1,4-dihydro-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid 3-methyl-5-benzylester | 170750-35-3

• 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: 1,4-dihydro-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid 3-methyl-5-benzylester
• 英文别名: 1,4-dihydro-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-3,5-pyridine-dicarboxylic acid 3-methyl-5-benzyl ester；5-O-benzyl 3-O-methyl 4-(3,4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 170750-35-3
• 化学式: C₂₅H₂₇NO₆
• 分子量: 437.492
• InChiKey: AISKJNJKTBNCKY-UHFFFAOYSA-N

物化性质

• 沸点：
  562.2±50.0 °C(predicted)
• 密度：
  1.185±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,4-dihydro-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid 3-methyl-5-benzylester 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1,4-dihydro-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-1-(3-phenylpropyl)-3,5-pyridinedicarboxylic acid 3-methylester
  参考文献：
  名称：

  N-Alkylated 1,4-Dihydropyridines: New Agents to Overcome Multidrug Resistance.

  摘要：

  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。

  DOI：

  10.1248/cpb.43.818
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 在 哌啶 、 溶剂黄146 、 三乙胺 作用下， 以 苯 为溶剂， 反应 5.0h， 生成 1,4-dihydro-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid 3-methyl-5-benzylester
  参考文献：
  名称：

  N-Alkylated 1,4-Dihydropyridines: New Agents to Overcome Multidrug Resistance.

  摘要：

  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。

  DOI：

  10.1248/cpb.43.818

文献信息

• 1,4-dihydropyridine compounds useful as reverse resistance agents
  申请人：Ajinomoto Company, Inc.

  公开号：US05292757A1

  公开（公告）日：1994-03-08

  1,4-dihydropyridine derivatives of Formula 1 or pharmaceutically acceptable salts thereof: ##STR1## wherein the substituents are disclosed herein and which are useful against tumor cells which have acquired resistance to one or more drugs used as chemotherapeutic agents.

  化合物1或其药学上可接受的盐的1,4-二氢吡啶衍生物：##STR1## 其中所述取代基在此处披露，并且对已获得对用作化疗药物的一个或多个药物的肿瘤细胞具有抗性是有用的。
• 1,4-Dihydropyridine derivatives useful against tumour cells
  申请人：Ajinomoto Co., Inc.

  公开号：EP0511790A1

  公开（公告）日：1992-11-04

  Compounds of formula 1 and pharmaceutically acceptable salts thereof, wherein each of R¹,R²,R³,R⁴ and R⁵ independently represents a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, a hydroxy group, a lower alkyloxy group having 1 to 3 carbon atoms, or a nitro group, or two substituents adjacent to each other on the benzene ring are combined together to form an alkylenedioxy group having 1 to 3 carbon atoms;    at least one of R⁶ and R⁷ represents an alkyloxycarbonyl group or an alkylaminocarbonyl group in which the alkyl moiety has a nitrogen-containing substituent and where only one of R⁶ and R⁷ represents an alkyloxycarbonyl group or an alkylaminocarbonyl group in which the alkyl group has a nitrogen-containing substituent, the other is an alkyloxycarbonyl group;    each of R⁸ and R⁹ independently represents a hydrogen atom or a lower alkyl group having 1 to 5 carbon atoms;    n represents an integer of 2 to 9;    X represents a methylene group or oxygen atom, wherein the methylene is optionally substituted with a lower alkyl group having 1 to 5 carbon atoms, or a lower alkyloxy group having 1 to 5 carbon atoms; and,    R¹⁰ represents an aryl group or an aralkyl group, wherein the aryl moiety in the aryl group and aralkyl group is optionally substituted with a substituent selected from a halogen atom, a lower alkyl group having 1 to 5 carbon atoms, a lower alkyloxy group having 1 to 5 carbon atoms, a hydroxy group an aryl group, an aryloxy group, an aralkyl group, or an aralkyloxy group, or two substituents adjacent to each other on the benzene ring are combined together to form an alkylenedioxy group having 1 to 3 carbon atoms; are effective at reducing the resistance of cancer cells which have acquired resistance to chemotherapeutic agents used in cancer treatment.

  式 1 的化合物 及其药学上可接受的盐，其中 R¹、R²、R³、R⁴ 和 R⁵ 各自独立地代表氢原子、具有 1 至 3 个碳原子的低级烷基、羟基、具有 1 至 3 个碳原子的低级烷氧基或硝基，或苯环上相邻的两个取代基结合在一起形成具有 1 至 3 个碳原子的亚烷基二氧基； R⁶ 和 R⁷ 中至少有一个代表烷氧基羰基或烷基氨基羰基，其中烷基具有含氮取代基；如果 R⁶ 和 R⁷ 中只有一个代表烷氧基羰基或烷基氨基羰基，其中烷基具有含氮取代基，则另一个代表烷氧基羰基； R⁸ 和 R⁹ 各自独立地代表氢原子或具有 1 至 5 个碳原子的低级烷基； n 代表 2 至 9 的整数； X 代表亚甲基或氧原子，其中亚甲基任选被具有 1 至 5 个碳原子的低级烷基或具有 1 至 5 个碳原子的低级烷氧基取代；以及 R¹⁰ 代表芳基或芳烷基，其中芳基和芳烷基中的芳基任选被选自卤素原子、具有 1 至 5 个碳原子的低级烷基或具有 1 至 5 个碳原子的低级烷氧基的取代基取代、1至5个碳原子的低级烷氧基、羟基、芳基、芳氧基、烷基或芳氧基，或苯环上相邻的两个取代基结合在一起形成1至3个碳原子的亚烷基二氧基； 能有效降低已对用于癌症治疗的化疗药物产生抗药性的癌细胞的抗药性。
• US5292757A
  申请人：——

  公开号：US5292757A

  公开（公告）日：1994-03-08
• 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。