1-(3-bromo-2-hydroxy-5-nitrophenyl)ethanone | 90004-97-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-bromo-2-hydroxy-5-nitrophenyl)ethanone
• 英文别名: 5-Nitro-2-hydroxy-3-brom-acetophenon；3'-bromo-2'-hydroxy-5'-nitroacetophenone
• CAS: 90004-97-0
• 化学式: C₈H₆BrNO₄
• 分子量: 260.044
• InChiKey: NUPQONVDLVCQBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-bromo-2-hydroxy-5-nitrophenyl)ethanone 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638
• 作为产物：
  描述：

  2-羟基-5-硝基苯乙酮 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 以56%的产率得到1-(3-bromo-2-hydroxy-5-nitrophenyl)ethanone
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638

文献信息

• Design, synthesis and biological evaluation of thiazolyl-halogenated pyrroles or pyrazoles as novel antibacterial and antibiofilm agents
  作者：Yuanchen Zhong、Huan Liu、Feifei Chen、Qian He、Xiaofei Zhang、Lefu Lan、Chunhao Yang

  DOI：10.1016/j.ejmech.2024.116221

  日期：2024.3

  The formation of biofilm is one of the important factors for bacteria to develop drug-resistant. A series of halogenated-pyrroles or pyrazoles containing thiazole groups as antibacterial agents were designed and synthesized to target biofilms. Among them, compound showed antibacterial activity against various Gram-positive bacteria, particularly against vancomycin-resistant (MIC ≤0.125 μg/mL). Additionally

  生物膜的形成是细菌产生耐药性的重要因素之一。设计并合成了一系列含有噻唑基团的卤代吡咯或吡唑作为抗菌剂，以针对生物膜。其中，化合物对多种革兰氏阳性菌均表现出抗菌活性，特别是对万古霉素耐药菌（MIC≤0.125 μg/mL）。此外，该化合物在亚 MIC 剂量下可显着抑制生物膜形成。此外，与吡咯霉素 C 相比，该化合物表现出显着较低的哺乳动物细胞毒性，并且还评估了其在不同物种中的肝微粒体代谢稳定性。进一步的感染模型实验证明该化合物是有效的。
• US3933472A
  申请人：——

  公开号：US3933472A

  公开（公告）日：1976-01-20
• Development of Serine Protease Inhibitors Displaying a Multicentered Short (&lt;2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa
  作者：Erik Verner、Bradley A. Katz、Jeffrey R. Spencer、Darin Allen、Jason Hataye、Witold Hruzewicz、Hon C. Hui、Aleksandr Kolesnikov、Yong Li、Christine Luong、Arnold Martelli、Kesavan Radika、Roopa Rai、Miles She、William Shrader、Paul A. Sprengeler、Sean Trapp、Jing Wang、Wendy B. Young、Richard L. Mackman

  DOI：10.1021/jm0100638

  日期：2001.8.1

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.