benzo[b]thiophene-2-carboxylic acid (4-[4-(2-methoxyphenyl)piperazin-1-yl]-trans-butenyl)amide | 1145355-05-0

• 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: benzo[b]thiophene-2-carboxylic acid (4-[4-(2-methoxyphenyl)piperazin-1-yl]-trans-butenyl)amide
• 英文别名: N-[(E)-4-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-enyl]-1-benzothiophene-2-carboxamide
• CAS: 1145355-05-0
• 化学式: C₂₄H₂₇N₃O₂S
• 分子量: 421.563
• InChiKey: CECKJAHVLJLQBE-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  73
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(4-(2-methoxy)phenylpiperazin-1-yl)-trans-but-2-en-1-amine 、 苯并噻吩-2-羧酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以51%的产率得到benzo[b]thiophene-2-carboxylic acid (4-[4-(2-methoxyphenyl)piperazin-1-yl]-trans-butenyl)amide
  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

• <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.