1,4-dihydro-2-methyl-6-<2-(1H-imidazol-1-yl)ethyl>-4-(2-nitrophenyl)pyridinedicarboxylic acid diethyl ester | 103417-72-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1,4-dihydro-2-methyl-6-<2-(1H-imidazol-1-yl)ethyl>-4-(2-nitrophenyl)pyridinedicarboxylic acid diethyl ester
• 英文别名: Diethyl 2-(2-imidazol-1-ylethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 103417-72-7
• 化学式: C₂₃H₂₆N₄O₆
• 分子量: 454.483
• InChiKey: PZSKEXIHJQBKRF-UHFFFAOYSA-N

物化性质

• 沸点：
  634.0±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二甲基-4-(2-硝基苯基)-1,4-二氢-3,5-吡啶二甲酸二乙酯 在 盐酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 氯苯 为溶剂， 反应 32.0h， 生成 1,4-dihydro-2-methyl-6-<2-(1H-imidazol-1-yl)ethyl>-4-(2-nitrophenyl)pyridinedicarboxylic acid diethyl ester
  参考文献：
  名称：

  Design of an antithrombotic-antihypertensive agent (Wy 27569). Synthesis and evaluation of a series of 2-heteroaryl substituted dihydropyridines

  摘要：

  An approach to the design of potential combined antithrombotic-antihypertensive agents is described. A series of 1,4-dihydropyridines bearing a 1H-imidazol-1-yl or pyrid-3-yl substituted side chain in the 2-position were synthesized and tested for antihypertensive activity in spontaneously hypertensive rats and for inhibition of TXA2 synthetase in rabbit platelets, in vitro. 1,4-Dihydro-2-(1H-imidazol-1-ylmethyl)-6-methyl- 4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 3-ethyl 5-methyl diester (1) was shown to be similar in potency to nitrendipine as an antihypertensive agent. Compound 1 inhibited TXA2 synthetase in rabbit and human platelets in vitro and reduced plasma TXB2 levels in rats at antihypertensive dose levels. The reductions in thromboxane production observed in vivo and in vitro were accompanied by enhanced levels of 6-KPGF1 alpha, reflecting diversion of the arachidonic acid cascade toward prostacyclin synthesis.

  DOI：

  10.1021/jm00164a028

文献信息

• 1,4-Dihydropyridines
  申请人：JOHN WYETH & BROTHER LIMITED

  公开号：EP0172029A1

  公开（公告）日：1986-02-19

  The invention concerns compounds of formula or salts thereof; wherein: Ar is an optionally substituted aryl radical; R represents hydrogen or an optionally substituted alkyl or aralkyl group; R' and R' are the same or different and are selected from hydrogen and saturated or unsaturated, cyclic or acyclic aliphatic hydrocarbon residues optionally substituted by one or more groups selected from halogen, OH, carboxy, CN, alkoxy, alkylthio, aryloxy, alkoxycarbonyl, amino, substituted amino, and optionally substituted aryl; A represents a group of formula -XR3 wherein X is (i) a group of formula - (CHR6)P-Y-(CHR7)q- or (ii) a group of formula - (CHR6)r-O-(CHR7) in which formulae: Y represents -S-, NR6 or a direct bond, p and q each represent O, or 2 providing that p and q do not both represent zero when Y is a direct bond; one or r and s represents O, or 2 and the other is zero; R6, R7 and R6 independently represent hydrogen or lower alkyl, and R3 is an optionally substituted nitrogen ring heteroaryl radical optionally containing other ring heteroatoms selected from oxygen, nitrogen or sulphur; B represents hydrogen, carboxyl, lower alkoxycarbonyl, lower alkyl optionally substituted by amino, lower alkoxy, lower alkoxycarbonyl or carboxyl, or amino optionally substituted by one or two lower alkyl groups, which compounds possess antihypertensive and antithrombotic activity.

  本发明涉及式 或其盐类；其中 Ar是任选取代的芳基；R代表氢或任选取代的烷基或芳烷基；R'和R'相同或不同，选自氢和饱和或不饱和、环状或非环状脂族烃残基，任选被一个或多个基团取代，这些基团选自卤素、OH、羧基、CN、烷氧基、烷硫基、芳氧基、烷氧基羰基、氨基、取代氨基和任选取代的芳基； A 代表式-XR3 的基团，其中 X 是 (i) 式-(CHR6)P-Y-(CHR7)q- 的基团，或 (ii) 式-(CHR6)r-O-(CHR7)的基团。 在这些式子中Y 代表-S-、NR6 或直接键，p 和 q 各自代表 O 或 2，条件是当 Y 为直接键时，p 和 q 不同时代表零；r 和 s 中的一个代表 O 或 2，另一个为零；R6、R7 和 R6 独立地代表氢或低级烷基，R3 是任选取代的氮环杂芳基，任选含有选自氧、氮或硫的其他环杂原子；B 代表氢、羧基、低级烷氧基羰基、任选被氨基取代的低级烷基、低级烷氧基、低级烷氧基羰基或羧基，或任选被一个或两个低级烷基取代的氨基，这些化合物具有抗高血压和抗血栓活性。
• US5068337A
  申请人：——

  公开号：US5068337A

  公开（公告）日：1991-11-26
• Design of an antithrombotic-antihypertensive agent (Wy 27569). Synthesis and evaluation of a series of 2-heteroaryl substituted dihydropyridines
  作者：John L. Archibald、Gerald Bradley、Albert Opalko、Terence J. Ward、Janet C. White、Christine Ennis、Nicholas B. Shepperson

  DOI：10.1021/jm00164a028

  日期：1990.2

  An approach to the design of potential combined antithrombotic-antihypertensive agents is described. A series of 1,4-dihydropyridines bearing a 1H-imidazol-1-yl or pyrid-3-yl substituted side chain in the 2-position were synthesized and tested for antihypertensive activity in spontaneously hypertensive rats and for inhibition of TXA2 synthetase in rabbit platelets, in vitro. 1,4-Dihydro-2-(1H-imidazol-1-ylmethyl)-6-methyl- 4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 3-ethyl 5-methyl diester (1) was shown to be similar in potency to nitrendipine as an antihypertensive agent. Compound 1 inhibited TXA2 synthetase in rabbit and human platelets in vitro and reduced plasma TXB2 levels in rats at antihypertensive dose levels. The reductions in thromboxane production observed in vivo and in vitro were accompanied by enhanced levels of 6-KPGF1 alpha, reflecting diversion of the arachidonic acid cascade toward prostacyclin synthesis.