N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)-5-fluoro-1H-indole-2-carboxamide | 1092953-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)-5-fluoro-1H-indole-2-carboxamide
• 英文别名: N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxybutyl]-5-fluoro-1H-indole-2-carboxamide
• CAS: 1092953-83-7
• 化学式: C₂₃H₂₅Cl₂FN₄O₂
• 分子量: 479.382
• InChiKey: DISKLDRQYHVOPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  71.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-amino-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)butan-2-ol 、 5-氟吲哚-2-甲酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以64%的产率得到N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)-5-fluoro-1H-indole-2-carboxamide
  参考文献：
  名称：

  N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists

  摘要：

  In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl- and 2-OCH3-phenylpiperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (K-i = 1 nM) for D3 and similar to 400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors, further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders.

  DOI：

  10.1021/jm900095y

文献信息

• 4-PHENYLPIPERAZINE DERIVATIVES WITH FUNCTIONALIZED LINKERS AS DOPAMINE D3 RECEPTOR SELECTIVE LIGANDS AND METHODS OF USE
  申请人：The United States of America, as Represented by the Secretary, Department of Health and Human Serv

  公开号：US20140296249A1

  公开（公告）日：2014-10-02

  Dopamine D 3 receptor antagonists and partial agonists are known to modulate the reinforcing and drug-seeking effects induced by cocaine and other abused substances. By introducing functionality into the butylamide linking chain of the 4-phenylpiperazine class of ligands, improved D 3 receptor affinity and selectivity, as well as water solubility, is achieved. A series of linking-chain derivatives are disclosed wherein functionality such as OH, OAc, and cis or trans-cyclopropyl groups have been introduced into the linking chain. In general, these modifications are well tolerated at D 3 receptors and achieve high selectivity over D 2 and D 4 receptors.

  多巴胺D3受体拮抗剂和部分激动剂已知可以调节由可卡因和其他滥用物质引起的加强和寻药效应。通过在4-苯基哌嗪配体的丁酰胺连接链中引入功能基团，可以实现改善的D3受体亲和力和选择性，以及水溶性。披露了一系列连接链衍生物，其中引入了OH、OAc和顺式或反式环丙基基团等功能基团。总的来说，这些修饰在D3受体上耐受性良好，并且在D2和D4受体上实现了高选择性。
• <i>N</i>-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists
  作者：Amy Hauck Newman、Peter Grundt、George Cyriac、Jeffrey R. Deschamps、Michelle Taylor、Rakesh Kumar、David Ho、Robert R. Luedtke

  DOI：10.1021/jm900095y

  日期：2009.4.23

  In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl- and 2-OCH3-phenylpiperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (K-i = 1 nM) for D3 and similar to 400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors, further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders.