4-(2-Imidazol-1-yl-ethoxy)-3-oxo-butyric acid ethyl ester | 90444-47-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(2-Imidazol-1-yl-ethoxy)-3-oxo-butyric acid ethyl ester
• 英文别名: Ethyl 4-(2-imidazol-1-ylethoxy)-3-oxobutanoate
• CAS: 90444-47-6
• 化学式: C₁₁H₁₆N₂O₄
• 分子量: 240.259
• InChiKey: LLNFUGNHMMUYGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  70.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate 、 4-(2-Imidazol-1-yl-ethoxy)-3-oxo-butyric acid ethyl ester 在 ammonium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 2-(2-Imidazol-1-yl-ethoxymethyl)-6-methyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl 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
• 作为产物：
  描述：

  1-(2-羟乙基)咪唑 、 4-氯乙酰乙酸乙酯 在 sodium hydride 作用下， 生成 4-(2-Imidazol-1-yl-ethoxy)-3-oxo-butyric acid ethyl 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

• Dihydropyridine anti-ischaemic and antihypertensive agents
  申请人：Pfizer Limited

  公开号：EP0100189A2

  公开（公告）日：1984-02-08

  1,4 Dihydropyridine derivatives of the formula:- wherein R is aryl heteroaryl; R' and R2 are each independently C1-C4 alkyl or 2-methoxyethyl; Y is -(CH2)n- -CH2CH(CH3)- or -CH2C(CH3)2-; n is 1 to 3; and X is a 5 or 6 membered nitrogen containing aromatic heterocyclic ring which may optionally be substituted by one or more C1-C4 alkyl, phenyl, benzyl, CN, -N(R3)2, (CH2)mCO2H, (CH2)mCO2(C1-C4 alkyl) or (CH2)mCON(R3)2 group wherein each R3 is independently H or C1-C4 alkyl and m is 0 or 1; and their pharmaceutically acceptable acid addition salts, and pharmaceutical preparation containing such compounds, have utility as anti-ischaemic and antihyperen- sive agents.

  式中的 1，4 二氢吡啶衍生物 其中 R 为芳基杂芳基；R'和 R2 各自独立地为 C1-C4 烷基或 2-甲氧基乙基；Y 为-(CH2)n--CH2CH(CH3)-或-CH2C(CH3)2-；n 为 1 至 3；X 是 5 或 6 位含氮芳香杂环，可任选被一个或多个 C1-C4 烷基、苯基、苄基、CN、-N(R3)2、(CH2)mCO2H、(CH2)mCO2(C1-C4 烷基)或 (CH2)mCON(R3)2 基团取代，其中每个 R3 独立为 H 或 C1-C4 烷基，m 为 0 或 1；及其药学上可接受的酸加成盐，以及含有此类化合物的药物制剂，具有抗缺血和抗高血压作用。
• US4515799A
  申请人：——

  公开号：US4515799A

  公开（公告）日：1985-05-07
• US4616024A
  申请人：——

  公开号：US4616024A

  公开（公告）日：1986-10-07
• 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.