2-(3,4-dimethoxyphenyl)-5-(9H-fluoren-9-ylmethylamino)-2-propan-2-ylpentanenitrile | 742683-38-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-(3,4-dimethoxyphenyl)-5-(9H-fluoren-9-ylmethylamino)-2-propan-2-ylpentanenitrile
• CAS: 742683-38-1
• 化学式: C₃₀H₃₄N₂O₂
• 分子量: 454.612
• InChiKey: YKOUSPHUKOKEPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-甲基-2-(3,4-二甲氧基苯基)丁腈 在 正丁基锂 、 三乙胺 作用下， 反应 17.0h， 生成 2-(3,4-dimethoxyphenyl)-5-(9H-fluoren-9-ylmethylamino)-2-propan-2-ylpentanenitrile
  参考文献：
  名称：

  Design, Synthesis, and in Vitro Activity of Catamphiphilic Reverters of Multidrug Resistance:  Discovery of a Selective, Highly Efficacious Chemosensitizer with Potency in the Nanomolar Range

  摘要：

  On the basis of the results obtained in previous research, three series of compounds (A-C), derived from verapamil, were designed and synthesized to obtain drugs able to revert multidrug resistance (MDR), an acquired resistance that frequently impairs cancer chemotherapy. The ability of the obtained compounds to revert MDR was evaluated on anthracycline-resistant erythroleukemia K 562 cells, measuring the uptake of THP-adriamycin (pirarubicin) by continuous spectrofluorometric monitoring of the decrease of the fluorescence signal of the anthracycline at 590 nm (lambda(ex) = 480 nm), after incubation with cells. Cardiovascular activity, which is responsible for unwanted side effects, was also evaluated. The results obtained show that many of the compounds studied are potent reverters of MDR and are endowed with reduced cardiovascular activity. One of the compounds (7, MM36) presents a pharmacological profile (unprecedented nanomolar potency, high reversal of MDR, low cardiovascular activity) that makes it a promising drug candidate to treat MDR and a useful tool for studying P-glycoprotein.

  DOI：

  10.1021/jm980440p

文献信息

• Design, Synthesis, and in Vitro Activity of Catamphiphilic Reverters of Multidrug Resistance:  Discovery of a Selective, Highly Efficacious Chemosensitizer with Potency in the Nanomolar Range
  作者：Elisabetta Teodori、Silvia Dei、Patricia Quidu、Roberta Budriesi、Alberto Chiarini、Arlette Garnier-Suillerot、Fulvio Gualtieri、Dina Manetti、Maria Novella Romanelli、Serena Scapecchi

  DOI：10.1021/jm980440p

  日期：1999.5.1

  On the basis of the results obtained in previous research, three series of compounds (A-C), derived from verapamil, were designed and synthesized to obtain drugs able to revert multidrug resistance (MDR), an acquired resistance that frequently impairs cancer chemotherapy. The ability of the obtained compounds to revert MDR was evaluated on anthracycline-resistant erythroleukemia K 562 cells, measuring the uptake of THP-adriamycin (pirarubicin) by continuous spectrofluorometric monitoring of the decrease of the fluorescence signal of the anthracycline at 590 nm (lambda(ex) = 480 nm), after incubation with cells. Cardiovascular activity, which is responsible for unwanted side effects, was also evaluated. The results obtained show that many of the compounds studied are potent reverters of MDR and are endowed with reduced cardiovascular activity. One of the compounds (7, MM36) presents a pharmacological profile (unprecedented nanomolar potency, high reversal of MDR, low cardiovascular activity) that makes it a promising drug candidate to treat MDR and a useful tool for studying P-glycoprotein.