8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid | 1443367-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid
• 英文别名: 8-[(4-Methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid；8-[(4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid
• CAS: 1443367-04-1
• 化学式: C₁₈H₁₃NO₆
• 分子量: 339.304
• InChiKey: OVNIVCKVZJXFDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  8-氨基-4-氧代-4H-1-苯并吡喃-2-羧酸乙酯 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid
  参考文献：
  名称：

  8-Benzamidochromen-4-one-2-carboxylic Acids: Potent and Selective Agonists for the Orphan G Protein-Coupled Receptor GPR35

  摘要：

  8-Amido-chromen-4-one-2-carboxylic acid derivatives were identified as novel agonists at the G protein-coupled orphan receptor GPR35. They were characterized by a beta-arrestin recruitment assay and optimized to obtain agonists with nanomolar potency for the human GPR35. The compounds were found to exhibit high selectivity versus the related GPR55. The most potent agonists were 6-bromo-8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (85, EC50 12.1 nM) and 6-bromo-8-(2-chloro-4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (90, EC50 11.1 nM), both of which were >1700 fold selective versus GPR55. Most compounds were considerably less potent at rat and mouse than at human GPR35. 6-Bromo-8-(2-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (87) was the only derivative that activated GPR35 of all three species at similar, low micromolar concentration. Compounds 85 and 90 are the most potent agonists at the human GPR35 known to date and might thus serve as powerful pharmacological tools to further elucidate the receptor's (patho)physiological role and its potential as a future drug target.

  DOI：

  10.1021/jm400587g

文献信息

• Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein
  作者：Brad E. Sleebs、Kate E. Jarman、Sonja Frolich、Wilson Wong、Julie Healer、Weiwen Dai、Isabelle S. Lucet、Danny W. Wilson、Alan F. Cowman

  DOI：10.1016/j.ijpddr.2020.10.008

  日期：2020.12

  library and the Medicines for Malaria Box and demonstrated the reproducibility and robustness of the assay for high-throughput screening purposes. The screen of the known drug library identified the known leukotriene antagonist, pranlukast. We used pranlukast as a model inhibitor in a post screening evaluation cascade. We procured and synthesised analogues of pranlukast to assist in the hit confirmation

  该恶性疟原虫导致人类疟疾的寄生虫必须侵入红细胞以提供自我复制和生存的环境。为了发生入侵，寄生虫必须与宿主红细胞表面的几种配体结合，以实现粘附、紧密连接的形成和进入。关键的相互作用包括红细胞结合样配体和网织红细胞结合样同源物 (Rhs) 与宿主红细胞表面的结合。网织红细胞结合样同源物 5 (Rh5) 是该家族中唯一对入侵至关重要的成员，它与 basigin 宿主受体结合。Rh5 的本质特性使其成为重要的疫苗靶点，但迄今为止，Rh5 尚未成为小分子干预的目标。在这里，我们描述了一种高通量筛选试验的发展，以识别干扰 Rh5-basigin 相互作用的小分子。为了验证该检测的实用性，我们筛选了一个已知的药物库和疟疾药物盒，并证明了该检测在高通量筛选方面的可重复性和稳健性。已知药物库的筛选鉴定了已知的白三烯拮抗剂普仑司特。我们在筛选后评估级联中使用普仑司特作为模型抑制剂。我们采购并合成了普仑司特的类
• 8-Benzamidochromen-4-one-2-carboxylic Acids: Potent and Selective Agonists for the Orphan G Protein-Coupled Receptor GPR35
  作者：Mario Funke、Dominik Thimm、Anke C. Schiedel、Christa E. Müller

  DOI：10.1021/jm400587g

  日期：2013.6.27

  8-Amido-chromen-4-one-2-carboxylic acid derivatives were identified as novel agonists at the G protein-coupled orphan receptor GPR35. They were characterized by a beta-arrestin recruitment assay and optimized to obtain agonists with nanomolar potency for the human GPR35. The compounds were found to exhibit high selectivity versus the related GPR55. The most potent agonists were 6-bromo-8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (85, EC50 12.1 nM) and 6-bromo-8-(2-chloro-4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (90, EC50 11.1 nM), both of which were >1700 fold selective versus GPR55. Most compounds were considerably less potent at rat and mouse than at human GPR35. 6-Bromo-8-(2-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (87) was the only derivative that activated GPR35 of all three species at similar, low micromolar concentration. Compounds 85 and 90 are the most potent agonists at the human GPR35 known to date and might thus serve as powerful pharmacological tools to further elucidate the receptor's (patho)physiological role and its potential as a future drug target.