2-methyl-3-(2-(piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-methyl-3-(2-(piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 2-methyl-3-(2-(piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-4Hpyrido[1,2-a]pyrimidin-4-one；2-Methyl-3-(2-piperidin-1-ylethyl)-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
• 化学式: C₁₆H₂₅N₃O
• 分子量: 275.394
• InChiKey: ASSZTWSUZMHAFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  35.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-3-(2-(piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one 在 盐酸 作用下， 以 乙醇 为溶剂， 以0.03 g的产率得到2-methyl-3-(2-(piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-4Hpyrido[1,2-a]pyrimidin-4-one dihydrochloride
  参考文献：
  名称：

  Revised Pharmacophore Model for 5-HT_2A Receptor Antagonists Derived from the Atypical Antipsychotic Agent Risperidone

  摘要：

  Pharmacophore models for 5-HT2A receptor antagonists consist of two aromatic/hydrophobic regions at a given distance from a basic amine. We have previously shown that both aromatic/hydrophobic moieties are unnecessary for binding or antagonist action. Here, we deconstructed the 5-HT2A receptor antagonist/serotonin-dopamine antipsychotic agent risperidone into smaller structural segments that were tested for 5-HT2A receptor affinity and function. We show, again, that the entire risperidone structure is unnecessary for retention of affinity or antagonist action. Replacement of the 6-fluoro-3-(4-piperidinyl)-1,2-benz[d]-isoxazole moiety by isosteric tryptamines resulted in retention of affinity and antagonist action. Additionally, 3-(4-piperidinyl)-1,2-benz[d]isoxazole (10), which represents less than half the structural features of risperidone, retains both affinity and antagonist actions. 5-HT2A receptor homology modeling/docking studies suggest that 10 binds in a manner similar to risperidone and that there is a large cavity to accept various N-4-substituted. analogues of 10 such as risperidone and related agents. Alterations of this "extended" moiety improve receptor binding and functional potency. We propose a new risperidone-based pharmacophore for 5-HT2A receptor antagonist action.

  DOI：

  10.1021/acschemneuro.8b00637
• 作为产物：
  描述：

  3-(2-氯乙基)-2-甲基吡啶并[1,2-a]嘧啶-4-酮 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 、 乙腈 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 28.0h， 生成 2-methyl-3-(2-(piperidin-1-yl)ethyl)-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  消除杂环正电子发射断层扫描放射性配体的铜介导的 18F-氟化

  摘要：

  用氟 18 (18F) 标记的分子用于正电子发射断层扫描，以可视化、表征和测量体内的生物过程。尽管最近在将 18F 掺入芳烃方面取得了进展，但开发通用且有效的方法来标记药物发现计划所需的放射性配体仍然是一项重大任务。这个完整的描述描述了杂环正电子发射断层扫描 (PET) 放射性配体的放射合成方法，使用铜介导的 18F 氟化芳基硼试剂与 18F 氟化物作为模型反应。该方法基于一项研究，该研究检查了药物开发中常用的杂环的存在如何影响代表性芳基硼试剂的 18F-氟化效率，以及超过 50 种（杂）芳基硼酸酯的标记。这组数据允许将这种去风险策略应用于七种结构复杂的药物相关含杂环分子的成功放射合成。

  DOI：

  10.1021/jacs.7b03131

文献信息

• FUJITA H.; SHIMOJI Y.; KOJIMA S.; NISHINO H.; KAMOSHITA K.; ENDO K.; KOBA+, ANN. REPT. SANKYO RES. LAB., 1977, 29, 75-98
  作者：FUJITA H.、 SHIMOJI Y.、 KOJIMA S.、 NISHINO H.、 KAMOSHITA K.、 ENDO K.、 KOBA+

  DOI：——

  日期：——
• Derisking the Cu-Mediated ¹⁸F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
  作者：Nicholas J. Taylor、Enrico Emer、Sean Preshlock、Michael Schedler、Matthew Tredwell、Stefan Verhoog、Joel Mercier、Christophe Genicot、Véronique Gouverneur

  DOI：10.1021/jacs.7b03131

  日期：2017.6.21

  Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach

  用氟 18 (18F) 标记的分子用于正电子发射断层扫描，以可视化、表征和测量体内的生物过程。尽管最近在将 18F 掺入芳烃方面取得了进展，但开发通用且有效的方法来标记药物发现计划所需的放射性配体仍然是一项重大任务。这个完整的描述描述了杂环正电子发射断层扫描 (PET) 放射性配体的放射合成方法，使用铜介导的 18F 氟化芳基硼试剂与 18F 氟化物作为模型反应。该方法基于一项研究，该研究检查了药物开发中常用的杂环的存在如何影响代表性芳基硼试剂的 18F-氟化效率，以及超过 50 种（杂）芳基硼酸酯的标记。这组数据允许将这种去风险策略应用于七种结构复杂的药物相关含杂环分子的成功放射合成。
• Revised Pharmacophore Model for 5-HT_2A Receptor Antagonists Derived from the Atypical Antipsychotic Agent Risperidone
  作者：Urjita H. Shah、Supriya A. Gaitonde、José L. Moreno、Richard A. Glennon、Małgorzata Dukat、Javier González-Maeso

  DOI：10.1021/acschemneuro.8b00637

  日期：2019.5.15

  Pharmacophore models for 5-HT2A receptor antagonists consist of two aromatic/hydrophobic regions at a given distance from a basic amine. We have previously shown that both aromatic/hydrophobic moieties are unnecessary for binding or antagonist action. Here, we deconstructed the 5-HT2A receptor antagonist/serotonin-dopamine antipsychotic agent risperidone into smaller structural segments that were tested for 5-HT2A receptor affinity and function. We show, again, that the entire risperidone structure is unnecessary for retention of affinity or antagonist action. Replacement of the 6-fluoro-3-(4-piperidinyl)-1,2-benz[d]-isoxazole moiety by isosteric tryptamines resulted in retention of affinity and antagonist action. Additionally, 3-(4-piperidinyl)-1,2-benz[d]isoxazole (10), which represents less than half the structural features of risperidone, retains both affinity and antagonist actions. 5-HT2A receptor homology modeling/docking studies suggest that 10 binds in a manner similar to risperidone and that there is a large cavity to accept various N-4-substituted. analogues of 10 such as risperidone and related agents. Alterations of this "extended" moiety improve receptor binding and functional potency. We propose a new risperidone-based pharmacophore for 5-HT2A receptor antagonist action.