1,3-dihydro-4-(4-fluorobenzoyl)-5-methyl-2H-imidazol-2-one | 77671-25-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,3-dihydro-4-(4-fluorobenzoyl)-5-methyl-2H-imidazol-2-one
• 英文别名: 4-(4-fluorobenzoyl)-1,3-dihydro-5-methyl-2H-imidazol-2-one；1,3-dihydro-4-(4-fluorobenzoyl)-5-methyl-2H-imidazole-2-one；4-(4-Fluorobenzoyl)-5-methyl-1,3-dihydro-2H-imidazol-2-one；4-(4-fluorobenzoyl)-5-methyl-1,3-dihydroimidazol-2-one
• CAS: 77671-25-1
• 化学式: C₁₁H₉FN₂O₂
• 分子量: 220.203
• InChiKey: ZSJAVAWYXAWBMZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 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：

  1,3-dihydro-4-(4-fluorobenzoyl)-5-methyl-2H-imidazol-2-one 以 水 为溶剂， 反应 57.0h， 生成 1,3-dihydro-4-<4-<2-(hydroxymethyl)-1H-imidazol-1-yl>-benzoyl>-5-methyl-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
• 作为产物：
  描述：

  对氟苯甲酸 、 2,3-二氢-5-甲基-2-氧代-1H-咪唑-4-羧酸 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 1,3-dihydro-4-(4-fluorobenzoyl)-5-methyl-2H-imidazol-2-one
  参考文献：
  名称：

  Cardiotonic 1,3-dihydro-4-[[(imidazol-1-yl)aryl]carbonyl]imidazol-2-ones

  摘要：

  本发明提供了一种具有心血管特性的新型咪唑酮酰基芳基咪唑类化合物，特别是作为治疗充血性心力衰竭的强心剂。本发明还提供了含有这种化合物的药物制剂。此外，本发明还公开了一种制备这种化合物和其中间体的新方法。

  公开号：

  US04556665A1

文献信息

• 4-Aroylimidazol-2-ones and their use as pharmaceuticals
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US04405635A1

  公开（公告）日：1983-09-20

  Novel 4-aroylimidazol-2-ones of the following general structure which are useful as antihypertensives, cardiotonics, antithrombotics, bronchodilators and uterospasmolytics ##STR1## wherein Ar is 2-furyl, 2-thienyl or phenyl, the latter of which may optionally be substituted with one or two X groups; X is halogen, hydroxy, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, methylenedioxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfoxide, C.sub.1-4 alkylsulfone, CF.sub.3, --SO.sub.2 N(R.sub.2).sub.2, NR.sub.3 R.sub.4, pyrrolidino, piperidino, morpholino, piperazino or N'-alkyl-piperazino, R is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkylcarbonyl or benzyl; each of R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are hydrogen or C.sub.1-4 alkyl; and the pharmaceutically acceptable salts thereof.

  以下是上述结构的4-芳基咪唑啉-2-酮类化合物的中文翻译：Ar为2-呋喃基、2-噻吩基或苯基，后者可以选择性地用一个或两个X基团取代；X为卤素、羟基、C.sub.1-4烷基、C.sub.1-4烷氧基、亚甲二氧基、C.sub.1-4烷硫基、C.sub.1-4烷基亚氧基、C.sub.1-4烷基磺醚基、CF.sub.3、--SO.sub.2 N(R.sub.2).sub.2、NR.sub.3 R.sub.4、吡咯啉基、哌啶基、吗啉基、哌嗪基或N'-烷基-哌嗪基，R为氢、C.sub.1-4烷基、C.sub.1-4烷基羰基或苄基；R.sub.1、R.sub.2、R.sub.3和R.sub.4中的每一个均为氢或C.sub.1-4烷基；以及其药学上可接受的盐。
• 4-(4-Guanidinobenzoyl)-2-imidazolones and Related Compounds: Phosphodiesterase Inhibitors and Novel Cardiotonics with Combined Histamine H2 Receptor Agonist and PDE III Inhibitor Activity
  作者：D. Glaß、A. Buschauer、H. Tenor、S. Bartel、L. Will-Shahab、E.-G. Krause

