3-(1-Benzyl-piperidin-4-yl)-5,5-di-(2-thienyl)-imidazolidin-2-one | 895149-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-(1-Benzyl-piperidin-4-yl)-5,5-di-(2-thienyl)-imidazolidin-2-one
• 英文别名: 1-(1-benzylpiperidin-4-yl)-4,4-dithiophen-2-ylimidazolidin-2-one
• CAS: 895149-08-3
• 化学式: C₂₃H₂₅N₃OS₂
• 分子量: 423.603
• InChiKey: PAWBGCCWTWGZPD-UHFFFAOYSA-N

物化性质

• 沸点：
  554.7±50.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1-Benzyl-piperidin-4-yl)-5,5-di-(2-thienyl)-imidazolidin-2-one 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、137.89 kPa 条件下， 反应 8.0h， 生成 4,4-di-(2-thienyl)-1-(piperidin-4-yl)-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：

  1-苄基-4-羟基哌啶 在 三苯基膦 、 红铝 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 28.0h， 生成 3-(1-Benzyl-piperidin-4-yl)-5,5-di-(2-thienyl)-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

文献信息

• Discovery of Diaryl Imidazolidin-2-one Derivatives, a Novel Class of Muscarinic M3 Selective Antagonists (Part 1)
  作者：Ilaria Peretto、Roberto Forlani、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、Chiara Bigogno、Paola Misiano、Giulio M. Dondio、Andrea Rizzi、Elisabetta Armani、Gabriele Amari、Maurizio Civelli、Gino Villetti、Riccardo Patacchini、Marco Bergamaschi、Maurizio Delcanale、Carolina Salcedo、Andrés G. Fernández、Bruno P. Imbimbo

  DOI：10.1021/jm061159a

  日期：2007.4.1

  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.