(E)-6-((2-amino-4-hydroxy-5-methylphenyl)diazenyl)-3,4-dihydroquinolin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (E)-6-((2-amino-4-hydroxy-5-methylphenyl)diazenyl)-3,4-dihydroquinolin-2(1H)-one
• 化学式: C₁₆H₁₆N₄O₂
• 分子量: 296.329
• InChiKey: ANMQADUROYWADA-FMQUCBEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.58
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  100.07
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  6-硝基-3,4-二氢-2(1H)-喹啉酮 在 盐酸 、 亚硝酸特丁酯 、 氯化铵 、 锌 作用下， 以 甲醇 、 乙醇 、 水 、 乙腈 为溶剂， 反应 2.75h， 生成 (E)-6-((2-amino-4-hydroxy-5-methylphenyl)diazenyl)-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  [EN] INHIBITORS OF BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4)
  [FR] INHIBITEURS DE PROTÉINE 4 CONTENANT UN BROMODOMAINE (BRD4)

  摘要：

  某些实施例涉及BRD4溴结构域的小分子选择性抑制剂。本文描述的化合物可用于调节支气管NFκB-BRD4轴，该轴在对病毒分子模式的急性中性粒细胞反应中起作用。本文描述的化合物可作为各种人类疾病和病况的预防和治疗药物开发。

  公开号：

  WO2018112037A1

文献信息

• [EN] INHIBITORS OF BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4)<br/>[FR] INHIBITEURS DE PROTÉINE 4 CONTENANT UN BROMODOMAINE (BRD4)
  申请人：ZHOU JIA

  公开号：WO2018112037A1

  公开（公告）日：2018-06-21

  Certain embodiments are directed to small molecule selective inhibitors of the BRD4 bromodomain. Compounds described herein can be used to modulate the bronchiolar NFkB-BRD4 axis, which plays a role in acute neutrophilic response to viral molecular patterns. Compounds described herein can be developed as preventive and therapeutic agents for various human diseases and conditions.

  某些实施例涉及BRD4溴结构域的小分子选择性抑制剂。本文描述的化合物可用于调节支气管NFκB-BRD4轴，该轴在对病毒分子模式的急性中性粒细胞反应中起作用。本文描述的化合物可作为各种人类疾病和病况的预防和治疗药物开发。
• Inhibitors of bromodomain-containing protein 4 (BRD4)
  申请人：Zhou Jia

  公开号：US11117865B2

  公开（公告）日：2021-09-14

  Certain embodiments are directed to small molecule selective inhibitors of the BRD4 bromodomain. Compounds described herein can be used to modulate the bronchiolar NFkB-BRD4 axis, which plays a role in acute neutrophilic response to viral molecular patterns. Compounds described herein can be developed as preventive and therapeutic agents for various human diseases and conditions.

  某些实施方式涉及BRD4溴结构域的小分子选择性抑制剂。本文所述化合物可用于调节支气管NFκB-BRD4轴，其在响应病毒分子模式的急性中性粒细胞反应中发挥重要作用。本文所述化合物可开发为预防和治疗多种人类疾病和状况的药物。
• INHIBITORS OF BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4)
  申请人：Zhou, Jia

  公开号：EP3554503A1

  公开（公告）日：2019-10-23
• Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3-induced acute airway inflammation
  作者：Zhiqing Liu、Bing Tian、Haiying Chen、Pingyuan Wang、Allan R. Brasier、Jia Zhou

  DOI：10.1016/j.ejmech.2018.04.006

  日期：2018.5

  A series of diverse small molecules have been designed and synthesized through structure-based drug design by taking advantage of fragment merging and elaboration approaches. Compounds ZL0420 (28) and ZL0454 (35) were identified as potent and selective BRD4 inhibitors with nanomolar binding affinities to bromodomains (BDs) of BRD4. Both of them can be well docked into the acetyl-lysine (KAc) binding pocket of BRD4, forming key interactions including the critical hydrogen bonds with Asn140 directly and Tyr97 indirectly via a H2O molecule. Both compounds 28 and 35 exhibited submicromolar potency of inhibiting the TLR3-dependent innate immune gene program, including ISG54, 1SG56, IL-8, and Gro beta genes in cultured human small airway epithelial cells (hSAEC5). More importantly, they also demonstrated potent efficacy reducing airway inflammation in a mouse model with low toxicity, indicating a proof of concept that BRD4 inhibitors may offer the therapeutic potential to block the viral induced airway inflammation. (C) 2018 Elsevier Masson SAS. All rights reserved.