4-ethyl-1,3-dihydro-5-<4-(2-methyl-1H-imidazol-1-yl)benzoyl>-1-(1-oxo-2-phenylethyl)-2H-imidazol-2-one | 116174-56-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-ethyl-1,3-dihydro-5-<4-(2-methyl-1H-imidazol-1-yl)benzoyl>-1-(1-oxo-2-phenylethyl)-2H-imidazol-2-one
• 英文别名: 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-1-(1-oxo-2-phenylethyl)-2H-imidazol-2-one；4-Ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl) benzoyl]-1-(1-oxo-2-phenylethyl)-2H-imidazol-2-one；5-ethyl-4-[4-(2-methylimidazol-1-yl)benzoyl]-3-(2-phenylacetyl)-1H-imidazol-2-one
• CAS: 116174-56-2
• 化学式: C₂₄H₂₂N₄O₃
• 分子量: 414.464
• InChiKey: XQNQPJXQURUCHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  84.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  二(苯乙酸)酸酐 、 sodium;5-ethyl-4-[4-(2-methylimidazol-1-yl)benzoyl]-1H-imidazol-3-id-2-one 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以16%的产率得到4-ethyl-1,3-dihydro-5-<4-(2-methyl-1H-imidazol-1-yl)benzoyl>-1-(1-oxo-2-phenylethyl)-2H-imidazol-2-one
  参考文献：
  名称：

  Cardiotonic agents. 7. Prodrug derivatives of 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one

  摘要：

  The cardiotonic agent 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one (1) was found to have low bioavailability when administered orally to rats and dogs. A series of N-acyl derivatives, an underutilized prodrug of acidic NH compounds, has been synthesized and tested for their ability to improve the oral bioavailability of 1. Reaction of the monosodium salt of 1 with various anhydrides afforded the N-1 monoacylimidazolones with surprisingly high regioselectivity. In addition to the prodrugs, acylation of 1 with propionic or phenylacetic anhydride led to the novel 3H-pyrrolo[1,2-c]imidazole-3,5(2H)-diones 6. The prodrugs showed a significant increase in the partition coefficients with a minor decrease in the aqueous solubility. The benzoyl derivative 4b exhibited the highest stability in both pH 1.5 and 7.4 buffer solutions. Further evaluation of 4b showed rapid conversion to 1 in canine plasma (t1/2 = 38 min), and human plasma (t1/2 = 10 min). Oral studies indicated that the bioavailability of 4b was increased to > 75% (compared to < 20% for 1), and hemodynamic studies demonstrated that the selective inotropic profile of 1 was retained.

  DOI：

  10.1021/jm00085a014

文献信息

• Prodrug derivatives of the cardiotonic agent
  申请人：Berlex Laboratories, Inc.

  公开号：US04743612A1

  公开（公告）日：1988-05-10

  Orally active prodrug derivatives of the cardiotonic agent 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2 -one are disclosed. Pharmaceutical formulations containing such compounds are also provided.

  本发明揭示了心脏强效药物4-乙基-1,3-二氢-5-[4-(2-甲基-1H-咪唑-1-基)苯甲酰基]-2H-咪唑-2-酮的口服前药衍生物。还提供了含有这些化合物的制药配方。
• Prodrug derivatives of the cardiotonic agent 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)-benzoyl]]-2H-imidazol-one
  申请人：BERLEX LABORATORIES, INC.

  公开号：EP0264729A2

  公开（公告）日：1988-04-27

  Orally active prodrug derivatives of the cardiotonic agent 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)­benzoyl]-2H-imidazol-2-one are disclosed. Pharmaceutical formulations containing such compounds are also provided.

  本研究公开了强心剂 4-乙基-1,3-二氢-5-[4-(2-甲基-1H-咪唑-1-基)苯甲酰基]-2H-咪唑-2-酮的口服活性原药衍生物。还提供了含有此类化合物的药物制剂。
• US4743612A
  申请人：——

  公开号：US4743612A

  公开（公告）日：1988-05-10
• Cardiotonic agents. 7. Prodrug derivatives of 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one
  作者：Kenneth J. Shaw、Paul W. Erhardt、Alfred A. Hagedom、Cynthia A. Pease、William R. Ingebretsen、Jay R. Wiggins

  DOI：10.1021/jm00085a014

  日期：1992.4

  The cardiotonic agent 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one (1) was found to have low bioavailability when administered orally to rats and dogs. A series of N-acyl derivatives, an underutilized prodrug of acidic NH compounds, has been synthesized and tested for their ability to improve the oral bioavailability of 1. Reaction of the monosodium salt of 1 with various anhydrides afforded the N-1 monoacylimidazolones with surprisingly high regioselectivity. In addition to the prodrugs, acylation of 1 with propionic or phenylacetic anhydride led to the novel 3H-pyrrolo[1,2-c]imidazole-3,5(2H)-diones 6. The prodrugs showed a significant increase in the partition coefficients with a minor decrease in the aqueous solubility. The benzoyl derivative 4b exhibited the highest stability in both pH 1.5 and 7.4 buffer solutions. Further evaluation of 4b showed rapid conversion to 1 in canine plasma (t1/2 = 38 min), and human plasma (t1/2 = 10 min). Oral studies indicated that the bioavailability of 4b was increased to > 75% (compared to < 20% for 1), and hemodynamic studies demonstrated that the selective inotropic profile of 1 was retained.