dibenzyl 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl phosphate | 1032315-58-4

• 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: dibenzyl 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl phosphate
• 英文别名: dibenzyl 2-(2'-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl-phosphate；Dibenzyl [6-(2-fluorophenyl)-[1,3]dioxolo[4,5-g]quinolin-8-yl] phosphate
• CAS: 1032315-58-4
• 化学式: C₃₀H₂₃FNO₆P
• 分子量: 543.488
• InChiKey: CWTLCGVZBPTMDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dibenzyl 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl phosphate 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 6.17h， 生成 sodium 2-(2'-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl-phosphate
  参考文献：
  名称：

  WO2008/70176

  摘要：

  公开号：
• 作为产物：
  描述：

  焦磷酸四苄酯 、 6-(2-氟苯基)[1,3]二氧杂环戊并[4,5-g]喹啉-8(5H)-酮 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以67%的产率得到dibenzyl 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-yl 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

• NOVEL HYDROPHILIC DERIVATIVES OF 2-ARYL-4-QUINOLONES AS ANTICANCER AGENTS
  申请人：Kuo Sheng-Chu

  公开号：US20100168064A1

  公开（公告）日：2010-07-01

  2-aryl-4-quinolones are converted into phosphates by reacting with tetrabenzyl pyrophosphate to form dibenzyl phosphates thereof, which are then subject to hydrogenation to replace dibenzyl groups with H, followed by reacting with Amberlite IR-120 (Na+ form) to form disodium salts. The results of preliminary screening revealed that these phosphates showed significant anti-cancer activity. A novel intermediate, 2-selenophene 4-quinolone and Λ/, Λ/-dialkylaminoalkyl derivatives of 2-phenyl-4-quinolones are also synthesized. These novel intermediates exhibited significant anticancer activities.

  2-芳基-4-喹啉酮通过与四苄基焦磷酸酯反应转化为磷酸酯，然后进行氢化反应以取代二苄基基团为氢，接着与Amberlite IR-120（Na+形式）反应形成二钠盐。初步筛选结果表明，这些磷酸酯具有显著的抗癌活性。还合成了一种新型中间体2-硒吡咯烷-4-喹啉酮和2-苯基-4-喹啉酮Λ/，Λ/-二烷基氨基烷基衍生物。这些新型中间体表现出显著的抗癌活性。
• 2-SELENOPHENE-4-QUINOLONES AS ANTICANCER AGENTS
  申请人：China Medical University

  公开号：US20130253006A1

  公开（公告）日：2013-09-26

  2-aryl-4-quinolones are converted into phosphates by reacting with tetrabenzyl pyrophosphate to form dibenzyl phosphates thereof, which are then subject to hydrogenation to replace dibenzyl groups with H, followed by reacting with Amberlite IR-120(Na + form) to form disodium salts. The results of preliminary screening revealed that these phosphates showed significant anti-cancer activity. A novel intermediate, 2-selenophene 4-quinolone and N,N-dialkylaminoalkyl derivatives of 2-phenyl-4-quinolones are also synthesized. These novel intermediates exhibited significant anticancer activities.

  2-芳基-4-喹啉酮通过与四苄基焦磷酸酯反应转化为磷酸酯，然后经过氢化反应将二苄基基团替换为氢，随后与Amberlite IR-120（Na+形式）反应形成二钠盐。初步筛选结果表明，这些磷酸酯显示出显著的抗癌活性。同时，还合成了一种新型中间体2-硒吡咯-4-喹啉酮和2-苯基-4-喹啉酮的N,N-二烷基氨基烷基衍生物。这些新型中间体表现出显著的抗癌活性。
• 2-PHENYL-4-QUINOLONES AS ANTICANCER AGENTS
  申请人：China Medical University

  公开号：US20130252999A1

  公开（公告）日：2013-09-26

  2-aryl-4-quinolones are converted into phosphates by reacting with tetrabenzyl pyrophosphate to form dibenzyl phosphates thereof, which are then subject to hydrogenation to replace dibenzyl groups with H, followed by reacting with Amberlite IR-120(Na + form) to form disodium salts. The results of preliminary screening revealed that these phosphates showed significant anti-cancer activity. A novel intermediate, 2-selenophene 4-quinolone and N,N-dialkylaminoalkyl derivatives of 2-phenyl-4-quinolones are also synthesized. These novel intermediates exhibited significant anticancer activities.

  2-芳基-4-喹啉酮通过与四苯基焦磷酸酯反应转化为磷酸酯，然后经过氢化替换二苯甲基基团为氢，接着与琥珀酸树脂IR-120（Na+型）反应形成二钠盐。初步筛选结果显示，这些磷酸盐表现出显著的抗癌活性。此外，还合成了一种新型中间体2-硒吡咯烷-4-喹啉酮和2-苯基-4-喹啉酮的N,N-二烷基氨基烷基衍生物。这些新型中间体表现出显著的抗癌活性。
• NOVEL HYDROPHILIC DERIVATIVES OF 2-SELENOPHENE-4-QUINOLONES AS ANTICANCER AGENTS
  申请人：China Medical University

  公开号：US20130244983A1

  公开（公告）日：2013-09-19

  2-aryl-4-quinolones are converted into phosphates by reacting with tetrabenzyl pyrophosphate to form dibenzyl phosphates thereof, which are then subject to hydrogenation to replace dibenzyl groups with H, followed by reacting with Amberlite IR-120 (Na + form) to form disodium salts. The results of preliminary screening revealed that these phosphates showed significant anti-cancer activity. A novel intermediate, 2-selenophene 4-quinolone and N,N-dialkylaminoalkyl derivatives of 2-phenyl-4-quinolones are also synthesized. These novel intermediates exhibited significant anticancer activities.

  2-芳基-4-喹啉酮通过与四苄基焦磷酸盐反应转化为二苄基磷酸盐，然后经过氢化反应，用氢取代二苄基基团，接着与Amberlite IR-120（Na+形式）反应形成二钠盐。初步筛选结果表明，这些磷酸盐具有显著的抗癌活性。另外，还合成了一种新的中间体2-硒吡咯烷-4-喹啉酮和2-苯基-4-喹啉酮的N,N-二烷基氨基烷衍生物。这些新的中间体表现出显著的抗癌活性。
• US8440692B2
  申请人：——

  公开号：US8440692B2

  公开（公告）日：2013-05-14