5,5-双(4-氟苯基)咪唑烷-2,4-二酮 | 70028-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 5,5-双(4-氟苯基)咪唑烷-2,4-二酮
• 英文名称: 5,5-Bis(4-fluorophenyl)imidazolidine-2,4-dione
• CAS: 70028-85-2
• 化学式: C₁₅H₁₀F₂N₂O₂
• mdl: MFCD06655621
• 分子量: 288.253
• InChiKey: OQEQEUCZWDWVLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.066
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,5-双(4-氟苯基)咪唑烷-2,4-二酮 在 palladium on activated charcoal 盐酸 、 氢气 、 potassium carbonate 、 三苯基膦 、 红铝 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 20.0~85.0 ℃ 、137.9 kPa 条件下， 反应 41.0h， 生成 3-(1-(3-Chlorobenzyl)-piperidin-4-yl)-5,5-di-(4-fluorophenyl)-imidazolidin-2-one
  参考文献：
  名称：

  Discovery of Diaryl Imidazolidin-2-one Derivatives, a Novel Class of Muscarinic M3 Selective Antagonists (Part 1)

  摘要：

  Pharmacophore-based structural identification, synthesis, and structure-activity relationships of a new class of muscarinic M3 receptor antagonists, the diaryl imidazolidin-2-one derivatives, are described. The versatility of the discovered scaffold allowed for several structural modifications that resulted in the discovery of two distinct classes of compounds, specifically a class of tertiary amine derivatives (potentially useful for the treatment of overactive bladder by oral administration) and a class of quaternary ammonium salt derivatives (potentially useful for the treatment of respiratory diseases by the inhalation route of administration). In this paper, we describe the synthesis and biological activity of tertiary amine derivatives. For these compounds, selectivity for the M3 receptor toward the M2 receptor was crucial, because the M2 receptor subtype is mainly responsible for adverse systemic side effects of currently marketed muscarinic antagonists. Compound 50 showed the highest selectivity versus M2 receptor, with binding affinity for M3 receptor K-i = 4.8 nM and for M2 receptor K-i = 1141 nM. Functional in vitro studies on selected compounds confirmed the antagonist activity toward the M3 receptor and functional selectivity toward the M2 receptor.

  DOI：

  10.1021/jm061159a
• 作为产物：
  描述：

  在 溶剂黄146 作用下， 生成 5,5-双(4-氟苯基)咪唑烷-2,4-二酮
  参考文献：
  名称：

  3-Alkyl-(5,5′-diphenyl)imidazolidinediones as new cannabinoid receptor ligands

  摘要：

  Twenty-four 3-alkyl-(5,5'-diphenyl)imidazolidinediones were synthesized and evaluated as new cannabinoid receptor ligands. Three compounds exhibited a Ki value around 100 nM against [H-3]-SR 141716A binding obtained from human CB1 transfected CHO cells membranes. The lack of change of affinity in the presence of a non hydrolyzable GTP analogue seems to indicate they are cannabinoid antagonists. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00353-4

文献信息

• A convenient preparation of symmetrical and unsymmetrical 1,2-diketones: application to fluorinated phenytoin synthesis
  作者：Philip C. Bulman Page、Andrew E. Graham、B.Kevin Park

  DOI：10.1016/s0040-4020(01)88265-x

  日期：1992.1

  1,2-Diketones are efficiently produced in two steps by reaction of aldehydes with anions derived from 2-substituted dithianes followed by treatment of the resulting alcohols with NBS in aqueous acetone; phenytolin derivatives were prepared from these diketones by a standard method involving treatment with urea and potassium hydroxide under reflux.

  通过醛与衍生自2-取代的二噻吩的阴离子反应，然后在丙酮水溶液中用NBS处理所得的醇，可分两步高效生产1,2-二酮。通过标准方法由这些二酮制备苯妥英衍生物，该方法涉及在回流下用尿素和氢氧化钾处理。
• ORGANIC COMPOUNDS
  申请人：Nozulak Joachim

  公开号：US20090099243A1

  公开（公告）日：2009-04-16

  The invention relates to compound of the formula (I) in which the substituents are as defined in the specification; in free base form or in acid addition salt form; to its preparation, to its use as medicament and to medicaments comprising it.

  本发明涉及式(I)的化合物，其中取代基如规范中所定义；以自由碱或酸盐形式存在；其制备方法，以及其作为药物的用途和包含它的药物。
• Azole Derivatives With Antimuscarinic Activity
  申请人：Peretto Ilaria

  公开号：US20090005364A1

  公开（公告）日：2009-01-01

  The present invention relates to compounds of formula (I) wherein R1, R2, x, X, Y and B are as defined in the description for the treatment of muscarinic acetylcholine receptor mediated diseases, in particular M3 muscarinic receptor mediated diseases.

  本发明涉及式（I）的化合物，其中R1，R2，x，X，Y和B如所述的描述中所定义，用于治疗肌肉型乙酰胆碱受体介导的疾病，特别是M3肌肉型受体介导的疾病。
• WO2006/66924
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of Diaryl Imidazolidin-2-one Derivatives, a Novel Class of Muscarinic M3 Selective Antagonists (Part 2)
  作者：Ilaria Peretto、Claudia Fossati、Giuseppe A. M. Giardina、Alessandra Giardini、Matilde Guala、Elena La Porta、Paola Petrillo、Stefano Radaelli、Luigi Radice、Luca F. Raveglia、Enza Santoro、Roberta Scudellaro、Francesca Scarpitta、Alberto Cerri、Sergio Menegon、Giulio M. Dondio、Andrea Rizzi、Elisabetta Armani、Gabriele Amari、Maurizio Civelli、Gino Villetti、Riccardo Patacchini、Marco Bergamaschi、Franco Bassani、Maurizio Delcanale、Bruno P. Imbimbo

  DOI：10.1021/jm061160+

  日期：2007.4.1

  Synthesis and biological activity of a novel class of quaternary ammonium salt muscarinic M3 receptor antagonists, showing high selectivity versus the M2 receptor, are described. Selected compounds exhibited potent anticholinergic properties, in isolated guinea-pig trachea, and good functional selectivity for trachea over atria. In vivo, the same compounds potently inhibited acetylcholine-induced bronchoconstriction after intratracheal administration in the guinea pig.