2,6-bis(morpholinomethyl)cyclohexanone dihydrochloride | 6333-29-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2,6-bis(morpholinomethyl)cyclohexanone dihydrochloride
• 英文别名: 2,6-bis-morpholinomethyl-cyclohexanone; dihydrochloride；2,6-Bis-morpholinomethyl-cyclohexanon; Dihydrochlorid；Cyclohexanone,6-bis(4-morpholinylmethyl)-,dihydrochloride；2,6-bis(morpholin-4-ylmethyl)cyclohexan-1-one;hydrochloride
• CAS: 6333-29-5
• 化学式: C₁₆H₂₈N₂O₃*2ClH
• 分子量: 369.332
• InChiKey: SCBXUVILBQDHCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.06
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-bis(morpholinomethyl)cyclohexanone dihydrochloride 、 乙酰乙酸乙酯 在 montmorillonite K₁₀ Clay 、 ammonium acetate 作用下， 以 水 为溶剂， 反应 1.0h， 以52%的产率得到ethyl 2-methyl-8-methylene-5,6,7,8-tetrahydroquinoline-3-carboxylate
  参考文献：
  名称：

  Design, synthesis, and antitumor evaluation of novel methylene moiety-tetheredtetrahydroquinoline derivatives

  摘要：

  通过环保型 K-10 蒙脱石粘土催化反应，曼尼希碱、可烯化酮和 NH$_{4}$OAc 在水中发生单锅多组分反应，合成了新型亚甲基系四氢喹啉（THQs）和环五[$b$]吡啶。(9a) 、2-甲基-8-亚甲基-5,6,7,8-四氢喹啉-3-基乙酮 (9b)、1-(2-甲基-7-亚甲基-6,7-二氢-5$H$-环戊并[$b$]吡啶-3-基)乙酮 (11a)人乳腺癌（MCF-7）、前列腺癌（PC3）、神经母细胞瘤（SH-SY5Y）和小鼠成纤维细胞（L929）细胞系进行了浓度依赖性（50-300 μM）和时间依赖性（24-72 h）试验，并以 IC$_{50\, }$ 值表示。 结果表明，与 9b 和 11a 相比，化合物 9a 在 72 小时后对所有细胞株诱导的 IC$_{50\, }$ 值最低，从 111 ± 1.1 μM 到 128 ± 1.3 μM。

  DOI：

  10.3906/kim-1907-71
• 作为产物：
  描述：

  聚合甲醛 、 吗啡啉盐酸盐 、 环己酮 在 溶剂黄146 作用下， 生成 2,6-bis(morpholinomethyl)cyclohexanone dihydrochloride
  参考文献：
  名称：

  The Use of Substituted Phenols in the Mannich Reaction and the Dehalogenation of Aminomethylhalophenols

  摘要：

  DOI：

  10.1021/jo01090a008

文献信息

• The Use of Substituted Phenols in the Mannich Reaction and the Dehalogenation of Aminomethylhalophenols
  作者：F. F. BLICKE、F. J. McCARTY

  DOI：10.1021/jo01090a008

  日期：1959.8
• Evaluation of some Mannich bases of cycloalkanones and related compounds for cytotoxic activity
  作者：JR Dimmock、KK Sidhu、M Chen、RS Reid、TM Allen、GY Kao、GA Truitt

  DOI：10.1016/0223-5234(93)90148-8

  日期：1993.1

  A number of Mannich bases of cycloalkanones and related quaternary ammonium compounds were prepared for cytotoxic evaluation in order to examine the theory that sequential release of alkylating agents produces increased bioactivity compared to related compounds containing only 1 potential alkylating site. Many of the compounds had significant activity against murine L1210 cells and various human tumours. Some correlations between structure and activity were noted but the biological data did not support the view that potential sequential liberation of cytotoxic species produced compounds with increased potency. The formation of various oximes and oxime benzoates as candidate prodrugs was achieved but in general these compounds were not cytotoxic at the concentrations utilized. This observation may be due to the fact that the oximes were much more stable in deuterated phosphate buffered saline over a period of 48 h at 37-degrees-C than the Mannich bases, as revealed by H-1-NMR spectroscopy.
• Design, synthesis, and antitumor evaluation of novel methylene moiety-tetheredtetrahydroquinoline derivatives
  作者：Essam Hamied Ahmed HANASHALSHAHABY、Canan ÜNALEROĞLU、Ayşe AK CAN、Alp ÖZGÜN、Bora GARİPCAN

  DOI：10.3906/kim-1907-71

  日期：——

  Novel methylene-tethered tetrahydroquinolines (THQs) and cyclopenta[$b$]pyridines were synthesized by one-pot multicomponent reactions of Mannich bases, enolizable ketones, and NH$_4}$OAc in water by an environmentally friendly K-10 montmorillonite clay-catalyzed reaction. The cytotoxic activities of 1-(2-methyl-8-methylene-5,6,7,8-tetrahydroquinolin-3-yl)ethanone (9a), ethyl 2-methyl-8-methylene-5,6,7,8-tetrahydroquinoline-3 carboxylate (9b), and 1-(2-methyl-7-methylene-6,7-dihydro-5$H$-cyclopenta[$b$]pyridin-3-yl)ethanone (11a) were tested against rat glioblastoma (C6), human breast cancer (MCF-7), prostate cancer (PC3), neuroblastoma (SH-SY5Y), and mouse fibroblast (L929) cell lines in a concentration-dependent (50-300 μM) and time-dependent (24-72 h) manner and expressed as IC$_50\, }$values. The results showed that compound 9a induced the lowest IC$_50\, }$values in all cell lines ranging from 111 ± 1.1 μM to 128 ± 1.3 μM when compared to 9b and 11a after 72 h. As an evaluation of antibacterial properties, a swarming motility assay was performed with the Pseudomonas aeruginosa PA01 strain and compound 9a showed higher inhibition of swarming motility.

  通过环保型 K-10 蒙脱石粘土催化反应，曼尼希碱、可烯化酮和 NH$_4}$OAc 在水中发生单锅多组分反应，合成了新型亚甲基系四氢喹啉（THQs）和环五[$b$]吡啶。(9a) 、2-甲基-8-亚甲基-5,6,7,8-四氢喹啉-3-基乙酮 (9b)、1-(2-甲基-7-亚甲基-6,7-二氢-5$H$-环戊并[$b$]吡啶-3-基)乙酮 (11a)人乳腺癌（MCF-7）、前列腺癌（PC3）、神经母细胞瘤（SH-SY5Y）和小鼠成纤维细胞（L929）细胞系进行了浓度依赖性（50-300 μM）和时间依赖性（24-72 h）试验，并以 IC$_50\, }$ 值表示。 结果表明，与 9b 和 11a 相比，化合物 9a 在 72 小时后对所有细胞株诱导的 IC$_50\, }$ 值最低，从 111 ± 1.1 μM 到 128 ± 1.3 μM。