6-Bromo-4-oxo-8-[[4-(tritritiomethoxy)benzoyl]amino]chromene-2-carboxylic acid | 1450590-56-3

• 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: 6-Bromo-4-oxo-8-[[4-(tritritiomethoxy)benzoyl]amino]chromene-2-carboxylic acid
• 英文别名: 6-bromo-4-oxo-8-[[4-(tritritiomethoxy)benzoyl]amino]chromene-2-carboxylic acid
• CAS: 1450590-56-3
• 化学式: C₁₈H₁₂BrNO₆
• 分子量: 424.177
• InChiKey: TZKQFDIFVZAYER-RLXJOQACSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 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：

  4-(tert-butyldimethylsilyloxy)benzoyl chloride 在 potassium fluoride 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 6-Bromo-4-oxo-8-[[4-(tritritiomethoxy)benzoyl]amino]chromene-2-carboxylic acid
  参考文献：
  名称：

  6-Bromo-8-(4-[³H]methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic Acid: A Powerful Tool for Studying Orphan G Protein-Coupled Receptor GPR35

  摘要：

  The potent and selective GPR35 agonist 6-bromo-8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (12) was obtained in tritium-labeled form, designated [H-3]PSB-13253, with a specific activity of 36 Ci (1.33 TBq)/mmol. Radiolabeling was achieved by methylation of ethyl 6-bromo-8-(4-((tert-butyldimethylsilyl)oxy)benzamido)-4-oxo-4H-Chromene-2-carboxylate (19) with [H-3]methyl tosylate followed by ester hydrolysis. The radioligand was characterized by kinetic, saturation, and competition assays at membrane preparations of Chinese hamster ovary cells recombinantly expressing the human GPR35. [H-3]12 labeled the receptor with high affinity (K-D = 5.27 nM). Binding was saturable (B-max = 12.6 pmol/mg of protein) and reversible. Affinities of selected standard ligands and a library of amidochromen-4-one-2-carboxylates were determined. Binding data mostly correlated with potencies determined in beta-arrestin assays. On the basis of the test results, several new fluorine-substituted 6-bromo-8-benzamidochromen-4-one-2-carboxylic acids were obtained, which represent the most potent GPR35 agonists known to date. 6-Bromo-8-(2,6-difluoro-4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (83; K-i = 0.589 nM, EC50 = 5.54 nM) showed the highest affinity with a K-i value in the subnanomolar range.

  DOI：

  10.1021/jm4009373

文献信息

• 6-Bromo-8-(4-[³H]methoxybenzamido)-4-oxo-4<i>H</i>-chromene-2-carboxylic Acid: A Powerful Tool for Studying Orphan G Protein-Coupled Receptor GPR35
  作者：Dominik Thimm、Mario Funke、Anne Meyer、Christa E. Müller

  DOI：10.1021/jm4009373

  日期：2013.9.12

  The potent and selective GPR35 agonist 6-bromo-8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (12) was obtained in tritium-labeled form, designated [H-3]PSB-13253, with a specific activity of 36 Ci (1.33 TBq)/mmol. Radiolabeling was achieved by methylation of ethyl 6-bromo-8-(4-((tert-butyldimethylsilyl)oxy)benzamido)-4-oxo-4H-Chromene-2-carboxylate (19) with [H-3]methyl tosylate followed by ester hydrolysis. The radioligand was characterized by kinetic, saturation, and competition assays at membrane preparations of Chinese hamster ovary cells recombinantly expressing the human GPR35. [H-3]12 labeled the receptor with high affinity (K-D = 5.27 nM). Binding was saturable (B-max = 12.6 pmol/mg of protein) and reversible. Affinities of selected standard ligands and a library of amidochromen-4-one-2-carboxylates were determined. Binding data mostly correlated with potencies determined in beta-arrestin assays. On the basis of the test results, several new fluorine-substituted 6-bromo-8-benzamidochromen-4-one-2-carboxylic acids were obtained, which represent the most potent GPR35 agonists known to date. 6-Bromo-8-(2,6-difluoro-4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (83; K-i = 0.589 nM, EC50 = 5.54 nM) showed the highest affinity with a K-i value in the subnanomolar range.