4-Ethyl-5-(4-fluorobenzoyl)-1,3-dihydroimidazol-2-one | 110369-25-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-Ethyl-5-(4-fluorobenzoyl)-1,3-dihydroimidazol-2-one
• CAS: 110369-25-0
• 化学式: C₁₂H₁₁FN₂O₂
• 分子量: 234.23
• InChiKey: AWUOJTAAQGNCIH-UHFFFAOYSA-N

物化性质

• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Ethyl-5-(4-fluorobenzoyl)-1,3-dihydroimidazol-2-one 在 sodium hydride 作用下， 反应 8.0h， 生成 4-ethyl-1,3-dihydro-5-<4-(2-methyl-1H-imidazol-1-yl)benzoyl>-1-(phenylmethyl)-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

• Cardiotonic agents. 2. (Imidazolyl)aroylimidazolones, highly potent and selective positive inotropic agents
  作者：Alfred A. Hagedorn、Paul W. Erhardt、William C. Lumma、Ronald A. Wohl、Elinor Cantor、Yuo Ling Chou、William R. Ingebretsen、John W. Lampe、David Pang

  DOI：10.1021/jm00391a013

  日期：1987.8

  A series of 4-alkyl-1,3-dihydro-5-[(1H-imidazolyl)benzoyl]-2H-imidazol-2-ones 9 was synthesized and evaluated in vitro for positive inotropic and cyclic AMP phosphodiesterase inhibitory activity. A wide range of inotropic and enzyme-inhibitory potencies was observed, substitution on the imidazolyl moiety being the major determinant of activity. The 4-ethyl-5-[4-(1H-imidazol-1-yl)benzoyl] congener 9g exhibited the highest potency in vitro. Incorporation of a methyl group at the imidazolyl 2-position gave 9h, which was less potent but remarkably selective in vivo for positive inotropic effects over heart rate and hypotensive effects.
• HAGEDORN, A. A., III;ERHARDT, P. W.;LUMMA, W. C., JR.;WOHL, R. A.;CARTOR,+, J. MED. CHEM., 30,(1987) N 8, 1342-1347
  作者：HAGEDORN, A. A., III、ERHARDT, P. W.、LUMMA, W. C., JR.、WOHL, R. A.、CARTOR,+

  DOI：——

  日期：——