4-溴-5-羟基-2-甲基-2H-吡嗪-3-酮 | 64178-59-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-溴-5-羟基-2-甲基-2H-吡嗪-3-酮
• 英文名称: 4-bromo-5-hydroxy-2-methyl-2H-pyridazin-3-one
• 英文别名: 4-bromo-5-hydroxy-2-methyl-2H-pyridazin-3-one；4-bromo-5-hydroxy-2-methylpyridazin-3-one
• CAS: 64178-59-2
• 化学式: C₅H₅BrN₂O₂
• 分子量: 205.011
• InChiKey: BNWUUAQSWHQZJW-UHFFFAOYSA-N

物化性质

• 熔点：
  283-284 °C(Solv: ethanol (64-17-5))
• 沸点：
  225.7±50.0 °C(Predicted)
• 密度：
  1.93±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-溴-5-羟基-2-甲基-2H-吡嗪-3-酮 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 (S)-2-(2,6-Dichloro-benzoylamino)-3-[4-(5-difluoromethoxy-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-phenyl]-propionic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Pyridazinone-Based α₄ Integrin Receptor Antagonists

  摘要：

  A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha(4)beta(1)/VCAM-1 and alpha(4)beta(7)/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the pyridazinone ring as well as the N-acyl phenylalanine scaffold. Potent dual antagonists of alpha(4)beta(1) and alpha(4)beta(7) were generated from an amide subseries; antagonists selective for alpha(4)beta(7) were identified from urea and carbamate-based subseries. The pharmacokinetic properties of selected members of the series have been determined in rats and demonstrate that the use of ester prodrugs and alterations to the amide linkage can lead to improved oral bioavailability in this series. An alpha(4),beta(7)-selective member of the carbamate subseries (36c), upon oral admininstration, demonstrated in vivo efficacy in the mouse DSS colitis model.

  DOI：

  10.1021/jm060031q
• 作为产物：
  描述：

  4,5-二溴-2-甲基-2H-吡嗪-3-酮 在 氢氧化钾 、 sodium methylate 作用下， 反应 15.0h， 生成 4-溴-5-羟基-2-甲基-2H-吡嗪-3-酮
  参考文献：
  名称：

  4,5-二卤代哒嗪-6-酮的同时烷基化-甲氧基化和5-卤代-4-羟基哒嗪-6-酮的合成

  摘要：

  通过同时进行的烷基化-甲氧基化反应，由1-烷基-4,5-二卤代哒嗪-6-酮合成了1-烷基-5-卤代-4-甲氧基哒嗪-6-酮。还制备了1-烷基-5-卤代-4-羟基哒嗪-6-。

  DOI：

  10.1002/jhet.5570330605

文献信息

• Pyridazinones as antagonists of alpha4 integrins
  申请人：Barbay Kent

  公开号：US20050192279A1

  公开（公告）日：2005-09-01

  The present invention relates to certain novel compounds of Formula (I): methods for preparing these compounds, compositions, intermediates and derivatives thereof and for the treatment of integrin mediated disorders.

  本发明涉及某些化合物的新颖结构，其化学式为（I）：制备这些化合物的方法，组合物，中间体及其衍生物以及用于治疗整合素介导的疾病。
• KONECNY V., CHEM. ZVESTI <CHZV-AN>, 1976, 30, NO 5, 663-673
  作者：KONECNY V.

  DOI：——

  日期：——
• Synthesis and Biological Evaluation of Novel Pyridazinone-Based α₄ Integrin Receptor Antagonists
  作者：Yong Gong、J. Kent Barbay、Alexey B. Dyatkin、Tamara A. Miskowski、Edward S. Kimball、Stephen M. Prouty、M. Carolyn Fisher、Rosemary J. Santulli、Craig R. Schneider、Nathaniel H. Wallace、Scott A. Ballentine、William E. Hageman、John A. Masucci、Bruce E. Maryanoff、Bruce P. Damiano、Patricia Andrade-Gordon、Dennis J. Hlasta、Pamela J. Hornby、Wei He

  DOI：10.1021/jm060031q

  日期：2006.6.1

  A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha(4)beta(1)/VCAM-1 and alpha(4)beta(7)/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the pyridazinone ring as well as the N-acyl phenylalanine scaffold. Potent dual antagonists of alpha(4)beta(1) and alpha(4)beta(7) were generated from an amide subseries; antagonists selective for alpha(4)beta(7) were identified from urea and carbamate-based subseries. The pharmacokinetic properties of selected members of the series have been determined in rats and demonstrate that the use of ester prodrugs and alterations to the amide linkage can lead to improved oral bioavailability in this series. An alpha(4),beta(7)-selective member of the carbamate subseries (36c), upon oral admininstration, demonstrated in vivo efficacy in the mouse DSS colitis model.
• Concurrent alkylation-methoxylation of 4,5-dihalopyridazin-6-ones and synthesis of 5-halo-4-hydroxypyridazin-6-ones
  作者：Su-Dong Cho、Woo-Yong Choi、Yong-Jin Yoon

  DOI：10.1002/jhet.5570330605

  日期：1996.11

  1-Alkyl-5-halo-4-methoxypyridazin-6-ones were synthesized from 1-alkyl-4,5-dihalopyridazin-6-ones by the concurrent alkylation-methoxylation. 1-Alkyl-5-halo-4-hydroxypyridazin-6-ones were also prepared.

  通过同时进行的烷基化-甲氧基化反应，由1-烷基-4,5-二卤代哒嗪-6-酮合成了1-烷基-5-卤代-4-甲氧基哒嗪-6-酮。还制备了1-烷基-5-卤代-4-羟基哒嗪-6-。