抑制D-氨基酸氧化酶（DAAO）及其使用方法，可以单独使用或与D-丝氨酸或D-丙氨酸结合，以促进NMDA受体介导的神经递质的变构激活，并作为治疗剂用于治疗患有一个或多个认知障碍的受试者，如精神分裂症，包括患有消极症状和认知障碍的受试者，创伤后应激障碍（PTSD）或疼痛等。
• INHIBITORS OF D-AMINO ACID OXIDASE
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20150218156A1

  公开（公告）日：2015-08-06

  D-amino acid oxidase (DAAO) inhibitors and methods of their use, either alone or in combination with D-serine or D-alanine, to facilitate allosteric activation of NMDA receptor-mediated neurotransmission and methods of their use as therapeutic agents for treating a subject afflicted with one or more cognitive-disorders, such as schizophrenia, including subjects suffering from negative symptoms and cognitive impairments, post-traumatic stress disorder (PTSD), or pain, are disclosed.

  本文介绍了D-氨基酸氧化酶（DAAO）抑制剂及其使用方法，无论是单独使用还是与D-丝氨酸或D-丙氨酸结合使用，以促进NMDA受体介导的神经递质的异构激活，并作为治疗剂治疗患有一种或多种认知障碍的受试者，例如精神分裂症，包括患有消极症状和认知障碍的受试者，创伤后应激障碍（PTSD）或疼痛。
• US9505753B2
  申请人：——

  公开号：US9505753B2

  公开（公告）日：2016-11-29
• 6-Hydroxy-1,2,4-triazine-3,5(2<i>H</i>,4<i>H</i>)-dione Derivatives as Novel <scp>d</scp>-Amino Acid Oxidase Inhibitors
  作者：Niyada Hin、Bridget Duvall、Dana Ferraris、Jesse Alt、Ajit G. Thomas、Rana Rais、Camilo Rojas、Ying Wu、Krystyna M. Wozniak、Barbara S. Slusher、Takashi Tsukamoto

  DOI：10.1021/acs.jmedchem.5b00482

  日期：2015.9.24

  A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives were synthesized as inhibitors of D-amino acid oxidase (DAAO). Many compounds in this series were found to be potent DAAO inhibitors, with IC50 values in the double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione pharmacophore appears metabolically resistant to O-glucuronidation unlike other structurally related DAAO inhibitors. Among them, 6-hydroxy-2-(naphthalen-1-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione 11h was found to be selective over a number of targets and orally available in mice. Furthermore, oral coadministration of D-serine with 11h enhanced the plasma levels of D-serine in mice compared to the oral administration of D-serine alone, demonstrating its ability to serve as a pharmacoenhancer of D-serine.