1,1'-亚甲基二(2-甲基哌啶) | 63963-55-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1,1'-亚甲基二(2-甲基哌啶)
• 英文名称: methylenebis(2-methylpiperidine)
• 英文别名: 1,1'-Methylenebis(2-methylpiperidine)；2-methyl-1-[(2-methylpiperidin-1-yl)methyl]piperidine
• CAS: 63963-55-3
• 化学式: C₁₃H₂₆N₂
• 分子量: 210.363
• InChiKey: LDMRWZAGEZWQBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  槐角苷 、 1,1'-亚甲基二(2-甲基哌啶) 以 1,4-二氧六环 为溶剂， 以67%的产率得到4-{5,7-dihydroxy-6,8-bis[(2-methylpiperidin-1-yl)methyl]-4-oxo-4H-chromen-3-yl}phenyl-β-D-glucopyranoside
  参考文献：
  名称：

  Synthesis of aminomethyl derivatives of sophoricoside

  摘要：

  研究了天然异黄酮槐糖苷（染料木素-4-O-β-D-葡萄糖苷）的氨甲基化。结果表明，进行氨基甲基化最方便的方法是使用酰胺基。合成了槐糖苷的 6,8-双取代衍生物。

  DOI：

  10.1007/s10600-012-0151-2
• 作为产物：
  描述：

  二氯甲烷 、 2-甲基哌啶 以 甲醇 为溶剂， 30.0 ℃ 、600.0 MPa 条件下， 反应 96.0h， 以56%的产率得到1,1'-亚甲基二(2-甲基哌啶)
  参考文献：
  名称：

  Matsumoto, Kiyoshi; Hashimoto, Shiro; Ikemi, Yukio, Heterocycles, 1984, vol. 22, # 6, p. 1417 - 1420

  摘要：

  DOI：

文献信息

• Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents
  作者：Mykhaylo Frasinyuk、Dimple Chhabria、Victor Kartsev、Haritha Dilip、Samvel N. Sirakanyan、Sivapriya Kirubakaran、Anthi Petrou、Athina Geronikaki、Domenico Spinelli

  DOI：10.3390/molecules27144637

  日期：——

  Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.

  尽管进行了广泛的研究并存在许多不同的抗癌剂，但癌症治疗仍然是一个严重和具有挑战性的问题。因此，开发具有更好治疗效果和更少副作用的新型抗癌药物以对抗这种持久的疾病仍然是必要的。在本研究中，我们报道了一系列新型苯并噻唑和色酮衍生物，这些衍生物被合成并评估其作为DDR途径的主调节因子ATR激酶抑制剂的抗癌活性。使用MTT测定法在HCT116和HeLa细胞系中对25种化合物的细胞存活率进行了测试，这涉及到将化合物在最终浓度为10µM的条件下孵育72小时。发现孵育化合物2c、7h和7l的细胞的存活率≤50％，因此这些化合物被用于剂量反应研究。在测试的化合物中，其中三种（2c、7h和7l）显示出更高的效力，其中化合物7l在两种细胞系中都表现出最佳的IC50值。发现化合物2c和7l对HCT116和HeLa两种细胞系同样具有细胞毒性，而化合物7h对HeLa细胞系的细胞毒性更好。对于这三种化合物，进行了免疫印迹分析，以分析在HeLa和HCT116细胞中Chk1在Ser 317处的磷酸化抑制。发现化合物7h在3.995µM的浓度下可抑制HeLa细胞中的pChk1在Ser 317处的磷酸化。在用各种浓度的3种化合物（2、5和10µM）处理HeLa细胞时，进一步分析了Chk1和pChk1的表达，其中化合物7h在2和5µM的浓度下表现出Chk1的抑制作用，而化合物7l在5µM的浓度下观察到pChk1的表达。为了支持这些结果，通过分子对接研究了化合物与ATR激酶结构域的结合相互作用，发现化合物2c、7h和7l的结合相互作用类似于已知的mTOR/ATR抑制剂Torin2。对这组分子的进一步研究正在进行，以了解它们对ATR途径的特异性。
• MATSUMOTO, KIYOSHI;HASHIMOTO, SHIRO;IKEMI, YUKIO;OTANI, SHINICHI, HETEROCYCLES, 1984, 22, N 6, 1417-1420
  作者：MATSUMOTO, KIYOSHI、HASHIMOTO, SHIRO、IKEMI, YUKIO、OTANI, SHINICHI

  DOI：——

  日期：——
• IOVU, M.;IQBAI, M., REV. ROUM. CHIM., 1984, 29, N 4, 333-343
  作者：IOVU, M.、IQBAI, M.

  DOI：——

  日期：——
• Matsumoto, Kiyoshi; Hashimoto, Shiro; Ikemi, Yukio, Heterocycles, 1984, vol. 22, # 6, p. 1417 - 1420
  作者：Matsumoto, Kiyoshi、Hashimoto, Shiro、Ikemi, Yukio、Otani, Shinichi

  DOI：——

  日期：——
• Synthesis of aminomethyl derivatives of sophoricoside
  作者：S. P. Bondarenko、M. S. Frasinyuk、V. P. Khilya

  DOI：10.1007/s10600-012-0151-2

  日期：2012.3

  Aminomethylation of the natural isoflavonoid sophoricoside (genistein-4-O-β-D-glucoside) was studied. It was shown that the most convenient method for performing the aminomethylation was the use of aminals. 6,8-bis-Substituted derivatives of sophoricoside were synthesized.

  研究了天然异黄酮槐糖苷（染料木素-4-O-β-D-葡萄糖苷）的氨甲基化。结果表明，进行氨基甲基化最方便的方法是使用酰胺基。合成了槐糖苷的 6,8-双取代衍生物。