  DOI：10.1002/ardp.19953281005

  日期：——

  phosphodiesterase (PDE) inhibitor enoximone and guanidine‐type histamine H2 receptor agonists such as arpromidine. All compounds are para‐substituted 4‐benzoyl‐5‐alkyl‐2‐imidazolones. H2 agonism was incorporated by p‐(hetero)arylalkyl substituents, in particular by an imidazolylpropyl guanidine group. In addition analogous ureas, cyanoguanidines, alkyl guanidine carboxylates, and amides were prepared. These

  合成了一系列新型正性肌力药物，旨在结合咪唑酮型磷酸二酯酶（PDE）抑制剂依诺昔酮和胍型组胺 H2 受体激动剂阿普米啶的药效团。所有化合物都是对位取代的 4-苯甲酰基-5-烷基-2-咪唑酮。通过对（杂）芳基烷基取代基，特别是通过咪唑基丙基胍基团引入 H2 激动作用。此外，还制备了类似的脲、氰基胍、烷基胍羧酸盐和酰胺。这些官能团要么直接连接到苯环上，要么通过适当的间隔基连接。筛选化合物在分离的电刺激豚鼠乳头肌中的正性肌力活性和抑制 PDE III（cGMP 抑制的 cAMP PDE，从豚鼠心脏分离）。获得的强心剂要么是 PDE III 抑制剂，其中一些药物的效力是依诺昔酮的 3 倍，要么是结合了 PDE III 抑制剂和组胺 H2 受体激动剂活性的药理学杂种。这些混合物是乳头肌中最有效的正性肌力物质，可能是由于它们的协同作用机制。通过用 H2 拮抗剂法莫替丁 (10 μM) 预处理以及使用离体
• 4-(4-Phenyl-1-piperidinyl)methyl-5-acyl-1,3-dihydro-2H-imidazol-2-ones
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US04329471A1

  公开（公告）日：1982-05-11

  1,3-Dihydro-2H-imidazol-2-ones having 5-acyl and 4-(4-phenyl-1-piperidinyl)methyl substituents, are useful as cardiotonics, antihypertensives and antithrombotic agents. The compounds are obtained by the reaction of an appropriate substituted piperidine with a substituted 4-bromomethyl-1,3-dihydro-2H-imidazol-2-one.

  具有5-酰基和4-(4-苯基-1-哌啶基)甲基取代基的1,3-二氢-2H-咪唑-2-酮，可用作心脏强心剂、降压剂和抗血栓剂。该化合物是通过将适当取代的哌啶与取代的4-溴甲基-1,3-二氢-2H-咪唑-2-酮反应得到的。
• 4-Aminomethyl-5-acyl-1,3-dihydro-2H-imidazol-2-ones
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US04381393A1

  公开（公告）日：1983-04-26

  1,3-Dihydro-2H-imidazol-2-ones having 5-acyl and 4-(substituted amino)methyl substituents, are useful as cardiotonics, antihypertensives and antithrombotic agents. The compounds are obtained by the reaction of an appropriate amine with a substituted 4-bromomethyl-1,3-dihydro-2H-imidazol-2-one.

  具有5-酰基和4-(取代氨基)甲基取代基的1,3-二氢咪唑-2-酮在心脏强心剂、降压剂和抗血栓剂方面具有用途。该化合物是通过适当胺与取代的4-溴甲基-1,3-二氢咪唑-2-酮反应而得到的。
• Process for the preparation of imidazolonecarbonylarylimidazoles
  申请人：Schering A.G.

  公开号：US04709043A1

  公开（公告）日：1987-11-24

  Novel imidazolonecarbonylarylimidazoles 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.

  本发明描述了具有心血管特性的新型咪唑烷酰基芳基咪唑，特别是作为治疗充血性心力衰竭的心脏强效药物。此外，还提供了含有这种化合物的制药配方。此外，还揭示了一种制备该化合物和中间体的新方法。