4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one | 101184-07-0

• 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]-2H-imidazol-2-one
• 英文别名: 4-ethyl-1,3-dihydro-5-<4-(2-methyl-1H-imidazol-1-yl)benzoyl>-2H-imidazol-2-one；4-ethyl-1,3-dihydro-5-(4-(2-methyl-1H-imidazol-1-yl)benzoyl)-2H-imidazol-2-one；4-ethyl-5-[4-(2-methylimidazol-1-yl)benzoyl]-1,3-dihydroimidazol-2-one
• CAS: 101184-07-0
• 化学式: C₁₆H₁₆N₄O₂
• 分子量: 296.329
• InChiKey: XFOHEDONFCZBOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one 在 三乙胺 作用下， 以 异丙醇 为溶剂， 反应 8.0h， 生成 2H-咪唑-2-酮,1-乙酰基-4-乙基-1,3-二氢-5-[4-(2-甲基-1H-咪唑-1-基)苯甲酰]-
  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
• 作为产物：
  描述：

  对氟苯甲酸乙酯 在 sodium hydroxide 、 甲烷磺酸 、 phosphorus pentoxide 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 生成 4-ethyl-1,3-dihydro-5-[4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one
  参考文献：
  名称：

  Cardiotonic agents. 2. (Imidazolyl)aroylimidazolones, highly potent and selective positive inotropic agents

  摘要：

  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.

  DOI：

  10.1021/jm00391a013

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。
• Pyrrolo[1,2-c]imidazolone derivatives as PDE inhibitors
  申请人：Berlex Laboratories, Inc.

  公开号：US04937258A1

  公开（公告）日：1990-06-26

  This invention relates to novel pyrrolo[1,2-c]imidazolones and their pharmaceutically acceptable salts. The compounds of the invention are PDE inhibitors with primarily cardiovascular effects especially cardiotonic effects.

  本发明涉及新型吡咯并[1,2-c]咪唑酮及其药学上可接受的盐。本发明中的化合物是PDE抑制剂，主要具有心血管效应，特别是心脏强效作用。
• Cardiotonic 1,3-dihydro-4-[[(imidazol-1-yl)aryl]carbonyl]imidazol-2-ones
  申请人：Schering A.G.

  公开号：US04556665A1

  公开（公告）日：1985-12-03

  Novel imidazolonecarbonylarylimidazoles of the formula: ##STR1## are described having cardiovascular properties, especially as cardiotonic agents in the treatment of congestive heart failure. Pharmaceutical formulations containing such compounds are also provided. Further, a novel process for the preparation of the compounds and intermediates useful thereto of this invention is disclosed.

  本文描述了一种式为##STR1##的新型咪唑酮酰基芳基咪唑衍生物，具有心血管特性，特别是作为心力衰竭治疗中的强心剂。本文还提供了含有这种化合物的制药配方。此外，本发明还揭示了一种制备这种化合物及其有用中间体的新方法。
• 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。
• ERHARDT, PAUL W.;HAGEDORN, ALFRED A. (III)
  作者：ERHARDT, PAUL W.、HAGEDORN, ALFRED A. (III)

  DOI：——

  日期：——