8-amino-6-bromo-4-oxo-4H-chromene-2-carboxylic acid ethyl ester | 156904-82-4

• 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-amino-6-bromo-4-oxo-4H-chromene-2-carboxylic acid ethyl ester
• 英文别名: ethyl 8-amino-6-bromo-4-oxo-4H-chromene-2-carboxylate；ethyl 8-amino-6-bromo-4-oxochromene-2-carboxylate
• CAS: 156904-82-4
• 化学式: C₁₂H₁₀BrNO₄
• 分子量: 312.12
• InChiKey: LLHNRAVVVZFEGE-UHFFFAOYSA-N

物化性质

• 沸点：
  447.3±45.0 °C(Predicted)
• 密度：
  1.663±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-amino-6-bromo-4-oxo-4H-chromene-2-carboxylic acid ethyl ester 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 6-bromo-8-(3-methylbenzamido)-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
• 作为产物：
  描述：

  5-溴-2-羟基-3-硝基乙酰苯 在 盐酸 、 tin(II) chloride dihdyrate 、 potassium tert-butylate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-amino-6-bromo-4-oxo-4H-chromene-2-carboxylic acid ethyl ester
  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

• Readily available chromenone receptors for carboxylates
  作者：César Raposo、Mercedes Crego、Ma Luisa Mussons、Ma Cruz Caballero、J.R. Morán

  DOI：10.1016/s0040-4039(00)76921-8

  日期：1994.5

  Several carboxylate group receptors able to bind syn and anti electron lone pairs have been prepared making use of an aminochromenone fragment. Symmetric ureas and sulfuryl amides permit the establishment of four linear hydrogen bonds with the carboxylate. The flat geometry of the sulfuryl amides complexes and the higher acidity of their hydrogens yield the best association constants.

  利用氨基色酮片段已经制备了几种能够结合Syn和反电子孤对的羧酸酯基受体。对称的脲和硫磺酰胺可与羧酸酯建立四个线性氢键。磺酰酰胺配合物的平面几何形状和氢的较高酸度可产生最佳的缔合常数。
• 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.
• Raposo Cesar, Crego Mercedes, Mussons M. Luisa, Caballero M. Cruz, Moran +, Tetrahedron Lett, 35 (1994) N 20, S 3409-3410
  作者：Raposo Cesar, Crego Mercedes, Mussons M. Luisa, Caballero M. Cruz, Moran +

  DOI：——

  日期：——
• 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.