ethyl 6-Chloro-8-nitro-4-oxo-4H-chromene-2-carboxylate | 1237524-81-0

• 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: ethyl 6-Chloro-8-nitro-4-oxo-4H-chromene-2-carboxylate
• 英文别名: Ethyl 6-chloro-8-nitro-4-oxochromene-2-carboxylate
• CAS: 1237524-81-0
• 化学式: C₁₂H₈ClNO₆
• 分子量: 297.652
• InChiKey: WTMIJSJITATTJT-UHFFFAOYSA-N

物化性质

• 沸点：
  435.5±45.0 °C(Predicted)
• 密度：
  1.542±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 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：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 6-Chloro-8-nitro-4-oxo-4H-chromene-2-carboxylate 在 盐酸 、 tin(II) chloride dihdyrate 、 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， 反应 48.33h， 生成 6-Chloro-8-[(2-fluoro-4-methoxybenzoyl)amino]-4-oxochromene-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
• 作为产物：
  描述：

  在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以2.86 g的产率得到ethyl 6-Chloro-8-nitro-4-oxo-4H-chromene-2-carboxylate
  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