5-methylamino-7-chloro-4-hydroxy-3-(3-methoxyphenyl)-2(1H)-quinolone | 1186586-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-methylamino-7-chloro-4-hydroxy-3-(3-methoxyphenyl)-2(1H)-quinolone
• 英文别名: 7-chloro-4-hydroxy-3-(3-methoxyphenyl)-5-(methylamino)-1H-quinolin-2-one
• CAS: 1186586-45-7
• 化学式: C₁₇H₁₅ClN₂O₃
• 分子量: 330.771
• InChiKey: JQLVRHWSVSHKPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 5-amino-7-chloro-4-hydroxy-3-(3-methoxyphenyl)-2(1H)-quinolone 在 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 10.0h， 以71%的产率得到5-methylamino-7-chloro-4-hydroxy-3-(3-methoxyphenyl)-2(1H)-quinolone
  参考文献：
  名称：

  Development of N-[11C]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET radioligands for the glycine-binding site of NMDA receptors

  摘要：

  In this study, we synthesized and evaluated several amino 4-hydroxy-2(1H)-quinolone (4HQ) derivatives as new PET radioligand candidates for the glycine site of the NMDA receptors. Among these ligands, we discovered that 7-chloro-4-hydroxy-3-{3-(4-methylaminobenzyl) phenyl}-2-(1H)-quinolone (12) and 5-ethyl-7-chloro-4-hydroxy-3-(3-methylaminophenyl)-2(1H)-quinolone (32) have high affinity for the glycine site (K-i values; 11.7 nM for 12 and 11.8 nM for 32). In vitro autoradiography experiments indicated that [C-11]12 and [C-11]32 showed high specific binding in the brain slices, which were strongly inhibited by both glycine agonists and antagonists. In vivo brain uptake of these C-11-labeled 4HQs were examined in normal mice. Cerebellum to blood ratio of accumulation, of both [C-11]12 and [C-11]32 at 30 min were 0.058, which were slightly higher than those of cerebrum to blood ratio (0.043 and 0.042, respectively). These results indicated that [C-11]12 and [C-11]32 have poor blood brain barrier permeability. Although the plasma protein-binding ratio of [C-11]32 was much lower than methoxy analogs (71% vs 94-98%, respectively), [C-11]32 still binds with plasma protein strongly. It is conjectured that still acidic moiety and high affinity with plasma protein of [C-11]32 may prevent in vivo brain uptake. In conclusion, [C-11]12 and [C-11]32 are unsuitable for imaging cerebral NMDA receptors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.014

文献信息

• Development of N-[11C]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET radioligands for the glycine-binding site of NMDA receptors
  作者：Takeshi Fuchigami、Terushi Haradahira、Noriko Fujimoto、Yumiko Nojiri、Takahiro Mukai、Fumihiko Yamamoto、Takashi Okauchi、Jun Maeda、Kazutoshi Suzuki、Tetsuya Suhara、Hiroshi Yamaguchi、Mikako Ogawa、Yasuhiro Magata、Minoru Maeda

  DOI：10.1016/j.bmc.2009.06.014

  日期：2009.8

  In this study, we synthesized and evaluated several amino 4-hydroxy-2(1H)-quinolone (4HQ) derivatives as new PET radioligand candidates for the glycine site of the NMDA receptors. Among these ligands, we discovered that 7-chloro-4-hydroxy-3-3-(4-methylaminobenzyl) phenyl}-2-(1H)-quinolone (12) and 5-ethyl-7-chloro-4-hydroxy-3-(3-methylaminophenyl)-2(1H)-quinolone (32) have high affinity for the glycine site (K-i values; 11.7 nM for 12 and 11.8 nM for 32). In vitro autoradiography experiments indicated that [C-11]12 and [C-11]32 showed high specific binding in the brain slices, which were strongly inhibited by both glycine agonists and antagonists. In vivo brain uptake of these C-11-labeled 4HQs were examined in normal mice. Cerebellum to blood ratio of accumulation, of both [C-11]12 and [C-11]32 at 30 min were 0.058, which were slightly higher than those of cerebrum to blood ratio (0.043 and 0.042, respectively). These results indicated that [C-11]12 and [C-11]32 have poor blood brain barrier permeability. Although the plasma protein-binding ratio of [C-11]32 was much lower than methoxy analogs (71% vs 94-98%, respectively), [C-11]32 still binds with plasma protein strongly. It is conjectured that still acidic moiety and high affinity with plasma protein of [C-11]32 may prevent in vivo brain uptake. In conclusion, [C-11]12 and [C-11]32 are unsuitable for imaging cerebral NMDA receptors. (C) 2009 Elsevier Ltd. All rights reserved.