5-cyano-4-(3,4-dimethoxy-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3-carboxylic acid ethyl ester | 846547-59-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-cyano-4-(3,4-dimethoxy-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3-carboxylic acid ethyl ester
• 英文别名: 5-Cyan-4-(3,4-dimethoxy-phenyl)-2,6-dimethyl-1,4-dihydro-pyridin-3-carbonsaeure-aethylester；Ethyl 5-cyano-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate
• CAS: 846547-59-9
• 化学式: C₁₉H₂₂N₂O₄
• 分子量: 342.395
• InChiKey: XJYXXAJXABFECB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-cyano-4-(3,4-dimethoxy-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3-carboxylic acid ethyl ester 在 chromium(VI) oxide 作用下， 生成 5-cyano-4-(3,4-dimethoxy-phenyl)-2,6-dimethyl-nicotinic acid ethyl ester
  参考文献：
  名称：

  191.杂环化合物的新合成。第七部分 9-氨基-6：8-二甲基-7：10-二氮杂菲

  摘要：

  DOI：

  10.1039/jr9460000884
• 作为产物：
  描述：

  3-氨基巴豆腈 、 3-氨基巴豆酸乙酯 、 3,4-二甲氧基苯甲醛 在 乙醇 作用下， 生成 5-cyano-4-(3,4-dimethoxy-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  191.杂环化合物的新合成。第七部分 9-氨基-6：8-二甲基-7：10-二氮杂菲

  摘要：

  DOI：

  10.1039/jr9460000884

文献信息

• N-Alkylated 1,4-Dihydropyridines: New Agents to Overcome Multidrug Resistance.
  作者：Koji OHSUMI、Kazuo OHISHI、Yoshihiro MORINAGA、Ryusuke NAKAGAWA、Yasuyo SUGA、Takaaki SEKIYAMA、Yukio AKIYAMA、Takashi TSUJI、Takashi TSURUO

  DOI：10.1248/cpb.43.818

  日期：——

  New N-alkylated 1, 4-dihydropyridine derivatives were synthesized and their ability to overcome multidrug resistance was examined in vincristine-resistant P388 cells (P388/VCR cells). Compounds that possessed an arylalkyl substituent on the dihydropyridine ring nitrogen were more potent than verapamil in potentiating the cytotoxicity of vincristine against P388/VCR cells. However, neither drug effectively enhanced the antitumor activity of vincristine in tumor-bearing mice. Introduction of basic nitrogen-containing substituents on the side chain of 1, 4-dihydropyridines gave improved activity in vitro and in vivo. The piperazine derivative 12c and 12o were more than 10 times as potent as verapamil in vitro. Four compounds selected for in vivo testing showed superior antitumor activity in P388/VCR-bearing mice in combination with vincristine. The structure-activity relationships of the compounds are discussed.

  新合成的N-烷基化1,4-二氢吡啶衍生物，在长春新碱耐药的P388细胞（P388/VCR细胞）中检测了其克服多药耐药的能力。在二氢吡啶环氮上带有芳烷基取代基的化合物，比维拉帕米更能增强长春新碱对P388/VCR细胞的细胞毒性。然而，这两种药物均未有效地增强长春新碱在携带肿瘤的小鼠中的抗肿瘤活性。在1,4-二氢吡啶的侧链上引入含有碱性氮的取代基，在体外和体内均能提高活性。哌嗪衍生物12c和12o在体外比维拉帕米强10倍以上。选出四种化合物进行体内测试，它们与长春新碱联合使用时，在携带P388/VCR的肿瘤小鼠中显示出优越的抗肿瘤活性。讨论了化合物的构效关系。