(E)-3-(5-Imidazol-1-ylmethyl-1-methyl-1H-pyrrol-2-yl)-2-methyl-acrylic acid ethyl ester | 118896-55-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E)-3-(5-Imidazol-1-ylmethyl-1-methyl-1H-pyrrol-2-yl)-2-methyl-acrylic acid ethyl ester
• CAS: 118896-55-2
• 化学式: C₁₅H₁₉N₃O₂
• 分子量: 273.335
• InChiKey: ODLIHSBPOWCIPJ-FMIVXFBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.05
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (E)-3-(5-Imidazol-1-ylmethyl-1-methyl-1H-pyrrol-2-yl)-2-methyl-acrylic acid ethyl ester 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以90%的产率得到(E)-1-methyl-2-<(1H-imidazol-1-yl)methyl>-5-(2-carboxyprop-1-enyl)pyrrole
  参考文献：
  名称：

  [(1H-Imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl]pyrroles as thromboxane synthetase inhibitors

  摘要：

  Several [(1H-imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl] pyrroles were prepared and evaluated in vitro as thromboxane synthetase inhibitors in human platelet aggregation studies. A number of structures, e.g. 10b,f,g,i (respective IC50 values: 1 microM, 50 nM, 42 nM, 44 nM) showed superior in vitro inhibition of TXA2 synthetase when compared to the standard dazoxiben (1). However, it was found that in vitro potency did not translate into nor correlate with in vivo activity when these compounds were evaluated in mice in a collagen-epinephrine-induced pulmonary thromboembolism model. (E)-1-Methyl-2-[(1H-imidazol-1-yl)methyl]-5-(2-carboxyprop-1-enyl) pyrrole (10b) was found to offer protection against collagen-epinephrine-induced mortality in mice, thereby demonstrating that oral administration is an effective route for absorption of this drug. Additional evidence for the oral effectiveness of 10b in lowering serum TXB2 levels was obtained by performing ex vivo radioimmunoassay experiments with rats. A 13-week study of 10b in rats with reduced renal mass was conducted in order to evaluate the role of TXA2 production in hypertension and renal dysfunction. Although serum and urinary TXB2 levels in rats were found to be lowered during this study by 10b, the levels of urinary protein excretion remained comparable to that of the control group.

  DOI：

  10.1021/jm00124a027
• 作为产物：
  描述：

  2-<(1H-imidazol-1-yl)methyl>pyrrole 在 sodium hydride 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 19.33h， 生成 (E)-3-(5-Imidazol-1-ylmethyl-1-methyl-1H-pyrrol-2-yl)-2-methyl-acrylic acid ethyl ester
  参考文献：
  名称：

  [(1H-Imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl]pyrroles as thromboxane synthetase inhibitors

  摘要：

  Several [(1H-imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl] pyrroles were prepared and evaluated in vitro as thromboxane synthetase inhibitors in human platelet aggregation studies. A number of structures, e.g. 10b,f,g,i (respective IC50 values: 1 microM, 50 nM, 42 nM, 44 nM) showed superior in vitro inhibition of TXA2 synthetase when compared to the standard dazoxiben (1). However, it was found that in vitro potency did not translate into nor correlate with in vivo activity when these compounds were evaluated in mice in a collagen-epinephrine-induced pulmonary thromboembolism model. (E)-1-Methyl-2-[(1H-imidazol-1-yl)methyl]-5-(2-carboxyprop-1-enyl) pyrrole (10b) was found to offer protection against collagen-epinephrine-induced mortality in mice, thereby demonstrating that oral administration is an effective route for absorption of this drug. Additional evidence for the oral effectiveness of 10b in lowering serum TXB2 levels was obtained by performing ex vivo radioimmunoassay experiments with rats. A 13-week study of 10b in rats with reduced renal mass was conducted in order to evaluate the role of TXA2 production in hypertension and renal dysfunction. Although serum and urinary TXB2 levels in rats were found to be lowered during this study by 10b, the levels of urinary protein excretion remained comparable to that of the control group.

  DOI：

  10.1021/jm00124a027