sodium 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl hydrogen phosphate | 1207854-61-2

• 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: sodium 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl hydrogen phosphate
• 英文别名: Phosphoric acid mono-[6-(2-fluoro-phenyl)-[1,3]dioxolo[4,5-g]quinolin-8-yl] ester mono-sodium salt；sodium;[6-(2-fluorophenyl)-[1,3]dioxolo[4,5-g]quinolin-8-yl] hydrogen phosphate
• CAS: 1207854-61-2
• 化学式: C₁₆H₁₀FNO₆P*Na
• 分子量: 385.22
• InChiKey: ZLFNSIWQUXGDSY-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.39
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl dihydrogen phosphate 在 碳酸氢钠 作用下， 以 水 为溶剂， 以75.3%的产率得到sodium 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl hydrogen phosphate
  参考文献：
  名称：

  Synthesis and Preclinical Evaluations of 2-(2-Fluorophenyl)-6,7-methylenedioxyquinolin-4-one Monosodium Phosphate (CHM-1−P-Na) as a Potent Antitumor Agent

  摘要：

  CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] (1) has a unique antitumor mechanism of action. However, because 1 has relatively low hydrophilicity, it was evaluated only via ip administration, which is not clinically acceptable. In this study, we synthesized the monosodium phosphate salt (CHM-1-P-Na, 4) of 1 as a hydrophilic prodrug. Compound 4 was rapidly converted into 1 following iv and po administration and also possessed excellent antitumor activity in a SKOV-3 xenograft nude mice model. Compound 4 also had clear-cut pharmacological effects oil enzymes related with tumor cells. Neither 4 not 1 significantly affected normal biological function in a safety pharmacology profiling study. Compound 1 caused apoptotic effects in breast carcinoma cells via accumulation of cyclin B1, and importantly, the endogenous levels of the mitotic spindle checkpoint proteins BubR1 directly correlated with cellular response to microtubule disruption. With excellent antitumor activity profiles, 4 is highly promising for development as all anticancer clinical trials candidate.

  DOI：

  10.1021/jm901292j

文献信息

• Synthesis and Preclinical Evaluations of 2-(2-Fluorophenyl)-6,7-methylenedioxyquinolin-4-one Monosodium Phosphate (CHM-1−P-Na) as a Potent Antitumor Agent
  作者：Li-Chen Chou、Chien-Ting Chen、Jang-Chang Lee、Tzong-Der Way、Chi-Hung Huang、Shih-Ming Huang、Che-Ming Teng、Takao Yamori、Tian-Shung Wu、Chung-Ming Sun、Du-Shieng Chien、Keduo Qian、Susan L. Morris-Natschke、Kuo-Hsiung Lee、Li-Jiau Huang、Sheng-Chu Kuo

  DOI：10.1021/jm901292j

  日期：2010.2.25

  CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] (1) has a unique antitumor mechanism of action. However, because 1 has relatively low hydrophilicity, it was evaluated only via ip administration, which is not clinically acceptable. In this study, we synthesized the monosodium phosphate salt (CHM-1-P-Na, 4) of 1 as a hydrophilic prodrug. Compound 4 was rapidly converted into 1 following iv and po administration and also possessed excellent antitumor activity in a SKOV-3 xenograft nude mice model. Compound 4 also had clear-cut pharmacological effects oil enzymes related with tumor cells. Neither 4 not 1 significantly affected normal biological function in a safety pharmacology profiling study. Compound 1 caused apoptotic effects in breast carcinoma cells via accumulation of cyclin B1, and importantly, the endogenous levels of the mitotic spindle checkpoint proteins BubR1 directly correlated with cellular response to microtubule disruption. With excellent antitumor activity profiles, 4 is highly promising for development as all anticancer clinical trials candidate.