7-溴-4-氧代-4H-色烯-2-羧酸 | 113850-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 7-溴-4-氧代-4H-色烯-2-羧酸
• 英文名称: 7-bromo-4-oxo-4H-chromene-2-carboxylic acid
• 英文别名: 7-bromo-4-oxochromene-2-carboxylic acid
• CAS: 113850-96-7
• 化学式: C₁₀H₅BrO₄
• 分子量: 269.051
• InChiKey: VACMFRPTBQYGGH-UHFFFAOYSA-N

物化性质

• 熔点：
  252-256°C
• 沸点：
  397.8±42.0 °C(Predicted)
• 密度：
  1.874±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  7-溴-4-氧代-4H-色烯-2-羧酸 在 盐酸 、 4-二甲氨基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium azide 、 氯甲酸乙酯 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 对甲苯磺酰氯 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 tert-butyl ((4-oxo-7-(4-phenylpiperazin-1-yl)-4H-chromen-2-yl)methyl)carbamate
  参考文献：
  名称：

  [EN] LYSYL OXIDASE-LIKE 2 INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE LA LYSYL OXYDASE-LIKE 2 ET UTILISATIONS DESDITS INHIBITEURS

  摘要：

  本文描述了一些LOXL2抑制剂化合物，制备这些化合物的方法，包含这些化合物的药物组合物和药物，以及使用这些化合物治疗与LOXL2活性相关的疾病、疾病或疾病的方法。

  公开号：

  WO2017015221A1
• 作为产物：
  描述：

  3-溴乙酸苯酯 在 三氟化硼乙醚 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 33.5h， 生成 7-溴-4-氧代-4H-色烯-2-羧酸
  参考文献：
  名称：

  Optimization of Chromone-2-carboxamide Melanin Concentrating Hormone Receptor 1 Antagonists:  Assessment of Potency, Efficacy, and Cardiovascular Safety

  摘要：

  Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.

  DOI：

  10.1021/jm060683e

文献信息

• Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups
  作者：Tao Xing、Shuyan Yu、Meng Qin、Mengdi Zhang、Yuheng Ma、Zhibin Xiao

  DOI：10.1016/j.bmcl.2023.129539

  日期：2023.11

  7 of the parent nucleus of the chromones can enhance the anti-inflammatory activity of the chromones. The molecular docking studies predicted the mode of interaction between the compounds and protein. Additionally, these studies have demonstrated that the amide bond is the key radical to the anti-inflammatory effect. Based on the summary of the aforementioned studies, it can be inferred that compound

  炎症是免疫系统对感染、损伤或刺激等各种刺激的最初生物反应。广泛的研究表明，越来越多的疾病是由炎症机制引发的。目前，抗炎药物因其治疗优势而广泛应用于临床。然而，我们也不能忽视潜在的副作用。本工作采用联合药物设计原理，设计合成了一系列以色酮为母核的酰胺类化合物。生物学评价结果表明，与阳性药物布洛芬相比，四种化合物表现出较低的EC 50值。值得注意的是，化合物5-9 对 RAW264.7 细胞中脂多糖 (LPS) 诱导的一氧化氮 (NO) 的产生表现出最佳的抑制活性 (EC 50 = 5.33 ± 0.57 μM)。构效关系(SAR)表明，色酮母核5位和8位吸电子基团或6位和7位给电子基团的存在可以增强色酮的抗炎活性。分子对接研究预测了化合物与蛋白质之间的相互作用模式。此外，这些研究表明酰胺键是抗炎作用的关键基团。根据上述研究的总结，可以推断化合物5-9具有作为抗炎药物的潜力，值得进一步研究。
• LEVAL, ALBERT;TIMAR, TIBOR, SYNTH. COMMUN., 20,(1990) N, C. 641-648
  作者：LEVAL, ALBERT、TIMAR, TIBOR

  DOI：——

  日期：——
• LYSYL OXIDASE-LIKE 2 INHIBITORS AND USES THEREOF
  申请人：Pharmakea, Inc.

  公开号：EP3325462A1

  公开（公告）日：2018-05-30
• Optimization of Chromone-2-carboxamide Melanin Concentrating Hormone Receptor 1 Antagonists:  Assessment of Potency, Efficacy, and Cardiovascular Safety
  作者：John K. Lynch、Jennifer C. Freeman、Andrew S. Judd、Rajesh Iyengar、Mathew Mulhern、Gang Zhao、James J. Napier、Dariusz Wodka、Sevan Brodjian、Brian D. Dayton、Doug Falls、Christopher Ogiela、Regina M. Reilly、Thomas J. Campbell、James S. Polakowski、Lisa Hernandez、Kennan C. Marsh、Robin Shapiro、Victoria Knourek-Segel、Brian Droz、Eugene Bush、Michael Brune、Lee C. Preusser、Ryan M. Fryer、Glenn A. Reinhart、Kathryn Houseman、Gilbert Diaz、Ann Mikhail、James T. Limberis、Hing L. Sham、Christine A. Collins、Philip R. Kym

  DOI：10.1021/jm060683e

  日期：2006.11.1

  Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.
• [EN] LYSYL OXIDASE-LIKE 2 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LA LYSYL OXYDASE-LIKE 2 ET UTILISATIONS DESDITS INHIBITEURS
  申请人：PHARMAKEA INC

  公开号：WO2017015221A1

  公开（公告）日：2017-01-26

  Described herein are compounds that are LOXL2 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with LOXL2 activity.

  本文描述了一些LOXL2抑制剂化合物，制备这些化合物的方法，包含这些化合物的药物组合物和药物，以及使用这些化合物治疗与LOXL2活性相关的疾病、疾病或疾病的方法。