O-Methyl-lophocerin | 63110-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: O-Methyl-lophocerin
• 英文别名: 1-Isobutyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin, O-Methyl-lophocerin；6,7-dimethoxy-2-methyl-1-(2-methylpropyl)-3,4-dihydro-1H-isoquinoline
• CAS: 63110-79-2
• 化学式: C₁₆H₂₅NO₂
• 分子量: 263.38
• InChiKey: XLYGKISSKFHOEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  O-Methyl-lophocerin 、 碘甲烷 以 乙腈 为溶剂， 反应 4.0h， 以93%的产率得到6,7-dimethoxy-2,2-dimethyl-1-(2-methylpropyl)-3,4-dihydro-1H-isoquinolin-2-ium;iodide
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels

  摘要：

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.

  DOI：

  10.1021/jm0607395
• 作为产物：
  描述：

  异戊酰氯 在 磷酸酐 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 3.75h， 生成 O-Methyl-lophocerin
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels

  摘要：

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.

  DOI：

  10.1021/jm0607395

文献信息

• Simplified Derivatives of Tetrandrine as Potent and Specific P-gp Inhibitors to Reverse Multidrug Resistance in Cancer Chemotherapy
  作者：Rong Zeng、Xiu-Ming Yang、Hong-Wei Li、Xue Li、Yu Guan、Tao Yu、Peng Yan、Wen Yuan、Sheng-Li Niu、Jing Gu、Ying-Chun Chen、Qin Ouyang

  DOI：10.1021/acs.jmedchem.2c02061

  日期：2023.3.23

  Targeted inhibition of a drug efflux transporter P-glycoprotein (P-gp) is an important strategy to reverse multidrug resistance in cancer chemotherapy. In this study, a rationally structural simplification to natural tetrandrine was performed based on molecular dynamics simulation and fragment growth, leading to an easily prepared, novel, and simplified compound OY-101 with high reversal activity and

  靶向抑制药物外排转运蛋白 P-糖蛋白 (P-gp) 是逆转癌症化疗中多药耐药性的重要策略。本研究基于分子动力学模拟和片段生长对天然粉防己碱进行了合理的结构简化，得到了一种易于制备、新颖且简化的化合物OY-101，具有高逆转活性和低细胞毒性。通过逆转活性测定、流式细胞术、平板克隆形成测定和药物协同分析证实其与长春新碱（VCR）对耐药细胞Eca109/VCR具有优异的协同抗癌作用（IC 50 = 9.9 nM，RF = 690） 。进一步的机制研究证实OY-101是一种特异性、高效的P-gp抑制剂。重要的是，OY-101增加了体内VCR 致敏性，但没有明显的毒性。总体而言，我们的研究结果可能为设计新型特异性 P-gp 抑制剂作为抗肿瘤化疗增敏剂提供替代策略。
• Alkaloid Studies. V.¹ Synthesis of 1-Isopropyl and 1-Isobutyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  作者：Carl Djerassi、J. J. Beereboom、S. P. Marfey、S. K. Figdor

  DOI：10.1021/ja01607a081

  日期：1955.1
• Synthesis of Isoquinoline Alkaloids. I. Lophocerine¹
  作者：J. M. BOBBITT、TSU-TEH CHOU

  DOI：10.1021/jo01090a018

  日期：1959.8
• Alkaloid Studies. XVII.¹ The Structure of the Cactus Alkaloid Pilocereine²
  作者：Carl Djerassi、S. K. Figdor、J. M. Bobbitt、F. X. Markley

  DOI：10.1021/ja01566a047

  日期：1957.5
• Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels
  作者：Amaury Graulich、Jacqueline Scuvée-Moreau、Livia Alleva、Cédric Lamy、Olivier Waroux、Vincent Seutin、Jean-François Liégeois

  DOI：10.1021/jm0607395

  日期：2006.11.30

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.